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On June 16, 2011 the ICH guideline Q11 on development and manufacture of drug substances (chemical entities and biotechnological/biological entities) was published as a Step 3 document. Interestingly the European Medicine Agency (EMA) is publishing this document even before the International Conference on Harmonsation (ICH) was able to update their Webpage. In the next days to come also FDA (USA) and PMDA (Japan) will publish the same document on their webpage. The guideline will have a major impact on manufacture and development of APIs. It is defined in the introduction to this Guideline that it describes approaches to developing process and drug substance understanding and also provides guidance on what information should be provided in CTD sections 3.2.S.2.2 - 3.2.S.2.6. It provides further clarification on the principles and concepts described in ICH guidelines on Pharmaceutical Development (Q8), Quality Risk Management (Q9) and Pharmaceutical Quality Systems (Q10) as they pertain to the development and manufacture of drug substance. The guideline consists of 27 pages. The first chapters 1 - 9 contain requirements to be met but from page 17 on 5 examples have been listed for illustrative purposes - Example 1: Linking Material Attributes and Process Parameters to Drug Substance CQAs - Chemical Entity
- Example 2: Use of Quality Risk Management to Support Lifecycle Management of Process Parameters
- Example 3: Presentation of a Design Space for a Biotechnological Product Unit Operation
- Example 4: Selecting an Appropriate Starting Material
- Example 5: Summary of Control Elements for select CQAs
A company can choose to follow different approaches in developing a drug substance. For the purpose of this guideline, the terms "traditional" and "enhanced" are used to differentiate two possible approaches. In a traditional approach, set points and operating ranges for process parameters are defined and the drug substance control strategy is typically based on demonstration of process reproducibility and testing to meet established acceptance criteria. In an enhanced approach, risk management and more extensive scientific knowledge are used to select process parameters and unit operations that impact critical quality attributes (CQAs) for evaluation in further studies to establish any design space(s) and control strategies applicable over the lifecycle of the drug substance. As discussed in ICH Q8 for drug product, a greater understanding of the drug substance and its manufacturing process can create the basis for more flexible regulatory approaches. The degree of regulatory flexibility is generally predicated on the level of relevant scientific knowledge provided in the application for marketing authorisation.
Traditional and enhanced approaches are not mutually exclusive. A company can use either a traditional approach or an enhanced approach to drug substance development, or a combination of both. Conference Tip: The leader of the ICH Q11 Expert Working Group, Brian Withers will inform about the practical implication of the new Guideline at the 14th European API Conference on 16 - 18 November 2011 in Munich Source: EMA Website
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