European Medicine Agency (EMA) along with International Conference on Harmonisation (ICH) have published the draft of the new ICH Q 11 guidance for API development and manufacture. The regulatory authority is now awaiting comments from the industry across international markets before its stipulated deadline September 30, 2011.

ICH guideline Q11 focuses on the development and manufacture of drug substances which cover chemical entities and biotechnological/biological entities.

It offers approaches to developing process and drug substance understanding and the information to be  provided in CTD sections 3.2.S.2.2 – 3.2.S.2.6. Further it provides 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.

“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 and control strategies applicable over the lifecycle of the drug substance.”

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 authorization.

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.

This guideline is applicable to drug substances as defined in the Scope sections of ICH Guidelines Q6A and Q6B, but might also be appropriate for other types of products following consultation with the appropriate regulatory authorities. It is particularly relevant to the preparation and organization of the contents of sections 3.2.S.2.2 – 3.2.S.2.6 of Module 3 of the Common Technical Document (ICH M4Q). The guideline does not apply to contents of submissions during the clinical research stages of drug development. Nevertheless, the development principles presented in this guideline are important to consider during the investigational stages, according to the guideline.

However, the regional requirements for post-approval changes are not covered by this guideline.

The objective of manufacturing process development for the drug substance is to establish a commercial manufacturing process capable of consistently producing drug substance of the intended quality.

In the section on Drug Substance Quality Link to Drug Product, the guideline has emphasized that the drug substance should be determined through consideration of its use in the drug product as well as from knowledge and understanding of its physical, chemical, biological, and microbiological properties or characteristics, which can influence the development of the drug product. This is because the solubility of the drug substance can affect the choice of dosage form.