Regulatory news - January 2019

Europe

European Medicines Agency (EMA)

EMA head office relocation updates

The EMA head office will relocate to the Netherlands in early March 2019 and the Agency are now preparing for its move to the temporary building, the Spark building in Amsterdam Sloterdijk. In parallel with this the Agency is working to ensure continuation of its main activities; focusing on authorisation, maintenance and supervision of medicines as well as ongoing Brexit preparedness and implementation activities. An annex has been produced to summarise the prioritisation of continued work in the multiannual work programme. This will be reviewed after the office relocation has been completed to assess which other activities can be resumed in the second half of 2019.

The Agency will leave it’s premises in London on 1^st March 2019 and from 4^th March 2019, the official address of the EMA will be that of the permanent building:

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

For further information, see here.

EMA Guideline on Content, Management and Archiving of the TMF

The EMA GCP Inspectors Working Group has adopted the Guideline on content, management and archiving of the clinical trial master file (paper and/or electronic) which will come into effect on 18 June 2019.

The guideline, which is intended to assist sponsors and investigators/institutions in complying with the requirements of the current legislation (Directive 2001/20/EC and Directive 2005/28/EC), as well as ICH E6 Good Clinical Practice Guideline, applies to legal representatives and contract research organisations (CROs), including any third party vendors and service providers. This guidance already prospectively considers the specific requirements of the Clinical Trials Regulation (EU) No 536/2014 (CTR) with respect to the TMF to ensure its application once the CTR comes into effect.

For the full article please see here. The full guideline is here.

United Kingdom (UK)

Medicines and Healthcare products Regulatory Agency (MHRA)

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

The MHRA have issued further guidance for stakeholders on the regulation of medicines, medical devices and clinical trials if there’s no Brexit deal. The guidance has been produced in response to the consultation on EU exit no-deal legislative proposals and covers the arrangements for medicines and clinical trials if the UK leave the EU on the 29^th March 2019 with a no-deal Brexit scenario. The guidance is a more comprehensive version of the technical notice published in August 2018, including changes based on responses received to the MHRA’s consultation in October 2018. The key points to come out of this guidance are as follows:

• The UK’s participation in the European medicines regulatory network would cease and the MHRA would take on responsibilities for the UK that are currently undertaken through the EU system.
• For medicines currently authorised by the EMA as Centrally Authorised Products (CAP), these will fall under a process called grandfathering and will be automatically transferred into UK Marketing Authorisations (MA).
• The assessment timelines for new product applications containing new substances or biosimilars which have received a positive opinion from the CHMP will be reduced to 67-days and for new active substances an accelerated 150-day assessment will apply. The government are also working with industry to identify options to reduce the current national licensing timeframe from 210 to 180-days.
• There will be certain requirements around legal presence in the UK for MAHs; the MAH should be established by the end of 2020 and QPPV should be established in the UK from EU exit day.
• A QP for products manufactured in the UK or directly imported into the UK from a country not on an approved country list (to include all EU and EEA countries) must operate and reside in the UK.
• For clinical trials of IMPs, existing MHRA and Eithics Committee approvals will continue to be recognised and there will be no need to re-apply. For trials in the UK, the trial sponsor or legal representative must be located in the UK or in a country on the list of approved countries.
• The UK will aim to align wherever possible with the EU Clinical Trials Regulation, expected to come into effect in 2020.
• QP certification of IMPs carried out in the EU/EEA countries will be recognised by the UK.

The proposals released in this guidance note are subject to parliamentary approval and further guidance from the government and the MHRA are anticipated in due course.

To read the full guidance note, please see here.

MHRA announces contingency legislation covering regulation of medicines and medical devices in a no-deal scenario

The UK government has published three pieces of draft legislation, covering the regulation of medicines, medical devices and clinical trials as part of its contingency planning in the event of the UK leaving the EU with no agreement.

The draft legislation are subject to parliamentary approval and allow for continued sale of and access to medicines, medical devices and clinical trials in the UK:

• Human Medicines Regulations 2012, as amended by the Human Medicines (Amendment etc) (EU Exit) Regulations 2019
• The Medical Devices (Amendment) (EU Exit) Regulations 2019
• The Medicines for Human Use (Clinical Trials) (Amendment) (EU Exit) Regulations 2019

These draft legislative pieces aim to ensure the MHRA’s continued regulation of medicinal products in the UK by tweaking certain existing regulations, as summarised in the article above.

For further information, see here.

MHRA releases letter to industry on conversion of Centrally Authorised Products (CAPs) to UK Marketing Authorisations (MAs)

The MHRA have released a letter requesting MAHs with CAPs to take preparatory actions in the event of a no-deal Brexit. In such case the MHRA intends to convert existing CAPs into UK MAs and the letter lists additional actions on top of those released in their letter to industry in November last year in order to facilitate the grandfathering process. The MHRA has assigned a Product Licence number to CAPs based on the existing UK practice for national licences. The latest letter clarifies that MAHs can opt out of the grandfathering process for their CAPs by notifying the MHRA by the 22^nd April 2019, as of which date those products will no longer be licenced in the UK.

To read the full article and the letter to industry, see here.

Department of Health and Social Care (DHCS)

Change to DHSC email address

From the 1^st February 2019 all dh.gsi.gov.uk email addresses will cease to exist. Please ensure all future email communications are sent to firstname.surname@dhsc.gov.uk.

USA

Food and Drug Administration (FDA)

FDA planning new guidance, hires in cell and gene therapies for 2019

The FDA plans to hire at least 50 new clinical reviewers in preparation for an expected surge in cell and gene therapies entering early development. The agency expects to receive at least 200 IND applications annually, which they predict will translate into between 10 and 20 cell and gene therapy approvals each year by 2025.

The agency is also planning to introduce a new guidance in 2019 on regenerative medicine advanced therapy designation, accelerated approvals and different areas of product development.

In addition the FDA are also planning to specific guidance on development for inherited blood disorders such as haemophilia and allowing individual researchers to pool clinical data after following a common manufacturing protocol.

Further recommendations are planned to be released:

• for certain neurodegenerative diseases that will urge drugmakers to take more traditional development approaches if a therapy creates genetic alterations to treat they symptoms instead of treating the underlying cause and recommendations
• on new manufacturing techniques and minor changes that can be introduced without performing new clinical investigations and bridging studies, instead possible supplying additional real-world data for CAR-T therapies.

Click here to read the full article.

Brazil

Agência Nacional de Vigilância Sanitária (ANVISA)

Brazil breakthrough in advanced therapy regulations

This month ANVISA published their regulatory framework for clinical trials of advanced investigational therapies, optimising a risk-based authorisation process throughout clinical development.

Under the new regulation, advanced therapies are defined under two distinct categories:

• Conventional therapies: minimally manipulated products for homologous biological use
• Advanced therapies: substantially manipulated or minimally manipulated products with non-homologous application.

Advanced therapy products are further classified according to their risk; Class I (minimal manipulation, for non-homologous use or different biological function) and Class II (substantial manipulation – tissue engineering, gene therapy, cell production/laboratory). For Class I products the documentation required to initiate a clinical trial is simplified and the trial may commence after documentation is submitted to the Agency, however for Class II products approval must be obtained by ANVISA prior to trial start.

Click here to read the full article.

Public consultations

EUROPEAN COMMISSION

EUROPEAN MEDICINES AGENCY (EMA)

PHARMACEUTICAL INSPECTION CONVENTION/PHARMACEUTICAL INSPECTION COOPERATION SCHEME (PIC/S)