Update on FDA Pharmaceutical cGMPs for the 21st Century - A Risk-based Approach

The US Food & Drug Administration announced a significant new initiative in August 2002. The announcement, titled Pharmaceutical Current Good Manufacturing Practices (cGMPs) for the 21st Century was made to enhance and modernize the regulation of pharmaceutical manufacturing and product quality. It was made to bring a 21st century focus to this critical FDA responsibility.

The objectives of the new initiative included:

• Encouraging early adoption of new technological advances by the industry
• Facilitating application of modern quality management techniques
• Encouraging implementation of risk-based approaches that focused both industry and Agency attention on critical areas
• Ensuring that regulatory review, compliance, and inspection policies are based on current good science
• Enhancing the consistency and coordination of FDA's drug quality regulatory programs by further integrating quality systems approaches into the Agency's business processes and regulatory policies

Over the past four years the Agency has released periodic reports documenting its progress and plans.

• February 20, 2003 - Listed accomplishments and first steps toward achieving FDA's goal in the initiative
• September 2003 - Outline of Agency implementation plan for achieving objectives announced previously

The Agency formed a number of multidisciplinary working groups to continue to shape the initiative, under the oversight of the cGMP Steering Committee. In addition the Agency has formed a Council on pharmaceutical quality, which has been charged with policy development, coordination, and continuing change management, including the ongoing implementation of specific quality management systems within FDA. Summarized here are a number of the specific accomplishments under the initiative, thus far:

• Adoption of quality systems model for Agency operations
• Development of quality systems guidance for cGMP regulation
• Implementation of a risk-based management plan
  • Developed a strategic action plan
  • Developed a risk-based model for inspectional oversight
  • Conducting an ongoing data analysis
  • Issued in 2003, Guidance for Industry Part 11, Electronic Records, Electronic Signatures - Scope and Application. Many barriers to scientific and technological advances were removed, and the risk-based approaches to managing computer systems were encouraged.
  • ONDC Pharmaceutical Quality Assessment System developed.
• Science-based regulation of product quality
  • PAT team and the Manufacturing Science Working Group have continued their collaboration and significant progress has been made in building consensus on
    • the principles of manufacturing science and process understanding.
    • PAT guidance has been issued
    • A support structure for the PAT guidance was reported in FDA's earlier reports to be evolving in the pharmaceutical community including the American Society of Testing Materials (ASTM) E 55 committee on pharmaceutical application of process analytical technology.
      
    • Additional progress has been made as reported below
  • International Collaborations: FDA continued its collaboration with international health and regulatory partners. They continued to collaborate within the ICH framework. FDA is seeking membership in PICS (Pharmaceutical Inspection Cooperation Scheme).
    
  • Implementing the Future of Pharmaceutical Manufacturing regulation
    • Risk-based approaches: FDA has implemented a risk based approach to regulating pharmaceutical manufacturing. The approach will be applied to the review, compliance, and inspectional components of FDA regulation
    • Quality systems approach: The FDA has issued Quality Systems Approach to Pharmaceutical cGMPs
    • Enhanced internal regulatory coordination - The Agency has developed a staff of highly trained individuals, known as the Pharmaceutical Inspectorate to conduct inspections of highly complex operations
    • Analysis of cGMP requirements is ongoing

Since the 2003 progress Report, the Agency has:

• Developed a risk-based approach for manufacturers to use to comply with Part 11 electronic records requirements
• Developed a technical dispute resolution process
• Changed procedures for drug cGMP warning letters to give greater consistency and uniformity to the letters.
• Continued to be engaged in the ICH process. ICH Q8, dealing with pharmaceutical development and Q9 dealing with quality risk management, have been signed off at Stage 4.
• Science-based policies and standards to facilitate innovation
  • Aseptic processing final guidance has been issued
  • PAT Guidance - A framework for innovative pharmaceutical development, manufacturing, and quality assurance has been issued
  • The FDA PAT team has worked with ASTM International to establish the technical committee E55 on pharmaceutical application of PAT. Focusing on process monitoring and control, instead of testing, requires process control standards consistent with guiding principles of the control theory. The E 55 committee is tasked with developing standards related to process analytical technology with the primary focus on process understanding and control.
  • The Agency has developed a system to use comparability protocols for the review process for post approval changes.
• Improved the integration of the pre-approval and cGMP inspection programs
• Implemented its quality management systems
• The Agency is updating its current thinking on validation
• The Agency has developed a risk-based inspection site selection procedure

The above is but a brief summary of most of the accomplishments by the Agency on the progress of its cGMP initiatives. To read a complete and detailed summary, please visit the FDA homepage for CDER, CBER and ORA.