Most standards are well written and understood, but many are not and have been subject to multiple interpretations not only
by industry but also by FDA itself.
Until recently, more than 25 years had passed since the last major changes were made to FDA's regulatory systems. Cognizant
of new challenges facing both industry and the agency, FDA has initiated several new programs.
"Pharmaceutical cGMPs for the 21st Century: A Risk-Based Approach" was announced on August 21, 2002. This new initiative is
intended to commence "a systematic reappraisal of FDA's approaches to product quality regulations." FDA's current inspection
program is overburdened with new obligations and an increasing number of firms requiring inspection, while the number of completed
inspections has been decreasing over the past several years.2
FDA hopes to incorporate the most up-to-date concepts of risk management and use its resources effectively and efficiently
to address the most significant public health risks, including:
- encouraging the early adoption of new technological advances by the pharmaceutical industry
- facilitating modern quality management techniques, including implementation of quality systems approaches to all aspects
of pharmaceutical production and quality assurance
- encouraging risk-based approaches that focus both industry and agency attention on critical areas
- ensuring that regulatory review and inspection policies are based on state-of-the-art pharmaceutical science
- enhancing the consistency and coordination of FDA's drug quality regulatory programs, in part by integrating enhanced quality
systems approaches into the agency's business processes and regulatory policies concerning review and inspection activities.
As a result of the initiative, multidisciplinary working groups are developing guidance documents in various phases of completion.
These documents are available on the agency's website (
- Part 11, Electronic Records, Electronic Signatures — Scope and Application
Formal Dispute Resolution: Scientific and Technical Issues Related to Pharmaceutical cGMP
Sterile Drug Products Produced by Aseptic Processing: Current Good Manufacturing Practices
Comparability Protocols — Protein Drug Products and Biological Products, Chemistry, Manufacturing, and Controls Information
PAT — A Framework for Innovative Pharmaceutical Manufacturing and Quality Assurance
FDA is also making important changes to its inspection program, including:
- The Office of Regulatory Affairs (ORA) and the Center for Drug Evaluation and Research (CDER) signed a memorandum of understanding
establishing a Pharmaceutical Inspectorate (PI) within ORA. This PI will be staffed with highly trained individuals within
ORA who will devote most of their time to conducting human drug quality inspections and other complex or high-risk pharmaceutical
- To serve as a member of the PI, an investigator will have to obtain and maintain a Level III Drug Certification. This certification
signifies that an individual has received extensive training on advanced technology in the pharmaceutical manufacturing process
and how those technologies are evaluated during an inspection.
- A board has been established to review certification packages; select candidates for membership into the PI; and develop,
update, and maintain the curriculum for the Level III Drug Certification program.
- The pre-approval inspection compliance program has been revised, giving field offices more opportunity to utilize a risk-based
approach in determining the necessity of pre-approval inspections.
- The agency is emphasizing a risk-based approach in selecting inspection sites to ensure its limited resources are appropriately
FDA is looking internally at quality systems and controls to enhance the consistency and predictability of their internal
inspection program. The key message FDA wants to deliver is that "FDA is regulating product quality to serve the patient,
and drug companies should view the patient as a customer, too." In the past, a lack of knowledge of what affected product
quality led to FDA micromanagement of the inspection processes. FDA is adopting a more scientific and systems-based approach.
If processes are well understood and controlled, FDA will be able to redefine their inspection approach.