Joint Position Paper on Pharmaceutical Excipient Testing and Control Strategies

This article presents collaborative positions among excipient manufacturers, drug product manufacturers, and members of the US Pharmacopeia on key issues pertaining to the control of pharmaceutical excipients stemming from a recent Pharmaceutical Quality Research Institute workshop.

The Product Quality Research Institute (PQRI) Workshop on Excipient Testing and Control Strategies was held Oct. 11–12, 2006 in Bethesda, Maryland. The workshop was designed to provide industry, the US Food and Drug Administration, and the US Pharmacopeia an opportunity to interact on topics related to the testing and release of pharmaceutical excipients. Results of a recent PQRI industrywide survey on the control of pharmaceutical excipients were discussed in detail (1). Roundtable discussions about the impact of FDA regulations, guidances, and the Federal Food, Drug, and Cosmetic Act (FD&C Act) on excipient control strategies were held, and stakeholder concerns were identified (2–4). Ideas were discussed for potential changes in compendia, guidances, and regulations to mitigate or remove redundant, duplicative, or unnecessary testing on excipient batches that do not add value. Topics covered in this article apply to pharmaceutical excipients that have compendial monographs in United States PharmacopeiaNational Formulary (USPNF), European Pharmacopoeia (PhEur), or Japanese Pharmacopoeia (JP).

Commonly used ways to control and communicate the quality attributes of excipients manufactured using a continuous flow process were discussed in a roundtable format. Some current practices for skip testing of excipients were examined. Ways to improve pharmaceutical product quality by characterization and control of physical and chemical properties of critical excipients were explored. Advantages of using independent third-party audits to effectively assess and ensure quality of excipients were described. The issue of excipient manufacturers producing pharmaceutical-grade excipients that are not tested according to USP–NF was discussed. The workshop assessed the status of compendial harmonization and its expected reduction of overall testing requirements.

Each attendee had an opportunity to participate in five discussion topics in a roundtable format. The workshop concluded with a presentation of summaries of roundtable discussions about each topic to the entire assembly. Each presentation was followed by a question-and-answer session. This article presents the highlights and recommended action items for each of the five topics.

Continuous-flow manufacturing and skip-lot testing used for excipients in the context of 21 CFR Part 211.84 regulations

The workshop topic description was as follows:
The definition of 'continuous process' as currently used by excipient manufacturers does not clearly define a lot. This workshop will arrive at a commonly agreed definition of a 'lot' or 'batch' in a continuous-flow process and a commonly agreed way to control quality of excipients manufactured using a continuous-flow process. Skip-lot testing is not currently used effectively and efficiently by stakeholders, and this workshop will help identify and discuss best practices for use of skip-lot testing.

Survey results noted that less than 20% of drug-product manufacturers accept material based on excipient manufacturer's process controls and in-process tests not mentioned on a certificate of analysis (CoA) but providing assurance of USP–NF requirements. This is an area where opportunities exist for excipient manufacturers and drug-product manufacturers to research and subsequently use information and knowledge that lie in the manufacturing process-controls and in-process test-result domains of an excipient manufacturer. Assessment of such information also could confirm or otherwise indicate certain physicochemical quality aspects of an excipient batch or qualities of an excipient produced under continuous manufacturing conditions.

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