Last week’s round-up;
13-17 July 2020

published 20 Jul 2020

New EMA opinion on nitrosamines

The CHMP has finalised its opinion on the presences of nitrosamines in human medicines, which is available on the EMA’s nitrosamine impurities website. The opinion requires pharmaceutical companies to take measures in order to limit as much as possible the presence of nitrosamines in their drug products and to ensure that the levels of these impurities do not exceed set limits. Such measures include the implementation of appropriate control strategies to prevent or limit the presence of nitrosamines as well as the improvement of manufacturing processes, where necessary. Companies will also be required to carry out the necessary risk assessments and evaluation and conduct appropriate tests if the risk of nitrosamine contamination is identified.

EU Notified Bodies designated under the EU MDR (2017/745)

There are currently 15 Notified Bodies(NB) designated under MDR with GMED France being the latest NB to be designated and also the first NB to receive designation in France. A full list of NB’s currently designated are listed below and on the Nando Database linked here

Manufacturers don’t know for certain if and when their NB will be designated and are advised to regularly check the Nando database to see status of NBs designate.

      1. BSI (Netherlands) – 2797 (MDR scope)
      2. BSI (UK) – 0086 (MDR scope)
      3. CE Certiso (Hungary) – 2409 (MDR scope)
      4. DARE!!! Services (Netherlands) – 1912 (MDR scope)
      5. DEKRA Certification (Germany) – 0124 (MDR scope)
      6. DEKRA Certification (Netherlands) – 0344 (MDR scope)
      7. DNV GL Presafe (Norway) – 2460 (MDR scope)
      8. GMED (France) – 0459 (MDR scope)
      9. IMQ (Italy) – 0051 (MDR scope)
      10. Intertek IMNB (Sweden) – 2862 (MDR scope)
      11. MDC Medical Device Certification (Germany) – 0483 (MDR scope)
      12. MEDCERT (Germany) – 0482 (MDR scope)
      13. NSAI (Ireland) – 0050 – (MDR scope)
      14. TÜV Rheinland LGA (Germany) – 0197 (MDR scope)
      15. TÜV SÜD (Germany) – 0123 (MDR scope)

CMDh updates

The CMDh has revised the following documents (available with tracked changes): • Flow chart of the Decentralised Procedure. • CMDh Best Practice Guide on the processing of renewals in the Mutual Recognition and Decentralised Procedures. • CMDh Best Practice Guide on Multilingual Packaging. CMDh has also published its Procedural guidance during Covid-19 pandemic, which includes a new template for notification of implementation of a change under a previously agreed ECMP.

MHRA COVID-19 Flexibilities

MHRA is offering to provide temporary inspection flexibility for manufacturers of human plasma-derived medicines, in exceptional circumstances. For 3rd country plasma collection sites that have been previously inspected by MHRA, they will implement a control measure in line with EMA recommendations and a Statement of Next Inspection (SONI) will be issued. For 3rd country sites that have not been previously inspected, MHRA gives 2 separate options depending on whether a partent company has been previously inspected or not. Full details of the guidance and all the MHRA COVID-19 Flexibilities can be found here:

EDQM evaluation of impurity found in paracetamol API

The EDQM is actively working with a pharmaceutical company and other stakeholders to evaluate the detection of 4-chloroaniline, a carcinogenic impurity found in the active substance paracetamol that is manufactured by the company. The company concerned holds a Certificate of Suitability (CEP) for this active substance. The evaluation is underway to better understand the potential impact of this impurity as well as the extent of the issue.

Brexit:  Joint technical notice by the European Commission, EMA and HMA

EC, EMA and HMA have announced that, since ‘The Withdrawal Agreement’ provides for a transition period end 31st Dec 2020 and no extension was requested as of 1st July 2020, there is no possibility of further extension beyond that date. Sponsors of EU CTs are reminded of the legal situation applicable after the end of the transition. Two specified areas that must be implemented prior to end of transition period are as follows; EU based QP will be required for IMP release and the sponsor or legal representative for the trial must be established within the EU. Further discussion can be found here:

New metformin recalls

Following last month’s voluntary recall of extended-release (ER) metformin by five pharmaceutical companies from the US market, the FDA has announced that another two manufacturers have issued further recalls of ER-metformin due to the presence of elevated levels of the potential carcinogen NDMA. Six pharmaceutical companies have been affected by the voluntary recalls. The FDA has also published a paper on the investigations carried out to study the initial discrepancies between FDA testing and testing by a private laboratory. The private laboratory, which had filed a Citizen Petition, reported higher NDMA levels in more metformin products than the FDA test results. On investigation, the cause of the discrepancy was found to be the presence of another chemical, N,N-dimethylformamide (DMF), that interfered with NDMA mass spectrometry measurements in the analytical methods used by the FDA. Further information on the latest ER-metformin recalls may be found here: 

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