Proposal for a Directive
Amgen welcomes this opportunity for commenting and offers the following recommendations:
- Art. 4(26): Clarify that in vitro diagnostics are not included within the definition of a combination of a medicinal product with a product other than a medical device. The definition should be revised to: 26) ... means a combination of a medicinal product with a product other than a medical device (as defined by Regulation (EU) 2017/745 and Regulation (EU) 2017/746)
- Art. 12: he term bio-hybrid should be removed entirely given its use creates significant confusion, implying a novel approval pathway. The article refers to biosimilar medicinal product, but then introduces the term bio-hybrid, which is used inconsistently in the Directive. Further, framing and limitations for bio-hybrid in recital (29) are not included in Art. 12 and differs significantly is not defined. Changes in therapeutic indications implies a novel indication could be added; it is unclear how such a change would not differ significantly in properties with regard to safety or efficacy from the reference products (RP). Currently, a manufacturer needs to demonstrate biosimilarity in their initial marketing authorisation without substantive differences from the RP. Then a post-approval variation may be submitted to add indications, etc. different than the RP. It should be made unambiguously clear if the intent is to confirm current practice and standards for post-approval changes to a biosimilar.
- Art. 57: New requirements to report on public financial support for the R&D of a product will create unnecessary burden on MAH without truly providing insights into public financial support of R&D. Tracking support for a single product/molecule goes against the structure of how research works. R&D does not happen in a single molecule vacuum, but instead in a trial-and-error research environment.
- Art. 59: The requirement to place the product on the market of all member states where the product is already authorised should consider the limited role that Marketing Authorisation Holders (MAHs) have in the access processes. The proposed provision could lead to penalties for reasons outside the MAHs control. We support EFPIAs advocacy to replace place on the market with shall make the product available for ordering, considering actual demand and patient need.
- Art. 80-83: Changes to the Regulatory Data Protection (RDP) system in Europe will hurt the innovation ecosystem without having a significant effect on time to access for patients. The incentive to gain extra years of RDP by launching within all member states within two years of approval does not consider the limited role MAH holders have in the access processes. The proposal is unlikely to change MAHs' actions bringing a product to market; the uncertainty will undermine EU's competitiveness in attracting investment in innovative R&D.
- Art. 153.1b: Provision for waiving of import testing should be extended to countries following the unilateral reliance approach for inspections by trusted non-EU regulatory authorities in Articles 188.4a & 190.1d.
- Art. 166 1c & 1d: In the provision for alignment of physical with financial flow, we recommend establishing waivers for transactions that occur within the same company group (e.g., subsidiaries). Absence of such waivers would create unnecessary burden with questionable benefit for patients. We note that financial/tax is managed by other legislations. Amgen welcomes the provisions for electronic product information (ePI), and recommends expediting implementation.
Proposal for a Regulation
Amgen welcomes proposals in the Regulation shortening CHMP opinion timelines to 180 days, allowing reliance for inspections, streamlining of PRIME, and establishing regulatory sandbox. Moreover, Amgen welcomes the supply chains provisions currently included in the Regulation as they will ensure an EU wide approach to address supply chain challenges. We offer the following recommendations:
- Art. 70: The tier system establishing categories of Unmet Medical Need (UMN) could push investment away from areas of need instead of towards it. The definition of High UMN (HUMN) for orphan medicinal products establishes a new standard that will be challenging to achieve. For UMN and HUMN we call for a predictable set of criteria addressing disease severity and burden on patients, families, and caregivers. We recommend maintaining only the current system of demonstration of significant benefit and deleting the additional new demonstration of exceptional therapeutic advancement. We recommend a clear patient focused governance on how the criteria and definition will be used for UMN determinations. We request flexibility in the application of UMN criteria so that the determinations are appropriate for a specific disease area, (e.g., oncology). The current definitions and application of UMN and HUMN could slow down R&D investment or move research into other disease areas where the definition of UMN seems more likely to be fulfilled.
- Art. 71: Changes to the Market Exclusivity (ME) system and reductions in the IP incentives for orphans will hurt the innovation ecosystem for orphan research in Europe and undermine what has been a success story for the EU. Moving to a single ME for a product will significantly reduce investment in new indications for a molecule that could be used for multiple orphan diseases leading to additional unmet medical need. The EU should increase the ME incentive for additional orphan indications for a molecule.
- Art. 58 should be revised to ensure that Scientific Advice is inclusive of medicinal products used with an IVD/companion diagnostic, by adding this within scope of the definitions, and ensuring notified bodies can be included as experts in scientific advice procedures. Article 58(1) should add the following at the end: and for medicinal products used with an in vitro diagnostic medical device. Article 58(3) should be revised as follows: other bodies.
- Art. 59 should be revised to ensure medicinal products used with an IVD/companion diagnostic are in scope for parallel scientific advice. We suggest revising the article as follows: In case of medicinal products used with a medical device or an in vitro diagnostic medical device, undertakings or, as relevant, not-for-profit entities may request scientific advice as referred to in Article 58(1) in parallel with the consultation of the expert panels referred to in Regulation (EU) 2017/745 or Regulation (EU) 2017/746.
- Art. 75: Mode of Action (MoA) Paediatric Investigation Plans (PIPs) is framed in the Regulation recitals in a way that ensures that they are scientifically, clinically meaningful and feasible, and do not place a disproportionate burden on innovators to conduct unlimited numbers of studies or trials. The obligation should be limited to carrying out one PIP, based on the products MoA, in a single condition for which there is such an UMN, at the MAHs request.