As the U.S. Food and Drug Administration (FDA) continues to inspect large and mid-sized supplement firms as part of its 36-month good manufacturing practice (GMP) rollout, inspectors are becoming savvier in both the observations they are making and the questions they are asking. “The FDA is on a fast learning curve; we need to be as well,” said Loren Israelsen, executive director of the United Natural Products Alliance, speaking about the need of supplement manufacturers to adapt to the rapidly-changing regulatory framework and inspection protocol.
With each supplement facility inspection, the FDA issues a 483 letter that details all the specific areas of non-compliance noted by inspectors. After reviewing a number of 483 letters that were made public by the FDA, Israelsen has pointed to a number of recurring areas of non-compliance that supplement manufacturers ought to be aware of and seek to correct. These include:
- Failure to prepare a written master manufacturing record for each unique formulation of a dietary supplement.
- Failure to establish component specifications for strength and composition.
- Failure to fill out material rejection and rework sheets.
- Failure to collect information regarding customer hospitalizations in in-bound complaints in order to determine if a MedWatch report needs to be submitted.
- Failure to establish a sampling plan for obtaining representative samples of components.
- No documentation to explain the rationale behind the testing performed and the specifications for various raw materials using USP methods intended for use in testing drug products but no evidence that these testing methods are suitable for use in testing dietary supplement ingredients and finished products.
- Indicating "Pass" instead of identifying specific ID test results.
- Non-use of metal detection equipment for liquid dietary supplement products.
- GMP training is not conducted on a continuing basis to assure that employees remain familiar with CGMP requirements.
- Failure to conduct appropriate tests or examinations or rely on a certificate of analysis to determine whether components met established specifications.
- The firm's training records do not reflect training of personnel in dietary supplement GMPs.
- Batch records are general and printed out blank.
Israelsen urges supplement companies to read the public 483 letters and learn from other companies’ inspections. “By reviewing and learning from these 483’s, the yet to be inspected can gain key insights and assess their own state of GMP compliance or non compliance,” Israelsen told NBJ. “The goal here is to get better, produce products of increasingly reliable quality and work toward a level playing field where companies are competing at a level of quality that rewards the investments to operate at GMP standards. These inspections are a key step in that direction.”
Those interested in reading more 483 letters can go online to the FDA Office of Regulatory Affairs’ Reading Room.
Related NBJ Links:
GMP Q&A with CFSAN’s Brad Williams
Supplement Firms Prepare for FDA's Next Phase of GMP Audits
LeDoux: Failure to Prepare for GMPs Could Lead to Very Unfortunate Outcomes
Related Functional Ingredients magazine links:
Can Your Suppliers Kill You?