Part Two of Larissa Gould’s report from the EMA focuses on the different types of legal basis for Marketing Authorisation in the EU and the impact of the Commission notice on the application of Articles 3, 5 and 7 of Regulation (EC) No 141/2000’

If you are concerned about your Marketing Authorisations with uncertainty around Brexit, do get in touch. S-cubed is able to act on your behalf in the EU.

Stephanie Prilla on the legal basis for MA available in the EU

Stephanie Prilla gave a comprehensive overview of the different types of legal basis for Marketing Authorisation available in the EU. Stand-alone ‘full’ applications include those made under Articles 8(3) (a complete dossier with a full data set), 10a (well established use with literature data), 10(b) (fixed combination) and 10(c) (informed consent). Article 8(3) applications can be ‘full’, where the data set comprises all of the applicants’ data, or ‘mixed’ where a full stand-alone application is made but published literature is also provided as either supportive data or to replace some of the non-clinical or clinical data. Abridged applications can be made under articles 10(1) generics, 10(3) hybrids and 10(4) (biosimilar) and must refer to a stand-alone MA already approved in the EU under Articles 8(3), 10a or 10(b). The differing data requirements for each type of abridged application were discussed and the point was made that the legal basis is the choice of the applicant with necessary product development dependent on choice of legal basis. Where bioequivalence studies are required to generate data, the comparator product used must be approved in the EU with an exception for biosimilar products, where the comparator product can be from outside the EU. A detailed description of the non-standard MAs granted based on a dossier not containing comprehensive data, namely MA under exception circumstances and conditional MA, were discussed. MAs under exception circumstances are only granted for products where it is foreseen that it would never be possible to collect comprehensive clinical data. Unless there are major advances in technology allowing collection of such data, these MAs will always be ‘exceptional’ but subject to specific obligations relating to safety (e.g. data from ongoing study, PASS, carcinogenicity testing) with annual reassessment of the balance of benefit and risk. MAs granted under exception circumstances must be renewed after 5 years. The second type of non-standard MAs concern products treating an unmet clinical need, used in emergency situations or those designated as orphan medicines, where the benefits of early access outweigh the risks due to limited data. A ‘conditional’ MA is granted for 1 year and a full data package must be generated according the timelines agreed with the EMA, after which the conditional MA will be converted to a full MA with a 5 year validity. In practice, this conversion from conditional to full MAA has occurred with 4 years. The EMA confirmed that proactively developing a product for a conditional or exception MA decreased assessment time, compared to when this route was established after MA application. It was advised that, once Industry has sufficient evidence of promising data, the EMA should be approached to confirm if these data were likely to support a conditional MA.

Commission notice on the application of Articles 3, 5 and 7 of Regulation (EC) No 141/2000

A presentation by Maria Sheenan was given on the EMA experience of the impact of the ‘Commission notice on the application of Articles 3, 5 and 7 of Regulation (EC) No 141/2000’ entered into force November 2016 (2016/C 424/03) on products with orphan designation (OD). The notice has 4 key elements:

  • Prevalence in the EU of approximately zero Confirmed that OD possible in case of risk that persons in the EU may become affected. To date 2 products with OD have been affected.
  • Availability of products Confirmed that significant benefit can’t be based on shortages of other products. To date 1 OD product and 1 product with MA have been affected.
  • Hospital formulations Confirmed that ‘magistral formula’ and ‘officinal formula’ may be considered as satisfactory treatment if they are well known and safe and  established a general practice within the EU. To date 4 OD products and 3 products with MA have been affected.
  • Reassessment following new indication or the modification of an existing indication Confirmed that verification of the significant benefit compared to existing treatments following this major change, to ensure continued compliance with Article 7(3) for the orphan MA. To date 17 products with MA have been affected, 7 of these did not need reassessment as the extension of indication was based on paediatric patients or patients with no other treatment available. Reassessment of 10 orphan products was required as indication extension broadened target population, namely a new line of treatment and new subgroups (based on new mutations, severity or biomarkers).

The third and final part of the Larissa’s report will be posted next week, where she focuses on medicines and devices, and Brexit. You can read part one here.