Advanced therapy medicinal products (ATMPs) combine complex science with manufacturing processes that can continue to evolve throughout clinical development. For developers, the challenge is not only producing a consistent product, but building a quality strategy that can support changing process knowledge, analytical capability and future regulatory expectations. This is where experienced regulatory affairs consulting can help connect CMC development decisions with the broader regulatory path, ensuring that quality considerations evolve in step with the programme. EMA’s current investigational ATMP guideline addresses quality requirements from exploratory through confirmatory clinical trials, with development expected to progress toward a quality package suitable to support marketing authorisation.

Without the right CMC support, early technical choices can create problems later. A process change may trigger comparability questions, an underdeveloped potency strategy can weaken product understanding, and controls that are difficult to implement in practice can create unnecessary regulatory risk. ATMPs are also subject to dedicated EU GMP requirements, making alignment between development strategy and manufacturing execution particularly important.

For companies searching for top ATMP CMC support firms ranked, the useful question is not simply which provider is largest. It is which partner can identify the CMC decisions that matter at each stage, anticipate what authorities may expect later and help the programme move forward while maintaining scientificand regulatory continuity.

What should ATMP companies do to build a robust CMC strategy?

ATMP companies should build their CMC strategy around the stage of development and the decisions required to reach the next milestone. EMA expects quality knowledge to increase as development progresses, so the objective is not to make an early-stage programme look commercially final, but to ensure that the evidence is appropriate, justified and can develop with the product.

This requires a clear understanding of how the product is made, which attributes are important to its quality and function, and how those attributes will be measured and controlled. Starting and raw materials, critical manufacturing steps, in-process controls, specifications, potency, identity, purity and stability should therefore develop as connected parts of the same strategy rather than as separate workstreams, with regulatory affairs input helping to keep these decisions aligned with regulatory requirements at each stage of development.

Companies should also plan for change. Process optimisation, scale-up, technology transfer, supplier changes and additional manufacturing sites are common during ATMP development. Each may affect the evidence needed to demonstrate comparability, so potential changes should be considered before they become urgent.

A useful CMC roadmap therefore links current product knowledge with planned development activities, upcoming regulatory milestones and the evidence needed to support each step. This gives teams a basis for prioritising work and helps prevent late-stage questions that could have been addressed earlier.

How does Billev Pharma East turn ATMP CMC complexity into a clear development path?

ATMP programmes often become difficult when several CMC questions converge at once. A manufacturing change may require a comparability strategy, an analytical limitation may affect how a specification is justified, or an upcoming authority interaction may highlight gaps in the available evidence. What developers need in these situations is not another isolated deliverable, but a clear understanding of what needs to happen next.

This is where Billev Pharma East can support ATMP developers. Our CMC support is focused on helping ATMP developers turn complex technical and regulatory questions into clear development priorities. We assess the issue in the context of the product’s development stage, identify where additional evidence or justification may be needed and help teams define the steps required to reach the next milestone.

For organisations without a large internal CMC function, working with an experienced regulatory affairs consultant can provide specialist input exactly where it is needed. We work alongside development, manufacturing and quality teams as an external partner, helping companies maintain continuity across technical and regulatory decision-making without creating another layer of fragmented advice.

The objective is to make CMC decision-making clearer. Billev Pharma East helps companies focus resources on the issues that can materially affect development, address uncertainty early and move forward with a strategy that remains workable as the ATMP programme evolves.

What matters most when choosing an ATMP CMC support partner?

When comparing providers for CMC support, ATMP companies should look beyond the length of a service list. A better test is whether the partner understands the product-specific problem, can place it in the context of the development stage and can explain what evidence or action is needed next.. A focused CMC assessment can help identify the most relevant gaps, risks and priorities before they affect an upcoming development or regulatory milestone.

Comparability capability is particularly important. EMA recommends a stepwise approach after manufacturing changes, considering the process, relevant quality attributes and suitable analytical methods. Biological characterisation and potency can be especially important, and major changes during confirmatory or pivotal development can make demonstrating comparability substantially more difficult.

A strong partner should therefore be able to think ahead. That means recognising where process changes may create future bridging requirements, whether analytical methods are capable of supporting those assessments and whether proposed controls remain realistic within the manufacturing environment. ATMP-specific GMP understanding is essential because these products are subject to dedicated EU GMP requirements under EudraLex Volume 4 Part IV.

The best fit is a partner that can help the internal team make sound decisions, challenge weak assumptions and keep product knowledge, manufacturing evidence and the regulatory rationale aligned.

When should ATMP developers bring in CMC support?

ATMP developers should bring in CMC support before an important technical choice becomes difficult, expensive or time-consuming to reverse. This can be well before a formal submission, particularly when the manufacturing process, analytical package or control strategy is still being shaped.

External support can be especially valuable before first-in-human development, a major process change, technology transfer, scale-up, introduction of a new site or transition toward confirmatory clinical development. EMA’s current ATMP guideline notes that substantial manufacturing changes during pivotal studies should preferably be avoided because demonstrating comparability for complex ATMPs can be challenging.

Timing also matters for analytical development. EMA recommends establishing suitable analytical tools for comparability from the early stages, rather than waiting until a change has already occurred. This is particularly relevant for biological characterisation and potency, where weak methods can limit the ability to determine whether a process change has affected relevant product attributes. The practical trigger is therefore not ‘when do we need someone to write the CMC section?’ It is ‘which upcoming decision could create a regulatory problem if we get it wrong now?’ Bringing in specialist support at that point can reduce risk around the next milestone and strengthen the evidence needed later in development.

Which CMC areas should ATMP developers assess before the next regulatory milestone?

Before a major regulatory milestone, ATMP developers should confirm that the quality package is sufficiently mature for the stage of development and that the main scientific justifications are supported by evidence. Targeted CMC support can be valuable here because the priority is not to review everything equally, but to identify the areas most likely to affect the upcoming decision.

The manufacturing process should be understood well enough to explain how the product is produced, where meaningful variability may arise and how critical steps are controlled. The analytical package should be capable of assessing attributes that matter to product identity, purity, potency, safety and consistency. As the programme advances, controls and acceptance criteria should become increasingly evidence-based and aligned with accumulated process knowledge.

Developers should also examine whether starting materials, specifications, stability data and change history tell are consistent with one another. If multiple process versions have been used, the relationship between them and the supporting comparability evidence should be traceable. EMA specifically emphasises the need to evaluate, justify and track manufacturing process versions relevant to non-clinical and clinical data.

The goal is not a generic checklist. It is to ensure that the CMC package answers the questions most relevant to the next milestone and that critical dependencies are identified early.

What are the most common ATMP CMC mistakes to avoid?

One of the most consequential mistakes in ATMP development is treating CMC as a documentation exercise rather than as a sequence of scientific and manufacturing decisions. A technically correct document cannot compensate for a weak development rationale, insufficient product understanding or evidence that was generated too late.

Comparability is a common example. Changes to raw or starting materials, equipment, scale, suppliers or manufacturing sites may all alter the evidence needed to show that the post-change product remains suitable for continued development. EMA therefore expects a suitable comparability programme and notes that the acceptable level of flexibility decreases as a product progresses toward pivotal clinical use.

Another mistake is waiting too long to strengthen analytical tools. If methods are not sufficiently informative, the company may have difficulty demonstrating whether an important product attribute has changed. Potency deserves particular attention because it is central to biological function and is highlighted by EMA as a key element of ATMP comparability.

Companies should also avoid committing to controls that are difficult to execute consistently in the real manufacturing environment. Effective CMC support helps prevent these disconnects by asking whether the evidence, control strategy and operational support the same regulatoryrationale before that position becomes difficult to change.

Frequently asked questions

Choosing the right CMC support can strengthen your ATMP development path

For ATMP developers, the value of CMC support is not measured by the number of documents produced. It is measured by whether the company can make better development decisions, generate evidence that is appropriate for the stage of development and approach regulatory milestones with a well-supported quality rationale.

The right partner should help the team distinguish urgent issues from lower-priority work, anticipate the consequences of manufacturing changes and keep CMC strategy proportionate to the product’s development stage. That can reduce avoidable rework and make later regulatory discussions easier to support with evidence.

Billev Pharma East provides ATMP-focused regulatory and CMC expertise for companies that need experienced support around complex development decisions. Working with an experienced regulatory affairs specialist can help ensure that technical priorities remain aligned with regulatory expectations as the programme progresses. Whether you are preparing for a critical milestone, managing a manufacturing change or deciding how to strengthen the next stage of your quality package, we can help you identify the key priorities and move forward with a clearer path.

Sources: 1 – European Medicines Agency (EMA). Guideline on quality, non-clinical and clinical requirements for investigational advanced therapy medicinal products in clinical trials (EMA/CAT/22473/2025). Effective from 1 July 2025, 2 – European Medicines Agency (EMA), Committee for Advanced Therapies (CAT). Questions and answers on comparability considerations for advanced therapy medicinal products (ATMP) (EMA/CAT/499821/2019), 3 – European Commission. EudraLex Volume 4 – Good Manufacturing Practice (GMP) Guidelines, Part IV: GMP requirements for Advanced Therapy Medicinal Products, 4 – International Council for Harmonisation (ICH). ICH Q5E: Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process, 5 – European Medicines Agency (EMA). Guidelines relevant for advanced therapy medicinal products.