FEJ: ET Stait: El End: Establishment fnspection Report Guthy-Re11kcr LLC Santa Monica, CA 90405-3268 3007513615 11 /07/201 J 01 /06/2012 TABLE OF CONTENTS Sununary ........................................................................................................................................... 1 Ad111inistrative Data ................................................ .............................................. ............................ 3 History....................... ....... ................................................................................................................. 5 Interstate Conunerce/ Jurisdiction .................................................................................................... 7 Individual Responsibility and Persons Interviewed .......................................................................... 7 Finn's Training Progra1n ................................................................................................................. 10 Manufacturing/Design Operations .. ................................................................................................ JI Manufacturing Codes ......................................................... .......... ............................ ....................... 12 Co1nplaints .................................................... .................................................................................. 12 Recall Procedures............................................................................................................................ 14 Objectionable Conditions and Management's Response ................................................................ 14 OBSERVATION 1 ..................................................................................................................... 15 OBSERYA'fION 2 ............................................ ............................................ ............................. 17 OBSERVATION 3 ................................................................... .................................................. 18 OBSERVATION 4 ..................................................................................................................... 21 OBSERVA'fION 5 ..................................................................................................................... 30 OBSERVATION 6 ..................................................................................................................... 31 Refusals ......................................................... :................................................................................. 32 General Discussion with Management ........................................................................................... 32 Additional lnfonnaiion ................................................................................................................... 34 Knowledge of GR subsidiaries ............... .................................................................................... 34 Change in vitamin distribution and responsibility ...................................................................... 34 Proactiv benzoyl peroxide overage formulations .................................................................. ..... 35 Samples Collected ................................................................ ...... ..................................................... 35 \ 1olunta1y Corrections ..................................................................................................................... 35 Exhibits Collected ........................................................................................................................... 36 Attachments .................................................................................................................................... 40 SUJ\t1MARY This was a directed surveillance inspection of one of the Corporate Headqumtcrs locations of GuthyRenker, LLC, (GR) a marketer and distributor of consumer products including over-the-counter (OTC) topical drug products, human dietary supplements and cosmetics. This ins ection was revealed initiated after an inspection of a contract manufacturer 1 of 41 Establishment Inspection Report Gulhy-Renker LLC Santa Monica, CA 90405-3268 FEI: 3007513615 EI Start: EI End: 11/07/2011 01 /06/2012 multiple lots of topical OTC drug products (distributed by GR) were not meeting active ingredient label claim throughout their applied shelf life. GR contacted LOS-DO recal.ls after lhe contract manufacturer inspection to initiate a voluntary recall of multiple lots of Proactiv Repairing Treatment/Lotion, Proactiv Renewing Cleanser, and Proactiv Concealer Plus. Tbe inspection was conducted per CPGM 7356.002: "Drng Manufacturing Inspections" and inc]uded limited coverage of CPGM 7321.008: "Dietary Supplements" and CPGM 7329.00 l "Cosmetics Program". The inspected firm is one of two Corporate Headquarters locations for GR LLC; an inspection was also conducted at the Palm Desert Corporate Headquarters location (FEl 3007134760; labeled distributor location) . The inspections focused on GR LLC corporate-based quality system operations including oversight of contract vendors and the OTC drug product stability program, investigations into quality-related deviations, and complaint handling. The Santa Monica office inspection can be found in FACTS under assignment 1356047. Tfos is the first inspection of Guthy-Renker LLC and its subsidiaries by the US Food and Drng Administration. Guthy-Renker LLC markets and distributes a variety of products from DVD sets and exercise equipment to acne treatments and shampoos. Products regulated by the US Food and Drug Administration include over-the-counter (OTC) drug products (acne medications, sunscreens, etc.), cosmetics (facial and hair care), and dietary supplements (vitamins). The inspected locations are dual Corporate Headquarters offices with the Santa Monica corporate office housing the finn 's Product Development and Consumer Affairs (complaint handling) departments and the Palm Desert office housing the fom's Quality Compliance (formerly Quality Control) department. At the conclusion of the inspection a 6~item FDA 483 was issued to the firm for: • failure to repoli serious adverse events associated with consumer use of dietary supplements (vitamins); • failure to repo1t se1ious adverse events associated with consumer use of over-the-counter topical drug products; • responsibilities and procedures applicable to the quality control un.i.t are not in writing and fully followed; • results of stability testing not used to determine expiration dates of topical over-the-counter drng products; • lack of written procedure and lack of perfo11nance of annual product review for over-thecounter drug products including provisions for a review of complaints and investigations; and • an inadequate number of batches of drug products placed on stability or inadequate maintenance of stability records to determine an appropriate expfration date for topical overthe-counter drug products. Firm management has hired the following consulting fim1s: - to aid i11 the recall )rocess; - to aid in evaluation of stability data for over-the-counter drug products and ,_.._,__,.___. b (4 for assistance in restructuring the Quality Control department and related ualit operations. Firm management did not comment on issued observations or planned/im lemented corrections to the Hsted observations during the closing meeting on 116112. General Counsel, 2of41 FEI: EI Sta1t: EI End: Establishment Inspection Report Guthy-Renker LLC Santa Monica, CA 90405-3268 3007513615 11/07/2011 01 /06/2012 stated that a written response to the Inspectional Observations would be submitted to the Los Angeles District Office. Guthy-Renker LLC (Palm Desert) initiated recalls of three topical over-the-counter acne drug products in November 2011. The recalls were conducted for multiple lots of Proactiv Renewing Cleanser (2.5% benzoyl peroxide; sub-potent), Proactiv Repairing Lotion/Treatment (2.5% benzoyl peroxide; sub-potent), and Proactiv Concealer Plus (sulftu- 8 %; super-potent) which fai led to meet active ingredient label claim throughout their applied shelf life. The recall of Proactiv Concealer Plus was expanded during the inspection. The recalls, D-(1167-1 169)-2012, were classified by CDER as Class III. No reconciliation exam was performed as the inspected locations are office locations and do not receive product for manufacturing. DOCs 675797, 675799 and 675800 document the interstate commerce of distributed over-thecounter topical acne drug products distributed by Guthy-Ren.ker LLC (Palm Desert; labeled distributor location) and vitamins distributed under the financial control of Guthy-Renker LLC. I provided the following guidance documents to Mr. Bennet M. Van de Bunt, co-CEO on 1/6/12: • Topical Acne Drug Products for Over-the-Counter Human Use - Revision of Labeling and Classification of Benzoyl Peroxide as Safe and Effective; • Enforcement Policy - OTC Sunscreen Drug Products Marketed Without an Approved Application; and • Questions and Answers: FDA announces new requirements for over-the-counter (OTC) sunscreen products marketed in the U.S. • Guidance for Industry: Questions and Answers Regarding Adverse Event Repo1ting and Recordkeeping for Dietary Supplements as Required by the Dietary Supplement and Nonprescription Drug Consumer Protection Act • Guidance for Industry: Postmarketing Adverse Event Reporting for Nonprescription Human Drug Products Marketed Without an Approved Application Firm representatives were directed to W\VW.fda.gov for additional information on regulated products and were informed that new regulatory requirements for sunscreen products, including new testing and labeling requirements would go into effect summer of 2012. ADMINISTRATIVE DATA Inspected firm: Location: Guthy-Renker LLC 3340 Ocean Park Blvd., Ste 3055 3of41 FEI: ET Start: EI End: Establishment Inspection Rc110rt Guthy-Renker T.LC Santa Monica, CA 90405-3268 Phone: PAX: Mailing address: Website: Dates of inspection: Days in the facility: Participants: 3007513615 11/07/201) 01 /06/2012 Santa Monjca, CA 90405-3268 310-581-6250 310-581-3232 3340 Ocean Park Blvd., Ste 3055 Santa Monica, CA 90405-3268 W\VW.guthy-rcnker.com 11171201 J' 11/8/2011, 11/ 10/2011, 11/14/2011, 11/ 18/2011, 11/22/20 I J, 11/28/2011, 11/29/2011, 11/30/2011, 12/2/201 l, 12/6/2011, 12/8/2011, 12/12/201I,12121/2011, 12/29/2011, 1/3/2012, 1/5/2012, 1/6/2012 18 Sonia R Peterson, Jnvestigator, LOS-DO On 11/7/ l l I, Investigator Peterson, presented credentials and issued a FDA 482, Notice of Inspection, to Mr. Dirk van de Bunt, Executive Vice President and ChiefAdministralive Officer for Gut by-Renker LLC. Mr. van de Bunt stated that he was the most responsible person for GuthyRenker currently available at the location. The suite number (3055) and the firm's designation as a limited liability corporation (LLC) were mistakeuly left off of the FDA 482 when issued. GR occupies the entire third floor of the office building as well as additional office space within the building on the first and second floors. On 11/14/2011 two FDA 482s, Noticc(s) ofinspection, were issued to 11r. Dirk van de Bunt, EVP and ChiefAdm;n;s1ra1;ve Officer of GR LLC. The two FDA 482's were issued for Vendor Services, LLC and Guthy-Renker Nutritional Products, LLC when information was provided which indicated that dietary supplements, including vitamins and sexual enhancement products, 'vere distributed by these Guthy-Renker subsidiaries. Mr. van de Bunt sai d he was the most responsible individual available for the entities. On 1l /1511 1 1 started an inspection at the Palm Desert Corporate HQ of GR LLC. Inspections were also opened in Palm Dese11 for Vendor Services, LLC, and Guthy-Renker Nutritional Products, LLC. Please refer to the EIR of Gutlly-Renker LLC, Palm Desert for issued FDA inspectional documents (FEJ 3007134760). On 1/6/12 I presented credentials and issued a 6-item FDA 483, Inspectional Observations, to Mr. Bennet M. Van de Bunt, co-ChiefExecunve Officer (co-CEO) of Guthy-Renker LLC. FDA 483's were also issued to Mr. B. Van de Bunt for Guthy-Renker LLC (Palm Desert), Vendor Services, LLC (Santa Monica) and Vendor Services, LLC (Palm Deseit). The following individuals were also present during the closing discussion: Dirk van de Bunt, EVP and ChiefAdmi11istralive Officer; 6 General Counsel;, Shelly Elkins, Director ofConswner Affairs; and Robann Rollins, Senior Director of lnvento1J' and Qua/U Control. Keith Nelson, Director of Quality Compliance for Guth '-Renker LLC; and ) ounsel D-o!~ 6L----' ...._......_..... and were present via conference call. 4of41 FEl: EI Start: EI End: Establishment Inspection Report Guthy-Renkcr LLC Santa Monica, CA 90405-3268 3007513615 11/07/2011 01/06/2012 GR hired outside counsel, for assistance with recall activities and the FDA inspection. The majority of the inspection conducted at both the Santa Monica and Palm Desert office locations included at least one representative from n conference call, or in-person. The ·epresentalives include: Affidavits (see Attachments) were prepared during the inspection lo cover information provided as well as interstate documents collected for distributed products. GR LLC representatives (Keith Nelson, Robann Rollins, Dale Snider, Kimber Maderazzo, and Dirk van de Bunt) read the affidavits and affirmed they were true and accurate to the best of their knowledge. Film representatives would not sign or write a statement on the affidavit at the advice of legal counsel based on the fact that such activity was against company policy. IfJSTORY This is the fust inspection by the US FDA of Guthy-Renker LLC (GR LLC) and its subsidiaries which are involved in distribution and marketing of FDA regulated products including OTC drug products, dietary s1.1pplements and cosmetics. Guthy-Renker LLC is a limited liability corporation which was incorporated in the state of Delaware, doing business in California, in 2008. The firm was previously known as Guthy-Renker Corporation (surrendered in November 1993) and is the operating entity for parent company Guthy-Renk.er Partners, lnc. and its subsidiary Guthy-Renker Holdings, LLC. Guthy-Renker Partners, lnc. is fully owned by five individuals: Mr. Bill Guthy, Mr. Greg Renker, Mr. Lenny Lieberman, Mr. Bennet (Ben) Van de Bunt, and Mr. Kevin Knee, or their associated trusts. Info1mation provided by Mr. Dirk van de Bunt outlines the above business structure between GR LLC, its parent companies a.11d subsidiaries (Exhibit 1). A list of business entities with assodated distributed product(s) and most responsible person is included in Exhibit 2. California Business Search details for each entity are included as attachments to this report. GRLLC operates from two office locations in Southern California. The Palm Desert office (41 -550 Eclectic Street, Suite 200, Palm Desert, CA 92260-1967) is the official headquarters Jocation for the company reflected jn the business search and on distributed product labels. The firm operates out of a ~ t2 ffice building. Office hours are The Palm Desert location holds a cmTent drug facility registration and current device registration for a Youthful Essence therapeutic electric massager. The Santa Monica office location (3340 Ocean Park Blvd., Suite 3055, Santa Monica, CA 90405-3268) is the main operating headquarters for the company. The Santa Monica office js located in a co1voratc business park. 2 The firm occupies office space on each of the three floors totaling D ft . The office operates 5 of 41 FEI: Establishment Inspection Report Guthy-Renker IJ,C Santa Monica, CA 90405-3268 EI Start: EI End: 3007513615 11/07/2011 0110612012 Each of the headquarter locations is headed by a coCEO (Mr. Bennel Van de Bunl - Santa Monfoa; and Mr. Kevin Knee - Palm Desert) who reports to the company's Board of Directors. Information on associated GR locations, includjng physical addresses, is included in Exhibit 3. As a direct marketing company GR LLC primarily deals in direct customer distribution of products from warehouse locations (Guthy-Renker J;ulfillment Services) within the US. Product is also shipped between GR warehouse locations and from US warehouses to furl her distribution points in countries including Canada, b 4 etc. GR LLC does distribute some finished roducts, including OTC drug products to otJ1er distributors \:vithin the US including nd Finished products are manufactured for the firm by contract vendors located primarily within the United States. WAREHOUSED DISTRIBUTION LOCATION(S) Guthy-Renker LLC GRFS (CPU2), Foothill Ranch, CA Plus Proactiv Renewing Cleanser Proactiv Repairing Gu thy-Renker LLC (b)(4 GRFS (CPU2), Guthy-Renker LLC Foothill Ranch, CA Lotion/ Treatment I L (various V-i-ta_ m_in_s_ _ brands) GRFS (CPU2), Foothill Ranch, CA (b) (4 (b) (4 (b)(4 _c_G_R_L~L-c-·c-20_1_J)_;_L~~~~~LG_1R~~-P_E_m_ill_p_ris_e_s~~=~==~:: : ('I I GR Nutritional Products LLC c2010) Services, Des _ _ _ _, Moines IA A list of contract vendors used by GR LLC and is subsidiaries is included in Exhibit 4. Information on warehousing locations for finished products is included in Exhibit 5. 6 of 41 FEI: 3007513615 EJ Sta11: 11 /07/2011 EI End : 01106/2012 EstabJishmcnt Inspection Rcpoi-t (Juthy-Renker LLC Santa Monica, CA 90405-3268 h1November2011 GR LLC (Palm Desert) initiated a voluntary reca ll of Proactiv Renewjng C lea nser (2.5% benzoyl peroxide; s ub-potent), Proactiv Repairing Lotion/Treatment (2.5% bcnzoyl peroxide; sub-potent), and Proactiv Concealer Plus (sulfur 8 %; super-potent) which were found not to meet active ingredient label claim tlu·oughout their applied shelflife. The Concealer Plus reca11 was expanded dming the current hispect ion. The majmily of recall communication was handled by D. Stone, LOS-DO Recall Coordinator. Official Correspondence (including FMD-145) should be addressed to: Mr. Bem1et Van de Ilunt, Co-CEO Guthy-Renker LLC 3340 Ocean Park Blvd. Suite 3350 Santa Monica, CA 90405 INTERSTATE COMMERCE/ JURISDICTION GR LLC markets and distributes a variety of products from DVD sets and exercise equipment to acne treatments and shampoos. Products regulated by the US Food nnd Dmg Administration include over-the-counter (OTC) drug products (acne medications, sunscreens, etc.), cosmetics (facial and hair care), and dietary supplements (vi1amins) and include brands such as Proactiv, Wen, Sheer Cover, and V itapower. Mr. D . van de Bunt repo1ted that smaller volume brands are handled by GR2, a division of GR LLC; brands include Principal Secret, Youthful Essence, and Natural Advantage. A li st of OTC drug products handled by GR LLC is included in Exhibit 6. Regulated products are marketed and dis tributed lo customers worldwide via infomercials, websites, home-shopping nePNorks D ~ , further dish·ibulors and mall-based shopping kiosks. Mr. Dale Snider, Director ofGlobal Freight and Logistics, provided estimates of interstate and wholesale shipments for regulated products handled by GR LLC and its subsidiaries (Exhibit 7). A list of GRLLC gross revenues, by product, for 20] 0 is included in E xhibit 8. DOC 675797, 675799 ru1d 675800 document interstate commerce of Proactiv Repairing Treatment and R enewing Cleanser; Sheer Cover Dai ly Plus Vitamins and Vitacle.:1r vitamins; and Proactiv Conceal~r Plus, which are distributed by GR LLC (Palm Desert) and/or its subsidiary Guthy-Renker Nutritional Products LLC (Palm Dese1t; see additional information section for information on change in vitamin distribution practices). INDIVlDUAL RESPONSlHJLlTY AND PERSONS INTERVIEWED Organizational Charts for Guthy-Renker LLC are included in Exhibit 9. 7of41 FEI: ET Start: EI End: Establishment Inspection Report Guthy-Renker LLC Santa Monica, CA 90405-3268 3007513615 11 /07/2011 01/06/2012 Mr. Bennet (Ben) M. Van de Bunt is a Co- ChiefExecutive Officer for Guthy-Renker LLC. He has been with GR LLC since 1993 and has been in his cuiTent position since summer of2009. On 1/6/12 Mr. B. Van de Bunt said that he was no longer a co-President for the firm aud stated that the title of President was not cmrently filled. Mr. B Van de Bunt is responsible for daily functioning of Guthy-Renker LLC including maximizing shareholder interests and has five direct reports: Dirk van de Bunt, Executive Vice President and ChiefAdministrative Officer; Seth Radwell, ChiefMarkel in 0 zcer Georg Richter, CMe/Opera!ing Officer; Lenny Lieberman, Production Studio; and 6 .._.~6....£.li' Administrative Assis/ant. The Product Development, Quality Control/Compliance, Consumer Affairs, and Global Supply Chain departments all repo1t up through Mr. B. Van de Bunt via his direct reports. He has hire/fire and spending authority and reports to firm owners Mr. Bill Guthy and Mr. Greg Renker who are on the firm's Board of Directors. Mt.. B Van de Btmt was not available during the sta1t of inspection and was not available during discussions held during the inspection to discuss inspectional concerns. Mr. B. Van de Bunt operates out of the Santa Monica office. Dirk Vv'. van de Bunt, Executive Vice President am/ CltiefAdministrative Officer, has been wi th Guthy-Renker for approximately 5 years and in his current position for three years. He oversees Human Resources, legal, business affairs, marketing se1vices, customer and marketing data and faciJities at the Santa Monica location. He has hire/fire authority and spending authority and reports to Mr. Bennet Van De Bunt, Co-CEO (brother), as well as lo Seth R.adwell, Chief Marketing Officer. Mr. D. van de Bunt identified himself as the most responsible individual avai lable at the Santa Monica location at tin1e of inspection start and served as the primary fom contact for the inspection. Mr. D. van de Bunt operates out of the Santa Monica office. SbeJJey E. Elkins, Director of Consumer A;ffail"s, has been with Guthy-R.enker since April 2010 and is responsible for managing resolution for customer compJajnts escalated from the call centers including, but not limited to, adverse events, better business bureau complaints, and legal complaints. The Consumer Affairs department is located at the Santa Monica office and handles complaints for Guthy-Renker LLC distributed products (over-the-counter drug products, cosmetics, etc) as well as products distributed by GR subsidiaries including Vendor Services LLC (Triverex brands) and Guthy-Renker Nutritional Products LLC (various branded vitamin products). She has hire/fire authority and spending authority for her area. Ms. Elkins reports to Ms. Karen Vaughn, Vke President of Call Center Management, who rep011s to Mr. Georg Richter Chief Operating Officer. Ms. Elkins provided consumer complaint information including complaint logs, monthly trending reports, individual complaint records and associated GMP forms. Ms. Elkins operates out of the Santa Monica office. Kimber L. Maclerazzo, Senior Vice President of Global Product Development, has been with Guthy-Renker for approximately 8 years, and has been jn her current position since 2008. Her responsibilities include making new product formulas (with help from contract manufacturers or private formulators) including product design, brand strategy, ingredient lists, directions for use, and premarket product stability. She rcp011s to Ms. Karen Barner, Senior Vice Pres;dent, who reports to Lcm1y Lieberman who handles studio productions for Guthy-Renker. Ms. Maderazzo provided 8 of 41 Establishment Inspection Report Guthy-Renker LLC Santa Monica, CA 90405-3268 FEl: E I Sta1i : 3007513615 ET End: 01 /06/2012 11/07/2011 some product stability information including information on knowledge of product stability failures, timelines for transfer of QA responsibilities, stability reports and raw test data from contract vendors, product development procedures and Product development training information, and product specification infonuation for over-the counter drug products, vitamins, and sexual enhancement herbal supplements. Ms. Maderazzo operates out of the Santa Monica office. Natalie S. Schlemer, Ewcutive Directo1' Global Product Development, Product Research rmd Fol'mula Developme11t, has been with GR for 10 years and in her current position for approximately 6 years. Her position responsibHities include activities related to launching of new p roducts including competitive analysis, timelines for product development and review of prin1ary (premarketed or lab batch) product stability. She reports to Kimber Maderazzo: Senior Vice President of GIobal Product Development. Ms. Schlemer operates out of the Santa Monica office. Tina (NMI) Lam, Director of Global Product Development Product Research and Formula Developme11t, has been with GR for five years and in her current position for approximately two years. She has no direct reports and no hire/fire or spending authority. Ms. Lam reports to Ms. Schlemer and has daily responsibility for new product development from concept to launch which includes safety testing and review of raw materials for equivalence when changes are necessary. Although she rcpo1ted having no roles or responsibility related to launched product stability Ms. Lam reported that she does occasionally receive stability data from contract vendors, mainly when requested to support tl1e initially applied product expiration period. Ms. Lam operates out of the Santa Monica office. 6) General Co1111sef provides in-house counsel for Guthy-Renker. She handles human resource issues, contract agreements, claims review, advertising review, and consumer complaints (adverse event repo11ing). She is identified as the firm contact for the overthe-counter drng product recall injtiated by Gulhy-Renker LLC (Palm Desert) in November 2011 and has been with Guthy-Renker for approximately 15 years. 6 rovided some information on the on-going product recall, information on knowledge of product stability failures, consumer complaint involvement, and Master Agreements held with contract vendors . ..__._,_"'""'--:;;o~s;.:o;..:r.:.: ts:...t;.;.:o~M .;.:;. r. Dirk van de Bunt, Ewcufive Vice President and ChiefAdministrative . .._.._.__,___ _~operates out of the Santa Monica office. Robaun (NMI) Rollius) Se11i.o1· Director ofJ11ve1tto1y, Quality Control a11d Ordel' Mauage111e11t, has been with Guthy-Renker for approximately 15 years and has been with the quality department for 6 years. She has hire/fire authority for her direct reports, spending authority for her areas of responsibility, and now reports to Mr. Walter Gross, Vice President ofFuljillmenl. Ms. Rollins has responsibility for the Quality Control department which is based out of the Palm Desert office. Quality Control/Quality Compliance (QC) responsibilities include vendor audits, out-ofspecification result<>, deviations, quality agreements with contract vendors, customer service review, and since approximately October 2011 , product stability. Ms. Rollins also has knowledge of coding and kitting activities associated v11ith fu lfillment center packaging activities. Ms. Rollins provided 9of41 Establishment Inspection Report Guthy-Renker LLC Santa Monica, CA 90405-3268 PEI: EI Start: EI End: 3007513615 11/07/2011 01/06/2012 some duplicate stability information previously provided by K. Maderazzo, some information on QC and QA procedures, information on coding practices for product kitting at fulfillment services locations, information on quarantine of recall product at warehouse locations, and some information on change in department responsibility for product stability. Ms. Rollins later corrected her title and said that she no longer has responsibility for Order Management. (William) Keith Nelson, Director of Quality Control, has been with Guthy-Renker since 2007 and has been in his cmrent position since January 2009. Mr. Nelson has hire/fire authority for his areas of responsibility which include contraci vendor audits; deviations and associated investigations; document control; escalated complaint review and investigation; and stability since approximately October 2011. Mr. Nelson said that he does not have spending authority. He reports to Robann Rollins, Sen;or D;rector ofJnvent01y, Quality Control. Mr. Nelson provided information on investigations into logged deviations, training practices for Quality Compliance employees, contract vendor audits and FDA inspectional observations, and information on draft stability procedures. Mr. Nelson operates out of the Palm Dese1t office. Dale W. Snider, Director of Global Freight mu/ Logistics has been with Guthy-Renker for approximately 13 years and bas been in his current position for 4 years. He reports to Andrea Anderson, Vice Pres;dent ofSupply Chain. Mr. Snider reported his responsibilities to include oversjgbt of movement of all large freight (bulk distributed) products including over-the-counter, cosmetic, and dietary supplement products. Mr. Snider has hire/fire and spending authority for his areas of responsibility. Mr. Snider provided jnformation on warehouse locations, product warehousing and distribution information, and provided shipping records for selected products covered during the inspection. Mr. Snider operates out of the Palm Desert office. FIRM'S TRAINING PROGRAM Guthy-Renker does not have a company-wide written training procedure. SOP QC-045: "GR QC Training Procedure" is a draft procedure which Mr. Nelson, Director of Quality, said was being implemented only for the Quality Compliance (QC; formerly Quality Control) department (Exhibit 10). Training recommendations were discussed with department representatives during the inspection and again with firm management during the closing discussion on 1/6/12. A summary of training programs for Santa Monica based departments is included below. Product Development (PD) Ms. Maderazzo said that GR PD does not maintain training files for its empJoyees. Ms. Maderazzo stated that new PD procedures are discussed and created in department meetings with employee input. I mentioned to Ms. Maderazzo that training files should be kept for employees involved jn quality-related functions to document training that is received. Consumer Affairs 10 of 41 FE!: EI Start: EI End: Establishment Inspection Report Guthy-Renker LLC Santa Monica, CA 90405-3268 3007513615 11/07/2011 0110612012 Ms. Elkins said that training files were not maintained for GR Consumer Affairs employees. Ms. Elkins reported that training for call center employees is h·acked through sign-in sheets at the call center locatio11s which are used for billing back to GR. Ms. Elkins stated that call center employee training is provided via multiple formats including training sessions, on-the-job training and information sheets. Training is provided at the call center locations by GR representatives or by the call center's in-house trainers using training materials prepared by GR. Examples of some of the training tools used for call center employee training were provided by Ms. Elkins and are included in Exhibit 11 . .MANUFACTURING/DESIGN OPERATIONS Guthy-Renker LLC is a d irect marketing firm that distributes finished products to consumers and further distributors. These products incJude over-the counter topical acne drug treatments, cosmetics, and dietary supplements (vitamins) which are manufactured by contract vendors mainly in the United States. The locations visited du1ing the current inspection consist of Corporate Headquarters locations in Santa Monica and Palm Desert, California. No manufacturing, analytical or microbial testing, or product ·warehousing occurs at these locations. GR personnel wl10 have involvement in and oversight for quality control, product development, and consumer complaints of distdbuted products are located at the corporate headquarter facilities: Quality Compliance (QC) at the Palm Deselt Jocation and Product Development and Consumer Affairs (complaint handling) at the Santa Monica location. The Quality Assurance depa1tment which was previously involved \·Vilh oversight of the drug product stability program was tenninated in 2008 (Exhibit 12). Dnring the inspection I focused on GR LLC corporate-based quality system operations including oversight of the OTC drug product stability pro&1ram and consumer complaint handling. I reviewed stability testing results for OTC drug products, consumer complaint logs and associated complaint files, and related GR procedures. The QC department's responsibilities include u-acking and investigation of product and process deviations, performing audi ts of contract vendors, working with the consumer affairs department on consumer complaint issues, and more recently oversight of amrnal product stability. Mr. Nelson said that prior to October 201 1 product stability was not included in his responsibi lities. While reviewing stability information I became aware that contract_vendor ad received a FDA 483 in March 2011 for stability issues related to manufactured OTC drug products. Exh ibit 13 contains the letter from . ddressing incomplete stability study data which refers to the FDA fospection. Per JV[r. Nelson lotified GR about the inspection and meetings were held to discuss corrections and the firm response to the listed observations. Ex hibit 14 contains e-mail conununication and sup ortin documentation between GR and ·elated to the ·nspcction. J asked for a copy of the DA 483 and was provided a redacte copy include m Exhibit 15. I asked Mr. Nelson how he determined which observations were related to GR products and he mentioned that meetings were held between nd GR to discuss the inspection. 1 was to ld that 11 of 41 FEI: EI Stmt: EI End: Ji:stublishmcnt Inspection Report Guthy-Renker LLC Santa Monica, CA 90405 -3268 3007513615 11 /07/2011 01 /06/2012 no meeting minutes were maintained for these meetings. I asked :Mr. Nelson to provide information on GR products that were involved in the bscrvations and was provided a partial FDA 483 (Exhibit 16); Mr. Nelson said that he had to request the information from The provided document indicates that GR products were affected by Observation 1 which dealt with stability testing. GR QC did not appear to inquire if any GR products were redacted from the supplied lnspectional Observations to determine if contract vendor practices affected products manufactured for GR. I discussed the lack of knowledge of GR affected products with Mr. Nelson and Ms. Rollins during the inspection. I suggested that GR should find out if their distributed products are involved in contract vendor inspectional observations and suggested that fuhtre di scussions related to manufactured products be documented . are .included in Observations 2-6 of the issued FDA 483. Qua lily system observations . . MANUFACTURING CODES Codes applied to finished products distributed by GR and its subsidiaries consist of a manufacturing code and expiration date when applicable. A list of alpha codes used by contract vendors is included in Exhibit 4. Examples of codes for finished products reviewed dwing the inspection are as follows: Proacliv Concealer Plus Light shade (over-the-counter drug product; sulfur 8.5%), "T1230A" EXP 07I14 where: --~~~~~~~~~~~~~~~~~~~~~~~~~-, COMPLAINTS Consumer complaints for finished products distributed by Guthy-Re11kcr LLC and its subsidiaries are handled by t11e Guthy-Renker Consumer Affairs department based in Santa Monica. Ms. Elkfos, D;rector ofConsumer Affairs, repo1ted that consumer complaints can be received 24 how·s a day 12 of 4 J Establishment rnspection Report Guthy-Renkcr LLC Santa Monica, CA 90405-3268 FEJ: EI Sta11: EI End: 3007513615 1 l/07/201 l 01 /06/2012 tlu·ough call centers, mail , review of social media and website submission forms. Incoming calls are handled by call center personnel located at Guthy-Rcnker Fulfillment Services locations (Arden, No1th Carolina and Foothill Ranch, CA as well as th.ird-pruty call center locations operated by ·n nd Ms. Elkins said that social media sites (facebook, twitter, etc.) are reviewed for consumer complaints by. 6 Ms. Elkins stated that call center employees wil! handle general complaints including refunds, cancellations, and basic quality concerns (i.e. damaged shipments) but when complaints are of a more serious nature, indicate legal involvement, or indi cate customer repmis to outside entities (i.e. Food and Dmg Administration, Better Business Bureau, etc) then they are to be escalated for furt11er review to the adverse events team in Arden, North Carolina and/or to Consumer Affairs in Santa Monica. Ms. Elkins said that when a consumer identifies an associated product Jot, the complaint is forwarded to GR QC to obtain the manufactured product's Certi fkate of Analysis. Exhibit 17 contains flow charts provided by Ms. Elkins which outline the complaint escalation process. Ms. Elkins reported holding weekly calls with a consultant Medical Advisor, to discuss complaints and help deteimjne if reported adverse events are ser:ious adverse events. The Medical Advisor's resume is included as Exhibit 18. 11.-..~..o.4.o----' During the inspection Ms. Elkins stated that only one MedWatch report had been filed since she started working with GR. Med Watch reports for 'omplaints which liad been filed by the company since 2009 were provided for review; a b) ( ·eport could not be located. I searched the yearly complaint logs, and yearly and monthly trending data (Exhibit 19 and 20) for complaints ·which appeared to indicate possible serious adverse events. I requested copies of complaint files for seve1:al complaints related to distributed over-the-counter drug, cosmetic and dietary supplement products. Ms. Elkins informed me that none of the complaints I requested had been reported through Med Watch. Failure to properly handle and report serious adverse events related to use of dietary supplements and over-the-counter drug products arc included as Observations 1and2 of the issued FDA483. Ms. Elkins said that there is currently no official annual review of complaint data however complaint trending logs are maintained on a basis. Ms. Elk.ins said that she reviews the trending reports and compares the number of incidents to number of units so ld during that time period. Ms. Elkins said that she would take additional action if the percentage of complaints for a given product was greater than one percent; however the complaint frequency had not reached that limit for any of the products since she has been in her position. Lack of an annual product revievv is included as Observation 5. Tluee complaints are listed in FACTS for Guthy-Renker distributed WEN hair care products. The compJaints (Santa Monica: 123249; and Palm Desert: 121463, 122653) indicate customer use of WEN cleansing conditioner followed by large amotmts of hair loss. Ms. Elkins and ..___._.__.___ __. GR General Counsel, were aware of complaints, in general, associated with use of \\TEN. Ms. Elkins said that hair loss cao be due lo nd stated that if the customer is still using the product they are advised to stop further use. _...._&.-_,said that GR had !tired an outside consultant to review the product for possible causes of 13 of 41 Establishment Inspection Report Guthy-Renker LLC Santa Monica, CA 90405-3268 FEI: 3007513615 EI Start: 11107/2011 01/06/2012 El End: hair Joss. I reviewed two deviation files that indicated The investigations indicated that product had been sent out for testin an outside lab and included a letter from outside consultant, The letter dated 3/3 1/09 indicated review of product fonnulations and fragrances, and concluded that .... ~r-l.,;,,J_.-------------------------- ·om pIaints should be monitored to assure no increase in complaints. A copy of the consultant summary is included in Exhibit 21. Label proofs with ingredient listings for WEN cleansing conditioners are included in Exhibit 22. ':'-'--<.~----------- RECALL PROCEDURES Gu thy-Renker 1rns a RecalL/Market Withdrawal Procedure, QC-034, effective 10/15/ l 0 (J~xhibi t 23). GR LLC, Palm Desert, initiated its first recall in November 2011 and worked with the LOS-DO recall coordinators for communication ofrequired infonnation. The recall was initiated for over-thecounter acne drng products which failed to meet label claim for active ingredient throughout the products' applied expiration period. The initial recall included multiple lots of Proactiv Renewing Cleanser (benzoyl peroxide, 2.5%; sub-potent; 2 year expiration), Proactiv Repairing Lotion/Treatment (benzoyl peroxide, 2.5%, sub-potent; 2 year expiration) and two lots of Proactiv Concealer Plus (sulfur, 8%, super-potent; ltu·ee year expiration period) which were manufactured by multiple contract vendors within the United States. The Concealer product recall was expanded during the cmTent inspection after an additional lot of light shade (lot T l 230A) tested out-ofspeciffoution at the 3 month test interval. Information on the recaU for Proactiv Renewing Cleanser and Proactiv Repairing Treatment along with a search funclion for affected product lots can be found · at W\>V\V.pabottlereplacement.com. OBJECTIONABLE CONDITIONS AND MANAGEMENT'S RESPONSE On 116/2012 a 6-item FDA 483, Inspectional Observations, was issued to Mr. Bennet M. Van de Bunt, Co-CEO of Guthy- Renker LLC. Mr. Van de Bunt identified himself as the most responsible individual for the firm. Also present during the closh1g discussion were: Dirk van de Bunt, EVP and ChiefAdministrative Officer; General Counsel; Shelly Elkins, Director of Consumer Affairs; and Robann Rollins, Senior Director o Inventory and Quality Control. Keith epresentatives ( 11..0J~----~ 6 Nelson, Director ofQuality Compliance, and ( and were all present via conference call. Firm representatives and associated cotmsel were notified that the issued FDA 483 contained my observations and did not represent final agency determination of the firm' s regulatory status. The firm representatives were informed of sanctions available to the FDA including waming letter, regu1ato1y meetings, fines, seizure and injunction should the finn be found to be in violation of the FD&C Act. I informed firm management that the listed observations were not all-inclusive of deficiencies that may exist al their fitm and informed them that it was their reSJ)Onsibility to ensure that GR adhered to government regulations for regulated products. 14 of 41 1 FEI: EI Stm1: EI End: Establishment Inspection Report Gulhy-Renker LLC San1a Moni ca, CA 90405-3268 3007513615 J 1/07/2011 01/06/2012 Finn management was informed of their option to subrnit a written~Angeles District Office, via the District Director, within 15 business days. - - - - - General Co unsel, said and Mr. B. Van de Dunt nodded in agreement that a written response would be 1 submitted. calculated the 15 h business day lo fall on January 27, 2012. Observations listed on form FDA 483 ODSERVATION 1 You did not follow writ1en procedures for the requirements to review and investigate a product complaint. QC-032 "01stomer Compla ints Procedure" (effective l 0/18/10) includes guidelines and responsi bilities for handling consumer complai nts inc lud ing reports of serious adverse events. Consumer complaints, associated with use of dietary supplements, w hich meet the defined criteria for serious ndversc events are not classified as such fo r reporting through the Med\Vatch system. Reviewed complaints include: ____ __, a.) Customer complaint 101001-018364 received on 10/1/10 for a vitamin reaction with medication causing internal bleeding w ith hospital visit. The complainant repo1ted use of Sheer Cover Daily Plus vitamins. ___...... b.) Customer complaint 001030862/\ received on 10/18/1 I for J10spitalization due to ..._,'-'-....__ complainant reported use of Vitae Iear Da ily Multivitamins. The Reference: 21 CFR 11 1.553 Supporting Evidence and Relevance: Exhibit 24 contains QC.032: "Customer Complaints Procedure", effective 10/18/ 10, which identifies responsibilities and processes for handJing adverse events. The procedure defines a serious adverse event as one which "(A) results in .. . (ii) a life-threatening experience, (iii) inpatient hospitalization ... or (B) requ1res based on reasonable medical judgment, a medical or surgical intervention to prevent an outcome described in (A) above." Exhibits 25 and 26 contain consumer complaint records listed in the Observation along with supporting documentation (GMP forms, MedWatch rcpm1s, etc.) and product specification infonnation. 15 of 41 f....d-----' vhich required treatment at a hospital facility. The complainant repo1ted use of OTC acne treatments Proactiv Renewing Cleanser and Proactiv Repairing Treatment (active ingredient: benzoyl peroxide). The complaint, which appears to meet the defmed criteria for a serious adverse event, was not classified as suell for reporliog tbrough the .MedWatch system. Reference: 21 CFR 2 l l .198(a) Supporting Evidence amJ Relevance: See Exhibit 24 for QC-032: Customer Complaints Procedure, Effective I 0/ 18/10. Exhibit 27 contains 1hc complaint repo11 and related documentation for customer complaint 100311000054 which was provided by Ms. Elkins. QC-032: "Customer Complaints Procedme", effective I 0/18/ 10, outlines complaint handling guidelines and responsibi lities for "al1 products marketed by GR LLC ... including complaints for OTC drug products". Section 5.5 of QC-032 defines a serious adverse events to incJude "An adverse Drug Reaction Event that (A) results in (i) death, (ii) a Ji fe threatening experience, (iii) inpatient hospitalization, (iv) a persistent disability or incapacity, or (iv) a congenital anomaly or birth defect 17 of 41 FEI: Establishment Inspection Report Guthy-Renker LLC 3007513615 11107/201 1 01/06/2012 EI Start: EI End: Santa Monica, CA 90405-3268 or (B) requires, based on reasonable medical judgment, a medical or surgical inte rvention to prevent an outcome described in (A) above." The Consumer Affairs department, in conj unction with general counsel and GR' s consu Itant Medical Advisor are not always classifying escalated complaints as serious adverse events when they meet the criteria listed in QC-032. Failure to properly handle reported adverse events associated with di snibuted dietary supplements can lead to serious adverse events not being reported through the MedWatch system. Discussion with Management: During the inspection I discussed with Ms. Elkins and the requirements ofrepo11ing serious adverse events associated with use of dietary s upplemen ts and over-the-counter drug products. I shared g uidance document criteria that indicate factors that could be considered a serious adverse event and mentioned that simi lar ctiteria are listed in GR's QC-032. I further explained that the criteria for repo1iing did not require confirmation that the disttibuted supplement caused the serious reaction only that the complainant reported the reaction and the product to be linked. I explained the purpose of Med Watch as a monitoring system and explained that filed reports were noi admi ssions that an associated product ca used the problem only that there may b e a connection between the serious adverse event and use of the product. I referred Ms. Elkins and~r-l.06..,__ ___. to the serious adverse event repo11ing guidance on www.fda.gov for additional infonna ti on on reporting serious adverse events. On 12/2111 1 Ms. Elkins said that GR was beginning to review past complaints to see if additional Med-Watch reports needed to be filed. Ms. Elkins provided one additional filed complaint packet for GR LLC distributed Sheer Cover Mineral Foundation SPF 15 (Exhibit 28). The complaint was received on 1118/11 for ith ER visit associated with use of the OTC drug product. The Med Watch form indicates filing occurred on 12/2/1 1. Dudng the closing discussion on I /6/12 finn management did not provide any additiona l details regarding corrective actions which bad been or were being implemented in response to the stated observations. confirmed that a written response would be submitted to the Los Angeles DistTict Office. OBSERVATION 3 The responsibilities and procedures applicable to the quality control unit are not in \\ riting and fully followed. 1 For example, per QA-012 "OTC Drug Product Stability Program for Production Batches" (effective 2/28/05) the stability testing program for over-the-counter (OTC) drug products distributed by your firm was handled by the Quality Assurance unit. In approximately J une 2008 the Quality Assurance unit w<1s discontinued. 18 of 41 Establishment Jnspection Report Guthy-Renker LLC Santa Monica, CA 90405-3268 fEI: EI Start: EI End: 3007513615 11107/2011 0 1/06/2012 Quality Assurance responsibilities related to oversight of the stability program and review of product stability dnta were not officially transferred to the Quality Control or Product Development depat1ment to ensure that finished OTC drug products distributed by your furn continued to meet specifications for safety and efficacy throughout their applied shelf life. New procedures covering OTC drug product stability were not drafled and/or implemented by Quality Control/Compliance until 2011. Reference: 21 CFR 211.22(d) Supporting Evidence and Relevance: Stability data results reviewed during the inspection (Observation 4) indicate that distributed overthe-counter acne drug products have experienced active ingredient stability failures as far back as 2004 \Vhen stability was still under the control of the GR Quality Assurance (QA) department. The QA department was terminated in 2008. Review of information provided by document controJ, revision hjstory of draft and implemented procedures, Quality Agreements and GR procedure tables of contents indicate that a new, interim stability procedure was not implemented for finished products containing benzoyl peroxide until October 2011. Additional stabil ity procedures being written by GR QC are still in draft form. /\.history of out-of-specification product stability test results combined with a Jack of communication regarding transfer of quality assurance responsibilities has resulted in a lack of oversight of the stability program by Guthy-Renker for distrjbuted over-the-counter topical drug products. On 11/10/11 Ms. Maderazzo stated that on-going product stability was handled by the Quality depaiiment Jocated in Palm Dese1t ai1d mentioned that a SOP for stability was currently being worked on. Ms. Maderazzo said that Product Development had created an interim stability procedure in October 2011 when it became apparent that there were issues with benzoyJ peroxide containing fini shed products. When I began my inspection of the Palm Desert location on 11/15/1 l I was informed by Ms. Rollins, Senior Director of Quality and Order Management, that no additional stability data was held at the Palm Desert office. Ms. Rollins said that t he QC department took over responsibility for product stability in approximately October 2011. She said that the Product Development department in Santa Monica had prior responsibility for product stability. After 1 met with GR QC I again spoke with Ms. Maderazzo who clarified her prior statement and said that Guthy-Renker Product Development (PD) was responsible for stability of pre-marketed products. She said that the PD department worked with contract vendors to gather information 011 products to determine an initial expiration date prior to product .launch. Ms. Maderazzo said that Product Development did issue PD-003: "Benzoyl Peroxide Containing Over-the-counter Anti-Acne Drug Product Stability Program (Production Batches)" in October 2011 when it became clear that the products were having stability problems. During the inspection I asked to review Quality Agreements held between Guth contract vendors. I was provided one quality agreement between GR and dated July 2009 (Ex4ibit 29). I was told that this was the only quality agreement held between GR and its contract vendors. Page 15 of the agreement contains Appendix 1, a list of Quality Contacts for Guthy-Renker 19 of 41 Establishment Inspection Report Guthy-Renker LLC Santa Monica, CA 90405-3268 FEI: 3007513615 EI Start: El End: 11/07/201 l 01/06/2012 and rhich lists Keith Nelson as the GR contact for QC Testing and Deviations (among other responsibilities) and Kimber Madcrazzo as tbe GR contact for Stability. The Quality Agreement also contains a list of GR SOPS for use in product manufacturi ng (Appendix IIJ, Exhibit 29, p. 17) which identifies QA -012 as the SOP for "OTC Drug Stability Program for Production Batches". Exhibit 30 contains QA-012 "OTC Drug Product Stability Program for Production Batches" (efTective 2/28/05) which indicates that stability oversight for distributed products was previously the responsi bili ty of Guthy-Renker Quality Assurance. QA-012 identifies that the "Director of Quality Assurance is responsible for implementing and monitoring the OTC drng stability program» (Exhibit 30, page 1, section 3.2) and that contract vendors are to submit completed Jong term stability reports to ''the Guthy-Renker research and development director along wieh all associated test documents" (ExhibH 30 a e 5, section 6.6. 1.4). ·The rocedure identifies these individuals on the signature page as and vho are no longer employed by GR. as terminated along with the QA department in 2008 (see Exhibit 12). Exhibit 31 contains information on QA procedures along with owners and target dates of completion. The list indicates that "KM" (Kimber Maderazzo) was the owner of QA -01 2 "OTC Drug Product Stability Program for Production Batches". Exhibit 32 contains additional information on QA SOP conversion provided by QC and document conh·ol. The QA SOP Conversion spreadsheet (Ex hi hit :n , p. 1) indicates that PD-003 "Pre-Production (Primary) Stability Program for OTC Drug and Cosmetic Products, due 9/1/20 11, replaced QA-012. The second spreadsheet (Exhibit 32, p. 2) further indicates progression of draft PD-009 becoming QC-022, QC025, and QC-026. · Exl1il>it 33 contains a version of QA-12 relyped in 2009 by Cheryl Martinez who is the current QC and lnvent01y Control Manager for GR2 (a division of GR LLC). Ms. Mru1inez reported that when QA employees were terminated the QA roles and responsibilities were trnnsferred to Quality Control and Product Development. Ms. Mmiinez sai) (4) - 1-8 ., ~ ' 't9352A 2;:23, .2. rs 12, 18 ')--:XPl 2/l 1 T0013A ---' ': 2::14 'tt229B' 20.tl t 123oi3· :OK A'.f 2 201:1 2010 T1230A AP0056A; AP0057A AP0071A; AP0072A .. ';:.** .. I 2010 ,______ ":. i • . - ·2.i1, 2.J4 '· ' .·u» <4> ·t9244A,J;5 . - 2.15 f2, 18 OK AT 2 MONTHS 2010 2011 .... ;(b) (4) - .. :.z;is . - · 18 . oz " - ·:T9244A, 2 ;.01! ' 2.5%; SPEC. 2.25-2.75%) (24 MONTH EXP.) . -~999 :*·* 2010 .'"*' .2010 2010· .. ··2010 .. .20i0 .. - --. • 1 . !f<>!< '*"' -- 18 2.06 18 2.14 1_$.:Mo : or<.·(~OW) :1S¥'0NTl-I(~<)Wj ·t8}v10N11t.(kOW) . .·'· l sJ;;1dNTH (I :o\y)_' ··lS.; M;.ONTff{~OWJ- ' ·•. ... .. ' .. •. - 24 of 41 - .. ' . .. . .. 'i 8·MONTH (~OW} . ·12 ·· : · " .,. ** ·** ' -. ·OK AT 2rM.0NfrHs -· . ~010 - MO°&tHS J 222 ·. . . ., ..... .. .. .. .. . d Establishment Inspection Report Guthy-Renkcr LLC FEI: 3007513615 El Start: Santa Monica, CA 90405-3268 ETEnd: 11107/2011 OJ /06/2012 · J2oro ] ** ** Stability summaries do not list finished product lot codes. I. I asked for associated .lot codes but did not receive the information during the inspection. Uepairing Treatment/Lotion GU0902002 (KO) (4) Reviewed stability data did not reveal any OOS data points for this formulation which was first manufactured in 201]. Products ecifications are included in Exhibit 79. Stability summary data are included in Exhibits 80-81. from and Please refor to the "Additional Information" seclion for infmmation provided on the overage formulations . b-d.) PROACTIV RENEWfNG CLEANSER Exhibit 82 contains a spreadsheet showing formulation progression for Proactiv R.enewing Cleanser. Exh ibit 83 contains label proof examples for Proactiv Renewing Cleanser (Benzoyl Peroxide 2.5%). A two year expfration period was initially applied to the distributed finished product marketed in the United States. The expiration period was reduced to 1 year in May 2011 for some fonnulations. Renewing Cleanser formula P0409 d(b) (4fl A sununary of annual stability data is included in the table below. Product specifications are included in Kxhibit 84. Stability summaries and raw data are included Exhibits 85-106. The provided stability data indicate that the finished product was not meeting !he product's applied expiration date for active ingredient assay since approximately 2004. in MFG/formula LOT!l!:XP YEAR TEST POINT OOS MFGD. :Kb) (4) '· 2004 ··T4322A · EXPH/06 t4~.3~A ,__,.,..----~-i-.-~-~.....,,·~,E~ "X,.,P._~t-~l_lO~ __ (24 MONTH EXll.) 18, 24 - 2 .f3;.2.•03 ·No JSffioiltli'test; 24. :2.10. -~-'- . '; 2005 · T5194B 24 18 ·24 ' 200fr · 1~0llA }8; 24 20Q5 '2007 ··:··' .-: '.2008 2009 . .. . . . t5193Aj 8xro7101 EXPOl/0.8 T7152A ASSAY RESULT (BPO 2.5%; SPEC. 2.25-2.75%) ·- 2.13 ·;::. .· . :2,18; 2.04 l--,-~--;.,-~~-'--~~~__,.--~-,-,.--'-=---:---=-'~-1 . l8~;24.. . :1;01:; L88. . T80l5A ·· :EXi>ourn T9047A · 12, l8, 24· EXx>02/l l . . · ··2·.08, L86; l.79 ·.·-.,-- ff2~T8_·.'-----....i.....:..f_.1_:0,_.2'-·,_o_.·2 ._·_··--~ ..__ - -_ _____.... '· ·_:.2_0_1_0_ . -'-'-:T_·a_OlS·B _... 25 of 41 FEI: EI Stm1: EI End: Establishment Inspection Report Guthy-Renkcr LLC Santa Monica, CA 90405-3268 ~~'IJ ~~) · EXPOi/J~ I I 2007 AP724813; AP7249A; 3007513615 11/07/2011 01 /06/2012 .) frn - ' No 9 month test; 12 AP7253A ' 2007 AP7247A; AP7248A No 9 month test; 12 2.19 2007 AP7250B; AP 725IA No 24 month test, 36 NA;l.85 2007 AP7310A 18,24 2008 AP8029A; AP8030A 12, 18, 24 2.1]' 2.08 2.24, 2.07, 2.01 2008 AP8024A; AP8025A 18, 24 2.08, 2.00 2009 AP9159A; AP9160A; No 18 month, 24 NA; 2.03 AP9161A ·, 1.818 (raw, p.4) AP91315B 24 month 2009 AP9132A; AP9133A; AP9134A No 12, no J.8, 24 NA; NA; 1.94 2010 AP0025B 12 2.22 ;2010 'L9035Al ·RXP 01/20ll -(OO l 2A ·2n11 ..t1d80A • - 2009 0 (b) (4) I 2009 24; -- - rs at$pe'c,of 2:2s W29@ 9 month~ ---· :2:29@.9'monfhS; l& - -· --\. )"!lonth not ,performed , . 2::16 •. - - __ _____:. Ueoewing Cleanser GR0902300 ([b) (4[) A smmnary of annual stability data is included in the table below. Product specifications are included in Exhibit 107. Stability summaries and raw data are included in Exhibits 108·110. VEAR M.li'G/formula LOT/EXP MFGD Kb} (ii) I 2010 2010 T0197A EXP07/12 T0194A TEST POINT OOS (24 MONTH EXP.) -Not OOS at I 2 month ASSAY RESULT (BPO 2.5%; SPEC. 2.25-2.75%) NA (2.26) study cancelled; 12 2.23 12 2.16 EXP07/12 2010 T0196A . EXIJ07/12 _l_ --· 26of41 Establishment Inspection Report Guthy-Renker LLC Santa Monica, CA 90405-3268 FEI: EI Start: 3007513615 El End : 01 /06/201 2 11/07/2011 Rencwin Clennser GRll02600 No stability data reviev.red. Ms. Maderazzo said that product has not been marketed. Specifications are included in Exhibit 111. · Renewing Cleanser GR0902700 ( A summary of annual stability data is included in the table below. This is the first Proactiv Renewing Cleanser formulation to use The provided stability data indicate t ha.... t 1-=-h-e-=fm :---;fa"""" h-ed..,p1-·o"""d-uc_t_w_a_s_n_o_t ,-n-ee_t.,.. m_g_i··ts-a-p"""" - p ""'1e- .-e-x_p_u -at...1on date for active ingredienL assay since 2009. Expiration of some pa11 numbers was reduced to 12 months beginning in May 2011. Expiration for some prut numbers was fu1ther reduced to 6 months in November 2011. Product specifications are included in Exhibit 112. Stability summaries and raw data are included in Exhibits J 13-129. -- YEAR MFG/fonnula TEST POINT OOS (24 MONTH EXP.) LOT/EXP :MFGD . 1·200,9 I D) (4) . ·200.9 ··2009 - ·, 2010 f oz 'T9245..t\:; "'t9245A; 2 ·oz T9245A·; 6 oz . •, I ~ i• ,1 •; - T0070B ~. 12, 1°8 ~. 12._ , 18 2010 I .. 20l 1 'Tl216A**** .. 20H : Tl~14A*"'~' * 2009 I A9363A I. A9364B·, A9365A 2009 2009 "Kb) (4) ;_tot47A r;~q~/1 1 . J b) (4) I I ;2(>"10 ·· :rz . APOOI"3A ., · 12 2 010 . A1~00.5 3B· .. . 2ot'o ,. ,APQ054A UN.KNOWN . '.1i ·:· ~ ) ·?:2-1 ~. 2;:0.~~ L93 . I -- ·2;i&):oo - - !· i --:-- ---,- 2.2.0 : '· ·+'l'A '•'. .. .. 2.24 . ' 2.14 --"- --· 2.17; 2. 19 and 2. 12 - - - -· 18 nio ok.(2:3"34). ' .. ?·'7 .. 2:-12 -~ - -. . '· .. ·1'i-e!1ding fow UNKN0\\7N· 12 mo.ok (2:28) . .. ' *** *Testing perf01med at contract labJb) (4 on (D) (4) lmanufactured product. Lots not 20l0· dJStnbuted Rcnewin J Cleanser GR0902700 27 of 41 II I -:i 99 ·: 18 - ' J m:onih. .ok . .(2.53%) . '3 -18 18 month ok (2.34%) Validation lots -·- :2':21 , i.1.'2~ t;93. ,_ 11, 1'8 18 " -EXP3/12 \•', ASSAY RESULT (BPO 2.5%; SPEC. 2.25-2.75%) - --·.:. I I FEI: Establishment Inspection Report Guthy-Renker LLC Santa Monica, CA 90405-3268 EI Start: EI End: 3007513615 l 1/0712011 01 /06/2012 Reviewed armual stability data did not reveal any OOS data oints for this formulation which was APl l lOA) and T1042B, T1043D exp 2113). Product first manufactured in 2011 by specifications were not obtained for this overage formu at1on. Please refer to the "Additional Infmmation" section for i11fonnation provided on the overage formulations. Rcncwin Cleanser GR0902702 Reviewed stability data did not reveal any OOS data points for this formulation which was first manufactured in 2011 with a reduced 12 month expiration period. Jn November the expiration period was fu11her reduced for some part numbers to 6 months. Product specifications are included in Exhibit 130. Lots placed on stability did not receive an expiration date (Exh~bit 131). Please refer to the "Additional Information" section for infonnation provided on the overage formulations. c.) Proactiv Concealer Plus Exhibit 132 contains specification and label information fOJ Proactiv Concealer Plus. A tlu·ee year expiration period is applied to finished product distributed in the United States. The product is manufactured at only one contract vendor, The product is manufactured in four shades of one formulation with a label claim of 8% sulfur. Exhibits 133 tlu·ough 147 contain stability summa1y reports and raw test data for out-of-specification test points for: light. medium, mediumdark, and dark shades of the finished product. Exhibit 148 contains a list of Concealer lots distributed by GR LLC over the past three years. Exhibit 149 contains info1mation on quantities of Concealer received by GR from contract vendor A summary of annual stability data points for Proactiv Concealer Plus LlGHT (Exhibits 133-138) can be found in the below table. The provided stability data indicate that since approximately 2009, finished product was not meeting specifications for active ingredient assay. LOT/EXP TEST ASSAY RESULT (SULFUR CLAIM YEAR POINT MFGD. 8%; SPEC. 7.20-8.80%) oos (36 MONTH EXP.) 2006 2007 2008 2009 2010 I 20 11 T6171A T7082A T8044A EXP02/ .l I T9062A EXP02/12 T0 198A EXP07/ 13 Tl230A EXP07/ 14 9.15 9.43 . 10.86 36 18,24,30 8.89; 8.96; 9.68 NOT OOS at 12 months 7/21 / J 1 (8.65%) 3 j 9.10% 36 36 A summary of annual stability data points for Proactiv Concealer Plus MEDIUM (F:xhibits 139144) arc found in the table below. Armual stability study data for Proaciiv Concealer Plus Medium 28 of 41 FBI: Establishment Inspection Report Guthy-Renker LLC Santa Monica, CA 90405-3268 El Start: EI End: 3007513615 11/07/20 11 0110612012 in 2006, 2007, and 2008 indicate that the product was out-of-specification for active ingredient sulfur assay by the 30 month test interval. The product has a labeled expiration period of3 years. This shade was not included on the issued FDA 483 due to the fact that stability data for currently marketed product is not exhibiting stability failures. Firm representatives were infom1ed that they should closely monitor stability results of recall-related products to ensure that they remain within specification. YEAR LOT/EXP MFGD. 2005 T5047A EXP02/08 2006 T6172A EXP06/09 2007 T7058A 2008 T8011A EXP12/10 2009 T9044A EXP02/12 2010 Three lots (T0078A; T0342A; T0343A) distributed by GR LLC (See Exhibit 148). 2011 T1200A EXP04/14 TEST POINT OOS (36 MONTH EXP.) ASSAY RESULT (SULFUR CLAIM 8%; SPEC. 7.20-8.80%) 1,2,30 9.05; 9.11; 9.11 30,36 9.89; 10.12 30;36 9.53; 9.53 24;30;36 8.98; 9.75; 10.2 1 Not OOS at 30 months (8/19/ 11; 8.63 %) No data provided * Not OOS at 3 months (10/22/ 11; 8.72%) A summary of annual stability data points for Proactiv Concealer Plus MEDIUM-DARK (Exhibit 145) is found in the table below. The provided stability data indicate that lots manufactmed in 2008 were not meeting specification for active ingredient assay throughout the applied shelf life of 3 years. Additionally, stability data was not provided/maintained for lots manufactured in 2007 and 2009 (Observation 6). ASSAY RESULT YEAR LOT/EXP TEST POINT OOS MFGD. (SULFUR CLAIM 8%; (36 MONTH EXP.) SPEC. 7.20-8.80 % ) 18,24,30,36 9. 10; 9.05; 9.83; 9.98 2008 T8053A EXP02/11 Two lots (T9254A; 2009 No data provided * T9257A) distributed by GR LLC (See Exhibit 148). A sununary of annual stability data points for Proactiv Concealer Plus DARK (Exbibits 146-147) is included in the table below. The provided stability data indicate that lots manufactured in 2007 and 2010 were not meeting specification for active ingredient assay tlu·oughout the applied shelf life of 3 years. Additionally, stability data was not provided/maintained for lots manufactured in 2008 (Observation 6). I YEAR ILOT/EXP ITEST POINT oos 29 of41 IASSAY RESULT Establishment Inspection Heport Guthy-Renker LLC Santa Monica, CA 90405-3268 MFGD . 2007 (36 MONfH EXP.) FEl: El Start: 3007513615 El End: 01106/2012 11 /07/2011 - (SULFUR CLAIM 8%; SPEC_. 7.20-8.80%) ---- 2008 T7046A 36 Two lots, T8047A and No data provided T8309A, distributed by GR LLC (See Exhibit 148). 2009 NA No lots distributed 2010 T0119A EXP04/ 13 12 9.35 * ·- 9.39 During the inspection and again during the closing discussion with management on 1/6/12 I mentioned that some of the reviewed data indicated trending of assay results to either decrease (benzoyl peroxide) or increase (sulfur; concealer) and would need to be monitored to ensure that non-recalled fornrnlations stayed within label claim for their applied shelf life. r s uggested that should products appear to be trending to the high or low extremes of the specification, additional uency and/or placement of additional lots testing may be wmrnnted lo include increased testing freq_ on stability. I also mentioned that appropriate action should be taken if add itional lots or products are not meeting label claim thr011gh their applied shelf life. Discussion with Management: GR contacted LOS-DO Recalls to initiate a recall of Proa(;tiv Repairing Trc'1lmcnl/Lulion, Prnacliv Renewing Cleanser and Proactiv Concealer Plus prior to the inspection. The recall was launched by GR during the inspection on November 22, 2011. The recall for Proactiv Concealer Plus was expanded during the inspection after lot T 1230A (light) was fow1d to be out-of-specification at the three monlh test interval. During the closing discussion on 1/6/12 finn management did not provide any additional details regarding conective ac!ions wl1ich had been or were being implemented in response to the stated observations. 6 onfirmed that a w1jtten response would be submitted to the Los Angeles District Office. OBSERVATION S Written procedures are not established for evaluations done at least annually and including provisions for a review of complaints, recalls, returned or salvaged drug products, and investigations conducted for each drug product For example, your firm does not have a procedure which covers requirements fo r annual drug product review and no ammal drng product review is being conducted and documented for consumer complaints and associated investigations which are handled at the corporate level for over-the-counter drng prnducts manufactured by your contract vendors. 30 of 41 FEI: EI Start: EI End: Establishment Inspection Repor{ Guthy-Rcnkcr LLC Santa Monica, CA 90405-3268 3007513615 11 /07/2011 01/06/2012 Reference: 21CFR211.180(e)(2) Supporting Evidence and Relevance: Exhibit 150 contains Tables of Contents for Guthy-Renker LLC procedures. The firm does not have a wiitten procedure detailing requirements for an annual product review of drug products and is not conducting annual product review for quality functions which are handled at the corporate headqui:irter level including consumer complaints (Consumer Affairs), product recalls (legal and QC), and investigations for drng product deviations (QC). On 11/15/11 Ms. Rollins said that no annual product review was being conducted by the Quality department. She also stated that GR does not review the annual product reviews conducted by contract vendors of GR products. I explained to Mr. Nelson and Ms. Rollins that since GR conducts quality functions which require an annual review GR would need to have procedures iJ1 place and conduct amrnal product reviews for quality operations related to distributed OTC drug products. I mentioned that the review should include consumer complaints, recalled products, stability trending of marketed products, and investigations into product deviations. I also explained that since GR and its subsidiaries use multiple contract vendors conducting an annual product review and/or reviewing the ammal product reviews completed by the contract vendors may provide additional information on trends in product manufacturing. Discussion with Management: . During the closing discussion on 116/12 firm management did not provide any additional details regarding corrective actions which had been or were being in1plemented in response to the stated confirmed that a written response would be submitted to the Los observations. Angeles District Office. OBSERVATION 6 An adequate number of batches of each drug product are not tested nor are records of such data maintained to determine an approptiate expiration date. For example, a.) No annual stability study data was maintained for distributed lots of Proactiv Concealer Medium-Dark (sulfur 8%) manufactured in 2009 (T9254A, T9257A) which are given a three year expiration period. b.) No annual stability study data was mainttlinecl for distributed lots of Proact iv Concealer Dark (sulfur 8%) 31 of 41 Guthy-Renkcr LLC EI Staii : 3007513615 l 1107/2011 Santa Monica, CA 90405 -3268 El End: 01/06/201 2 FEI: Establislnnent Inspection Re1rnl"t manufactured in 2008 (T8047A, T8309A) which are given a three year expiration period. c.) No am1ual stability study data was maintained fo r distributed lots of Proactiv Concealer Medium (sulfur 8%) manufactured in 2010 (T0078A; T0342A; T0343A) which are given a three year expiration period. Reference: 21 CFR 211. 166(b) Supporting Evidence and Relevance: Stabilily summ aries reviewed during the inspection revealed gaps in annual stability data for some distributed products (r efer to Observation 4). Jcross referenced the missing data with information provided on distributed produ ct lots and found that there were years in whjcb product was m anufactured for distribution but no lots were placed on annual stability. Some of the stability gaps that I mentioned to firm management incJude: lack of annual stability data for years in which product was manufactured; lack of stabiiit testing at appropriate intervals during shelflife for products and lack of s ta bility data covering all dis.t rjbuted product manufactured by contract vendor sizes. I explained to firm management that at all times GR should have data to fully s upport the expiration dates applied to marketed over-the-counter drug products. I explained that due to changes in contract vendors, employees, and m aterials, stability data suppo1t of applied expiration dates should be looked at as a continuous life-cycle approach rather than a one-time occurrence. I discussed that this should take in to account testing of representative sizes (bracketing; as p er GR procedure) as well as appropriate intervals for stability testing: I reconunended that stability testing should be conducted at intervals appropriate to supp011 applied exp iration dates and fmther m entioned that assays at expiration (i.e. 1wo-year shelfl ife) should be conducted in a timely manner in order to provide relevant data for s upport of the applied expiration period. Discussion with Management: During the c1osing discussion on 1/6112 firm management did n ot provide any additional details regarding corrective actions which had been or were being implemented in response to the stated confirmed that a \vrittcn response would be submitted to the Los observations. Angeles District Office. REFUSALS No refusals were encountered during the inspection. GE1\1ERAL DISCUSSION WITH MANAGEMENT 32 of 41 Establishment Inspection Report Gulhy-Renker LLC Santa J\fonica, CA 90405-3268 FEI: 3007513615 ET Start: 11 /07/2011 El End: 01/06/2012 On 1/6/2012 a 6-ilem FDA 483 , Jnspectional Observations, was issued to Mr. Bennet M. Van de Bunt, Co-CEO of Guthy-Renker LLC. Mr. Van de Bunt identified himself as the most responsible individual for the firm. Also resent durin the closing discussion were: Dirk van de Bunt, EVP and ChiefAdministrative Officer; General Counsel; Shelly El kins, Director of Consumer A.ffairs; and Robann Rollins, Senior Director o Jnvenf01y and Qualify Control. Keith ..........., Nelson Director of ua!U Com J/;ance, and representatives ( _ __,___..__ _____,, and were all present via conference call. ____ Firm representatives and associated counsel were notified that the issued FDA 483 contained my observations and did not represent final agency determination of the fim1 's regulatory status. The finn representatives were informed of sanctions available to lbe FDA including warning letter, regulatory meetings, fines, seizure and injunction should the firm be found to be in violation of the FD&C Act. I informed firm management that the listed observations were not all-inclusive of deficiencies that may exist at their firm and informed them that it 'vVas their responsibility to ensure that GR adhered to government regulations for regulated products. Firm management was informed of their option to submit a written response to the Los Angeles District Office, via the District Director, within 15 business days. General Counsel, said and Mr. B. Van de Btmt nodded in agreement that a written response·would be submitted. calculated the 15th business day to fall on January 27, 2012 . Additional items discussed with the firm include: 1. QC-032: "Customer Complaint Handling": During the inspection and again during the closing di scussion on 1/6/12 I suggested that the procedure clearly define the criteria for escalation of complaints. I further suggested that training should be provided and documented in a manner that will assure that consumer complaint handlers are knowledgeable about the applicable procedures, especially in regard to complaint escalation. 2. Lot tracking: Currently the Consumer affairs department relies on the complainant to provide lot information for products related to incoming complaints. During the inspection I asked Ms. Elkins if Consumer Affairs ever looks up the lots that were distributed to customers and she said that she did not know hovv to that would be done. I mentioned that the company should have a way to delermine which lots are distributed to end users and should be able to access that information. I explained that identifying product lots associated with reported complaints may help in tracking and trending of adverse reaction that may need finiher investigation. 3. Procedural Responsibilities: During the inspection and agafo during the closing discussion I suggested that GR procedures clearly define responsibilities of affected depai1ments, including responsibilities of contract vendors where applicable. l also mentioned that 33 of 41 Establishment Inspection Report FEI: Guthy-Renker LLC El Start: EI End: Santa Monica, CA 90405-3268 3007513615 11 /07/2011 0110612012 training on procedures should ensure that the affected depmtments/employees were knowledgeable about their responsibilities. 4. Assay methods: During the inspection I noticed procedure PDTM-001: "Analytical Test Method Benzoyl Peroxide Assay by HPLC For bulk and :finished product' \ effective June 2011 (Exhibit 151). I reviewed the procedure and noticed that it referenced a past version of the U SP and appeared to contain inaccurate calculations. Ms. Maderazzo reported that this method was only released to a contrnct vendor not yet involved in finished product manufacturing. I discussed with K. Maderazzo and firm management the importance of having test methods reviewed by knowledgeable employees to ensure that the data/fr1formation contained therein was accurate. Additionally I explained that methods used for product testing needed to be validated and/or verified to ensure they can produce consistent, reliable and specific, results, and be stability indicating where appropliate. 5. Microbial contamination and rework: Deviations reviewed during the inspection indicated that GR has approved use of preservatives to treat raw materials wruch do not meet incoming micro specification. Although the resulting finished products tested within specification I cautioned firm representative about ·use of micro-contamjnated raw materials. I explained that since a number of their products are intended for use on acne-prone skin that extra consideration should be given to reconditioning practices to ensure that finished products do not pose any added risks to the end user. ADDITIONAL INFORMATION KNOWLEDGE OF GR SUBSIDIARIES The inspection was initiated at Guthy-Renker headquaners in Santa Monica, California. During the inspection info1mation was provided that indicated that additional Guthy-Renker subsidiaries were involved in distribution of FDA regulated products (Guthy-Renker NutTitional Products, LLC: vitamins; and Vendor Services LLC: sexual enhancement herbal supplements). FDA 482 Notices of Inspection were issued when this knowledge was shared and clarified by the fom. CHANGE IN VITAMIN DISTRJBUTION ANO RESPONSIBILITY Dming the ins pections I noticed that label proofs provided for distributed vitamin products indicated Guthy Renker Nutrition and Guthy-Renker LLC as product distributors. I asked Mr. Dirk van de Bunt for inf01mation on who distributed the finished products as well as information on the relation ship between Guthy-Renker Nutrition, Guthy-Renker Nutritional Products LLC, and Guthy-Renker LLC. Mr. D. van de Bunt inf01med me that Guthy-Renker Nutritional Products LLC previously distributed vHamins however in 2011 all vitamins were being distributed under the financial control of Guthy-Ren.ker LLC. Mr. D. van de Bunt said that there was no separate entity by the name of Guthy Renker Nutrition. 34of41 Establishment Inspection Report Guthy-Renker LLC Santa Monica, CA 90405-3268 FEI: 3007513615 EI Stait: 11/07/2011 01 /06/2012 EI End: PROACTIV llENZOYl. PEROXIDE OVERAGE FORMULATIONS Proactiv Renewing Cleanser and Proactiv Repairing Treatment were reformulated in 2011 to include an overage of active ingredient benzoyl peroxide. Information provided by Ms. Maderazzo on the justification for a benzoyl eroxide fmmula overage is included in Exhibit 152. Ms. Maderazzo said that GR worked with 6 n some of their benzoyl peroxide products and the provided information is a summary of that collaboration. Additional information on fommla overage, stability, and expiration dating is included in the draft summary for Deviation 2362 (I~xhibit 153). SAMPULS COLLECTED DOCs 675797 and 675800 were collected to document the interstate commerce of topical over-thecounter acne drug treatmen1s distributed by GR LLC (Palm Desert; labeled dish'ibutor location). DOC 675799 was collected to document the interstate commerce of vitamins distributed by GR LLC (Palm Desert; labeled disti"ibutor location) and/or Gu thy-Renker Nutritional Products LLC (Palm Desert; labeled distributor location), a Guthy-Renker LLC subsidiary. Per Mr. D. van de Bunt and the provided business entity chart (see Exhibit 2) vitamins distributed in 2011 were financially handled by Guthy-Renker LLC and not Guthy-Renk.er Nutritional Products, LLC. Vitamins distributed in 2010 were financially handled by Gu thy-Renker Nutritional Products LLC (see !he additional info1mation section titled "Vitamins" for further information on vitamin distribution). documentary samples consist of copies of shipping records obtained from Mr. Dale W. Snider, Director ofGlobal Freight and Logistics for GR LLC, Palm Dese1i, and label proofa obtained during the inspection. ·ne VOLUNTARY CORRECTIONS This is the first inspection of the firm by the US FDA. During the current inspection Ms. Elkins, Director of Consumer Affairs, reported that the Consumer Affairs and Quality departments were working to review previously received consumer complaints to determine if they needed to be submjtted as serious adverse event repo1ts. Guthy-Renker LLC (Palm Desert) initiated a voluntary recall jn November 2011 of OTC drug products (Proactiv Renewing Cleanser, Proactiv Repairing Treatment/Lotion and Proactiv Concealer Plus) which did not meet active ingredient label claim througbout their marketed shelf life. On 1/6/12 GR General Counsel, stated that the firm took the inspection and reported observations very seriousl:;; and would be submitting a written response to the Los Angeles Distti.ct 35 of 41 Establishment Inspection Report Guthy-Renker LLC Santa Monica, CA 90405-3268 FEI: 3007513615 EI Start: EI End: 11107/2011 01106120 12 Office detailing their Ian for correction. The written response was promised within 15 business calculated to be January 27, 2012. days which EXHIBITS COLLECTED 1. GR Entities, Subsidiaries and Affiliates, 1 page. 2. Guthy-Renker LLC Domestic Entities with Sales in the US (Sales for 2011 and 2010), 3 pages. 3. What happens in each GR location along with phys ical address of GR related locations, 3 pages. 4. Contract Vendor contact infmmation, 3 pages. 5. Product Shipper and Warehouse info1mation, 3 pages. 6. Master OTC Product List, 9 pages. 7. Interstate and wholesale percentages for distributed products, 2 pages. 8. Guthy-Renker LLC 2010 Gross Revenue (ranges) by Product, 1 page. 9. Guthy-Renker LLC Organizational chart (partial), 10 pages. 10. QC-045 GR QC Training Procedure, DRAFT, 11 pages. 11. Examples of training tools for employees involved incompliant handling, 9 pages. l 2. Termination dates of GR QA cmploye_es, 1 page. 13. tability study letter dated 11I 17/1 1, 2 pages. 14. E-mail conununication and supporting documentation between GR and ·elated to DA inspection, 6 a es. --lll...lo...&....&1 15. Redacted FDA 483 from nspcction, 5 pages. 16. Redacted 83 (partial) indicating GR affected products, 2 pages. 17. Consumer Affairs flow charts for complaint escal ation, 2 pages. Medical Advisor for Guthy-Renker LLC, 4 pages. 18. CmTiculum Vitae for 19. CD-R containing complaint logs from 2009 to 2011, 1 disc. 20. CD-R containing complaint trending logs for 2010 and June through October 201 1, with 6 rend data printouts, 8 pages (includes 1 disc). 21. Consultant summary evaluation for WEN, 3 pages. 22. Label proofa for Wen cleansing conditioner listing product ingredients, 7 pages. 23. QC-034 "Recall/Market WithdrawaP', 8 pages. 24. QC-032: "Customer Complaints Procedure" effective 10/ 18/ 10, 14 pages. 25. Complaint packet for complaint number 101001-018364, 21 pages. 26. Complaint packet for complaint nwnber 001O'.W862A, 14 pages. 27. Complaint packet for complaint number 1003 11-000054, 7 pages. 28. Complaint packet for complaint number 00 I 0455 19A, 10 pages. 36 of 41 Establishment Inspection Report Guthy-Renker LLC Santa Monica, CA 90405-3268 29. Quality Agreement between GR and FEI: 3007513615 El Start: El End: 11 /07/2011 0 1/06/2012 17 pages. 30. QA-012 "OTC Drug Product Stability Program for Production Batches", 6 pages. 3 J. QA SOP list with owners and largel completion dates, I page. 32. QA SOP conversion tables, 6 pages. 33. DRAFT retyped version ofQA-012, 6 pages. 34. DRAFT PD-009 Over-the-Counter Primary Stability Program (Production Batches), 1I pages. 35. PD-003 "Bcnzoyl Peroxide Containing Over-the-counter Anti-Acne Drug Product Stability Program (Production Batches)", 10 pages. 36. DRAIT QC-022 Primary Stability Program of OTC Drug Products: 15 pages. 37. DRAFT Stability Protocol for GR (Insert Product Description), 26 pages. · 38. DRAFT "QC-026 On-Going Stability Program for OTC Drug Products", 8 pages. 39. List of product lots distributed by GR LLC, 22 pages. 40. Information on stability issues communicated by contract vendor 41. Information on slability issues communicated by contract vendor · 10 pages. 58 pages. 42 . Spreadsheet showing fonnula progression for Proactiv Repairing Lotion/Treatment, 1 page. 43. Label proofs for Proactiv Repairing Treatment/Lotion, 13 pages. 44. Product specifications for Proactiv Repairing Lotion P0207, 24 pages. 45. Stability summary data for Proactiv Repairing Lotion P0207, T6158A, 11 pages. 46. Stability summary data for Proactiv Repairing Lotion P0207, T7011A, 10 pages. 47. Stability summary data for Proactiv Repairing Lotion P0207, T8014A, 12 pages. 48. Stability sunmuiry data for Proactiv Repairing Lotion P0207, T9057A, 21 pages. 49. Stability summary data for Proactiv Repairing Lotion P0207, T0105A, 11 pages. 50. Stability summary data for Proactiv Repairing Lotion P0207, A6279A et al, 22 pages. S 1. Stability sununary data for Proactiv Repairing Lotion P0207, A7047A, 12 pages. 52. Stability s ummary data for Proactiv Repairing Lotion P0207, A 7057B, 9 pages. 53. Stability summary data for Proactiv Repairing Lotion P0207, AP7254A, 16 pages. 54. Stability summary data for Proactiv Repairing Lotion P0207, AP7243A, 31 pages 55. Stability summary data for Proactiv Repairing Lotion P0207, AP8045A, 65 pages. 56. Stability sm1U11ru·y data for Proactiv Repairjng Lotion P0207, L9021A1, 3 pages. 57. Stability summary data for Proactiv Repairing Lotion P0207, L0026A, 1 page. 58. Stability summary data for Proacliv Repairing Lotion P0207, LI085A, 1 page. 59. Filled goods specification for Proactiv Repairing Lotion GRl l 03200, 2 pages. 60. Product Specifications for Proactiv Repairing Treatment GR0902000, 22 pages. 61. Stability summary data for Proactiv Repairing Treatment GR0902000, T9244A l oz., 10 pages. 37of41 Establishment Inspection Report Guthy-Renker LLC Santa Monica, CA 90405-3268 FEI: EI Start: 3007513615 EI End: 01/06/2012 11107/2011 62. Stability summary data for Proactiv Repairing Treatment GR0902000, T9244A 2 oz., IO pages. 63. Stability summary data for Proactiv Repairing Treatment GR0902000, T9244A 3.5 oz., 10 pages. 64. Stability summary data for Proactiv Repairing Treatment GR0902000, T9352A, 18 pages. 65. Stability summary data for Proactiv Repairing Treatment GR0902000, T0013A, 15 pages. 66. Stability summary data for Proactiv Repairing Treatment GR0902000, T1229B, 1 page. 67. Stability summary data for Proactiv Repairing Treatment GR0902000, Tl230B, 3 pages. 68. Stability summary data for Proactiv Repairing Treatment GR0902000, Tl230A, 2 pages. 69. Stability summary data for Proactiv Repai1fog Treatment GR0902000, AP0056A, 19 pages. 70. Stability summary data for Proactiv Repairing Treatment GR0902000, AP0071A, 24 pages. 71. Stability summary data for Proactiv Repairing Treatment GR0902000, 1000036772, 2 pages. 72. Stability summary data for Proactiv Repairing Treatment GR0902000, 1000038194, 1 page. 73. Stability sununary data for Proactiv Repairing Treatment GR0902000, 1000038195, 1 page. 74. Stability summary data for Proactiv Repairing Treatment GR0902000, 7000000820, 1 page. 75. Stability summary data for Proactiv Repairing Treatment GR0902000, 7000000821, 1 page. 76. Stability summary data for Proactiv Repairing Treatment GR0902000, 7000001502, 2 pages. 77. Stability summary data for Proactiv Repairing Treatment GR0902000, 7000002474, 20 pages. 78. Stability sununary data for Proactiv Repairing Treatment GR0902000, 7000001740, 1 page. 79. Product Specifications for Proactiv Repairing Treatment GR0902002, 10 pages. 80. Stability sununary data for Proactiv Repairing Treatment GR0902002, Apex, APl 10 lA, 3 pages. 81. Stability summary data for Proactiv Repairing Treatment GR0902002, Thibiant, Tl 164A et al, 3 pages. 82. Spreadsheet showing formu la progression for Proactiv Renewing Cleanser, 2 pages. 83. Label proofs for Proactiv Renewing Cleanser, 6 pages. 84. Product specifications for Proactiv Renewing Cleanser P0409, 9 pages. 85. Stability summary data for Proactiv Renewing Cleanser, P0409, T4322A, 14 pages. 86. Stability summary data for Proactiv Renewing Cleanser, P0409, T4338A, 8 pages. 87. Stability raw data for Proactiv Renewing Cleanser, P0409, T5193A, 9 pages. 88. Stability sununary data for Proactiv Renewing Cleanser, P0409, T51 94B, 20 pages. 89. Stability summary data for Proactiv Renewing Cleanser, P0409, T 601lA,20 pages. 90. Stability sununary data for Proactiv Renewing Cleanser, P0409, T7152A, 17 pages. 91. Stability summary data for Proactiv Renewing Cleanser; P0409, T8015A, 16 pages. 92. Stability sunu1rnry data for Proactiv Renewing Cleanser, P0409, T9047A, 21 pages. 93. Stability summary data for Proactiv Renewing Cleanser, P0409, T0013B, 13 pages. 38 of 41 FEI: EI Start: EI End: Establishment Inspection Report Guthy-Renker LLC Santa Monica, CA 90405-3268 3007513615 11/07/2011 0 1/06/2012 94. Stability summary data for Proactiv Renewing Cleanser, P0409, 147H7, 21 pages. 95. Stability suimnary data for Proactiv Renewing Cleanser, P0409, 146H7, 16 pages. 96. Stability summary data for Proactiv Renewing Cleanser, P0409, l 48H7, 23 pages. 97. Stability summary data for Proactiv Renewing Cleanser, P0409, 134K7, 27 pages. 98. Stability summary data for Proactiv Renewing Cleanser, P0409, AP8024A, 67 pages. 99. Stability summary data for Proactiv Renewing Cleanser, P0409, 77A8, 50 pages. 100. Stability summary data for Proactiv Renewing Cleanser, P0409, AP9159A, 21 pages. 101. Stability summary data for Proactiv Renewing Cleanser, P0409, AP91 35B, 49 pages. 102. Stability summary data for Proactiv Renewing Cleanser, P0409, AP9132A, 26 pages. 103. Stability summary data for Proactiv Renewing Cleanser, P0409, AP0025B, 49 pages. 104. Stability summary data for Proactiv Renewing Cleanser, P0409, L9035Al, 3 pages. 105. Stability summary data for Proactiv Renewing Cleanser, P0409, L0012A, 1 page. 106. Stability summary data for Proactiv Rene\'ving Cleanser, P0409, Ll080A, 1 page. 107. Product specifications for Proactiv Renewing Cleanser GR0902300, 17 pages. 108. Stability summary data for Proactiv Rene·wing Cleanser, GR0902300, T0197A, 2 pages. 109. Stability summary data for Proactiv Renewing Cleanser, GR0902300, T0194A, 11 pages. 110. Stability sununary data for Proactiv Renewing Cleanser, GR0902300, T0196A, 11 pages. 111. Product specifications for Proactiv Renewing Cleanser GRl 102600, 4 pages. 112. Product specifications for Proactiv Renewing Cleanser GR0902700, 32 pages. 113. Stability summary data for Proactiv Renewing Cleanser, GR0902700, T9245A, 18 pages. 114. Stability summary data for Proactiv Renewing Cleanser, GR0902700, T9245A, 7 pages. 115. Stability summary data for Proactiv Renewing Cleanser, GR0902700, T ,9245A, 6 oz, 13 pages. 116. Stability summary data for Proactiv Renewing Cleanser, GR0902700, T0070B, 11 pages. 117. Stability summary data for Proactiv Renewing Cleanser, GR0902700, T0147A, 14 pages. 118. Stability summary data for Proactiv Renewing Cleanser, GR0902700, 1 page. 119. Stability summary data for Proactiv Renewing Cleanser, GR0902700, 12 pages. 120. Stability summary data for Proactiv Renewing Cleanser, GR0902700, A9363A, 18 pages. 121. Stability summary data for Proactiv Renewing Cleanser, GR0902700, A9364B, 2 pages. 122. Stability sununary data for Proactiv Renewing Cleanser, GR0902700, 1000037373, 13 pages. 123. Stability summary data for Proactiv Renewing Cleanser, GR0902700, 1000038181, 18 pages. 124. Stability summary data for Proactiv Renewing Cleanser, GR0902700, 1000038185, 11 pages. 125. Stability summary data for Proactiv Renewing Cleanser, GR0902700, AP0013A, 21 pages. 126. Stability summary data for Proactiv Renewing Cleanser, GR0902700, AP0053B, 18 pages. 39 of 41 i- Establishment Inspection Report Guthy-Renker LLC Santa Monica, CA 90405-3268 FEI: 3007513615 EI Start: 11107/2011 01 /06/20 12 EI End: 127. Stability sununary data for Proactiv Renewing Cleanser, GR0902700, 026JO, 2 pages. 128. Stability sununary data for Proactiv Renewing Cleanser, GR0902700, 028JO, 5 pages. 129. Stability summary data for Proactiv Renewing Cleanser, GR0902700, Tl042B et a1, 6 pages. 130. Product specifications for Proactiv Renewing Cleanser GR0902702, 12 pages. 13 1. Stability summary data for Proactive Renewing Cleanser, GR0902702, Tl l 65A el al, 4 pages. 132. Label Proofs and Product specifications for Proactiv Concealer Plus, 14 pages. 133. Stability summary data for Proactiv Concealer Plus Light, T6171A, 7 pages. 134. Stability summary data for Proactiv Concealer Plus Light, T7082A, 6 pages. 135. Stability summary data for Proactiv Concealer Plus Light, T8044A, 7 pages. 136. Stability summary data for Proactiv Concealer Plus Light, T9062A, 13 pages. 137. Stability smmnary data for Proactiv Concealer Plus Light, T0198A, 2 pages. 138. Stability summary data for Proactiv Concealer Plus Light, T1230A, 12 pages. 139. Stability sununary data for Proactiv Concealer Plus Medium, T5047A, 15 pages. 140. Stability summary data for Proactiv Concealer Plus Medium, T6172A, 9 pages. 141 . Stability summary data for Proactiv Concealer Plus Medium, T7058A, 11 pages. 142. Stability summary data for Proactiv Concealer Plus Medium, T8011A, 1!£p~g'e~~/1t 143. Stability sunnnary data for Proactiv Concealer Plus Medium, T9044A, 2 pages. 144. Stability summary data for Proactiv Concealer Plus Medium, Tl200, 2 pages. 145. Stability summary data for Proactiv Concealer Plus Medium-Dark, T8053A, 16 pages. 146. Stability summary data for Proactiv Concealer Plus Dark, T7046A, 7 pages. 147. Stability smmnary data for Proactiv Concealer Plus Dark, T011 9A, 9 pages. 148. Concealer lots distributed by GRLLC, 3 pages. 149. Quantity of concealer received from contract vendor Thibiant, 4 pages. 150. SOP table of Contents for Guthy-Renker: Internal, Fillers, and FFC's (Fulfillment Centers), 9 pages. 151 . PDTM-001: Analytical Test Method Benzoyl Peroxide Assay by HPLC for Bulk and Finished Product, 4 pages. 152. Justification for benzoyl peroxide formula overage, 2 pages. 153. Deviation 2362 DRAFT for review of 20% overage formulations for expiration dating. Attachments 5-8 and 9-14 related to method and process validation and contract vendor stability data were not included, 35 pages. ATTACHMENTS 40 of 41 Establishment Inspection Report Guthy-Renker LLC FEI: 3007513615 EI Start: 11/07/2011 Santa Monica, CA 90405-3268 El End: 0110612012 • Unsigned Affidavit of William Keith Nelson, Director ofQuality Control, on 11 /17/ 11, 2 pages. • Unsigned affidavit of Robmm (NMI) Rollins, Senior Director of Quality Control and Order .Management, on 11/17/ 11 , 1 page. • Unsigned Affidavit of Kimber L. Maderazzo, Senior Vice President of Global Product Development, on 1/3/12, 2 pages. • Unsigned Affidavit of Dirk W. van de Bunt, EVP and ChiefAdministrative Officer, on 115112, 1 page. • FDA 482 Notice of Inspection, issued on 11/7/2011 to Mr. Dirk W. van de Bunt, Executive Vice Pres;dent and CMefAdministrative Officer, 2 pages. • FDA 483, Inspectional Observations, issued on 11612012 to Mr. Bennet M. Van de B unt, coChiefExecutive Officer, 4 pages. • California Secretary of State Business Search Results for Guthy-Renker, 1 page. • California Secretary of State Business Entity Detail for Guthy-Renker Partners Inc., 1 page. • California Secretary of State Business Entity Detail for Guthy-Renker Holdings LLC., 1 page. • California Secretary of State Business Entity Detail for Gu thy-Renker LLC., 1 page. Sonia R Peterson, Investigator, LOS-DO 41 of 41 DEPART.ME NT OF HEALT H AND HUMAN S ERVICES FOOD AND ORUO AOMINTSTRATJON D!SlRJCT ADORESS >J{O PHONE M.11/.BER '""" ' c 10) OF INSl'l:CTIOll 11 /07 /20 11 - 01/06/2012* 19701 Fairchi ld Irvi ne , CA 92 612 ( 94 9) 608-2900 Fa x : ( 949) 608-4 417 Ind u str y I n fo rma t i on ~ www. f d a . gov/oc/i n dustr y FEI NUMBER 300751 361 5 NAJ.!E ANO lTT1.E OF INOMDUIJ. TO \\HOM REPORT ISSUED TO: Bennet M. Van de Bun t , Co- Ch ief Ex ecut ive Off icer FIRM NAAl.E STREET ADORESS Gut hy - Ren ker LLC 334 0 Ocean Park Blvd ., Ste 3055 CITY, STA TE, ZIP CODE. ~NTRY TYPE ESTASUSINENTINSPECTEO Sant a Mo n ica , CA 9040 5- 32 68 Corpor ate Headq ua r t ers This document lists observations made by the FDA representative(s) during the inspection of your facility. They are inspcctional observations, and do not represent a final Agency determination regarding your compliance. If you have an objection regarding an observation, or have implemented, or plan to implement, corrective action in response to au observation, you may discuss the objection or action with the FDA rcpresentative(s) during the inspection or submit this information to FDA at the address above. If you have any questions, please contact FDA at the phone number and address above. DURING AN INSPECTION OF YOUR FIRM I OBSERVED: OBSERVATION 1 You did not follow written procedures for the requirements to review and investigate a product complaint. QC-032 "Customer Complaints Procedure" (effective 10/18/ 10) includes guidelines and responsibilities for handling consumer complaints including reports of serious adverse events. Consumer complaints, associated with use of dietary supplements, which meet the defined criteria for serious adverse events are not classified as such for reporting through the MedWatch system. Rev}ewed complaints include: a.) Customer complaint 101001-018364 received on 10/ 1/10 for a vitamin reaction with Coumadin medication causing internal bleeding with hospital visit. The complainant reported use of Sheer Cover Daily Plus vitamins . . b.) Customer complaint 001030862A received on I 0/18/11 for hospitalization due to anaphylactic shock. The complainant reported use ofVitaclear Daily Multivitamins. QUALITY SYSTEM OBSERVATION 2 Procedures describing the handling of written and oral complaints related to drug products are deficiently written or followed. QC-032 "Customer Complaints Procedure" (effective 10/18/10) includes guidelines and responsibilities for handling consumer complaints including reports of serious adverse events for over-the-counter (OTC) drug products. Customer complaint number 100311-000054 received on 3/11/ 10 reported a chemical bum and anaphylactic shock which required steroid treatment at a hospital facility. The complainant reported use of OTC acne treatments Proactiv Renewing Cleanser and Proactiv Repairing Treatment (active ingredient: benzoyl peroxide). The complaint, which appears to met the defined criteria for a serious adverse event, was not classified as such for repo1ting through the MedWatch system. EMPl.OYEE(S) 6!GNAnJRE SEE REVERSE OF THIS PAGE FOlll\I FDA 4ll (09.ila) Sonia R Peters o n, I nves t igator 0-- --.- - .c;,; =-- ___.,,,,. ---=:::.:.::_ - ...,...._ 01/06/2012 - ,.... ........... PllEV!OUS EDmo~ OllSOtEl1l OATE ISSUEO ~ INSPECTIONAL OBSERVATIONS '~ PACI! I 0 1' 4 PAGES '· DEPARTJ\lENTOF HEALTif AND HUMAN SERVICES FOOD AND DRUG ADMINJSTRATION DATE(S) OF INSPECTION DISTRICT ADDRESS NI:) PHONE NlJl,lllER 19701 Fairchild Irvine, CA 92612 (94 9) 608-2900 Fax: ( 949) 6 08-4417 I ndustry I nfo rmat i o n : www . fda.gov/oc /i ndustry 11/07 /2011 - 0 1/06 /2 012* FE! NUMlla1 3007513615 NAME mo TITl.E Of' l~OUAI. TO IM~ REPORT ISSUED TO: Ben net M. Van de Bunt, Co-Chief Executive Officer FIRMN.U!E STREET AOOO£SS Guthy-Re nker LLC 3340 Ocean Park Blvd ., Ste 3055 . CITY, STA1C. 2P """"•COUNTRY TYPE ESTABUSHr.IEIIT INSPECTEO Santa Moni ca , CA 90405- 3268 Corporat e Headquarters OBSERVATION 3 The responsibilities and procedures applicable to the quality control unit are not in writing and fully followed . For example, per QA-012 "OTC Drug Product Stability Program for Production Batches" (effective 2/28/05) the stability testing program for over-the-counter (OTC) drug products distributed by your firm was handled by the Quality Assurance unit. In approximately June 2008 the Quality Assurance unit was discontinued. Quality Assurance responsibilities related to oversight of the stability program and review of product stability data were not officially transferred to the Quality Control or Product Development department to ensure that finished OTC drug products distributed by your firm continued to meet specifications for safety and efficacy throughout their applied shelf life. New procedures covering OTC drug product stability were not drafted and/or implemented by Quality Control/Compliance until 2011. OBSERVATION 4 ~ ..: .. i. ~ :>~~·~.~:::/::. ~-. ·.····:\·.; ·.· . Results of stability testing are not used in determining expiration dates. Expiration periods applied to over-the-counter drug products distributed by your firm do not reflect the resu·lt·i: -~·~·: .'\ active ingredient stability assay data compiled by your contract vendors (CV). Some examples include: 4 ~-(. fj1ual stabiJ;ty data fo.- Proactiv Repairing Lotion (benzoyl peroxide 2.5%; GR formut'611 'lcv ~~ 4 6 1 in 2009 indicate that the fuiished product failed active ingredient assay for benzoy~xide at th ( onths. The distributed fmished product received an applied expiry period of2 years. (b) (4) tmonths test intervals. Annual 2010 assay data for lot T0105A (EXP 4/12) failed a 6) b.) Annual ~)bility data for Proactiv Renewing Cleanser (benzoyl peroxide 2.5%; GR formuJ!f0} <4 J ICV formu1,6f(i j indicate that finished products have failed active ingredient assay pnor to the 24 month expiration date between 2004 and 2010. Lot TOO 13B manufactured in 20 l 0 failed active ingredient assay aerJmonths. The distributed finished product received an applied expiration period of 24 months (EXP 1/2012). c.)Annual stability data for Proactiv Renewing Cleanser (benzoyl peroxide 2.5%; GR formula GR<6J C4 ) lcv formul~~) (4) Iindicate that finished progyc lots T0194A (EXP 7/12) and TO 196A (EXP 7/12) manufactured in 2010 failed active ingredient assay at thIDonth test point. The distributed products received an applied expiration period of 2 years. d.) Annual stability data for Proactiv Renewing Cleanser (benzoyl peroxide 2.5%; GR formula G :o) (4J EMPlOYEE(S) SIGW.TIJRE SEE REVERSE OF THIS PAGE FORM FDA •83 (09/08) Son ia R Peterson , Investigator~.,;'"~ ''-<;;:::::::::-~-.::;. PIUlVJOusmmo~ otlSOlEIE I no OATE\SSUEO INSPE~~OBSERVATIONS 01/06 /2012 PAGB 2 OF 4 PAGES DEPARTMENT OF HEALT H AND HUMAN SERVICES FOOD AND DRUG AOMINISTRATION DATE(S) OF lf'5PECTION DISTRIC TADDRESS m£J PHONE NIJ!!eal 197 01 Fairchild Irvine, CA 92612 (94 9) 608-2900 Fax : (949) 608-4417 Industry I n formation: www . f da.gov/oc/industry 11/07/2011 - 01/06/2012* FEJNUMBER 3007513615 NAME ANO TIDE OF INOMOUAL TO\"diS for sulfur assay at t onth test interval. The manufactured product has a labeled expiration period of 3 years. OBSERVATION 5 Written procedures are not established for evaluations done at least annually and including provisions for a review of complaints, recalls, returned or salvaged drug products, and investigations conducted for each drug product. ... ·?:'• ::(\ . ., For example, your firm does not have a procedure which covers requirements for annual drug product review and " no annual drug product review is being conducted and documented for consumer complaints and associated investigations which a.re handled at the corporate level for over-the-counter drug products manufactured by your contract vendors. OBSERVATION 6 An adequate number of batches of each drug product are not tested nor are records of such data maintained to determine an appropriate expiration date. For example, a.) No annual stability study data was maintained fo r distributed Jots of Proactiv Concealer Medium-Dark (sulftir 8%) manufactured in 2009 (T9254A, T9257 A) which are given a three year expiration period. b.) No annual stability study data was maintained for distributed lots of Proactiv Concealer Dark (sulfur 8%) manufactured in 2008 (T8047A, T8309A) which are given a three year expiration period. c.) No annual stability study data was maintained for distributed lots of Proactiv Concealer Medium (sulfur 8%) manufactured in 2010 (T0078A; T 0342A; T0343A) which are given a three year expiration period. ,. / EMP!.OYEE(S) SIGIV.T\JRE SEE REVERSE OF THIS PAGE FORM l'DA -1&3 (09/0t) Sonia R Peterson , Inves t igator --- ----~ ~ '" 7 ·- ...____ --~::::.:--~~ - --___ ....--- ...__ ~- l'RlivtOUS EDITIOll OQSOUm! INSPECTION AL OBSERVATIONS .. DATI: ISSUED 01/06/2012 PAGID OF 4 PAGES DE PARTMENT OF HEALTH AND HUT\IAN SERVICES FOOD AND DRUG ADMINISTRATION OISTRJCT AllllRE.SS ANO P ~'E NUMBER DATE(S) Of' INSPECTION 1 9701 Fairch ild I r vi n e , CA 92 612 ( 9 4 9 ) 608-2900 Fax: (949) 608-4 417 Indu s t ry Information : www. fda . gov /oc/industry 11/07/2011 - 01/06/2012* FEl l'l\JMBER 300751 3615 NAME l.Jl'J TlTlE Of' INOl\/IOUAI. TO~ REPORT ISSUED TO: FIRM w..w; Bennet M. Van de Bu nt , Co-Chi ef Ex ecutive Officer STREET ADORESS Gu t hy- Renker LLC 3340 Ocean Park Blvd . , Ste 3055 CITY, STATE, ZJP CODE, COUtmlY Santa Monica , CA lYPE ESTABIJSHl,IENT INSPECTED 9 0 4 05- 3268 Corporate Head quarters *DATES OF INSPECTION: I l /07/2011 (Mon), ll/08/201 l(Tuc), 11/I0/201l(Thu), 11/14/201l(Mon), 11/1 8/2011(Fri), 11/221201 l(fue), 11/28/201 l(Mon), I l/29/201 !(Tue), 11/30/2011(\Ved), 12/02/201l(fri), 12/06/201l(fue), 12/08/201l(Thu), 12/12/201 l(Mon), 12/21/2011(Wed), 12/29/201 l(Thu), 01/03/2012(Tue), 01/05/2012(Thu), Ol/06/20!2(Fri) .. ' '.. . . . ': .·~. :· ; • l , ' !: . ·. .. ' ------ EMPtDYEE(S) SIGNA1VRE SEE REVERSE OF THIS PAGE FORM POA 483 (09/01) Sonia R Peterson, Investigator PRP.VIOUS EDmON oosoumi INSPECI'IONAL OUSERVATIONS DATE ISSUED 01/06/20 1 2 PAGIJ 4 OF 4 PAGES '• Establishment Inspection Report Guthy-Renker. LLC Santa Monica, CA 90405-3268 FEJ: 3007513615 El Start: El End: 08112/20 15 08/20/2015 Table of Contents Sum1nary ............................................................................................................................................... I t\d1ninistrative Data .............................................................................................................................. 3 History ................................................................................................................................................... 4 Interstate Commerce/Jurisdiction ...................................... ................................................................... 5 Individual Responsibi lity and Persons Interviewed .............................................................................. 6 Finn's Training Progra1n .................................. ..................................................................................... 7 Manufacturing/Design Operations ........................................................................................................ 7 Cleansing Conditioner Fonnulations ................................................................................................ 8 Wen Product/Ingredient Studies ..................................................................................................... 12 Legal ly Privileged Review.............................................................................................................. 13 C leansing Conditioner Labeling ..................................................................................................... I 3 Leave-fn Conditioner ...................................................................................................................... 16 Actiphyte of Wild Cheny Bark vs. Actiphyte of Wild Cherry Fruit Extract ................................. I 6 Adverse Event Intake/Processing/Reporting .................................................................................. 17 Manufacturing Codes .......................................................................................................................... l 9 Co1nplaints .......................................................................................................................................... 20 CFSAN CAERS Complaints .......................................................................................................... 21 Recall Procedures................................................................................................................................ 22 Objectionable Conditions and Management's Response .................................................................... 22 Refusals ............................................................................................................................................... 22 General Discussion with Management ............................................................................................... 22 Sa1nples Collected ....................................................................................................................... ........ 23 Vol untary Corrections......................................................................................................................... 23 Ex hi bits Collected ............................................................................................................................... 24 Attachments ........................................................................................................................................ 26 Summary This directed inspection of the Corporate Headquarters of Guthy-Renkcr, LLC in Santa Monica, CA was conducted per FACTS Assignment 11517872 and the associated assignment memo dated 3/ 10/15. The inspection covered Wen by Chaz Dean Cleansing Conditioner formulations and formulation changes: receipt and handling of hair loss complaints reported lo be associated with use of Wen products; Cleansing Conditioner label ing and manufacturing deviations; and studies, investigations, and other data regarding the safety and use of Wen hair care products or ingredients contai ned in those products. The inspection focused primarily on Wen Cleansing Conditioner 1 of26 Establishment Inspection Report Guthy-Renker, LLC Santa Monica, CA 90405-3268 FEI: El Start: EI End: 300751 3615 08/12/20 15 08/20/2015 fo rmulations manufactured between 2011 and 2015 which are distributed by G uthy-Renker, LLC (GR). Wen products are also distributed by Chaz Dean Studios (Studio); GR management reported tl1at GR does not have responsibility for Studio products. GR firm management reported that similar Wen products distributed by the two entities may have different ingredients/fonn ulati.ons; at minimum, the preservative system used in the Cleansi ng Conditioners was reported to be different. A concurrent inspection for Postmarketing Adverse Drug Experience (PADE) reporting requirements was conducted under FACTS Assignment 11476675(8/11/15 to 8/20/ 15). The previous inspection of GR was conducted from November 2011 through January 2012 and focused on Corporate Headquarter responsibilities related to marketing and distribution of FDA regulated over-the-counter drug and dietary supplement products. The inspection concluded with issuance of a 6-item FDA 483, Inspectional Observations, for: failure to report serious adverse events; responsibilities and procedures applicable to the qualit'j control unit not in writing and fully followed; stability testing results not used to determine expiration dates for OTC drug products; no annual product review; and an inadequate number of batches of drug products placed on stability. Co1TecOons implemented lo the previous inspectionaJ observations were addressed as part of the PADE inspection (FACTS 11476675). Most of the reported corrections appear to be implemented; seizure adverse events associated with OTC Drug and Dietary Supplement use in 2012 and 2013 were f01wardcd for further review by the Agency. The current inspection found Guthy-Renker, LLC continuing to operate as a direct-marketing fim1 providing marketing, distribution, and quality oversight for FDA regulated OTC drug, dietary supplement and cosmetic products. The finn is responsible for handling complaints and adverse events for distributed products and repo1ting serious adverse events (SAE) received for OTC drug and djetary supplement products; the firm does not submit MedWatch repo1ts for SAE associated with cosmetic product use. No manufacturing and no .finished product storage occurs at this location. GR has responsibility for processing complaints and adverse events associated with Wen product distributed by Guthy-Renker, LLC. GR reported ownership of some of the Cleansing Conditioner formu lations; other Cleansing Conditioner fo1mulations (primarily seasonal var.ieties) .. GR has received multiple were reported to be owned by contract manufacturerf6JC4> complaints reporting hair loss, breakage, thinning, etc. associated with use of Wen products. Firn1 management reported that complaint volume increased slightly when the class action lawsuit regarding Wen was mentioned on social media but otherwise has remained essentially constant over time. No FDA 483, Inspectional Observations, was issued; several items were discussed with firm management during the inspection and at the closing meeting with management. Between 2011and2012 the finn issued recalls for four OTC drug products which fai led to meet active ingredient claim throughout their expiration period. No samples were collected during this inspection. 2 of26 Establishment Inspection Report Guthy-Renker, LLC Santa Monica, CA 90405-3268 FE!: EI Start: 3007513615 EI End: 08/20/2015 08112/2015 The firm reported current litigation regarding Wen products and hair loss and would not provide product/ingredient related studies which were reported to be under legally privileged review. GR firm management reported that GR legal counsel would be willing to meet with Agency Attorneys to discuss the information. T he firm is not registered with the US FDA. The facility is the Corporate Headquarters for GuthyRenker, LLC (GR) which is a direct-marketing firm responsible for marketing and distribution of FDA Regulated OTC drug, dietary supplement and cosmetic products; no FDA regulated products are manufactured, packed or stored for distribution at this location. Firm management was informed of the VCRP and voluntary filing of Cosmetic Product Ingredient Statements. Administrative Data Inspected firm: Location: Phone: FAX: Mailing address: Website: Dates of inspection: Days in the facility: Participants: Guthy-Renker, LLC 3340 Ocean Park Blvd Third Floor Santa Monica, CA 90405-3268 310-581-6250 310-581-3232 3340 Ocean Park Blvd Third Floor Santa Monica, CA 90405-3268 www.guthy-renker.com; www.wen.com 8112/2015, 8/13/2015, 8/17/20 15, 8/18/2015, 8/20/2015 5 Sonia R. Peterson, Investigator On 8/12/15 I introduced myself, presented credentials and issued an FDA 482, Notice of Inspection (Attachment), to Mr. Georg (NMl) Richter, Co-President and Chief Operating Officer for GuthyRenker, LLC. Mr. Richter identified himself as the most responsible individual for the firm at the facility at time of inspection start. On 8/20115 I beld a closing meeting with finn management for the concurrent Wen (FACTS 11517872) and PADE (FACTS 11476675) inspections; no FDA 483 , lnspectional Observations, was issued however several items were discussed with firm management. See the "General Discussion with Management" section for additional information on discussion items related to the Wen inspection. Mr. Bill Gutby, Co-Founder, was present for a portion of the closing meeting. 3 of26 Establish ment Inspection Report Guthy-Renker, LLC FEI: EI Start: Santa Monica, CA 90405-3268 EI End: 30075136 15 08/1 2/2015 08/20/2015 History This is the second inspection by the US FDA of Guthy-Renker, LLC (GR) a direct marketing company involved in marketing and di stribution of FDA regulated products including over-thecountcr (OTC) drug products, dietary supplements and cosmetics. Guthy-Renker LLC is a limited liabi lity corporation founded by Bill Guthy and Greg Renker; the fitm was incorporated in the state of Delaware in 2008. Distribution of FDA-regulated products has been consolidated under two legal entities since the last inspection: Guthy-Renker, LLC and Meaningful Beauty, LLC. Film management repo1ted that all quality-related activities for FDA regulated products are handled by employees of Guthy-Renker. GR provides quality-related operations for brands distributed by Guthy-Renker, LLC and Meaningful Beauty, LLC to include handling of deviations and change control, complaint (quality and adverse event) review/routing/investigation, and serious adverse event (SAE) reporting for OTC and dietary supplement products. Wen products owned by GR are distributed by Guthy-Renker, LLC (Palm Desert). Examples of Wen Cleansing Conditioner label proofs can be found in Exhibits 10-36. GR operates out of two locations in Southern California: Palm Desert (41-550 Eclectic Street, Suite 200, Palm Desert, CA 92260-1967) and Santa Monica (inspected location). Ms. Malakian reported that operations at the PaJm Desert office are being phased out; Palm Desert operations currently include Supply Chain, Accounti11g and Information Technology. Guthy-Renker Product Development, Quality, Executive, Legal, Supply Chain, Finance, Markefa1g, and Operations departments were repotied to operate from GR Santa Monica. GR, Santa Monica, is located in a lhree-story building in a corporate business park; Guthy-Renker operations occur on all three floors with the main visitor entrance located on the third floor. GR operates Monday through Friday from 9 am to 6 pm. Ms. Malakian reported shortened business hours on Fridays between Memorial Day and Labor Day (9 am to 3 pm). No recalls have been conducted for Wen product. On 8/20/1 5 Mr. Bill Guthy, Co-Founder and Co-Chairman for Gutby-Renker, LLC, stated that O fficia l fi rm corresponde.nce should be addressed to: Mr. John Graza!, Vice President of Quality Assurance Clo Guthy-Renker, LLC 3340 Ocean Park Blvd. Santa Monica, CA 90405 The firm is not registered with the US FDA. The facility is the Corporate Headquarters for GuthyRenker, LLC (GR) which is a direct-marketing firm responsible for marketing and distrjbution of FDA Regulated OTC drug, dietary supplement and cosmetic products; no FDA regulated products are manufactured, packed or stored for distribution at this location. 4 of26 Establishment Inspection Report Guthy-Renker, LLC Santa Monica, CA 90405-3268 FEI: 3007513615 E1 Start: 08/ 12/20 15 EI End: 08/20/2015 Interstate Commerce/Jurisdiction GR LLC markets, distributes, and provides quality-control activities for FDA-regulated over-the-counter (OTC) drug products (acne medications, sunscreens, etc.), cosmetics (facial and hair care), and dietary supplements (vitam ins) under brands including Proacliv, Meaningful Beauty Wellness, X-Out, Sheer Cover, Natural Advantage, Wen by Chaz Dean and Principal Secret. The firm has consolidated distribution activities for FDA-regulated products under two legal entities since the last FDA inspection in 20 12: Guthy-Renker, LLC and Meaningful Beauty, LLC. A list of GR LLC associated locations (contract manufacturers, contract testing laboratories), call centers, fulfillment service distribution locations, and GR related locations for all GR regulated products is included in Exhibit 1. A list of Wen Cleansing Conditioners (GR-owned formula) with formula number/version, filled good item code and associated manufacturing locations is included in Exhibit 2. A list of Cleansing Conditioner fini shed and seasonal; good item numbers and associated label codes manufactured by(bff•> formulation owned by tb1<4J is included in Exhibit 3. The associated seasonal varieties are as follows: E C leansing Conditioner Va riety Associated Label Codes Fall Ginger Pumpkin CD.LAB093, CD.LAB130, CD.LAD131 Winter Vanilla Mint CD.LAB094, CD.LABl38, CD.LAB144 Spring Gardenia Green Tea Summer Mango Coconut CD.LABI05, CD.LABJ39 CD.LABl28, CD.LAB l29, CD.LABl63, CD.LABl64 Winter Cranberry Mint CD.LAB188 Spring Orange Blossom CD.LAB187 Summer Honey Peach CD.L/\B J99 Winter White Citrus CD.LAB229 Spring Honey Li lac CD.L/\8266 Summer Coconut Lime Verbena CD.LAB272 Fall Tuscan Pear CD.LAB322 A list of current Wen product formu lations. item codes and manufacturers (other than Cleansing Conditioner) distributed by Gulhy-Renker, LLC is incJuded in Exhjbit 4. As a direct marketing company GR primarily deals in direct customer distribution of products from warehouse locations in the United States and abroad. Primary distribution centers for GR in the US, Guthy-Renker Fulfillment Services (East and West), are located in Arden, North Carolina and Foothill Ranch, CA, respectively (see Exhibit 1, p. 5). Firm management reported that GR Wen products are sold through GR infomercials, websites (i.e. www.wen.com, www.amazon.com), retail locations (Sephora) and mall-based kiosks (NAK and ZOOM). GR Wen product is sold internationally through QVC (Germany, United Kingdom and Japan: Exhibit 5) however firm management reported that Wen product distributed through QVC in the United States is product owned by Chaz Dean Studios (Studio). Wen Cleansing Conditioner is/has been manufactured for GR by multiple contract , {bJ(~> CfiJ(-..Ymanufacturers in the United States including: (bJ<•i - 5 of26 Establishment I nspection Report FEI: El Start: Guthy-Renker, LLC EI End: Santa Monica, CA 90405-3268 3007513615 08/12/2015 08/20/2015 and Cb><4> No product is manufactured, stored or distributed from the Corporate HQ location in Santa Monica. (bff4J , Firm management provided distrihution volume of domestically distributed product between 8/2014 and 7/20 15 (Exhibit 6). Based on the provided information Chaz Dean (Wen) is the firm's second highest selling brand. In the rolli ng 12 month period GR LLC distributed over 2 million Chaz Dean Kits. Wen product brochures included with shipments for entry (CD.CATO I 0) and continuity (CD.CATO 11) customers are included in Exhibits 7-8, respectively. Individual Responsibility an d Persons I nterviewed Individuals who were present during the inspection and/or provided information during the inspection include: M r . Georg (NMI) Richter, Co-President and Chief Operating Office1; was present for the opening meeting and identified himself as one of the two most responsible individuals for Guthy-Renker in absence of the firm 's Co-Founders and Co-Chai11nen, Mr. Bill Guthy and Mr. Greg Renker. Mr. Richter reported responsibility for dai ly operations including product manufacturing, distribution, logistics and customer service. He reports to GR Co-Founders and Co-Chairmen Bill Guthy and Greg Renker. John Grazal, Vice President of Quality Assurance, has been employed by GR since April 20 12. He has previous pharmaceutical experience with AstraZeneca and reported current responsibi lities to include oversight, management and leadership of che Quality Assurance team and communication of quality issues to executive management. He has hire, fire and spending authority for the quality group and reports to Mr. Dirk van de Bunt, EVP and ChiefAdministrative Officer (CAO). Mr. Graza] was present during the inspection on 8/J 7, 18, and 20/2015 and provided some of the information contained in this report. Silva (NMJ) Mala kia n , Co-Director of Quality Assurance, has been employed with Guthy-Renker since July 2012. She has responsibility for Guthy-Renker Quality systems including product complaint handling (quality complaints and adverse events), serious adverse event repo1ting, validation, product stability, and technology transfer for manufacturers. She reported having hire, fire and spending authority for her areas of responsibility. Ms. Malakian has previous experience with cosmetic, OTC, implantable medical device, and biotech products. She repo1ts to Mr. John Graza!, Vice President of Quality Assurance. (WiUiam) Keith Nelson , Co-Director of Quality Assurance, has been with Guthy-Renker for approximately nine years and has been in his current position for approximately 5 years. M r. Nelson has responsibility for daily quality operations and oversight of contract manufacturing organizations involved in production of GR d istributed products and deviations surrounding product manufacture. Mr. Nelson provided information 011 contract manufacturing operations, product recalls and associated communication to the LOS-DO Recall Coordinators, manufacturing batch records, manufacturing deviations and affected production lots, and corrections implemented to Observations cited during the 6 of26 Establishment Inspection Report Gutby-Renker, LLC Santa Monica, CA 90405-3268 FEI: 3007513615 EI Start: 08/ 1212015 EI End: 08120/2015 2012 FDA Inspection. He has input in employee hiring and firing but reported no spending authority and reports to Mr. John Graza I, Vice President of Quality Assurance. Lisa McCa be, Senior Director of Global Supply Chain , has been in her current position since January 2015; she was previously the Director of Global Supply Chain for approximately 1 year. Ms. McCabe provided information on transition from Kathon to Kathon-free formulations for Wen Cleansing Conditioner, status ofKathon containing product kits in inventory, and first distribution dates for the top five Cleansing Conditioner varieties. She reports to Mr. Barry McMul len, Senior Vice President of Operations. Mr. Daniel J. Kolhoff, Director of Regulatory Affairs, repo1ted over five years in his current position . He stated his daily responsibilities include formulation review, label review, and international compliance. Mr. Kolhoff provjded information on the label creation process from GR-owned and contract manufacturer-owned product formulas, labeling order of ingredients for Wen Cleansing Conditioner, and ingredient lists provided by contract manufacturers for manufacturer-owned formulations. He has hire, tire, and spending authority and repo1is to Ms. Stephanie Blackman, Senior Vice President ofBusiness Affairs and Legal and General Counsel. Maureen M. Koo, Director of Product Development, has been in her current position for approximately 2 years with 4.5 years prior experience as a GR Product Development Manager. Ms. Koo reported her areas ofresponsibility to include oversight of product development to include the product development process, relationships with research and development laboratories, and ensuring projects are complete and on-time. She has hire, fire, and spending authority for her areas ofresponsibility and reports to Mr. Scott Bruce, Senior Director ofGlobal Product and Packaging Development. Firm's Training Program l reviewed the firms Training Procedure QA-109 "GMP Training Program" effective 12/23/13 as weU as training files for GR employees involved in complaint call intake and documentation in ~ medical assessment of adverse events/serious adverse events, and packaging and labeling development. Training topics arc dcte1mined by the employee position description and includes a combination of SOP review, GMP training, and PowcrPoint training presentations. The reviewed training files appeared to include documentation of training in the employees areas of responsibility. Manufacturing/Design Operations Gulhy-Renker, LLC operates as a Direct Marketing finn which distributes FDA regulated products directJy to consumers, as well as through retail stores, on-line merchants, and further distributors. FDA regulated products include over-the-counter drug products (topical acne and sunscreen; monograph), cosmetics, and dietary supplements which are manufactured for Guthy-Renker by contract manufacturing facilities. No manufacturing, storage, or distribution occurs at the inspected location. The current inspection covered contract manufactw"ing oversight, distribution practices, formulation changes, product and ingredient safety testing, complaint handling and label ing of Wen 7 of26 Establishment Inspection Report Guthy-Renker, LLC Santa Monica, CA 90405-3268 rm: 3007513615 El Start: 08112/2015 08/20/2015 El End : by Chaz Dean C leansing Conditione rs distributed by Guthy-Ren.ker, LLC. Finn managemenl reported that GR owns Wen product distri buted by Guthy-Ren.ker, some of the product fonnulatioos, and is responsible for product labeling and complaint handling for GR distributed Wen products. Similar Wen products may be distributed by Chaz Dean Studios however the product ingredients may be different (i.e. different preservative system). GR is only responsible fo r complaint handli ng of Wen products distributed by Guthy-Renker. The contract between Gutby-Renker and Chaz Dean Studios, with amendments. is included in E xhibit 9. Cleansing Conditioner Formuu1tions GR provided information on Cleansing Conditioner varieties distributed by Guthy-Renker, LLC which may include product formula, label proofs, AET (antimicrobial effectiveness testing), HETCAM (Hen's Egg Test- Chorio Aliantoic Membrane), RlPT (Repeat Insult Patch Test), and stability studies. Product fonnulas for routine varieties (avai lable year-round) were reported to be owned by 4 Guthy-Renker, with the exception of the formula for r>14> _(b>C > 4 b (a.k.a. (bf!-4> >rm ) which is owned by (bH l •. ProJuct fo1mulas for seasonal varieties (manufactured only for one or two seasons) were reported to be owned b~lb1C4) ; GR does not have documentation covering these product fom1ulations. Ms. Malak ian reported that GR may have created a formu la number for some of the f6)l41 .owned products however GR does not have formulation information as the formulas arc owned by (bffil . The table below includes Cleansing Conditioner varieties distributed by GR (GR owned formulations) with associated Exhibit numbers. Wen Cleansing Conditioner variety Sweet Almond Mint (SAM) Routine/ Kath on/ Kath on- GR Formula Number/version Exhibit Free Seasonal GR~l Routine J Kathon Exhibit 10 Formulas pp 1-8; studies pp. 9-50; labels pp 5194 Kathon-Free Exhibit 11 Formulas pp 1-14; studies pp. 15-62; labels pp 6380: batch record pp. 81- ~ GR!bH4J ( ingredient trade name change: (b)14) _ GR">H4l ) _J (glycerin supplier change) G.R<•l (reduce formula percent-Wheat Tein and Actiphytes from (bfl.C)i:o (bl(l) %) GRll>l<4> E:J l (pH specification in citric acid) 8 of26 207 I Establishment Inspection Report Guthy-Renker. LLC Santa Monica, CA 90405-3268 Tea Tre.e FEI: 3007513615 08/ 12/2015 08/20/2015 EI Stru1: El End: GRll>1<4) Routine GR_ 4 - Kathon; SOY (INC! change for Lipovol ALM) Exhibit 12 Formulas pp 1-5; studies pp. 6-44; labels pp 4558 GR1b><4> (Change from soy to wheat based) G~ fb)(4) Kathon; Wheat Exhibit 13 Formulas pp 1- IO; studies pp. 11-48; labels pp 4955 Kathon-free Exhibit 14 Formulas pp 1-12; studies pp. 13-33; labels pp 34- ) GR(b)<4l I (glycerin change) GRJb>C4J (preservative change) GR (6}f4> (Wheat Tein and Actiphyte reduction) 43 I GR!D)(4) (pH increase/reduce citric acid) Fig Routine GRt(6>T4l Kathon Exhibit 15 Formulas pp 1-1 O; studies pp. 11-52; labels pp 5376; batch record pp. 77 - 125 Kathon-Free Exhibit 16 Formulas pp 1- 12; studies pp. 13-35; labels pp 3641 Kathon Exhibit 17 Formulas pp l -1 O; studies GR(6ff4> fb)(4) GRi(6Jl4J - ) I (glycerin change) GFb)f4J (preservative change) GR'b1C4l (Wheat Tein and Actiphyte reduction) GRt'b)(4J (pH increase/reduce citric acid) Pomegranate Routine G Cb><•> G~ '(D)(4) ') pp. 11 -60; GRfH4> (preservative change) 9 of26 Kath on-Free labels pp 61 77 Exhibit 18 Formulas pp 3007513615 FEl: El Start: Establishment Inspection Report Guthy-Renker, LLC Santa Monica, CA 90405-3268 08/ 12/2015 08/20/2015 El End: GR lllH~> 1-15; studies pp. 16-57; labels pp 5872 (Soy and Actiphyte reduction) G OJH•) (pH increase/reduce citric acid) Lavender - orf'I> Kathon-Free (preservative change) Exhibit 21 Formulas pp 1-15; studies pp. 16-38; labels pp 39- GRfblt•1 (Wheat Tein and Acriphyte reduction) 50 G.RP'JC4l (pH increase/reduce citric acid) Cucumber Aloe Routine GRll>>T•> Kath on G~ l e1x4i - Fonnulas pp I -12; studies pp. 13-54; labels pp 55- l GR\bl\4J (glycerin change) GRf> 141 Grub><•> (wheat Tein and Acriphytc reduction) GR 1>)(41 86 Kat hon-Free (preservative change) - Exhibit 22 Exhibit 23 Formulas pp 1-12; stud ies pp. 13-34; labels pp 35- 47 (pl 1 increase/reduce citric acid) The table below includes Cleansing Conditioner varieties distributed by GR (product formula owned bY.bH4l ) with associated Exhibit numbers. I 0of26 FE1: EI Strut: Establishment Inspection Report Guthy-Renker. LLC Santa Monica, CA 90405 -3268 (b)(4) (b}(4) (b)(4) (b)(4) ~ (a.k.a. lbl !4 > Routine 3007513615 08/ 12/2015 08/20/2015 Ef End: GRlbJ(4J j Kath on Formula p 1; studies pp. 238; labels pp 39-42 )) GRH•l - J Studies pp I21 ; labels pp 22 -30 Winter VaniUa Mint (a.k.a. Chocolate Mint) Seasonal Spring Gardenia Green Tea Seasonal Summer Mango Coconut G~bJC4> J Kath on Exhibit 27 Studies pp I31; labels pp 32-40 GR(6H•1 J Kath on Exhibit 28 Studies pp 116; labels pp Seasonal GR!blr•> - 17-22 - Kath on Exhibit 29 Studies pp I37; labels pp 38 -5 1 Winter Cranberry Mint Seasonal GRlb)(4> J Kathon-Free Exhibit 30 Stud ies pp I37; labels pp 38-40 Spring Orange Blossom Seasonal GR!b)(4J l Kathon-Free Exhibit 31 Studies pp I37; labels pp 38-40 Summer lioney Peach Seasonal GRlb><•> Kathon-Free I Exhibit32 Studies pp I37; labels pp 38-40 Winter White Citrus Seasonal GR (not yet marketed) J Kathon-Free Exhibit 36 Labels pp l-3 Ms. Malakian reported that the Cleansing Conditioners we.re refonnulate ) to comply with original formulations frorrfbfi4> Wen Product/I ngredient Sttulies GR provided RJPT, HET-CAM and AET test results for a majority of the early Cleansing Conditioner fonnulations (see Exhibits in table above). Ms. Koo, Director of Product Development, reported that during the time of K.athon preservative replacement GR Product Development decided to bracket the Cleansing Conditioner studies (RIPT and HET-CAM) to cover multiple varieties. She 12 of26 FEI: Establishment Ins pection Report Guthy-Renker, LLC Santa Monica, CA 90405-3268 El Start: El End: 30075136 15 08/ 12/20 15 0812012015 slated that a "kitchen-sink" formula was manufactured by which would represent all Cleansing Conditioners except Sweet Almond Mint. The formula was reported to include ingredients from all of the cleansing conditioners; a separate study was done on SAM. T he kitchen sick formulation is included in Exhibit 42 along with j ustification memo and study reports. Legally Privilege percentages • The infonnation is double checked • Fonnula with CAS numbers is created • Ingredient list is built based on ingredient percentages o Ingredients included in fonnulation at greater than or equal to l % in order from highest quantity to lowest quantity fonnat with INCi numbers and ingredient 13of26 FEI: Establishment Inspection Report Guthy-Renker, LLC Santa Monica, CA 90405-3268 o EI Start: El End: 3007513615 08/ 12/2015 08/20/2015 Ingredients included at less than I % listed next typically with fragrances and colors at the bottom. Mr. Kolhoff reported that since GR does not have access to manufacturer-owned fomrnlations the manufacturer will generally provide a list of ingredients in the product which will either contain a break between the ingredients in the formu lation above and below I% (Exhibit 49, p. 1) or wi ll Ji st ingredients with percentage ranges (Exhibit 49, p. 2). l asked M r. Kolhoff how the ingredients would be listed for those with ingredient ranges around 1%. He stated that the current practice would be to include the ingredients in order of predominance since the actual ingredient percentage is not known. Mr. Kolhoff reported tbat actual batch records are not reviewed for determination of product labeling. l reviewed product labels and fonnulations with Mr. Kolboff and asked why the earlier labels appear to include ingredients at percentages under 1% in the product formulation (i.e. Actiphytes of: Wi ld Cheny Bark, Rosemary, Chamomile) above those with percentages higher than 1% (i.e. Incromine (Stearamidopropyl Dimethylamine); See Exhibit 10 pp l-2, 5-6, 68 and 73 (Discussion). He stated that other GR employees (Product Development - US team) were involved in product labeling for US products before he took over in late 2012. He stated (bat the individuals previously involved with the ingredient statements were no longer with Guthy-Renker. A change control initiated in January 2013 to harmonize the directions for use for Wen CD Cleansing Conditioners is included in Exh ibit 50. Ms. Malakian repo11cd that the excluded item codes were either discontinued or the directi ons for use were not applicable due to the size of the container. I reviewed change control logs, deviation logs, label proofs, and product formulations for Wen Cleansing Conditioners. I asked GR firm management to request certain batch records from their contTact manufacturers for comparison with product formulations a nd label proofs provided by GR (see Exhibits ll , 15, and 52, 53). r observed one planned deviation in 201 J wherc<6><4> was omitted from Cleansing Conditioner batches manufactured at contract manufacturcr(bH4> but the ingredient was left on the labeled ingredient statement. I also observed discrepancies between product formulations (ingredient percentages) and the order that ingredients were listed on the product labels. Wheat Tein Formula Omission via Planned Deviation Treviewed the deviation and planned deviation logs from 201 1 to 2015 to try and identify any deviations for product ingredients, manufacturing issues, or out of specification testing results; I selected multiple deviations for further review. Planned Deviation 2321 (and 232 1 revision) was (contract manufacturer) to fill product without (lilC4 issued for GR approval fo1(b)<4 > % in Chaz Dean Sweet Almond Mint and Cucumber Aloe Cleansing Conditioner and Re-Moist Intensive Hair Treatment (Exhibit SJ, pp. 1-2). The deviation states that removing the material "will not alter the fin ished product's function, stability nor consumer safety" however the deviation does not address the removal of the omitted ingredient from the product label. The 14 of26 FEI: Establishm ent Inspection Report 3007513615 08/12/2015 EJ Start: El End: Guthy-Renker, LLC Santa Monica, CA 90405-3268 08/20/20 15 deviation was approved in October 2011 and covered a deviation time period of October 20, 2011 to October 30, 2011 for multiple SKUs including CD.0069 (PO 97 190), CD.0071 (PO 97190) ; CD.0072 (PO 97192), CD.0095 (PO 97475 and 97193). I asked Mr. Nelson to provide information on tbe Item Codes, products, Jots, quantity and last date of product distribution (Exhibit 51, p. 3). The products were identified as follows: • • CD.0069 : Chaz Dean (Wen) Cucumber Aloe Cleansing Conditioner (GRlbH4> o 2 oz. lot T l 319A; last distribution 111 1112 o 2 oz. lot Tl 3 l 8A; last distribution 2/ 15/12 ) ____ CD.0071 : Chaz Dean (Wen) Sweet Almond Mint Cleansing Conditioner (GRfbl/45 o 12 oz. lot Tl 312A; last distribution 11/29/ 11 • CD.0072 : Chaz Dean (Wen) Sweet Almond Mint Cleansing Conditioner (GR(bfC4> o 16 oz. lotT1301A; last distribution 12112/11 • CD.0095 : Chaz Dean (Wen) Sweet Almond Mint Cleansing Conditioner (G o 16 oz. lot Tl306A; last distribution 2/16/12 o __, o 16 oz. lot T1319D; last distribution 5/25/12 16 oz. lot Tl 319A; last distribution 6/12112 o 16oz. lotT1318B; lastdistribution7/20/ 12 4 ,_ tb>_<_> ) -~--' l asked Mr. Nelson to request batch records for lot codes T 130 I A and Tl3 l 8B which, based on GR lot coding convention for their contract manufacturers, would bracket production dates between the 301 st day of 201 1 (10/28111) and the 318111 day of 2011 ( I 1/ 14/2011 ). Mr. Nelson provided !b}1l) batch records and stated that lot Tl 3 l 8B was manufactured with bJ<4l (see Exhibit 52, p. 5) however Jot Tl 30 I A did not contain (bH4 J (see Exhibit 53, p. 5). I asked Mr. Nelson to and be provided further confirm which of the previously provided Jots did not contain (6)(4! the updated chart in Exhibit 51, p. 4. Exhibit 52 contains the batch record for T 13 18B filled using bulk batch 3440488 and label CD.LAB054 (Exhibit 52, p. 23). Exhibit 53 contains the batch record for T1301A filled using bulk batch 3378764 and label CD. LAB054 (Exhibit 53, p. 23). Neither batch record contained an example of the label applied to the product but both indicated use of the same label code, CD.LAB054. Exhibit 10, p . 73 contains the label proof for CD.LAB054; the label includes Hydrolyzed Wheat Protein as the tenth ingredient and based on the batch records was applied to product which included and did not include <•l (Discussion). I asked Mr. 'elson why the deviation djd not include coverage of the need for label revision due to the ingredient omission. Mr. Nelson stated that the deviation occurred during the time period when the quality depat1ment was short staffed (GR dissolved the ir Quality Assurance department in 2008; see 2012 EIR for GR and associated firms for additional info.). Exhibit 54 contains Planned Deviation 2037 issued to extend investigative response receival dates for multiple deviations. Although the (bf!4J Cbl(4l deviation is not listed in the extension the document references reduction in quality staffing and was issued in April 2011. 15 of 26 Establishment Inspection Report Gutby-Renker, LLC Santa Monica, CA 90405-3268 FEJ: 3007513615 El Start: EJ End: 08/]2/2015 08/20/2015 Ingredient Order of P redominance I reviewed a few product formulations and associated product labels for Cleansing Conditioners manufactured between 2011and2015. I used the comparison table provided by the finn (Exhibit 2) to determine which labels went with which formulas. I noticed that earlier labels (i.e. Exhibit 10, p. 68 (CD.LAB053) and Exhibit 10, p. 73 (CD.LB054)) !b><4 > (see E xhibit 10 pp. 1-6). Product labels reviewed for later fo rmulations appear to list ingredients abovc(6f(4} (see E xhibit 11, p. 1-12 (GRl 208100) and Exhibit 11, p. 76 (CD.LAB189). I asked Mr. Kolhoffwhy the ingredients were not listed in order of predominance for CD.LAB054. He stated that the label review for these products occurred before he started to conduct domestic label review for regulatory. He stated that the individuals previously in charge oflabel review were no longer employed with Guthy-Renker and he did not know what their criteria were for Jisting ingredients on the label. Ingredient listing was discussed with firm management during the closing meeting. Leave-flt Conditioner The change control covering replacement of Kathon in the Wen Cleansing Conditioners indicates that the change was for continued marketing as a leave-in conditioner. Ms. McCabe stated during was no longer able to sel 1Katbon inventory and the inspection that in 2013 the (Sf(~rQVC wanted Kathon-free inventory (GR Wen products are distributed through QVC in Japan, Germany and the United Kingdom; Exh.ibit S). Ms. Malakian provided information on raw material Kathon CG (methylchloroisolhiazolinone (MCI) and methylisothiazolinone (Ml)) which was used as the preservative in early formulations of Wen Cleansing Conditioner (Exhibit 55); and Euxyl (phenoxyethanol and ethylhexylglycerin) the preservative which replaces Kathon in the current Wen Cleansing Conditioner fomrnlations (Exhibit 56). Ms. Malakian stated that the fum has not conducted any studies specifically related to leave-in treatment directions for the Cleansing Conditioners. Actiphy te of Wild Cherty Bark vs. Actipltyte of Wild Clten y Fruit Extract During label review I noticed that some products list Actiphyte of Wild Cherry Bark (i.e. SAM and Tea Tree) and some products list Actiphyte of Wild Cherry Fru it (i.e. Fig and Ginger Pumpk in). I asked Ms. Malakian what the difference was between Actiphyte of Wild Cherry Bal'k and Actiphyte of Wild Cherry Fruit and Ms. Malakianprovided the infom1ation contained in E xhibit 57, pp. 1-2. I noticed that the composition statements both listed Wild Cherry Fruit Extract but also noticed that the product name for the composition statement identified to be for "BARK" was not the same as that listed in the product fomrnla statements !bH4) (Exhibit 57, (Exhibit 11 , p. 111)). Ms. p. 2) vs. Actiphyte of Wild Cheny Bal'k b>C4l Malakian said that the Compo~ i tion statements were provided by the material supplier, Active Organics. She later provided Material Safety Data Sheets fo r Actiphyte of Wild Che1ry Fruit tb1<4> and Actiphyte of Wild Cheny Bark(b)(4) (Exhi bit 57, pp. 3-10). The MSDS list Wild 16of26 Establishment Inspection Report Guthy-Renker. LLC FEl: 3007513615 El Start: 08112/2015 0812012015 El End: Santa Monica, CA 90405-3268 Cherry Fruit and Wild Cherry Bark in the INCI names, respectively. Ms. Malakian stated that some products use Wild Cherry Bark and some use Wild Chen-y Fruit. A dverse Event Tntake/Processing/Reporting I reviewed QA-I 04 "Product Complaint Handling Process'', revision 5, dated 2/2/15. Ms. Malakian stared that in March 2014 QA-104 "Customer Complai nt Procedure" and QA-1 05 "Adverse Event Reporting" were combined into one procedure. The "Product Complaint Handling Procedure" covers complaint (quality and adverse event) receipt, processing, evaluation, ti·ending, investigation a nd filing of serious adverse events. The genera] process flow for adverse events is as follows: (b}(4) (b) (4) (bJ(4) (b){4) .[]. (b)(4) GR has an "Adverse Event Hair Care Survey (HA1RAER0114Y' (Exhibit 58) which is included as attachment QA-133C to QA-133 'ib>l4 l CRS User System Operation" (effective March 31, 2014). The Survey is used by the CCCAT during receipt of hair-related adverse events. I asked if the 17of26 FEI: EI Start: EI End: Establishment Inspection Report Guthy-Renker, LLC Santa Monica, CA 90405-3268 3007513615 08/ 12/2015 08/20/2015 customer service agents or CCCAT agents followed any script for handling adverse event/complaints reported for hair loss. Ms. Malakian requested the call scripts from the call center (Exhibit 59). The received script has a reference to the "lawsuit" across in (b)14f the top of the first page. I asked Ms. Malakian ifthere were versions of the script prior to the lawsuit. Ms. Malakian reported that the "lawsuit" verbiage is intended to alert the agent to forward the call to the CCCAT agents. The script contains responses regarding hair loss, the lawsuit, and FDA/government action regarding Wen. On 8/13115 I received arfb><4> searchable file containing adverse events exported from (6)141 An exact copy of the tile from the thumb drive is included in .Exh ibit 60. The file contains (bH4 > adverse event records (bl<•) lines with one for the column headers). I filtered the list for "Count1y Sort" (United S; US, USA, USDTUSA, UST, USTUSA and USUSA~ USTCANADA was reported to be a Canada complaint); "Prod Lev 3 Desc'' (CD Cosmetics); "Product Desc" (Wen* Kit·• Wen Cleansinal:> Conditioner*·> and Wen lbJC4> and "Subiect Desc" J (Hair Loss *); the search returnec:f>><4> record entries between 8/30/201 J and 8/12/2015. Further filtering by year returned the following: • 2011: lDf~J records (August 30, 2011 - December 31, 20 I 1) • 2012: bH4> 4 • • 2013:<"> records (January 1, 2015 - August 12, 2015) Tselected multiple examples of Wen hair loss complaints for further review with Ms. Malakian in the (b)!4> system. Examples ofEI generated complaint reports for adverse evems related to hair loss/hair breakage after Wen use are included in Exhibits 61-75. 1 also observed reports of hair toss complaints (eyelash, eyebrow, hair loss/thinning) for use of product(s) from the following brands: Meaningful Beauty, Proactiv, Endless Youth, XOut, VitaClear, Sheer Cover, Triverex (discontiJmed dietary supplement) and VitaPower (total of<4> reports between 9/ 18/2011 and 7/25/20 I 5; filter for ··subject Desc" bl<4 f ; "Prod Lev 3 Desc" dbH4 ) ; "Country Sort" = (b}(4) ). Mr. Grazal reported that GR does not conduct quality investigations for adverse event complaints; investigations will be initiated for quality defect complaints which include a product lot number. He repo11ed that Certificates of Manufactw·e (COM) or Certificates of Analysis (COA) are reviewed by the Quality department at time of product release along with any associated deviations. Ms. Malakian reported that complaints arc trended on a monthly basis and investigations may be opened in response to upward trends. Ms. Malak:ian reported that aside from the studies conducted on the Cleansing Conditioners, an overall quality investigation for Wen hair loss complaints has not been opened by the Quality department. An excerpt from the Product Complaint Trend Review data for Adverse Events conducted by GR in June 2015 is included in Exhibit 76. The Chaz Dean (Wen) data page states that "Hair Loss Complaints remain flat at ITTiJ (May af>H4> ), however overall represents an increase in the total number of complaints for this category". The graph indicates that Cbll4 > complaints for hair loss were received for Chaz Dean (Wen) brand products in the last 12 18of26 FEI: EI Start: Establishment Inspection Report Guthy-Renker, LLC Santa Monica, CA 90405-3268 El End: 3007513615 08/12/2015 08/20/20 15 months; hair loss is the number one complaint category for this brand. I asked Ms. Malakian lo provide complaint trend data fo r Wen Cleansing Conditioner (shipments, hair loss adverse events, and ratio) between November 201 I and August 20 I 5 (Exhibit 77). The data includes number of units shipped in a given month (kits and individual units combined; single unit or a kit counts as one shipped unit), complaint count received during that month, and ratio of complaints per number of total units shipped. The ratio for " All Cleansing Conditioners" was highest in April 2015 <6)(4 %; t&Tl•J complaints received). Wen kits may be standard issue or customized by returning customers and may contain more than one product variety in one kit. Ms. Malakian stated that the ratio of hair loss complaints has remained fairly constant; however the fim1 did notice a spike after announcement of the Wen class action lawsuit. Manufacturing Codes Wen products distributed by GR , LLC include a lot code printed either on the bottom of the bottle or on the s ide of the label. The lot code includes a one or two dig it alpha code designating the product manufacturer. Exhibit 78 contains QA-116 "Lot Coding Requirements for Gulhy-Renker Items" a long with an internal document listing the contract manufacturers and associated A lpha code. Cosmetic products do not contain expiration dates or dates of manufacture. Examples of codes applied to Wen Cleansing Conditioners are as follows: " AP3127A" (Sweet Almond Mint Cleansing Conditioner I 6 oz.; CD.O 151; Kathan-Free) "AP" "3,, d b) (4) ~==============::--~~~~~-' =,(b){4) :::::::::---=============:::..._~~~~~~~ "12 7" =(6f<•> "A" :::ll>l(•i - ~~~~~~~~~~~~~~~~~ "Tl301A" (Sweet Almond Mint Cleans ing Conditioner 16 oz.; CD.0072) "'1'"' "1 " "30 I" "A" = (bj(4) =(b)(4) ={b)(4) = {b)(4) "Tl318B" (Sweet Almond Mint Cleansing Conditioner 16 oz.; CD.0095) "T" = b)<-0 :---===========:::::::::::--~~~~~~~~ "1 "' "318" " B" = {b)(4) =Fr•> ~6)(4) "GR3058B" (Fig Cleansing Conditioner, 16 oz.; CD.0075) "GR'. =f>H4l 19 of26 Establishment Inspection Report Guthy-Renker, LLC Santa Monica, CA 90405-3268 =~ "3" '·058" =FN "B" FEJ: 3007513615 E I Start: 08/12/2015 08/20/2015 El End: ) =f 41 I reviewed one deviation (Dev 2040) which repo11ed use of lot codes for Wen product which were not in GR format; the products included Wen C leansing Conditioners Fig, Lavender and Tea Tree produced afb'C•l for a marketing test (deviation opened in 2011). The product code is a 5-digit numerical code fo llowed by an 8-digit numerical code. Mr. Nelson said U1at the product was purchased from Chaz Dean Studio as a marketing test and therefore the lot codes were not in GR format. A list of associated lot codes with product descriptions is included in Exhibit 79. Complaints 1 reviewed the firm's product complaint handling procedure as well as a,Cb1C4 > generated file for qual ity complaints associated with Wen products. Firm management stated that GR is responsible for complaint handling for GR distributed product; the Studio is responsible for complaint handling for Wen product distributed by Chaz Dean Studios. A contract between GR and Chaz Dean Studios is included in Exhibit 9. Complaint information is received primarily through call centers however complaints and adverse events may a lso be received via letter, e-mail, social media, the GR legal department, and external sources (FDA, Better Business Bureau, etc.). Quality complrunts and adverse events received through the cal l center are escalated to the CCCAT for entry into Cb><4 > CRS, the finn's complaint record system . GR QA performs investigations into product quality complaints based on a tiered approach when associated lot codes are provided. Minimum investigation criteria for product quality complaints associated with an identifiable product lot incl udes review of the Ce1tificate of Manufacture/ Certifi cate of Analysis and trend review for the specific lot and product. The .firm also conducts investigations for product lots associated with Se1ious Adverse Events (OTC and dietary supplement products) and observed increases during complaint trend review (i.e. increase trend in broken containers, etc.). Mr. Graza! reported that quality investigations are not conducted for reported adverse events as the quality depaitment reviews Certificates of Manufacture and/ or Certificates of Analysis at time of product release. GR docs not submit SAE events for cosmetics. There are four product complaints listed in FACTS for Guthy-Rcnker, Santa Monica; three for Wen hair care products and one for Proactiv. A summary of the Wen complaints is included below: • 123249: Complaint received in November 2011 fo r hair loss associated with Wen Cleansing Conditioner Fig Scent; no lot code was provided. Complainant reported purchase of product from the QVC Charu1el. During the inspection GR firm management repo11cd that Wen products distributed by Guthy-Rcnker are not sold through QVC in the United States. GR has received muliiple complaints for hair Joss associated with use of Wen by Chaz Dean hair care products. GR has conducted studies of Wen hair care products/ingredients and Mr. 20 of26 FEI: Establishment Inspection R eport Guthy-Renker, LLC Santa Monica, CA 90405-3268 EI Start: El End: 3007513615 08/12/2015 08/20/2015 Grazal reported that study results have not indicated that hair loss is attributable to the products/i ngredients. • 137270: Complaint received in June 2014 for hair loss associated with Wen hair care products. The complaint originated from the ~4 > Reporting System and indicates that the complaint was also reported to other sources including Wen Hair Care; no product lot code was provided. GR received the complaint from the FDA and entered the information in 4 11>>< > As no lot code or identifying patient information was provided, firm management reported that they were not able to contact the customer for further product information or conduct an investigation into the product lot. GR has received multiple complaints for hair loss associated with use of Wen hair care products between 2011 and 2015. GR has conducted studies of Wen hair care products/ingredients and Mr. Grazal reported that study results have not jndicated that hair loss is attributable to the products/ingredients. • 138190: Complaint received in July 2014 for eye pain, headache, vision loss, and diagnosis of Herpes Zoster associated with use of Wen Sweet Almond Mint Cleansing Conditioner and Re-Moist Intensive Hair Treatment. The complaint includes two lot numbers (AP2356A and AP2277A) and indicates that the complaint was reported to the product manufacturer. l was not able to find a similar quality or adverse event complaint for these symptoms or lot numbers in the (b) <4> database. l asked GR QA if they were aware of any similar report and they stated that they were not aware of any Herpes complaint related to use of Wen; they also stated that they could not find a similar complaint in c1>n•> based on the lot numbers or complaint symptoms. CFSAN CAERS Complaints In addition to the FACTS complaints associated with GR Santa Monica, CFSAN has received multiple adverse events through CAERS for Wen hair care products. Guthy-Renker was sent a letter by the FDA in January 2014 which included a list of CAERS lot/batch numbers reported in Adverse Events. During the cun-ent inspection l asked Ms. Malakian to assist in confirming the contract manufacturing locations for the received lot codes included with the Assignment. Ms. Malakian confirmed contract manufacturing locations, varieties, and preservative systems for GR distributed product and helped to identifying product codes which were not associated with Guthy-Renker distributed product. Ms. Malakian stated that the lot codes reported as long strings of numbers are similar to the lot code format used by Chaz Dean Studio. She further stated that she has seen the numerical code listed on one line or separated into two printed lines with the 5-digit number on the first line and the 8 digit number on the second line. An updated Wen AER data sheet is included as an Attach ment to trus repo11. 21 of 26 FEJ: Establishment Inspection Report Guthy-Renker. LLC Santa Monica, CA 90405-3268 El Start: El End: 3007513615 08/ 12/2015 08/20/20 15 Recall Procedures The firm has a recall procedure in place. The firm recalled four OTC drug products under two recalls since late 2011. All recalled products were not meeting active ingredient label claim (stability failures) am] includt:: Proacliv Renewing Cleanser; Proactiv Repairing Treatment; Proactiv Concealer Plus; and Proactiv Sheer Finish Compact Foundation (Salicylic Acid). Finn management was not able to provide a close-out letter for the Proactiv Sheer Finish Compact Foundation recall; GR will be resubmitting recall information for this product. Objectionable Conditions and Management's Response I did not issue an FDA 483, Inspectional Observations, at the conclusion of this inspection. Several items were discussed with firm management during the closing meeting. See the "General Discussion with Management" section for more information on discussion items. Refusals There were no refusals. See the "Legally Privileged Review" section for infom1ation on Wen product/ingredient studies which were not provided by Guthy-Renker during the cuii-ent inspection. General D iscussion with Management On 8/20/ l 5 J held a closing meeting with management. No FDA 483, l nspectional Observations, was issued but multiple items were discussed with firm management. Firm representatives in attendance at the closing meeting include: Bill Guthy, Founder; Dirk Van De Bunt, EVP and CAO; Barry MacMullen, SVP Operations; Kimber Maderazzo, SVP Brand Management; John Graza!, VP QA; Silva Malaldan, QA Director; Keith Nelson, QA Director; Lisa McCabe, Senior Director Supply Chain; Diana Baronian, Senior QA Specialist; and Stephanie Blackman, General Counsel. Items cliscussed with firm management include: l. Documen tation: I discussed documentation issues with fin11 management during the inspection and again during the closing meeting with management on 8/20/15. 1 observed some possible discrepancies in verbiage recorded in lb~ complaint files in which the "Verbatim" (reported to be recorded at time of call) information did not always agree with descriptions provided by later case review. 1 mentioned to firm management that anyone recording comments in the case report should document whether the information was coming from conversation with the complainant, review of the recorded call or review of the complaint file, etc. lo help clarify where information is coming from. in the batch w ithout correction of product 2. Product Labeling (Omission of l'b>"T4) Jabel): 1 mentioned to Mr. Nelson during the inspection and to firm management during inspection close that product Jabels need to reflect the product formulation. l men tioned that 22 of26 FET: Establishmen t Inspection Report Guthy-Renker, LLC Santa Monica, CA 90405-3268 El Start El End: 3007513615 08/12/2015 08/20/20 15 omission o bl <4l in manufactured batches (Deviation M <4> should have been accompanied by a change to the product label. 1 stated that a product which lists an ingredient that is does not contain may be considered misbranded. The firm has not distributed the lots mentioned in the deviation since 2012. I mentioned to Mr. Nelson that since the fill dates cover a span of approximately 19 days there may be other lots of product wluch were manufactured during that time which were not specifi cally covered under the I observed examples of ingredient deviation but also did not include !bH4l removal/replacement after the 201 J timeframe where the quality unit was reviewing labeling to reflect the ingredient modification. 3. Product L abeling (Order of Predominance): I reviewed SAM fonnulations and product labels for G (D)l4 /CD.LAB054 and GR'6H4l /CD.LAB 189. I noticed that earlier labels (i .e. Exhibit JO, p. 73 (CD.LB054)) listed Actiphyte ingredients (WiJd Chen·y Bark, Rosemary and Chamomile; 0. 1 formula percent) above Tncromine (Stearamidopropyl Dimethylamine; l.O formula percent (see Exhibit 10 pp. 1-6)). Product labels reviewed for later formulations appear to list ingredients above t % in the order of predominance followed by ingredients included at less than 1% Listed in any order (see Exhibit 11, p. 1-12 (GR and Exhibit 11, p. 76 (CD.LAB189). I mentioned to film management that cosmetic ingredients should be listed in the order of predominance. 4. Review of manufacturing Batch Records : firm management reported that GR has final responsibility for product release however the fim1 does not typically receive manufacturing batch records fo r review. Firm management reported that release decisions are based on review of Ce1tificates of Manufacture and/or Certificates of Analysis provided with each lot as well as review or any associated deviations reported by the manufacturer. I mentioned to fi rm management that they should, at minimum, be periodically requesting ~md reviewing batch records for contract manufactured products to help ensure that manufacturing deviations are being reported and to verify that the manufactured product is consistent with product labeling. Samples Collected No samples were collected during this inspection. Commercial product is not manufactured, held, or distributed by the Corporate IIQ location. Voluntary Corrections Sec the EIR dated 8/2015 for Postmarketing Adverse Event Reporting (FACTS 8/20115) for status of conections to the 2012 FDA Inspection. 23 of26 11476675~ 8111/15 - FEl: El Start: EI End: Establishment Inspection Report Guthy-Renker, LLC Santa Monica, CA 90405-3268 3007513615 08/ 12/20 IS 08/20/2015 Exhibits Collected 1. List of associated faci Iities and addresses, 13 pp. 2. Wen Cleansing Conditioner information cross reference lists, 4 pp. r>< > 4 -owned Wen Conditioner reference list (613 and seasonal), I pp. 4. Other Wen products, 2 pp. 5. Chaz Dean Retail markets, I pp. 6. Rolling 12 month shipped units detail, 1 pp. 7. Wen product brochures included with shipments for entry (CD.CATOl O) customers, 12 pp. 8. Wen product brochures included with shipments for continuity (CD.CATO J J) customers, 12 pp. 9. Agreement between Guthy-Renker and Chaz Dean with amendments 1-3, 31 pp. 10. Sweet Almond Mint Cleansing Conditioner GR071340ICDB information, 94 pp. 1 I. Sweet Almond Mint Cleansing Cond itioner GR1208100, 207 pp. 12. Tea Tee Cleansing Conditioner GMc•> COB infom1ati on, 58 pp. 13. Tea Tee Cleansing Conditioner G~> in formation, 55 pp. 14. Tea Tee Cleansing Conditioner G (6)1'if information, 43 pp. 4 15. fig Cleansi ng Cond itioner GRP'Jr 1 information, 125 pp. 16. Fig Cleansing Cond itioner GR,(6}14) information, 41 pp. 17. Pomegranate Cleansing Conditioner GR!l:!Ti•l information, 77 pp. 4 18. Pomegranate Cleansing Conditioner GR< > info1mation, 72 pp. 19. Lavender Cleansing Conditioner GRlhH•J information, 57 pp. 4 20. Lavender Cleansing Conditioner GR!6l"1 > information, 26 pp. 4 2 1. Lavender Cleansing Conditioner GRlb>r > information, 50 pp. 4 infonnation, 86 pp. 22. Cucwnber Aloe Cleansing Conditioner G 1DIT r4 23. Cucumber Aloe Cleansing Conditioner GRC6H > information, 47 pp. 4 24.~ )GR!bf< > V10026-01 , 42pp. 4 25 lb~> ) GR'6> 110028-0 l , 6 pp. 26. Fall Ginger Pumpkin Cleansing Condjtioner GRlb)(4) f.bH4> , 30 pp. -=::::::::::::::::= 4 4 27. Winter Vanilla Mint Cleansing Conditioner GR(b>< J of.'>>< > 40 pp. 4 28. Spring Gardenia Green Tea Cleansing Conditioner (soy) GR~ __ _ _ _ _ __ 01, 22 pp. 29. Summer Mango Coconut Cleansing Conditioner (soy or rice) GR'b><4> ~l , 51 pp. 30. Winter Cranberry Mint Cleansing Conditioner (soy) GR(bf(•> , 40 pp. 31. Spring Orange Blossom Cleansing Conditioner (soy) tD) <•> 1, 40 pp. fbl_c•_>~---- 40 pp. 32. Summer Honey Peach Cleansing Conditioner (Soy) GR_ 33. Winter White Citrus Cleansing Conditioner (soy) GRCb><4 > '40 pp. 4 34. Spring Honey Lilac Cleansing Conditioner (soy) GR(bJ< > 40 pp. 3. 24 of26 FEI: Establis hment Inspection Report Guthy-Renker, LLC Santa Monica, CA 90405-3268 ETStart: 3007513615 08/12/20 15 El End: 08/20/2015 35. Summer Coconut Lime Verbena Cleansing Conditioner (soy) lb><•> ~: '30 pp. 36. Fall Tuscan Pear Cleansing Conditioner (soy) GRlb><•> , 3 pp. ~~~~~~~~ 37. Change control CC-2012-0194, 8 pp. 38. Kathon-Free (Euxy1) CC first mfg. dates, 1 p. 39. Kathon CC on hand quantities, 2 pp. 40. Kathon-Free (Euxyl) first distribution dates top five, 1 p. 41. CC-010, Lavender and Tea Tree back to fb)c•) from Soy (excerpts), 3 1 pp. 42. Kitchen Sink Cleansing Conditioner composite from Cb><•> (Kathan-Free), 25 pp. 43. Febrnary 18, 2014 GR response to CFSAN, 7 pp. for RIPT and HET-CAM 44. Response study reference 1, RIPT Sweet Almond Mint, dated 10/27106, 10 pp. 45. Response study reference 2, RlPT Cucumber Aloe, dated 4/l 7/07. 10 pp. 46. Response study reference 5, Tri Princeton Claims Support Studies, dated April 9, 2010, 29 pp. 47. GR Attorney contact info., I p. 48. PKG-00 1 Artwork Routing and Approval Procedure, 7 pp. 49 1b><•> ingredient declaration examples for Winter Cranberry Peppermint and Spring Cleansing Conditioner, 3 pp. 50. CC-2012-0167, 12 pp. 5 1. Deviation 232 1, 4 pp. t contract manufacture batch record T l 3 18B, 50 pp. 52. (bH4 > contract manufacture batch record T l 301 A, 47 pp. 53. (DJ<•> 54. Deviation 2037, 3 pp. 55. Kathon ingredient information, 17 pp. 56. Euxyl info1mation, 21 pp. 57. Actiphyte of Wi ld Cherry Fruit and Bark info., l 0 pp. 58. GR Adverse Event Hair Care Swvey (HAJRAERO 114), 4 pp. 59. Hair loss script, 3 pp. pO. DVD containing adverse event (regulated GR prod) and Wen complaint files with descriptors, 32 pp. 61. 001351669A, 9 pp. 62. 00 l 642563A, 5 pp. 63. 001655246A, 5 pp. 64. 001654286A, 5 pp. 65. 00 1001325A. 4 pp. 66. OO J914359A, 6 pp. 25 of26 FEI: Establishment Inspection Report Guthy-Renker, LLC Santa Monica, CA 90405-3268 El Start: El End: 3007513615 08/12/2015 08/20/2015 67. 00191513 IA, 4 pp. 68. 001124721A, 4 pp. 69. 001516625A, 5 pp. 70. 001956171A, 5 pp. 71. 00l854510A, 5 pp. 72. 001062752A, 4 pp. 73. 001597149A, 5 pp. 74. 001927231A, 5 pp. 75 . 001953628A, 5 pp. 76. GR Product Complaint Trend Adverse Event excerpt for June 2015, 3 pp. 77. Cleansing Conditioner complaint/ship ratio, 2 pp. 78. QA-116 Lot Coding Requirements for Guthy-Renker Items with mfg. code reference, 12 pp. 79. Deviation 2040 and Marketing Test product codes, 3pp. Attachments • FDA 482, Notice of lnspection, issued on 8112/15 to Mr. Georg (NMI) Richter, Co-President and Chief Operating Officer for Guthy-Renker, LLC, 3 pp. • FACTS Assigmnetn sheet, 4 pp. • Assignment memo dated 3/10/15, 8 pp. • Wen AER Data Update chart with missing manufacturer, formulation, variety and distributor information provided by Ms. Malakian, 2 pp. • www.Guthy-Renker.com printouts for Wen order links, 4 pp. • Assignment Attachment A, 5 pp. Sonia R. Peterson, Investigator 26 of26