Fast-tracking advanced therapies without compromising regulatory success

Advanced therapies are transforming treatment possibilities, but their development comes with complex regulatory hurdles. Speaking to Drug Target Review, Dr Christian Schneider, Chief Medical Officer Clinical Development Services Consulting at Pharmalex (part of Cencora), outlined the main challenges facing developers and practical steps to navigate them effectively while minimising delays and maximising approval prospects.

The twin hurdles: potency and comparability

The rapid evolution of advanced therapy medicinal products (ATMPs) and other complex biologics has created a fast-moving and intricate regulatory environment. For developers, one of the most pressing challenges is meeting Chemistry, Manufacturing and Controls (CMC) requirements – particularly given the inherent variability of biological materials and the difficulty of scaling production.

Two issues are central to regulatory success in this space – establishing a potency critical quality attribute (CQA) and ensuring comparability between batches.

“A potency CQA – which should be measurable, scalable and reasonable to assess during the compressed timelines of a commercial programme – can help to ensure the final product is consistently manufactured.”

A potency CQA is a defined, measurable characteristic linked to the therapy’s intended effect. Identifying it early helps align product testing with regulatory expectations and reduces the risk of delays. Comparability, meanwhile, ensures that products manufactured at different stages of development maintain consistent safety, efficacy and quality profiles, even as manufacturing processes evolve.

Schneider emphasises that monitoring manufacturing process changes is essential from the outset. He recommends developers retain Phase I samples wherever possible for later batch comparison, build a clear comparability narrative and design potency assays that are quantitative, stability-indicating and demonstrate lot-to-lot consistency. Without this, even the most promising therapies can stall in the regulatory pipeline.

Meeting Chemistry, Manufacturing and Controls (CMC) requirements is one of the biggest challenges in advanced therapy development, as biological variability and scaling complexities make consistent production difficult. Image credit: Shutterstock / mkfilm

Early engagement: more than just a meeting

One of the strongest themes in Schneider’s approach is the importance of engaging with regulators early and strategically. This begins with a well-defined regulatory plan that aligns with the target product profile (TPP) – a document capturing the product’s characteristics, target patient population, differentiation from existing treatments and potential risks.

“Regulators are happy to offer scientific advice and early engagement helps developers understand the regulatory agency and build key relationships.”

Schneider advises developers to be deliberate about which meetings to request, such as the FDA’s INTERACT or pre-IND meetings, and to understand each event’s prerequisites and timelines. This is where external consultants can add value – helping to frame agendas, develop briefing documents , craft questions that elicit actionable guidance, and do dry-runs including an estimate on what to expect from the Agency interaction.

In Europe, a national authority with specialist expertise in the relevant therapeutic area can be a valuable first point of contact.

Multi-region development: planning is everything

Globalisation has expanded the opportunities for drug developers – but also magnified regulatory complexity. Requirements differ not just between continents but sometimes between countries within the same region.

Schneider’s mantra is rooted in the need for developers to anticipate regulatory differences between regions. For example, the FDA and EMA do not always reach the same conclusion on orphan drug designation. In Europe, developers of oncology products and ATMPs must also address the joint clinical assessment (JCA) – a process in which EU member states jointly evaluate clinical evidence on a medicine’s relative effectiveness – required under the EU’s new health technology assessment regulation.

By leveraging the joint scientific consultation, companies can secure early feedback from both the EMA and national health technology assessment (HTA) bodies while designing pivotal trials. This integrated planning reduces the risk of costly redesigns later in development.

Underused fast-track pathways

Expedited regulatory pathways – including the FDA’s Priority Review, Breakthrough Therapy, Accelerated Approval and Fast Track, as well as the EMA’s PRIME designation – are increasingly common, with 79 percent of US product launches in 2024 making use of at least one. Research shows these mechanisms can, on average, accelerate time-to-market by up to 3.5 years. 

Yet Schneider warns against chasing speed at the expense of substance.

“Equally critical to long-term success is the need for robust data and evidence.”

The challenge, he says, is to integrate these fast-track tools into a strategy that still delivers a comprehensive clinical and economic evidence package. Safety, efficacy and durability remain the cornerstones of any successful approval – and cutting corners on evidence can erode the very advantage these pathways offer.

“Make haste, slowly”: lessons from the field

At Cencora’s Cell and Gene Therapy Summit, Schneider spoke on a panel titled Navigating special regulatory pathways for advanced therapy development success. The discussion highlighted real-world experiences with regulatory mechanisms such as RMAT and PRIME, offering practical guidance for biotech teams.

His parting advice is rooted in a classic adage:

“Make haste, slowly.”

The message is clear: rushing without careful planning can be as dangerous as moving too slowly. Clear goals, realistic expectations and transparent communication with regulators form the bedrock of a sound regulatory strategy.

The role of experienced partners

For smaller biotech teams, the sheer scope of regulatory requirements can be daunting. Schneider highlights the value of experienced partners in smoothing the path from early development to commercial launch. These experts can:

• Facilitate productive interactions with regulatory bodies
• Prepare and submit compliant documentation
• Give an indication on regulatory expectations and chances of acceptance of a given concept upfront
• Guide companies through evolving frameworks
• Support the design and execution of long-term follow-up studies

In a space where the rules are both intricate and evolving, this guidance can mean the difference between approval and delay.

Traditional models of regulation

Advanced therapies are transforming treatment options, but their development tests the limits of traditional regulatory models. Developers need to prepare for current requirements and anticipate how these will evolve in the future.

Schneider advises developers to engage early with regulators, build consistent manufacturing processes, use expedited pathways without compromising evidence and plan with a global regulatory framework in mind. He stresses that regulatory planning should be integrated into core product strategy, not treated as an administrative formality.

Delays in advanced therapy development are costly, and approvals require meeting strict regulatory standards. Schneider’s advice provides a clear framework for bringing treatments to market efficiently and in compliance.