2019 – What a year

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

 

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.

Ivowen attended TOPRA Symposium 2019

This year’s TOPRA Annual Symposium was held in Dublin in October. The Annual Symposium is an essential meeting for regulatory professionals to gain both an understanding of current and evolving regulatory requirements, as well as insights into future plans for regulations in the Human medicines, Veterinary medicines and Medical Device sectors.

Three members of our Team attended the Symposium this year, Majella Ryan, Alice D’Alton and Nanda Naik. This year was particularly satisfying for Ivowen as we had an exhibition stand at the three day event.

As well as exhibiting, Ivowen attended the sessions including ‘Life after Brexit’. This session was a live discussion of predictions and concerns about the possible outcome of ongoing negotiations with the EU.

Now that an extension has been granted, which will delay the UK exit until January 2020, we are left wondering if we will finally know the UK position when Ivowen attend the Medicines for Europe regulatory conference being held in Amsterdam on 29th – 31st January.

In the meantime, we await instruction from the regulators on whether UK will still be available on the CESP portal later this week. Ivowen is registered on the new MHRA submissions portal so either way we have you covered.

Ivowen will keep you up to date in the coming days and weeks

Please contact us, Ivowen are dedicated to keeping you up to date with the latest regulatory updates and innovations. We remain at your disposal to assist in all of your regulatory endeavours today and into the future.

Written by Alice D’Alton.

Brexit – because it affects you too…

The European Union is arguably the world’s most powerful bloc and very soon it’s about to lose the United Kingdom, one of its biggest members. How and when the UK leaves the EU will have further implications that ripple around the globe.

So if you’ve heard about Brexit but haven’t been keeping up with every twist and turn of the developments, no worries! Ivowen team will provide you with everything you need to know to have your products designed for UK and Brexit affected markets authorised successfully.

What is happening?

EMA

The European Medicines Agency (EMA) will physically relocate to the Netherlands in early March 2019.

https://www.ema.europa.eu/documents/press-release/ema-relocation-updates_en.pdf

EMA will leave its premises in London on 1 March 2019.

It was confirmed that from 4 to 8 March, the Agency will operate on the basis of extended teleworking. During the course of the following week  EMA staff will gradually move into the Spark building.

From 4 March 2019 onwards the official address of EMA will be that of the permanent building, located in Amsterdam Zuidas:

European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands

Meetings and visits will take place at the Spark building:

Orlyplein 24, 1043 DP Amsterdam, The Netherlands

 

UK guidance on Brexit

Following the outcome of the EU referendum, MHRA still feels responsible for playing a crucial role in medicines and devices regulations as well as vigilance and market surveillance.

As part of the MHRA response to exiting the EU the following Brexit guidance was issued:

Technical information on what the implementation period means for the life science sector

Update on negotiations and further guidance for pharmaceutical companies planning in advance of the final negotiated settlement

Further guidance note on the regulation of medicines, medical devices and clinical trials if there’s no Brexit deal

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.

 

MHRA guidance on Brexit

Bearing in mind the worst-case scenario if the UK leaves the EU with no deal, the UK would no longer be part of the EU medicines and medical devices regulatory networks and  consequently submissions related to human medicines would need to be submitted directly to the MHRA.

The webinar below is relevant for all pharmaceutical companies involved in making medicines regulatory submissions and vigilance activities. It also ensures that stakeholders can be informed of any IT plans and preparations. There is also a section on how all medicines related clinical trial sponsors will register and submit:

https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/772918/Making_submissions_to_the_MHRA.pdf

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.

 

UK legislation on medicines and medical devices

Legislation has been published which, in the event of the UK leaving the EU with no agreement, will cover the regulation of medicines, medical devices and clinical trials and allow for the continued sale.  The Brexit guidance is available here:

  1. Human Medicines Regulations 2012, as amended by the Human Medicines (Amendment etc) (EU Exit) Regulations 2019
  2. The Medical Devices (amendment) (EU exit) Regulations 2019
  3. The Medicines for Human Use (Clinical Trials) (amendment) (EU exit) Regulations 2019

The 2012 Regulations (as amended by the 2019 Regulations) make reference to various pieces of EU guidance, as that stood immediately before the exit day (29 March 2019).

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.

 

EU Commission and EMA Q&As

The EU Commission & EMA have published an updated list of questions and answers related to the UKs withdrawal from the EU on the 1st February:

https://ec.europa.eu/info/sites/info/files/medicinal_products_for_human_and_veterinary_use-qa_en.pdf

This confirms that dual labelling between UK & Ireland is acceptable where the labels meet the requirements of the Directive and reflect the SPC in Ireland (see Q24).

The focus of this Q&A is on the regulation of medicinal products  within the centralised procedure.

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.

 

Brexit Stakeholder Event

Brexit Stakeholder Event – Ivowen was there

Following the UK’s departure from the European Union, the HPRA, together with medicines agencies in Europe, is making preparations to ensure continuity to deliver on patient and animal health remits even if the UK fully exits the current systems as scheduled. There are potential implications for the European network as a whole and particularly for Ireland with its shared marketplace, see meeting agenda below:

Agenda for Brexit Stakeholder event 1 Feb 2019

Contact us if you would like some more information on this event or Brexit in general

 

Written by Karolina Dobrychłop

Clinical Trials Regulation EU No 536/2014 – What does this mean for you?

When the Clinical Trial Regulation (No. 536/2014) comes into effect in 2018, there will be a major change on how clinical trial applications are submitted and how clinical trials are conducted in the EU.

The goal of the new Regulation is to create an environment that is favourable to conducting clinical trials in the EU, with the highest standards of safety for participants and increased transparency of trial information.

 

Below you will find a brief summary of the changes:

Directive 2001/20/EC (Current)

  • Multiple submission for one trial (1 submission per each MS)
  • Double submission with a MSC: to NCA and EC
  • Individual assessment by Each MSC with no IT collaboration tool available
  • No Single MSC decision (NCA and ECs)
  • Limited EudraCT data availability to the public

Regulation 536/2014 (New)

  • Single e-submission to all MSCs
  • Harmonised dossier for one trial and
  • e-submission of structured data and documents by MSCs
  • Specific timeline
  • Joint assessment for PART I  facilitated by collaboration tool
  • Single MSC decisions
  • Single web-based EU portal
  • Distribution of the burden among users
  • View all CT relation information

 

Transition period (3 years) Directive 2001/20/EC (current) to Regulation 573/2014

  • Starts when Regulation becomes applicable (~ Oct 2018)
  • 1st Year: Clinical Trials can be submitted under old/current (Directive) or new (Regulation) system
  • 2nd & 3rd Year: Trials authorised under old system can remain under that system, New/initial Clinical Trials should comply the Regulation System
  • All Clinical Trials to switch to the Regulation 3 years after implementation (~ Oct 2021)

 

Typical Documents to be submitted:

  • Part I: Cover letter (very important), EU AF, Protocol, IB, GMP compliance documents, IMPD, Auxiliary Medicinal Product Dossier, Scientific Advice, PIPs, and labelling, proof of payment, etc.
  • Part II: Recruitment arrangements, SI/ICF/ICF procedure, suitability of the investigator, suitability of the facilities, proof of insurance cover or indemnification, financial and other arrangement, proof of payment, etc.

 

Part I Timetable Coordinated assessment (also applies to Mono-national Clinical Trials)

  • Day 0: Validation
  • D26: Draft Part I Assessment Report made available by the RMS (reporting MS) to the CMS
  • D38: All CMS share considerations
  • D45: RMS finalises the Part Assessment Report
  • D57: Sponsor submits response (w/n 12days)
  • D69: Co-ordinated assessment between MSs (12 days)
  • D76: RMS files conclusion (7days)

 

Part II Timetable National evaluation

D0: Validation

D45: Final assessment report from each MSC submitted

D57: Sponsor submits response

D76: Final assessment by the MSC shall be performed (w/n 19 days)

Submission of Part I and II in parallel (recommended) or submission of Part I followed by Part II (not less than 2 years after Part I)


Important Notes:

  • New MSs can only be added after the notification date of the initial authorisation decision
  • Withdrawal of MS: the whole application has to be withdrawn and resubmitted

Transparency:

EU Database will be publically accessible by default, with exceptions justified on any of the following grounds

  • Protection of personal data
  • Protection of commercially confidential information in particular taking into account the MA status of the medicinal product, unless there is an overriding public interest in disclosure
  • Protecting confidential communication between Member State in relation to the preparation of the assessment report
  • Ensuing effective supervision of the conduct trial Member States

 

Where can I find more information?

Information on Clinical trials – Regulation EU No 536/2014, General information, Guideline EU

Clinical Trial Portal and Database, Transparency, Safety reporting, Clinical trials conducted outside the EU, Contact points can be found here: https://ec.europa.eu/health/human-use/clinical-trials/regulation_en

 

We can help…

Ivowen are fully equipped to submit for Clinical Trials Applications on your behalf. Please contact us for more information and for support of your dossier compilation or updates.

 

Written by: Fiona Downey

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.

EF photo