WARNING LETTER
San Diego Compounding Pharmacy MARCS-CMS 520259 —
- Delivery Method:
- UPS
- Recipient:
-
Recipient NameJerome A. Greene, R.Ph.
- San Diego Compounding Pharmacy
5395 Ruffin Rd., Suite 104
San Diego, CA 92123
United States
- Issuing Office:
- Los Angeles District Office
United States
Division of Pharmaceutical Quality Operations IV | |
WARNING LETTER
VIA UNITED PARCEL SERVICE
SIGNATURE REQUIRED
September 25, 2017 CMS# 520259
Jerome A. Greene, R.Ph.
Owner and Chief Executive Officer
San Diego Compounding Pharmacy, P.C.
5395 Ruffin Rd., Suite 104
San Diego, CA 92123
Dear Mr. Greene:
From October 17, 2016, to November 15, 2016, a U.S. Food and Drug Administration (FDA) investigator inspected your facility, San Diego Compounding Pharmacy, P.C., located at 5395 Ruffin Road, Suite 104 in San Diego, CA 92123. During the inspection, the investigator 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 investigator 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 November 15, 2016. FDA acknowledges receipt of your facility’s response, dated November 15, 2016, in which you state that your firm has “…decided to not renew [your] LSC [Licensed Sterile Compounding] License with the California State Board of Pharmacy.” 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.
B. Failure to Meet the Conditions of Section 503A
During the inspection, the FDA investigator noted that drug products produced by your firm failed to meet the conditions of section 503A. Specifically, the investigator noted that your firm did not receive valid prescriptions for individually-identified patients for a portion of the drug products you produced.
Therefore, you compounded 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. In the remainder of this letter, we refer to your drug products that do not qualify for exemptions under section 503A as the “ineligible drug products.”
Specific violations are described below.
C. Violations of the FDCA
Adulterated Drug Products
The FDA investigator 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 investigator observed that your firm failed to measure pressure differentials during aseptic processing to help ensure proper airflow (i.e., from areas of higher quality air to adjacent areas with lower quality air).
The manufacture of the ineligible drug products is subject to FDA’s CGMP regulations, Title 21, Code of Federal Regulations (CFR), parts 210 and 211. The FDA investigator 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 monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)).
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.[2] 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 that you have “…decided to not renew [your] LSC License with the California State Board of Pharmacy” and “[i]f [you] were to re-apply for State Licensure, [you] would be in total compliance with both state and federal laws.”
Regarding issues related to the conditions of section 503A of the FDCA, we remind you that receipt of valid prescriptions for individually-identified patients is one of the conditions for the exemptions under section 503A, and this condition applies to both sterile and non-sterile drug products.
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.[3]
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 if you decide to resume production of sterile drugs, your management first undertake a comprehensive assessment of operations, including facility design, procedures, personnel, processes, maintenance materials, and systems. In particular, this review should assess your aseptic processing operations. A third party consultant with relevant sterile drug manufacturing expertise should assist you in conducting this comprehensive evaluation.
E. Conclusion
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.
If you decide to resume sterile operations, 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 if you have taken any specific steps to correct the violations cited in this letter, or you may inform us that you do not intend to resume production of sterile drugs. If you intend to resume production of sterile drugs in the future, 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 violated the FDCA, include your reasoning and any supporting information for our consideration. In addition to taking appropriate corrective actions, you should notify this office 15 days prior to resuming production of any sterile drugs in the future.
Please address your reply to:
CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
United States Food and Drug Administration
19701 Fairchild
Irvine, California 92612
If you have any questions about the content of this letter, please contact Jessica Mu, Compliance Officer, at 949-608-4477 and reference unique identifier CMS 520259 on all correspondence.
Sincerely,
/S/
Acting for CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
Cc: Virginia Herold, Executive Officer
California State Board of Pharmacy
1625 N. Market Blvd., Suite N-219
Sacramento, CA 95834
[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.
[2] Your ineligible drug products are not exempted from the requirements of section 502(f)(1) of the FDCA by regulations issued by the FDA (see, e.g., 21 CFR 201.115).
[3] In this letter, we do not address whether your proposed corrective actions would resolve the CGMP violations noted above.