Guardian Pharmacy Services Response to FDA Form 483 Issued on April 23, 2018 FEI No. 30 126697 15 Page 1of10 Guardian Pharmacy Services 7920 Elm brook Dr Ste 108 Dallas, TX 75247 (214) 221-8181 Fax (214) 221-8282 May 29, 2018 LCDR John W. Diehl, M.S. Director, Compliance Division Office of Pharmaceutical Quality Operations, Division II FDA/Office of Regulatory Affairs Dallas District Office 4040 North Central Expressway, Suite 300 Dallas, TX 75204 RE: Guardian Pharmacy Services. WAIVER for Publication of Response to FDA Form 483 Issued on April 23, 2018; FEI No. 3012669715 Dear Mr. Diehl; On behalfof Guardian Pharmacy Services (hereafter referred to as GPS), located in Dallas, Texas, I hereby authori ze the United States Food and Drug Administration (FDA) to publicly disclose the informat ion described below on FDA 's website. I understand that the information that is disclosed may contain confidential commercial or financial information or trade secrets within the meaning of 18 U.S.C. §1905, 2 1 U.S.C. §33 10), and 5 U.S.C. §552(b)(4) that is exempt from public disclosure under those statutory provisions and/or relevant FDA regulations. I agree to hold FDA harmless for any i1tjury caused by FDA's sharing the information with the public. Information to be disclosed: GPS' Response to FDA Form 483 issued April 23, 2018; fEI No. 30 126697 15. The waiver shall extend only to GPS ' Response to the FDA Form 483 issued April 23, 2018, and not to any of the supporting or underlying documents imp Iicated or involved in the FDA Form 483 issued Apri l 23, 2018 such as Attachments and Exhibits. Authorization is given to FDA to disclose the above-mentioned information which may include confidential commercial or financial or trade secret information. As indicated by my signature, I am authorized to provide thi s consent on behalf of GPS, and my full name, title, address, telephone number, and facsimile number is set out above for verification. In the event there are any questions regarding the disclosure of such in formation, I hereby request pre-disclosure notification so that we can address any such questions prior to disclosure of the material. Thank you. Sincerely, "') / Jac~l{fi(~YZ4J Jack R. Munn, RPh Owner Guardian Pharmacy Services Response to FDA Form 483 Issued on April 23, 20 18 FEI No. 30 126697 15 Page 2of10 May 29, 2018 LCDR John W. Diehl, M.S. Director, Compliance Division Office of Phannaceutical Quality Operations, Division II FDA/Office of Regulatory Affairs Dallas District Office 4040 North Central Expressway, Suite 300 Dallas, TX 75204 RE: Response to Inspcctional Observations Issued to Guardian Pharmacy Services (GPS) on April 23, 2018; F EI No. 3012669715 GPS would like to take this opportuni ty to respond to the inspectional observations listed within Form 483 dated April 23, 20 18; FEI No. 301 26697 15. During FDA's in spection, GPS engaged cooperative ly and constructively with FDA as GPS would like to assure FDA that it is commi tted to providing patients with the highest quality compounded preparations and takes FDA's observations and its professional responsibilities very seriously GPS is a Texas licensed compound ing pharmacy, wh ich compounds medications in compliance with Texas law, USP Chapter 795 and USP Chapter 797 respectively, and in compliance with Section 503A of the Federal Food, Drug, and Cosmetic Act (hereafter referred to as Section 503A). For the past years, GPS has been providing the highest quality compounded medications to its patients for a multitude of conditions to fulfill their otherwise unmet medica l needs. As a Section 503A pharmacy compliant with Texas state law, we would like to note that many of the observat ions included within the Form 483 are based on current good manu facturing practices ("cGMP"). Section 503A specifica lly exempts 503A pharmacies compliant with state law from complyi ng with Section 50 I(a)(2)(13) of the Federal Food Drug and Cosmetic Act, which requires compliance with cGMP. Therefore, GPS is not required to meet the cGMP regu lations that are cited within the Form 483. FDA 's gu idance, pub Iished July 2, 2014 reiterated that drugs compounded in compliance with Section 503/\ wi ll be exempt from ce11ain sections of the Food, Drug, and Cosmetic Act, including cGMP requirements. FDA further recognized this to be correct within the released fDA inspections notice stating that FDA wi ll not cite violations based on cG M P regulations fo r 503A pharmacies. GPS takes great satisfaction in compounding in compliance with Texas state pharmacy law as well as in compliance with Section 503A. As such, GPS is fully entitled to the exemption from cGM P set forth in Section 503A and objects to any observation in the Form 483, which inappropriately relies on cG MP regulations. While GPS is addressing all of FDA 's inspectional observations, its cooperation with fDA should not be interpreted as GPS' admi ssion or agreement that it is required Guardian Pharmacy Services Response to FDA Form 483 Issued on April 23 , 20 18 FEI No. 3012669715 Page 3 of 10 to comply with cGMP regulations, thereby leaving GPS exposed to repeat citations for fa iling to confirm with cGMP regulations. Without conced ing that any of the Observations are applicable, set forth below are FDA 's Observations, followed by GPS ' responses thereto. Guardian Pharmacy Services Response to FDA Form 483 Issued on April 23, 2018 FEI No. 3012669715 Page 4of10 GUARDIAN PHARl\llACY SERVICES RESPONSE TO FDA INSPECTION OBS ERV ATIONS Observation 1 Aseptic processing areas are deficient regarding the system for monitoring environmental conditions. Response to Observation I : 1. SOP 3.030, "Environmental Monitoring of the Clean Room Facility, ver. 2.0., eff 211/20 13, is current as of 5/15/2018 and will be followed. Monthly personnel sampling and ISO 5 surface sampling will be documented appropriately. Documentation of same will be monitored by PIC or Quality Control Officer. 2. Semi-arurnal recertification or the ISO 5 laminar flow hoods, ISO 7 buffer room, and ISO 8 anteroom contracted with AirScanTech was conducted 5114/2018. The results of the ce11ification process report shovved the sterile processing areas passed all requirements; specifically, particle counts in ISO 8 ante room were 802 particles per cubic foot (allowed l 00,000 particles per cubic foot); particle counts in the ISO 7 buffer room were 353 particles per cubic foot (allowed 10,000 particles per cubic foot). Biological testing in al 1areas of the sterile processing area showed no growth. Observation 2 Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the room and equipment to produce aseptic conditions. Response to Observation 2: 1. Sterile IPA is being used in the cleaning and disinfecting of the ISO 5 laminar flow hoods, ISO 7 buffer room, and ISO 8 anteroom effective 4/15/2018. 2. Effective 4/15/2018, sterile IPA 70% is used for cleaning and disinfecting all appropriate areas when and where Sterile IP A is designated. The Sterile IP A 70% used comes in sterile unit of use containers. The containers are used one time and discarded. 3. The cleaning procedure effective 4/15/2018 reflects the use of sterile Hypo-ChJor as a disinfectant which has replaced BruClean. The rinsing procedures use sterile water and sterile IPA as referenced above. If necessity compels a change from this product, an equivalent replacement will be used. Guardian Pharmacy Services Response to FDA Form 483 Issued on Apri l 23, 2018 FEI No. 301 2669715 Page 5of10 4. Decon Spore 200, a sterile sporicidal agent has replaced Texcide. The sporicidal agent is used alternately with Hypo-Chlor disinfectant. If necessity compels a change from this product, an equivalent replacement will be used. 5. The firm uses the manufacturers recommendations for preparation, dilution, concentration , application and contact times for these products. Documentation from the manufacturers is on fil e at the firm 's office. 6. Sterile Criti-Clean, lint free wipes moistened with Sterile IPA (as described above) are used for cleaning purposes within the ISO 5 laminar airflow workbench where aseptic processing of sterile preparations occur. If necessity compels a change from this product, an equivalent replacement will be used. 7. Effective 4/ 17/2018 the daily, weekly, and monthly cleaning activities are regularly verified and documented to ensure the cleaning is perfmmed and is effective. Hi storic records have been located, collated, and logged appropriately. Observation 3 Air is recirculated to production areas without adequate measures to control recirculation of dust. Response to Observation 3: The room is in compliance with TSBP standards as evidenced by the recertification of the rooms by AirScan. I . Successful smoke test studies performed within the IS O 5 laminar flow hoods \Vere documented by video on 5/14/2018. Observation 4 Equipment used in the manufacture, processing, packing or holding of drug products is not of appropriate design to faci litate operations for its cleaning and maintenance. Response to Observation 4: l. The Nuaire ISO 5 laminar airflow workbench (model 30 1-630) has been removed from the sterile processing environment. Guardian Pharmacy Services Response to FDA Form 483 Issued on April 23, 201 8 FEI No. 301 266971 5 Page 6 of IO Observation 6 Written records are not always made if investigations into unexplained discrepancies. Response to Observation 6: 1. Discrepancies will be noted, investigated and documented. 2. Service teclmicians were sent from the company that maintains the air conditioning system who fixed the malfunction. In the event the sterile processing area is shut down due to an air conditioning malfunction, the area will be cleaned according to SOP prior to resuming compounding. Observation 7 The responsibilities and procedures applicable to the quality control unit are not fully followed . Response to Observation 7: Atmual review of SOP manual will be documented. Updates to SOP will be documented. Review and monitoring records have been updated reviewed and signed by PIC or Quality Control Offi cer. Equipment calibration has been performed and documented. Processing data generated during the production of drug preparations, Logged f ormula Worksheets, are reviewed and initialed for each compounded preparation dispensed . Observation 8 Procedures designed to prevent microbiological contaminati on of drug products purporting to be sterile do not include validation of sterilization process. Response to Observation 8: 1. T he CLUTent procedure, SOP 9.110, conforms with the requirements in USP and the Texas State Board of Phannacy. Our firm will continue to re-evaluate all SOPs in order to continue to improve processes. All personnel that compound sterile preparations will be evaluated and monitored for adherence to the SOP. 2. All sterile processing personnel have completed media fill as required by SOP and will be monitored to assure compliance. Guardian Pharmacy Services Response to FDA Form 483 Issued on April 23, 2018 FEI No. 3012669715 Page 7of10 3. Biological indicators are placed in various sites of the autoclaves and dry heat oven to verify proper function of the equipment. All processes are documented and monitored by PIC or Quality Control Officer. 4. Current procedures for bubble point testing have been updated to an SOP 8.050, Filter Integrity Test (Bubble Point). All sterile processing personnel will follow SOP. Documentation of bubble point tests are currently documented and monitored by PIC, Quality Control Officer or designee. 5. All sterile processing perso1mel have been counseled as to the proper function of disinfecting devices and equipment during sterile processing. Educational observational revicvv of the sterile operator in question has been performed by PJC or pharmacist designee. Observation 9 Each batch of drug product purporting to be steri le and pyrogen-free is not laboratory tested t determine conformance to such requirements. Response to Observation 9: GPS is a Texas licensed compounding pharmacy, which compounds medications in comp lia nce with Texas law, USP Chapter 795 and USP C hapte r 797 respectively, and in compliance with Section 503A of the Federal Food, Drng, and Cosmetic Act (hereafter referred to as Sect io n 503A). As a result GPS is not held to certa in requireme nts of cGMP . l. Endotoxin testing is culTently being performed according to revised SOP 9. l 23b using the Cape Cod system. Some of the preparations undergoing terminal sterilization by autoclave or dry heat oven have been deleted from our production line. Oil based preparations and suspensions will be evaluated for testing when suitable methods are available. 2. Steri lity testing is currently being performed according to revised SOP 9.120. Some of the preparations undergoing terminal sterilization by autoclave or dry heat oven have been deleted from our production line . Our firm has begun to perform sterility tests on all sterile preparations to which we are extending beyond use dates . 3. Sterility testing is currently being performed according to revised SOP 9.120. 4. Our firm has ordered appropriate ATCC organisms for use in growth promotion testing of in-house prepared growth media. Tryptic Soy Broth (TSB) agar plates and Fluid Thioglycollate Medium (FTM) agar plates will be challenged with the appropriate organisms. 5. The test sample sent to Pharmetrics Laboratory was a small sample from a preparation compounded for a specific patient with a 24 hour beyond use date Guardian Pharmacy Services Response to FDA Form 483 Issued on April 23, 2018 FEI No. 30 126697 15 Page 8 of IO (BUD). The process was in compliance with USP 797 for a patient specific prescription. Observation 10 Testing and release of drug products for distribution do not include appropriate laboratory determination of satisfactory conformance to the final specifications and identity and strength of each active ingredient prior to release. GPS is a Texas licensed compounding pharmacy, which compounds medications in compliance with Texas law, USP Chapter 795 and USP Chapter 797 respectively, and in compliance with Section 503A of the Federal Fooc/, Drug, and Cosmetic Act (hereafter refened to as Section 503A). As a result, GPS is not held to certain requirements of cGMP. Response to Observation 10: A. Potency testing is required if an extended BUD is assigned to the finished preparation. BUD dating is assigned according to USP 797, data found in appropriate literature and GPS sponsored testing by out sourced laboratories. B. Our firm will find suitable methods of testing of non-steri le preparations according to USP 795. C. Antimicrobial effectiveness tests for drug preparations containing preservatives are not a requirement of USP Chapter 795 and USP Chapter 797. Observation 11 . Written procedures are not fo llowed for the cleaning and maintenance of equipment, including utensils, use in the manufacture, processing, packing or holding of a drug product. Response to Observation 11: GPS is a Texas licensed compounding pharmacy, which compounds medications in compliance with Texas law, USP Chapter 795 and USP Chapter 797 respectively, and in compliance with Section 503A of the Federal Food, Drug, and Cosmetic Act (hereafter referred to as Section 503A). As a result, GPS is not he ld to certain requirements of cGMP. GPS does not manufacture drug products. Guardian Pharmacy Services Response to FDA Form 483 Issued on Apri l 23, 2018 FEI No. 3012669715 Page 9of10 A. GPS will investigate the availability of a pharmaceutical grade detergent for use in the dishwashing system currently in operation. Improvements to the current procedure will include a second rinse cycle to fmther remove any residue that may be on the glassware, stir bars and utensils. B. GPS has revised SOP 8.040 to reflect current practice and vvill investigate a test method to evaluate hold time integrity. Observation 12 There is a failure to thoroughl y review the failure of a batch or any of its components to meet any of its specifications whether or not the batch has been already distributed. Response to Observation 12: 1. All appropriate personnel have reviewed SOP 9.080 for clear understanding. In the event a recall is indicted, the SOP will be followed. 2. A second endotoxin test was performed on Ropivacaine 2mg/ml, Lot# 53550:42 which passed, therefore no recall was required. 3. As a result of a consumer complaint, a recall was performed on Glycopyrrolate 0.2mg/ml, Lot# 53766: 14. All remaining doses were retrieved from the facility. 4. M itomycin I ml syringe 0.4mg/ml, Lot# 55337:00 was sent to Eagle Analytical Services. The test was performed 4 days after the BUD assigned to the preparation. Observat ion 13 There is no written program designed to assess the stability characteristics of drug products. Response to Observation 13: I. BUD dating is assigned according to USP 797, data found in appropriate literature and GPS sponsored testing by out sourced laboratories. 2. GPS SOP 9.050 clarifies the method used to assign BUD to compounded preparations. Guardian Pharmacy Services Response to FDA form 483 Issued on April 23, 20 18 FE! No. 301 2669715 Page IO of IO Observation 14 Procedures describing the handl ing of all written and oral complaints regarding a drug product are not followed. Response to Observation 14: All personnel have revie\ved SOP 5.030. A close adherence to the compliance software in place so as to be timely in such reviews. Observation 15 Records of calibration check of automatic, mechanical or electronic equipment, includi ng computers or related systems are not maintained. Response to Observation 15: OPS is a Texas licensed compounding pharmacy, whi ch compounds medications in compliance with Texas law, USP Chapter 795 and USP Chapter 797 respectively, and in compliance with Section 503A of the Federal Food, Drug, and Cosmetic Act (hereafter referred to as Section 503A). As a result, OPS is not held to certain requirements of cOMP. The minihelic pressure gauges of the lSO 5 laminar airflow workbenches were located on the two ISO 5 workbenches that have been removed from the ISO 7 buffer room.