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The recommendations were originally made by EMA’s Pharmacovigilance Risk Assessment Committee (PRAC), which confirmed the previously known risk of allergic reactions and also identified a small risk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.

Evaluación única de informes periódicos de seguridad

• La Agencia Española de Medicamentos y Productos Sanitarios informa del inicio de la evaluación única de informes periódicos de seguridad (PSUSA) en la que participan exclusivamente medicamentos nacionales (NAPs) (medicamentos autorizados por Reconocimiento Mutuo, Descentralizado o puramente Nacional).
• Los medicamentos nacionales con Informes Periódicos de Seguridad cuya fecha de cierre de datos sea el 1 de septiembre de 2014 o posterior, entrarán a formar parte de la evaluación única europea por principio activo, que ha comenzado en enero 2015.
• En esta nota se indica cómo se deberá presentar la documentación por parte de los titulares de autorización de comercialización y cómo se realizará la evaluación europea.
• En paralelo a esta publicación se ha actualizado el documento de preguntas y respuestas de la nueva legislación de farmacovigilancia.

Nueva aplicación para la gestión telemática de fichas técnicas y prospectos

La Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) puso en funcionamiento en marzo de 2013 una aplicación Web que permite a los titulares de la autorización de comercialización de un medicamento la gestión telemática de las fichas técnicas y prospectos durante los procesos de autorización de un nuevo medicamento (ver Nota informativa Referencia: MUH, 2/2013) posteriormente se amplió el ámbito de actuación a determinadas variaciones (ver Nota informativa Referencia: MUH, 21/2013). Para mejorar el funcionamiento de esta tarea se procede ahora a un cambio en la aplicación, este cambio se implementa por titular de autorización y afecta a todos los medicamentos de este laboratorio y a todos los procedimientos con presentación de ficha técnica o prospecto.

CMDh updates best practice for PSUR work sharing

The Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) has revised its best practice guidance for transitional arrangements for PSUR work sharing. The guide is intended to facilitate the completion of the informal European Work Sharing of PSURs for Nationally Authorised Products (NAPs).

The principles for submissions and evaluation have also been updated to specify the required process for submitting PSURs to National Competent Authorities (NCAs) for products authorised via National Procedure, MRP and DCP. Assessment reports will now be published on the CMDh website and therefore additional steps have been added to ensure compliance.

For more information visit the CMDh website

If you are planning PSUR submissions and would like our expert input into the preparation and/or submissions of the reports, please contact us on info@revipharm.es 

Qualified person responsible for pharmacovigilance in the EU

As part of the pharmacovigilance system, the marketing authorisation holder shall have permanently and continuously at its disposal an appropriately qualified person responsible for pharmacovigilance in the EU (QPPV) [DIRECTIVE 2010/84/EU Art 104(3)(a)].The QPPV appointed by the marketing authorisation holder shall be appropriately qualified and shall be at the marketing authorisation holder’s disposal permanently and continuously. The QPPV shall reside and operate in the EU.

EMA: PRAC recommends new measures to minimise known heart risks of hydroxyzine-containing medicines

Medicines can still be given for their approved uses, with new restrictions

EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has completed a review of medicines containing the antihistamine hydroxyzine. This follows concerns over the risk of possible effects onheart rhythm with these medicines, which are available in most EU countries. Their approved uses (indications) vary considerably between countries and may include use to treat anxiety disorders, for relief of pruritus (itching), as premedication before surgery, and for treatment of sleep disorders.

The PRAC considered that hydroxyzine was associated with a small but definite risk of QT interval prolongation and torsade de pointes (alterations in the electrical activity of the heart that can lead to abnormal heart rhythms and cardiac arrest). Based on the assessed data, the risk did not differ between indications, and the Committee recommended that hydroxyzine could continue to be used provided that measures to minimise the risk of problems with heart rhythm were taken.

These measures include using the medicine at the lowest effective dose for as short a time as possible. Use is not recommended in the elderly. The maximum daily dose should be no more than 100 mg in adults (50 mg in the elderly if use cannot be avoided), and 2 mg per kg body weight where used in children up to 40 kg in weight. Use must be avoided in patients who already have risk factors for heart rhythm disturbances or are taking other medicines that increase the risk of QT prolongation. Care is also needed in patients taking medicines that slow the heart rate or decrease the level of potassium in the blood, as these also increase the risk of problems with heart rhythm.

The PRAC recommendation follows a detailed review of the available evidence, which included published studies and data from regular safety monitoring, as well as consultation with experts in the treatment of children and the elderly. PRAC confirmed the known possibility of QT interval prolongation and torsade de pointes with hydroxyzine, and noted that such events were most likely to occur in patients who had risk factors. The risk can therefore be decreased by restricting hydroxyzine use in those most at risk of heart rhythm problems and reducing exposure to the medicine. The Committee recommended further study and monitoring to ensure that these measures were effective. The product information should be updated accordingly.

The PRAC recommendation will now be forwarded to the Co-ordination Group forMutual Recognition and Decentralised Procedures – Human (CMDh), which will adopt a final position and provide guidance to patients and healthcare professionals. In the interim, patients who have any concerns should consult their doctor or pharmacist.

Pharmacovigilance audits

The entry into force of the new legislation on pharmacovigilance in July 2012, established legal requirements for marketing authorisation holders to perform audits of their pharmacovigilance systems, including risk based audits of their quality systems.

Pharmacovigilance audit activities ashould verify the appropriateness and effectiveness of the implementation and operation of a pharmacovigilance system, including its quality system for pharmacovigilance activities. 

The marketing authorisation holder shall place a note concerning critical and major audit findings of any audit relating to the pharmacovigilance system in the pharmacovigilance system master file (PSMF). Based on the audit findings, the marketing authorisation holder shall ensure that an appropriate plan detailing corrective and preventative action is prepared and implemented. Once the corrective and preventive actions have been fully implemented, the note may be removed.

Información a los laboratorios titulares de medicamentos de uso humano que contienen mometasona furoato en suspensión para pulverización nasal. Decisión de la Comisión C(2015) 290 final, de fecha 19.1.2015 (Nº EMA: EMEA/H/A-30/1375)

Fecha de publicación: 5 de febrero de 2015

Categoría: INDUSTRIA, ARBITRAJES DE LA UNIÓN EUROPEA, MEDICAMENTOS DE USO HUMANO.

Referencia: MUH, 9/2015

La Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) informa de la publicación en su página web de la Decisión de Ejecución de la Comisión C(2015) 290 final, de fecha 19 de enero de 2015, en el marco del arbitraje por el artículo 30 de la Directiva 2001/83/CE, para los medicamentos de uso humano que contienen la sustancia activa mometasona furoato en suspensión para pulverización nasal.

La AEMPS informa de la publicación en su página web de la Decisión de Ejecución de la Comisión C(2015) 290 final, de fecha 19 de enero de 2015, mediante la actualización de la tabla activa con los Arbitrajes de la Unión Europea: “Acuerdos del CMDh y Decisiones de la Comisión Europea relacionadas con el CHMP y el PRAC”.

Se informa a los titulares de las autorizaciones de comercialización nacionales afectados por la citada Decisión, de la obligatoriedad de presentar la solicitud de modificación correspondiente y según el “Procedimiento para la Implementación Nacional de las Decisiones de la Comisión Europea, relacionadas con las Opiniones del Comité de Medicamentos de Uso Humano (CHMP) derivados de arbitrajes art. 30 y art. 31 de la Directiva 2001/83/CE y art. 29 del Reglamento (CE) 1901/2006”.

Memoria Técnica para la industria farmacéutica

Obligatorio:
- Laboratorios farmacéuticos (fabricantes e importadores)
- Fabricantes de principios activos estériles o de origen biológico,
- Laboratorios titulares de la autorización de comercialización y representantes locales del titular de autorización de comercialización para el almacenamiento de medicamentos en España

Información a los laboratorios titulares de medicamentos de uso humano que contienen “valproato y sustancias relacionadas”. Acuerdo del CMDh de fecha 21.11.2014. (Nº EMA: EMEA/H/A-31/1387)

Fecha de publicación: 4 de febrero de 2015

Categoría: INDUSTRIA, ARBITRAJES DE LA UNIÓN EUROPEA, MEDICAMENTOS DE USO HUMANO.

Referencia: MUH, 8/2015

La Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) informa de la publicación en su página web del Acuerdo del Grupo de Coordinación para Procedimientos de Reconocimiento Mutuo y Descentralizado-humano (CMDh), de fecha 21 de noviembre de 2014, en el marco del arbitraje por el artículo 31 de la Directiva 2001/83/CE, para los medicamentos de uso humano que contienen la sustancia activa “valproato y sustancias relacionadas (ácido valproico, valproato sódico, valproato semisodio, valpromida)”.

La AEMPS informa de la publicación en su página web del Acuerdo del CMDh, de fecha 21 de noviembre de 2014, mediante la actualización de la tabla activa con los Arbitrajes de la Unión Europea: “Acuerdos del CMDh y Decisiones de la Comisión Europea relacionadas con el CHMP y el PRAC. Medicamentos de Uso Humano”.

Se informa a los titulares de las autorizaciones de comercialización nacionales afectados por el citado Acuerdo, de la obligatoriedad de presentar la solicitud de modificación correspondiente y según el “Procedimiento de Implementación Nacional de los Acuerdos del CMDh y Decisiones de la Comisión Europea relacionadas con las Recomendaciones del Comité para la Evaluación de Riesgos de Farmacovigilancia (PRAC) derivados de arbitrajes art. 31 y art. 107i (decies) de la directiva 2001/83/CE”.

Pharmacovigilance system master file

The legal requirement for marketing authorisation holders to maintain and make available upon request a pharmacovigilance system master file (PSMF) was introduced by Directive 2010/84/EU amending Directive 2001/83/EC (Recitals (7) and (35), Article 23(4), Article 104(3)(b)) and Regulation (EU) No 1235/2010 amending Regulation (EC) No 726/2004 (Recitals (22) and (25), Article 16(4), to harmonise and strengthen the conduct of pharmacovigilance activities in the EU.