Steering Pharmaceutical Manufacturing into the 21st Century

Control and monitor measurements can then be used to provide confidence that the process is reliably under control, from batch to batch. The FDA is in the midst of determining the best practices for applying these concepts to the regulation of drug product manufacturing [3, 4]. In cases where the structure of the organization needs to be adjusted, we’re doing that, too [5].

Adopting a standards-based approach to drug product regulation was not one of the working groups in the 21st Century Initiative. However, it is part of FDA’s overall strategy. The Agency is directed, through the National Technology Transfer and Advancement Act (NTTAA) [6] to seek out and use standards where they are applicable to the regulatory process. Specifically, CDER is currently engaged in creating a network of standards for implementation of Process Analytical Technology (PAT) within ASTM International [7].

Coordinating efforts will be crucial, as is the case with any project involving many people working on so many different tasks. Some people, no doubt, consider that FDA’s progress has been excruciatingly slow, while others may believe that progress has been recklessly fast.

In fact, FDA’s progress with 21st Century Initiative and PAT is an evolving process, occurring on many fronts, and progressing at different rates, but all efforts are moving in the same direction. Steering the process in a transparent manner will ensure that the Agency doesn’t lose sight of its goals by focusing too much on process minutia.

References

1. “Pharmaceutical cGMPs for the 21st Century – A Risk-Based Approach, Final Report – Fall 2004” is the full title of this 32-page report that summarizes the results of two years worth of discussion on 16 topics ranging from administrative to inspectional to review topics. It includes references to larger, more detailed reports on many of the working groups. The report is available at: www.fda.gov/cder/gmp/gmp2004/GMP_finalreport2004.htm#_Toc84065753



2. International Conference on Harmonization (ICH) guidelines can frequently serve this role. These are available in the quality “Q” section of the ICH.org web site, and are accessible via: www.ich.org/cache/compo/276-254-1.html.



3. A pilot program is under way in the Office of New Drug Quality Assessment (ONDQA), formerly the Office of New Drug Chemistry (ONDC). Officially named “Submission of Chemistry, Manufacturing, and Controls Information in a New Drug Application Under the New Pharmaceutical Quality Assessment System; Notice of Pilot Program,” information on being part of this pilot is available in the Federal Register notice at: first.fda.gov/fedreg/05/cd0536.pdf.



4. The Office of Generic drugs is exploring a new way to prioritize review resources and focus on the important elements of the CMC section of the application. Details of this method can be accessed via: www.fda.gov/cder/ogd/QbR.htm.



5. The ONDQA (formerly ONDC) personnel have been reorganized so that they are a coherent group and not distributed among the clinical review divisions. Details are available in the White Paper on ONDC’s New Risk-Based Pharmaceutical Quality Assessment System at: www.fda.gov/cder/gmp/gmp2004/ondc_reorg.htm.



6. The National Technology Transfer and Advancement Act (NTTAA) and its accompanying directive to government agencies, Circular A-119, can be accessed via: standards.gov/standards_gov/index.cfm.



7. ASTM International Technical Committee E55: Pharmaceutical Applications of Process Analytical Technology
   E55.01: PAT Systems Management
   E55.02: PAT System Implementation & Practice
   E55.03: General Pharmaceutical Standards
   E55:90: Executive Subcommittee
   E55:91: Terminology More detail is available at: www.astm.com/cgi-bin/SoftCart.exe/COMMIT/SUBCOMMIT/E55.htm?L+mystore+aech5735+1138386598.

About the Author

Jon E. Clark is the Associate Director for Policy Development and GMP in the CDER Office of Pharmaceutical Science. He has been heavily engaged in the Pharmaceutical Quality CGMPs for the 21st Century initiative, the Product Quality Research Institute (PQRI), International Conference on Harmonization (ICH) and a member of ASTM E55. He frequently represents CDER's drug quality and CMC policy in public speaking engagements, working groups and publications.

Previously, Clark spent one year in the CDER Office of Information Management developing electronic submission policy with the ICH; three years developing and presenting CMC chemistry policy in the Office of New Drug Chemistry; and seven years in the Office of Generic Drugs reviewing Abbreviated New Drug Applications while managing the Computer Assisted Review Database System with the University of Maryland. He joined the Agency in 1992, after 12 years as an organic synthesis research chemist in the private sector, first at Beecham Laboratories then at Schering Plough Research.

He received his Bachelor in Chemistry at the University of Michigan in 1980 and his Master in Chemistry at Rutgers University in 1987.