The European Commission (“Commission”) intends to change the rules on regulatory data protection (“RDP”) of medicinal products. The Commission stated in its Impact Assessment for the revised pharmaceutical legislation that it wants to strike a balance between “providing attractive incentives for innovation and supporting timely patient access to medicinal products across the EU.” To achieve this, it has proposed replacing the old 8 + 2 (+1) RDP system with a new system that will offer innovators variable durations of RDP. However, this new system may raise a number of concerns for innovator companies. We summarize the new rules on RDP and then discuss the possible implications below.
Regulatory Data Protection
The Commission published a proposal for a revised Directive on the Union Code Relating to Medicinal Products for Human Use (the “Directive”) today (26th April 2023). Chapter VII of the Directive sets out the new rules on RDP.
As with the previous system under Directive 2001/83/EC, the Directive provides for a period of data protection, during which other marketing authorization applicants cannot refer to the pre-clinical tests and clinical trial data for the authorized reference medicinal product. This is immediately followed by a two-year period of market protection during which the generic/biosimilar product may not be placed on the market. Under the Directive, new medicines will have a minimum period of regulatory protection of eight years, which includes six years of regulatory data protection and two years of market protection. Such medicines may benefit from additional periods of regulatory data protection if they satisfy certain criteria, which may increase the total period of regulatory protection up to a maximum of 12 years (as compared to the current maximum of 11 years). The Directive retains the concepts of the global marketing authorization, whereby the period of RDP for all products within the same global marketing authorization starts on the date of the initial MA, and the European reference product, whereby the RDP applies in all Member States (even those where the reference product is not authorized).
Unlike the previous system, the Directive no longer provides a fixed period of eight years of regulatory data protection. Instead, the RDP period consists of a standard period of six years (applying to all marketing authorizations (“MA”) with a complete dossier) plus conditional periods (applicable to only some medicinal products).
Article 81(2) of the Directive sets out the various conditional periods. MAs may be eligible for one or more of these conditional periods. The conditional periods are granted following a request by the MA holders (“MAHs”):
+2 years for medicinal products supplied in Member States:
Products can get an additional two years of RDP if the MAH can show that it meets the conditions in Article 82 within two years of the MA grant. This deadline is extended to three years for MAHs who are micro, small and medium-sized enterprises (“SMEs”), not-for-profit entities or MAHs who, at the time of the relevant MA grant, have received not more than five centralized MAs for the MAH or members of its group. Article 82 requires that the MAH has released and “continuously supplied” a “sufficient quantity” of the medicinal product in the presentations necessary to cover the needs of patients in the Member States where the MA is valid.
To obtain the additional two years of RDP, the MAH must apply for a variation 34 – 36 months after the MA is granted (or 46 – 48 months for SMEs/not-for-profits/entities with five centralized MAs or less, as discussed above). The MAH must provide documentation from Member States where the MA is valid to evidence that it has released and continuously supplied the product (this requires a confirmation from the Member State, but a positive pricing and reimbursement decision under Articles 2 and 6 of Council Directive 89/105/EEC is considered equivalent). Alternatively, if the MAH fails to satisfy this requirement, the MAH must have a relevant statement of non-objection to prolong the period of regulatory data protection under Article 82 from the relevant Member States. MAHs can obtain such documentation by making a request to each Member State. If the Member State fails to respond to such request within 60 days, it will be deemed to have granted a statement of non-objection to prolong the period of RDP.
+6 months year for addressing unmet need
Products can also receive an additional six months of RDP if at the time of the granting of the initial MA the product addresses an unmet medical need. Article 83 sets out that a medicinal product will be considered to meet an unmet need if they are an orphan medicinal product, or if:
- at least one of its indications relates to a life threatening or severely debilitating disease; and
- the following conditions are met:
- there is no medicinal product authorised in the EU for such disease, or, where despite medicinal products being authorised for such disease in the EU, 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
- the following conditions are met:
This extension also applies to products with a conditional MA if a standard MA is granted for the product within four years of the grant of the conditional MA.
+6 months for New Active Substances (“NAS”) undergoing clinical trials against the relevant comparator
An additional six months’ RDP will be given to medicinal products that contain a NAS and whose initial MA includes clinical trials that use a “relevant and evidence-based comparator” in accordance with scientific advice provided by the European Medicines Agency (“EMA”) on the basis of relevant scientific guidelines (Article 81(3) requires the EMA to provide scientific guidelines setting out criteria for proposing a comparator for a pivotal trial). As such, MAHs will need to seek scientific advice from the EMA before starting pivotal clinical trials in order to be eligible for this conditional period of data protection.
+1 year for a new indication providing significant clinical benefit
Products can receive an additional year of RDP if they are authorized during the RDP period for an additional therapeutic indication that will provide a “significant clinical benefit” over existing therapies. This extension can only be granted once and will not apply to orphan products that benefit from extended periods of market exclusivity (please refer to our blog on orphan medicinal products for more information, available here).
Other RDP Periods
The Directive also provides additional RDP periods for:
- Evidence for change of prescription status: Article 55 provides one year of data protection for “significant non-clinical tests or clinical studies” that led to an amendment in the prescription status; or
- Repurposed medicinal products: Article 84 provides a standalone regulatory data protection period of four years for a medicinal product with respect to a new therapeutic indication not previously authorised in the EU if:
- adequate non-clinical or clinical studies were carried out in relation to the therapeutic indication demonstrating that it is of significant clinical benefit; and
- the medicinal product is authorized as a generic, hybrid, biosimilar or bio-hybrid medicinal product and has not previously benefitted from data protection, or 25 years have passed since the granting of the initial MA of the medicinal product concerned.
The four-year period referenced above can only be granted once for each medicinal product.
There are possible derogations from the RDP provisions, namely:
- if the MAH grants an applicant access to their data; or
- when a relevant authority grants a compulsory license the data and market protection is suspended in relation to the party that has the license.
The Commission stated the aim of its review of the legislation is to balance innovation with patient access. Therefore, it wants to reward products that it considers bring the greatest benefit (focusing on unmet medical need), while also speeding up access to generics and biosimilars. As such, it has suggested a variable RDP system. However, RDP is a crucial strategy to incentivize innovators to develop new products and/or new indications as the clinical development of medicines is extremely costly (e.g., due to the high cost of running clinical trials and high failure rates). Although the maximum possible period of combined regulatory data protection and marketing protection under the new rules is longer than under the current system (12 years versus 11 years), some medicinal products will have a reduced period of protection if they cannot satisfy the conditions for the conditional periods of RDP discussed above. The extensions will not be confirmed until the MA filing (or later, in the case of the extension for release and continuous supply), which will mean there is a lack of certainty for innovators looking to factor RDP considerations into their cost/benefit analyses during the product’s development. As such, there is a risk that innovators may be less incentivized to develop and launch new medicines in the EU.
The EC’s Impact Assessment also stated it “aimed at simplification and streamlining of regulatory procedures.” However, the variable system of RDP is more complex than the current system, as each MA could have a different amount of data protection. The Commission will need to ensure that RDP periods are clearly set out to avoid unnecessary confusion and disputes for innovator and generic pharmaceutical companies. Also, the Directive will impose a higher regulatory burden on MAHs, who, if they wish to obtain the possible extensions of the data protection, will need to seek scientific advice from the EMA during the clinical development phase, obtain additional evidence to support extension requests, and submit variations to their MAs at the appropriate time.
Finally, we would note that how the legislation works in practice will significantly depend on what is set out in guidelines. The Commission needs to provide clear guidance on key topics in the Directive. For example, it is unclear what “sufficient supply” means in the context of the additional two years of regulatory data protection under Article 81(2) and how it would be applied in practice. Member States may grant a statement of non-objection to prolong the period of regulatory data protection for this requirement, but there does not appear to be any clear incentive for a Member State to issue such a statement of non-objection. Would the extension of data protection on this basis be lost if the MAH subsequently fails to maintain the sufficient supply?
Article 82(5) expressly deals with “issues” in the application of this requirement (e.g., with respect to discussing issues on the practical application or providing guidance and seeking input from national pricing and reimbursement regulators). This Article may indicate that the Commission acknowledges and expects this requirement will lead to confusion and/or disagreements without additional clarification and guidance.
Another issue may arise with respect to the ability to obtain an additional 6 months’ regulatory data protection for comparator studies, since comparator studies may not always be available to all products (e.g., innovative products where conducting a comparative clinical trial is not feasible). As such, there is a risk that innovators may feel that the most innovative products may not be adequately rewarded under the new Directive.
This blog is based on the wording of the EU’s proposal published on 26 April 2023. This wording could significantly change during the legislative process. Our Dublin, Brussels, Frankfurt and London teams will continue to monitor this legislation. We will be hosting a webinar to discuss the impact on 9 May. To sign up for the webinar please click here.