Common Violations in cGMP Compliance Inspections for Dietary Supplements

May 14, 2012 By

Current Good Manufacturing Practices (cGMPs) for Dietary Supplements have been in effect since June 2010 and the FDA has been increasing inspections each year since. In 2011, 145 FDA inspections were conducted and the aim is to complete over 200 inspections in 2012. FDA has indicated that 25% of these inspections result in violations, and are issued a “483”. If these violations are not properly addressed they can lead to a formal warning letter, which is posted on the FDA website for public viewing.

The typical violations found include:

  • Failure to keep batch production records
  • Failure to qualify suppliers/vendors
  • Failure to adequately identify incoming ingredients
  • Failure to set in process specifications or document controls that specs are met
  • Failure to create set master manufacturing records (MMRs)
  • Failure to adhere to MMRs, deviations without corrective action or documentation
  • Failure to test finished products

A review of warning letter trends has revealed that there is little compliance for keeping proper Master Manufacturing Records (MMR). Within those records there have been failures to establish specifications for identity, purity, strength, composition, and limits on contaminants. It has also been found that some with adequate established MMRs failed to meet specifications, to qualify their suppliers, and keep proper documents of the steps used and outcomes.

Investigators have also found failure to show adequate quality control procedures put in place. It was noted that there was a lack of review, material review, dispositions, and no QC SOPs during several inspections.

Qualifying vendors through a Vendor Verification Program (VVP) is necessary in order to ensure quality and the identity of the material and seems to also be a lacking area. COA from vendors should include specs for identity, description, limits on contaminants, results, strength, and tolerances. These requirements are essential for preparing finished product specs and it is the duty of the product owner to consolidate all the specs required to test against the finished product to ensure quality.

A Vendor Verification Program should consist of:

  1. Confirming the test results of certificates of analysis
  2. Audits
  3. Re-qualifying the vendor at intervals.

The FDA expects the violations seen so far to be corrected and will become stricter along with starting more technical reviews of specifications, procedures, and lab controls. With the FDA expecting a higher compliance rate in the future and increasing technicality of inspections, this may create a higher demand for 3rd party cGMP auditors in the US.

The question is how do you prepare yourself for FDA inspections and ensure that your facility is cGMP compliant? Here are some tips that can help you get ready for cGMP compliance inspections:

  1. Ensure all QA/QC and all other personnel affected by cGMP regulations are familiar with the sections of 21 CFR part 111 that apply to their department and ensure those personnel receive training on those requirements
  2. Review documentation regularly
  3. Be ready to justify testing methods for raw and finished products
  4. Internal mock inspection to ensure personnel are ready
  5. Consult SIDI guidelines
  6. Address notice of violations immediately with FDA, as fixing a violation during an inspection period and demonstrating this may result in the FDA listing the violation as only an internal observation.

Finally, remember that compliance can only be found through due diligence and ensuring that you are aware of the requirements and are using industry resources available to you.

All the best to a compliant future! We can be reached at 1-866-647-3279 or at