A Dubious Foundation for Quality Control

Dipak Sarker, the author of Quality Systems and Control for Pharmaceuticals, states that his book is a "pocket guide" meant to "balance size with practicality and cost and therefore accessibility to nonexperts." The book is meant to support in-house short-course training events, and its intended audience includes undergraduates, postgraduates, industry professionals, practicing clinicians, researchers, and scientists making the transition to industry. Without a doubt, this is quite an ambitious agenda for a pocket guide, and it is not surprising that the author stumbles along the way.

The first section includes information about quality systems' structure, introduces the concepts of Three Sigma and Six Sigma, and describes the total quality-management system. In addition, the author explains that compliance with current good manufacturing practice (CGMP) is achieved "when the process of manufacture is clearly defined."

Quality Systems and Control for Pharmaceuticals, Dipak K. Sarker, Wiley, Hoboken, NJ, 2008, 204 pp., ISBN 978-0-470-05692-9.

Later in the text, the concept of good laboratory practice (GLP) is introduced with regard to the analytical laboratory. Then, in a section about valid analytical methodologies, the author again discusses GLP as it applies to the analytical laboratory.

These citations conflict with FDA regulations. The US Code of Federal Regulations defines nonclinical laboratory studies as in vivo or in vitro experiments in which test articles are studied prospectively in systems under laboratory conditions to determine their safety. Thus, from FDA's perspective, the analytical laboratories must meet CGMPs, not GLPs.

The book's analysis of the "qualified person" (QP) brings further confusion. At a time of multinational pharmaceutical companies, it is critical to understand the different approaches taken in various parts of the world. Sarker describes the responsibilities and importance of the QP, but does not make it clear that only certain regions of the world follow the QP concept. For example, many of the activities of the European QPs are the responsibility of the qualityassurance (QA) departments in the US instead.

The book's section about process and manufacturing validation provides a good introduction to topics such as cleaning validation, software and programmable logic controllers, and hazard analysis of critical control points. The discussion includes references to several relevant international organizations. The author stresses the requirement for a suitable validation plan or protocol. This advice is critical because such plans too often are inadequate in practice, especially with regard to analytical methodology.

The subchapter on valid analytical methodologies states they can be obtained from the specifications of FDA or other regulatory bodies. Yet if one accepts the ICH Q6A guideline's definition of "specification" (i.e., tests, analytical procedures, and acceptance criteria), much of this information is confidential and not subject to release by FDA. Pharmacopoeial compendia are much better sources for such information because their analytical procedures have been validated and their results evaluated.

The longest chapter in the book covers GMPs. It divides standard products into nonsterile and sterile medicines and points out their different inherent risks and consequent release protocols. The author correctly notes that specialized conditions for sterile manufacturing and the nature of sterile drugs themselves often require additional staff training.

A detailed discussion of the manufacture of materials requiring specialized production facilities begins by examining parenterals. The author refers to strict ISO standards for manufacturing processes, particularly for the cleanliness of the production suite, but does not mention the extensive FDA guidance that is available in this area (e.g., Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing —Current Good Manufacturing Practices).

Another chapter covers in-process and on-process quality-control testing and control. The reader will find the introduction to process analytical technologies (PAT) useful. PAT approaches allow every dosage unit in a batch to be examined prospectively. Some products require traditional in-process testing at various points in the manufacturing process, and 21 CFR 211.110 specifically requires in-process testing as part of CGMPs. The author does not discuss this in-process testing, however.

Unfortunately, the author did not fully meet the goals he outlined in the preface. The target audience is too broad and has too great a diversity of experience and backgrounds to be encompassed easily in one book. Furthermore, as noted above, the book contains errors and misconceptions that could lead novices astray.

This book can provide a broad introduction to quality systems and the control of pharmaceuticals, especially in an in-house training setting with an experienced instructor who can dispel the misconceptions that the book contains. The student would be well served by taking subsequent courses to gain greater depth than this text offers.

Eric Sheinin is the president of Sheinin and Associates, 13917 Bergenfield Dr., North Potomac, MD 20878, tel. 301.424.2606, fax 301.424.2831, esheinin@comcast.net. He also is a member of Pharmaceutical Technology's editorial advisory board.