Last week’s round-up;
20-24 July 2020

published 27 Jul 2020

MHRA News: Medical Device “Certificates of Compliance” / “Attestation of Conformity” have no legal standing under MDR

Certificates of compliance or Attestation of Conformity documents have no legal standing under the UK Medical Device Regulations 2002 (UK MDR). They are not evidence that the manufacturer of the device has met the requirements of the UK MDR, nor are they CE Certificates. The certification body may have issued these following a review of the technical documentation for the medical device. However, this is not a regulatory requirement and so the certificate issued has no regulatory validity. Evidence of registration and declaration of conformity are documents of regulatory validity and may be requested from the manufacturer or the EU Authorised Representative.

New EMA guideline on Water quality for pharmaceutical use

The EMA has issued a new guideline on the quality of water for pharmaceutical use that will replace its current guidance and position statement on water quality when it takes effect in February 2021. The new guideline applies to the manufacture of active substances and drug products for both human and veterinary use, ATMPs and where relevant, to IMPs, and should be consulted for new marketing authorization applications and variations to existing authorizations.

Recommendations are provided with respect to the minimum acceptable quality of water for different uses and applications, including the manufacture of sterile and nonsterile medicinal products, active substances and water used for cleaning and rinsing equipment and containers/closures for pharmaceutical products. This new guideline should be read in conjunction with EMA’s 2017 Questions and answers on production of water for injections by non-distillation methods – reverse osmosis and biofilms and control strategies document.

EC has issued an updated draft Q&A on the Clinical Trials Regulation (CTR)

EC has issued an updated draft Q&A on the Clinical Trials Regulation (CTR). Updates to this draft document are as follows:

    • Section 1 on the scope of the CTR question 1.7 details clarification on what is not considered normal clinical practice and 1.19 details language requirements and an associated Annex II.
    • Section 2 changes concern the processes for the subsequent addition of a Member State.
    • Section 3 details an updated 3.4 concerning the timing of submission of modifications.


There are various modifications to section 7 on safety reporting and it includes a new question 7.19 which clarifies how RSI for the development of biosimilar drug products should be written.

MHRA to return to on-site GxP Inspections

MHRA is currently making careful preparations for a safe return to normal UK on-site inspection scheduling. During the last few weeks they have been engaging with industry trade associations and the NHS to discuss the practical arrangements that may be required to facilitate on-site inspection starting in September and scaling up to a full programme from October 2020. The conduct of the inspections will vary according to the requirements of each GxP area and may include a hybrid model of on- and off-site activities that support a single inspection cycle.Further information will be made available later in the summer. Details of the announcement can be found here:

Pharmeuropa 32.3 Public Consultation

Pharmeuropa 32.3 is now available for public consultation and includes 48 new and revised draft texts. A list of the draft texts is available for perusal at the link below, and it includes draft monographs on Raman spectroscopy, Extractable elements in plastic materials for pharmaceutical use and Cyclo-olefin polymers. These draft monographs are not currently considered official standards, however, once they are adopted by the Ph. Eur. Commission they will become applicable and the legally binding standards for the products concerned in all Ph. Eur. member states. Users should submit their comments by the 30th September 2020.

EMA sets up infrastructure for real-world monitoring of COVID-19 treatments and vaccines

EMA has set up an infrastructure to support the monitoring of COVID-19 treatments and vaccines when used in day-to-day clinical practice. This is underpinned by three contracts for observational research that EMA has signed with academic and private partners, to be ready to effectively monitor vaccines performance in the real world, and to support the safe and effective use of both vaccines and medicines.The latest contract was finalised in mid-July with Utrecht University and the University Medical Center Utrecht as coordinators of the CONSIGN project (‘COVID-19 infectiOn aNd medicineS In preGNancy’).

This project will collect data on the impact of COVID-19 in pregnancy. In June, EMA contracted the company IQVIA with a project to build a framework for the conduct of multicentre cohort studies on the use of medicines in COVID-19 patients. In May, EMA commissioned the ACCESS project (‘vACcine Covid-19 monitoring readinESS’) for preparatory research into data sources and methods that can be used to monitor the safety, effectiveness and coverage of COVID-19 vaccines in clinical practice, once authorised.Full discussion on the supportive infrastructure and other aligned collaborations, can be found here:

Quality Risk Management – Transportation Risks

Quality Risk Management (QRM) in transportation tends to be a significant weakness for many wholesalers, according to the MHRA inspectorate. A new blog post by the department details one practical approach for ensuring good transportation QRM, based on the theory within ICH Q9. It covers risk assessment, control, communication within and outside the organisation, and periodic review. Common weaknesses seen by inspectors are also listed, such as QRM not being understood by managers or being used as an excuse to avoid developing appropriate mitigation:

Medical Device Coordination Group (MDCG) issues a template for Clinical Evaluation Assessment Reports

MDCG has issued a new template for clinical evaluation assessment reports, which will be used by NBs to clearly document the conclusions of its assessment of the clinical evidence presented by the manufacturer in the clinical evaluation report (CER) and related clinical evaluation that was conducted. This is a core requirement of the Medical Device Regulation (EU) 2017/745 (MDR). As part of the assessments performed NBs will assess the suitability of using data from claimed equivalent devices, clearly document its conclusions on the claimed equivalence, and on the relevance and adequacy of the data for demonstrating conformity.

The NB will verify that the clinical evidence and the clinical evaluation are adequate and shall verify the conclusions drawn by the manufacturer on the conformity with the relevant general safety and performance requirements. Finally the NB will consider the clinical evaluation and the benefit-risk determination, and whether specific milestones need to be defined to allow the notified body to review updates to the clinical evidence that result from post-market surveillance and PMCF data. The document in full can be found here:

Public consultation extension of Ph. Eur. nitrosamine analysis chapter

Following the closure of the public consultation for the new Ph. Eur. general chapter on the analysis of N-nitrosamine impurities in active substances (2.4.36), the EDQM is now accepting comments from stakeholders who were not able to take part in the consultation due to restrictions brought on by the COVID-19 pandemic. The general chapter proposes three procedures relying on GC-MS, LC-MS/MS and GC-MS/MS analytical techniques, which cover seven N-nitrosamine impurities. The stakeholders concerned are required to contact their respective national pharmacopoeia authority (NPA) or the EDQM as soon as possible in order to announce their intent to comment. Comments will be received until the 31st August 2020.

Search Real Regulatory