Streamlining the Inspection Process

An FDA pilot program gives firms with a history of proper GMP compliance hope for less-demanding future inspections.

An FDA pilot program testing a new format for drug manufacturing and packaging inspections could lead to a less cumbersome inspection process for firms with a history of proper compliance.

The pilot program, which began January 1 and ends June 30, covers the Philadelphia, Los Angeles, New Jersey, New York, Dallas, and San Juan, PR, inspection districts. The agency has not given a timetable for expanding the program nationwide if it proves successful.

According to a program guidance document issued by the agency's Office of Regulatory Affairs, the pilot program streamlines the inspection process by dividing it into six systems: quality, facilities and equipment, materials, production, packaging and labeling, and laboratory control. If any one system is deemed out of control, then the firm as a whole is deemed out of control.

When a firm has a record of "satisfactory GMP compliance, with no significant recall, or product defect or alert incidents, or with little shift in manufacturing profiles . . . within the previous two years," FDA's inspection team may choose to do an "abbreviated inspection." This option allows for as few as two of the six systems to be audited but specifies that one must be the quality system and that the other five systems be examined on a rotating basis. Inspection of the quality system may require limited coverage in the areas not being formally examined.

The "full inspection," which involves auditing at least four of the six systems with the quality system mandatory, is to be used when "little to no information is known about a firm's GMP compliance; or for firms where there is doubt about GMP compliance; or follow-up to previous regulatory actions."

The systems-based method came about because FDA recognized that it does not have enough resources to audit every aspect of GMP compliance for each facility. The current system bases reviews on "profile classes," which enable the agency to generalize inspection coverage from a small number of specific products to all the products in that class. The systems approach further generalizes inspection coverage from a small number of profile classes to an overall evaluation of the firm. "Coverage of a system should be sufficiently detailed . . . so that the system inspection outcome reflects the state of control in that system for every profile class," the agency states. "Multiple visits to a firm will not be needed to cover all profile classes [and] delays in approval decisions will be avoided because up-to-date profile class information will be available at all times."

Among other things, inspection of the quality system should consider discrepancy and failure investigations related to manufacturing and testing, documentation, evaluation and approval of change control, the impact of reprocessing and reworking on validation and stability, correct courses of action on rejects and stability failures, and the status of required validations and revalidations.

Evaluations of the facilities and equipment system should include air-handling systems, cleaning procedures and validation, contamination prevention controls, as well as qualification, calibration, and maintenance of storage equipment.

Some of the considerations for evaluating the materials system are identification, inventory, and testing or validation of a supplier's test results for components, containers and closures; and the rejection and quarantine of any material not meeting acceptance requirements.

The production system is more relevant to processing than it is to packaging, but considerations include preventing objectionable microorganisms in nonsterile drug products and validation and security of the data-handling system.

The packaging and labeling system's evaluation includes considering the acceptance operations for packaging and labeling materials; the control system for making changes to packaging and labeling operations; adequate storage for labels and labeling; control of labels similar in size, shape, and color; proper examination of the finished labels; proper use of lot numbers and destruction of excess labeling bearing lot numbers; adequate packaging records including specimens of all labels used; proper inspection and documentation of printers; conformance to tamper-evidence requirements; and validation of all packaging and labeling operations.

A packaging and labeling system failure could entail failure to establish or follow a control system for implementing packaging and labeling changes, a pattern of failure to document investigation of discrepancies, a lack of validation of computerized systems, anything that may introduce a potential for mislabeling, and a lack of packaging validation.

Because the laboratory control system has little relevance to packaging, it will not be discussed here.

The document can be viewed at http://www.fda.gov/ora/cpgm/7356_002/7356-002-Draft.html.