Relying on the Certificate of Analysis (CofA) of component suppliers significantly reduces testing costs and laboratory turnaround times, which in turn allows for shorter production timelines. As a result, the use of a CofA to demonstrate the quality of a component is common practice. The FDA accepts this practice, but only after the component supplier has been qualified.
This, unfortunately, is not common practice. In 2013 the FDA issued 43 Warning Letter observations of 21 CFR 111.75(a)(2)(ii)(A) that requires the qualification of suppliers prior to the use of a CofA for test results. To ensure that a supplier is providing quality components with the expected identity, purity, strength, composition, and the lack of potential contaminants all component suppliers must be qualified.
The first step of a supplier qualification is to have the supplier complete a questionnaire. This should be done prior to the receipt or use of any components. The questionnaire should include a GMP self-assessment, regulatory history, full disclosure of the component manufacturing process, and a copy of the supplier component specification. A list of any potential allergens or contaminants should also be received.
The specification must provide all physical, chemical, and microbiological tests being performed with references to the test methods. Challenges often arise if the supplier utilizes an alternate test methodology, so it is critical to completely understand and compare test methods. It is also imperative that the supplier specifications are consistent with your component specifications. Further, the questionnaire is a good place to establish sales and quality personnel contacts and determine whether delivery expectations can be met.
Confirmation testing is usually the next step of a supplier qualification. This involves performing all tests on your specification, which is not necessarily the same as that of the supplier. Suppliers frequently provide material to multiple industries and markets, and the specification is likely to reflect testing parameters not relevant to your intended use. Typically confirmation testing must be successfully completed on three unique supplier lots of material. However, consideration must be given to the type of material being qualified. Botanical ingredients and minerals are far more likely to contain contaminants such as heavy metals and pesticides. Botanical extracts may have residual solvents present. All types of botanicals, particularly organic, carry a much higher microbiological burden. These materials should, therefore, require an evaluation of more than three unique lots. In addition, the lots used may have to include representation from the entire growing season.
Ideally, on-site audits of the component suppliers are also conducted. Many companies rely on outside expert consultants to perform their supplier audits, but these may also be managed internally. A risk assessment will allow for appropriate prioritization of the audits. High-risk suppliers should be audited annually, while low-risk suppliers may only require an audit every three years. The risk assessment should include factors such as the volume and criticality of the material, complexity of manufacturing process, potential for contamination, country of origin, supplier regulatory history, questionnaire responses, and previous audit results.
Periodic requalification of the supplier should be conducted by way of additional confirmation testing, completion of questionnaire updates, and continuing risk-based audits. Requalification confirmation testing is typically conducted annually or after the receipt of 10 unique supplier lots, whichever comes first. Documentation of all supplier qualification and requalification activities must be reviewed and approved by the Quality Unit and maintained on-file as a supplier qualification dossier.