ABSTRACT
Good Manufacturing Practices (GMPs) is a universal concept with a dual purpose: to make pharmaceutical products both safe and consistent in their effectiveness. Remarkable changes are taking place in the basic approach to achieve these goals. The key regulations and guidelines for the manufacturing of finished pharmaceuticals (as opposed to raw material or active ingredient manufacturing) in this respect are:
1. 21 Code of Federal Regulations, Parts 210 and 211 (Part 210 — Current Good Manufacturing Practice in Manufacturing, Processing, Packing, or Holding of Drugs; General Part 211 — Current Good Manufacturing Practice for Finished Pharmaceuticals) (https://www.fda.gov/cder/ dmpq/cgmpregs.htm)
2. The World Health Organization (WHO): Quality Assurance of Pharmaceuticals: A compendium of guidelines and related materials, Volume 2, Good Manufacturing Practices and Inspection (https://www.who.int/medicines/ organization/qsm/activities/qualityassurance/ gmp/gmpcover.html)
3. The Rules Governing Medicinal Products in the European Union: Volume 4, Good Manufactur-
ing Practices (https://pharmacos.eudra.org/F2/ eudralex/vol-4/home.htm)
4. The European Agency for the Evaluation of Medicinal Products — International Conference on Harmonisation (ICH) Guidelines (https://www.emea.eu.int/index/indexh1.htm)
5. Health Products and Food Branch Inspectorate of Canada. Good Manufacturing Practices Guidelines — (https://www.hc-sc.gc.ca/hpfbdgpsa/inspectorate/gmp_guidelines_2002_ tc_e.html)
6. Therapeutic Goods Administration, Government of Australia — Australian Code for Good Manufacturing Practices (https://www.health. gov.au/tga/docs/html/gmpcodau.htm)
The U.S. Food and Drug Administration (FDA) oversees the quality of drug products using a two-pronged approach including a review of information submitted in
applications as well as an inspection of manufacturing facilities for conformance to requirements for current Good Manufacturing Practices (CGMPs). These two programs have served the United States well by helping to ensure the quality of drug products available. Now, as we approach the 25th anniversary of the last major revision to the drug CGMP regulations, the U.S. FDA has undertaken a program to overhaul the entire process of CGMP compliance so that:
• The most up-to-date concepts of risk management and quality systems approaches are incorporated while continuing to ensure product quality
• The latest scientific advances in pharmaceutical manufacturing and technology are encouraged
• The submission review program and the inspection program operate in a coordinated and synergistic manner
• Regulation and manufacturing standards are applied consistently
• Management of the program encourages innovation in the pharmaceutical manufacturing sector
• FDA resources are used most effectively and efficiently to address the most significant health risks
Over the last two decades, significant changes in the environment of pharmaceutical regulation have occurred and have resulted in incremental adjustments in the FDA’s regulatory approach to product quality. These changes include:
• Increased number of pharmaceutical products and a greater role of medicines in health care
• Decreased frequency of FDA manufacturing inspections as a result of fewer resources available for pharmaceutical manufacturing inspections
• The FDA’s accumulation of experience with, and lessons learned from, various approaches to the regulation of product quality
• Advances in the pharmaceutical sciences and manufacturing technologies
•
• quality
• Globalization of the pharmaceutical industry
The cumulative impact of these changes has been greater than the sum of the parts and warrants a systematic reappraisal of the FDA’s approaches to product quality regulation. The following principles will guide implementation of the reappraisal:
Risk-based orientation —
In order to provide the most effective public health protection, the FDA must match its level of effort against the magnitude of risk. Resource limitations prevent uniformly intensive coverage of all pharmaceutical products and production. Although the agency has been implementing risk-based programs, a more systematic and rigorous risk-based approach will be developed.
