In addition to updates on how ICH regulatory members are implementing ICH guidelines, the ICH Assembly at its meeting in Charlotte, NC, on 14-15 November 2018 also was informed of progress made on a survey for monitoring the adequacy of regulators and industry in implementing and adhering to ICH guidelines, according to the recently released minutes of the meeting.
Results from the survey are expected next June, and ICH observers were invited to volunteer to participate, with those who agreed to do so including Malaysia’s NPRA, Mexico’s COFEPRIS and South Africa’s SAHPRA.
The Assembly also approved the application of Iran’s NRA for observership, which means the ICH is now made up of 16 members and 28 observers.
The Assembly endorsed as an ICH reflection paper the US Food and Drug Administration’s (FDA) reflection paper on “Further Opportunities for Harmonization of Standards for Generic Drugs,” including minor amendments, and agreed that its publication on the ICH website would be deferred until the approval of the remit of the Informal Generic Drug Discussion Group (IGDDG).
Theresa Mullin, associate director for strategic initiatives at FDA, previously said the reflection paper would target scientific and technical standards of generic drugs, noting three possibilities:
- A series of ICH guidelines on bioequivalence standards for simple dosage forms;
- A series of ICH guidelines on bioequivalence standards for complex dosage forms;
- A survey of existing ICH guidelines for updating as needed to incorporate recommendations for generic drugs.
ICH said the IGDDG will be established for a one-year term, and a call for expression of interest for members and observers to nominate experts would be issued.
The Assembly also noted that Japan’s MHLW/PMDA crafted a reflection paper on “Strategic Approach to International Harmonization of Technical Scientific Requirements for Pharmacoepidemiological Studies Submitted to Regulatory Agencies to Advance More Effective Utilization of Real-World Data” and that it had been circulated to the Assembly ahead of the meeting, and that a revised document with a narrower focus would be further provided which would include a proposal for the establishment of a discussion group.
The Assembly further said that a PhRMA-drafted reflection paper on “Model Informed Drug Development” was expected to be circulated to the ICH Assembly in 2019. The Assembly also announced the publication of an article, “ICH: Recent Reforms as a Driver of Global Regulatory Harmonization and Innovation in Medical Products"
in the journal Clinical Pharmacology & Therapeutics
Regarding requests from working groups to meet at the next ICH meeting in Amsterdam, the Netherlands on 1-6 June 2019, the Assembly noted “that any such requests would be taken under consideration by the ICH MC [management committee].” A list of WGs agreed by the ICH MC to meet face-to-face in Amsterdam will be made available to the Assembly, and also on the ICH website, following the ICH MC teleconference to be held at least eight weeks ahead of the meeting, the minutes said.
As far as updates from the individual working groups, here’s a rundown of just some of the updates in the minutes:
E8(R1) EWG: Revision on General Considerations for Clinical Trials (Rapporteur: Dr. LaVange – US FDA; Regulatory Chair: Dr. Sweeney – EC, Europe): The rapporteur reported to the Assembly on the outcome of the
E8(R1) expert working group (EWG) meeting and the progress made on the development of the draft E8(R1) Technical Document on the Revision on General Considerations for Clinical Trials. “Steps 1 and 2a/b are expected to be reached electronically between January and February 2019,” ICH said.
E9(R1) EWG: Addendum to Defining the Appropriate Estimand for a Clinical Trial/Sensitivity Analyses (Rapporteur: Mr. Hemmings – EC, Europe; Regulatory Chair: Dr. Ando – Japan’s MHLW/PMDA): The rapporteur reported to the Assembly on the outcome of the E9(R1) EWG meeting and the progress made on analyzing and addressing the comments received from the regional public consultations which ended in April 2018, as well as the progress made on the development of training materials and the finalization of the Addendum.
E11A EWG: Paediatric Extrapolation (Rapporteur: Dr. Yao – US FDA): The rapporteur reported to the Assembly on progress made on the development of the E11A draft Technical Document on Pediatric Extrapolation.
E14/S7B IWG: The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs, Dr. Leishman (PhRMA): Rapporteur reported to the Assembly on the progress made by the group, including on the review of the CiPA (Comprehensive in vitro Proarrhythmia Assessment) validation data and the finalization of a Concept Paper for the development of Q&A for S7B/E14.
E17 IWG: Multi-Regional Clinical Trials (Rapporteur: Dr. Dunder – EC, Europe; Regulatory Chair: Dr. Otubo – Japan’s MHLW/PMDA) The rapporteur reported on the progress made on the finalization of the Training Materials, with case studies supportive of harmonized implementation activities of the recently released E17 ICH Guideline on General Principles for Planning and Design of Multi-Regional Clinical Trials.
E19 EWG: Optimisation of Safety Data Collection (Rapporteur: Dr. Thanh Hai – US FDA; Regulatory Chair: Dr. Mol - EC, Europe) The rapporteur reported on the progress made on the development of the E19 draft Technical Document on Optimisation of Safety Data Collection. In addition, progress has been made towards the finalization of the Step 1 Technical Document and that Steps 1 and 2a/b are expected to be reached electronically by March 2019.
S11 EWG: Nonclinical Safety Testing in Support of Development of Paediatric Medicines (Rapporteur: Dr. Keller – PhRMA; Regulatory Chair: Dr. van der Laan – EC, Europe) Further to Assembly electronic endorsement of Step 2b of the S11 draft Guideline on 18 September 2018, the draft Guideline is currently undergoing public regulatory consultation in the ICH Member regions. Steps 3 and 4 are expected by November 2019.
M7(R2) Maintenance EWG/IWG: Addendum to Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk (Rapporteur: Dr. Honma – Japan’s MHLW/PMDA; Regulatory Chair: N/A): The rapporteur reported to the Assembly on the outcome of the M7(R2) Maintenance EWG meeting, including its progress on the development of a list of compounds to be evaluated in the second Addendum, the update of the M7(R1) Guideline text regarding the treatment for HIV (Human Immunodeficiency Virus), and on the development of a Q&A document to clarify and address quality and safety issues.
M9 EWG: Biopharmaceutics Classification System-based Biowaivers (Rapporteur: Dr. Welink – EC, Europe; Regulatory Chair: Dr. Seo – US FDA): Further to Assembly endorsement of Step 2b at the meeting in Kobe, Japan in June 2018, the ICH says that the M9 draft guideline is currently undergoing consultation in the ICH Member regions until the beginning of 2019. Steps 3 and 4 are expected by November 2019.
Q12 EWG: Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management (Rapporteur: Ms. Boam – US FDA; Regulatory Chair: Ms. Kruse – EC, Europe): Further to Assembly endorsement of Step 2b at the November 2017 meeting in Geneva, the Q12 draft guideline underwent public consultation in the ICH Member regions until last December. The group will hold an interim meeting from 11 to 15 February 2019 in Tokyo, Japan. Steps 3 and 4 are expected by November 2019.
M8 EWG/IWG: The Electronic Common Technical Document (eCTD) (Rapporteur: Mr. Gray – US FDA; Regulatory Chair: Dr. Menges – EC, Europe): Further to the eCTD v4.0 Q&As and Specification Change Request Document v1.2, as well as the eCTD v3.2.2 Q&As and Specification Change Request Document v1.31 reaching Steps 3 and 4 at the meeting in Kobe, Japan, in June 2018, the M8 EWG/IWG did not receive any new Change Requests which would require an update of these documents.
The Assembly also noted the following dates for future ICH Assembly meetings:
- Tuesday 19 – Wednesday 20 November 2019 in Singapore (to be confirmed);
- Tuesday 26 - Wednesday 27 May 2020 in the Americas (location to be confirmed);
- Tuesday 17 - Wednesday 18 November 2020 in Europe (location to be confirmed);
- Tuesday 1 - Wednesday 2 June 2021 in Asia (location to be confirmed).