Posted on 08 Oct 2018

Regulatory News - October 2018

EMA launched a new version of its corporate website. The new version of the EMA website ( has a number of new features to improve user experience, including:

  • An improved search, allowing users to find content easily and to filter their search results. EMA plans to further refine this functionality in the future
  • A ‘responsive’ design for cleaner display on mobile devices
  • Simpler URLs based on the location and title of web pages or documents
  • An updated visual design offering users a clearer reading experience and simpler navigation

Practical guidance for procedures related to Brexit for medicinal products for human use approved via MRP/DCP”. The “Practical Guidance” has been developed by the coordination group for Mutual recognition and Decentralised procedures Huma (CMDh) taking into consideration that as of 30 Mar 2019 the United Kingdom will become the third country. As a result, MAHs and applicants of medicinal products for human use approved via MRP/DCP approved via MRP/DCP need to ensure that the necessary changes are made by the 30 Mar 2019, unless indicated otherwise in the guidance below or subject to the terms of any withdrawal agreement. This guidance is also in line with the EMA’s Practical guidance for procedures related to Brexit for medicinal products for human and veterinary use within the framework of the centralised procedure but adapted to nationally authorised products approved under MRP/DCP. This document complements the CMDh Q&A to provide procedural and practical guidance regarding the submission of changes.

EMA updated post-authorisation procedural advice for users of the centralised procedure. Changes of this update (15 Aug 2018) concern:

  • Type II variations
  • 3.2. Do I need to notify the Agency of my intention to submit a Type II variation application?
  • 3.15 When do I have to submit revised product information? In all languages?
  • Extension of market authorisation
  • 4.3. Do I need to notify the Agency of my intention to submit an extension application?
  • 4.15. When do I have to submit revised product information? In all languages?
  • Post- Authorization Measures (PAMs)
  • 15.8. When shall I submit my PAM?

Zhejiang Tianyu no longer authorised to manufacture the valsartan active substance for EU medicines. The suspension of Zhejiang Tianyu’s CEP – a certificate verifying that the quality of its valsartan meets European requirements – comes after the detection of low levels of N-nitrosodimethylamine (NDMA) in the valsartan produced by the Chinese company. NDMA is classified as a probable human carcinogen (a substance that could cause cancer) based on results from laboratory tests. The levels of NDMA found so far in batches of valsartan from Zhejiang Tianyu are considerably lower than levels found in the active substance from Zhejiang Huahai, which triggered a recall of several valsartan medicines in July 2018. The certificate for Zhejiang Huahai had already been suspended and the company is also not permitted to supply valsartan active substance to the EU.

Prescriber guide to help avoid medication errors with Amglidia. All healthcare professionals who are expected to prescribe Amglidia (glibenclamide oral suspension) will be provided with a guide to help ensure that the medicine is prescribed and used correctly. Amglidia is a medicine used for the treatment of neonatal diabetes, a form of diabetes that occurs in the first 6 months of life. Amglidia is available as an oral suspension in two strengths: 0.6 mg/ml and 6 mg/ml, and each strength is available in two presentations: either with a 1-ml oral syringe or with a 5-ml oral syringe. The strength and the size of the oral syringe to be used depends on the dose prescribed. It is important that only the syringe provided with the pack is used to measure Amglidia. Dosing errors may occur due to confusion between milligram (mg) and millilitre (ml), or use of incorrect strength or size of the syringe and how the dose is measured, which may result in too high or too low blood sugar levels. To avoid medication errors, prescribers will be given a guide specifying which strength and presentation to use and what details to include on each prescription.

New measures to minimise the risk of rare but serious liver injury with Esmya. EMA concluded the review of medicine for uterine fibroids and recommended that several measures be put in place to minimise the risk of rare but serious liver injury with Esmya (ulipristal acetate). Certain women may start treatment with Esmya once the new measures are implemented. The measures include contraindication in women with known liver problems; liver tests before, during and after stopping treatment; a card for patients to inform them about the need for liver monitoring and to contact their doctor should they develop symptoms of liver injury. In addition, use of the medicine for more than one treatment course has been restricted to women who are not eligible for surgery. Esmya is used to treat moderate to severe symptoms of uterine fibroids (benign tumours of the womb). Following reports of serious liver injury, including liver failure leading to transplantation, the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) performed a review and recommended that use of the medicine should be restricted and that studies should be performed to determine the effects of Esmya on the liver and whether the new measures are effective in minimising the risks.

Educational material to ensure Myalepta is used correctly. Educational materials will be provided to patients and healthcare professionals to ensure that the medicine Myalepta (metreleptin) is prepared and injected correctly, and to prevent the risk of medication errors. Myalepta is a medicine used to treat lipodystrophy, where patients have a loss of fatty tissue under the skin and build-up of fat elsewhere in the body such as in the liver and muscles. Myalepta is given as a daily injection under the skin of the abdomen (belly), thigh or upper arm. The medicine comes as a vial of powder to which water is added to make a solution for injection. The recommended daily dose depends on the patient’s body weight and sex, which the doctor can then adjust based on the patient’s response to treatment. Patients, their parents or carers can inject the medicine once they have been trained by their doctor or nurse. To avoid medication errors, healthcare professionals and patients will be given educational material with detailed instructions on how to prepare the solution and how to inject the correct dose. This includes written training materials as well as a video with instructions on how to prepare the solution for injection and how to inject it.

EMA’s guidelines open for consultation:

  • Draft Q&A’s on Data Monitoring Committees issues. The aim of this question-and-answer document is to supplement the CHMP Data Monitoring Committee Guideline (Doc Ref. EMEA/CHMP/EWP/5872/03) by providing clarification on the role and necessity for a Data Monitoring Committee (DMC) in different phases of drug development and throughout the product lifecycle as well as with regard to the responsibilities for implementing DMC decisions.
  • Draft guideline on the use of minimal residual disease as a clinical endpoint in multiple myeloma studies. The guideline aims to address the use of undetectable minimal residual disease (MRD) as an intermediate efficacy endpoint in controlled randomised clinical studies in patients with multiple myeloma (MM), adequately designed to demonstrate efficacy by relevant hard endpoints. MRD as an endpoint in this context would allow earlier approval of new drugs pending final confirmatory data.
  • Draft guideline on biosimilar medicinal products containing recombinant granulocyte-colony stimulating factor. This document is an annex to the guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues. It provides guidance for a demonstration of comparability of two recombinant granulocyte colony-stimulating factor-containing medicinal products medicinal products.
  • Draft guideline on similar biological medicinal products containing the recombinant granulocyte-colony stimulating factor (rG-CSF). The proposed guideline will replace annex to a guideline on similar medicinal products containing biotechnology-derived proteins as active substance: Non-Clinical and Clinical Issues - Guidance on similar medicinal products containing a recombinant granulocyte-colony stimulating factor, EMEA/CHMP/BMWP/31329/2005.
  • Draft guideline on clinical investigation of medicinal products in the treatment of epileptic disorders. This document provides guidance on the development of medicinal products for the treatment of epileptic disorders.