Case Study: Aseptic Processing Contamination and the
Pharmaceutical Quality System
COMMENTARY
Aseptic Processing Contamination Case Studies and the
Pharmaceutical Quality System
Richard L. Friedman
Food & Drug Administration, Center for Drug Evaluation & Research, Division of Manufacturing & Product Quality
ABSTRACT: This paper summarizes parenteral drug contamination case studies presented at industry conferences and a Food and Drug Administration advisory committee meeting in the period of 2000-2004. CGMP deficiencies associated with each contamination event are discussed. The key role of a well-functioning quality system in contamination prevention is emphasized.
Introduction
While many references (1–7) discuss principles of aseptic process control, fewer publications illustrate the practical impact of substandard production practices on a product purporting to be sterile. By examining case studies, the tangible consequences of a breakdown of one or more elements of current good manufacturing practice (CGMP) can be explored. (8.9)
Three prevalent themes are central to the vast number of aseptic processing contamination problems:
• poor personnel practice
• loss of environmental control
• flawed operational design
One or a combination of these CGMP deviations has led to contamination of aseptically processed products, including parenterals, ophthalmics, and aqueous inhalers (10, 11). While personnel practice or a loss of environmental control are normally named as the immediate source of a sterility problem, the investigation into root cause (12) frequently also concludes that changes in operational design are needed to implement a lasting solution.
Quality is built into a product produced by aseptic manufacture when sound process, equipment, and facility design is employed to minimize or eliminate potential contamination hazards. Modern design approaches include systematic evaluation of potential process vulnerabilities and holistic awareness of how daily dynamic operational factors can interact (13, 14).
This process understanding should
Aseptic Processing Contamination Case Studies and the
Pharmaceutical Quality System
Richard L. Friedman
Food & Drug Administration, Center for Drug Evaluation & Research, Division of Manufacturing & Product Quality
ABSTRACT: This paper summarizes parenteral drug contamination case studies presented at industry conferences and a Food and Drug Administration advisory committee meeting in the period of 2000-2004. CGMP deficiencies associated with each contamination event are discussed. The key role of a well-functioning quality system in contamination prevention is emphasized.
Introduction
While many references (1–7) discuss principles of aseptic process control, fewer publications illustrate the practical impact of substandard production practices on a product purporting to be sterile. By examining case studies, the tangible consequences of a breakdown of one or more elements of current good manufacturing practice (CGMP) can be explored. (8.9)
Three prevalent themes are central to the vast number of aseptic processing contamination problems:
• poor personnel practice
• loss of environmental control
• flawed operational design
One or a combination of these CGMP deviations has led to contamination of aseptically processed products, including parenterals, ophthalmics, and aqueous inhalers (10, 11). While personnel practice or a loss of environmental control are normally named as the immediate source of a sterility problem, the investigation into root cause (12) frequently also concludes that changes in operational design are needed to implement a lasting solution.
Quality is built into a product produced by aseptic manufacture when sound process, equipment, and facility design is employed to minimize or eliminate potential contamination hazards. Modern design approaches include systematic evaluation of potential process vulnerabilities and holistic awareness of how daily dynamic operational factors can interact (13, 14).
This process understanding should
References: are welcome (31, 32). This openness is reflected in the recently issued Guidance on Sterile Drug Products Produced by Aseptic Processing (September 2004), which Sterile Drug Products Produced by Aseptic Processing, September, 2004. 2. Annex 1, Manufacture of Sterile Medicinal Products, European Union GMPs, European Commission, 2003. 3. Block, S. S. Disinfection, Sterilization, and Preservation, 5th Edition. Lippincott, Williams and Wilkins: Philadelphia, PA, 2000. Report No. 22, 1996. 200.51, Federal Register May 26, 2000 65 (FR 34082). Pharmaceutical Science. July 20, 2004. River Grove, IL, 2004. 25. FDA Advisory Committee for Pharmaceutical Science, October 22, 2002.