The EU Pharmaceutical Package: Regulatory Protection Changes
In this second article of the series, “A Deep Dive into the EU Pharmaceutical Package Changes,” our Regulatory experts present a more detailed analysis of the proposed changes introduced to Regulatory Data Protection (RDP) and market protection rules by the new directive that will replace directives 2009/35/EC and 2001/83/EC.
For an introduction, check out our first article in the series, “The EU Pharmaceutical Package: Introduction to Changes.”
The RDP is the period of time during which an applicant for biosimilar, generic, or hybrid approval cannot rely on the data of the original applicant to support their marketing application.
The Pharmaceutical Package proposal shortens the baseline RDP from eight years to six years, and introduces a modular approach enabling an extension of RDP from six up to ten years under certain conditions.
In addition, the proposal offers companies interested in treatment repurposing the chance to obtain an RDP period. Drug repurposing is the process of identifying new uses for existing medicines in indications outside the scope of the original approved product information.
For those products, an RDP of four years can be granted if the product hasn’t been previously protected or if it has been 25 years since the initial product authorization.
The new Pharmaceutical Package modifies the rules of market protection as well. A market protection is a period of time during which a biosimilar, generic or hybrid cannot be placed on the market, even if it has already received a marketing authorization.
The current regulation includes a two-year market protection with a possibility to extend the protection by one year, whereas the new one proposes a fixed duration of two years for all products without any possibility of extension.
Who benefits most from the proposed changes?
Companies who fulfill all the criteria below will be eligible for the maximum ten years of data protection:
- Launch the product in all 27 Member States within two or three years from marketing authorization (+two years).
- Fulfill the unmet need (UMN) definition (+six months).
- Conduct comparative clinical trials (+six months).
- Provide a new indication with significant clinical benefit (+one year).
The RDP under the proposed Pharmaceutical Package is a modular approach that introduces a large range of protection periods that vary between six to ten years, depending on the above factors.
Regulatory Data Protection (RDP): Current vs New Pharmaceutical Package
Y: Year, UMN: Unmet Medical Need, CT: Comparative Trial
These criteria raise challenges in particular for small and medium entities (SMEs). Combined with market protection, the total protection for a new drug could be up to 12 years in the new Pharmaceutical Package.
The Package also includes an incentive to encourage the development of “priority antimicrobials” (Commission Regulation (EC) 2023/0132 (COD) Article 40) by issuing a voucher that grants one additional year of RDP. The voucher can be used by an antimicrobial developer or sold to another marketing authorization holder (MAH).
How does the new EU Pharmaceutical Package regulation compare to US regulation?
The US regulation for biologicals products offers 12 years of total exclusivity, which aligns with the EU regulation proposal when all conditions are met. For non-biologic (New Chemical Entity) products, the US regulation is limited to five years compared with the proposed EU regulation which would offer up to 12 years in total.
Globally, the EU regulation will remain very attractive compared with the US.
What are the challenges with the new proposal?
The current eight years of RDP has proven highly effective to support the development of innovative therapies. The proposed changes limit the RDP and create a modulating system which is less predictable for developers.
The criteria to reach the maximum RDP extension are more challenging, and some of them require more clarity (e.g., UMN definition).
Comparative clinical trials
The European Commission mentioned an additional six months of RDP if the MAH conducts comparative clinical trials. By nature, in very rare diseases with high UMN, comparative trials are not always possible and are replaced by historical controls.
SMEs will find it complicated and potentially unfeasible to launch in all 27 member states over two years in order to benefit from the RDP extension.
However, the Commission is enabling some leeway by allowing certain developers to have three years to launch. Those developers are the not-for-profit entities, the SMEs (as in Commission Recommendation 2003/361/EC), or developers that have received fewer than five centralized marketing authorizations.
Hopefully, the European Commission will consider extending this requirement to four years.
UMN for medicinal products is currently defined as a “condition for which there exists no satisfactory method of diagnosis, prevention or treatment authorised in the Community or, even if such a method exists, in relation to which the medicinal product concerned will be of major therapeutic advantage to those affected.” (Commission Regulation (EC) No 507/2006 Article 4)
The proposed definition in the Pharmaceutical Package:
- A product addresses UMN if it relates to a “life threatening or severely debilitating disease” and there is no medicinal product authorized in the EU for such disease, or
- Where despite medicinal products, the disease is associated with a “remaining high morbidity or mortality,” and
- The use of the medicinal product results in a “meaningful reduction in disease morbidity or mortality for the relevant patient population.” (Commission Regulation (EC) 2023/0132 (COD) Article 83)
The lack of clarity of “remaining high morbidity or mortality” and “meaningful reduction in disease morbidity or mortality for the relevant patient population” are particularly concerning.
Strict criteria may interfere with innovation, causing significant impact in patient populations. This definition will not contribute to a future-proof system, since not all patients are the same and UMN is evolving over time.
The proposed Pharmaceutical Package remains under discussion. Industry stakeholders can submit feedback to the European Commission on their website by 1st August 2023, before final adoption by the European Parliament and EU Council.
Our experts will address incentives for orphan medicinal products in the next article in this series. Check out our first article in the series, “The EU Pharmaceutical Package: Introduction to Changes.”