The data reported on the COA, however, must be based on the manufacturer's analytical testing results and include, as recommended
by the IPEC COA guide, the identity and location (including country) of the manufacturer. When a distributor provides its
own COA, the manufacturer and the site are identified. If the distributor repackages the excipient or packages from bulk,
the distributor must sample, analyze, and include its results in its own COA. A distributor-developed COA should identify
the original manufacturer and manufacturing location. Traceability of the exipient manufacturer is required to enable the
recall of material.
Furthermore, the position paper suggests that if a distributor receives material into a holding tank, only materials from
the same manufacturer's site or terminal conforming to the same specifications should be mixed. Distributors that load or
package from bulk excipient should follow the WHO GTDP and IPEC GDP principles regarding definition of batches, analysis of
material, and preparation of COAs. The distributor also should have an effective change-management program in place.
The excipient user bears the responsibility for all excipients used and, therefore, must know the origin and complete supply
chain (i.e., excipient pedigree) for each batch of each excipient. Apart from performing appropriate testing of each incoming
excipient lot, the position paper states that the user should audit both the excipient manufacturer and all distributors in
the supply chain, or use the results of an audit. FDA has indicated that it is permissable to use a qualified third-party
to conduct these audits and IPEC has published audit guides that can be used for this purpose. It's also important for the
user to periodically verify the chain of custody described above to ensure the pedigree's accuracy. All these steps can be
completed as part of supplier qualification and supply-chain management.
The final topic addresed in the IPEC excipient pedigree paper is labeling. IPEC recommends excipients never be labeled as
compendial material (e.g., USP–NF) solely based upon test results. To protect the supply chain, non-GMP material should never be relabeled as compendial grade
based solely on conformance to the compendial monograph. The original material must have been manufactured and distributed
in conformance with appropriate GMP and GDP requirements, including testing, storage, repackaging, and relabeling.
Verifying the pedigree of an excipient with a paper trail (or electronic paper trail) only works with the cooperation of everyone
involved in the supply chain. If a single party fails to adopt these preventive measures voluntarily, verification may eventually
be mandated by more burdensome and costly regulations.
Arthur J. Falk, PhD, is president and CEO of International Pharmaceutical Excipient Auditing (IPEA), tel. 908.735.812, firstname.lastname@example.org
. The IPEC documents mentioned in this article can be downloaded for free at