The agency also is conferring with private corporations, universities, and independent consultant groups to improve the way it manages its responsibilities. It is clear FDA believes there is no alternative but to continue in this direction.³

Challenges Certain challenges face both FDA and the biopharmaceutical industry. Policy, regulation, and procedures must be known and practiced consistently so that industry can align practices with FDA expectations. The demands on manufacturers and regulators are increasing to the point where the system must change if it is to continue to function.

Future challenges facing pharmaceutical manufacturing organizations include:

• manufacturing agility
• drugs aimed at smaller populations
• custom drugs for genetic populations.

In September 2004, FDA issued the final report on its "Pharmaceutical GMPs for the 21st Century" initiative. The report addresses the outcomes of the original program and some additional efforts, in varying degrees of completion, that will become ongoing programs. Of significant interest, FDA formed the Council on Pharmaceutical Quality, which has been charged with policy development, coordination, and continuing change management, including the ongoing implementation of specific quality management systems within FDA's operations.

Additionally, FDA issued a draft guidance titled Quality Systems Approach to Pharmaceutical Current Good Manufacturing Practice Regulations.⁴ Although this document is neither intended to create expectations for pharmaceutical manufacturers beyond current regulations or requirements, nor is it intended to be a guide for inspections, it will have a significant effect on future regulatory inspectional expectations and outcomes. The entire report is available at http://www.fda.gov/.

Quality Systems FDA has expressed interest in quality systems, both internal to the agency and as they apply to industry. What are quality systems and how are they used? Depending on whom you ask, you will receive a different response. The World Health Organization (WHO), International Conference on Harmonization (ICH), and American Society for Quality (ASQ) all differ on the topic to some degree. Even within individual companies, the definition often varies and the interpretation and use are unclear. However, one thing is clear: industry is empowered — and required — to define appropriate quality systems.

FDA has provided its definition of quality system within the draft guidance referenced above. It reads: "Quality System — formalized business practices that define management responsibilities for organization structure, processes, procedures and resources needed to fulfill product/service requirements, customer satisfaction, and continual improvement. In the cGMP regulatory context, the quality system establishes the foundation to promote the effective functioning of the five other major systems."⁴ FDA also states that the overarching philosophy in both the cGMP regulations and in robust modern quality systems is that quality should be built into the product, and testing alone cannot be relied on to ensure product quality. The guidance document goes into detail on acceptable models for quality systems and states that the cGMP regulations are inherently flexible to enable manufacturers to implement a quality system in a form that is appropriate for their specific operations.

Defining quality systems requires careful thought and consideration. Quality systems need nurturing and support as they evolve. Every enterprise should have a quality manual that outlines its philosophy and expectations. Subordinate to that, standards and procedures that outline the execution and expectation of the quality philosophy and requirements are needed. Those procedures yield data and metrics that management must review for acceptability and corrective action. This structure, including all the operational specific systems required to ensure product quality, should constitute an enterprise's quality system.

One useful way of defining quality systems is to say that they cover all the business-process systems that can, in any way, affect product quality or compliance. For example: raw material ordering and qualification, pest control, manufacturing, packaging and labeling, and others. Within this broad definition of quality systems it is important to identify the subset of processes formally owned by and the responsibility of the Quality Assurance Unit, for example: complaint reviews, product review, disposition, audits, and change control. Within the overall quality systems, these constitute the Quality System itself.