EU Pharma Package: Global (Orphan) Marketing Authorization Compromise Proposal

Background

In our fifth alert in this EU Pharma Package Series, we provided an analysis of the background and ongoing legal debates regarding the concept of the global marketing authorization (GMA), We discussed in particular the missed opportunities in the Pharma Package to further codify and clarify the GMA, in view of its central role in determining the regulatory data protection (RDP) rights of a medicinal product.

In addition, we discussed the proposal for the introduction of a GMA specifically for orphan medicinal products, the global orphan marketing authorization (GOMA).

Lack of further clarity regarding GMA

In the compromise text, Article 5(2) of the proposed Directive states that:

“When an initial marketing authorisation has been granted in accordance with paragraph 1, any development concerning the medicinal product covered by the authorisation such as additional therapeutic indication, strengths, pharmaceutical forms, administration routes, presentations, as well as any variations of the marketing authorisation shall also be granted an authorisation in accordance with paragraph 1 or be included in the initial marketing authorisation. All those marketing authorisations shall be considered as belonging to the same global marketing authorisation, in particular for the purpose of the marketing authorisations applications under Articles 9 to 12, including as regards the expiry of the regulatory data protection period for applications using a reference medicinal product”.

This provision will succeed the current Article 6(1), second paragraph of Directive 2001/83/EC:

“when a medicinal product has been granted an initial marketing authorisation, any additional strengths, pharmaceutical forms, administration routes, presentations as well as any variations and extensions must also be granted an authorisation or be included in the initial marketing authorisation. All these marketing authorisations are considered as belonging to the same GMA, in particular for the purpose of the application of Article 10(1) [of Directive 2001/83/EC]”.

The wording of both provisions is highly similar, although there are two points we want to flag:

• • The compromise text notably includes the mention of “additional therapeutic indication”, but only mentions variations and not extensions. Both wording changes are the result of codifying some of the existing case law of the Court of Justice of the EU and have limited effect in practice as applications for additional therapeutic indications and extension applications both fall under the umbrella of “variations”.
  • The compromise text now includes an explicit reference to the two purposes of the GMA, namely (i) the fact that a generic/(bio-)hybrid/biosimilar application can refer to any marketing authorization (MA) that is part of the same GMA as reference medicinal product and (ii) the calculation of the expiry date of the period of RDP. Article 80(1) of the proposed Directive further clarifies that, for MAs that belong to the same GMA, the period of data protection shall start from the date when the initial MA was granted in the EU. By way of contrast, the current provision only contains a high-level reference to the application of Article 10(1) of Directive 2001/83/EC, which contains the general rule on RDP.

Notable changes for orphan medicinal products

As was proposed by all three EU institutions, the proposed Regulation of the Pharma Package (implicitly) introduces the notion of the GOMA, by stating in Article 71(3) that “where a marketing authorisation holder holds more than one orphan marketing authorisations for the same active substance, those authorisations shall not benefit from separate market exclusivity periods. The duration of the market exclusivity shall start from the date when the first orphan marketing authorisation was granted in the Union”.

Market exclusivity for orphan medicinal products (OME) is traditionally linked to the specific clinical indication with an orphan designation. Each indication with an orphan designation currently confers 10 years' OME for the particular indication. Under the compromise text, this will be reduced to nine years.^[1]Moreover, the two-year OME extension for completing a pediatric investigation is abolished and replaced by the six-month extension of the supplementary protection certificate (SPC), which was previously only available for non-orphan products and required giving up the orphan designation to obtain this reward.

Furthermore, non-orphan indications for the same product (active substance) require a separate MA. Recital 98 of the proposed Regulation clarifies in this respect that the separate MAs for the orphan and non-orphan indications are covered by the same GMA. Note that this refers to the “regular” GMA, not the GOMA — which is not a concept explicitly used in the wording of the Pharma Package. The reason for this is that OME runs in parallel with “regular” RDP, from which the orphan medicinal product also benefits, as OME has a broader scope of protection. OME also protects orphan medicinal products against similar (innovative) products from entering the market, rather than only generic/(bio-)hybrid/biosimilar products. Therefore, an orphan MA can also form part of a “regular” GMA.

Lastly, once the Pharma Package enters into application, both innovative and generic/biosimilar manufacturers will be able to apply for and — as was proposed by the Parliament and Council — even obtain an MA prior to the expiry of OME where the remainder of the OME period is less than two years. The decision granting the MA will only formally enter into force upon the expiry of the OME period. Under the current regime, MA applications for similar products are not even accepted during the entire OME period (Article 71(1) and 71(6) of the proposed Regulation). This can be compared to the Bolar exemption — which will be discussed in our client alert next week.

Conclusion

Despite the fact that ongoing legal proceedings underscore the need for the EU legislator to further refine and clarify the GMA concept through targeted legislative amendments, it is unfortunate that none of the EU institutions used the opportunity of the EU Pharma Package to fully codify existing case law and improve the wording of the GMA provision, for example, regarding the constitutive elements by which a particular GMA can be identified.

With respect to orphan medicinal products, a cautious convergence towards the rules for regular medicinal products can be noted — with the introduction of a GOMA, the six-month SPC extension, and a Bolar-like exemption for orphan MAs.

New in the compromise text is the transitional provision in Article 180(7a), which clarifies that the new OME durations shall not apply to orphan MA applications submitted before the entry into application of the Pharma Package (which will be 24 months after entry into force). For those products, Article 8(1) of Regulation (EC) No 141/2000 shall continue to apply. However, this only applies to the initial MA. For any other applications containing the same active substance, the GOMA shall immediately start applying, even if the MA application is submitted before the entry into application of the Pharma Package.