EMA: Ambroxol and bromhexine expectorants: safety information to be updated

Risk of allergy and skin reactions to be included in the product information

The CMDh¹ has endorsed by majority vote recommendations to update the product information for ambroxol- and bromhexine-containing medicines with information about the small risk of severe allergic reactions and severe cutaneous adverse reactions (SCARs). The medicines are widely available in the EU for use as expectorants (to help clear mucus from the airways).

The recommendations were originally made by EMA’s Pharmacovigilance Risk Assessment Committee (PRAC), which confirmed the previously known risk of allergic reactions and also identified a small risk of SCARs, a group of skin conditions which include erythema multiforme and Stevens-Johnson syndrome.

Regulatory information - Transitioning to mandatory use of electronic application forms

25/02/2015

Electronic application forms to be used for all human and veterinary centralised procedure applications from July 2015 and for all other human and veterinary EU procedures from January 2016

The European Medicines Agency (EMA) is announcing the transition to the mandatory use of electronic application forms for initial marketing authorisations, variations and renewals for human and veterinary medicines.

As of 1 July 2015 it will be mandatory for companies submitting applications for centralised procedures to use the electronic application form.

From 1 January 2016 the application forms in Word format published by the European Commission will no longer be available and only the latest version of the electronic application form will be used for all EU procedures, including national procedures.

The electronic application forms offer a convenient, online version of the currently used paper versions, which are published and maintained on the European Commission’s EudraLex website. These electronic forms are designed to reflect and capture the same content as the paper-based application forms. EMA first made these forms available to companies in July 2012, following a successful pilot phase. Since the initial release, the forms have been significantly improved and a further release based on change requests will be made available this Spring.

The mandatory use of these forms is expected to reduce the administrative burden for both the regulatory authorities and the industry, while at the same time improving data quality and consistency during data entry.

A user acceptance testing (UAT) period is now open until 5 March 2015. EMA encourages all interested parties to take part in the exercise.

In order to receive the test package and to provide feedback, companies wishing to participate should send an email to gareth.wilson@ext.ema.europa.eu. Companies that are part of a trade association are encouraged to send their feedback on the test results to their trade association so that consolidated feedback can be sent to EMA by 5 March at the latest.

Pharmacovigilance responsibilities of the MAH at EU

The marketing authorisation holder in the EU is responsible for the respective pharmacovigilance tasks and responsibilities laid down in Directive 2001/83/EC, Regulation (EC) No 726/2004 and the Commission Implementing Regulation (EU) No 520/2012 on the Performance of Pharmacovigilance Activities Provided for in Regulation (EC) No 726/2004 and Directive 2001/83/EC in order to assure responsibility and liability for its authorised medicinal products and to ensure that appropriate action can be taken, when necessary.

For this purpose, the marketing authorisation holder shall operate a pharmacovigilance system and shall establish and use a quality system that is adequate and effective for performing its pharmacovigilance activities.

Regulatory information - EMA introduces weekly start dates for the assessment of type II variations from March 2015

20/02/2015

The new timetables are expected to increase submission flexibility and streamline assessment of applications

From March 2015, the European Medicines Agency will introduce weekly start dates to facilitate the assessment of certain type II and worksharing variation applications for medicines for human use. These changes are one of the outcomes of the Agency’s structural reorganisation which was initiated in September 2013 to improve the efficiency and effectiveness of its operations. They are expected to offer more flexibility to applicants and streamline the assessment of applications by allowing certain variations to conclude outside of the plenary meeting of the Committee for Medicinal Products for Human Use (CHMP).

The new process will be applicable to most type II including grouped and worksharing variations. For these variations, companies will be able to send their applications to the Agency according to the weekly submission slots and the assessment will start on a weekly basis. The CHMP will adopt its scientific opinion at different time points either outside the CHMP meeting or at the meeting, depending on the start date of the review.

Assessment of responses to requests for supplementary information will also follow the weekly-start timetables.

The validation period between submission and procedure start as well as the assessment timelines as provided for in the legislation will remain unchanged. Linguistic review of product information changes for these variations will continue to follow the monthly review cycle starting five days after the CHMP monthly plenary meeting.

The new process will not apply to variations for which amendment of the marketing authorisation by the European Commission is required within two months from CHMP opinion. Similarly, it will not apply to variations involving the Pharmacovigilance and Risk Assessment Committee (PRAC) or the Committee for Advanced Therapies (CAT) either. These variations will continue to follow the existing monthly-start timetables.

Further details can be found in the post-authorisation guidance on type II variations which has been revised to reflect these changes. The new weekly-start timetables have also been published on the Agency’s website.

Safety signals: recommendations now available in all EU languages

18/02/2015

Translations will facilitate consistent implementation of product-information changes across the EU and reduce administrative burden for stakeholders

The European Medicines Agency (EMA) has started to translate its recommended changes to product information based on the assessment of safety signals into all official languages of the European Union (EU). The translations should be used by pharmaceutical companies to update the product information of their medicines.

This initiative is expected to accelerate the implementation of changes to product information and to ensure consistency across EU countries, thus leading to better information for patients on their medicines.

The EMA service will reduce the administrative burden and costs for the pharmaceutical companies, which, until now, have had to conduct translations individually with duplication of effort. It will also support the work of national medicines regulatory authorities in the EU, which are responsible for assessing the product informationproposed by pharmaceutical companies for nationally authorised products. The administrative and assessment burden should be minimised since companies’ proposals will be based on agreed translations.

A safety signal is information on a new or incompletely documented adverse event that is potentially caused by a medicine and that requires further investigation. The Agency's Pharmacovigilance Risk Assessment Committee (PRAC) is responsible for assessing validated safety signals reported for any medicine authorised in the EU. When a causal relationship between the medicine and the reported adverse event is confirmed, the PRAC can, for example, recommend that the product information of the medicine be changed to protect public health.

PRAC recommendations are submitted to the Committee for Medicinal Products for Human Use (CHMP), for endorsement, if the signal concerns a centrally authorised medicine, or communicated to the Coordination Group for Mutual Recognition and Decentralised Procedures - Human (CMDh) if the signal concerns a nationally authorised medicine.

Translations in all official EU languages, as well as Norwegian and Icelandic, will now be made available three weeks after publication in English, following a review of the translations' quality by the national medicines regulatory authorities of the EU Member States.

Translations of the January PRAC recommendations on safety signals have been published today: see PRAC recommendations on safety signals.