QUALITY RISK MANAGEMENT Q9(R1)

Risk management principles are effectively utilized in many areas of business and government including finance, insurance, occupational safety, public health, pharmacovigilance, and by agencies regulating these industries. In the pharmaceutical sector, the principles and framework of ICH Q9, coupled with the official ICH training material that supports this guideline, are instrumental in enhancing the application of effective quality risk management by industry and regulators. The importance of quality systems has been recognized in the pharmaceutical industry and it is evident that quality risk management is a valuable component of an effective quality system.

 

It is commonly understood that risk is defined as the combination of the probability of occurrence of harm and the severity of that harm. However, achieving a shared understanding of the application of risk management among diverse stakeholders is difficult because each stakeholder might perceive different potential harms, place a different probability on each harm occurring and attribute different severities to each harm. In addition, subjectivity can directly impact the effectiveness of risk management activities and the decisions made. Therefore, it is important that subjectivity is managed and minimized. In relation to pharmaceuticals, although there are a variety of stakeholders, including patients and medical practitioners as well as government and industry, the protection of the patient is of prime importance when managing the risk to product quality and availability, when availability risks arise from quality/manufacturing issues.

The manufacturing and use of a drug (medicinal) product, including its components, necessarily entailsome degree of risk. The risk to its quality isjust one component of the overall risk. It is important to understand that product quality is assured based on appropriate riskbased decision-making throughout the product lifecycle,  such that the attributes that are important to the quality of the drug (medicinal) product are maintained and the product remains safe and effective.

An effective quality risk management approach can further ensure the quality of the drug (medicinal) product to the patient by providing a proactive means to identify and control potential quality issues during development, manufacturing, and distribution. This includes an appropriate application of root cause analysis that can identify and address the root cause(s) and other causal factors (e.g., human-related) of such issues. A proactive approach to quality risk management is beneficial, as it facilitates robust product design and continual improvement, and it is of strategic importance in achieving an effective pharmaceutical quality system. (See ICH Q10 for guidance in relation to an effective pharmaceutical quality system.) Additionally, use of quality risk management can improve the decision-making if a quality problem arises.

In the development phase and as part of validation, quality risk management is part of building knowledge and understanding risk scenarios, so that appropriate risk control can be decided upon for use during the commercial manufacturing phase. In this context, knowledge is used to make informed risk-based decisions, trigger re-evaluations and stimulate continual improvements. Effective and proactive quality risk management can enable better, more informed and timely decisions throughout the lifecycle. This can provide regulators with greater assurance of a company’s ability to deal with potential risks and avert problems, and can beneficially affect the extent and level of direct regulatory oversight.

The application of digitalization and emerging technologies in the manufacture and control of drug (medicinal) products can lead to risk reduction, when such technologies are fit for their intended use. However, they can also introduce other risks that may need to be controlled. The application of quality risk management to the design, validation and technology transfer of advanced production processes and analytical methods, advanced data analysis methods and computerized systems is important

The purpose of this document is to offer a systematic approach to quality risk management that leads to better, more informed, and timely decisions. It serves as a foundation or resource document that is independent of, yet supports, other ICH Quality documents and complements existing quality practices, requirements, standards, and guidelines within the pharmaceutical industry and regulatory environment. It specifically provides guidance on the principles and some of the tools of quality risk management that can enable more effective and consistent risk-based decisions, both by regulators and industry, regarding the quality of drug substances and drug (medicinal) products across the product lifecycle. It is not intended to create any new expectations beyond the current regulatory requirements.

An understanding of formality in quality risk management may lead to resources being used more efficiently, where lower risk issues are dealt with via less formal  means, freeing up resources for managing higher risk issues and more complex problems that may require increased levels of rigor and effort. An understanding of formality can also support risk-based decision-making, where the level of formality that is applied may reflect the degree of importance of the decision, as well as the level of uncertainty and complexity which may be present.

Appropriate use of quality risk management can facilitate but does not obviate industry’s obligation to comply with regulatory requirements and does not replace appropriate communications between industry and regulators. Quality risk management should not be used in a manner where decisions are made that justify a practice that would otherwise, in accordance with regulations and/or guidance, be deemed unacceptable.