Standardizing Excipient Information to Achieve Supply-Chain Security

The use of various documents and guides by the International Pharmaceutical Excipients Council can facilitate the flow of information among excipient manufacturers, distributors, and users.
Mar 01, 2013

Efficient and controlled information exchange among excipient manufacturers, distributors, and excipient users is crucial to ensure that the optimal information is obained by the user to better control the drug product. The author discusses the use of various documents and guides by the International Pharmaceutical Excipients Council to facilitate this information flow.

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On July 6, 2012, FDA issued a Notification to Industry indicating that oils, glycerin, and proteins commonly used in the production of human and animal food, medical products, cosmetics, and other FDA-regulated products may contain toxins if they are derived from the Jatropha plant (1). A common response to this type of notification is for pharmaceutical manufacturers (i.e., excipient users) to inundate their excipient suppliers with questionnaires requesting information regarding raw-material sourcing of their excipients regardless of the excipient purchased or its origin. This approach rarely results in a successful exchange of key information and will many times slow the flow of crucial information to companies that need this information to provide to regulators and other interested parties.

A more proactive approach would be to adopt the standardized excipient-information approaches afforded by documents provided by the International Pharmaceutical Excipients Council (IPEC). By using these documents, excipient users have information about excipient raw-material sources and other information needed to answer regulators' questions without the need to ask further questions of their suppliers. Instead of reacting to a regulatory or industry news headline by sending out questionnaires pertaining to a supplier's source and method of manufacture of an excipient, a pharmaceutical manufacturer can take a more beneficial and economical approach by first reviewing existing information already available from its supplier. These approaches are explained in IPEC guides, including among others: the IPEC Excipient Information Package (EIP) Template and User Guide; the IPEC Quality Agreement Guide and Template; the IPEC Excipient Composition Guide; the IPEC Excipient Qualification Guide; and the IPEC–PQG Excipients GMPs Guide, which offers GMP appropriate for the manufacture of excipients and is a joint initiative between IPEC and the Pharmaceutical Quality Group (PQG).

A recent example potentially concerning excipients was the use of "gutter oil" to manufacture antibiotic APIs. Gutter oil is a term used in China to describe illicit cooking oil, which has been recycled from waste oil collected from various sources, such as restaurant fryers, drains, grease traps, and slaughterhouse waste. The potential health effects of gutter oil are unclear because experts have expressed opposing opinions on the safety of the intermediate produced using this oil. The topic, however, became a source of questions from pharmaceutical manufacturers to their excipient suppliers regarding the security of the supply chain of excipients sold in the United States, irrespective of whether or not the excipient could be derived from this material. This incident is another example of where a standardized excipient information package could be used to obviate the need for customer questionnaires and improve the flow of information between excipient manufacturers and users.

Pharmaceutical companies' understanding of the source, quality, and performance of the excipients they use in their drug products is crucial to ensure the safety, quality, and efficacy of the medicines they produce. Excipients have a wide range of applications and are essential components of the drug-product formulation. Characteristics that excipients bring to formulated drug products include appearance, manufacturability, stability, and delivery of the active ingredient. Understanding their composition, performance attributes, manufacturing, and supply chain is essential.

Pharmaceutical users should refer to excipient information previously provided from their suppliers during the user's supplier-qualification processes, such as through the EIP. In the Jatropha and "gutter oil" examples, pharmaceutical companies would have been able to quickly identify excipients that were not subject to the alert and that needed no further follow-up. The informed pharmaceutical user could focus their efforts on the few relevant excipients and APIs.