November 2020

EU, ICH and Brexit Pharma Regulatory Update

Read the latest information on all things Brexit, nitrosamines and the implementation of the clinical trials regulation from regulatory expert Pete Gough.

EU News

New Head of European Medicines Agency (EMA)

On June 25, 2020, it was announced that the EMA Management Board nominated Emer Cooke as the new Executive Director of the Agency. Cooke took up the position on November 16, 2020.

Clinical Trial Regulation Implementation

The Clinical Trials (CT) Regulation 536/2014 published on May 28, 2014 has yet to be implemented as it requires a new portal, the Clinical Trials Information System (CTIS), to be operational for new processes to be functional. At its Management Board meeting on June 11, the EMA proposed December 2021 as the go-live date for the CTIS and CT regulation implementation.

Once the CTIS goes live, a three-year transition period to the new system will commence. In the first year of this transition, sponsors of clinical trials will be allowed to submit applications using either the existing EudraCT system or the CTIS. In years two and three, new CTA applications must be done via the CTIS. Trials authorized via EudraCT can continue but must be transferred to the CTIS by end of the three-year transition period.

Nitrosamine Contamination

On June 23, 2020, the EMA and the Heads of Medicines Agencies (HMA) jointly published the 98-page document “Lessons learnt from presence of N-nitrosamine impurities in sartan medicines.” It makes a total of 40 recommendations, including 21 on the revision of the existing guidelines as well as possible changes to legislation.

A June 25, 2020, a Committee for Medicinal Products for Human Use (CHMP) Assessment Report recommended extending the requirement to conduct a risk assessment to consider the possibility of the presence of nitrosamine contamination to biological medicinal products. This requirement applies to both new marketing authorization applications and all existing products.

In August 2020, the EMA provided a deadline for the completion of the risk assessments and report of the outcome for biological products and, at the same time, further extended the deadline for products with chemically produced APIs to:

  • March 31, 2021 for chemical medicines
  • July 1, 2021 for biological medicines

Water Quality Guideline

In July 2020, the EMA issued an update to the “Guideline on the quality of water for pharmaceutical use,” which becomes effective on February 1, 2021. This revision is the first in 18 years.

The guidance lists the four types of water that can be used for manufacturing drug substances and finished drug products:

  • Water for injection, which is mainly used for sterile products
  • Purified water, which is used for non-sterile products and certain active substances
  • Potable water, which can be used for manufacturing active substances and the early stages of cleaning equipment
  • Water for the preparation of extracts, which is a new category for herbal products

This new guidance permits the use of potable water for producing the fermentation media and cell culture media in making active substances for biological products, whereas the preceding draft called for using higher-grade purified water for producing such media.

Brexit

Starting in September, 2020 the Medicines and Healthcare products Regulatory Agency (MHRA) started issuing a series of guidance documents on the requirements that will become effective on January 1, 2021, when the transition period ends. The guidance covers:

  • Clinical trials
  • Devices
  • Licensing
  • Importing and exporting
  • IT systems
  • Pharmacovigilance
  • Pediatrics

These guidance documents continue to be updated through the final months of 2020. Some of the provisions may change if the EU and the UK agree to a trade deal. The position of Northern Ireland, which is to effectively remain in the EU, is different from that of Great Britain (GB) in several key respects, but exactly what this will mean in practice is still unclear.

The key points in this guidance are:

  • Existing centrally authorized products (CAPs) that are currently on the GB market will automatically be converted to GB marketing authorizations (MAs) on January 1, 2021.
    • For converted CAPs, the UK company will have one year to provide the MHRA with baseline data but will have to nominate a UK contact for the MHRA within one month.
  • Products with UK MAs issued via mutual recognition (MR) and decentralized (DC) procedures that are held by an EU legal entity will have two years from January 1, 2021 to move the MA to a UK-based legal entity, but they will again have to nominate a UK contact for the MHRA within one month of January 1, 2021.
  • Medicines that are manufactured and Qualified Person (QP) certified in the European Economic Area (EEA) will not need additional QP certification if imported into GB.
    • From January 1, 2023, wholesalers importing directly from the EEA will need to appoint a Responsible Person for Imports (RPi), but a system for ensuring that imported product has been QP certified will need to be in place by January 1, 2021.
  • Medicines that are manufactured and quality control (QC) tested in the EEA and the existing EU MRA countries will not need re-testing when imported into GB.
    • From January 1, 2023, medicines that are QC tested in the EEA will need re-testing on import to GB unless the EU and UK have signed a mutual recognition agreement.

International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) News

The 2020 ICH biannual meetings, scheduled to be held in Canada in May and in Greece in November, were both converted to virtual meetings due to the COVID-19 pandemic and the resulting global travel restrictions. The next ICH meeting is scheduled for June 2021 in South Korea.

The ICH Assembly held a virtual meeting on May 27, 2020 and endorsed work on the following new topics:

  • Revision of M4Q(R1) Common Technical Document (CTD)
  • Structured product quality submissions

Have a question on the updates?