As we mark the last few days of 2024, we look back on the regulatory achievements of the year. Were they impactful and useful for the off-patent industry, or did they miss the mark?
A couple of weeks back, industry stakeholders reflected on lessons learned for biosimilars in 2024 and what still needs to be done.
In this end-of-year review, we look at the regulatory landscape more broadly, with experts sharing with Generics Bulletin their hopes and dreams for the future.
Europe Casts A Wide Net Of New Proposals
The European region has seen a lot of new regulatory developments this year, spanning from the revision of the EU pharmaceutical legislation to the environmental risk assessment, which may pose a slight headache for off-patent drug makers.
- EU Pharma Package Needs More Work
One of the biggest regulatory developments in Europe was focused on the revision of the EU pharmaceutical legislation, as the regulatory component was an important part of the package, said Beata Stepniewska, head of regulatory affairs at Medicines for Europe.
“2025 will also be marked by work on the new pharmaceutical legislation. The final EU Council position is likely to be agreed under the Polish presidency and will be negotiated with Parliament under the Danish presidency in the second half of 2025,” she explained to Generics Bulletin.
Sandoz’s head of global regulatory affairs Michael Banks described the ongoing reform as transformative but said it remained incomplete.
“Regulators must prioritize passing a robust, future-proof framework that balances innovation, accessibility, and affordability. Clear provisions for timely market access to generics and biosimilars are critical,” he commented.
- Good News For Not-So-Good Variations Regulation
The EU regulators also worked on changing the variations system, something that Medicines for Europe has urged for a while, but, again, more work needs to be done to reach its full potential.
“The new regulation is admittedly not ground-breaking yet. For more significant changes we must wait until the completion of the Pharma Review, including digitalization and reporting to databases,” said Stepniewska.
Banks expects 2025 to be the year of its practical implementation. “Regulators must focus on refining the guidelines to fully enable a risk-based approach, particularly for biologics, and address any operational challenges that arise,” he cautioned.
However, not all is lost, as positive changes can be anticipated in the upcoming revised Variations Classification guideline, which is expected to be published in 2025. This may include the downgrading of some categories, especially for biologic products, Stepniewska explained.
- Obtaining Originator Data For Environmental Risk Assessment
Another aspect that needs more clarity is the updated EU guideline on environmental risk assessment for medicinal products, which introduced a new dimension for generic applications.
“Now, applicants must provide a scientific evaluation of environmental impact rather than a general statement,” said Banks.
“While this promotes sustainability, it poses challenges in obtaining originator data, especially for older reference products, potentially requiring generics manufacturers to generate new data,” he added, noting that “regulators should work on creating transparent, practical solutions to support applicants.”
- Strive For A Faster MA Process
The European Medicines Agency has been struggling with the speed of the regulatory process and the availability of sufficient resources to run the marketing authorization process in a timely manner for several years now, said Stepniewska.
Next year, she hopes that Medicines for Europe will have a joint discussion with the EU regulator and see visible improvement.
“It needs to be short-, mid-, and long-term plans to be set up by the Heads of Medicines Agencies to improve the availability of resources for off-patent applications, while the industry needs to be more transparent and communicate better on delays in their development and submission plans,” she explained.
UK To Start The Year With Windsor Framework
In the UK, the Medicines and Healthcare products Regulatory Agency celebrated the finally resolved backlog of new product license approvals, but the uncertainty of the post-Brexit agreement between the UK and EU looms.
MHRA Beats New Product License Backlog
While the EMA has yet to find ways to streamline its application process, the MHRA has seemingly figured it out. The UK agency solved the backlog of new product license approvals, marking a very important milestone for the industry.
Revisit Our Past Editions Of Regulatory Recap:
- Regulatory Recap: FDA’s Rx Advertising Draft Needs A Stronger Voice, Say Commentators
- Regulatory Recap: US Senate Passes Anti-Patent Thicket Bill, EU Council Debates Pharma Package
- Regulatory Recap: Generic Medicines Work-Sharing Initiative Outlines Foreign Comparator Acceptability
- Regulatory Recap: FTC And Others Support Biosimilar Interchangeability Draft Guidance
- Regulatory Recap: BRICS Countries Discuss Building Independent Market For Biosimilars
- Regulatory Recap: EU’s Wastewater Directive Threatens Generic Industry, Medicines For Europe Says
- Regulatory Recap: Medicines For Europe Reiterates Support For ‘Bullet-Proof’ SPC Process
“At the start of the year, this stood at about 1,200 pending applications, and by the end, it had almost completely gone,” said Paul Fleming, technical director for the British Generic Manufacturers Association.
The MHRA announced a new guideline in March, outlining process changes for assessing established medicines that are aimed at shortening timeframes for assessment. The initiative was welcomed by the BGMA, but the trade group called on the agency to take more definite action on the backlog.
And while the problem has been solved, the MHRA needs to find a way to maintain a clean slate.
“We need to maintain this going forward and ensure there is no return of delays. We also need to ensure there is an acceleration in approvals back to around 12 to 15 months for new generic medicines,” Fleming told Generics Bulletin.
- Labeling Under Windsor Framework Is Here
As the clocks strike midnight, the uncertainties of the Windsor Framework will become a reality, as the new packaging requirements come into effect on 1 January 2025.
“Our industry will continue implementing the many changes brought by the Windsor Framework agreement next year and we hope that the impact of these stabilizes over the course of the next 12 months,” said Fleming, adding that the UK industry will also have to “see what impact there is on the UK from the European Pharma Review.”
Canada’s Pharmacare Package Created Uncertainty
While several regions saw reforms aimed at improving the off-patent industry, or at least attempts to do so, Canada was somewhat left at a crossroads.
“The ambiguity of the national pharmacare legislation passed by the Government of Canada this fall has created uncertainty for all players in the prescription drug supply chain in Canada,” commented Jeff Connell, vice president of corporate affairs at the Canadian Generic Pharmaceutical Association.
The reform was announced earlier in the year, establishing the foundations of the first phase of national universal pharmacare in the country and its multiple provinces and territories.
Connell said that CGPA “supports efforts to improve prescription drug coverage for Canadians,” and that “making prescription medicines more accessible is the key value proposition of our industry,” but the Canadian off-patent trade group remains cautious.
“We must work to ensure that the implementation of national pharmacare does not exacerbate drug shortages, which remain at record high levels in Canada, and further diminish our domestic manufacturing capacity,” Connell told Generics Bulletin.
Strengthening The Global Framework For Nitrosamine Impurities
In September, the US Food and Drug Administration released the second revision of its final guidance on nitrosamine drug substance-related impurities. It was implemented “without prior public comment because it has determined that prior public participation is not feasible or appropriate,” the agency said.
However, “while the FDA aligns with global regulators on controlling multiple nitrosamines to some extent, it resists higher limits for NDSRIs without extensive data and this presents significant compliance challenges for the generic industry,” the Association for Accessible Medicines highlighted to Generics Bulletin.
Other Honorable Mentions Of Regulatory Developments In 2024:
- Switzerland Eases Parallel Importing And Allows Biosimilar Substitution
- Canada Considers Joining FDA-EMA Complex Generic Advice Scheme, But Is It Working?
- IGBA Celebrates ICH Re-Election And CEO Committee Progress
- Off-Patent Group Trio Aims To Secure Transatlantic Drug Supply
- US Bill Recap: What Are The Latest Legislation Moves Covering Generics And Biosimilars?
- Philippines Seeks Feedback On Plan To Recognize BE Studies Under ASEAN Deal
- The BIOSECURE Act: What Does It Mean For The Off-Patent Industry?
The US off-patent trade group wants to see the FDA working with “industry and global health authorities to harmonize strategies for addressing nitrosamine concerns and to establish more practical timelines, particularly for generic companies supplying dozens or even hundreds of products to US and global patients.”
Looking ahead, global regulators must focus on strengthening the framework for nitrosamine impurities, urged Susana Almeida, secretary general of the International Generic and Biosimilar medicines Association.
“Nitrosamines, if not adequately managed, pose a significant safety risk. Regulatory alignment on controlling these impurities is crucial to safeguarding global medicine supplies,” said Almeida.
Regulators should follow the addendum to the International Council for Harmonisation’s M7 guideline, which “represents a critical step in incorporating the latest scientific insights into the evaluation and control of nitrosamine impurities.”
“We advocate for elevating regionally aligned nitrosamine guidance to the ICH level to ensure a globally harmonized approach, reduce inconsistencies, and prevent future regulatory divergence,” she encouraged.
Regulatory Aspirations For The Future
Setting up resolutions and goals for the new year is important for everyone, especially for regulatory agencies as their work needs to continue to address important issues.
- Global Harmonization For Bioequivalence And Foreign Comparator Acceptability
Another big international achievement was the ICH updating its M13A bioequivalence guideline for immediate-release solid oral dosage forms.
“At IGBA, we believe that its implementation will streamline regulatory processes by enabling the use of standardized data across multiple jurisdictions,” shared Almeida with Generics Bulletin, adding that the organization views “this milestone as a cornerstone for advancing access to affordable, quality-assured medicines worldwide.”
Sandoz’s Banks seconded this thought, saying that the update “marked a significant change by removing the previously mandatory requirement for fed bioequivalence studies,” with the FDA subsequently revising “over 700 product-specific guidance to reflect this change, eliminating fed study requirements.”
Next, there is a need for harmonization of BE standards and to develop criteria to legally accept foreign comparators. “Without alignment between international harmonization and country- or region-specific legislation, the potential benefits of single global development remain unrealized,” said Almeida.
- Age Of Digitalization Needs Regulation
In a world where technology and artificial intelligence have been incorporated into our daily lives, regulators still need to address this in healthcare.
“Rapid advancements in areas like digital therapeutics, precision medicine, and AI in drug development require regulatory frameworks to adapt proactively. Collaboration with industry stakeholders will ensure that regulations remain agile and supportive of innovation while safeguarding patient safety,” hoped Banks.
BGMA’s Fleming said that the UK’s MHRA has the capabilities to do so. “We really need to see greater modernization of the regulatory systems with more digitization and use of AI. The MHRA has the platform to do this if it makes full use of its Regulatory Connect system, including the potential for self-regulation.”
The EMA has also moved towards digitalization this year with projects such as the SPOR data management services, the pilot program for electronic product information, and the resumed work on the Regulatory Optimisation Group, for which Medicines for Europe has high hopes, said Stepniewska.
“We also expect continuous progress in digitalization and digital projects at the EMA, particularly in establishing the Product Management Service as the ‘one source of truth’ for structured, standardized, and consistent authorized product data across the European Medicines Regulatory Network,” she added.
- Tackling Global Drug Shortages
Finally, the CGPA’s Connell hopes to see global agencies addressing a very critical problem – drug shortages.
“Looking ahead to 2025, we need all major international regulators to take real and concrete action to address the root causes of drug shortages. Importantly, this includes taking seriously the economic factors that are causing supply chain disruptions,” he said.
This past year, we saw multiple regions, such as the US, EU, Canada, and Australia, address their respective drug shortages and propose ideas on how to tackle the problem. But was it enough?
“To date, we have, unfortunately, seen regulators focused on adding additional – and often unnecessary – regulatory burden on manufacturers that will only increase their costs and do little to alleviate shortages,” Connell concluded.
