Postmarketing regulatory process breakout report
Preparation and review of supplements for routine postmarketing changes are generally recognized as burdensome, and both FDA
and industry are seeking a better utilization of limited resources. Manufacturers continue to express difficulty in determining
what status a change should fall into: prior approval supplements (PAS), changes being effected (CBE), or annual reports.
FDA does not always concur with the strategy as proposed by the manufacturer. Additionally, the requirements for filing supplements
for routine changes can hinder a firm's willingness to invest in continual improvement.
Participants in this breakout session felt that revisions to the current postmarketing regulatory process should be considered
to use a risk-based approach for review and approval of process or control changes. Where manufacturers can demonstrate process
understanding and product knowledge within a QbD environment, a streamlined or more flexible approach to regulatory strategy
should be available. This should encourage the regulated industry to embrace new and improved technologies and/or regulatory
agreements in support of improvements to product quality and efficiency.
Discussants also explored the impact to the inspection process as a result of managing certain types of changes through the
quality system. They proposed:
- Current postapproval regulatory process warrants revision based on risk assessment
- Current process acts as an impediment to improvement in processes of a firm
- All CBE supplements possibly be eliminated and that postmarketing approval process options be reduced to PAS and annual reports
- Both critical and noncritical changes can be managed through a firm's quality system
- Multi-site companies should have a single robust global change management system
- Change management system should include multi-disciplinary review
- Change management system should be supported by knowledge management system
- Annual reports should be limited to a summary or index of changes
- Supporting data should be maintained by the manufacturer
- GMP inspection process should remain an audit of the effectiveness of a firm's quality system.
Implementation of quality risk-management breakout report
The ICH Q9 document on risk management has been issued by FDA as a guidance and is at Step 5 (implementation) in the ICH process.
In addition, there is an official ICH Q9 briefing pack available online at
http://www.ich.org/, that provides valuable training presentations. However, there is still concern from industry and regulators in developing
a shared understanding of the implementation of quality risk-management tools. Exploring the concerns, analyzing the more
difficult issues, and sharing case studies can achieve a common understanding. This breakout session explored some of the
controversial and difficult aspects of implementing quality risk management, including the importance of a clearly defined
risk question, implementation of risk management over the product life cycle as part of an overall quality strategy, and a
sharing of training successes.
Quality risk-management principles are used over the life cycle of the product and as part of decision-making for pharmaceutical
quality systems. The most common tools appear to be Failure Mode Effect Analysis (FMEA) and Fishbone analysis. Quality risk
management has shown to be an effective tool in the design of new facilities and in the classification of quality attributes
and processing parameters as critical and noncritical.
The characteristics of a good quality risk-management process include integration into the pharmaceutical quality system rather
than residing in a separate department. A multi-disciplinary group within a firm brings the strength of varied experiences
and knowledge. Employing a trained, independent yet knowledgeable facilitator can help ensure the team maintains a focus on
the process while still being open to new ideas. By bringing an objective analysis to subjective issues, vested interests
(e.g., "silos") can begin to diminish. Quality risk management works best when it is used proactively and should not be used
to justify a bad decision. When new information becomes available that can impact a prior quality risk assessment, iterative
processes can ensure the quality assessment is not static. Moreover, at the end of the risk assessment, additional risk factors
arising as the result of accepting, mitigating, or reducing a risk factor should also be evaluated. Participants in this workshop
session noted that the pharmaceutical industry can effectively learn from the device industry, which has mandatory requirements
for conducting risk assessments.
An effective pharmaceutical quality system requires quality risk management as an enabler integrated into processes and decisions.
For example, using quality risk management in evaluating a change to a validated process can help identify any ramifications
of making a change. With this knowledge, a site can determine the appropriate level of testing to ensure the change does not
negatively impact the ability to meet predetermined quality attributes.
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