Are you truly up to speed on the most effective strategies to expedite the approval process for your innovative product in Europe's evolving regulatory landscape?
In the United States (US), the Food and Drug Administration’s (FDA) well-established incentives for advancing groundbreaking medicines continue to make headlines, including Accelerated Approval, Priority Review, Fast Track Designation, and Breakthrough Designation. Yet, the intricacies of these programs require substantial effort to obtain a comprehensive understanding.
However, it's crucial to acknowledge that the European Medicines Agency (EMA) and the Medicines and Healthcare products Regulatory Agency (MHRA) have regulatory incentives with a similar aim, but these might remain less familiar to US-based sponsors.
By unravelling the complexity of these programs and discerning their distinctions from the FDA's initiatives, you can significantly enhance your development endeavours, reaching patients across Europe—an arena that continues to assert its dominance as the second-largest pharmaceutical market worldwide.
Introduced in 2016, the PRIority MEdicines (PRIME) initiative remains a key response to the FDA's Breakthrough Designation. While PRIME designation mirrors accelerated assessment criteria, it can be secured at an earlier stage of product development. A notable proportion of designations continue to be awarded to orphan medicines.
Advantages of PRIME designation extend to early Rapporteur appointments. These are reviewers from EU Member States who oversee marketing authorization application (MAA) evaluations. Notably, Scientific Advice for PRIME-designated products is dispensed within an expedited 40 days, compared to the conventional 70-day period.
Yet, securing PRIME designation remains statistically challenging, with only 25% of applications proving successful. Even "advanced therapy medicinal products," encompassing cell and gene therapies, the approval rate stands at 40%. Refusals often stem from the inability to establish significant therapeutic superiority related to study design issues or that the drug development is deemed already too advanced to expect that it can still benefit from intense regulatory support as part of the PRIME scheme.
Compared to the U.S. Accelerated Approval, CMA continues to be a less common occurrence (approximately 10.6% of new drug approvals from 2018-2022, in contrast to roughly 26.3% receiving accelerated approvals in the same period).
CMA is still predicated upon an unmet medical necessity implying the absence of satisfactory methods or a substantial enhancement over existing options —whether it pertains to a severely debilitating/life-threatening ailment, an emergent situation, or an orphan disease.
While CMA enables authorization based on relatively incomplete clinical data (e.g., Phase 2 uncontrolled trials), a positive benefit-risk balance is still a prerequisite. Furthermore, it's vital to demonstrate the capacity to furnish comprehensive data post-approval through mandatory Specific Obligations. Generally, common practice remains that the confirmatory trial is already ongoing during the application phase.
It's essential to emphasize that obtaining accelerated approval from the FDA does not guarantee eligibility for CMA, and vice versa. Each path mandates its own compelling regulatory justification.
At the heart of exceptional circumstances lies a profound understanding of the challenges posed by ultra-rare diseases. These medical conditions, often affecting very small patient populations, can pose significant obstacles to the collection of clinical data to the extent required for traditional benefit-risk analyses. As a result, the regulatory landscape recognizes the need for flexibility, allowing for the authorization of therapies even when obtaining comprehensive evidence is not achievable.
However, the exceptional circumstances pathway is not a free pass from rigorous examination. Rigorous evaluation, continuous monitoring, and robust post-authorization commitments remain integral to this framework. This pathway epitomizes regulatory agility—one that recognizes the medical challenges and ensures that promising treatments and solutions can reach those in need when conventional regulatory paths encounter insurmountable hurdles.
Unlike the FDA's Accelerated Approval, accelerated assessment in Europe mirrors the essence of Priority Review. It reduces the evaluation period for an MAA from 210 to 150 days (excluding instances where questions lead to clock stops). However, instances where significant objections from the Agency arise, requiring extended resolution time, revert the process back to the standard timeline.
While accelerated assessments are not common (in 2022 approximately 12% of MAAs were granted accelerated assessment), it is notably less common than Priority Review (approximately 34% in 2022). To qualify for Accelerated Assessment in Europe, the product must exhibit "major public health interest" in terms of therapeutic innovation, offering substantial therapeutic advantage for a condition devoid of satisfactory diagnostic, preventive, or treatment approaches.
While the FDA frequently employs the rolling review, its notable use in the EU emerged during the COVID-19 pandemic. Europe’s dynamic regulatory landscape is poised to offer a more robust framework for rolling review within the draft revision to the Pharmaceutical legislation. The updated legislation is primed to permit the EMA to initiate review of data packages for individual modules of MAAs before the entire application is submitted. This approach allows the EMA to provide feedback to the applicant early in the development process, and the applicant can make changes to their application as needed, aiming for reduction in the overall marketing authorisation procedure timeline. However, the final implementation of this legislation is still to be realised. Notably, the UK's Innovative Licensing and Access Pathway (ILAP) introduces provisions for rolling reviews, bridging the gap between the two regulatory frameworks.
Early access programs in Europe are designed to provide timely access to promising pharmaceutical products for patients with serious or life-threatening conditions. These programs address unmet medical needs, offer hope to patients with limited treatment options, while also maintaining stringent safety and ethical standards through regulatory oversight.
The Early Access to Medicines Scheme (EAMS) is a regulatory pathway in the European Union (EU) that allows patients with serious or life-threatening conditions to gain access to promising medicines before they receive full marketing authorization.
It is designed to address the unmet medical needs of patients who have limited or no treatment options. Manufacturers can apply for EAMS designation for their experimental drugs, which undergo a streamlined evaluation process by regulatory authorities. EAMS provides a framework for collecting and assessing data on a drug's safety and efficacy while it is being used in the real world, helping inform future regulatory decisions. It offers a balance between patient access and safety, ensuring that benefits outweigh risks.
Compassionate use programs, also known as expanded access programs, enable patients to access investigational drugs outside of clinical trials when they have exhausted all other treatment options. These programs are typically initiated by pharmaceutical companies in response to individual patient requests or physician recommendations. Access to the drug is granted on a case-by-case basis, considering factors such as the severity of the patient's condition and the drug's potential benefits. Regulatory agencies, such as the EMA, may provide guidance and oversight to ensure safety and ethical standards are met. Compassionate use programs can be a vital lifeline for patients facing life-threatening diseases who have no other viable treatment options.
In January 2021, the UK introduced the ILAP. While sharing similarities with EMA's PRIME, ILAP enhances regulatory collaboration. MHRA now aids sponsors in crafting target product profiles and approval roadmaps, accommodating clinical data for MAA evaluation through rolling reviews.
Previous ILAP blogs:
In the realm of oncology, the UK's participation in Project Orbis facilitates synchronized reviews with the FDA for innovative applications. Additionally, the UK has retained the EU's concepts of CMA and exceptional circumstances marketing authorizations, underscoring its commitment to expedited access.
Most recently, the MHRA has announced an international recognition framework set for rollout in January 2024. This comprehensive system enables the MHRA to engage with regulatory authorities worldwide, fostering harmonization and cooperation in the evaluation of medicines and medical devices. It champions mutual recognition of regulatory decisions, data sharing, and alignment of standards to ensure the efficient approval of healthcare products while upholding safety and efficacy standards. This framework not only enhances global collaboration but also bolsters the UK's standing as a trusted partner in the international healthcare regulatory community.
Shifting focus beyond regulatory approval to encompass market access is pivotal. Failing to adopt this comprehensive approach can lead to substantial delays, with Health Technology Assessment (HTA) bodies demanding comprehensive data packages that demonstrate clinical and/or cost effectiveness.
For products eligible under ILAP in the UK, payer interactions are seamlessly integrated into the process. The EUnetHTA 21 consortium's parallel advice procedures with the EMA are designed to streamline the evaluation and approval process for new medical technologies and medicines in Europe. These procedures offer numerous benefits, including efficiency, improved planning, transparency, and ultimately faster patient access to innovative healthcare solutions.
Come January 2025, the Health Technology Assessment Regulation, introduced in January 2022, will be in full effect. This framework seeks to harmonize and improve the assessment of health technologies across European Union (EU) member states. Its expected impact includes streamlining the evaluation process for new medical technologies, enhancing transparency, and promoting consistent decision-making. Ultimately, HTA-R aims to facilitate access to innovative healthcare solutions while ensuring their safety and effectiveness.
Leveraging multiple expedited programs is a prudent strategy for companies with pioneering therapies addressing significant unmet needs. For instance, products designated under PRIME are likely to leverage accelerated assessment, potentially enhancing the odds of securing CMA. ProPharma, with its extensive knowledge of the multiple accelerated programs available throughout the product development journey, offers unrivalled expertise in crafting and executing potent strategies that draw from potentially various initiatives, ultimately fast-tracking treatment accessibility.
Sponsors should consider at an early stage of their drug development whether their product would qualify for expedited pathways, and which, followed by determining the most effective and efficient route (regulatory agency-wise). Expedited programs have individual and often overlapping requirements to be fulfilled. In order to make the best use of the programs available requires a robust understanding of the system and relevant experience.
Our consultants, armed with decades of global development expertise, adeptly navigate FDA and European agencies' evolving requirements. If you believe your product qualifies for any of these expedited programs and want to seek tailored guidance, connect with ProPharma. We harness our expansive knowledge and hands-on experience with regulatory bodies to ensure seamless interactions and development strategies. Reach out to us to explore our services and embark on this journey today.
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