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Successful Regulatory Approval of Medical Products Depends on Robust Product Characterization.

The analytical data package defines the characteristics and structure of the therapeutic medical products and proves the safety, efficacy, purity, quality, and strength of the product. This in-depth analysis is not only required for compliance with FDA and other regulatory guidelines but for critical decisions as the product moves through each development phase until reaching the commercial-scale manufacturing stage.


The intent of the product characterization studies is to document which operational parameters are purposely varied to determine their effect on product quality attributes and process performance. Initial and confirmation experiments can be designed to examine the ranges and explore potential wider ranges that will normally be used in manufacturing operations. These studies, designed to characterize the process and determine acceptable ranges for process parameters, are usually performed at a laboratory scale. Laboratory scale studies are suitable and capable to perform in a manner that is representative of the full-scale process. Any differences between the actual and expected performance of the laboratory models and model predictions should be appropriately considered in the study design.


Challenges during the product characterization stage can be due to product complexity including drug substances with multiple active molecules, molecular diversity in products with a natural source origin, or synthetic molecules that are polydisperse mixtures. Additional complications may be encountered based on the molecular structure or the drug delivery technology employed.


Pilot-scale models of small molecules that are representative of the commercial manufacturing process may be used to support Product Performance Qualification (PPQ) data. For solid and liquid oral dosage forms, 10% of the intended commercial batch size and/or 100,000 units are typically considered as representative and provide sufficient assurance for the determination of a degree of control and process characterization, while still uncovering preliminary situations that need additional attention.


Raw materials, component attributes, equipment, and process parameters should be comparable and indicative of the process intended for the commercial product. A full-scale confirmation/evaluation should be completed to support PPQ. ICH Q8 provides guidance for the Pharmaceutical Development report (Section 3.2.P.2) contained in Module III of the Common Technical Document (CTD). Pharmaceutical manufacturers are required to include a comprehensive and detailed description of medical products and the manufacturing process applying "scientific approaches and quality risk management principles”. The regulator’s expectation is that this document demonstrates an adequate degree of understanding of the manufacturing process.


The overall control strategy and the design space(s) relationship supported by multiple risk assessments should describe the multi-layered understanding of process controls and product characterization in an extended design space. This multi-layer understanding not only provides assurance of the product SISPQ but reduces the possibility of a manufacturing process drift outside of the design space ranges that would require the initiation of a regulatory post-approval change process. The degree of regulatory flexibility can be established on the level of relevant knowledge provided, scientific approaches, and quality risk management displayed in the report.

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