News from the CMDh meeting held in February 2018
CMDh positions following PSUSA procedure for nationally authorised products only
The CMDh, having considered the PSURs on the basis of the PRAC recommendation and the PRAC assessment reports, agreed by consensus on the variations of the marketing authorisations of medicinal products containing the following active substances:
- ibuprofen / pseudoephedrine
- interferon alpha-2a
- misoprostol (gastrointestinal indication)
- nitrous oxide, nitrous oxide / oxygen
Further information regarding the above mentioned PSUSA procedures, including information on the implementation, will be published on the EMA website, or here.
Fixed dose combinations containing pseudoephedrine and medicinal products containing pseudoephedrine as single agent
In the framework of the PSUSA for ibuprofen / pseudoephedrine, the PRAC noted that pseudoephedrine is also authorised as a single agent or in fixed dose combination products with other active substances. The PRAC considered that the risk of severe skin reactions including acute generalised exanthematous pustulosis would also be relevant to be included in the single agent or fixed dose combinations of pseudoephedrine as the risk is equally relevant for the combination products as the mono component. The updates should be in line with those proposed in the frame of the PSUSA, and the same timelines apply (e.g. 105 days from the adoption of the CMDh position).
Sodium containing effervescent, dispersible and soluble medicines - risk of cardiovascular events
In April 2015, PRAC concluded on a signal of cardiovascular events for sodium containing formulations of effervescent, dispersible and soluble medicines. High levels of sodium in medicines might be associated with a risk of cardiovascular conditions including hypertension and stroke. Warnings were required for those products containing ≥ 17mmol of sodium from any source in the maximum daily dose and that are used long term (continuous daily use for more than one month) or regular exposure (repeated use for more than two days every week).
Details of the PRAC recommendation and the required product information updates can be found here.
MAHs for authorised products were advised to wait for publication of the updated excipient guideline before implementing the warnings. CMDh would like to advise Marketing Authorisation Holders that the revised annex to the excipient guideline was published in October 2017, and is available here.
Product information updates should now be implemented for existing MAs by October 2018 via type IAIN notification, unless modification is required to the existing text, which would require submission of a Type IB variation. The change may also be submitted within the scope of another planned type IB or type II variation under chapter C that affects the product information. No variation is required if the change has previously been implemented.
Concomitant use of benzodiazepines/benzodiazepine like products and opioids
In August 2016, the FDA decided to add warnings to the drug labelling of prescription opioids (indicated for pain or cough) and benzodiazepines. The decision can be found here, and it concerns the serious risks of respiratory depression, coma and death, associated with the combined use of certain opioids and benzodiazepines. Separate wording has been proposed for opioids for pain, substitution therapy or cough and for benzodiazepines.
Following this, national competent authorities have received corresponding variations for national approved products in the EEA.
With the aim of having harmonised texts within the EEA, CMDh has agreed on a proposed text to be included for benzodiazepines and benzodiazepine like products (i.e. z-drugs), with regards to the warnings for concomitant use with opioids. A corresponding text for opioids was also agreed.
The proposed text is guidance on key messages that should be included, taking into account any necessary adaptation to the current product information of the individual product.
Variations according to the proposed text should be submitted as Type IB under category C.I.z as no harmonised national translations are available in all concerned member states.
If the message is already covered in the product information of concerned products, with a similar wording, there is no need to submit additional variations.
The proposed text for benzodiazepines and benzodiazepine like products and a corresponding text for opioids will be published on the CMDh website under "Advice from CMDh”.
Questions and Answers on ASMF
In January, the CMDh has agreed an update of the Q&As on ASMF to reflect that since January 2018 the use of eCTD format is mandatory for human medicinal products in accordance with the EU eSubmission roadmap.
The updated Q&As have been published on the CMDh website under "Questions and Answers” following the January CMDh meeting.
EU Work-sharing Articles 45 & 46 of the Paediatric Regulation - Public Assessment Reports
The CMDh has agreed on a public assessment report for paediatric studies submitted in accordance with Article 45 of the Paediatric Regulation for:
including recommendations for the text to be included in SmPCs and package leaflets.
Marketing Authorisation Holders of medicinal products with same active substance and pharmaceutical form are requested to include this information in their SmPCs and package leaflets within 90 days of publication of the public assessment reports, in accordance with the Best Practice Guide - Article 45, EU work-sharing procedure.
The CMDh has also agreed on public assessment reports for paediatric studies submitted in accordance with Article 46 of the Paediatric Regulation for:
- Certican (everolimus)
- TOBI (tobramycin nebuliser solution)
- Asmanex Twisthaler (mometasone furoate)
The public assessment reports will be published on the CMDh website under "Paediatric Regulation, Assessment reports”.
Further information regarding the Februrary 2018 CMDh meeting can be found on the CMDh/HMA website, or here.