Last year, the new General Chapter <1080> Bulk Pharmaceutical Excipients - Certificate of Analysis was included in the USP (First Supplement to USP 30; 1 August 2007). This chapter is orientated towards the recommendations of the American IPEC (International Pharmaceutical Excipients Council) association.
The chapter gives detailed information on how a Certificate of Analysis (COA) for excipients should be structured. It also presents a template for a COA and defines the most important terms in Appendix I.
The main GMP requirements to the manufacturers of excipients have already been described in the USP General Chapter <1078> Good Manufacturing Practices for Bulk Pharmaceutical Excipients.
The primary competence and responsibility for the COA for pharmaceutical excipients lies with the manufacturer. The excipient user should at least perform suitable identity tests on each batch before releasing the excipient for use in pharmaceutical production. The regulatory requirements define that, for excipients, conformity with all specifications must be checked. A pharmaceutical manufacturer also has the opportunity to take over results from the excipient supplier's COA. However, as a prerequisite he must have ascertained the supplier's reliability (suitable tests, GMP compliance, regular reference analyses, etc.) by means of appropriate auditing and qualification of the supplier.
Neither does the excipient manufacturer have to perform analytical tests for all specifications on every batch of a substance, provided that he can ensure in a different way (validation study results, in-process controls, etc.) that the batch fulfils all specifications before being released. However, in this case, all specification parameters must be checked periodically by means of analytical methods in order to revalidate the reference system. And it must also be indicated on the COA if individual parameters are checked with reduced frequency (e. g. only 1 batch out of 10).
In addition, the USP Chapter lists two kinds of tests (Type A and Type B): Type A tests usually have to be performed on each batch (identity, assay, etc.), whereas Type B tests can be eligible for reduced testing (heavy metals, lead, arsenic, residue on ignition, etc.). The USP mentions four possible examples in which a reduced testing frequency appears to be justified.
Another topic is that of electronic signatures. The text explains under which conditions an electronically signed COA is acceptable.
This new USP chapter will certainly help all pharmaceutical manufacturers in convincing their excipients suppliers that they should provide them with appropriate Certificates of Analysis for their excipients.
Please also see the "European Conference on Good Manufacturing Practices for Pharmaceutical Excipients" conducted by the American IPEC in Munich, Germany, from 1-2 December 2008. You will find more details at www.ipec-conference.org.
Dr Günter Brendelberger
On behalf of the European Compliance Academy (ECA)