Attending to 61° SIMPOSIO AFI as speaker at the workshop + Booth n. 58.
8-9-10 june 2022 Rimini (Italy)
In August 2020 the International Coalition of Medicines Regulatory Authorities (ICMRA) established a working group “Remote GCP and GMP Regulatory Oversight Inspections” that has published a report entitled “Reflections on the regulatory Experience of remote Approaches to GCP and GMP regulatory Oversight during the COVID-19 Pandemic”
ICMRA is a voluntary association of internationally cooperating medicines regulatory authorities
The International Coalition of Medicines Regulatory Authorities (ICMRA) set up this working group to focus on the transition from GCP and GMP inspections to remote inspections during the pandemic. The working group was chaired by the UK MHRA and included representatives from the US FDA, EMA, Health Canada, Swiss-medic, HPRA Ireland, AEMPS Spain, ANSM France, PEI Germany, MHLW/PMDA Japan, TGA Australia, ANVISA Brazil, HSA Singapore, WHO, and Saudi FDA.
The purpose of this paper is to report reflections based on combined experience during conducting remote assessments, inspections, and determinations of GCP and GMP regulatory activities conducted globally shared through the workgroup during 2020-21.
Obviously, variable experience is reported across inspection types and areas, sites, and jurisdictions.
Experiences with different types of digital means, such as visual technology, are also discussed.
Essentially the ICMRA working group conveyed that remote inspections cannot replace regular and routine on-site GMP inspections, but they have allowed regulators to maintain a minimal oversight program. Some regulators expressed interest in continuing to supplement their inspections with remote inspections and/or hybrid approaches in the future, or even replacing an on-site inspection completely in some cases, such as to address an urgent concern, to support an application evaluation and approval decision, or to review certain corrective/preventive actions.
https://www.icmra.info/drupal/sites/default/files/2021-12/remote_inspections_reflection_paper.pdf
The U.S. Food and Drug Administration (FDA) has issued draft guidance to clarify how benefit-risk assessment (BRA) considerations are integrated into the agency’s premarket and postmarket decisions for new drugs and biologics marketing applications.
According to the FDA, BRA considers in addition to the extensive safety and effectiveness evidence presented, other factors such as the nature and severity of the condition that the product is intended to treat or prevent, the benefits and risks of other available therapies for the disease, and risk management tools that may be needed to ensure that the benefits outweigh the risks.
Examples of regulatory options to reduce and manage risks include the following:
BRA Lifecycle Approach / Periodic Benefit-Risk Evaluation Reports
The U.S. Authority views BRA as a life-cycle approach. In fact, it recognizes that knowledge of the risks and benefits of a product changes over time as new information about the safety and efficacy of that product becomes available.
According to FDA, sponsors find it useful to have a structured approach to producing the evaluations of new information, as well as the decisions made based on that new information.
In addition, the ICH E2C(R2) guideline recommends, although optionally, developing a Periodic Benefit-Risk Evaluation Report (PBRER).
In any case, sponsors should not wait for a periodic safety update to report a potentially serious safety concern. Any New information about a potential serious safety concern that could have an impact on a drug’s benefit-risk profile should be communicated promptly to FDA.
FDA Guidance Document “Benefit-Risk Assessment for New Drug and Biological Products“
USP recently added a new chapter “1469” on nitrosamine impurities to the U.S. Pharmacopeia. With this addition, USP intends to help both the Authority and pharmaceutical manufacturers assess the presence of nitrosamine impurities and implement appropriate control strategies and analytical procedures.
This chapter is aligned with current scientific and regulatory approaches developed to ensure appropriate control of nitrosamine impurities by eliminating or reducing their presence in drug substances and drug products. Thus, the approach described ensures product quality with respect to safety.
BRIEF OVERVIEW OF THE NEW CHAPTER: <1469> nITROSAMINE IMPURITIES
The new chapter has a more substantial structure articulated in nine paragraphs:
USP: Protecting patients from harmful nitrosamine impurities
EMA supports recommendations developed by the International Coalition of Medicines Regulatory Authorities (ICMRA) to facilitate the use of global track & trace systems. The agency states that the ICMRA paper identifies “common technical denominators that allow different systems to exchange and use the available information on medicines and their supply chains in order to protect public health“.
Given the globalized production and distribution of medicines, the rapid exchange of information between regulatory authorities is essential to protect the integrity of the supply chain and patient safety. Track and trace systems are therefore considered a useful tool to mitigate the risk of drug shortages and to fight against falsified medicines.
In this paper, international regulators emphasise that the interoperability of track and trace systems helps to protect public health by improving information sharing in case of quality defects and supporting pharmacovigilance activities.
ICMRA developed the recommendations in consultation with the World Health Organization (WHO), representatives from international medicines regulatory authorities and experts from the private sector.
Interoperability of track and trace systems: key to public health protection published
On July 27, 2021, ICH published the long-awaited draft of the Q13 Guideline on Continuous Manufacturing of Drug Substances and Drug Products.
The purpose of the guideline is to provide legal and scientific considerations for the design, implementation and operation of continuous manufacturing. In addition to batch definitions, the document describes the different approaches to continuous manufacturing and provides guidance on control strategy and approval issues.
The new guideline ICH Q13 Continuous Manufacturing of Drug Substances and Products covers active ingredient and drug production manufacturing as well as the production of therapeutic proteins and combined or integrated active ingredient and drug production.
ICH Q13 aims to:
The current status of the document corresponds to Step 2 of the ICH process and is open for comment. At this stage, the draft guideline, based on comments received from the ICH Expert Working Group (EWG), is distributed to regulatory authorities in the ICH regions for review in accordance with national or regional procedures. An EWG meeting is scheduled in November 2021 to discuss the comments received. The final guideline is expected to be signed in November 2022 (Step 3).
draft of the Guideline ICH Q13 Continuous Manufacturing of Drug Substances and Products
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
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 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.
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:
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 Annex
ICH Q12: Implementation Considerations for FDA-Regulated Products