human medicines 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

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.


EMA’s Q&A on the integration of EudraGMDP and OMS

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by Giuliana Miglierini

A new step in the integration at the central level of data needed to manage regulatory procedures is going to be activated on 28 January 2022: starting from this date, member states’ national competent authorities (NCAs) shall use the data available in EMA’s Organisation Management System (OMS) to issue all type of certificates regulated under the EudraGMDP database, for human, veterinary and experimental medicines, as well as active substances (API).

A Questions & Answers guideline on the integration of EUdraGMDP and OMS has been released by EMA; the document reflects the points of discussion which arose in the course of a webinar organised by EMA to better inform about the new modalities for the release of the certificates and other services provided through the OMS system, and how to face the change request process.

The new procedures to uniquely identify the interested parties

As discussed few weeks ago on this blog, the use of the OMS dictionary became mandatory for all centrally authorised products (CAPs) since 1st November 2021. The integration of OMS with EudraGMDP database is a specific requirement arising from the new Veterinary Medicinal Products Regulation ((EU) 2019/6), which will become fully applicable on 28 January 2022.

The new procedures refer to different types of certificates, including the Manufacturing and Importation Authorisations (MIA), the Wholesale Distributor Authorisations (WDA), GMP and GDP certificates and API Registration certificates. GDP certificates will maintain their current validity, with re-inspections to occur after 5 years at the latest. Any new GMP certificate/authorisation for Clinical trials issued after 28 January 2022 will be also impacted. CEP certificates of suitability issued by the EDQM fall out of the scope of EudraGMDP, and are thus not impacted.

Should there be two different organisations with the same legal address, each of them will have a distinct ORG ID in the system; a single organisation with two different locations will have two LOC IDs. Multiples ORG IDs will be generated for marketing authorisation holders (MAHs) located in one country and having subsidiaries in other countries, as the identification is specific to the single subsidiary/location. A particular case may be represented by India, where some plots are recognised as one address by National postal services. In that case, just one LOC ID will be available; on the contrary, should the plot be not recognised as a single address, different LOC IDs will be generated.

In case of a single warehouse for human and veterinary medicines for a single company with a single address, the OMS will only have 1 contact; in these instances, NCAs will select if the certificate applies to human or veterinary medicinal products.

In the case of transfer of the location under another organisation, the OMS system is provided with the technical functionality to move the location from an organisation to another. Nevertheless, advices EMA, the activation of this procedure requires a careful verification and validation of the supporting documentation in order to avoid breaking the business rules of both EudraGMDP and OMS.

Changes requests and Super users

Since the end of January, NCAs shall extract from the OMS database all data relative to the specific organisation (i.e. name and location address details, including the legally registered address).

It is thus of paramount importance that all interested parties which appear on documents recorded in EudraGMDP – i.e. pharmaceutical companies, contract manufacturing organisations (CMOs), importers and distributors, both EU and non-EU – shall verify the correctness of their data registered in the database prior to the submission of any new or updated application for manufacturing or wholesale distribution authorisation with national competent authorities.

Should the submission of a change request be needed, anyone among the interested parties may provide to file it with EMA. Change requests can be submitted starting from 28 January 2022; the requests have to be validated by EMA against the reference sources (e.g. Trade registry and Postal services) before the OMS Data stewards can proceed to change the data in the system.

The availability of the correct information is particularly important in the case of CMOs located in extra-EEA countries, and which may request inspections or need to update their GMP certificates. EMA’s advices companies to promptly liaise with their partners to manage in due time any change request needed to correct data recorded in the OMS.

The “Organisation Super users” can verify all of the users affiliated to their respective organization through the EMA’s Account management portal; they can also change the user roles and users affiliated at any point in time. EMA suggests companies to have at least two Super users, in order to guarantee one of them is always available and active. A single Super user can be affiliated with different organisations.

Other answers provided by the guideline

The Q&As guideline published by EMA consists of 87 questions and their corresponding answers. Question n°2 addresses the issue of the legal basis of GDP certificates for Veterinary medicines: as the new Regulation and its associated secondary legislative acts still do not include such a legal basis, EMA will update the GDP module of EudraGMDP after January 2022 in order to provide consistency in the approach. It shall thus be possible for NCAs to voluntary use the database to record GDP certificates for companies distributing veterinary medicines. The guideline also indicates that national competent authorities are prepared to the handle the new framework and can plan in advance activities needed in the near time to issue WDA and API Registration certificates for veterinary Organisation.

Even if the use of OMS is yet mandatory for CAPs only, the Q&As guideline indicates that NCAs need to ensure that the relevant organisations are available in OMS before submitting information into the system, both for CAPs and non-CAPs. The suggestion is thus to ensure that the OMS data is present and correct for all organisations/sites, even if its use in electronic application forms (eAF) is not mandatory for the time being.

Details of manufacturing sites such as buildings or plots are not registered in OMS, but they have to be included in the GMP certificate; this extra information will be inserted in the ‘Restrictions’ section of the certificate. There is no change to the procedures for the issuing of GMP certificates.

When a change to an organisation occur in the OMS, the dictionary part of EudraGMDP gets refreshed, but no change is reflected in the documents already issued unless there is a specific action on them. The synchronisation between the two databases occurs on the following business day after the change was registered.

In case of transfer of the company to a new location, the change has to be registered in the OMS before new certificates can be issued; according to the guideline, this should not represent a problem while the current certificate are still valid.

During the webinar some doubts have been expressed as for the possible confusion arising from the guidance document “Manufacturer organisations in the OMS dictionary” (EMA/465039/2018), which divides OMS data responsibility for manufacturers and MAHs/Applicants. This document shall be reviewed by the Agency, says EMA’s guideline.