The Windsor Framework changed the regulation of medicinal products that were formerly in the scope of the EU centralised procedure so that these products are now licensed UK-wide under UK law.
Products not within this scope are authorised UK-wide under UK and applicable EU law (as amended by Regulation (EU) 2023/1182 and Directive (EU) 2022/642), as has been the case since 1 January 2021.
As a result, UK authorised products are now placed into one of two Categories:
Category 1 are UK products which fall under the mandatory or optional scope of the EU Centrally Authorised Procedure.
Category 2 are UK products which do not fall within the scope of Category 1 will be Category 2 products.
To assist MAHs in verifying the category of each of their products, a decision ladder has been created by the MHRA. The MHRA has also publish lists of Category 1 products and Category 2 products.
Which category your product falls under, will decide the pharmacovigilance requirements of that product.
Category 1 will be subject to UK legislation only. These products will legally be required to follow Part 11 of the HMRs for pharmacovigilance.
Category 2 will be subject to UK and EU requirements as applicable. These products will be legally required to follow Part 11 of the HMRs for pharmacovigilance with further pharmacovigilance requirements outlined in Schedule 12A of the HMRs.
However, it should be note that all existing exemptions that apply to all UK medicines remain in place irrespective of Category.
The Risk Management Plan (RMP) documents the risk management system considered necessary to identify, characterise and minimise a medicinal product’s important risks.
The RMP should be updated throughout the life cycle of the product, for example;
if there is a change in the list of the safety concerns
when there is a significant change in the existing additional pharmacovigilance activities
if an emerging safety issue is confirmed.
The RMP should be assigned a new RMP version number and a date each time it is updated and submitted for assessment.
An updated RMP can be submitted as a standalone [currently C.I.11] variation, when necessary, but it is most often submitted as a consequence of or part of another variation.
The format and content of the RMP should follow the RMP template; Guidance on the format of the risk management plan (RMP) in the EU – in integrated format which consists of seven parts.
For a generic medicinal product, hybrid products and/or fixed combination products with no new active substance the safety concerns should be aligned to those of the originator product that are available;
either from the originator’s approved RMP
or from the list of safety concerns of the substance published on the CMDh website.
RMPs are approved per each medicinal product, not per MAH, therefore only one RMP should be submitted for an MRP or DCP with different MAHs. The RMP must remain identical in RMS/all CMS throughout the product life cycle.
The RMP should be provided in eCTD section 1.8.2. To facilitate the assessment a ‘tracked changes’ version of the RMP, in Microsoft word, should also be provided in the ‘working-documents’ folder outside eCTD.
The QPPV’s actual signature or the evidence that the RMP was reviewed and approved by the QPPV should be included in the finalised approved version of the document; for eCTD submissions this would be the RMP submitted with the last eCTD sequence of the procedure (usually the closing sequence).
Feel free to contact us here at ERA to assist you with all things regulatory in Ireland, UK and across the EU.
We take the pain out of regulatory so that you can take your medicine to the next level.
Written by
Fiona Downey
Fiona Downey 1
https://eureg.ie/wp-content/uploads/2014/08/pharma-vigilance.jpg262228ERAadministratorhttps://eureg.ie/wp-content/uploads/2023/10/European-Regulatory-Affairs-Logo.svgERAadministrator2024-07-19 09:53:292024-07-19 09:53:29Back to Basics – The Risk Management Plan (RMP)
The electronic application forms (eAFs) we are familiar with are in the process of being replaced later this year by a web based digital application form in a new eAF portal. The new eAF portal will look somewhat similar to the current IRIS portal.
This project, known as DADI (Digital Application Dataset Integration), is intended to be used for both CAP (Centrally Authorised Products) & NAP (Nationally Authorised Products) applications to make the future of form-filling and submission-handling more efficient at an EU level.
The Human medicinal product Variation application form will be the first to go live in DADI format. Every person involved in drafting an eAF will need to have an EMA account and user access. Companies who use consultants to prepare eAFs will need to make sure that they assign an EMA role to the consultant.
The next stages of DADI will cover the
Veterinary variation application form
Initial MAA form for Human and Veterinary products
Renewal form for Human and Veterinary products
How will it work?
The eAF will be filled in using the new eAF portal (via user interface).
The user will then finalise the eAF by generating a PDF rendition
This PDF version must still be included in the eCTD submission, as before.
It will not be possible to submit the form directly from the eAF portal
When will it happen?
As outlined in the EMA roadmap (link provided below) the two immediate key deliverables are as follows:
Key deliverables
Go-Live Time Lines
Year
Quarter
Launch of Human variations web-form (parallel use of old and new variation forms as part of a Transition period)
2022
Q4 (October)
Use of variation web form only
2023
Q2 (April)
It is important for all industry stake-holders to keep up to date with the development of these new web-based forms by consulting the EMA website for updates at the various launch stages.
Where can I find information?
DADI Network Project Webinar – 18/01/2022 – Live broadcast is availablehere.
The updated DADI roadmap, including key milestones, is available here.
The updated version of the DADI Questions and Answers documents is available here.
The “Common factors in the Fast Healthcare Interoperability Resources (FHIR) data standard for Art57(2) and eAF”documents are available in the following link.
The project will be implemented in phases, through a set of projects known as SPOR (Substances, Products, Organisations and Referentials) data management services for Human products. The Union Product Database will be the source of data for Veterinary products.
What is SPOR?
SPOR datasets
Description of data types
Status
Substance Management Services (SMS)
Harmonised data and definitions to uniquely identify the ingredients and materials that constitute a medicinal product.
Under Development
Product Management Services (PMS)
Harmonised data and definitions to uniquely identify a medicinal product based on regulated information (e.g. marketing authorisation, packaging and medicinal information).
Under Development
Organisations Management Services (OMS)
Data comprising organisation name and location address, for organisations such as marketing authorisation holders, sponsors, regulatory authorities and manufacturers.
Operational
Referentials Management Services (RMS)
List of terms (controlled vocabularies) to describe attributes of products, e.g. lists of dosage forms, units of measurement and routes of administration.
Operational
Once the above PMS and SMS are in place, pharmaceutical companies should start preparing to replace their current data submission format in Article 57 Database from the eXtended EudraVigilance Product Report Message (XEVPRM) format to the new ISO IDMP compatible format (HL7 FHIR). Webinars and training will be provided by EMA in due course.
What do Marketing Authorisation Holders have to do at this stage?
Marketing authorisation holders need to check their data in SPOR (OMS) to ensure it is accurate and up to date. For CAPs the use of OMS data in the current eAF is already mandatory.
Marketing authorisation holders with authorised MA(s) need to check their data in Article 57 database (xEVMPD) to ensure it is accurate and up to date.
Should you need any support at this stage in getting ready for the new Application Form format please feel free to contact us & the Ivowen team will be here to help.
Written by Marian Winder
https://eureg.ie/wp-content/uploads/2021/02/Changing-medicine-24-02-21.jpg160240ERAadministratorhttps://eureg.ie/wp-content/uploads/2023/10/European-Regulatory-Affairs-Logo.svgERAadministrator2022-03-15 11:41:452023-11-06 11:18:19When will DADI application forms replace the current eAFs?
The UK has left the EU and the transition period after Brexit comes to an end this year.
The MHRA have issued new guidance for industry and organisations effective from 01st January 2021. From this date the MHRA will be the UK’s standalone medicines and medical devices regulator.
Areas covered in the new guidance include:
Clinical Trials
From 1 January 2021, for registering clinical trials, existing and established international registers will still be used, such as ISRCTN registry (UK), or ClinicalTrials.gov (USA), to ensure the public is aware of your trial. For trials involving both UK and EU sites a record in the EU Clinical Trials Register will exist (other than adult Phase 1 studies). In the UK, any favourable opinion given by a research ethics committee is subject to the condition that the clinical trial is registered on a publicly accessible database. The time frame for publishing the summary of results is within 6 months of the end of trial for paediatric clinical trials or within one year of the end of trial for non-paediatric clinical trials. You do not need to submit this clinical trial summary report to the MHRA as well; however, you must send a short confirmatory email to CT.Submission@mhra.gov.uk once the result-related information has been uploaded to the public register and provide a link.
Pharmacovigilance
Guidance on qualified person responsible for pharmacovigilance (QPPV) including pharmacovigilance system master files (PSMF) from 1 January 2021
From 1 January 2021, the following legal obligations will apply to holders of UK marketing authorisations (MA). These include those that cover the whole of the UK, or are specific to Northern Ireland or to Great Britain (England, Wales and Scotland):
To operate a pharmacovigilance system for UK authorised products.
To have an appropriately qualified person responsible for pharmacovigilance (QPPV) that resides and operates in the EU or the UK and is responsible for the establishment and maintenance of the pharmacovigilance system for UK authorised products.
To maintain and make available upon request a pharmacovigilance system master file (PSMF) that describes the pharmacovigilance system for UK authorised products. The PSMF must be accessible electronically or physically from the UK at the same site at which reports of suspected adverse reaction may be accessed.
Statutory guidance concerning the QPPV for UK authorised products is described in the Good Pharmacovigilance Practices (GVP) Module I. This guidance will be supplemented by the ‘Exceptions and modifications to the EU guidance on good pharmacovigilance practices that apply to UK marketing authorisation holders’, which will be published in due course.
New guidelines have been outlined for Marketing Authorisations, to include Conditional MAs, registering new packaging information, guidance on the handling of applications for Centrally Authorised Products (CAPs), Article 29 applications, converting parallel distribution notices to UK parallel import licences, handling of ASMFs and CoS from January 2021, reference medicinal products, converting CAPs to UK MAs, guidance on licencing biosimilars, bioequivalence/therapeutic equivalence studies and renewing marketing authorisations.
New Submission Registrations
For planned applications for submission to the UK (for example, a Marketing Authorisation for the UK market), you will need to submit the information through the MHRA national portals.
All current Eudravigilance Gateway users who wish to gain access to the new MHRA Gateway will need to first gain access to MHRA Submissions. The steps for gaining MHRA Gateway access are contained within MHRA Submissions. MHRA Submissions will not be used to send or receive ICSRs.
If you need any clarification or support to help you to navigate the end of transition period please contact us and Ivowen will gladly assist you in a timely manner.
Written by Mary Canning
https://eureg.ie/wp-content/uploads/2020/07/Brexit-clock-image-22-07-20.jpg422750ERAadministratorhttps://eureg.ie/wp-content/uploads/2023/10/European-Regulatory-Affairs-Logo.svgERAadministrator2020-11-06 12:15:002023-11-06 11:15:33BREXIT – MHRA post-transition period information
In response to the significant impact the COVID-19 pandemic is having on European regulatory activity, the European Commission, the European Medicines Agency and the Heads of Medicines Agencies network (EC, EMA and HMA, respectively) have approved a number of measures to help the management of marketing authorisations for human medicinal products considered crucial during the pandemic period.
The objective of these measures agreed at European level is to promote regulatory flexibility, facilitate, simplify and accelerate the administrative procedures, as far as possible, in order to respond more efficiently to emerging needs during this period.
As a result, the EC recently published questions and answers on regulatory expectations for medicinal products for human use during the COVID-19 pandemic:
This Q & A document which provides guidance to marketing authorisation holders (MAH) includes the following topics:
renewal applications
sunset clause
an exceptional change management process (ECMP) for crucial medicines for use in COVID-19 patients
circumstances under which the validity GMP certificates and authorisations to manufacture/import can be extended
circumstances under which the validity GDP certificates and wholesale authorisations can be extended
adaptions to the work of a Qualified Person (QP)
the possibility of adapting quality requirements for medicines intended to be used for the treatment of COVID-19 patients
the impact on reporting into EudraVigilance of Individual Case Safety Reports (ICSRs)
flexibility in the labelling and packaging requirements to facilitate the movement of medicinal products within the EU
Further to the European Commission’s Q&A document, the CMDh has agreed additional questions and answers that provide practical information on how to specifically address and apply the provisions determined by the European Commission for MR/DC procedures:
The CMDh document addresses issues such as the impact of COVID-19 on assessment timelines, how to use the ECMP procedure (which is only applicable for products that are crucial for the treatment of COVID-19 patients) and QP declarations based on a desktop audits. It also includes a useful annex that details Member States’ email addresses and links to relevant published guidance on MS websites.
Both documents will be updated and supplemented with additional information, as appropriate during the pandemic.
Everyone at Ivowen is working tirelessly to keep our clients applications on track. We are liaising with the National Competent Authorities all the time to ensure we avoid delays and get the best results possible in these unprecedented times.
If you need any assistance in this regard please don’t hesitate to contact us.
Written by Claire Brown.
https://eureg.ie/wp-content/uploads/2020/05/Corona-virus-image-11-05-20-1.jpg405720ERAadministratorhttps://eureg.ie/wp-content/uploads/2023/10/European-Regulatory-Affairs-Logo.svgERAadministrator2020-05-11 16:24:572023-11-06 11:15:46European Procedural Guidance during COVID-19 Pandemic
The European Medicines Agency (EMA) has recently published an overview of pharmacovigilance activities that outlines just how strong and reliable a system we have in the EU. The report was prepared by EMA in collaboration with the National Competent Authorities (NCA). The report includes quantitative data covering the period between 2015 and 2018 and shows that the European regulatory network for medicines is held accountable for the implementation of the pharmacovigilance legislation.
It shows that the EU pharmacovigilance system is strong and protects public health.
Some key outcomes 2015-2018
More than 500 new or updated risk management plans were assessed by the PRAC each year, ensuring the safety monitoring and risk minimisation is proportionate and planned. In addition, nearly 7,000 risk management plans were assessed by the Member States for nationally authorised medicines during the reporting period.
Enhanced EudraVigilance database of suspected side effects, resulting in improved reporting and greater analytical power;
Evaluation of nearly 9,000 potential signals (information about new or changing safety issues potentially caused by a medicine) by EMA’s signal management team over the period covered by the report, and a similar number of potential signals assessed by Member States;
Radical simplification and improvement of the way periodic safety update reports are handled, by establishing a common repository with a single portal for access;
Continued development of the ‘Article 57 database’, which now contains information on more than 800,000 medicinal products authorised through central, decentralised, mutual recognition and national procedures across the European Economic Area.
For more details on the report please refer to EMA web page where you can access the press release issued.
The pharmacovigilance legislation established now reinforces the need for and format of various reports, including:
Risk Management Plans (RMP);
Periodic Safety Update Reports (PSUR);
Post-Authorisation Safety and efficacy Studies (PASS);
Pharmacovigilance System Master Files (PSMF).
Should you require assistance with respect to setting up a pharmacovigilance system, or the preparation and submission of pharmacovigilance related data we encourage you to contact us.
Written by Alice D’Alton.
https://eureg.ie/wp-content/uploads/2020/04/PV-image-23-04-20.jpg406594ERAadministratorhttps://eureg.ie/wp-content/uploads/2023/10/European-Regulatory-Affairs-Logo.svgERAadministrator2020-04-23 10:14:042023-11-06 11:15:47Pharmacovigilance most of all
The United Kingdom has formally left the EU as of 31 January 2020 and has become what is referred to as a third country.
On 1 February 2020 a transition period started which is due to end on 31 December 2020.
During the transition period, EU pharmaceutical law will continue to be applicable to the UK, meaning that pharmaceutical companies can continue to carry out activities in the UK until the end of 2020.
Companies have until 31 December 2020 to make the necessary changes to ensure that their authorised medicines comply with EU law and can remain on the EU market.
The UK will remain on CESP for the duration of transition period (after that, if no further extension to the transition period is proposed, it will be necessary to use the MHRA portal for submissions https://pclportal.mhra.gov.uk/)
Marketing authorisation holders and applicants can still be established in the UK in 2020
Qualified Persons for Pharmacovigilance (QPPVs) and pharmacovigilance system master files (PSMFs) can still be based in the UK until the end of 2020.
Manufacturing sites, Quality control testing and Batch release sites can also still be based in the UK until the end of 2020
orphan designation holders can still be located in the UK until 31 December 2020
minor use/minor species (MUMS)/limited markets classification holders can still be located in the UK until 31 December 2020
The withdrawal agreement foresees that following its departure from the EU on 31 January 2020, the UK will no longer participate in EU institutions and their decision-making. For the CMDh this means that as of 1 February 2020, no one who represents the UK, or is appointed or nominated by the UK can systemically participate in the CMDh meetings.
During the transition period, the UK will not be able to act as RMS in MRP/DCP, but the UK can participate in MRP/DCP as CMS.
Ivowen are here to assist you with all your Brexit related needs and dossier amendments.
For more information on Ivowen’s services and how we can help you, contact us.
Written by Alice D’Alton
https://eureg.ie/wp-content/uploads/2023/10/European-Regulatory-Affairs-Logo.svg00ERAadministratorhttps://eureg.ie/wp-content/uploads/2023/10/European-Regulatory-Affairs-Logo.svgERAadministrator2020-02-10 11:40:492023-11-06 11:08:32BREXIT – EVERYTHING stays the same for 2020
Ivowen attended the Medicines for Europe conference in January (Regulatory and Pharmacovigilance), the annual EuDRAcon conference in May, exhibited at TOPRA in October and joined our clients from around the world at CPhI in November.
We all saw Brexit come and go, Twice !! We wait to see what lies in store for the next deadline in January 2020.
The FMD came into effect across Europe in February in most member states.
Bulgaria joined CESP, eCTD became mandatory for all human procedures, lots of new guidance was published (to keep us all on our toes) and Nitrosamines in medicinal products moved to the top of everyone’s agenda.
With the festive season now upon us and 2020 on the horizon, Ivowen are setting our sights on the year ahead.
We will be attending the Medicines for Europe conference in January 2020 (Regulatory and Pharmacovigilance) and we encourage you to contact us before mid-January with any specific questions you might like us to ‘ask the regulators’. This is a great opportunity to ask those difficult questions that you just could not get a straight answer to in 2019, on the ever present grey areas of Regulatory procedures.
To help you to plan ahead here are some helpful updates, in brief, as full articles will be posted in 2020:
Falsified Medicines Directive – Where we are now:
Implemented on 9th Feb 2019 in all MS except Greece, Italy and Belgium
The European Commission has produced a video to explain more about the safety features.
The HPRA have extended the use and learn period, initially to Sep 2019 and extended it again to end on a phased basis starting from 31st January 2020.
The MHRA is also taking a pragmatic, flexible approach to how they enforce the new legal requirements.
Nitrosamines
Step 1: MAHs should conduct a risk evaluation to identify products at risk of N-nitrosamine formation or (cross-)contamination and report the outcome by 26 March 2020 at the latest.
Ivowen are here to assist you in 2020 and will continue to provide the top quality service you have come to expect from us.
For more information on Ivowen’s services and how we can help you, contact us.
Written by Alice D’Alton.
https://eureg.ie/wp-content/uploads/2019/12/Hot_Air_Baloon.jpg356570ERAadministratorhttps://eureg.ie/wp-content/uploads/2023/10/European-Regulatory-Affairs-Logo.svgERAadministrator2019-12-06 09:52:522023-11-06 11:08:332019 – What a year
Ivowen have provided some practical guidance and documents below, which may help you prepare for Brexit for products authorised by the DCP and MRP procedures.
Do you still need to change your MAH(s) in any of the EU Member States because of Brexit?
If so, refer to the following updated guidance issued in January 2019 which details the documentation and requirements to submit a Marketing Authorisation Holder transfer:
If you need any clarification or support to complete a Marketing Authorisation Holder transfer, Ivowen will gladly assist you in a timely manner. Contact us for more information or to make an enquiry.
Is the UK your current RMS?
If so, you need to initiate an RMS switch as soon as possible. The guidance issued in July 2018 along with the template issued in June 2018 is required to complete this process. This template needs to be completed and sent to a specific e-mail address at the proposed new RMS. The list of contacts points to send the completed template is provided below:
If you need any clarification or support a RMS switch, Ivowen will gladly assist you in a timely manner. Contact us for more information or to make an enquiry.
Do you need to change your UK batch release site, etc., if it currently within the UK?
If so, you can refer to the updated guidance document issued in December 2018, which provides information on the type of variation that is required to change functions such as batch release site(s), QC testing site(s), packaging site(s), deletion of site(s) for batch release and changes to the QP for Pharmacovigilance (QPPV) and PSMF where these functions still reside within the UK:
If you need any clarification or support to complete variations to support changes needed as a result of Brexit, Ivowen will gladly assist you in a timely manner. Contact us for more information or to make an enquiry.
Do you supply product to Cyprus?
If so, the Cypriot Competent Authority has issued a newsletter to Stakeholders on the 14 January 2019 which lists 105 products authorised via an exceptional marketing authorisation affected by Brexit which are considered critical. The Drugs Council in Cyprus recommends that pharmaceutical companies register these products via an exceptional marketing authorisation using another reference state other that the UK.
If you need any clarification or support to complete an Exceptional Marketing Authorisation to avoid no supply of these critical products on the Cypriot market, Ivowen will gladly assist you in a timely manner. Contact us for more information or to make an enquiry.
With the festive season upon us and 2019 on the horizon, Ivowen are setting our sights on the year ahead. So what’s going on in 2019 and beyond, including and excluding Brexit…
What’s happening in early 2019?
We will be attending the Medicines for Europe Regulatory and Scientific Affairs and Pharmacovigilance conferences in January and we encourage you to contact us before mid-January with any specific questions you might like us to ‘ask the regulators’.
Brexit follows quickly on the tail of the new year, and we will all be hopefully ready and able for this new challenge. Take our Brexit quiz here to see if you are Brexit ready and contact us to help.
What’s happening in later on in 2019?
We are also looking forward to attending the annual TOPRA symposium this year, hosted in Dublin, and we hope to see you at our stand to discuss how we can assist you with your regulatory needs in 2019 and beyond.
What about us?
Ivowen consists of an amazing team with extensive experience of the pharmaceutical industry. Our aim is to understand our customer’s needs and offer services that meet those needs in a timely and efficient way.
As part of EuDRAcon, a pan European network of regulatory consultants, we can provide expert advice on all matters regulatory for the EU and beyond, including Brexit
We hope that in 2019 Ivowen can help you with your specific and unique requests.
And for now…
The office will be closed from the afternoon of Friday 21st December 2018 until Wednesday 2nd January 2019. Merry Christmas and a Happy New Year for 2019!
For more information on Ivowen’s services and how we can help you, contact us
Written by Mary Canning
https://eureg.ie/wp-content/uploads/2018/12/CHristmas-trees.jpg449800ERAadministratorhttps://eureg.ie/wp-content/uploads/2023/10/European-Regulatory-Affairs-Logo.svgERAadministrator2018-12-04 10:32:102023-11-06 11:15:34To 2019 and beyond (Brexit)…
