Establishment Inspection Report Professional Compounding Centers of America, LLC Houston, TX 77099-5132 FEI: EI Start: 1629694 2/15/2017 EI End: 2/23/2017 TABLE OF CONTENTS Summary ........................................................................................................................................... 1 Administrative Data .......................................................................................................................... 2 History............................................................................................................................................... 3 Interstate Commerce ......................................................................................................................... 3 Jurisdiction ........................................................................................................................................ 3 Individual Responsibility and Persons Interviewed .......................................................................... 4 Firm's Training Program ................................................................................................................... 4 Manufacturing/Design Operations .................................................................................................... 5 Manufacturing Codes ........................................................................................................................ 9 Complaints ........................................................................................................................................ 9 Recall Procedures............................................................................................................................ 10 Objectionable Conditions and Management's Response ................................................................ 10 Refusals ........................................................................................................................................... 15 General Discussion with Management ........................................................................................... 15 Additional Information ................................................................................................................... 16 Samples Collected ........................................................................................................................... 16 Voluntary Corrections ..................................................................................................................... 16 Exhibits Collected ........................................................................................................................... 16 Attachments .................................................................................................................................... 17 SUMMARY This unannounced Drug Process Inspection of Professional Compounding Center of America, LLC (henceforth PCCA) was conducted per CP 7356.002B, Drug Process Inspections of Repackers and Labelers as part of DAL-DO FY17 Workplan and Operation ID 37433. The previous FDA Drug Process Inspection for PCCA concluded on 3/14/2012, and Texas Department of State Health Services Drugs and Medical Devices Group (DMDG) concluded on 7/13/2016, both inspections were classified as NAI per CP7356.00B, Drug Process Inspection Repackers and Labelers. At the conclusion of these inspections, no Form FDA-483, Inspectional Observations were issued to the firm’s management for significate deficiencies. 1 of 18 Establishment Inspection Report Professional Compounding Centers of America, LLC Houston, TX 77099-5132 FEI: EI Start: 1629694 2/15/2017 EI End: 2/23/2017 This inspection of PCCA found the firm continues to be a drug component and product repacker and labeler. There have been no significate changes in the firm’s processes and/ or activities. The systems covered include: Quality, Facilities and Equipment, Materials, and Production Controls. During a review of the firm’s processes and records, three (3) deficiencies were found. These deficiencies include: 1) Firm’s quality unit failure to implement written procedures for drug product batch release or distribution; 2) Failure to establish and follow written procedures for cleaning and maintenance of equipment, including utensils, used in the manufacture, processing or holding of drug product; and 3) Failure to implement written production and process control function procedures. Discussions were held throughout this inspection with the firm’s management concerning the significance of drug process manufacturing cGMP regulatory requirements and potential consequences of not complying with cGMP regulatory requirements along with available consequences of a failure to comply. The firm’s management commented the documented deficiencies would be corrected. The firm was made aware all corrections will be followed up during the next FDA inspection. The profile classes evaluated and found to be acceptable, during the current inspection are “CRU”, “CSN”, and “EXC”. No refusals were encountered and no samples were collected during this inspection. ADMINISTRATIVE DATA Inspected firm: Location: Phone: FAX: Mailing address: Professional Compounding Centers of America, LLC 9901 S. Wilcrest Dr. Houston, TX 77099-5132 281-933-6948 281-933-6627 9901 S. Wilcrest Dr. Houston, TX 77099-5132 Dates of inspection: 2/15 – 17/2017 & 2/22 - 23/2017 Days in the facility: Participants: 5 Camerson E. Moore, Investigator On 2/15/2017, I displayed FDA Official credentials to Jim R. Smith, President, Megan Jeffrey Liotta, Quality and Regulatory Affairs Director, and Tamara Star Boxie, Quality and Regulatory Affairs Manager. Mr. Smith identified himself as the most responsible member of management with executive responsibilities in the absences of Mr. L. David Sparks, CEO (Exh. 1, pg. 2). There have 2 of 18 Establishment Inspection Report Professional Compounding Centers of America, LLC Houston, TX 77099-5132 FEI: EI Start: 1629694 2/15/2017 EI End: 2/23/2017 been no changes in Mr. Smith’s responsibilities since the previous two inspections. I issued the Form FDA 482 to Mr. Jim R. Smith, President (Attachment 2). On, 2/23/2017, I issued a three (3) item Inspectional Observation, Form FDA 483 (Attachment 1), to Mr. Fabian V. Zaccardo, COO. Any reference in this report to PCCA is for the Drug Product Repacker and Labeler, Professional Compounding Center of America, LLC located in Houston, TX. HISTORY Mr. Smith reported there have been no changes in the firm’s history and/ or activities since the previous DMDG inspection which concluded on 7/13/2016. He continued in stating the firm is a repacker and labeler of APIs, excipients, medical devices, and cosmetics. Drug components are repacked from bulk packaging into smaller containers and relabeled. Mr. Smith stated the firm performs no drug product manufacturing activities. All drug products are retested to confirm the product’s quality, identity, and potency. The firm’s FDA drug registration was verified as being current through December 31, 2017. Ms. Megan Jeffrey Liotta, Quality and Regulatory Affairs Director reported there have been no changes in the facility size and/ or operational hours since the previous inspection which concluded(b) (4) (b) (4) on 7/13/2016. The firm employs a total of (b) (4) Total: full-time and part-time employees). All official correspondence with the firm and FMD 145 should be addressed to: Mr. Fabian V. Zaccardo, COO, Professional Compounding Centers of America, LLC, 9901 S. Wilcrest Dr. Houston, TX 77099-5132. INTERSTATE COMMERCE & JURISDICTION (b) (4) PCCA, Houston, TX is a drug product repacker and labeler, which is a % wholesaler of the repackaged products. Approximately (b) (4) % of these repackaged products are shipped in states outside of Texas with annual sales exceeding $ (b) (4) . Ms. Liotta provided me a list of the firm’s 2015 – 2017 Drug product shipments along with warehouse and distribution locations (Exh.s 2 & 3). Warehouse and distribution locations include: (b) (4) and . I requested Ms. Liotta provide me a copy of the (b) (4) firm’s 2016 Brochure showing all drug, cosmetics, devices and other miscellaneous products sold through the firm’s website. Tamara Star Boxie, Quality and Regulatory Affairs Manager provided me an electronic media version of the firm’s distributed products (Exh. 6). Ms. Liotta provided me the names of 3 customers and suppliers (Exh.s 4 & 5). The firm’s customers include: 1) 3 of 18 Establishment Inspection Report Professional Compounding Centers of America, LLC Houston, TX 77099-5132 (b) (4) (b) (4) (b) (4) (b) (4) (b) (4) (b) (4) FEI: EI Start: 1629694 2/15/2017 EI End: 2/23/2017 2) (b) (4) and 3) (b) (4) . The firm’s suppliers include: (b) (4) I requested Mr. Fabian V. Zaccardo, COO provide me a copy of the firm’s shipping box label/ labeling. Mr. Zaccardo provided me the requested label/ labeling (Exh. 7). I requested Mr. Zaccardo provide me representative label/ labeling for the firm’s distributed Hydroxyurea USP, Part #: 30-2655, CAS: 127-07-1, For Prescription Compounding/ Rx Only and Dimethyl Sulfoxide USP (DMSO), P/N 301612, CAS 67-68-5, Hygroscopic, For Use As An Excipient. Mr. Zaccardo provided me the requested drug product label/ labeling (Exh.s 8 & 9). INDIVIDUAL RESPONSIBILITY AND PERSONS INTERVIEWED Jim R. Smith, President Mr. Smith reports to Mr. L. David Sparks, CEO (Exh. 1, pg. 2). His responsibilities are the same as those reported in the previous inspection. Mr. Smith was issued the Form FDA-482 (Attachment 2), Notice of Inspection, dated 215/2017. He was available only during the opening meeting of this inspection. Fabian V. Zaccardo, COO Mr. Zaccardo reports to Mr. L. David Sparks, CEO (Exh. 1, pg. 2). His responsibilities are the same as those reported in the previous inspection. Mr. Zaccardo was issued the Form FDA-483, Inspectional Observations, dated 2/23/2017 (Attachment 2). He was available during the inspection 2/15/17, 2/17/2017 and 2/23/2017. Megan Jeffrey Liotta, Quality and Regulatory Affairs Director Ms. Liotta responsibilities are the same as those reported in the previous firm inspections. She was available for the inspection on 2/15/2017. Tamara Star Boxie, Quality and Regulatory Affairs Manager (b) (6) Ms. Boxie reports to Megan Jeffrey Liotta, Quality and Regulatory Affairs Director. . Ms. Boxie was available (b) (6) throughout the entire inspection. FIRM'S TRAINING PROGRAM 4 of 18 Establishment Inspection Report Professional Compounding Centers of America, LLC Houston, TX 77099-5132 FEI: EI Start: 1629694 2/15/2017 EI End: 2/23/2017 Ms. Liotta provided me a copy of the firm’s procedure, Standard Operating Procedures, 200-001, Revision 11, 11/12/2014 for review. I reviewed the firm’s procedure without comment. I evaluated the firm’s implementation of the written procedure through my selection and review of the firm’s received customer complaints records. MANUFACTURING/DESIGN OPERATIONS Process Overview On 2/15/2017, I conducted a walk-through of the firm’s shipping/ receiving area, receiving inspection, bulk drug product and material storage, drug product repacking area, finished drug product inspection, finished drug product storage, and the firm’s laboratory. I observed the firm’s work order picking process from a work order generated bill of material (BOM) along with work order staging. The staged picked items are later transferred to the outside of one of the firm’s nonclassified Chemical Repack rooms for repackaging. Once the drug product has been repacked, the work order is transferred to the finished repackaged drug inspection area. I observed the firm’s quality unit inspector perform a visual inspection of a finished drug repackaged work order. The review of this process was made without comment. On 2/16/2017, I conducted a walk-though of the firm’s non-classified chemical repack rooms. PCCA (b) (7)(A) designated Room’s (b) (4) , and to drug product repackaging. Room number (b) (4) is designated for the repackaging of (b) (7)(A) . The firm has (b) (7)(A) . I examined the firm’s (b) (7)(A) measurement instruments, utensils, and cleaning supplies in each of the room. During my review of the firm’s cleaning supplies, I found foreign material build-up on the exterior of the firm’s (b) (4) spray bottles. I asked Mr. Zaccardo to examine the material build-up on the bottle’s exterior. He examined the exterior of the bottles. I asked Mr. Zaccardo if the bottles were reused and he replied yes. He continued in stating the bottles are refilled and returned to the designated production room. I asked Mr. Zaccardo if the firm had a written procedure for inspecting, cleaning and refilling the bottles to ensure no contamination exist and he provided no immediate comment. After a discussion with the firm’s shift supervisor, he replied the firm does not have a written (b) (4) procedure for cleaning and refilling the bottles. He continued in stating, the firm does have a chemical repack room inspection checklist that must be completed prior to starting a new work order. He proceeded in showing me a representative completed example of the Pre-Packer Cleaning Checklist for Room (b) (4) . I reviewed the record and asked Mr. Zaccardo if he could show me where on the record the firm’s employee inspected and deemed no contamination was present on the (b) (4) spray bottle and he replied the bottle inspection is not documented. See Observation 2 concerning foreign material being found on the exterior surface of the (b) (4) bottle and failure to have an (b) (4) bottle cleaning and refilling procedure. Quality Complaints 5 of 18 Establishment Inspection Report Professional Compounding Centers of America, LLC Houston, TX 77099-5132 FEI: EI Start: 1629694 2/15/2017 EI End: 2/23/2017 Ms. Boxie provided me a copy of the firm’s Handling Product Complaints, 100-006, Revision 9, 12/17/2014 for review. I reviewed the procedure without comment. I asked Ms. Liotta to provide me a list of the firm’s received 2015 – 2017 Customer Complaints. Ms. Liotta provided me a list of the firm’s complaints. I reviewed the firm’s list and selected 43 of the firm’s received complaint records. Ms. Boxie provided me the requested records for review. All records and supporting documents were reviewed without comment with the exception of Complaint # 2430323 discussed in Observation 3B. CAPA/ OOS/ Deviations Ms. Boxie reported the PCCA does not have a specific CAPA procedure. She continued in stating the firm’s deviation procedure is used for the firm’s out of Specification (OOS), out of tolerance (OOT), and CAPAs. Ms. Boxie provided me the following procedures: Deviation and Out of Specification Process, 200-013, Revision 7, 9/12/2016 & Revision 5, 5/28/14; Change Control Procedure, 200-006, Revision 13, 6/14/2016; and Investigation of Discrepancy and Out of Specification Results, 200-013, Revision 4, 2/18/2014 & Revision 3, 6/6/2011 for review. I reviewed the firm’s procedure without comment. I requested Ms. Boxie to provide me a 2015 – 2017 List of CAPAs/ OOS/Deviations. Ms. Boxie provided me the requested list. The list was reviewed and I requested Ms. Boxie provide me a total of 23 OOSs from the list. Included in this list were OOSs linked to the firm’s received customer complaints. Ms. Boxie provided me the requested records. I reviewed the firm’s records and found OOS # 16-110, dated 5/11/16, documented after receiving bulk finished drug product, Hyaluronidase Salt-free Lyophilized Bovine, Item # 30-3778, Lot # C172813 the firm’s warehouse employee placed the product in the refrigerator verses the freezer for storage until use. The firm’s investigation identified the issue as being a warehouse employee error. The firm’s documented actions included contacting the drug product supplier to determine the effect of the product being refrigerator for 3 months and later discarding the product. I asked Ms. Boxie if the firm had any other records to support the firm’s investigation and actions and she replied no. I asked Ms. Boxie if the firm took action to address the operator error and she replied the employee no longer works in the department. Following several discussions concerning the issue, I stated the firm failed to ensure no other product was placed in the refrigerator/ freezer in error and the operator error issue was never address. See Observation 3A regarding the firm’s failure to adequately investigate and initiate corrective actions to address the root cause of bulk finished drug product, Hyaluronidase Salt-free Lyophilized Bovine, Item # 30-3778, Lot # C172813, being placed in the refrigerator for 3 months before identifying the product was improperly stored. During my review of the firm’s OOS records, OOS # 14-089 referenced in Complaint # 2498723, dated 2/3/2015, Calcitriol USP 1000 NG/ML in A3 devlmond Oil NF, Item # 55-4788, Lot # 6262233, the firm was unable to locate the record. I explained to Mr. Zaccardo the firm is required to maintain and available upon request CAPA and OOS records. Mr. Zaccardo agreed and continued in stating, during this inspection, the firm is unable to locate and make available OOS # 14-089. See Observation 3B concerning the firm’s failure to maintain and provide in a timely manner OOS # 14-089 record. All remaining OOSs were reviewed without further comment. 6 of 18 Establishment Inspection Report Professional Compounding Centers of America, LLC Houston, TX 77099-5132 FEI: EI Start: 1629694 2/15/2017 EI End: 2/23/2017 In addition to OOSs, three (3) deviation records were also reviewed in this section, which were linked to firm received customer complaints. All were reviewed without comment. Change Control I requested Ms. Boxie provide me eight (8) of the firm’s documented change controls which were linked to received customer complaints and initiated OOSs. These included: 16-0418, 16-0205, 150134, 15-0343, 15-0325, 15-0580, 16-0422, 16-052. Ms. Boxie provided me the selected change controls. I reviewed the firm’s change control records without comment. Materials Receiving Inspection/Raw Materials Ms. Boxie provided me the firm’s Quality Control Testing Procedure, 300-001, Revision 12 for review. I reviewed the firm’s procedures without comment. The firm’s bulk drug product receiving inspection and testing process was reviewed as part of the firm’s batch record review. Production Control Batch Records Ms. Boxie provided me the following procedures for review: Receiving Process, 500-002, Revision 13, 5/9/14; Quality Control Testing Procedure, 300-001, Revision 12, 4/20/2016; Warehouse Operations, 500-006, Revision 1, 11/4/2014; Raw Material Repackaging Documentation & Process, 400-007, Revision 16, 10/1/2013; Label Control, 200-011, Revision 5, 5/26/2015; Quarantine and Disposal of Rejected Products, 200-007, Revision 13, 11/7/2014; Work Order Release, 400-015, Revision 5, 12/20/2016; Batch Record Review, 200-012, Revision 3, 11/15/16; and Sales Order Pulling and Shipping, 500-003, Revision 12, 2/16/2016. All procedures were reviewed without comment. I re-reviewed the firm’s 2015 – 2017 Drug product shipments. I requested bulk drug product receiving, inspection, laboratory testing, repack production batch, and shipping records for the following drug products: x HCG, Lyophilized powder EP, Item # 55-3560, Lot # C173305, WO # 08300503 x Benazepril Hydrochloride USP, Item # 30-4319, Lot # C167904, WO # 09181850 x Prazosin Hydrochloride EP, Item # 55-4819. C175204, WO # 411402 x Ranitidine Hydrochloride USP, 30-3023, C166255, WO # 391303 x Betahistine HCL USP, 30-1882, C166747 x Betahistine HCL USP, 30-4260, C175761 x Ibuprofen USP, 30-1192, C175881, WO # 09176944 x Hyaluronidage Lyophized, Bovine, Salt-Free, 30-3778, C172813 x Hydromorphone Hydrochloride USP CII, C181367 x Lidocaine Hydrochloride USP, 30-1213, C181072, WO # 415477 x Benzocaine USP, 30-1194, C179994 x Oxytocin USP Powder, 55-2843, C179445, WO# 05150473 7 of 18 Establishment Inspection Report Professional Compounding Centers of America, LLC Houston, TX 77099-5132 x x x x x FEI: EI Start: 1629694 2/15/2017 EI End: 2/23/2017 Acetylcysteine USP, 30-1601, C177783, WO # 12200100 Bismuth Subcarbonate USP, 30-1119, C170039, WO # 06242632 Prednisone USP, Micronized, 30-1435, C177678, WO # 413302 Isoproperenol Hydrochloride, 30-4295, C176624 Collagenase, 30-2877, C170748 Ms. Boxie provided me the requested records for review. I reviewed the complete batch records and found for Benazepril Hydrochloride USP, WO# 09181850, Item # 30-4319, CAS: 86541-74-4, Lot # (b) (4) C167904, Expiry Apr. 30, 2019, Qty. units of 100 GM, 2/9/2015, processed in Room # (b) (4) , the firm’s quality inspector failed to review, initial and date, signifying approval of the batch record. The same issue was observed during my review of the batch record for Ranitidine Hydrochloride USP, WO # (b) (4) 12280089, Item # 30-3023, CAS: 66357-59-3, Lot # C166255, Expiry Jul 31, 2017, Qty. units of 100 GM, 3/9/16, processed in Room # (b) (4) . The firm’s quality inspector failed to review, initial and date, signifying approve of the batch record. In both cases, the deficiencies were not found during the firm’s finished drug product batch record review and release process. The batch records were released for product distribution. I asked Mr. Zaccardo if the firm’s batch records underwent a quality unit review process prior to release for distribution and he replied yes. He continued in stating there appears to have been an oversight by both the inspector and quality unit performing the final drug product batch record review and release process prior to distribution. Mr. Zaccardo stated the missing signature should have been caught in the batch record review process. See Observation 1 concerning the quality unit’s failure to adequately implement the firm’s written procedures, Batch Record Review, 200-012, Revision 2, 4/24/2015 and Work Order and MBR Review and Verification, 200-012, Revision 1, 6/16/2014. While reviewing your firm’s Work Order # 06242632, Bismuth Subcarbonate USP, Item # 30-1119, Lot # C170039, Expiry 5/1/2018, Qty. units @ 100 GM, I found the record failed to include a drug product label as part of the record. Ms. Boxie reported the firm was going through their archives to locate the original physical record. Mr. Zaccardo reported the firm’s quality unit was unsuccessful in located the original hard copy batch record, Work Order # 06242632, Bismuth Subcarbonate USP, Item # 30-1119, Lot # C170039, Expiry 5/1/2018, to support and compare the electronic digital record to prove and/ or disprove the presence of the drug product label was included in the work order prior to the conclusion of this inspection. See Observation 3C regarding the firm’s failure to include a product label as part of the drug product’s batch record. All remaining batch records were reviewed without comment. (b) (4) Facilities & Equipment Environmental Monitoring (EM) Ms. Boxie provided me a copy of the following procedures for review: Building and Facilities, 100004, Revision 4, 6/28/2016, Warehouse Operations, 500-006, Revision 1, 11/4/14, and Operations Temperature and Humidity Monitoring, 200-009, Revision 12, 8/17/2015. I reviewed the procedures without comment. I requested Mr. Zaccardo provide me the firm’s 2016 – 2017 refrigerator and 8 of 18 Establishment Inspection Report Professional Compounding Centers of America, LLC Houston, TX 77099-5132 FEI: EI Start: 1629694 2/15/2017 EI End: 2/23/2017 freezer bulk and repacked finished drug product storage. Ms. Boxie provided me the requested records. I reviewed the records without comment. Equipment, Maintenance, & Calibration Ms. Boxie provided me the following procedures for review: Balance and Weight Calibration and Maintenance, 300-010, Revision 11, 2/22/2017 & Revision 10, 1/6/2017. I reviewed the procedure without comment. I requested the following 2015 – 2016 Instrument Calibration records: x (b) (4) Scale, S/N (b) (4) (Laboratory Test Instrument) x (b) (4) System, S/N (b) (4) (Laboratory Test Instrument) x (b) (4) Analyzer, Model (b) (4) , S/N (b) (4) (Laboratory Test Instrument) x (b) (4) , S/N (b) (4) (Used in Repacking Room (b) (4) for repack drug product weights) Mr. Zaccardo provided me a copy of the firm’s calibration records. All calibration records were reviewed without comment. Pest Control I re-reviewed the firm’s procedure, Building and Facilities, 100-004, Revision 4, 6/28/2016. I requested Mr. Zaccardo provide me the firm’s 2015- 2017 Pest Control records. Mr. Zaccardo provided me requested pest control records. All records were reviewed without comment. Repack Production Room Cleaning I requested Mr. Zaccardo provide me 2016 – 2017 Repack Cleaning Room records for Room #’s (b) (4) , and (b) (4) for review. Ms. Boxie provided me the requested records. I reviewed all the firm’s records without comment. MANUFACTURING CODES Ms. Liotta reported PCCA uses the bulk drug product lot number and expiry date issued by the supplier on all repackaged products. She continued in stating work order numbers are uniquely created and assignment for repacked orders by the firm’s (b) (4) system. COMPLAINTS A review of PCCA’s Handling Product Complaints, 100-006, Revision 9, 12/17/2014 along with received complaints was conducted in the Quality/ CAPA Controls section of this report. 9 of 18 Establishment Inspection Report Professional Compounding Centers of America, LLC Houston, TX 77099-5132 FEI: EI Start: 1629694 2/15/2017 EI End: 2/23/2017 RECALL PROCEDURES Ms. Liotta provided me copies of the firm’s Handling Recalls, 100-007, Revision 7, 7/28/16 and Handling Product Complaints, 100-006, Revision 9, 12/17/2014 for review. I reviewed the firm’s procedures without comment. Ms. Liotta stated PCCA has not initiated any reported and or unreported recalls since the firm’s previous inspection. OBJECTIONABLE CONDITIONS AND MANAGEMENT'S RESPONSE Observations listed on form FDA 483 OBSERVATION 1 Drug product production and control records, are not reviewed and approved by the quality control unit to determine compliance with all established, approved written procedures before a batch is released or distributed. Specifically, your firm’s quality unit failed to review and approve batch records for compliance with all established approved written procedures before releasing or distributing the batch as required by your firm’s procedure, Batch Record Review, 200-012, Revision 2, 4/24/2015 and Work Order and MBR Review and Verification, 200-012, Revision 1, 6/16/2014. For example: A. During review of your firm’s repackaging and relabeling batch record(s) for Benazepril Hydrochloride USP, WO# 09181850, Item # 30-4319, CAS: 86541-74-4, Lot # C167904, (b) (4) Expiry Apr. 30, 2019, Qty. units of 100 GM, 2/9/2015, processed in Room # (b) (4) , your firm’s quality unit failed to review, initial and date, signifying approve of your firm’s batch record. B. During review of your firm’s repackaging and relabeling batch record(s) for Ranitidine Hydrochloride USP, WO # 12280089, Item # 30-3023, CAS: 66357-59-3, Lot # C166255, Expiry Jul 31, 2017, Qty. units of 100 GM, 3/9/16, processed in Room # (b) (4) , your firm’s quality unit failed to review, initial and date, signifying approve of your firm’s batch record. (b) (4) —— Reference: 21 CFR 211.192 Supporting Evidence and Relevance: Exhibit 10, Page 7, Batch Record Review, 200-012, Revision 2, 4/24/2015, Appendix 1, Section 3, states, “Once the Work Order passes verification, then the QA personnel must initial and date the 10 of 18 Establishment Inspection Report Professional Compounding Centers of America, LLC Houston, TX 77099-5132 FEI: EI Start: 1629694 2/15/2017 EI End: 2/23/2017 “QA Approved by” field on the Work Order an then pass the Work Order on to Chemical Production to scan into (b) (4) ”. During my review of selected firm batch records, I found two work orders where the firm’s quality personnel failed to follow the firm written procedure. These work orders include: A. Benazepril Hydrochloride USP, WO# 09181850, Item # 30-4319, CAS: 86541-74-4, Lot # C167904, Expiry Apr. 30, 2019, Qty. units of 100 GM, 2/9/2015, processed in Room # (b) (4) (Exh. 12, pg. 14) B. Ranitidine Hydrochloride USP, WO # 12280089, Item # 30-3023, CAS: 66357-59-3, Lot # C166255, Expiry Jul 31, 2017, Qty. units of 100 GM, 3/9/16, processed in Room # (b) (4) , (Exh. 13, pg. 14) (b) (4) (b) (4) I asked Mr. Zaccardo how was PCCA able to ship Work Order Numbers 09181850 and 12280089 without the firm’s quality person signature missing for the finished repackage drug product inspection step and he replied the firm performs a finished batch record review prior to release and shipping (Exh. 12, pg. 10 and Exh. 13, pg. 10). It is through this process the firm ensures the drug product is within specification. Mr. Zaccardo reported no batch/ WO is released for distribution without this being performed by the firm’s quality unit. He continued in stating this should have been caught during batch record review and approval (Exh. 11, pgs. 3-4). This was just an oversight within the review, approval, and release for distribution operation. Mr. Zaccardo state PCCA would never distribute drug product that did not meet specification. I discussed my concerns with Mr. Zaccardo regarding the missing signature and how the firm knows the firm’s quality personnel actually inspected and released the work order. Mr. Zaccardo acknowledged my concerns and stated this should not have occurred for the released and distributed work orders. Discussion with Management: Mr. Zaccardo stated the firm will be correcting the reported deficiency. OBSERVATION 2 Written procedures are not established and followed for the cleaning and maintenance of equipment, including utensils, used in the manufacture, processing, packing or holding of a drug product. Specifically, A. Your firm fails to establish a written procedure for the cleaning and refilling of your firm's used to clean and sanitize (b) (4) bottles which holds purchased (b) (4) manufacturing equipment and utensils during finished drug product repackaging. For example, during my walk-through of your firm's drug repackaging production rooms, foreign material was observed on the exterior surface of (b) (4) spray bottles being used by your firm's production operator. Your firm's management stated your firm does not have a written 11 of 18 Establishment Inspection Report Professional Compounding Centers of America, LLC Houston, TX 77099-5132 FEI: EI Start: 1629694 2/15/2017 EI End: 2/23/2017 and approved procedure for the cleaning and refilling of (b) (4) bottles for production and cleaning activities. B. Your firm failed to follow your firm’s written Chemical Repack Room Cleaning and Inspection Procedures, 400-001, Revision 12, 7/14/16, Section 7, Equipment/ Supplies which states, “The Chemical Repacker will inspect the supplies below to ensure what is required to clean the areas are new, not expires, and have no contamination on or around the equipment or supplies prior to use”. Sub-section 7.3, identifies (b) (4) as being one of the supplies which are to be inspected to ensure no contamination is present on or around the equipment or supplies prior to use. —— Reference: 21 CFR 211.67(b) Supporting Evidence and Relevance: A. I asked Mr. Zaccardo if PCCA had a written procedure for the refilling of the (b) (4) bottles used during the sanitization of production surfaces and utensils and he replied no. B. I asked Mr. Zaccardo if the firm had established a written procedure for the maintenance and cleaning of the (b) (4) bottles and he replied yes. Mr. Zaccardo provided me a copy of the firm’s Chemical Repack Room Cleaning and Inspection Procedures, 400-001, Revision 12, 7/14/2016, and identified Section 7, Equipment/ Supplies, which documents the requirement, “The Chemical Repacker will inspect the supplies below to ensure what is requires to clean the areas are new, not expired, and have no contamination on or around the equipment or supplies prior to use” (Exh. 15, pg. 2). I reviewed the provided written procedure and found within Subsection 7.3, the item “(b) (4) ” (Exh. 15, pg. 3) was included on the list. On the firm’s Pre-Packer Cleaning Checklist (Exh. 15, pg. 10), I found no objective evidence to support the (b) (4) bottle was inspected for possible foreign contaminates in the firm’s cleaning records. The firm places a label on the exterior of the bottle followed by a strip of clear packing tape to affix the label (Exh. 14). In the absence of a procedure, the firm’s label fail to document the (b) (4) lot number and expiry date as required by the firm’s Chemical Repack Room Cleaning and Inspection Procedures, 400001. During my inspection of the entire firm’s Chemical Repack Rooms, I found foreign material build-up on the bottle exterior. I physically showed Mr. Zaccardo the build-up on the (b) (4) bottle exterior within the repack rooms. Mr. Zaccardo reviewed bottles and reiterated the bottles are cleaned but he was unable to provide and explanation for what was being observed. I stated to Mr. Zaccardo, the foreign material build-up concerns me, because of the possibility of finished repacked drug product cross contamination. Following my comments, Mr. Zaccardo stated he understood my concerns and would be taking immediate actions to correct the issue. Discussion with Management: 12 of 18 Establishment Inspection Report Professional Compounding Centers of America, LLC Houston, TX 77099-5132 FEI: EI Start: 1629694 2/15/2017 EI End: 2/23/2017 Mr. Zaccardo provided me copies of the firm’s updated Raw Material Repackaging Documentation & Process, 400-007, Revision 17, 2/21/2017; Chemical Repack Room Cleaning and Inspection Procedures, 400-001, Revision 13, 7/21/2016; and employee training records for review (Exh.s 17 & 17). See Voluntary Corrections section of this report for the firm’s management comments and further discussions. OBSERVATION 3 Written production and process control procedures are not followed in the execution of production and process control functions. Specifically, your firm’s quality unit failed to follow your firm’s written approved procedures. For example: A. Your firm failed to adequately implement your firm’s written procedure, Deviation and Out of Specification Process, 200-013, Revision 6, 9/11/2014, Sub-section 8.1.14, stating, “Production will initiate a meeting including, at minimum, QC, and Supply Chain to determine a root cause and disposition”. Your firm’s procedure continues in stating within Sub-section 8.2.4, “Preventive Actions (if applicable) shall be determined by investigation and Root Cause Analysis and reviewed by the Department Manager and Quality Assurance before implementation”. For example, OOS # 16-110, dated 5/11/16, documents you firm’s failure to place received drug product, Hyaluronidase Salt-free Lyophilized Bovine, Item # 30-3778, Lot # C172813 into your firm’s freezer. The product was placed into the fridge instead for 3 months. Your firm failed to conduct an adequate investigation to identify the root cause as required by your firm’s Deviation and Out of Specification Process, 200-013 procedure along with identifying and documenting preventive actions to address the possible recurrence of the documented issue. B. Your firm failed to adequately implement your firm’s written procedure, Deviation and Out of Specification Process, 200-013, Revision 6, 9/11/2014, which requires your firm to maintain records of your firm’s OOSs. For example, during this FDA inspection, your firm’s quality unit was unable to provide a copy of your firm’s OOS # 14-089 referenced in Complaint # 2498723, dated 2/3/2015, Calcitriol USP 1000 NG/ML in Almond Oil NF, Item # 55-4788, Lot # 6262233. Your firm’s management stated it was unable to locate the record, OOS # 14-089 mention in Complaint # 2498723 during this inspection. C. Your firm’s quality unit failed to follow your firm’s procedure Batch Record Review, 200012, Revision 2, 4/24/2015, APPENDIX 1, Work Order Verification Overview, Sub-section 10, which states, “…sample label must match information in Section 2 and must be identical to labels that are attached to the repackaged product. Note that the size of the sample label varies by Work Order and that larger labels are attached to the reverse of this Work Order”. For example, your firm’s quality unit failed to verify during your firm’s batch record review 13 of 18 Establishment Inspection Report Professional Compounding Centers of America, LLC Houston, TX 77099-5132 FEI: EI Start: 1629694 2/15/2017 EI End: 2/23/2017 process a labeled was attached to your firm’s Work Order # 06242632, Bismuth (b) (4) Subcarbonate USP, Item # 30-1119, Lot # C170039, Expiry 5/1/2018, Qty units @ 100 GM. Your firm’s quality unit approved Work Order # 06242632, Bismuth Subcarbonate USP, Item # 30-1119 on 5/14/15 with no drug product label being attached. Your firm’s management stated it was unable to locate the original hard copy batch record, Work Order # 06242632, Bismuth Subcarbonate USP, Item # 30-1119, Lot # C170039, Expiry 5/1/2018, to support the drug product label was included in the work order along with comparison to the provided electronic record content during this inspection. —— Annotation: Promised to correct by 11/03/2017 Reference: 21 CFR 211.100(b) Supporting Evidence and Relevance: A. Exhibit 18, Page 4, Deviation and Out of Specification Process, 200-013, Revision 6, 9/11/2014, Sub-section 8.1.14, stating, “Production will initiate a meeting including, at minimum, QC, and Supply Chain to determine a root cause and disposition”. The procedure continues in documenting the firm’s requirement within Sub-section 8.2.4, “Preventive Actions (if applicable) shall be determined by investigation and Root Cause Analysis and reviewed by the Department Manager and Quality Assurance before implementation”. During my review of selected firm OOSs, I found OOS # 16-110, dated 5/11/16, document the firm’s failure to store received bulk drug product, Hyaluronidase Salt-free Lyophilized Bovine, Item # 30-3778, Lot # C172813 in the firm’s freezer (Exh. 20). The firm’s warehouse employee placed the drug product into the fridge where it remained until it was found 3 months after being originally received. During my review of the firm’s documented investigation within OOS # 16-110, I found the firm failed to adequately investigate the issue to identify the root cause as required by the firm’s Deviation and Out of Specification Process, 200-013 procedure along with identifying and documenting preventive actions to address the possibility of recurrence. I discussed the OOS’s deficiencies with Mr. Zaccardo and he agreed there were several aspects of the investigation that had not been documented. Mr. Zaccardo provided me a copy of the firm’s procedure, Warehouse Operations, 500-006, Revision 1, 11/4/2014 to review the firm practices for the storage of received drug components and products (Exh. 19). I reviewed the firm’s procedure and found within Subsection 8.1, P/O and W/O Put Away, I found the procedure documents the firm’s requirements for handling received and repackaged drug components and products. Mr. Zaccardo stated he wanted to assure me the firm had an established process for handling received and repackaged drug components and products. B. Exhibit 18, Deviation and Out of Specification Process, 200-013, Revision 6, 9/11/2014 documents the firm’s requirements, process, and record keeping requirements for OOSs. I 14 of 18 Establishment Inspection Report Professional Compounding Centers of America, LLC Houston, TX 77099-5132 FEI: EI Start: 1629694 2/15/2017 EI End: 2/23/2017 requested PCCA provide ma a copy of the firm’s OOS # 14-089 referenced in Complaint # 2498723, dated 2/3/2015, Calcitriol USP 1000 NG/ML in Almond Oil NF, Item # 55-4788, Lot # 6262233 (Exh. 21). During my re-review of the firm’s records, I found an error was made in documenting the firm’s compliant number. The “correct” Complaint Number is 2430323, dated 2/3/2015. This error was not caught at the time of issuance but during the writing of this report. All remaining documented information within the observation is correct. Mr. Zaccardo reported the firm was unable to locate record, OOS # 14-089 mention in Complaint # 2430323 prior to the conclusion of this inspection. He continued in stating the firm will be reviewing its quality record storage procedure(s) and system. C. Exhibit 10, Page 10, firm’s procedure, Batch Record Review, 200-012, Revision 2, 4/24/2015, APPENDIX 1, Work Order Verification Overview, Sub-section 10, states, “…sample label must match information in Section 2 and must be identical to labels that are attached to the repackaged product. Note that the size of the sample label varies by Work Order and that larger labels are attached to the reverse of this Work Order”. During my review of selected batch records I found the firm’s quality unit failed to verify a labeled was affixed to Work Order # 06242632, Bismuth Subcarbonate USP, Item # 30-1119, Lot # C170039, Expiry 5/1/2018, Qty. units @ 100 GM (Exh. 22, pg. 5). The firm’s quality unit approved Work Order # 06242632, Bismuth Subcarbonate USP, Item # 30-1119 on 5/14/15 with no drug product label being attached. Mr. Zaccardo stated it was unable to locate the original hard copy batch record, Work Order # 06242632, Bismuth Subcarbonate USP, Item # 30-1119, Lot # C170039, Expiry 5/1/2018, to support the drug product label was included in the work order along with comparison to the provided electronic record content during this inspection. I asked Mr. Zaccardo without the presents of the label, how the firm’s quality unit released Work Order # 06242632 for distribution and he provided no response. (b) (4) Discussion with Management: Mr. Zaccardo stated the firm will be correcting the reported deficiency. REFUSALS No “Refusals” occurred during this firm visit. GENERAL DISCUSSION WITH MANAGEMENT The following people were present for the Closing Meeting discussion: x Mr. Fabian V. Zaccardo, COO x Tamara Star Boxie, Quality and Regulatory Affairs Manager 15 of 18 Establishment Inspection Report Professional Compounding Centers of America, LLC Houston, TX 77099-5132 FEI: EI Start: 1629694 2/15/2017 EI End: 2/23/2017 On 2/23/2017, I issued an Inspectional Observation, Form FDA 483 (Attachment # 1) to Mr. Fabian V. Zaccardo, COO since he was the highest-ranking member of management and most responsible individual with executive responsibilities. A summary of the issued Form FDA 483 was read aloud at the closing meeting. I asked Mr. Zaccardo if he had any questions concerning the observations. He stated he did not have any questions. He continued in stating the firm would be taking action to correct the cited deficiencies. I explained to the firm the observations listed would be further reviewed by the Agency, and if considered violations of the FD&C Act, legal sanctions could include seizure, injunction or other options if serious conditions are not corrected. I advised the firm it had a choice to provide a written response for each cited observation(s) and any response(s) received within 15 business days would be considered by FDA prior to any action(s). I stated the response should be addressed to the Dallas District Office along with providing the name and address for the documented submission. At this time the inspection was concluded. ADDITIONAL INFORMATION No “Additional Information” documented during visit. SAMPLES COLLECTED No “Samples Collected” during firm visit. VOLUNTARY CORRECTIONS Observation 2 On 2/22/17, Mr. Zaccardo provided me copies of the firm’s updated procedures: Raw Material Repackaging Documentation & Process, 400-007, Revision 17, 2/21/2017 and Chemical Repack Room Cleaning and Inspection Procedures, 400-001, Revision 13, 7/21/2016 for review. I reviewed the procedure without comment. I stated to Mr. Zaccardo, all the firm’s corrections will be reviewed and verified during the next FDA inspection. EXHIBITS COLLECTED 1. PCCA’s Organizational Chart, 2 pgs. 2. PCCA’s 2015 – 2017 List of Active Drug Products Shipments, 16 pgs. 16 of 18 Establishment Inspection Report Professional Compounding Centers of America, LLC Houston, TX 77099-5132 FEI: EI Start: 1629694 2/15/2017 EI End: 2/23/2017 3. 4. 5. 6. PCCA’s Warehouses/ distribution locations, 1 pg. PCCA’s Top 3 customers, 1 pg. PCCA’s(b) (4) suppliers, 1 pg. “Officially” Sealed Master Memory Stick in Form FDA 525 Electronic Media Copy of 2016 PCCA’s Product Brochure, 1 pg. 7. PCCA’s shipping box label/ labeling, 3 pgs. 8. PCCA’s representative label/ labeling Hydroxyurea USP, Part #: 30-2655, CAS: 127-07-1, For Prescription Compounding/ Rx Only, 1 pg. 9. PCCA’s representative label/ labeling Dimethyl Sulfoxide USP (DMSO), P/N 30-1612, CAS 67-68-5, Hygroscopic, For Use As An Excipient, 1 pg. 10. PCCA’s Batch Record Review, 200-012, Revision 2, 4/24/2015, 17 pgs. (Use for Obs. 3C) 11. PCCA’s Work Order and MBR Review and Verification, 200-012, Revision 1, 6/16/2014, 17 pgs. 12. PCCA’s batch record(s) for Benazepril Hydrochloride USP, WO# 09181850, Item # 30-4319, (b) (4) CAS: 86541-74-4, Lot # C167904, Expiry Apr. 30, 2019, Qty. units of 100 GM, 2/9/2015, processed in Room # (b) (4) , 32 pgs. 13. PCCA’s batch record(s) for Ranitidine Hydrochloride USP, WO # 12280089, Item # 30-3023, (b) (4) CAS: 66357-59-3, Lot # C166255, Expiry Jul 31, 2017, Qty. units of 100 GM, 3/9/16, 26 pgs. 14. PCCA’s (b) (4) Bottle Label/Labeling and Receiving records, Item # 50-3867, Lot # Y7105836165, 6 pgs. 15. PCCA’s Chemical Repack Room Cleaning and Inspection Procedures, 400-001, Revision 12, 7/14/2016, 15 pgs. 16. PCCA’s Raw Material Repackaging Documentation & Process, 400-007, Revision 17, 2/21/2017, 17 pgs. 17. PCCA’s Chemical Repack Room Cleaning and Inspection Procedures, 400-001, Revision 13, 7/21/2016, 14 pgs. 18. PCCA’s Deviation and Out of Specification Process, 200-013, Revision 6, 9/11/2014, 13 pgs. 19. PCCA’s Warehouse Operations, 500-006, Revision 1, 11/4/2014, 4 pgs. 20. PCCA’s OOS # 16-110 dated 5/11/2016, 5 pgs. 21. PCCA’s Customer Complaint # 2430323, dated 2/3/2015, 20 pgs. 22. PCCA’s batch record for Work Order # 06242632, Bismuth Subcarbonate USP, Item # 30-1119, Lot # C170039, Expiry 5/1/2018, Qty. units @ 100 GM, 10 pgs. (b) (4) ATTACHMENTS 1. PCCA’s Form FDA-483 issued to Fabian V. Zaccardo, COO, President, dated 2/23/2017, 4 pgs. 2. PCCA’s Form FDA-482 issued to Jim R. Smith, President, dated 2/15/2017, 3 pgs. 17 of 18 Establishment Inspection Report Professional Compounding Centers of America, LLC Houston, TX 77099-5132 Camerson E. Moore -S Digitally signed by Camerson E. Moore -S DN: c=US, o=U.S. Government, ou=HHS, ou=FDA, ou=People, 0.9.2342.19200300.100.1.1=200062 2537, cn=Camerson E. Moore -S Date: 2017.05.03 15:00:39 -05'00' Camerson E. Moore, Investigator 18 of 18 FEI: EI Start: 1629694 2/15/2017 EI End: 2/23/2017