ema Archives - European Industrial Pharmacists Group (EIPG)

Approval of the Data Governance Act, and EMA’s consultation on the protection of personal data in the CTIS


by Giuliana Miglierini The Data Governance Act (DGA) was approved and adopted in May 2022 by the European Council, following the positive position of the EU Parliament; the new legislation will entry into force after being signed by the presidents Read more

The transition towards EMA's new Digital Application Dataset Integration (DADI) user interface


by Giuliana Miglierini The Digital Application Dataset Integration (DADI) network project is aimed to replace the current PDF-based electronic applications forms (eAFs) used for regulatory submissions with new web-forms accessible through the DADI user interface. The European Medicines Agency (EMA) has Read more

IVD regulation in force: new MDCG guidelines and criticalities for innovation in diagnostics


by Giuliana Miglierini The new regulation on in vitro diagnostic medical devices (IVDR, Regulation (EU) 2017/746) entered into force on 26 May 2022. The new rules define a completely renewed framework for the development, validation and use of these important Read more


The transition towards EMA’s new Digital Application Dataset Integration (DADI) user interface

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by Giuliana Miglierini

The Digital Application Dataset Integration (DADI) network project is aimed to replace the current PDF-based electronic applications forms (eAFs) used for regulatory submissions with new web-forms accessible through the DADI user interface.

The European Medicines Agency (EMA) has released the updated timeline for the implementation of the project, which will at first affect variation forms for human medicinal products. The ongoing phase of User Acceptance Testing (UAT) by members of the DADI Subject Matter Expert (SME) Group (including representatives of EMA, national competent authorities and the industry) is expected to close in August 2022, followed by a second round of testing with external users, representatives of the different stakeholders.

The final release of the new form is currently scheduled for October 2022; a six month transition period shall then apply, during which both the PDF eAF and the web-based form can be used in parallel. Further information of the scope and implementation of the new DADI interface is available in the Q&A document published by EMA. An updated Fast Healthcare Interoperability Resources (FHIR) mapping spreadsheet is also available, containing all attributes that are required by the Notice to Applicants; the attributes have been made consistent with the ISO Identification of Medicinal Products (IDMP), so that the DADI form also supports the submission of structured data to EMA’s Product Management Service (PMS).

A short history of the project

The DADI project is aimed to improve the interoperability of data; it builds upon the Common European Single Submission Portal (CESSP) Phase 1 project (2016-2020). Seven national competent authorities (NCAs), from Austria, Germany, Spain, Ireland, the Netherlands, Norway and Sweden are also collaborating to the setting up of the DADI project.

Some results from the Horizon 2020’s UNICOM project (with no contractual obligations for EMA towards the UNICOM Consortium and the European Commission) also supported the DADI’s development; UNICOM is specifically targeted to ensure the availability of pan-European ISO IDMP compliant forms and IDMP implementation at national agencies.

The use of ISO IDMP rules is compulsory as for Commission Implementing Regulation (EU) 520/2012 (articles 25 and 26) for both marketing authorisation holders (MAHs), EMA and member states. These standardised definitions for the identification and description of medicinal products for human use shall facilitate the reliable exchange of information between the different parties involved in the regulatory processes. However, it should be noted that ISO IDMP covers human medicinal products only, not veterinary ones, and refers to the entire product lifecycle, including development. This differs from the PMS module, which covers only the Authorised Medicinal product part of IDMP.

How the DADI interface works

EMA’s plan is to gradually replace during 2022 and 2023 all the eAF forms for the various types of regulatory procedures, starting with the variation form for human medicinal products, so to achieve the availability of standard product master data for human and veterinary medicinal products. It is important to note that both the old forms based on the PDF format and the new web-forms are “electronic application forms”; EMA warns to expect that “the web-based forms will still be called electronic application forms (eAF)”, while in DADI communications, reference can be made to web-based application forms to distinguish them from the current PDF-based eAFs.

The implementation of the FHIR data exchange standard shall make possible to generate human- readable output (PDF files, with an attached FHIR XML) as well as machine-readable output for digital processing. Exchangeable contents based on FHIR are called “resources”. They all share some common characteristics, including how they are defined and represented on the basis of reusable patterns of elements, a common set of metadata, and a human readable part.

Some form fields could also be pre-populated with available product master data from the PMS for human medicines and the Union Product Database (UPD) for veterinary ones, so to facilitate applicants with the filling of the form. Additional metadata may be included in the FHIR XML backbone in order to facilitate regulatory activities.

Users will be able to download forms containing relevant product data, but it won’t be possible to export only product data nor to perform bulk exports in the web UI. Digital signature tools should be used to sign the PDF rendition of the web-form (details will follow from EMA).

Other expected benefits include shorter times to load substances drop down lists and a lower administrative burden for regulators, so to speed up the validation of applications and lowering the number of errors and discrepancies.

The main expected changes

No changes in the process to apply for or submit marketing authorisation applications will occur following the implementation of the DADI project. The current PDF output will remain, as well as the content of the output form included in the application.

The DADI project was developed on the basis of the Safe Agile principles of the Network Portfolio, and it will impact both centralised, decentralised, mutual recognition and national procedures. Ownership of the new web-forms is shared between EMA and NCAs, to acknowledge the collaborative work done to develop them.

At the level of national competent authorities, the new FHIR compliant XML shall be implemented by NCAs which are currently using the PDF forms’ Extensible Markup Language (XML) functionalities.

Specific guidance, training and webinars on the use of the new variation form should be made available by EMA close to its final adoption. Support in the use of the new web-forms will be available through the EMA Service Desk; the existing eAF Maintenance Group shall also continue its activities and act as an expert body.

Access to the new DADI interface should be based on EMA’s Identity and Access Management (IAM) system, and make use of specific access privileges. Consultants may be granted access by marketing authorisation holders (MAHs) to all products from that MAH, or only to specific applications containing products.

EMA also clarifies that the new DADI portal will remain distinct from the IRIS platform supporting product-related scientific and regulatory procedures, and it will be governed differently.

The challenges for the industry

The challenges and opportunities for the pharmaceutical industry linked to the implementation of the new DADI interface by April 2023, at the end of the transition period, has been addressed by an article by Amy Williams in Pharmaceutical Online.

Namely, the decision to implement the DADI has overwritten the expected publication of the IDMP’s EU Implementation Guide 2.2, thus asking the industry an effort to redefine its priorities along its entire regulatory portfolio to include all types of EU procedures. Submission of structured PMS data should also be accelerated by the adoption of the DADI, thus asking for an improved approach to data capture and alignment across the entire company. The need to resubmit post-approval data using EMA’s Extended EudraVigilance Medicinal Product Dictionary (xEVMPD) should be also considered.

The new phase of the DADI implementation indicates that “full IDMP-based regulatory data exchange, via a system-to-system interface between pharmaceutical companies and EMA, now won’t come into effect any time soon”, writes Renato Rjavec in Pharmaceutical Technology Europe. Compliance to data granularity requirements of IDMP should also be ensured, together with the availability of tools to extract relevant information from complex IDMP data model to appropriately generate the xEVPRM format of data exchange.


EMA’s consultation on draft Q&As on remote certification of batches by QP

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by Giuliana Miglierini

The last two years saw the implementation of a high degree of regulatory flexibility as a mean to respond to the many challenges posed by the travel bans consequent to the pandemic. After this “experimental” phase, regulatory authorities are now considering the possibility to allow the routine implementation of some remote procedures in the field of pharmaceutical production.

It is the case of the remote certification/confirmation of batches by the Qualified Person (QP): after the publication of a draft guideline in the form of Q&As (EMA/INS/169000/2022), the European Medicines Agency (EMA) has launched a short public consultation which will remain open up to 13 June 2022. Comments may be sent by email.

The guideline offers EMA’s point of view on the requirements for the physical attendance at the authorised manufacturing site applying to QPs in order to routinely run the remote certification of batches, outside emergency situations. The document has been drafted by the GMDP Inspectors Working Group; it is composed of four questions and their relative answers and it addresses some considerations arising from the experience gained on the application of the guidelines for human and veterinary medicines issued during the pandemic. These last ones were elaborated in cooperation between the European Commission, the Coordination group for Mutual recognition and Decentralised procedures – human (“CMDh”), the Inspectors Working Group, the Coordination group for Mutual recognition and Decentralised procedures – veterinary (“CMDv”) and EMA.

The Agency also warns that the contents proposed by new Q&As’ guideline may be subject to any other interpretation by the European Court of Justice, which is the ultimate responsible for the interpretation of the EU legislation.

The contents of the Q&As

The routine remote certification or confirmation of batches may in future apply to the activities carried out by the QPs within the EU and European Economic Area (EEA), with reference to manufactured or imported human and veterinary medicinal products and investigational medicinal products.

The first answer clarifies that it could be possible for the QP to routinely run remote batch certification or confirmation only if this type of practice is accepted by the relevant national competent authority (NCA) of the member state where the authorised site is located. To this instance, it should be noted that some NCAs may request some specific requirements to authorise the routine remote certification procedure, for example with reference to the location of the QPs.

Should the remote certification be allowed on a routine basis, specific requirements should be met in order to validate this practice, starting from its full compliance to the EU legislation and EU GMP guidelines.

The answer to question 2 specifies that all activities should take place in an EU/EEA country, and that the time spent by the QP at the authorised site should be commensurate with the risks related to the processes” hereby taking place. To this instance, it is of paramount importance the ability to demonstrate that the QP acting from remote has maintained full knowledge of the products, manufacturing processes and pharmaceutical quality system (PQS) involved in the remote certification/confirmation of batches. That also means that the QP should be highly reliant on the PQS of the authorised site, and this would be only possible by spending an adequate time on-site to verify the adequacy of the PQS with respect to the processes of interest. The pharmaceutical quality system should also include details of all the procedures used for the routine remote certification/confirmation of batches. The possible use of this type of remote procedure by the QP should be also clearly mentioned in the technical agreement governing the relationship between the authorisation holder and the QP, which should also specify all cases requiring the presence on-site of the QP. A robust IT infrastructure should be in place to guarantee the remote access of the QP to all the relevant documentation in the electronic format needed to achieve bath certification/confirmation, according to the provisions described in Annex 16 to the GMPs (Certification by a Qualified Person and Batch Release). To this instance, presence on-site should be always considered to solve issues that cannot properly be addressed from remote. The demonstration of the presence on-site of the QP falls under the responsibility of the Manufacturing/Importers Authorisation (MIA) holders.

These are also responsible to make available to the QPs all the hardware and software needed to guarantee the remote access to the relevant documentation (e.g. manufacturing executions systems, electronic batch records system, laboratory information systems etc.) as well as batch registers. All IT systems used for remote batch release should comply with the requirements of Annex 11 to the GMP (Computerised Systems).

On the same basis, it should be possible for NCAs to contemporaneously access for inspection all documentation and batch registers involved in routine remote certification/confirmation at the authorised site of batch release. MIA holders should also guarantee the QP is the only allowed person to access the batch certification/confirmation function and batch register, that the transferred data are complete and unchanged, and that an adequate system for electronic signatures is in place.

Question 3 simply clarifies that some members states may have some specific requirements about the country of residence of the QP, for example it should be the same where the authorised site involved in the remote certification procedure is located.

The last question discusses technical requirements linked to IT-security and data integrity for remote access, a type of procedure presenting a higher intrinsic risk in comparison to the same activities carried on-site. Here again, the main reference is Annex 11; all equipment and software used for remote certification of batches should always reflect the current technological developments.

Among the suggestions made by the Q&A draft guideline is the precise identification of all hardware transferred off-site to the QP, that should be inventoried and kept updated. Hard disks should be encrypted, and ports not required disabled.

Attention should be also paid to the configuration of any virtual private network (VPN) used by the QP to improve the security of the connection to the IT infrastructure of the authorised site and to prevent unauthorised accesses. Authentication should be based on recognised industry standards (e.g. two-factor or multifactor authentication, with automatic date of expiry). The transfer of data should be secured by strong transport encryption protocols; assignment of individual privileges and technical controls falls under the responsibility of the MIA holder


EDQM, the RTEMIS scheme for remote inspections and new application forms for CEPs

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by Giuliana Miglierini

Starting in 2022, the Real-Time Remote Inspections (RTEMIS) programme, established by the European Directorate for the Quality of Medicines & HealthCare (EDQM) as a pilot in November 2020 to provide a tool to face travel restrictions due to Covid-19, has turned permanent. Companies applying for Certificates of suitability to the monographs of the European Pharmacopoeia (CEPs) may thus receive a notification for a RTEMIS inspection, as a part of the activities of the EDQM. The Directorate is responsible in cooperation with the participating agencies, for assessing the GMP compliance and CEPs applications relative to manufacturing sites of active pharmaceutical ingredients (APIs). The final GMP certificate issued from the NCA incorporates, following the positive closure of a remote inspection clearly states that the inspection was performed as a “distant assessment”.

Companies can adhere to the RTEMIS programme on a voluntary basis; the tool will complement the other modalities available to the EDQM to inspect manufacturers of pharmaceutical active ingredients, i.e. on-site inspections and documentation-based GMP assessment. As for on-site inspections, RTEMIS is also subject to the payment of fees. According to the Directorate, remote inspections cannot replace the on-site ones in terms of value and effectiveness, but many prove useful to assess GMP compliance for companies which have been already inspected. The RTEMIS scheme will thus form the third pillar for the supervision of GMP compliance of API manufacturers registered in the EDQM’s CEP scheme.

To qualify for an RTEMIS inspection, the concerned company should make available a suitable IT infrastructure and hardware to support the remote interaction with the EDQM’s team. To this regard, the notification letter will also include details about the expected infrastructural requirements; interested companies can contact the EDQM HelpDesk for further information.

The pilot phase to validate the RTEMIS scheme for remote inspections ran by the EDQM with reference to several manufacturing sites in India, selected on the basis of their GMP compliance history and a risk assessment, and which participated to the project on a voluntary basis. According to EDQM, suitable Corrective and Preventative Action Plans were developed by the inspected companies to address minor and major deficiencies identified during the inspections, leading to a degree in GMP conformity that the Directorate indicates as “satisfactory”.

Key factors for remote inspections

The pilot phase of the RTEMIS programme closed at the end of 2021 and led to the identification of several key factors to be respected in order to guarantee the success of remote inspections. During this period, RTEMIS inspections ran by the EDQM with the support of European Economic Area (EEA) inspectorates.

At a minimum, an appropriate IT infrastructure and hardware at the inspected site should be available to support a stable connection with the EDQM’s inspectors. During the preparatory phase of the inspection great attention should be paid to choose a suitable web conference application, running connectivity tests before the established date for the inspection, as well as a secure platform for the sharing of all relevant documentation (often in advance of the inspection). The selection of the IT tool to be used can benefit of the initial support from the EDQM’s IT department. Another important feature that should be always kept in mind refers to the possibility to run parallel sessions of discussion between the inspectors’ team and the staff and experts of the inspected company.

In remote inspections, participants are often located far apart, for example EDQM’s inspectors based in Strasbourg (F) may interact with an inspected company in China or India. The great difference in time zone requires a great flexibility on both sides to set the schedule for connections. Flexibility is also needed to face the many challenges posed by remote inspections, often requiring approaches significantly different from the traditional ones used for on-site inspections. Digital connected tools such as smart glasses may be used, for example, by the staff at the inspected site to allow inspectors to perform a real-time virtual tour of the plants.

New forms for CEPs applications

The EDQM also updated all forms to be used to apply for the release of Certificates of Suitability to the European Pharmacopoeia monographs. The forms to be used in case of a new application, revisions and sister files are available at the dedicated page of the EDQM’s website

The revision is intended to facilitate the transfer of data the EDQM’s new IT tools, which have been implemented starting 1 April 2022. The new forms also better reflect data available within the EMA’s SPOR – Organisation Management Services (OMS) system, including company details, names and addresses. The EDQM recommend communicating other additional data linked to the ones present in EMA’s website, i.e. the ORG_ID and LOC_ID.

 Applicants should also insert localisation data for their manufacturing sites, in the form of GPS coordinates. To this instance, the internationally recognised WGS 84 system should be used, using latitude and longitude (with the + and – symbols) expressed in degrees to at least five decimal places, as described in policy document PA/PH/CEP (10) 118.

Tables detailing the marketed medicinal products containing a certain active substance and the respective list of accepted Active Substance Master Files/Drug Master Files (ASMFs/DMFs) have been also updated, in order to better reflect the commercialisation history of the products and the quality assessments already performed.

EDQM also advises companies to use the form “change of contact details” as the preferred tool to inform the Directorate about the change of the contact person for one or more CEP dossiers (ref. policy document PA/PH/CEP (10) 86).

EDQM’s website is also undergoing a complete revision, aimed to improve the user experience and to ensure a quick and easy access to all relevant information. The new version of the site will be accessible from the same web address www.edqm.eu and is expected to be online in April 2022.  


Revision of the PIC/S GMP Guide: Annex 13 and Annex 16

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by Giuliana Miglierini

The entry into force of EU Regulation 536/2014 “Clinical trials”, at the end of January, resulted in the parallel updating of some international guidelines. In particular, a new version of the GMP Guide PE016 was published by PIC/S (Pharmaceutical Inspection Co-operation Scheme) on 1st February 2022. The revision included Annex 13 on the manufacturing of Investigational Medicinal Products (IMPs), and the new Annex 16 on the certification and batch release to be performed by Authorised Persons (AP) (click here to access all PIC/S guidance related to GMP). The revision of PIC/s guidelines is aimed to reflect the last changes occurred in the corresponding EMA documents, so to maintain the alignment between the two regulatory references (as established by the cooperation agreement between EMA and PIC/S). PIC/S has invited all non- EEA Participating Authorities and applicants to transpose the new Annexes 13 and 16 into their own GMP Guides.

The new Annex 16

Annex 16 represents a completely new addition to the PIC/S GMP guide; the EU Annex 16 (part of the EU GMP Guide) was initially considered to be too EU-specific and difficult to transpose for PIC/S purposes. Following a consultation in 2017, PIC/S Participating Authorities agreed to make an attempt to transpose EU Annex 16, as the adaptation may support a better harmonisation of GMP standards at the international level.

Annex 16 refers to both human and veterinary medicinal products which are subject to the PIC/S Participating Authority or are made for export. Furthermore, the Annex applies to investigational medicinal products for human use, “subject to any difference in the legal provisions and more specific guidance published by PIC/S Participating Authorities under national law”. With reference to imported medicinal products, each PIC/S Participating Authority may independently and voluntary decide whether to adopt the guidance as a legally-binding standard.

Certain types of medicinal products (e.g. blood and immunological products) are not addressed by the Annex, as they are regulated by national laws and fall under the competences of National authorities; to this instance, Annex 16 applies to the certification process performed by the AP and to the subsequent release of the batches.

The marketing authorisation holder (MAH) remains the sole responsible for the safety, quality and efficacy of the marketed products. Authorised Persons are required to check each single batch to verify compliance to national and GMP requirements, as well as to those detailed within the marketing authorisation (MA). After certification by the AP, batches of finished products can be transferred to saleable stock and/or export. Specific and documented agreements are needed should this require transfer to a site different from the certification’s one. Authorised Persons should be clearly identifiable, with reference to any quality defect leading to investigation or batch recall. APs certifying the release of the finished product are responsible for verifying the conditions of storage and transport for the batch and the sample, if sent separately, and of all testing required upon importation (including sampling, where needed).

A formal Quality Risk Management (QRM) process is required when sampling is performed at a manufacturing site located in another jurisdiction; Annex 16 provides detailed guidance on the elements to be considered in this exercise. Documentation of the continuous training received by the AP in charge of certification and batch release should be always available, with specific reference to the product type, production processes, technical advances and changes to GMP.

Annex 16 provides detailed guidance on how to conduct the process of certification of each batch of finished product, independently of the number of sites involved. With reference to specific manufacturing or control steps performed at different sites, their respective AP has to provide confirmation of the performed activities, sharing responsibilities with the AP in charge of the final batch release.

The certification process should take into consideration the entire supply chain of both the active substance and the finished product, including manufacturing sites of the starting and packaging materials. The AP responsible for certification should be able to access results of the audits performed at the sites involved, in order to check the consistency of all activities with those described in the MA and within GMPs. Audits run by third parties should reflect requirements set forth in Chapter 7 of the PIC/S GMP Guide.

In particular, suppliers of active substances should comply with GMP and GDP requirements relating to the supply of the active ingredient used to the finished product manufacturing. Excipients should also fulfil GMP requirements, and be possibly manufactured and supplied in accordance with the PI 045-1 guideline. Specific guidance may also apply for other types of products, i.e. biological active substances and medicinal products for human use or radiopharmaceuticals. Annex 16 provides templates for the confirmation letters to be used for the partial manufacturing of a medicinal product and for the content of Batch Certificates.

The revision of Annex 13

Annex 13 has been revised in order to reflect the contents of the new EU Regulation n. 536/2014 on clinical trials, which will replace EU Annex 13. PIC/S Annex 13 discusses the manufacturing of Investigational Medicinal Products (IMP), apart from the reconstitution phase, which is not considered to be part of the process. Provisions set forth by Annex 13 should be taken into consideration with reference to the re-labelling or re-packaging of IMPs and to the preparation of radiopharmaceuticals used as diagnostic investigational medicinal products, occurring in hospitals, health centres or clinics and performed by pharmacists or other persons legally authorised in the country concerned.

All activities should refer to an appropriate Pharmaceutical Quality System to be in place, according to requirements set forth in Chapter 1 of Part 1 of the PIC/S GMP Guide.

 The characteristics of IMPs may intrinsically evolve along the development process, as new data become available that may require changes to, for example, the formulation or the dosage form. This has to be reflected into the respective product specifications and manufacturing instructions, that should also evolve in parallel and be fully traceable and documented. Annex 13 indicates that all deviations should be registered and investigated, and preventive and corrective actions put in place. The new Annex provides detailed guidance on the different items to be considered within the product specification file, as well as for the proper management of personnel, premises and equipment.

All the documentation generated during the clinical development phases should fulfil requirements specified by the PIC/S GMP Guide, Part I, Chapter 4. To this instance, relevant documentation includes specifications and instructions, orders, manufacturing formulae and processing instructions, packaging instructions and batch records. Detailed guidance is provided also for production, including packaging materials and manufacturing operations, the modification of comparator products, blinding operations, and the packaging and labelling of the IMP. Annex 13 also offers guidance on how to perform quality control and batch release, and how to address outsourced operations, complaints and recalls and or the destruction of batches of IMP products.


ACT EU: the EU’s vision for the future of clinical trials

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by Giuliana Miglierini

Just few days before the entry into force of the new Clinical Trials Regulation and of the Clinical Trials Information System (CTIS) on 31 January 2022, a new initiative has been announced to completely renew the European framework governing how clinical trials are designed and run. The strategic document ACT EU (Accelerating Clinical Trials in the EU) has been jointly developed by the European Commission, the European Medicines Agency (EMA), the Heads of Medicines Agencies (HMA) and national regulators with the aim to strengthen the European Union as a leading “focal point” for clinical research at the international level.

ACT EU shall support the achievement of the goals established by the European Pharmaceutical Strategy and the European medicines agencies network strategy (EMANS) to 2025. The initiative will be co-led by the European Commission, EMA and HMA; the proposed governance shall find inspiration on the model already in use by the Clinical Trials Information System, with an EUCTR Coordination Group with an adapted mandate and composition. The individual domains which form the overall matrix will be coordinated by the relevant functions available within the network. The formal public communication phase on ACT EU will start after the official endorsement of the initiative by HMA and EMA.

Six objectives and ten priorities of action for 2022-2023

The ACT EU strategy identifies six different goals for the future of European clinical research. Its leading role shall be optimised through a unified European position on clinical trials at the international level, a better ethical oversight and integration of ethics committees into the clinical trial and medicines regulatory lifecycle. Large-scale multinational clinical trials with broader geographical scope shall be incentivised, while reducing the administrative burden for sponsors and investigators.

A special attention will be paid to the generation of decisional evidence for unmet medical needs, rare diseases, and on vaccines and therapeutics for public health crises and pandemics. A truly high level and coordinated scientific advice is indicated as an important element in order to support the trial and marketing authorisation processes. The strategy confirms the need to adopt new patient-oriented medicines development and delivery models with pro-active engagement of all the stakeholders. The availability of an improved capacity both at the development and regulatory level is also deemed important to achieve the goals of the initiative.

These challenging objectives shall be pursued in years 2022-2023 through the activation of a set of ten specific priority lines of action. An initial exercise to map already existing initiatives within the European medicines regulatory network (EMRN) will be run, that will represent the basis for the consequent development of a governance rationalisation strategy. This might include, for example, the alignment of different expert groups and working parties in the EMRN and ethics infrastructure.

The smooth implementation of the Clinical Trials Regulation shall be monitored using a set of Key Performance Indicators (KPI), still to be developed; the modernisation of the good clinical practices (GCPs) should occur under specific ICH’s guidance. The attractiveness of Europe for larger, multinational trials should specifically address studies run in the academic setting. Furthermore, the academics and non-profit organisations may also play a leading role in the analysis of data arising from clinical trials.

Further actions will include the availability of a multi-stakeholder platform, including patients, and the engagement in the initiative of all enablers by mean of a targeted communication campaign. A tighter coordination of different aspects relevant to the planning of new clinical trials, i.e. the scientific advice on the trial approval and the design of the study, has been also announced. The increasing use of artificial intelligence and/or machine learning technologies in the clinical domain and issues pertaining complex and decentralised trials, as well as the interface between the In Vitro Diagnostics Regulation (IVDR) and the Clinical Trials Regulation will benefit of new targeted methodological guidelines.

As for safety monitoring of clinical trials, the priority is to start its integration into a pre- and post-marketing safety monitoring framework. At the educational level, the competences needed to face this challenging scenario for the future of clinical trials in the EU will require the activation of specific training curricula, inclusive of modules on drug development and regulatory science with links to universities and SMEs.

Four principles to guide all actions

The complexity of the ACT EU initiative will require also the development of a new approach to make available the resources needed to smoothly run all the planned activities, possibly including the exploitation of the expertise external to the European medicines regulatory network. The strategy indicates the intention to adopt a collaborative and integrative approach, so to achieve a large research impact in the EU.

To this instance, the four principles “Do, Require, Influence, Support” have been identified to guide the execution and coordination of the projects, the requirement of specific guidance to address the expectations on applicants/developers/researchers, the availability of key publications and leadership to support the transformation phase at all levels (including patient, the academic, etc.), and stakeholders interactions suited to support all the above mentioned objectives.

The initial mapping of existing activities should also led to the identification of the budget needed for meetings, inclusive also of the activities relative to stakeholder engagement, training, and communication. Any other activities falling outside the optimisation of the already existing ones would be self-funded by the respective organisations (EC/NCA/EMA).

Comments from EFPIA

According to EFPIA, the announcement of ACT EU represents the beginning of an exciting new phase for clinical research in Europe. The industrial association highlights that the innovative design of many clinical trials, especially the complex ones, requires an increased efficiency.



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.


Draft Guideline on the acceptability of names for human medicinal products

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The scope of this guideline is to provide information on the overall procedure for submitting and reviewing the acceptability of proposed (invented) names for human medicinal products processed through the centralised procedure, as well as detailed guidance on the criteria applied by the Name Review Group (NRG) when reviewing the acceptability of names. The main aim is to promote patient safety as an essential principle.

Based on the experience gathered by the NRG since the last revision of the guideline in May 2014, it became apparent that some areas of the guideline would benefit from further clarifications, in particular with regards to the requirements for acceptability of proposed (invented)1 names of medicinal products processed through the centralised procedure.

This 7th update of the guideline further clarifies specific aspects of the criteria applied to address safety and public health concerns, international non-proprietary names issues and product-specific concerns in proposed (invented) names. This update also provides further information on the conditional acceptability of invented names and the process for bilateral negotiations and proposes changes to the duration of the validity of an (invented) name and the review process of the NRG.

Consultation dates: 16/12/2021 to 16/03/2022

Reference number: EMA/CHMP/287710/2014 Rev. 7


EMA’s OMS has turned mandatory for centrally authorised products

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by Giuliana Miglierini

Since November 1st, 2021, the use of the Organisation Management Service (OMS) became mandatory for all Centrally Authorised Products (CAPs). The European Medicines Agency (EMA) has published a Questions & Answers document to better explain the new procedures, that will impact the source of data to be used to exactly identify the organisations filing CAP procedures with EMA.

The progression in the implementation of the new provisions

The use of the OMS system is now compulsory for all organisations filing CAP submissions, with the final goal to improve the interoperability of data and the overall efficiency of the regulatory process. Should applicants lack to use OMS data, the relevant applications will be filtered out of the EMA’a validation procedure and sent back to the applicant for remedial action.

The OMS data management service was launched in 2015, and applied to electronic application forms (eAFs) since 2017, and then to many other types of procedures. The availability of OMS data may prove critical to allow the smooth implementation, in early 2022, of the new Clinical Trial Information System (CTIS) and of the Clinical Trial application procedure; during the next year, EMA plans to integrate the OMS also with the Union Product Database (UPD), Variation applications (via DADI project) and Manufacturing/Importers Authorisations (MIAs), Good Manufacturing Practice (GMP) inspections and Wholesale distribution authorisations (via EudraGMDP).

Validated OMS data also need to be used with reference to the “applicant” and “contact person affiliated organisation” sections of pre-submission applications. With the new eAF release (eAF V.1.25.0.0) for Medical Devices, the compulsory use of OMS data will also refer to the “Device Manufacturer”, “Notified Body” and “Companion diagnostic” sections.

Remediation in case of lack to use OMS data includes the insertion of all relevant information in the OMS database before updating and re-submitting the application form. Should applicants not provide sufficient responses, the application may be completely or partially invalidated.

Discussions are undergoing to further extend the use of OMS data also to National Procedures (NP); according to EMA, this may be turn inevitable in the next couple of years, as current eAF forms will be progressively replaced by web-based application forms (through the DADI project), being the latter the same for centrally and nationally authorised products by design.

Any question on the use of the OMS can be sent to EMA’s e-mail addresses specified in the Q&As document.

What is new for applicants

The use of OMS master data (the so-called “OMS Dictionary”) is now mandatory for both Human and Veterinary centralised procedures, namely those making use of eAFs (initial marketing authorization applications, variations applications, and renewals) and well as other procedures (see the Q&A document for more detail). The name and contact details of the contact person are not OMS data, and do not need to be registered with the system; historical organisational data do not have to be registered as well.

To manage a CAP procedure, applicants now need to first register their organisation data with the OMS, or request the update of data already registered by submitting a “Change Request” before filing of the regulatory application.

All requests will be assessed by EMA OMS Data stewards, that will also update data in the systems if the requirements are met. This validation step is fundamental to avoid duplication of data, as all information is checked against the same reference sources (i.e. national business registry, DUNS and/or GMP/MIA certificates) and standardised according to the OMS rules agreed with the Network. The Service Level Agreement provide for EMA to process 75% of OMS requests within five working days and 90% within ten working days. Changes will become visible in the eAF the day after they had been processed, and only upon active refresh of the relevant lists.

The business process which makes use of OMS data is usually responsible to submit such a request, but it can arise also form other parties. More specifically, EMA advises the user who needs to use the data should take the lead in updating it. This may prove relevant, for example, to ensure all manufacturer organisations are included in the OMS Dictionary as needed.

EMA warns applicants to consider the turnaround time for processing the OMS change request when planning to submit applications: even if the application forms will not immediately change and everything may appear as usual, the background process has been now modified and may need additional activities to validate the change requests.

Changes in the eAF templates are planned to remove the free text fields for CAP applications, but until the new models will be available, the free text field for “organisations” should not be used. Planned availability and entry into force of the new versions are December 2021 for Human procedures (v1.26.0.0) and January 28th, 2022 for Veterinary procedures (in line with the veterinary regulation).

How to access the OMS

EMA’s data management system refers to four different domains of data, including the substance, the product, the organisation and referential (SPOR) master data in pharmaceutical regulatory processes.

The SPOR portal provides access to the respective four specific areas of service (e.g. SMS for substances, PMS for products, OMS for organisations and RMS for referential). SPOR is the mechanism used by EMA to implement the ISO IDMP standards, as required by articles 25 and 26 of the Commission Implementing Regulation (EU) No. 520/2012. Organisation master data, even if not covered by ISO IDMP, have been considered by EMA, National Competent Authorities and Industry in Europe to be essential in order to make the master data operating model work.

Applicants need to create an EMA account with SPOR user roles to conduct additional tasks, such as requesting changes to data, translating data or managing user preferences. Already granted credentials to access other active accounts for any EMA-hosted website or online application can also be used. OMS data can now no longer be captured in other EMA databases.

OMS master data include the organisation name and address, labelled by mean of unique identities (ID) (i.e. ‘Organisation_ID’ and ‘Location_ID’). Different categories of organisations are possible (i.e. ‘Industry’, ‘Regulatory Authority’ or ‘Educational Institution’), and of different size (i.e. ‘Micro’, ‘Small’, or ‘Medium’). The role played by a certain organisation is context-specific and cannot be defined within the OMS.