John J. Herr
- Town and Country Compounding and Consultation Services, LLC
106 Prospect Street #2
Ridgewood, NJ 07450-4433
- Issuing Office:
- New Jersey District Office
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Division of Pharmaceutical Quality Operations I
10 Waterview Blvd, 3rd FL
Parsippany, NJ 07054
Telephone: (973) 331-4900
FAX: (973) 331-4969
WL # 518371
October 17, 2017
VIA UPS Next Day Air
John J. Herr, Owner
Town & Country Compounding and Consultation Services, LLC
106 Prospect Street #2
Ridgewood, NJ 07450-4433
Dear Mr. Herr:
From July 19, 2016, to August 22, 2016, U.S. Food and Drug Administration (FDA) investigators inspected your facility, Town & Country Compounding and Consultation Services, LLC, located at 106 Prospect Street #2, Ridgewood, New Jersey 07450-4433. During the inspection, the investigators noted that drug products you produced failed to meet the conditions of section 503A of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. § 353a] for exemption from certain provisions of the FDCA. In addition, the investigators noted serious deficiencies in your practices for producing sterile drug products, which put patients at risk.
FDA issued a Form FDA 483 to your firm on August 22, 2016. FDA acknowledges receipt of your firm’s response, dated September 12, 2016. FDA also acknowledges your firm’s voluntary recall of sermorelin/GHRP-6 injection 6 mg/3 mg (Lot # 07172016@1), initiated on August 1, 2016, due to a sterility failure. Additionally, FDA acknowledges your firm’s voluntary recall of human chorionic gonadotropin (HCG) 1000 units/vial (Lot # 05272016@17), initiated on October 18, 2016, due to a failure to meet potency specifications. Based on this inspection, it appears that you produced drug products that violate the FDCA.
A. Compounded Drug Products Under the FDCA
Section 503A of the FDCA describes the conditions under which human drug products compounded by a licensed pharmacist in a State licensed pharmacy or a Federal facility, or a licensed physician, qualify for exemptions from three sections of the FDCA: compliance with current good manufacturing practices (CGMP) (section 501(a)(2)(B)); labeling with adequate directions for use (section 502(f)(1)); and FDA approval prior to marketing (section 505) [21 U.S.C. §§ 351(a)(2)(B), 352(f)(1) and 355(a)].1 Receipt of valid prescriptions for individually-identified patients is one of the conditions for the exemptions under section 503A.
In addition, for a compounded drug product to qualify for the exemptions under section 503A, bulk drug substances used to compound it must: (I) comply with the standards of an applicable United States Pharmacopeia (USP) or National Formulary (NF) monograph, if a monograph exists, and the USP chapter on pharmacy compounding; (II) if such a monograph does not exist, be components of drugs approved by the Secretary; or (III) if such a monograph does not exist and the drug substance is not a component of a drug approved by the Secretary, appear on a list developed by the Secretary through regulation (“503A bulks list”) (section 503A(b)(1)(A)(i) of the FDCA).
B. Failure to Meet the Conditions of Section 503A
During the inspection, the FDA investigators noted that drug products produced by your firm failed to meet the conditions of section 503A. For example, the investigators noted that your firm compounded drug products using GHRP-6. Drug products compounded using GHRP-6 are not eligible for the exemptions provided by section 503A(a), because GHRP-6 is not the subject of an applicable USP or NF monograph, is not a component of an FDA-approved human drug, and does not appear on the 503A bulks list.2
Therefore, you compounded drug products (collectively the “ineligible drug products”) that do not meet the conditions of section 503A and are not eligible for the exemptions in that section from the FDA approval requirement of section 505 of the FDCA, the requirement under section 502(f)(1) of the FDCA that labeling bear adequate directions for use, and the requirement of compliance with CGMP under section 501(a)(2)(B) of the FDCA.
Specific violations are described below.
C. Violations of the FDCA
Adulterated Drug Products
The FDA investigators noted that drug products intended or expected to be sterile were prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health, causing your drug products to be adulterated under section 501(a)(2)(A) of the FDCA. For example, the investigators observed that:
1. Your firm transferred (b)(4) vials (b)(4) from an ISO 5 hood to a freezer located in an ISO 7 area. Despite this barrier, sterile drug product in (b)(4) vials was still exposed to less than ISO 5 classified air. Furthermore, these (b)(4) vials remained in the (b)(4) for at least (b)(4) and up to (b)(4) before returning to the ISO 5 area for further processing.
2. Your firm did not use a sporicidal agent or sterile wipes within the ISO 5 and ISO 6 areas. Additionally, not all of the disinfectants used as part of your disinfection program for the aseptic processing area were sterile. Your firm also failed to disinfect supplies prior to introducing them into the ISO 5 hood from the ISO 6 area. Plastic flaps separating the ISO 6 cleanroom from the ISO 7 anteroom as well as the ISO 8 gowning room from the ISO 7 anteroom appeared to be soiled, and were not adequately cleaned.
3. Your firm produced penicillin and other highly potent drug products without adequate containment, segregation, or cleaning of work surfaces to prevent cross contamination. Your firm produced an injectable penicillin drug product from powder and then produced other non- penicillin injectable drug products in the same area of your facility; yet, your firm had no record of cleaning between productions of these drugs.
4. Your firm failed to demonstrate through appropriate studies that your hoods are able to provide adequate protection of the ISO 5 areas in which sterile products are processed. Therefore, your products may be produced in an environment that poses a significant contamination risk.
Furthermore, the manufacture of the ineligible drug products, those produced with GHRP-6, is subject to FDA’s CGMP regulations, Title 21, Code of Federal Regulations (CFR), parts 210 and 211. The FDA investigators observed significant CGMP violations at your facility, causing the ineligible drug products to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA. The violations included, for example:
1. Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)).
2. Your firm failed to establish an adequate system for cleaning and disinfecting the room and equipment to produce aseptic conditions (21 CFR 211.42(c)(10)(v)).
3. Your firm failed to perform operations related to the manufacture, processing, and packing of penicillin in facilities separate from those used for other drug products for human use (21 CFR 211.42(d)).
4. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).
It is a prohibited act under section 301(k) of the FDCA [21 U.S.C. § 331(k)] to do any act with respect to any human or animal drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being adulterated.
Misbranded Drug Products
The ineligible drug products you compounded are intended for conditions not amenable to self-diagnosis and treatment by individuals who are not medical practitioners; therefore, adequate directions for use cannot be written so that a layman can use these products safely for their intended uses. Consequently, their labeling fails to bear adequate directions for their intended uses.3 Accordingly, these ineligible drug products are misbranded under section 502(f)(1) of the FDCA.
It is a prohibited act under section 301(k) of the FDCA to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being misbranded.
D. Corrective Actions
We have reviewed your firm’s response to the Form FDA 483. We acknowledge your voluntary recall of sermorelin/GHRP-6 injection 6 mg/3 mg (Lot # 07172016@1), initiated on August 1, 2016, due to a sterility failure. We also acknowledge your voluntary recall of HCG 1000 units/vial (Lot 05272016@17), initiated on October 18, 2016, due to a failure to meet potency specifications.
Some of your proposed corrective actions for identified insanitary conditions were inadequate For example, in response to our observation of the transfer of (b)(4) vials, you indicated that your new media fill challenge SOP will require that you perform a (b)(4) media fill challenge that will simulate 100% of the volume of the lyophilization process. However, exposing sterile drug products, within (b)(4) vials, to less than ISO 5 quality air is a poor aseptic practice and cannot be adequately validated. In addition, the (b)(4) will generate particulates and will not provide an adequate environment to prevent contamination of sterile drug products within (b)(4) vials. Moreover, you did not provide any response indicating that you will commit to using sterile wipes. The use of non-sterile wipes increases the potential for contamination to be introduced into the aseptic processing areas and is an insanitary condition.
Regarding the insanitary conditions observed in the Form 483, we are unable to fully evaluate some of your corrective actions due to lack of adequate supporting documentation, for example:
1. You indicated that your firm would perform (b)(4) via (b)(4) in order to demonstrate uni-directional airflow under dynamic conditions. However, you did not provide any supporting documentation.
2. You indicated that you purchased a new sterile germicidal cleaner to replace your non-sterile disinfectant. However, you did not provide any documentation to support this corrective action.
3. You indicated that your revised SOP, 1.40 Compounding Area Requirements (Sterile) (Version 2.0), will “require that the ISO 5 hood be cleaned with a sporicidal cleaning agent on a (b)(4) basis”. However, you did not provide any supporting documentation, such as which sporicidal agent will be used or the required contact time to ensure sporicidal activity.
4. You indicated that a new SOP would be developed and implemented for handling hazardous and highly potent drugs to ensure that no cross-contamination occurs. However, your firm has not provided this SOP or any documentation to support this corrective action.
Please be aware that section 501(a)(2)(A) of the FDCA concerning insanitary conditions applies regardless of whether drug products you compound meet the conditions of section 503A, including the compounding of drug products using a bulk drug substance that complies with an applicable USP or NF monograph, is a component of an FDA-approved human drug, or appears on the 503A bulks list.
In addition, regarding issues related to the conditions of section 503A of the FDCA, you have not addressed the compounding of drug products using GHRP-6.
Should you continue to compound and distribute drug products that do not meet the conditions of section 503A, the compounding and distribution of such drugs would be subject to the new drug approval requirement, the requirement to label drug products with adequate directions for use, and the drug CGMP regulations. Before doing so, you must comply with the requirements of section 505 and 502(f)(1) and fully implement corrections that meet the minimum requirements of the CGMP regulations.4
In addition to the issues discussed above, you should note that CGMP requires the implementation of quality oversight and controls over the manufacture of drugs, including the safety of raw materials, materials used in drug manufacturing, and finished drug products. See section 501 of the FDCA. If you choose to contract with a laboratory to perform some functions required by CGMP, it is essential that you select a qualified contractor and that you maintain sufficient oversight of the contractor’s operations to ensure that it is fully CGMP compliant. Regardless of whether you rely on a contract facility, you are responsible for assuring that your drugs are neither adulterated nor misbranded. [See 21 CFR 210.1(b), 21 CFR 200.10(b)].
FDA strongly recommends that your management undertake a comprehensive assessment of operations, including facility design, procedures, personnel, processes, maintenance materials, and systems for human and animal drugs. In particular, this review should assess your aseptic processing operations. A third party consultant with relevant sterile drug processing expertise should assist you in conducting this comprehensive evaluation.
The violations cited in this letter are not intended to be an all-inclusive statement of violations at your facility. You are responsible for investigating and determining the causes of the violations identified above and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.
You should take prompt action to correct the violations cited in this letter. Failure to promptly correct these violations may result in legal action without further notice, including, without limitation, seizure and injunction.
Within fifteen (15) working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct the violations. Please include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. If you do not believe that the products discussed above are in violation of the FDCA, include your reasoning and any supporting information for our consideration. If you cannot complete corrective action within fifteen (15) working days, state the reason for the delay and the time within which you will complete the correction.
Your written notification should refer to the Warning Letter # 518371. Please address your reply to:
CDR Liatte Krueger
Compliance Officer/OPQ Division 1
U.S. Food and Drug Administration
New Jersey District Office
10 Waterview Boulevard, 3rd Floor
Parsippany, NJ 07054-1286
If you have questions regarding the contents of this letter, please contact Compliance Officer CDR Liatte Krueger at 973-331-4933.
Division Director/OPQ Division 1
New Jersey District Office
1 We remind you that there are conditions other than those discussed in this letter that must be satisfied to qualify for the exemptions in section 503A of the FDCA.
On June 9, 2016, FDA issued a final guidance titled, Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act. This guidance describes FDA’s interim regulatory policy for State-licensed pharmacies, Federal facilities, and licensed physicians that compound human drug products using bulk drug substances that do not otherwise meet the conditions of section 503A(b)(1)(A)(i) while the 503A bulks list is being developed. Specifically, the guidance sets out the conditions under which FDA does not intend to take action against a State- licensed pharmacy, Federal facility, or licensed physician for compounding a drug product using a bulk drug substance that is not the subject of an applicable USP or NF monograph or a component of an FDA-approved drug, until the substance is identified in a final rule as included or not included on the 503A bulks list. These conditions include that the substance may be eligible for inclusion on the 503A bulks list, was nominated with adequate support for FDA to evaluate it, and has not been identified by FDA as a substance that appears to present significant safety risks pending further evaluation. GHRP-6 was not nominated with adequate support for FDA to evaluate the substance, and, therefore, is not eligible for the enforcement discretion policy. For additional information, see the guidance at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM469120.pdf.
3 Your ineligible drug products are not exempted from the requirements of section 502(f)(1) of the FDCA by regulations issued by FDA (see, e.g., 21 CFR 201.115).
4 In this letter we do not address whether your proposed corrective actions would resolve the CGMP violations noted above.