The International Pharmaceutical Excipients Council (IPEC) is out with a new Certificate of Analysis (COA) Guide for Pharmaceutical Excipients, a voluntary guidance that it says should help industry manufacturers ensure that their products use only high-quality excipients.
COAs are legal documents signed by manufacturers and used by distributors to ensure that an excipient product meets the defined specifications. These documents are useful in proving the identity of a given product, and are expected by IPEC to be completed and go along with each batch or delivery of an excipient to a manufacturer.
The importance of excipient quality has recently come to light as an important subject, particularly in China, where substandard and falsified excipients have been behind a rash of counterfeiting scandals. The country recently instituted new rules aimed at requiring all manufacturers to ensure excipient quality-a development IPEC might be trying to capitalize on with its COA guide.
The document defines what IPEC calls a "uniform approach" to the content and format of COAs for excipients, as well as the roles and responsibilities borne by manufacturers and distributors of excipients.
"By providing this foundation for mutual understanding, the COA will serve as an important element of the overall supply chain controls needed to provide the user with assurance of excipient conformance to specification and its suitability for use in pharmaceuticals," IPEC wrote.
So what should an ideal COA contain? IPEC's guide explains, noting that of primary importance is information regarding the manufacturing site of the original manufacturer. "The intent is to enable the user to assure that a change in manufacturing location has not occurred without their knowledge," IPEC said.
While this detail seems small, it has received prominent attention in recent months from EU authorities and the European Fine Chemical Group, whose November 2012 report on APIs notes that suppliers have been known to switch manufacturing locations without warning, even as the primary distributor of the products (in their case, active pharmaceutical ingredients) remain the same.
The same analysis could just as easily be applied to excipients, IPEC wrote.
"The intent is to enable the user to assure that a change in manufacturing location has not occurred without their knowledge," IPEC said. "It is essential that the manufacturer be known to the user. To protect confidentiality through the supply chain, the use of codes for manufacturers and manufacturing sites on the COA is acceptable as long as the user can link the code to the manufacturer and site of manufacture."
The identity of the product, as well as its compendial trade names, the material and its grade and other information relevant to its identity, is perhaps the second most important detail to list, IPEC said.
Other details are important, as well. The excipient's date of manufacture, expiration date and retest date, as well as "other relevant statements regarding the stability of the excipient" should be included in the COA.
Much of the remainder of the document pertains to analysis pertinent to specific analyses conducted to confirm the product's identity and quality. In all cases, the test name, test method and acceptance criteria should be contained within the COA, as well as an analysis of the test results, alternative test results (if appropriate) and any retesting done to confirm results.
Other information, such as the standards of good manufacturing practice (GMP/CGMP) used in the course of manufacture, should also be contained within the COA, as well as information about who signed the COA.