REGULATORY GUIDANCE
ICH Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients (APIs) discusses the various sources of raw materials and makes recommendations on their handling.1 It defines an API starting material as "a raw material, intermediate, or an API that is used in the production of an API
and that is incorporated as a significant structural fragment into the structure of the API". This guideline provides recommendations
on a variety of topics, such as quality management, personnel, buildings and facilities, process equipment, documentation
and records, materials management, production and in-process controls, packaging and identification labeling, storage and
distribution, laboratory controls, validation, change control, rejection and reuse of materials, complaints and recalls, and
contract manufacturers. Furthermore, the guideline provides specific guidance for APIs manufactured by cell culture or fermentation
and also on APIs used in clinical trials. The guidance presented in this document can serve as the foundation of the raw material
management program for a company.
ICH Q8 Pharmaceutical Development introduces QbD as "a systematic approach to development that begins with predefined objectives and emphasizes product and
process understanding and process control, based on sound science and quality risk management."2 The QbD approach involves identifying product attributes that are of significant importance to the product's safety and
efficacy, design of the process to deliver these attributes, a robust control strategy to ensure consistent process performance,
validation and filing of the process demonstrating the effectiveness of the control strategy, and finally ongoing monitoring
to ensure robust process performance over the lifecycle of the product. Although the Q8 guidance is intended for drug product,
some of the concepts are applicable for raw materials as well and should be taken into account when creating a raw material
management program.
The ICH Q9 Quality Risk Management guideline provides principles and examples of tools for quality risk management that can be applied to different aspects of
pharmaceutical quality.3 These aspects include development, manufacturing, distribution, inspection, and submission or review processes throughout
the lifecycle of drug substances, drug (medicinal) products, and biological and biotechnological products. As will become
evident from this article, risk analysis and management pay a critical role in management of raw materials and as such, the
ICH Q9 guideline serves as a useful reference when creating a raw material management program.
Besides the ICH guidelines mentioned above, specific guidance also has been provided by the US Food and Drug Administration,4 European Medicinal Agency (EMA),5 and the Japanese Ministry of Health, Labor, and Welfare (MHLW).6 Although they provide regulatory expectations from the different jurisdictions, they all share the foundation laid by the
ICH guidelines.
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