Regulatory Strategies

The Agency understands that to enable successful implementation of PAT, flexibility, coordination, and communication with manufacturers is critical. The Agency believes that current regulations are sufficiently broad to accommodate these new strategies. Regulations can effectively support innovation (e.g., new drugs and drug delivery systems) as long as clear communication mechanisms exist between the Agency and industry, for example, in the form of meetings or informal communications between the Agency and manufacturers during drug development.

The first component of the PAT framework described above addresses many of the uncertainties with respect to new technologies and outlines broad principles for addressing anticipated scientific and technical issues. This information should assist a manufacturer who is proposing to the Agency innovative technologies that may call for a new regulatory path. The Agency encourages such proposals and has developed new regulatory strategies to consider such proposals. The Agency's new regulatory strategy includes (1) a PAT team approach for CMC review and CGMP inspections; (2) joint training and certification of PAT review, inspection and compliance staff; (3) scientific and technical support for the PAT review, inspection and compliance staff; and (4) the recommendations provided in this guidance.

The recommendations provided in this guidance are intended to alleviate the fear of delay in approval as a result of introducing new manufacturing technologies. Ideally PAT principles and tools should be introduced during the development phase. The advantage of using these principles and tools during development is to create opportunities to improve the mechanistic basis for establishing regulatory specifications. Manufacturers are encouraged to use the PAT framework to develop and discuss approaches for establishing mechanistic-based regulatory specifications for their products.

We also encourage the use of PAT strategies for the manufacture of currently approved products. Manufacturers may want to evaluate the suitability of a PAT tool on experimental and/or production equipment and processes. For example, when evaluating experimental on- or in-line process analyzers during production, it is recommended that risk analysis of the impact on product quality be conducted before installation. This can be accomplished within the facility's quality system without prior notification to the Agency. Data collected using an experimental tool should be considered research data.

When using new measurement tools, such as on/in-line process analyzers, certain data trends that may be intrinsic to the current acceptable process may be observed. Manufactures should scientifically evaluate these data to determine how or if such trends affect quality and implementation of PAT tools. FDA does not intend to inspect research data collected on an existing product for the purpose of evaluating the suitability of an experimental process analyzer or other PAT tools. FDA's routine inspection of a firm's manufacturing process that incorporates a PAT tool for research purposes will be based on current regulatory standards (e.g., test results from currently approved or acceptable regulatory methods). Any FDA decision to inspect research data would be based on exceptional situations similar to those outlined in Compliance Policy Guide Sec. 130.300. Those data used to support validation or regulatory submissions will be subject to inspection in the usual manner.