Regulations and industry guidelines focus on ensuring excipient safety by specifying risk assessments and shared responsibility.

Feb 02, 2018 By Cynthia A. Challener

Excipients are crucial ingredients in final drug formulations with potential impacts on product quality, stability, tolerance, release profiles, local distribution and availability, and thus overall efficacy and safety. Recent regulations have increased the requirements for drug manufacturers and excipient suppliers with respect to ensuring the quality and safety of excipients. The emphasis continues to be on the use of risk assessments and the growing recognition that excipient producers and pharmaceutical companies have shared responsibility for ensuring excipient safety.

Updated guidelines

Excipients are becoming a top priority among regulatory agencies. Regulatory bodies in the United States, European Union (EU), and Japan, as well as those in the ‘BRICK’ (Brazil, Russia, India, China, and Korea) countries, are modifying existing and/or introducing new regulations for finished pharmaceutical products that specifically address excipients, either directly or indirectly. Many of these regulations have an impact beyond domestic production of drug products, according to Priscilla Zawislak, global regulatory affairs advocacy manager with Dow Pharma Solutions. National pharmacopeias are also placing a greater emphasis on standards for excipients.

Regulations on excipient risk assessment were issued by the European Medicines Agency (EMA) in 2015 (1) with implementation required by March 21, 2016. An update of the annex to the European Commission’s guideline on excipient labeling by EMA on Oct. 9, 2017 (2) included the expansion of safety warnings for 10 excipients and the addition of five new excipients to the list, according to Mario DiPaola, senior scientific director at Charles River Labs.

“Recent draft guidance documents issued by FDA, such as the Abbreviated New Drug Applications (ANDA), Refuse to Receive, and Controlled Correspondence guidances, are examples of why drug product manufacturers must have a better understanding of what’s needed to comply,” adds Zawislak. “Open communication with suppliers about the composition, functionality, and performance of excipients in a drug product is essential. Excipients are no longer regarded as inactive and it is no longer sufficient to simply provide excipient specifications in an investigational new drug application (ANDA). FDA now requires drug product manufacturers to tell the full story about the role and interaction of the excipients with the API in final drug products,” she continues.

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