DIETARY SUPPLEMENT MANUFACTURING FACILITY FAILS TO ADEQUATELY PERFORM MICROBIOLOGICAL TESTING; FDA CITES INCORRECT USP CHAPTER
Dietary Supplement Warning Letters have within the past several months been issued at a frequency of two to three each week. Many of these Warning Letters demonstrate that the recipient fail to follow even the most basic Dietary Supplement regulations (21 CFR Part 111) which, in itself, remains quite interesting given that the regulations have now been in the public domain for several years.
Many of the Observations provided by the FDA to various Companies are quite basic and should be capable of being met by simply reading the regulations. However, when these Observations are reviewed, one gains the impression that the cited Companies have never even looked at them (21CFR Part 111).
The enclosed Observation, taken from the February 20, 2013 Warning Letter is more unique than many since it confuses USP<61> with USP<2021> and USP<2022>. What makes this Observation even more interesting is because the investigators, reviewers and those within the FDA issuing this Warning Letter appear to be ignorant that USP<2021>, and <2022> even exist. Even if the Client had used USP<61>, the FDA should have corrected the Company by reminding them that Dietary Supplement manufacturers should be using the USP “2000” series, not the less than “1000” series. It would have also represented an excellent opportunity on the part of the FDA to remind its Clients of the existence of these sections to include USP<2023> within the USP and that they pertain to Dietary Supplements.
The following discusses Observation #2 issued to Capco Custom Packaging.
2. “The United States Food and Drug Administration (FDA) inspected your firm located at 10225 Greenleaf Ave, Santa Fe Springs, California, from May 4 – 18, 2012. Our investigation revealed significant violations of the Current Good Manufacturing Practice (CGMP) regulation for dietary supplements, Title 21, Code of Federal Regulations, Part 111 (21 CFR Part 111). These violations cause your dietary supplement products to be adulterated under Section 402(g)(1) of the Federal Food, Drug and Cosmetic Act (the Act), 21 U.S.C. § 343(g)(1), because they have been prepared, packed, or held under conditions that do not meet the CGMP regulations for dietary supplements.”
“These observations were presented to you in an FDA-483 at the conclusion of our inspection on May 18, 2012. We have reviewed your responses dated June 11, 2012 and July 7, 2012, and specifically address your June 11, 2012 response below as it addresses violations of 21 CFR Parts 111 and 211.
Specific violations observed during the inspection include, but are not limited, to the following:”
- “You failed to determine whether the specifications you established for limits on contamination that may adulterate or may lead to adulteration of the finished batch of dietary supplement were met, as required by 21 CFR 111.73. (NOTE: 21 CFR 111.73 refers to “determining whether established specifications are met”, not whether one adheres to a USP method.) For example, your laboratory does not follow the USP Microbial Limits Method for Total Plate Count and Yeast and Molds as referenced in your batch records. Your total aerobic counts are not performed in duplicate in accordance with the USP. Additionally, your sample volumes for total aerobic count were 1mL and not 10mL as indicated in the USP.
We have reviewed your response letter, dated June 11, 2012, and have determined your response to be inadequate because you did not provide documentation to show that you have amended your protocols. You state in your letter that you commit to following the procedures in USP <61> for the Microbial Limits Method for Total Plate Count and Yeast and Molds, and to changing your protocols to be consistent with the USP procedure, including correct sample volumes and the performance of the analytical experiments in duplicate.
You also state in your letter that you commit to completing the amendment of your protocols for the Microbial Limits Method for Total Plate Count and Yeast and Molds by the end of the third quarter of 2012. However, as of November 1, 2012, we had not received a copy of your proposed new protocols. Therefore we could not evaluate the adequacy of your modified protocols.
Aside from using the incorrect USP General Chapter , the Observation demonstrates how one must follow a USP monograph, and, if not followed, can readily lead to an Observation. From the information within this Warning Letter, it appears that the Client did not perform standard testing in duplicate nor used the correct volume of sample for the testing (total aerobic count) that they were performing. Further, if they were following current USP<61>, the Client would be performing a mesophilic count (quantitative enumeration of mesophilic bacteria and fungi that may grow under aerobic conditions) , not a Total Aerobic Count which includes a much greater temperature range than the mesophilic count. Had the Client indicated that they were using USP<2021> Microbial Enumeration Tests—Nutritional and Dietary Supplements, they would have been correct in using the term “Total Aerobic Count” — even though its use does not correctly define “Total Aerobic Count” as presently used in practice.