An in-person audit performed by a properly trained auditor has no substitute, particularly where issues of safety, hygiene and personnel practices are indicated; these simply cannot be inspected remotely. But, a supplement brand owner can tell a lot about a firm and its operations by looking at the quality of its records from the comfort of their home office. The following steps can help monitor a contract manufacturer or ingredient supplier, and indicate how frequently on-site visits may be required.
Internet Regulatory Searches
FDA.gov has a trove of information. Has the firm been inspected? What was the outcome, and are regulatory actions pending? Available public data sets include:
- Warning Letters—Letters FDA writes to supplement brands that are possibly out of compliance with federal regulations. These are updated weekly. For older warning letters, see if there is a closeout letter indicating the firm came into compliance.
- Inspection Classifications—The assigned class of an inspection depends on the severity of FDA’s findings, if any, and whether a form 483 was issued, indicating GMP (good manufacturing practice) violations. FDA announced this dataset will be updated monthly, which began in November 2017. Brands can search by firm, inspection date and outcome.
- Inspection Citations—These are observed during inspections outlined in a 483. The citations are associated with completed and finalized inspections in a downloadable spreadsheet.
- Recalls and Serious Adverse Event Reports (SAERs)—Products manufactured or distributed by the contract manufacturer that need to be removed from commerce or are associated with negative usage outcomes.
- Tainted Products List—Products with hidden drug ingredients.
- Import Alerts—Notification on products and ingredients that will be stopped from entering the country.
Don’t forget to look at local news sources for information on mergers, acquisitions, bankruptcies, name changes, layoffs or other significant corporate events. Search social media, job openings and hiring websites to pinpoint potential staff shortages or rapid turnover in quality control (QC) or senior production positions, as those can be an indication of weak quality systems.
Quality Systems and Documentation Audit
Obtain the table of contents for the firm’s quality manual, or a standard operation procedure (SOP) list. Request specific SOPs and documents for processes critical to the product, plus SOPs for QC operations, deviations, investigations, complaints, testing programs and out-of-specification (OOS) results. Ask for training records for a subset of personnel who worked on the batches in the audit.
Get copies of at least three batch records for products the contract manufacturer has made in the past year or 18 months. Choose the batches to audit; don’t let the contract manufacturer select them. Ensure the audited products have approved product specifications, then create a batch record checklist based on the applicable regulations (for dietary supplements, 21 CFR 111, Subparts H and I) and verify:
- A master manufacturing record (MMR) exists for each product and batch size, approved by QC personnel. Check that the formulations are correct and agree with product labeling. The actual or representative label must be the correct version, matching the formulation.
- Instructions and actions required by the MMR are followed and recorded in the batch record, with complete information relating to the production and control of each batch. Check that all sections are filled out. Ensure it can be determined who made any corrections and why.
- Records of production lines and equipment are used, and references to cleaning and equipment are logged.
- Critical operations, such as weighing and adding of ingredients, are verified by a second person.
- All in-process testing and production checks are documented or cross-referenced in the batch record. This may include in-process inspections (e.g., bottle counts, seals, fill weights and yields at each stage of processing, including expected yields and deviations).
- Sampling instructions for tests are required to support label claims and documentation that all specifications are met. Exemptions or skip-lot-testing protocols must be documented.
- Test results are within specification and lab certificates are included with the batch record. Calculate label claims; don’t just assume the contract manufacturer got them right. Tip: Check units of measure on test reports, and whether the result is stated per daily dose or per capsule.
- Out-of-specification results from laboratory tests are properly investigated, and the root cause is found.
- Yield calculations are correctly performed and verified by QC, and investigated when outside the limits.
- The batch record is approved, and product is released from quarantine by QC before distribution.
After the Audit
It’s important to follow-up and get resolution for any issues found. After the review is complete, make a list of findings and share with the firm. Set an appointment for a review of major findings with the contract manufacturer’s management to go over anything that needs to be clarified, and any subsequent corrections they have made. This can often be done during a conference call. Don’t forget to ask for written evidence of fixes, such as new SOPs, records or other documents. Keep all records of the audit on file, as part of the vendor qualification program.
Request a written response to serious issues, and follow up with an in-person visit to ensure the necessary corrections have been made. After this audit process, a brand can better judge how soon and frequently it needs to visit suppliers.
Marian Boardley (marianboardley.com) is an independent consultant who manages projects for dietary supplement manufacturers and distributors. She helps clients in the food, drug and dietary supplement industries to implement compliance with dietary supplement, food and other cGMPs (current good manufacturing practices). She regularly trains staff to be ready for FDA inspections, and writes documentation for quality control (QC), laboratory and manufacturing operations. Boardley was born in Yorkshire, England, and is now a U.S. citizen residing on the Colorado Plateau.