Quality Considerations in the Establishment of Specifications for Pharmaceuticals

Abstract

The quality of a commercial pharmaceutical product is set by a well-designed, understood, and executed manufacturing process using high-quality raw materials. In addition, this built-in quality is verified at release and its stability is assured by random sampling and testing of critical product characteristics against established specifications. There are several approaches to how this verification testing is designed, depending on the underlying quality philosophy employed. This article explores different common approaches and briefly discusses the pros and cons of each. In the most general sense, quality can be defined as the extent to which a product meets customer expectation. The common practice in the pharmaceutical industry is to specify test acceptance criteria without clearly defining or relating these criteria to an underlying quality statement about the product. Fundamental to constructing such a quality statement is an assumed definition of what is meant by drug product in this context, that is, batch, individual dosage units, or some other basic unit. As a result, it is not always fully clear what a reasonable customer expectation is. In contrast to current practices, we propose that a transparent quality statement should be formulated for every pharmaceutical product and that the test(s) to verify that the required performance (as defined by the quality statement) should be designed using established statistical techniques.

Keywords:

• Acceptance value
• Coverage
• Operating Characteristic curve
• Quality by design
• Risk assessment

Acknowledgments

Dr. Sandell was with AstraZeneca R&D, Lund, Sweden, when this work was completed.