In-Pharmatechnologist.com sat down with Irwin Silverstein, COO and VP of the International Pharmaceutical Excipients Auditing, Inc., and John Giannone, incoming IPEC-Americas chairman, to discuss the updated guide as well as other concerns for excipient manufacturers and the lack of GMP certifications from the US FDA.
“It’s not clear in the USP that you’re not allowed to do skip lot testing,” Silverstein said, noting that the FDA’s GMP requirements call for either the supplier or customer to run the test. But the USP will not take issue with skipped tests if the manufacturers action still complies with the monograph requirements, Silverstein said.
Some of the tests also don’t provide any value in terms of patient safety, so under certain circumstances, the tests will not have to be conducted.
IPEC notes in the updated guide four instances in which alternatives to finished excipient testing “might be justified.” Such cases include:
- An impurity, by-product or unreacted raw material could not be present in the product because the raw materials and chemical reactions used could not contain or generate it above the specified limits;
- A stable process is indicated though a high Process Capability Index;
- When in-process analyses show that the property which is determined at reduced frequency is stable and within specification and when repeating a test on each batch would be redundant; and
- An analysis of a parameter on every batch in process has been shown to provide assurance that the final test requirement can be met and therefore the finished excipient can be tested at a reduced frequency.
These cases should not be considered all-inclusive or where alternatives are necessarily appropriate, IPEC warns, adding that for all testing, excipient suppliers should develop and maintain documentation outlining the process control systems and validation data justifying the use of alternatives.
Regardless of the skipped testing, IPEC wants pharmaceutical companies on an annual basis to confirm that the COAs are authentic and verified, Silverstein said. But this might be more difficult than expected because of the difficulty in ensuring the authenticity and signatures of all COAs issued by every excipient manufacturer that a pharma company uses.
“There’s no requirement in the US government to produce” a GMP certification for excipient manufacturers, Giannone said.
And although the recently passed FDASIA legislation will require pharmaceutical companies to provide lists of the sources of all of their ingredients, the FDA does not have the capability or the expertise to conduct audits of excipient companies.
“The FDA will have the option to conduct the audits,” Silverstein said.
Manufacturer, Supplier Sites
In addition, IPEC clarifies in the updated guide that the original manufacturer and manufacturing site must be identified if they are different from the supplier or supplier location so users can be assured that a manufacturing site has not changed without their knowledge. “It is essential that the manufacturer be known to the user,” IPEC notes. Codes to protect the confidentiality of the supply chain can be used in the COA, according to IPEC, as long as the user can identify both the manufacturer and its site.