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Certificates of analysis can be used to monitor the reliability of products and their suppliers, says Susan Schniepp, distinguished fellow at Regulatory Compliance Associates.
Q. I work in the warehouse and am responsible for maintaining the paperwork associated with incoming and outgoing shipments, including the certificates of analysis (CoA). Can you explain what should be on CoAs and how they relate to GMP compliance?
A. The International Pharmaceutical Excipients Council defines a CoA as “a legal document that certifies the quality of the excipient and demonstrates the batch conforms to defined specifications, has been manufactured under excipient GMP, and is suitable for use in pharmaceuticals” (1). The same definition can also apply to finished product. Basically, it is a document that confirms a product (an API, excipient, or final product) meets defined and expected criteria that render it suitable for use. It is typically issued by the quality assurance department and lists the actual test results performed as compared to the specification range for the various parameters tested. In addition to the test results and specification range, the CoA should also list the batch number or lot number of the material, the manufacturer and their location, the date the material was produced and, if applicable, the expiration date of the particular material associated with the CoA. It should also have the identity and signature of the person who approved the certificate along with the date of approval. The World Health Organization (WHO) has a document on their website titled, “Model Certificate of Analysis”. This document has a comprehensive list of information suitable to be included in a CoA. The model CoA was developed in conjunction with the Guidelines on the Implementation of the WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce (2).
The CoA plays an important role in GMP compliance. The safety of the pharmaceutical supply chain is of concern to regulators, manufacturers, practitioners, and patients. The process of assuring the suitability of suppliers of pharmaceutical ingredients or products typically starts with an audit. Once the audit is completed and the supplier has been approved, the purchasers need to be able to monitor the credibility of their suppliers. CoAs help because they assure the continued quality of the product by providing “a summary of testing results on samples of products or materials together with the evaluation for compliance to a stated specification” (3). The European regulations require that “Authentic Certificates of Analysis should be issued for each batch ….” (4).
The veracity of the CoA, however, still needs to be confirmed by the purchaser. When a supplier is new, the results of the CoA are usually confirmed for each shipment of the material by performing independent verification of the CoA results. Once a history of reliable and accurate results from the supplier is established, the purchaser will often perform skip lot testing, in which they verify the CoA results on a defined periodic basis, with the exception of the identity test, which should be performed for each shipment of material received (5).
Not all materials need to have the results of the CoAs retested to assure their accuracy. Some latitude is given for drug product containers and closures. Some of the tests that need to be performed to verify the results on the CoA for containers and closures may not be practical for the purchaser to perform. In this case, the CoA becomes the evidentiary proof that the material was safe for use. The 21 Code of Federal Regulations states, “Containers and closures shall be tested for conformity with all appropriate written specifications. In lieu of such testing by the manufacturer, a certificate of testing may be accepted from the supplier, provided that at least a visual identification is conducted on such containers/closures by the manufacturer…” (6). The purchaser still needs to establish the reliability of the container/closure suppliers through the audit process, but CoAs can be used to help determine the consistency of the supplier over a period of time by comparing and trending the CoA results.
CoAs are important documents for ensuring the safety of the supply chain. They allow users of pharmaceutical ingredients to monitor and trend the reliability of their suppliers over time and they provide information to the practitioner and patient that the product they are prescribing has meet the necessary requirements. The information contained in these documents is important for establishing the suitability of all the materials and their suppliers (API, excipients, components, containers, closures) used to manufacturer a pharmaceutical product. Using the CoA to track all your suppliers’ reliability over time just makes good business sense.
1. IPEC, Certificate of Analysis Guide for Pharmaceutical Excipients, International Pharmaceutical Excipients Council (IPEC, 2013).
2. WHO, Guidelines on the Implementation of the WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce.
3. European Commission, EudraLex Volume 4, Good Manufacturing Practice, Medicinal Products for Human and Veterinary Use, Part I, Basic Requirements for Medicinal Products, Chapter 4: Documentation (EC, 2010).
4. European Commission, EudraLex Volume 4, Good Manufacturing Practice, Medicinal Products for Human and Veterinarian Use, Part II: Basic Requirements for Active Substances used as Starting Materials (EC, 2014).
5. 21 CFR 211.84(d)(2), Testing and approval or rejection of components, drug product containers, and closures.
6. 21 CFR 211.84(d)(3), Testing and approval or rejection of components, drug product containers, and closures.
Vol. 31, No. 4
When referring to this article, please cite it as S. Schniepp, "CoAs Help Secure the Supply Chain" BioPharm International 31 (4) 2018.