Regulatory expectations on this subject are not specifically outlined, and interpretation of the requirements to meet cGMPs (current good manufacturing practices) may vary. When interpretation of regulations come into play, conservative interpretation and good “business sense" are important.
21 CFR Part 111 cGMPs specifically require establishing an appropriate specification which must, at a minimum, include an identity test for each receipt and allow acceptance of a raw material on the supplier’s certificate of analysis (COA), provided the supplier’s COA has been documented as “reliable" through a program to confirm test results reported.
Establishing the reliability of a supplier’s COA is not strictly defined. Many firms test the first three receipts with an annual recertification required. However, this frequency may be dependent on the number of receipts per year, country of origin and whether the supplier is considered a “low" or “high" risk.
One of the more challenging tasks is related to botanical ingredients and their associated identity testing. Specifications need to clearly require country of origin, plant part, genus and species. The identity test performed must utilize a certified Botanical Reference Material (BRM) and either a HPTLC (high performance thin layer chromatograph) or HPLC (high performance liquid chromatography) methodology.
Meanwhile, the “qualification" of a supplier is more complex than just the “verification" of a COA. Ideally, an actual on-site GMP audit of the supplier should be performed. However, this is often very difficult and expensive to execute due to either the sheer number of suppliers or their “global" locations. It is recommended that supplier audits be based on risk assessment.
The following factors should be considered as part of any qualification program:
1. Assess whether the supplier is considered a “low" or “high" risk
A. Low risk: mature company, favorable regulatory history, comprehensive specifications, strong technical dossier
B. High risk: opposite of above
2. If you are not able to directly audit a supplier (or hire a third-party audit firm), request a completion of a “Quality Questionnaire" that should include, at a minimum:
- Company information
- FDA bioterrorism registration
- Quality organizational structure
- Quality management system
- SOP index
- FDA inspection history
- GMP certifications (NSF, TGA, etc.)
- Testing capabilities (internal or outsourced)
A written “Supplier Qualification Program" is necessary to communicate the procurement and quality goals for the organization.
Joseph Mitchell is vice president of corporate quality, Pharmachem Laboratories Inc., Kearny, New Jersey.