FDA's Pharmaceutical Quality Initiatives: Implementation of a Modern Risk-based Approach - Pharmaceutical Technology

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FDA's Pharmaceutical Quality Initiatives: Implementation of a Modern Risk-based Approach
The US Food and Drug Administration announced its Pharmaceutical GMPs for the 21st Century initiative six years ago. This article reports on the outcome of a recent workshop on this topic and the action plan set forth.

Pharmaceutical Technology

The path ahead

The Pharmaceutical Quality Initiatives Workshop planning committee recommended that FDA consider several proposals and next steps. Five overarching focus areas emerged from the three-day workshop as key to addressing remaining challenges and moving toward the "desired state:"

  • Formalizing a regulatory agreement
  • Defining risk management, quality by design, and design space
  • Carrying out education, training, and future workshops
  • International harmonization with other regions
  • Maintaining momentum at FDA.

Regulatory agreement. By definition, this is an agreement envisioned (at the time of product approval) between FDA and the applicant on the management of postapproval CMC changes. More specifically, it is a customized, product-specific regulatory framework proposed by the applicant to manage and/or implement postapproval changes based on demonstrated product and/or process understanding and controls. The agreement could facilitate continual improvement and product life cycle management while providing a scientific basis for applicants to manage postapproval changes, thereby reducing the number of postapproval supplements. Regulatory flexibility is predicated on meaningful improvements to pharmaceutical development and scientific information submitted in an application.

Key recommendations:
  • An FDA and industry team needs to work together to develop a mock agreement in 2008
  • The mock agreement should demonstrate the regulatory flexibility that can be obtained by using QbD during pharmaceutical development and increase the role of a firm's internal quality system to manage change over a product's life cycle
  • The framework should be the same for biotechnology products, but details will differ.

Definitions and terminology. Workshop participants felt that common understanding of key terms associated with risk management and QbD must be cultivated collaboratively by industry and FDA. This terminology serves as a fundamental foundation for implementing quality initiatives and must be usable in all regions around the globe. Discussants proposed the following:

  • Risk-management relates to life-cycle management. A subsequent FDA-ISPE Workshop, "Product Quality Life Cycle Implementation: Practical Approach to Quality by Design," was held in June 2007, covering design space, quality control strategy, and critical quality parameters.
  • Terminology must be shaped in concert with the progress of ICH quality topics: pharmaceutical development (Q8), quality risk management (Q9), and quality systems (Q10).
  • FDA and the Pharmaceutical Research and Manufacturers of America (PhRMA) should cosponsor an ICH roundtable discussion on active pharmaceutical ingredients (API) to determine how to incorporate ICH Q8, Q9, and Q10 into API development
  • A 3–5 member FDA and industry team should be formed to draft, finalize, and publish definitions and examples in a suitable journal in 2008.

Education and training. As experience with new approaches is gained, more specific and highly technical discussions and real-world training opportunities, to be headed by industry, are needed by 2009, according to workshop participants. Technical guidance needs to be developed in collaboration with stakeholders such as ISPE. FDA will facilitate future educational conferences and workshops managed by industry to promote understanding of specific technical issues with examples and case studies encompassing QbD, process validation, and pharmaceutical development (ICH Q8), quality risk-management in defining the control strategy (ICH Q9), pharmaceutical quality systems (ICH Q10), and work being done with generic stakeholders to develop a model example for design space.


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