- Hieber's Pharmacy
- Issuing Office:
- Philadelphia District Office
| || |
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
Philadelphia District Office
900 U.S. Customhouse
200 Chestnut Street
Philadelphia, PA 19106
Telephone: (215) 597-4390
FAX: (215) 597-0875
RETURN RECEIPT REQUESTED
September 29, 2015
Joseph G. Bettinger, R.Ph., Owner
3500 5th Ave
Pittsburgh, PA 15213-3337
Dear Mr. Bettinger:
From September 8, 2014, to September 18, 2014, a U.S. Food and Drug Administration (FDA) investigator conducted an inspection of your facility, Hieber’s Pharmacy, located at 3500 5th Avenue, Pittsburgh, PA, 15213-3337. During the inspection, the investigator noted that you were not receiving valid prescriptions for individually-identified patients for a portion of the drug products you were producing. The investigator also observed that your firm produces domperidone products. Domperidone is not the subject of an applicable United States Pharmacopeia (USP) or National Formulary (NF) monograph, nor is it a component of an FDA-approved human drug product, and it does not appear on a list developed by the Secretary under 503A(b)(1)(A)(i)(III) of the Federal Food, Drug, and Cosmetic (FDCA) [21 U.S.C. § 353a(b)(1)(A)(i)(III)]. FDA issued a Form FDA-483 to your firm on September 18, 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)); 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. During the FDA inspection, the investigator observed that your firm does not receive valid prescriptions for individually-identified patients for a portion of the drug products you produce.
In addition, compounded drug products containing domperidone are not eligible for the exemptions under section 503A 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 of bulk drug substances that may be used for compounding 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.
In addition, 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, because you manufacture and distribute a portion of your drugs without valid prescriptions for individually-identified patients, 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 investigator 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
You compound drug products, for which you have not obtained valid prescriptions for individually-identified patients and domperidone drug products, that are intended for conditions that are 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, 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
Additionally, the FDA investigator observed CGMP violations at your facility, causing the drug products for which you have not obtained valid prescriptions for individually-identified patients and domperidone drug products to be adulterated under section 501(a)(2)(B) of the FDCA.
The violations include, 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 does not have, for each batch of drug product purporting to be sterile and/or pyrogen-free, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product (21 CFR 211.167(a)).
3. 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 from such stability testing to determine appropriate expiration dates (21 CFR 211.166(a)).
4. Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)).
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 adulterated.
C. Corrective Actions
FDA acknowledges your response to the Form FDA 483, dated October 7, 2014, in which you state that your firm “no longer provides ‘emergency use’ -- or any other sterile compounded preparations -- for office stock use effective immediately,” and “is committed to only dispensing compounded sterile preparations to individually identified patients based on a valid prescription from a prescriber in accordance with Section 503A of the Federal Food, Drug, and Cosmetic Act (‘FDCA’).” In addition, you referenced your purported compliance with the standards set forth in the United States Pharmacopeia (USP) for compounding preparations, specifically USP Pharmaceutical Compounding – Nonsterile Preparations and USP Pharmaceutical Compounding-- Sterile Preparations. However, as noted above, your firm manufactured and distributed a portion of drug products without valid prescriptions for individually-identified patients, and produces domperidone drug products, which are not permitted to be compounded from bulk drug substances under section 503A. The manufacture of such drugs is subject to FDA’s finished drug product CGMP regulations (21 CFR 210 and 211), among other requirements described above. 797>795>
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 your 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 section 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 (15) 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 the corrective actions cannot be completed within fifteen working days, state the reason for the delay and the time frame within which the corrections will be completed. Your written notification should refer to the Warning Letter Number above [15-PHI-20]. Please address your response to:
Yvette Johnson, Compliance Officer
FDA Philadelphia District Office
U.S. Food and Drug Administration
Room 900, US Customhouse
2nd & Chestnut Streets
Philadelphia, PA 19106
If you have questions regarding any issues in this letter, please contact Ms. Johnson via email at Yvette.Johnson@fda.hhs.gov
or by phone at 215-717-3077.
Anne E. Johnson
Acting District Director
 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.