Inside ICH: Quality Implementation and Harmonization Continue

The International Conference on Harmonization (ICH) Steering Committee and Expert Working Groups met in Cincinnati, on July 12–16, 2011. The following provides a summary of the major achievements made during the meeting.

The ICH Quality Implementation Working Group (IWG), composed mainly of members from previous ICH Q8 Pharmaceutical Development, Q9 Quality Risk Management, and Q10 Pharmaceutical Quality System working group members, continued to make excellent progress. The group completed three Points to Consider documents covering the criticality of quality attributes and process parameters, control strategy, and the level of documentation in enhanced (i.e., quality-by-design [QbD]) regulatory submissions.

The group was reminded that these documents are not intended to introduce new regulatory requirements but are intended to provide clarity for both regulators and industry and to facilitate preparation, assessment, and inspection related to applications filed for marketing authorizations. These documents will serve to provide supplementary information to the previously completed Q&A's and training materials for ICH's quality guidelines Q8, Q9, and Q10.

Three new Points to Consider documents are expected to be finalized at the November ICH meeting in Sevilla, Spain. These documents will address design space, modeling, and process validation/continuous process verification. The ICH Quality IWG will also organize two additional Q8, Q9, and Q10 training workshops, one in Ottawa, Canada, on Sept. 26–27, and the other in Seoul, South Korea, on October 4–5. These workshops will be similar to the three that took place in 2010 in Europe, Japan, and the United States. The training material, Q&As, and Points to Consider documents are available on the ICH website.

The ICH M7 Genotoxic Impurities guidelines involves the assessment and control of DNA reactive (i.e., mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk. This guideline is also moving forward. The working group searching for consistency between the Q3D Metal Impurities guideline and the Q11 Development and Manufacture of Drug Substances guideline identified three important focus areas: scope, methods, and risk mitigation. The final ICH M7 guideline will therefore try to apply these concepts to new and existing products. One issue the group has yet to resolve is whether or not excipients will be included in M7. The guideline is targeted to reach Step 2 (six-party consensus) by November 2012.

Meanwhile, the ICH Q3D expert working group has reviewed safety assessments for 27 metals and tentatively agreed to limits. The group had discussed the scope of the guideline and reached agreement that biotechnological drug products should remain in the guideline's scope. There remains some concern regarding limits for lead and mercury. The key issue stems from mineral-based excipients (e.g., TiO₂, calcium carbonate) because lead is naturally found at the source of the ore. The levels of lead are dependent on the ore source and can vary drastically over the span of several years.

A coalition created by the International Pharmaceutical Excipients Council, which includes members from various industry organizations, will be working on data collection during the next 6–10 months to assist in the finalization of levels for key metals. Besides the safety aspect, there is an ongoing larger discussion regarding control strategy. A section will be added to Q3D to reflect the limited risk associated with inclusion of metal impurities in biotechnologically derived drug substances. Q3D should reach Step 2 in June 2012.

The ICH Q11 group did not meet in Cincinnati, because the draft guideline reached Step 2 in April 2011. This guideline describes approaches to developing process and drug-substance understanding and provides guidance on what information should be provided in a common technical document. It also clarifies the principles and concepts described in ICH guidelines Q8, Q9, and Q10.

Georges France is the EFPIA Topic Leader for the ICH Quality Implementation Working Group (Q–IWG). Jean-Louis Robert is the EU Rapporteur for the Q–IWG and chair of the EU Committee for Medicinal Products for Human Use Quality Working Party.