Jajco, Inc. DBA Anchor Drugs Pharmacy MARCS-CMS 522517 —
- Delivery Method:
- Certified Mail
Recipient NameRaymond P. Jajeh, Pharm.D.
- Jajco, Inc. DBA Anchor Drugs Pharmacy
161 S. Spruce Avenue
South San Francisco, CA 94080
- Issuing Office:
- Los Angeles District Office
Los Angeles District
VIA CERTIFIED MAIL
RETURN RECEIPT REQUESTED
August 22, 2017 CMS# 522517
Raymond P. Jajeh, Pharm.D.
Jajco, Inc. dba Anchor Drugs Pharmacy
161 S. Spruce Avenue
South San Francisco, CA 94080
Dear Dr. Jajeh:
From May 20, 2016, to June 3, 2016, U.S. Food and Drug Administration (FDA) investigators inspected your facility, Jajco, Inc. dba Anchor Drugs Pharmacy, located at 161 S. Spruce Avenue, South San Francisco, CA 94080. 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 June 3, 2016. FDA acknowledges receipt of your facility’s response, dated June 22, 2016. 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)]. 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 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 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 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:
- Sterile operators demonstrated poor aseptic practices, such as exposing their bare hands within the ISO 5 hood while donning sterile gloves.
- Your firm’s sporicidal agent contact time appeared to be insufficient to achieve adequate levels of disinfection.
- On multiple days, there were inadequate pressure differentials between your cleanroom and ante room.
- The only air return vent observed in the ISO 7 cleanroom was on the high wall.
- Two air return vents observed in your ISO 8 ante room on the ceiling in close proximity to two HEPA filters.
- Your firm failed to demonstrate through appropriate studies that your hood is able to provide adequate protection of the ISO 5 area in which sterile products are produced.
Therefore, your products may be produced in an environment that poses a significant contamination risk.
Furthermore, 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 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 air supply filtered through high-efficiency particulate air filters under positive pressure in the aseptic processing areas (21 CFR 211.42(c)(10)(iii)).
3. Your firm failed to establish an adequate system for cleaning and disinfecting the clean room and equipment to produce aseptic conditions (21 CFR 211.42(c)(10)(v)).
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).
5. Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)).
6. Your firm failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of such stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)).
7. Your firm failed to ensure that manufacturing personnel wear clothing appropriate to protect drug product from contamination (21 CFR 211.28(a)).
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 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 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. 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.
Regarding the insanitary conditions observed during the inspection, some of your corrective actions appear to be adequate. However, we are unable to fully evaluate the following corrective actions due to a lack of adequate supporting documentation:
1. Air return vents -You stated that you would consult with HVAC specialists and a contractor to assess the re-location of the air return vents. However, you did not provide a timeline for implementing remediation measures. Furthermore, you did not indicate whether you will implement any interim controls until the corrective actions are completed. You also failed to indicate whether you will perform an assessment of potential product impact on aseptic production. The placement of your air return vents in relation to your HEPA filters may impact the ability of the HEPA-filtered air to adequately distribute throughout the cleanroom and ante room.
2. Inadequate pressure differentials - You provided no documentation to support your statement that the pressure differentials were observed to be above your specification during aseptic operations. Inadequate pressure differentials may allow for the influx of poor quality air into a higher classified area.
Moreover, the following corrective actions appear inadequate to address the insanitary conditions noted:
1. Sporicidal agent contact time - You indicated that Spor-Klenz requires a contact time of 30 seconds. However, this contact time does not conform to the recommended contact time on the product label for sporicidal disinfection.
2. Smoke studies - You provided a smoke study report, dated May 31, 2016, and a video of the smoke study titled, “02 Anchor Drugs Germfree Dynamic.” The smoke study was not performed under dynamic conditions. For example, the simulation of aseptic processing did not include equipment, such as syringes and vials, used in routine production. In addition, the video does not demonstrate unidirectional airflow over the critical work surface. Conducting smoke studies under dynamic conditions helps to ensure that unidirectional airflow is maintained while personnel are working in the ISO 5 area.
For more information on compounding, please see FDA’s website, at https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/default.htm.
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 condition on receipt of a prescription for an identified individual patient prior to compounding and distributing drug products.
In addition, regarding issues related to the conditions of section 503A of the FDCA, your corrective action appears deficient:
1. A footnote in your response references a written policy dated May 1, 2016 that allegedly “clearly describes” your firm’s practice to compound “only unique medications for identified individual patients pursuant to a valid prescription by a licensed prescriber.” It appears, however, based on prescription logs obtained by the investigators, that drug products were compounded without receipt of patient specific prescriptions and distributed at times after May 1, 2016.
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.
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 drugs you introduce into interstate commerce 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. 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.
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 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 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 Number above (522517).
Please address your reply to:
CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
United States Food and Drug Administration
Irvine, California 92612
If you have any questions regarding any issues in this letter, please contact Mr. Lance M. De Souza, Compliance Officer via email at firstname.lastname@example.org or by phone at (510) 337-6873 and reference unique identifier 522517.
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 Street
Sacramento, CA 95834
 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.
 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).
 In this letter we do not address whether your proposed corrective actions would resolve the CGMP violations noted above.