Posted on 04 May 2020

Regulatory News - May

Detailed EMA guidance on Individual Case Safety Reports (ICSRs) in the context of COVID-19.

The EMA has released a detailed guidance on Individual Case Safety Reports (ICSRs) in the context of COVID-19, regarding the validity and coding of ICSRs. This guidance contains updated information relevant to the latest published MedDRA MSSO information. Recommendations are also provided for the processing and submission of ICSRs associated with medicinal products used for the treatment or prevention of COVID-19 infection.

MHRA regulatory flexibilities resulting from COVID-19.

The MHRA’s website provides guidance on regulation during the COVID-19 outbreak. Of relevance to medical writers is the guidance on pharmacovigilance, which includes guidance on ICSRs and postponement or waiver for submission of PSURs for activities authorised only in the UK (submission frequencies/dates can be amended).

FDA’s COVID-19-Related Guidance Documents for Industry, FDA Staff, and Other Stakeholders.

The FDA is committed to providing timely recommendations, regulatory information, guidance, and technical assistance necessary to support rapid coronavirus disease 2019 (COVID-19) response efforts.

EMA: New testing and treatment recommendations for fluorouracil, capecitabine, tegafur and flucytosine

EMA’s safety committee (PRAC) has recommended that patients should be tested for the lack of an enzyme called dihydropyrimidine dehydrogenase (DPD) before starting cancer treatment with medicines containing fluorouracil given by injection or infusion (drip) and the related medicines capecitabine and tegafur, which are converted to fluorouracil in the body. As treatment for severe fungal infections with flucytosine (another medicine related to fluorouracil) should not be delayed, testing patients for DPD deficiency before they start treatment is not required. No pre-treatment testing is needed for patients treated with topical fluorouracil (applied to the skin to treat various skin conditions). Lack of a working DPD enzyme, which is needed to break down fluorouracil, causes fluorouracil to build up in the blood. This may lead to severe and life-threatening side effects such as neutropenia (low levels of neutrophils, a type of white blood cells needed to fight infection), neurotoxicity (damage to the body’s nervous system), severe diarrhoea and stomatitis (inflammation of the lining of the mouth). The PRAC assessed the available data and recommended measures to ensure the safe use of fluorouracil and fluorouracil-related medicines. Further information can be found here.

No change is needed in use of direct oral anticoagulants following EMA-funded study.

No change to the conditions of use of the direct oral anticoagulants Eliquis (apixaban), Pradaxa (dabigatran etexilate) and Xarelto (rivaroxaban) is needed following a review of the results of a European study of real-world data for these medicines. The study, commissioned by EMA and using real-world data from Denmark, France, Germany, Spain, the Netherlands and the United Kingdom, assessed the risk of serious bleeding with these 3 medicines when used to prevent blood clotting in patients with non-valvular atrial fibrillation (irregular rapid contractions of the heart) and compared this with other oral anticoagulants called vitamin K antagonists. The results were reviewed by EMA’s human medicines committee (CHMP), in consultation with EMA’s safety committee (PRAC), and were compared with data from other similar studies and in the published literature. EMA’s review concluded that the pattern of serious bleeding seen in patients taking Eliquis, Pradaxa and Xarelto was similar to that seen in the clinical trials on which the authorisation of the medicines were based. The data were not sufficient to allow robust conclusions to be drawn on comparisons between the 3 medicines. Further information can be found here.

Direct healthcare professional communication: Ulipristal acetate 5 mg for uterine fibroids not to be used during ongoing review of liver injury risk.

This direct healthcare professional communication (DHPC) contains important information for healthcare professionals prescribing, dispensing or administering the medicine(s). It also includes a communication plan with details of intended recipients and the dissemination date. The DHPC can be downloaded here.

The latest revision (v3) of the Guidance on how to manage clinical trials during the COVID-19 pandemic was published on 28 April.

This version contains key changes based also on the feedback from different stakeholders’ groups (patients’ organisations, academia and industry) before and during the drafting process. In order to provide organisations with an overview of the most important elements of this Guidance and the possibility to identify aspects for additional clarification, a webinar will be organised jointly by the European Commission, the European Medicines Agency and the Clinical Trials Facilitation and Coordination Group of HMA with the participation of the drafting team members on 15 May 15.00-17.00.
More information about the webinar can be obtained by clicking here.
The number of participants will have to be limited for technical reasons and thus early registration is advised by sending a message to: SANTE-PHARMACEUTICALS-B4@ec.europa.eu using “Registration to the webinar on the Guidance on clinical trials during COVID-19” in the subject line.
The link to allow access to the webex conference will be shared with participants later in May. In order to make the information available for broader public, the webex will be recorded and made public on the EMA and Commission website: EUTube.

EMA updated the Explanatory Note to GVP Module VII (Periodic safety update report).

On 04 May 2020, an update of the Guideline on good pharmacovigilance practices (GVP): Module VII – Periodic safety update report - Explanatory note has been published by the EMA. The updated Explanatory Note to GVP Module VII (EMA/670256/2017 Rev. 2) is available here.