Inside ICH: ICH Meets in Japan to Finalize Key Documents

The International Conference on Harmonization's (ICH) Expert Working Groups (EWGs) and Steering Committee met during the week of November 7, 2010, in Fukuoka, Japan. Quality Expert Working Groups meeting that week included those for the ICH Q4B guideline on the evaluation and recommendation of pharmacopoeial text for use in the ICH Regions, the Q3D guideline on metal impurities, the Q11 guideline on development and manufacture of drug substances (including chemical and biotechnological entities). The ICH Q8, Q9, Q10 Implementation Working Group also met, as did a new multidisciplinary expert working group comprised of safety and quality experts to discuss the ICH M7 guideline on the assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk.

During the Q4B discussions, Annex 7(R2) (dissolution) reached Step 4 (i.e., adoption by the ICH parties in North America, Europe, and Japan) of the harmonization process. Annex 13 (bulk and tapped density), Annex 14 (bacterial endotoxins test), and Annex 6 (uniformity of dosage units) are expected to reach Step 4 via postal signoff by the parties before the next ICH meetings in June 2011.

The work completed by the Q4B EWG enables industry to conduct a single pharmacopoeial test to meet the requirements of the pharmacopoeias in the three ICH regions rather than carrying out the tests in triplicate. When the last annexes of Q4B are completed, the EWG will have completed its remit and further meetings of this EWG are not expected. Also of interest, the ICH Steering Committee approved a maintenance procedure for Q4B that is similar to that used by ICH Guideline Q3C Impurities: Guideline for Residual Solvents that will allow for rapid revision of Q4B annexes should there be revisions to any pharmacopoeial texts that are the subject of an ICH Q4B annex.

The Q3D EWG reached agreement on the initial scope of the guideline which is similar to the scope for ICH Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances. The guideline is intended to be applicable to new products, but it is not applicable to herbal products or radiopharmaceuticals. The guideline would generally not be applicable to drug products in the early stages of clinical development. The EWG also agreed that several approaches could be taken to assess the presence of metal impurities in new drug products, and that the need for specific analytical testing should be based on a determination of the potential for metals to be present in the drug product and the associated risk. The EWG is on target to reach Step 2 (i.e., ICH party consensus) for this guideline in November 2011.

Considerable progress was made by the ICH Q11 EWG in Fukuoka. The latest draft of Q11 underwent a thorough review and editing by the group members. Several examples were added to the document to provide greater clarity for both industry and regulators. A Step 2 sign-off is expected during the first quarter of 2011.

The ICH Q8, Q9, Q10 IWG, also known as the Quality IWG, was established in June 2008 with the primary objective of facilitating the harmonized implementation of ICH Quality Guidelines Q8 Pharmaceutical Development, Q9 Quality Risk Management, and Q10 Pharmaceutical Quality System. The IWG has provided technical clarification with regard to terminology and has addressed the interrelationship among Q8, Q9, and Q10. Since its inception, IWG has published a series of 45 questions and answers which are available on the ICH website for industry and regulators. The group also has developed extensive training materials, and during 2010, it planned and carried out training workshops in each of the ICH regions. Unlike previous workshops on these ICH topics, the regional workshops were based on a specific case study and focused on the integrated implementation of the quality trio guidelines with presentations addressing product development, manufacturing as well as the regulatory processes of assessment and inspection.

A full day of breakout sessions provided for further training on the concepts addressed in these ICH guidelines such as design space, control strategy, quality risk management, and the pharmaceutical quality system. Based on feedback from workshop participants on the need for further clarification related to the implementation of Q8, Q9, and Q10, IWG will be drafting documents in 2011 on topics such as the level of detail needed in regulatory submissions, determination of criticality, control strategy, process validation, design space, and the role of modeling in quality by design.

Moheb Nasr is director of the FDA Office of New Drug Quality Assessment and a member of the Pharmaceutical Technology editorial advisory board. Robert Baum, executive director of Global Regulatory CMC Policy at Pfizer, is the ICH Quality Lead for the Pharmaceutical Research and Manufacturers of America.

This article represents the views of the authors and not of FDA.