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Edward NarkeEdward Narke is regulatory managing director and
cofounder, Design Space InPharmatics.

Stability is a critical quality attribute (CQA) of each and every pharmaceutical product, and stability testing is a crucial aspect of the drug development process, with stability data serving as one of the foundations of the chemistry, manufacturing, and controls (CMC) part of any marketing application. Without an expiry profile that is suitable for the intended distribution, a drug product will go nowhere regardless of how stellar its other attributes are.

Drug development stability studies incorporate several factors that affect the expiration dating of drug products. These include chemical and physical properties during the preclinical and early formulation stages, process development through packaging development, in addition to the desired supply chain. Ultimately, sponsors rely on their stability data to gain regulatory approval for expiry dating and the storage conditions for their marketed pharmaceutical products based on their data in hand.

Many guidelines have been promulgated by regulatory authorities on the subject of stability; however, the topic is hardly static, since issues are continually raised and practices challenged. Regulatory thinking also changes. For example, the Food and Drug Administration (FDA) withdrew its stability guidance in 2006 because some of the principles were inconsistent with the agency’s 21st century initiatives.

More recently, the International Conference on Harmonization (ICH) withdrew its Q1F guideline on storage requirements for Zone III and IV. As a consequence, the regulators of several countries and regions have now revised their own stability testing guidelines.

These changes globally have led sponsors to search for the right choice of stability storage conditions for global submissions. Although various regulatory agencies have derived their stability testing requirements from parent ICH guidelines, as exemplified, they may differ in some or several parameters of stability testing requests. Moreover, the minimum time period to be covered by data at the time of marketing application submission can differ and remains a cause for much debate.

The February AAPS Newsmagazine’s cover article, Pharmaceutical Stability: Doing the Right Thing versus Doing Things the Right Way, examines standards and approaches to stability testing in a global setting. The article was developed by the Regulatory Sciences section. Read the article and then participate in the discussion question below.

Discussion Point: My company plans to file a marketing application globally for a new product for which study conditions and the amount of stability data available at the time of filing may be an issue. How much data do we need to satisfy health authorities’ expectations, when does it need to be available, and are there opportunities to update the applications during the review?