This article is part of PharmTech's supplement "Injectable Drug Delivery."

Aseptic processes are some of the most difficult processes to conduct in the pharmaceutical industry. Because of the nature of aseptic processes, sterile products produced aseptically present a significantly higher risk to the patient than terminally sterilized products. Because of the high level of risk, an effective quality-risk-management program is necessary to protect the patient. An effective risk-management program aids in the careful control of the process, reducing the risk of contamination as well as wasted effort in controlling insignificant risks.

What is an aseptic process?

One thing all aseptic processes have in common is their high level of risk. They require careful control of the aseptic environment, of personnel practices and procedures, sterilization of equipment and components, extensive environmental monitoring, and many other controls. The number of controls required and the severe consequences of control failure make aseptic processing one of the highest-risk pharmaceutical processes. Quality risk management is an essential tool in ensuring product quality.

Quality risk management

Although quality risk management (QRM) is a relatively new concept to the pharmaceutical industry, it has been used in other industries for many decades, with some risk-assessment tools dating back to the World-War-II era. The pharmaceutical industry has been slow to adopt many of these tools because of the industry focus on regulatory compliance as the driving force for quality. This traditional compliance-based approach had its drawbacks that became more evident as the industry became more diverse and sophisticated. A "one-size-fits-all" approach to quality became increasingly unworkable, leading the US Food and Drug Administration to develop a quality systems approach to regulation.

The quality systems approach to the pharmaceutical industry was launched on a large scale with the FDA publication of Pharmaceutical CGMPs for the 21st Century—A Risk Based Approach in August 2002 (1). This initiative had the ambitious goal of transforming the FDA regulatory approach to the pharmaceutical industry into a science-based and risk-based approach with an integrated quality systems orientation.

In the time since the publication of the concept paper, this initiative has been largely successful, leading to publication of international guidance documents such as ICH Q9 Quality Risk Management, and the Parenteral Drug Association (PDA) Technical Report No. 44 on Quality Risk Management for Aseptic Processes (2, 3). The publication of ICH Q10 Pharmaceutical Quality System has further enhanced the risk-based approach to pharmaceutical manufacturing.

There are many potential uses for quality risk management in the pharmaceutical industry, including:

• Determining the scope, complexity, and frequency of internal and external audits
• Identifying, evaluating, and communicating the potential quality impact of quality defects, complaints, trends, and non-conformances
• Providing a framework for evaluation of environmental monitoring data
• Evaluating the impact of changes to the facility, equipment, or process on product quality
• Establishing appropriate specifications and identifying critical process parameters during product and process development
• Assisting facility design (e.g., determining appropriate material, equipment, and personnel flows, appropriate level of cleanliness for processing areas)
• Determining the scope and extent of qualification of facilities, buildings, and production equipment and/or laboratory instruments (including proper calibration methods)
• Determining acceptable cleaning validation limits
• Determining revalidation frequency
• Determining the extent of computerized system validation
• Identifying the scope and extent of verification, qualification, and validation activities
• Determining the critical and noncritical steps in a process to assist in the design of process validation.