Author: Federica Carra

In July 2021, the EDQM (European Directorate for the Quality of Medicines & HealthCare) renewed the document “Guidance for electronic submissions for Certificates of Suitability (CEP) applications“. The guidance provides explanatory guidance on the electronic submission of CEPs (Certificates of Suitability of Monographs of the European Pharmacopoeia).

The new version of the updated guideline will be implemented on October 01, 2021. The information and requirements described in this document are intended to facilitate the management and evaluation of CEP submissions and to maintain their lifecycle even if the submission is not an eCTD.

This guidance should be applied to all electronic submissions submitted to EDQM as part of CEP applications.

EDQM no longer accepts paper submissions; in fact, the eCTD format is mandatory for all submissions, with the exception of applications for TSE risk (PDF format) and for veterinary substances use only (eCTD format)

EDQM no longer accepts paper submissions; in fact, the eCTD format is mandatory for all submissions, with the exception of applications for TSE risk (PDF format) and for substances for veterinary use only (eCTD format).

Guidance for electronic submissions for Certificates of Suitability (CEP) applications

Adoption and Entry into Force of PIC/S Guidance on Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments (PI 041-1)

On July 1, 2021, the PIC/S Guidance on Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments (PI 041-1) became into force. The guidance has been developed primarily for inspectors, but also serves as a valuable resource for industry to provide clarity on areas of greatest risk and regulatory expectations.

The draft document was first published by PIC/S in 2016, and re-issued as a draft in 2018.

The primary focus of the guidance is on data management as it relates to GMP/GDP considerations.

The scope of the guidance includes both on-site and remote inspections, while follow-up inspections, conducted for cause to probe vulnerabilities found in the first inspection, are excluded.

Data governance principles are addressed by introducing the concept of the data lifecycle, i.e., “how data are generated, processed, reported, checked, used for decision-making, stored, and finally discarded at the end of the retention period,” following a risk-based approach.

For the original document, please see link below.

PIC/S Adapting EU GMP Annex 16 on Authorised Person and Batch Release

PIC/S is considering adopting Annex 16 of EU GMP and harmonizing its requirements. The new document will be called Authorized Person and Batch Release.

Following the revision of Annex 16 in 2016, PIC/S has been discussing whether to transpose Annex 16 in order to harmonize international requirements related to batch release and has now started step 2 of the adoption process which involves consultation of PIC/S Member Authorities with stakeholders.

This consultation will be launched on 15 June 2021 for a period of 3 months.

For the original document, please see link below.

FDA has officially endorsed the ICH Q12 guideline for post-approval change management

The guideline ICH Q12 “Technical and regulatory considerations for pharmaceutical product lifecycle management”, provide a globally agreed framework to facilitate the management of post-approval chemistry, manufacturing, and controls (CMC) changes in a more predictable and efficient manner across the product lifecycle.

This guideline establishes a harmonized approach to defining which elements in an application are considered necessary to ensure product quality (Established Conditions for Manufacturing and Control” – ECs) and therefore would require regulatory submission if changed after approval.

ICH Q12 Core Guideline

defines the concepts of:

• Post-Approval CMC (chemistry, manufacturing, and controls) changes,
• Established Conditions(ECs),
• Post-Approval Change Management Protocols(PACMPs),
• Product Lifecycle Management (PLCM)

ICH Q12 Annexes

FDA also published the Annexes to ICH Q12 which contains illustrative examples describing how to use the principles in the guidance as a framework for managing postapproval changes.

Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management Guidance for Industry

Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management Annex

ICH Q12: Implementation Considerations for FDA-Regulated Products

Revision of PIC/S GMP Guide (PE 009-15)

The PIC/S GMP Guide to Good Manufacturing Practice (GMP) for Medicinal Products has been revised to include a new Annex 2A and 2B:

• Annex 2A: Manufacture of Advanced Therapy Medicinal Products for Human Use (ATMP); and
• Annex 2B: Manufacture of Biological Medicinal Substances and Products for Human Use

Annex 2A provides PIC/S GMP requirements for ATMP – it is not a standalone document but it enables reasonable harmonisation with the standalone ATMP Guidelines published by the European Commission.  Annex 2B had very minor revisions and continues to harmonise with the EU Annex 2 for human use biological medicinal substances and products.

The revised GMP Guide (PE 009-15), with the new Annex 2A and 2B, will enter into force on 1 May 2021. All non-EEA Participating Authorities of PIC/S and Applicants have been invited to transpose the revised Chapters of the PIC/S GMP Guide into their own GMP Guides.

For the original document, please see link below.

Q3C(R8) Adoption of Part VI of Q3C(R8) (PDEs for 2-MTHF, CPME, TBA) by the Regulatory Members of the ICH Assembly under Step 4

The ICH Q3C(R8) Residual Solvents guideline has been updated and Permitted Daily Exposure (PDE) values have been added for the following substances:

• 2-methyltetrahydrofuran (50 mg/day)
• Cyclopentyl methyl ether (15 mg/day)
• Tertiary butyl alcohol (35 mg/day)

These values has been developed by the appropriate ICH Expert Working Group (EWG) based on the toxicity details.

On March 25, 2020, ICH had already published the document open for public consultation (Step 2). The proposed values were then adopted as final and included in the final draft of the document (step 4). This will allow for adoption by the regulatory parties of ICH regions, in accordance with the ICH Process (step 5), concluding the review.

For the original document, please see link below.