Quality Risk Management: Systems Control and Practical Considerations


The ten year QRM journey traveled by industry and regulators since the 2006 publication of ICH Q9 Quality Risk Management (QRM) has been a fruitful one as many beneficial changes have been implemented.  Industry and regulators had begun discussing QRM even before 2006.

Regulatory efforts such as the FDA’s 2002 Pharmaceutical Quality for the 21st Century initiative encouraged more holistic risk-based approaches to decision making in the area of pharmaceutical manufacturing.  The FDA initiative helped galvanize the still ongoing paradigm shift from reactive quality approaches to performance and management-based quality.  It was widely recognized that a harmonized, lifecycle based framework was needed to promote large-scale change.  This lifecycle approach was developed in a trio of International Conference of Harmonization (ICH) guidelines as follows:

  • ICH Q8 objective:  Design processes and leverage innovations to improve process understanding and pharmaceutical quality
  • ICH Q9 objective:  Identify, understand and manage risks throughout the lifecycle through objective, systematic, science-based decision making
  • ICH Q10 objective:  Design and use an effective quality system to assure ongoing state of control throughout the lifecycle (applies to both internal and outsourced operations).

A common thread in all of the guidelines was effective management of manufacturing and quality risks throughout the lifecycle.  The guidelines emphasized adaptation and continual improvement in response to lifecycle learnings, and the value of using contemporary technologies to manufacture more reliably.  Below are a few relevant excerpts:

  • ICH Q8(R2):  “Throughout the product lifecycle, companies have opportunities to evaluate innovative approaches to improve product quality (see ICH Q10).”
  • ICH Q9:  “Quality risk management is a systematic process for the assessment, control, communication, and review of risks to the quality of the drug product across the product lifecycle… Once a quality risk management process has been initiated, that process should continue to be utilized for events that might impact the original quality risk management decision, whether these events are planned (e.g., results of product review, inspections, audits, change control) or unplanned (e.g., root cause from failure investigations, recall).”
  • ICH Q10:  “Use of knowledge management and quality risk management will enable a company to implement ICH Q10 effectively and successfully.”  This includes “identifying and implementing appropriate product quality improvements, process improvements, variability reduction, innovations, and pharmaceutical quality system enhancements, thereby increasing the ability to fulfill a pharmaceutical manufacturer’s own quality needs consistently.”

Since the publications of these guidelines, there has been a growing understanding of the truly integral role of QRM, and recognition that the true test of quality system effectiveness is its ability to properly manage daily manufacturing and quality risks.

A pharmaceutical manufacturer is responsible for implementing robust daily operations that consistently yield good quality drugs.  This paper discusses how a mature quality system assures a state of control throughout the product lifecycle by vigilantly managing manufacturing and quality risks.  If the system is working, process and facility vulnerabilities that lead to operational variation and substandard pharmaceutical quality will be detected, understood, and addressed.

This paper also shares some practical considerations regarding a firm’s state of control and application of Quality Risk Management (QRM) when making decisions regarding facilities, equipment, processes, and raw materials.

An effective quality system will integrate lifecycle QRM to:

  • Review original risk acceptance decisions as new knowledge is gained
  • Mitigate risk by designing and adapting operations to ensure they are reliable, and
  • Assure active engagement of senior management so that state of control of the equipment, process and facility is maintained and reliable quality is consistently delivered to customers (patients).

This vigilant and risk-based quality culture assures that every batch, every day, continues to be safe and effective.

Industry technical organizations, regulatory agencies, and PIC/S have made major progress in promoting implementation of the quality risk management approaches discussed in this paper in both industrial and regulatory realms.  In the coming years, it is hoped that these QRM principles will be even more widely implemented in industrial quality systems.  Ultimately, daily risk management decisions on issues involving equipment, facilities, process design, process control, materials, maintenance, staff qualifications, supervision, and investigations will determine the quality of the drugs that are shipped from a given facility.

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