Mary Ann Gorko is principal statistician at AstraZeneca.

Mary Ann Gorko

The manufacture of pharmaceutical and biopharmaceutical drug products is a complex process that takes place in a highly regulated environment (1). Success requires a combination of scientific, engineering, and regulatory knowledge. One critical part of drug development is formulating the compound into a final drug product, ensuring that desirable physical and chemical properties remain stable for an acceptable period of time and meet regulatory and commercial requirements for specifications for the product (2).

	One key requirement is that the drug retain its physical and chemical properties such as potency, purity, and bioavailability for a set period of time, referred to as its shelf life (3). Once a shelf life has been defined for the drug, control strategies must be instituted to provide a high level of assurance that batches of drug product released into the market remain within specifications throughout the drug’s shelf life.

	One critical control strategy is the use of internal release limits. This article discusses how these limits are calculated and applied to ensure drug product quality. Click 

* is technical manager of statistics at AstraZeneca, maryann.gorko@astrazeneca.com; 

is senior director at Janssen Pharmaceutical R&D; 

is principal big data analyst at Novo Nordisk A/S; 

is senior principal statistician at AbbVie’s research department; 

is manager of statistics at Pfizer; and 

	*To whom all correspondence should be addressed.


	Vol. 42, No. 10
	October 2018
	Pages: 30, 32, 34, 36, 38–39

	When referring to this article, please cite it as S. Altan, Y. Dong, M.A. Gorko, N. V. Hartvig, M. Johnson, G. Larner, and S. Sherling, "Understanding Internal Release Limits," 

Articles

Internal release limits help ensure that a batch of drug product remains within specifications throughout its shelf life. This article explores what internal release limits are and why they are important.

Understanding Internal Release Limits

Representatives from PhRMA member companies discuss the growing concern about out-of-trend stability data, including possible statistical approaches and the implementation challenges to identifying OOT results.