Tag Archive for: Regulatory Affairs

Brexit clock image 22 07 20

BREXIT – MHRA post-transition period information

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.

Updated guidance on pharmacovigilance procedures

Detailed guidance on pharmacovigilance procedures from 1 January 2021 is published on the MHRA website: https://www.gov.uk/government/publications/guidance-on-pharmacovigilance-procedures-in-the-event-from-1-january-2021/updated-guidance-on-pharmacovigilance-procedures

 

Marketing Authorisations

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.

A useful webinar on how to gain access to MHRA submissions portal is available on the MHRA website at the following link https://www.gov.uk/government/publications/webinars-preparing-to-make-submissions-to-the-mhra-from-1-january-2021

Within the recent MHRA guidelines, the following areas are also covered:

  • Devices
  • Importing and Exporting
  • IT Systems
  • Paediatrics

IN DEPTH DETAILS ON THE NEW MHRA GUIDANCE CAN BE FOUND ON THE LINK BELOW:-

https://www.gov.uk/government/collections/mhra-post-transition-period-information

 

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

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CESP delivery system updated

The latest CESP system, version 2.0, was officially launched on October 1st 2015 (https://cespportal.hma.eu).

Ivowen has been using this facility regularly and can help to guide you through any aspects that you may be struggling with. There are a few new features which sets it apart from the old version:

  • The delivery file creation, has a new look and layout, with similar drop down menus but in a more user friendly format. The individual member states are now represented by the National Competent Authority logos, as well as their corresponding country flag.
  • The new dashboard feature is easy to find and provides you with real time statistics on what has been uploaded and subsequently delivered.
  • It incorporates a new tracking system which includes the following details:
  1. Delivery Created
  2. Delivery Completed
  3. Data Uploaded
  4. Data Delivered

You will still receive the e-mails confirming delivery, so you can file them.

  • There are also statistics presented in this space (in the form of bar charts) which provide an overview of your CESP activity in 2014 and 2015.
  • You can now also view delivery files which have been created but have not yet been utilised, and these delivery files can now also be re-downloaded but must not be re-used..
  • Furthermore, there is an Integrated delivery file system within CESP, which is very easy to use, but if you wish you can still work with your SFTP (e.g. FileZilla) as before.”

Please contact us if you would like any help with using CESP or have any other inquiries.

Written by Alice D’Alton

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CESP front page

CESP expands in Poland and Greece

Latest news from Poland and Greece for CESP

From 3rd April 2017 it will be possible to submit the following procedures via Common European Submission Portal (CESP) to Poland:

  • Initial Marketing Authorisation Applications (MAAs)
  • Variations
  • Renewals

The submissions may concern national and European procedures (MRP, DCP) both for human and veterinary medicinal products.

 

Also from 3rd April 2017 the following submissions should be transmitted through CESP for Greece:

  • All submissions for Mutual Recognition/Decentralised Procedures (MRP/DCP)
  • national procedures relating to approvals, variations, renewals, PSURs, ASMFs etc., as well as any other documentation should be submitted using CESP.
  • Responses to deficiencies and any other additional information that can be requested from the EOF within the claims of assessment.

 

 

What does this mean for you?

To date in Poland, only submissions concerning initial MAAs were possible via CESP. There are still some national requirements in Poland, however.  All documents that require an original signature can be either submitted

  • in electronic version with a valid electronic signature or
  • must be submitted in parallel to CESP in paper.
  • Documentation once submitted via CESP should be submitted via this channel throughout its whole lifecycle.

For submissions into Greece, additional CD/DVDs are no longer required.  In addition, for each submission, a corresponding reference number will be automatically assigned and will be sent directly to the applicant.

 

Where can I find more information?

Full details are available on the Polish Ministry’s website (in Polish) here.

Full information is for Greece (in Greek) here.

 

We can help…

Ivowen are fully equipped to prepare and submit any applications on your behalf.  Please contact us or our EuDRAcon partners for more information and for support of your dossier compilation or updates.

Written by Majella Ryan

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Falsified Medical Directive (FMD) and updated QRD template released February 2016

Falsified medicines are fake medicines that are designed to mimic real medicines. Due to the increase of falsified medicines on the market the EU has a strong legal framework for licensing, manufacturing and distribution of medicines. In July 2011 DIRECTIVE 2011/62/EU (http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2011:174:0074:0087:EN:PDF ) came into force; this directive aims to prevent falsified medicines entering the legal supply chain and thus reaching patients. One of the Directive’s measures is the introduction of safety features on medicines.

 

Update on Safety Features on Medicines:

On February 9th 2016 the EC published an implementation plan for the introduction of the safety features on the packaging of nationally authorised medicinal products for human use:

http://www.hma.eu/fileadmin/dateien/Human_Medicines/CMD_h_/Falsified_Medicines/CMDh_345_2016_Rev00_02_2016_1.pdf

In conjunction, a Regulation was also published laying down detailed rules for the safety features appearing on the packaging of medicinal products for human use:

http://ec.europa.eu/health/files/eudralex/vol-1/reg_2016_161/reg_2016_161_en.pdf

 

What do you need to do?:

The Delegated Regulation will apply in all European countries from the 9th February 2019 (3 years after its publication). Belgium, Greece and Italy have the option of deferring the application of the rules by an additional period of up to 6 years.

There are two safety features to be placed on the packaging of most prescription medicines and certain non-prescription medicines no later than 9 February 2019.

-1). a unique identifier (a 2-dimension barcode) and

-2). an anti-tampering device (ATD).

 

How does this affect your medicinal products and applications?

 New MAAs submitted from April 2016:

  • QRD:
    • Revised QRD template.
  • Revised dossier sections:
    • In the case of medicinal products where the ATD is placed on the immediate packaging because there is no outer packaging and the ATD affects the container and its closure system(s), applicants are required to include information on the ATD and how the ATD affects the container and its closure system(s) (sections 3.2.P.2.4 and/or 3.2.P.7 of the Notice to Applicants Volume 2B)

 Ongoing MAAs

  • QRD:
    • CHMP opinion in March 2016 advised to comply Revised QRD template
    • CHMP opinion from April 2016 onwards, applicants must comply with the revised QRD template
  • Revised dossier sections:
    • As per new MAAs

 Existing MAs

  • QRD:
    • Revised QRD template within 3 years – Can be implemented in Type IA, Type IB, Type II, Renewals, Line extension etc. where the submission affects the product information (PI). Approval of submissions must be no later than the 9th February 2019. If no regulatory procedure occurs within the required timeframe a notification is requested to be submitted pursuant to article 61(3).
  • Revised dossier sections:
    • If the ATD is placed on the immediate packaging and the ATD affects the container and its closure system(s), applicants are required to submit the appropriate variations to include the information on the ATD and how the ATD affects the container and its closure system(s) (see section B.II.e of the Variation Guidelines).
    • If the ATD does not affect the container and its closure system, or is placed on the outer packaging, no regulatory procedure is necessary. However, if the addition of the ATD has an impact on the readability of the packaging information, MAHs are requested to submit mock-ups as per http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004891.pdf

Medicinal product no longer needs to bear safety features

  • QRD:
    • Regulatory procedure to remove the standard statements regarding the unique identifier and ATD.
  • Revised dossier sections:
    • ATD on immediate packaging: Regulatory procedure to remove the statements regarding the ATD in the dossier. ATD on outer packaging – no regulatory procedure necessary.

Change of Legal Status

  • QRD:
    • Non-prescription to prescription following a MAH switch application: MAH should use the regulatory procedure to comply with the revised QRD and regulations. Non-prescription to prescription following a Commission referral or a PSUR assessment, the Commission Decision will cover, inter alia, the regulatory requirements to implement the safety features.
  • Revised dossier sections:
    • Non-prescription to prescription: MAH should use the regulatory procedure to include the information on the ATD and how the ATD affects the container and its closure system(s)

 

What does the new QRD template now include?

The new QRD template includes the following sections in: Particulars to appear on <the outer packaging> <and> <the Immediate packaging:

  1. UNIQUE IDENTIFIER – 2D BARCODE
  1. UNIQUE IDENTIFIER – HUMAN READABLE DATA

Updated QRD template in track changes is available here:

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2009/12/WC500029823.pdf

 

Are any medicinal products exempt from the above?

Yes, the medicinal products exempt from the above are listed in Annex I of the Regulation located here:

http://ec.europa.eu/health/files/eudralex/vol-1/reg_2016_161/reg_2016_161_en.pdf

 

Are any medicinal products not subject to prescription but that should include the safety features above?

Yes, the medicinal products not subject to prescription that shall bear the safety features, referred to in Article 45(2) are listed in Annex II of the Regulation located here:

http://ec.europa.eu/health/files/eudralex/vol-1/reg_2016_161/reg_2016_161_en.pdf

If you have any queries on the above, if you would like any help with complying with the new regulation or if you have any other queries please contact us .

Written by Emily Fletcher.

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Survey

Finally a survey we can all get behind! Regulatory Fees for Human Medicines

Like me, you probably get survey requests into your Inbox every day.

Like me, you probably ignore most of them.

Don’t ignore this one!

The European Commission is doing a survey on national regulatory fees for human medicines and it is available to everyone here.

Have your say, and encourage the EC and NCAs to move to an invoicing model, rather than an upfront payment with all the associated admin fees and forms.

TOPRA Reg Rapp 12 2015

Ivowen summarise TOPRA Annual Human Medicines Symposium 2015

Alice D’Alton from Ivowen was delighted to be asked to provide a summary of Session 4 at the recent TOPRA Annual Human Medicines Symposium 2015. The full summary is provided in the following link:

SESSION 4: Globalisation of pharmaceutical regulation – What do agencies discuss behind closed doors?

For further information or if you have any questions on the information provided, or any other question, please feel free to contact us.

Written by Alice D’Alton

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Ivowen to attend EGA PV and RA conference – January 2016

Ivowen will be attending the upcoming 9th EGA Pharmacovigliance, and the 15th EGA Regulatory and Scientific Affairs Conference in London from from 27th-29th January. Please contact us if you would like to arrange a meeting.

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Onwards and upwards at Ivowen

alice-dalton

I am delighted to announce the promotion of Alice D’Alton to the role of Regulatory Affairs and Business Manager.

Alice has been an integral part of the team here in Ivowen for over three years and has more than 10 years experience working in the pharmaceutical industry.

This new role within Ivowen will facilitate the evolving requirements of our growing business. We envisage an expansion of our services in the coming years, continued excellence in project management and ensuring our commitment to maintaining the highest levels of quality you have come to expect from us.

I am also delighted to welcome the newest members to our team; Nanda, Emily and Rishi. They will enhance our ability to guide you through regulatory strategy, dossier preparation, MA submissions through to national phase, post-approval variations, product development, quality overviews, medical devices and much more.

Please contact us for further information.

Published by Majella Ryan

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eSub roadmap eAF 02 2016 1

Points to note on the eAF

General

The eAF is mandatory for all procedures from 01/01/2016 (CP, MR, DC, National in eCTD/NeeS/Paper). However, Presubmission Meeting Requests, Article 61(3) & MAT forms remain the outside scope and can be submitted as paper or PDFs.

Please contact us if you require any assistance with any of the forms or any advice on any of the above procedures. For your convenience, the following is a summary of the important aspects of using the eAF.

  • Always check the e-submission website for the latest version of the eAF (http://esubmission.ema.europa.eu/eaf/)
    • Word versions will be removed from Notice to Applicants in January 2016
    • After 11/01/2016 only version 1.19 will be acceptable for new procedures
    • eAF should be printed for Paper submissions
    • Version 1.20 is planned for April 2016 (unless hotfixes are required before then)
    • It is important to note, and welcome news, that there is no need to update to a newer version of the eAF in the middle of a procedure
    • See the guidelines (update planned in January 2016) and release notes (lists the changes made to newer versions) for further information
    • In line with the proposed move towards a Single Submission Portal (SSP) in place of CESP and the EMA Gateway, there are plans to reformat the eAF into a data capture system that can be submitted directly through CESP. This is in a very preliminary stage.
  • Technical queries should be sent to EMA Service Desk via IT service portal (login)
    • Q&A documents should be consulted first
    • Fast web view warning in the dossier validation report for the eAF can be ignored
  • Procedural queries should be directed to the National Competent Authority (NCA) (and response sent to EMA Service Desk). Complicated queries should be sent to both parties.
  • Webinars are available for the NCAs (to try to reduce the requests for MS specific national requirements)

 

Using the eAF

  • Technical Validation of the form (internal):
    • Once signature is added and form validated, it is now locked. Locked forms cannot be amended. Therefore, the signature should be the last thing added to the form.
    • Always keep a copy of the unlocked form so that amendments can be made (e.g. during preparation or for requests from NCA for updated forms during a procedure)
    • Do not use bookmarks as these may cause invalidation issues
  • Annexes to the form should be filed separately in module 1.2 (do not use the PDF function to insert them into the eAF)
    • Form should be named; cc-form-eaf-var
    • Annex should be named; cc-form-annex-var (e.g. cc-form-5-19 or cc-form-proofpayment)
  • Electronic signature can be an image of a real signature (e.g. jpeg file – a scanned copy of wet signature. This however is not an electronic signature and is only used to close/lock the form) or can also be a line of text which states that signature is on file internally (e.g. “This form was authorised following company policies by Majella Ryan, Regulatory Affairs Manager of Ivowen with authorisation to sign. The signature is on file”)
    • The eAF does not accommodate multiple signatures at present. A separate annex should be provided if multiple signatures are mandatory for a particular NCA. Multiple name sections will be incorporated into version 2.0 but no mention of whether multiple signatures will also be accommodated.
    • The signature should be provided by the responsible MAH or can be provided by any authorised deputy
    • Please also check national requirements for signatures.
    • See Q&A guidance for further information
  • Workaround solutions (e.g. Annex B for multiple MAH or Product names) should always be mentioned in your cover letter
    • Some unforeseen variations (category z) are not adequately accounted for yet. Details of such changes should be outlined in the scope section of form and in the cover letter.
    • Duplicate sections only if products differ with regard to API or Pharmaceutical Form
    • Annex A or Annex B can be used for multiple MAH or Product names. Click on Annex A/B button in form and add the annex as a separate file in Module 1.2
    • Detailed instructions on how to use workaround solutions is available in the eAF Q&A document and the eAF Technical Guidance documents – both are published on the eAF webpage – if you need more advice contact EMA Service Desk.
  • No translations of the eAF are available, nor should they be requested.
  • Drug substances can be entered from controlled vocabulary lists or free text, and these each have different EV codes.
    • The focus should be on using substance, product, organisation and referential (SPOR)
  • Request for New Terms:
  • Strikethrough text function is not available in eAF but text can be copied and pasted (with text struck through) from Word or Outlook
  • In MRP/DCP one common application form is highly recommended, one per pharmaceutical form or strength for all member states in case of new MAA and one eAF for all involved products for all member states in case of variations and renewals.

 

Written by Majella Ryan

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Brexit

Preparing for Brexit

As the date for the withdrawal of the UK (also known as Brexit) from the EU approached closer, it pays to hope for the best and prepare for the worst.  With this in mind, the EMA have issued a guidance document on “Practical guidance for procedures related to Brexit for medicinal products for human and veterinary use within the framework of the centralised procedure, EMA, 19 June 2018” to prepare for the UK’s exit from the EU by the 30 March 2019.  

 http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2017/11/WC500239369.pdf

 

What does it mean?

For marketing authorisation applications (MAAs) that are expected to receive a Commission Decision (i.e. be approved) after 29 March 2019, the QPPV, PSMF (for medicines for human use), batch release sites, batch control sites, intended OMCL (if applicable) and nominated local representatives for Member States other than UK must be located in in the Union (EEA).

As published on the EMA website on the 10 July, a recent European Medicines Agency (EMA) survey shows that marketing authorisation holders for more than half (58%) of the 694 centrally authorised products (CAPs) with an important step in their regulatory processes in the United Kingdom (UK), are on track with their regulatory planning to ensure that their marketing authorisation remains valid once the UK leaves the European Union (EU).

This also means that 42% are NOT ready… Are you one of the 42%

The EMA urges those companies who have not yet informed EMA of their Brexit preparedness plans to do so as soon as possible to mitigate any risks to the continuous supply of medicines for human and veterinary use within the EU.

 

We can help…

Ivowen can help Clients prepare to implement the required changes by providing the following services:

  • Provide practical guidance on what needs to be in place by the above date to address situations where the UK is the current MAH, batch release site, batch control sites, location of QPPV& PSMF, transfer of orphan designation, etc.
  • Act as a MAH in the EU
  • Provide Pharmacovigilance (QPPV) services in the EU
  • Provide Pharmacovigilance System Master File and backup services located in the EU
  • Assist Clients in selecting and transferring RMS to another EU member state where the UK is current MAH
  • Preparation of Brexit related variations to be ready for above timelines
  • Assistance in changes needed to Product Information to reflect changes such as new MAH, batch release site(s), amend names of local representatives

Please contact us for further information at any time.

 

 

Need help with all the regulatory jargon?

Check out our updated GLOSSARY OF ABBREVIATIONS AND ACRONYMS.

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