recommendations Archives - European Industrial Pharmacists Group (EIPG)

A concept paper on the revision of Annex 11


This concept paper addresses the need to update Annex 11, Computerised Systems, of the Good Manufacturing Practice (GMP) guideline. Annex 11 is common to the member states of the European Union (EU)/European Economic Area (EEA) as well as to Read more

What happens after IP loss of protection


by Giuliana Miglierini What does it happen under a competitiveness perspective once intellectual property (IP) protection for medicinal products expired? And what is the impact of the new entries on generics and biosimilars already in the market? The role of competitor Read more

The FDA warns about the manufacture medicinal and non-pharmaceutical products on the same equipment


by Giuliana Miglierini A Warning Letter, sent in September 2022 by the US FDA to a German company after an inspection, addresses the possibility to use the same equipment for the manufacturing of pharmaceutical and non-pharmaceutical products. The FDA reject Read more

ICMRA, two pilot programmes to optimise regulatory assessment and inspections

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by Giuliana Miglierini

New flexible modalities for the management of regulatory procedures are becoming progressively accepted even for routine activities, upon the experience built during the pandemic. Efforts are ongoing at the global level in order to better harmonise the new approaches. To this instance, the International Coalition of Medicines Regulatory Authorities (ICMRA) has launched two pilot programmes focused, respectively, on the collaborative assessments of chemistry, manufacturing and control (CMC) and Post-Approval Change (PAC) submissions and related regulatory actions and on hybrid inspections.

Each programme is expected to last 1-1.5 years and should see the involvement of at least two regulatory regions, each one conducting three assessments or collaborative hybrid inspections. Recommendations resulting from the pilots shall be published in 2023, representing the basis of an initial common framework for collaborative assessment and hybrid inspections. The initiative follows the results of a workshop organised by ICMRA in July 2021, during which emerged the need for more convergence and reliance across regulatory authorities in order to support the timely supply of critical medicines.

ICRMA has invited industrial sponsors to participate to the initiative, with particular reference to those planning to file an application for a new product or for post approval changes of already approved products to more than one regulatory agency. All details and the procedure for application are available at this link.

Therapeutics which may be object of the submission include both small molecules and biological products. The submission may refer to products for the treatment of Covid-19, other medically necessary/critical medicines or products granted for access to fast-track procedures such as the Breakthrough (US), PRIME (EU) or Sakigake (JP) schemes.

Interested sponsors are required to check with the involved facility’s management to ensure readiness for inspection and possibility to host a collaborative hybrid inspection, with a particular attention to the availability of suitable IT infrastructures and interpretation services, and the possibility to coordinate at least two inspectorates across different time-zones.

Applications are open since 15 June 2022 and have to be forwarded using the EudraLink secure file transfer application provided by EMA. After a rolling review of the applications, starting of the first pilot is scheduled for September 2022.

The general objectives

The main goals of the initiative include the definition of best practices and standards in the quality assessment of CMC-related post-approval changes and collaborative hybrid inspections. A single list of questions to the sponsor or manufacturer should also be delivered, and answers be shared with the participating quality assessors and inspectors.

The exercise should lead to the identification of misalignments and potential areas of harmonization across participating regulatory regions. An improved convergence and collaboration among regulators in specific data expectations and assessment approaches for the assessment of manufacturing facilities for Pre-Approval and Pre-License Applications (PAIs & PLIs) and reviewing PACs and PAC Management Protocols may also be supported by the analysis of the data acquired during the two programmes.

Hybrid inspections

Hybrid inspections are based on the collaboration of at least two different National Regulatory Authorities (NRAs), one of which in charge of the on-site inspection activities, the second acting as a remote inspectorate. The respective tasks shall be coordinated and run using virtual technologies, so to enable real-time collaboration in the inspection activities, which should target facilities and products of interest for multiple regulatory agencies (see more details here and here).

The pilot is expected to reduce the need of multiple inspections or facility assessments and to support the identification of the best virtual platforms and information technology (i.e., video) to facilitate concurrent on-site inspection and distant assessment. Focus on the development of a common framework to accommodate time zone differences between the facility location and the distant inspectorates is also expected.

Best practices to prepare and conduct the hybrid inspection are another important outcome, as both the on-site and distant inspectorates needs to obtain from the activities all the information needed to run their respective assessments.

In the critical field of GMP expectations, a possible target of the pilot may be represented by how the inspection is reported and how deficiencies are classified by different regulators. Aligned reports and protocols may also support the sharing of information with other interested ICRMA inspectorates. In any case, each participating authority remains the sole responsible for the evaluation of the outcomes of the inspection and the enforcement of any consequent action, according to its own reference legal framework.

A final protocol describing how to execute a hybrid inspection is a main expected outcome of the fist pilot, to be then applied by the Working Group to evaluate at least 3-5 facilities with at least two regulatory agencies involved in the hybrid assessment.

Collaborative assessment

The second pilot aims to run collaborative quality assessment for a minimum of three different applications and a minimum of three regulatory agencies involved each time. The initial phase of the pilot should see a limited number of regulatory agencies (3-5) participating to the project, on the basis of specific confidentiality agreements.

Sponsors participating to the pilot shall submit a single application for the proposed CMC changes for assessment by multiple regulatory authorities; the initial focus is expected to be on post-approval change management protocols (PACMPs; chapter 4 of ICH Q12) for Covid-19 therapeutics. More in detail, participating regulatory agencies will agree on the procedure to be used for the collaborative assessment. They are expected to share and discuss in advance any information request or comment, prior to the interaction with the applicant. Any participating authority can maintain its independence to issue information requests, but in any case, the so obtained answers shall be shared with other NRAs and assessed on the basis of a common approach, so to avoid the need of multiple independent lists of clarification seeking comments.

The project also aims to achieve a single regulatory decision regarding the joint assessment (see more details here and here).

More specifically, priorities to be addressed should include for example the evaluation of information or data on specifications, stability, and/or PACMP that support site changes or additions.

As for the hybrid inspections, expected outcomes are represented by the identification of the best practices and standards in the quality assessment of post approval changes, including PACMPs, and of potential areas for alignment or harmonisation across regions.

A forum of discussion should be also created in order to facilitate convergence on the basis of such best practices. Each evaluation should lead to the preparation of lessons-learned summaries to share the acquired knowledge; new quality assessment guidance and standards might also be proposed, where appropriate.


EMA’s Industry stakeholders group (ISG)

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by Giuliana Miglierini

The Industrial Stakeholder Group (ISG) is a new initiative recently launched by the European Medicines Agency (EMA) in order to favour the dialogue with the industrial stakeholders. The first meeting of the ISG, the 21 June 2022, focused on the mandate of the Group and on the three priority topics to be addressed during the pilot phase: the Emergency Task Force (ETF), the issue of shortages of medicines and medical devices and the medical device expert panels.

The initiative is part of the activities planned by EMA for the implementation of its extended mandated, as for Regulation (EU) 2022/123.

The mandate of the ISG

The main scope of the ISG is to provide a dedicate forum to capture the industrial point of view and proactively inform on open issues during the implementation of EMA’s extended mandate. The ISG will focus on human medicines and will complement other existing tools, such as industry platform meetings, bilateral meetings, topic or project related meetings. The outcomes obtained from the pilot phase will form the basis of an analysis to evaluate if to extend the scope to other initiatives.

The Chair of the ISG is nominated by the Agency’s Executive Director; the group is composed by one member and one alternate from selected EU industry organisations relevant to the subject of discussion, on the basis of a call for expression of interest. Additional representatives of selected organisations and observers may also participate to specific meetings, according to the topics on the agenda. Observers include the European Commission, EMA’s committees (e.g. CHMP, ETF, CMDh, SPOC WP, SMMG), the EU Network, Notified bodies; ad-hoc observers may be also invited from member states and stakeholder groups.

Appointed members will be responsible to liaise with the respective industrial rganisations, so to contribute the discussion with their point of view and to keep them updated on the outcomes of the ISG meetings. The current schedule includes four quarterly meetings per year; the next two are fixed for the 26 September and 22 November 2022. The summary report of each meeting will be available in EMA’s website.

The Emergency Task Force

The new Emergency Task Force (ETF) builds upon the experience gathered during the pandemic and acts within EMA to advise and support on medicines for public health emergencies and preparedness.

The ETF is in charge of coordinating all efforts following the declaration of a public health emergency by health authorities, in strict coordination with all other relevant bodies including the European Health Emergency preparedness and Response Authority (DG HERA), the European Centre for Disease Prevention and Control (ECDC), the WHO and the European Commission.

The new ETF started operating on the new mandate on 22 April. Its composition is based on expertise, and it includes representatives of EMA’s Scientific Committees and Working Parties as well as selected patients and healthcare professionals and clinical trials experts from various member states.

There are three distinct area of activities for the Task Force. Scientific advice and support to clinical trials for the development of medicines to be used during the emergency will be directly managed and assessed by the ETF, free of charge and flowing a fast-track procedure. The new streamlined procedure should lead to the outcome in 20 days; deceleration criteria are also considered, i.e. premature evidence to address the medical need, high workload or lack of urgency. Expected benefits include the reduction of the use of medicines with insufficient evidence of efficacy and the increase of safe and harmonised use across the EU of new products from the pipelines ahead of authorisation. Activities of the ETF will cover all stages of development, from pre-authorisation (e.g. rolling applications or paediatric plans) to post-authorisation (e.g. major changes), investigational products and compassionate use.

The systematic assessment of the available evidence on medicines will be the focus of the scientific reviews, while recommendations will target medicines not yet authorised or topics of particular scientific or public interest. These may include, for example, the monitoring of new outbreaks and epidemics and the information on potential radiological, chemical or bioterrorism agents.

All lists of medicines under assessment to address a declared emergency will be made public to increase transparency, as well as the CHMP opinions on the use of medicines not yet authorised, Product Information, EPARs end Risk Management Plans.

Two dedicated mailboxes are also available, the first for sponsors of clinical trials to request EMA/ETF support for facilitating CTA and approval and sponsors agreement to conduct larger multinational trials ([email protected]), the second for manufacturers to discuss with EMA/ETF their development programs or plans for scientific advice prior to any kind of formal submission ([email protected]).

Shortages of medicines

EMA’s extended mandate in this area include the monitoring and mitigation of shortages of critical medicines and medical devices, and the setting up, maintenance and management of the European Shortages Monitoring Platform (ESMP). The action also includes the establishment of the Medicines Shortages Steering Group (MSSG), which will be supported by the Working Party of singles points of contacts in the members states (the EU SPOC Network) and a network of contact points from pharmaceutical companies (the i-SPOC system). A corresponding Executive Steering Group on Shortages of Medical Devices (MDSSG), to be created by February 2023, will be in charge of adopting the list of categories of critical medical devices and to monitor their supply and demand.

According to Regulation (EU) 2022/123, pharmaceutical companies are required to identify a i-SPOC to act as the reference contact for EMA should the Marketing Authorisation Holder (MAH) have medicinal products be included in the lists of critical medicines. All information has to be provided through the IRIS platform; the registration process opened on 28 June 2022 and is comprehensive of two steps (the IAM preliminary requirement for the creation of the account and the following IRIS submission).

Scheduled milestones will see the establishment of a list of the main therapeutic groups for hospital care (due by 2 August 2022), the registration of i-SPOCs from MAHs (by 2 September 2022), and the definition of shortages of medical devices and in vitro diagnostics (by 2 February 2023). The ESMP platform is expected to go live by 2 February 2025, and will represent a single reference point to make information available on shortages, supply and demand of medical products, including the marketing status and cessation.

Expert panels on medical devices

Regulation (EU) 2022/123 establishes the hangover of expert panels on medical devices from the Joint Research Centre (JRC) to EMA, thus adding a completing new type of activity for the Agency.

The new Secretariat is coordinating the activities of the Screening panel composed by 70 experts in charge of the decision whether to provide a scientific opinion, eleven thematic expert panels and expert panels sub-groups (for a total of approx. 130 experts), and a Coordination Committee inclusive of the Chair and vice-Chair of all the expert panels.

The main task of the expert panels is to provide opinion to the notified bodies for certain high-risk medical devices and in-vitro diagnostic, for the assessment of their clinical and/or performance evaluation. EMA is specifically involved in the coordination of the Clinical Evaluation Consultation Procedure (CECP) for medical devices and Performance Evaluation Consultation Procedure (PECP) for in-vitro diagnostics. Further details on the procedures and their interfaces with the ETF is available here.