Department of Health and Human Services
|Public Health Service
Food and Drug Administration
Detroit District Office
300 River Place, Suite 5900
Detroit, MI 48207
Telephone: (313) 393-8100
FAX: (313) 393-8139
RETURN RECEIPT REQUESTED
February 26, 2016
Mr. Joseph J. McCloskey, Owner
Diversified Pharmacy, Inc., dba University Compounding Pharmacy
2520 Livernois Road
Troy, MI 48083
Dear Mr. McCloskey:
From October 29, 2014, to November 13, 2014, U.S. Food and Drug Administration (FDA) investigators conducted an inspection of your facility, Diversified Pharmacy, Inc., dba University Compounding Pharmacy, located at 2520 Livernois Road, Troy, MI 48083. During the inspection, the investigators noted that you were not receiving valid prescriptions for individually-identified patients for a portion of the drug products you were producing and that you produce domperidone products. In addition, the investigators observed serious deficiencies in your practices for producing sterile drug products, which put patients at risk. For example, our investigators observed that your firm uses non-sterile wipes to clean the ISO 5 area and only infrequently performs air monitoring for viable and non-viable particles. At the conclusion of the inspection, the FDA investigators issued a Form FDA 483 to your firm on November 13, 2014.
Based on this inspection, it appears that you are producing drugs that violate the FDCA.
A. Compounded Drugs Under the FDCA
Section 503A of the FDCA [21 U.S.C. § 353a] describes the conditions under which certain compounded human drug products are entitled to exemptions from three sections of the FDCA: compliance with current good manufacturing practice (CGMP), section 501(a)(2)(B) of the FDCA [21 U.S.C. § 351(a)(2)(B)]; labeling with adequate directions for use, section 502(f)(1) of the FDCA [21 U.S.C. § 352(f)(1)]; and FDA approval prior to marketing, section 505 of the FDCA [21 U.S.C. § 355]. Receipt of valid prescriptions for individually-identified patients is one of the conditions for the exemptions under section 503A of the FDCA. During the FDA inspection, the investigators observed that your firm does not appear to receive valid prescriptions for individually-identified patients for a portion of the drug products you produce.
Another condition that must be met for a compounded drug to qualify for the exemptions under section 503A is that it is compounded from bulk drug substances that: (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, are 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, that appear on a list developed by the Secretary through regulation (section 503A(b)(1)(A)(i)).
Compounded drug products containing domperidone, are not eligible for the exemptions under section 503A of the FDCA, because domperidone 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 a list developed by the Secretary.
Accordingly, the drugs you compound without valid prescriptions for individually-identified patients and any drug products you compound using domperidone are not entitled to the exemptions in section 503A.
We remind you that there are a number of other conditions that must be satisfied to qualify for the exemptions in section 503A of the FDCA.
B. Violations of the FDCA
The drug products that you manufacture and distribute without valid prescriptions for individually-identified patients and the domperidone drug products that you manufacture and distribute are misbranded drugs in violation of section 502(f)(1) of the FDCA.
In addition, your sterile drug products are prepared, packed, or held under insanitary conditions whereby they may have been contaminated with filth, or whereby they may have been rendered injurious to health. As such, all sterile drug products you manufacture are adulterated within the meaning of section 501(a)(2)(A) of the FDCA [21 U.S.C. § 351(a)(2)(A)].
Furthermore, because you manufacture and distribute a portion of your drugs without valid prescriptions for individually-identified patients and manufacture and distribute drug products containing the bulk drug substance domperidone, the manufacture of such drugs is also subject to FDA’s Current Good Manufacturing Practice (CGMP) regulations for Finished Pharmaceuticals, Title 21,
Code of Federal Regulations (CFR), Parts 210 and 211. The FDA investigators observed significant CGMP violations at your facility, causing such drug products to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA.
Misbranded Drug Products
Because the domperidone drug products and drug products for which you have not obtained valid prescriptions for individually-identified patients are intended for conditions that are not amenable to self-diagnosis and treatment by individuals who are not medical practitioners, adequate directions cannot be written for them 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, causing them to be misbranded under section 502(f)(1) of the FDCA, and they are not exempt from the requirements of section 502(f)(1) of the FDCA [
see, e.g., 21 CFR § 201.115].
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 misbranded.
Adulterated Drug Products
FDA investigators observed that your sterile drug products 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 your firm uses non-sterile wipes to clean the ISO 5 area and only infrequently performs viable and non-viable air monitoring.
The FDA investigators also
observed CGMP violations at your facility, causing the drug products for which you have not obtained valid prescriptions for individually-identified patients to be adulterated under section 501(a)(2)(B) of the FDCA. The violations include, for example:
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)).
3. 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)).
4. Your firm failed to ensure that manufacturing personnel wear clothing appropriate to protect drug product from contamination (21 CFR 211.28(a)).
5. 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)).
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 of the components used to make the drug and results in the drug being adulterated.
C. Corrective Actions
FDA acknowledges your response to the Form FDA 483, received December 9, 2014, in which you state that your firm “compounds only pursuant to individual, named patient prescriptions.” In addition, you referenced your purported compliance with the USP- NF General Chapter <797> Pharmaceutical Compounding– Sterile Preparations.
As noted above, your firm manufactures a portion of drug products without valid prescriptions for individually-identified patients and your firm produces and distributes drug products containing the bulk drug substance domperidone, which is not permitted under section 503A. The manufacture of such drugs is subject to FDA’s drug CGMP regulations (21 CFR 210 and 211).
Furthermore, please be aware that section 501(a)(2)(A) of the FDCA concerning insanitary conditions applies regardless of whether the drugs are compounded and distributed after receipt of a valid prescription for an identified-individual patient,
FDA strongly recommends that your management immediately undertake a comprehensive assessment of your operations, including facility design, procedures, personnel, processes, materials, and systems. In particular, this review should assess aseptic processing operations. A third party consultant with relevant sterile drug manufacturing expertise could be useful in conducting this comprehensive evaluation.
In addition, you should also correct the violations of sections 501(a)(2)(A) and 502(f)(1) of the FDCA, noted above.
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 and 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 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 actions within fifteen working days, state the reason for the delay and the time within which you will complete the correction. Your written notification should be addressed to:
Tina M. Pawlowski, Compliance Officer
FDA Detroit District Office
U.S. Food and Drug Administration
300 River Place, Suite 5900
Detroit, MI 48207
If you have questions regarding any issues in this letter, please contact Ms. Pawlowski at (313) 393-8217 or via email at
Domperidone was nominated for inclusion on the list of bulk drug substances that can be used in compounding that must be developed through regulation pursuant to section 503A(b)(i)(A)(i)(III) of the FD&C Act (503A bulk drug substances list). On October 26, 2015, FDA issued a draft guidance titled,
Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act
. If finalized as written, this draft guidance will describe FDA’s regulatory policy for licensed pharmacists and licensed physicians that compound human drug products using bulk drug substances while the list is being developed. Specifically, the draft guidance states that until a substance has been considered and is identified in a final rule as being included or in the preamble of the final rule as not included on the 503A bulk drug substances list, FDA does not intend to take action against a licensed pharmacist or licensed physician for compounding a drug product from a bulk drug substance that is not the subject of an applicable USP or NF monograph or a component of an FDA-approved drug, provided that certain conditions are met, including that the substance appears on a list of substances that may be eligible for inclusion on the 503A bulk drug substances list, was nominated with sufficient supporting information for FDA to evaluate it, and has not been identified by FDA as a substance that appears to present safety concerns. Domperidone is not eligible for this policy because it appears on a list of substances that have been identified by FDA as presenting safety concerns.
For example, section 503A also addresses anticipatory compounding, which includes compounding (not distribution) before receipt of a valid prescription order for an individual patient. We are not addressing anticipatory compounding here.
This page was posted on March 13, 2019.