Conforming to the IPEC CoA Guide - Pharmaceutical Technology

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Conforming to the IPEC CoA Guide
Past IPEC-Americas excipient qualification committee chairs highlight changes to the IPEC guide on certificates of analysis for bulk excipients.

Pharmaceutical Technology
Volume 37, Issue 3, pp. 28-31

Important changes

The CoA Guide details required content and recommended format and includes a model CoA, to be used as an example. It is recognized that existing computer software used to generate the CoA may pose constraints that limit the ability to achieve the recommended format. For this reason, the format of the model CoA provided in the CoA Guide is offered only as an example. It should not be erroneously construed that the recommended format must be followed.

Date format. Because the CoA Guide is of international applicability, an unambiguous date format is required so that dates (e.g., re-evaluation or expiration date) can be clearly communicated. One example of an unambiguous date format offered in the CoA Guide is to use alpha characters to designate the month and four digits to designate the year: DD MMM YYYY (e.g., 14 JUL 2013). This best practice ensures that excipients used in the manufacture of drug products meet specification requirements at time of use and that confusion does not lead to use of expired excipients.

Original manufacturer. The original manufacturer and manufacturing site should be identified if different from the supplier and supplier location. Specifically, the name and address should appear directly or by reference (i.e., using a code) on the CoA.

Regardless of whether or not a code appears on the CoA, the excipient user is responsible for knowing the name of the original manufacturer and the address of the original manufacturing site for every lot received. Where a code is used, the excipient supplier is responsible for defining the code to the excipient user, upon request. Such information may require a confidential disclosure agreement (16).

In addition to being a legal document and the basis of the excipient manufacturer's certification that the excipient will continue to meet the specification up to the re-evaluation or expiration date, the CoA is a crucial element of the overall supply-chain controls that excipient manufacturers, distributors, and finished drug manufacturers should have in place. To facilitate traceability to the excipient manufacturer, inclusion of the name of the original manufacturer and address of the original manufacturing site or an appropriate code on the CoA was emphasized in discussions that IPEC-Americas had with FDA.

Verification of authenticity. The excipient user should periodically verify the authenticity and validity of the CoA. This can be efficiently accomplished during a supplier audit or otherwise by sending the CoA to the issuer to verify that it is authentic. The frequency of such verification may be based on risk assessment, which takes into consideration the reliability of the excipient manufacturer and the supply chain involved.

The CoA should include the name and title of the person who authorized it. A computer generated CoA, where proper controls are in place at the excipient maker, provides an equivalent or better degree of assurance that the CoA is appropriately authorized than an original hand-signed document. There is no legal requirement to have a hand-signed CoA in most countries provided that appropriate controls are in place for an alternative computer-generated signature process.

If a distributor issues a CoA on their letterhead, their CoA should be traceable back to the original manufacturer's CoA. Also, the distributor's CoA should include the original manufacturer's name and location or code (if used).

PQRI defined options to finished excipient testing. The CoA Guide 2000 included provisions for "reduced frequency testing" by the excipient maker. Since the CoA Guide 2000 was issued, the Product Quality Research Institute (PQRI) Joint Position Paper on Pharmaceutical Testing and Control Strategies was published. As reported in this position paper:

"In a post-workshop meeting, FDA representatives stated that it considers the practice of skip-testing not to be compliant with cGMPs because for those lots that are not sampled and tested, there is a lack of assurance that the finished excipient material will meet all of its specifications. FDA believes that if an attribute for a finished raw material has required criteria, there must be some measurement or test of the material on each lot to ensure that the criteria are met" (14).

FDA stated in their response to the PQRI article and in subsequent discussions with industry that in-process testing can be used in place of finished excipient testing to determine compliance to a specified test parameter and to release an excipient product as meeting the appropriate specifications, provided the excipient manufacturer has clearly identified/documented the in-process "measurement" that directly relates to the specified test parameter and the in-process test clearly demonstrates that each batch of excipient would pass the requirement, if tested. This type of assurance can be obtained during an audit of the supplier. Without assurance of the correlation of in-process testing with a finished excipient test result from (e.g., supplier audits), the user is required to perform any test that is not performed by the excipient maker on each lot.


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