In 2002, the US Food and Drug Administration publicly recognized a need for change with its current good manufacturing practices (CGMP) for the 21st century initiative (1). This new approach to GMP compliance and enforcement recognized that FDA and the drug and biologics industries were not
where they needed to be in terms of quality, manufacturing science, and risk management. This changing world of GMP applied
to human and veterinary drugs and biological drug products. Key to FDA's approach has been to request a holistic cradle-to-grave
management of quality issues.
Quality system: What is it?
The quality system should be an integrated framework within which the design, manufacture, packaging, labeling, and distribution
take place. Commitment from management is crucial; without it there is no quality system. The underlying principles are:
- Ensure quality is designed and built into the product
- Reliance on appropriate and documented processes and procedures
- Provide documented, objective evidence of what was done during design and manufacture
- Controlled and documented design
- Management responsibility and control of the quality system
- Process—the quality of a product is governed by the quality of the processes used in its manufacturing
- Validation of designs and processes
- Feedback loop for corrective and preventive actions. (A feedback loop helps find any flaws that may be in a validated process
or product. Validation is not 100%, it is a probability. Corrective and preventive action systems are the feedback loop to
continuously improve your products and processes.)
In the changing, evolving world of GMP regulations, quality concepts are changing. The original GMP regulations started with
a product-focus and quality control. Next was a shift to a process-focus and quality assurance. Now drug and biologics manufacturers
face an enormous paradigm shift with the new model of quality systems (see Figure 1).
Figure 1: Models of quality.
However, this new evolutionary step is not new to FDA because the medical device industry has already adopted the quality-system
approach in 1996 (2). Other industries also have adopted this approach (e.g., the automotive industry). Guidance is available
from American National Standards Institute and International Organization for Standardization (ISO) on what is required in
a quality system that parallels the medical device regulation (3, 4). FDA's approach has been to focus on quality by design
and the control and reduction of variability by encouraging the use of sophisticated process analytical technologies (PAT)
(5). Following the revised GMP guidance and the adoption of new technological advances, FDA hopes manufacturers will consistently
maintain high-quality products and improve their manufacturing efficiency. FDA believes this should help lower costs and prevent
shortages of critical medicines owing to failures that can result in product recalls. The estimated potential worldwide cost
savings from efficiency improvements in the pharmaceutical industry is as high as $90 billion (6).
In October 2006, FDA issued a final guidance on quality systems intended for use in the manufacturing of human and veterinary
drugs, including biological drug products (7). This guidance provides manufacturers with the ability to make technological
improvements more readily, with appropriate regulatory oversight, and it offers guidance for defining management responsibilities,
allocation of quality resources, dividing manufacturing duties between the quality unit and the production staff, and reviewing
records and evaluating data.
The quality systems approach describes the responsibilities of the "quality unit," which combines the duties of quality control
and quality assurance, "ensuring that the various operations associated with all systems are appropriately planned, approved,
conducted, and monitored." The quality unit also is responsible for ensuring that controls are implemented and used; seeing
that procedures and specifications are adhered to (at the manufacturer and at any contractors); approving or rejecting incoming
materials, in-process materials, and drug products; and reviewing production records and investigating unexplained discrepancies.