Meeting highlights from the CMDh meeting in September 2016
CMDh positions following PSUSA procedure for only nationally authorised products
The CMDh, having considered the PSURs on the basis of the PRAC recommendations and the PRAC assessment reports, agreed by consensus on the variations of the marketing authorisations of medicinal products containing the following active substances:
- antithrombin III
- bendamustine hydrochloride
- botulinum neurotoxin type a (150 kd) free from complexing proteins
- botulinum toxin a
- botulinum toxin a - haemagglutinin complex
- testosterone (all formulations apart from topical use and testosterone undecanoate injection)
- testosterone (topical use only)
- testosterone undecanoate (injection)
Further information regarding the above mentioned PSUSA procedures, including information on the implementation, will be published on EMA's website.
Medicinal products containing levonorgestrel
The CMDh noted that some medicinal products containing 750 mcg of levonorgestrel still contain an outdated frequency of administration (first tablet to be taken as soon as possible following unprotected intercourse or failure of a contraceptive method, second tablet to be taken 12 hours after the first tablet). The CMDh requests concerned MAHs to update the frequency of administration to the current state-of-the-art, i.e. 2 tablets (1500mcg total dose) to be taken at the same time, as soon as possible following unprotected intercourse or failure of a contraceptive method. MAHs are advised to contact the relevant national competent authority regarding the implementation of the change. Variation worksharing procedures should be used, where possible.
MAHs/Applicants are reminded that an Article 13 referral was finalised on Levonelle. More information on the impact on the product information and the implementation of the outcome of this procedure is available on HALMED's and EMA's website.
Please also note the request for update of the paediatric information included in SmPC sections 4.2 and 5.1 below under "EU Work-sharing Articles 45 & 46 of the Paediatric Regulation - Public Assessment Reports”.
EU Work-sharing Articles 45 & 46 of the Paediatric Regulation - Public Assessment Reports
The CMDh has agreed on public assessment reports for paediatric studies submitted in accordance with Article 45 of the Paediatric Regulation for:
- Priorix (Live attenuated measles virus (Schwarz strain), Live attenuated mumps virus (RIT 4385 strain, derived from Jeryl Lynn strain), Live attenuated rubella virus (Wistar RA 27/3 strain))
- Priorix Tetra (Live attenuated measles virus (Schwarz strain), Live attenuated mumps virus (RIT 4385 strain, derived from Jeryl Lynn strain), Live attenuated rubella virus (Wistar RA 27/3 strain), Live attenuated varicella virus (Oka strain))
No changes to the product information are requested as outcome of the procedures.
The CMDh has also agreed on public assessment reports for paediatric studies submitted in accordance with Article 46 of the Paediatric Regulation for:
- Beriate (human coagulation factor VIII)
- Tobi Nebulizer Solution (tobramycin)
- Berinert (C1-esterase inhibitor, human)
- Norditropin SimpleXx (somatropin)
- Norditropin Nordilet (somatropin)
- Genotropin / Genotropin MiniQuick (somatropin)
- Genotropin (somatropin)
- Covaxis/Triaxis/Adacel (Diphtheria, Tetanus, Pertussis (acellular, component) Vaccine (adsorbed, reduced antigen(s) content))
- OraVerse (phentolamine mesylate)
The public assessment reports will be published on the CMDh website, under "Paediatric Regulation, Assessment reports”.
The CMDh further requests MAHs of medicinal products containing levonorgestrel with the indication emergency contraception to implement the wording in the SmPC sections 4.2 and 5.1 as agreed in the paediatric Art. 46 assessment report on NorLevo/Vikela/PiDaNa (levonorgestrel), published in April 2016.
Zika virus infection: plasma- and urine-derived medicines safe to use - Manufacturing processes for these products successfully inactivate or remove virus
Assessments carried out by the European Medicines Agency (EMA) and competent authorities in the EU Member States have confirmed that there is no increased risk of contamination with the Zika virus for patients who take plasma-derived or urine-derived medicines.
Plasma-derived medicines are manufactured from human blood. They are used to treat and prevent serious diseases and include coagulation factors (treatments which help blood to clot) and immunoglobulins (proteins used in patients who need more antibodies in their blood to help fight infections and other diseases). Urine-derived products are manufactured from pooled human urine and include certain hormone-based treatments and urokinase products (medicines used to break up blood clots).
These medicines are produced from body fluids, which might be sourced in parts of the world where the Zika virus is prevalent. EU regulators sought reassurance that there is no risk of the virus contaminating the final product and thus affecting the patients taking it if the plasma or urine came from donors who had contracted the Zika virus.
EMA’s Committee for Medicinal Products for Human Use (CHMP) has addressed the potential risk from Zika virus for plasma-derived medicinal products. The CMDh has coordinated the assessment by EU Member States on the potential risk from Zika virus for urine-derived medicinal products. The CHMP concluded at its September meeting that the manufacturing processes used for plasma-derived products, including for example the solvent/detergent method to inactivate viruses, pasteurisation (liquid heat inactivation) and virus filtration, inactivate or remove the Zika virus from the finished product. The CHMP therefore considered that no additional safety measures such as the testing or exclusion of certain plasma donors was necessary.
Concerning urine-derived products, the CMDh, following the assessment of the data, concluded that the manufacturing processes for these products contain complementary steps with inactivation/removal capacity for enveloped viruses, which are considered sufficient for Zika virus safety of these products. Additional safety measures are thus not considered necessary.
The findings from these assessments on the viral safety of plasma-derived and urine-derived medicines are available in a report from the CHMP’s Biologics Working Party (BWP), or here.
Variation Regulation (EC) No 1234/2008
The CMDh has agreed an updated version of the Questions & Answers on variations. Several questions have been amended and a new Q&A on the update of generic marketing authorisations has been added. The amended document will be published on the CMDh website under "Questions and Answers”.
The CMDh has also agreed an update of Chapter 3 of the Best Practice Guide on variations - type IA minor variations. The timetable in the annex has been corrected to align it with the current Variation Regulation. The amended document will be published on the CMDh website under "Procedural Guidance, Variation”.
Orphan similarity assessment
The CMDh reminds applicants/marketing authorisation holders that applications for marketing authorisations/variations amending indications or an extension of a marketing authorisation have to contain a similarity report when an orphan-designated medicinal product is already authorised for a condition relating to the therapeutic indication proposed in their application. This is irrespective of the legal basis under which an application is submitted.
More news from the CMDh September meeting are available on the CMDh/HMA website.