Process understanding can be a foundation for innovation and continuous improvement in pharmaceutical development and manufacturing. FDAs Process Analytical Technology (PAT) initiative, part of the Agencys 21st Century cGMPs [1-5], reaffirms that message [5-7], but also aims to help the global pharmaceutical community reach a desired state, where:
Figure 1 illustrates a process for re-evaluating the inherent assumptions in current regulatory policies pertaining to quality assurance and identifying opportunities for improvement [9]. It also illustrates a proposed relationship of this re-examination to the journey towards the desired state. Since a higher degree of process understanding and controlfor example, control of variability is the critical directional vector towards the desired state, this vector is visualized in three dimensions as the Z axis, where the X and Y axes define the plane, or the minimal standards, on which the current state rests.Benchmarking progress: milestonesThe efficiency of our journey towards the desired state will depend on how rapidly the pharmaceutical community can develop a common understanding of that state, identify and address challenges to moving forward, and develop metrics or milestones to benchmark progress and guide this journey.With every passing milestone, the global pharmaceutical community should continually improve our ability to deliver, as efficiently as possible, the high pharmaceutical quality that patients expect and demand of us. Broadly, the milestones necessary to benchmark our progress have to gauge scientific and technical progress and measure efficiency improvements. The measures of efficiency will be essential to make the business case in terms of cost savings or return on investment. Efforts such as the 2005 Pharmaceutical Manufacturing Team of the Year Award competition also help to benchmark our progress [11].The matrix in Table 2 identifies some of the key scientific and quality system issues and challenges to be addressed [5]. Systems and tools that address these challenges effectively will be significant milestones in the journey towards innovation and continuous improvement in pharmaceutical manufacturing.FDA initiatives create a number of opportunities for the pharmaceutical manufacturing community, and make it possible to move from reactive to proactive pharmaceutical quality decision making. There will be many hurdles to clear on this journey to the desired state, but a science-based framework and consensus development, and shared global vision developed under ICH, can help overcome some of these hurdles.To facilitate continuous improvement and innovation, a common understanding of the relationships between in-process controls, final product control limits, and regulatory specifications and/or standards will be necessary. Development of standards for process quality may be a means to achieve a common understanding on process control in the context of pharmaceutical quality, and ASTMs International Committee E55 plays a critical role in making these standards a reality.Our progress toward the desired state will depend on how rapidly we all can agree on what that state is, identify and address challenges, and develop metrics to benchmark progress. The path to enlightened, proactive decisionmaking lies before us. It is up to us to follow it.References
- Product quality and performance are achieved and assured by design of effective and efficient manufacturing processes;
- Product specifications are based on a mechanistic understanding of how formulation and process factors impact product performance;
- Manufacturers are able to effect continuous improvement and continuous "real time" assurance of quality.
- Standard Practice for Process Understanding Related to Pharmaceutical Manufacture and Control
- Standard Practice for Risk Management as it Impacts the Design and Development of Processes for Pharmaceutical Manufacture.
- (a) utilizing pharmaceutical development information (e.g., ICH Q8) in regulatory decisions
- (b) using new technologies for more effective control of the formulation and manufacturing variables that impact product performance
- (c) taking a comprehensive systems approach to regulatory quality assessment for example, synergistic collaboration between CMC review, clinical pharmacology and biopharmaceutical review and cGMP inspections.
- (a) characteristics deliver the intended goals, reliably and efficiently
- (b) decision reliability, transparency and efficiency improve continuously
- (c) characteristics accommodate increasing system complexity
- (d) decisions facilitate continuous improvement in all applicable operations.
Editor's Note: To access a 2-page PDF containing Table 1 and other graphics for this article, click the Download Now button at the end of this story. |
- The PAT Initiative. http://www.fda.gov/cder/OPS/PAT.htm
- Pharmaceutical cGMPs for the 21st Century A Risk-Based Approach, Final Report, Fall 2004. http://www.fda.gov/cder/gmp/gmp2004/GMP_finalreport2004.htm
- The Critical Path to New Medical Products. FDA, March 2004. http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.html
- Guidance for Industry. PAT A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance. http://www.fda.gov/cder/guidance/6419fnl.htm
- Innovation and Continuous Improvement in Pharmaceutical Manufacturing. The PAT Team and Manufacturing Science Working Group Report. http://www.fda.gov/cder/gmp/gmp2004/manufSciWP.pdf
- Hussain, A. S. Process Analytical Technology: A First Step in a Journey towards the Desired State. The Journal for Process Analytical Technology. January 2005. http://www.patjournal.com/main.aspx
- ICH Q8: Pharmaceutical Development. http://www.fda.gov/cder/guidance/6672dft.pdf
- Torbeck, L. D. In defense of USP singlet testing. Pharmaceutical Technology. February 2005
- Quality-by-Design Approach for Regulatory Decisions: Seeking Applications for Establishing Drug Dissolution/Release Specifications, Creating Flexibility for Continuous Improvement and for Assessment of Therapeutic Equivalence. Food and Drug Administration Advisory Committee for Pharmaceutical Science, May 3-4, 2005. http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4137b1_Index.htm
- ASTM International. Committee E55 on Pharmaceutical Application of Process Analytical Technology. http://www.astm.org/cgi-bin/SoftCart.exe/COMMIT/COMMITTEE/E55.htm?E+mystore
- Shanley, A. and Thomas, P. Team of the Year: Our Finalists Tell Their Stories. Pharmaceutical Manufacturing, April 2005. http://www.pharmamanufacturing.com/articles/2005/261.html
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