What This Page Covers
This page covers biological medicinal products: recombinant proteins (monoclonal antibodies, bispecific antibodies, antibody-drug conjugates), vaccines (including mRNA vaccines against infectious diseases), blood-derived products, biosimilars, and advanced therapy medicinal products (ATMPs) including gene therapies, somatic cell therapies, and tissue-engineered products. It also addresses the drug-device combination dimension inherent to most biologics. For small-molecule pharmaceuticals, see Pharmaceuticals. For standalone medical devices, see Medical Devices. For dedicated combination product guidance, see Combination Products.
Three Categories, All With Different Development Requirements
“Biologics” covers products that share a biological origin but differ significantly in how they are developed, manufactured, and regulated.
Classical Biologics and Vaccines
Monoclonal antibodies, recombinant proteins, and vaccines. In the EU, they follow the centralised procedure if they are manufactured by a biotechnological process or if they are intended for specific indications. The development path is well-known but CMC is typically the most complex workstream: post-translational modifications, glycosylation patterns, aggregation profiles all must be characterised and controlled because they directly affect clinical performance. Key for success is to have a fully controlled process with adequate controls as full characterisation of the drug substance is hardly possible. In most cases it is best to start analytical method development early with adequate biological assays. The assays being used during development become the assays in the specification and stability programme. Waiting to build a robust analytical package can create comparability questions at scale-up.
Vaccines bring their own classification complexity. Traditional vaccines and mRNA vaccines against infectious diseases are classified as biologics (“immunological medicinal products”). But mRNA therapeutics for non-infectious indications (personalised cancer vaccines, protein-replacement therapies) are classified as gene therapy medicinal products under the ATMP framework. The classification depends on the indication, not the technology. This classification then determines which committee assesses the application, which guidelines apply, and which GMP framework governs manufacturing. EMA published a dedicated draft quality guideline for mRNA vaccines in March 2025, the first of its kind.
Biosimilars
Biosimilar development follows a stepwise comparability exercise: analytical and functional characterisation first, PK comparison second, and (where required) clinical efficacy data. The most important part is the pharmaceutical comparability between reference product batches obtained from EU market and the biosimilar product. Our CMC team has extended experience in the regulatory requirements for such a package, especially in the analytical techniques, the number of batches to investigate, the statistical approach, and how batches from non-EU markets can support the study.
The key question is always how much clinical data is actually needed. EMA's draft reflection paper (April 2025) proposes that comparative efficacy studies may not be required where analytical, functional, and PK similarity are robustly demonstrated. Implementation is expected in 2026. The MHRA already allows this. This substantially changes the development economics, but the quality and depth of the analytical programme become even more relevant.
The current wave of patent expiries on blockbuster biologics means the biosimilar pipeline is more competitive than ever; speed to market, device strategy (autoinjectors, prefilled syringes), and market access positioning matter as much as the regulatory dossier.
ATMPs: Gene Therapies, Cell Therapies, Tissue-Engineered Products
Assessed by EMA's Committee for Advanced Therapies (CAT), centralised procedure, manufactured under EU GMP Part IV (unchanged since 2017, now under revision with formal review targeted Q4 2026).
For autologous cell therapies (CAR-T products being the most established), the starting material is the patient's own cells, collected by apheresis. Each manufacturing batch produces a product intended for one specific patient. This creates strict requirements around chain of identity (COI) and chain of custody (COC): the QMS must maintain a permanent, bidirectional traceability link between patient and product at every handover point, from cell collection through manufacturing, cryopreservation, transport, and administration. COI/COC documentation must be tamper-proof, and labelling systems must prevent misidentification. GMP inspectors assess these controls with particular scrutiny because a batch mix-up in autologous therapy can result in patient harm or death.
Potency assays present a specific technical challenge. Unlike monoclonal antibodies where binding affinity and functional activity can be measured with well-established methods, the biological activity of cell therapy products often depends on complex mechanisms (e.g., T-cell cytotoxicity, engraftment capacity) that are difficult to reduce to a validated, quantitative release assay. Potency strategy should be discussed with regulators early because it defines the product specification, the comparability approach for process changes, and the lot release criteria.
Sterile filtration is not a viable option for living cells, so all manufacturing must be aseptic. Autologous products scale out (more batches), not up (bigger batches), which reshapes facility design, staffing, and QC capacity. And market access is exceptionally challenging since treatments are often costly and require reimbursement models that most healthcare systems are not designed for.
Blood-derived medicinal products. These substances of human origin (SoHO) are a special group of products which required extensive documentation and traceability from donor to patient. The related products can be used as such or incorporated into medicinal products or medical devices and must then follow the applicable EU Regulations.
The Drug-Device Dimension
Most biologics are administered by injection, which often makes the final commercial product a drug-device combination. Prefilled syringes, autoinjectors, pen injectors, and on-body delivery systems are regulated device components, not just primary packaging. In the EU, the device component must meet MDR Annex I requirements and receive a Notified Body opinion (MDR Article 117). Treating the device as a late-stage packaging decision is not the best idea.
We have teams in pharmaceutical development and medical device regulation. For drug-device combination products, these teams work as one integrated project team: CTD Module 3 on the drug side, MDR compliance and Notified Body interaction on the device side. And regulatory is obviously also involved.
What Is Needed Across the Development Journey
Developing a biologic, biosimilar, or ATMP requires different things at each stage. Select a phase to see the key requirements.
Discovery & Concept
Product classification: biologic, biosimilar, ATMP, or combination product. Regulatory pathway mapping (centralised procedure, CAT classification request). Reference product selection and sourcing strategy for biosimilars. Early regulatory engagement for ATMPs (e.g., CAT classification request).
Drug Substance Development and Characterisation
Adventitious agents safety evaluation. Analytical similarity study design for biosimilars. Donor qualification criteria and starting material characterisation for ATMPs. Early CMC: cell line or vector selection, process development strategy, analytical method development. Qualification of CDMOs involved in development.
Preclinical
Non-clinical programme design and conduct of all studies required prior to first-in-human, including validation of the programme with authorities (Scientific Advice, pre-IND meeting). Adventitious agents and TSE/BSE safety evaluation. Vendor qualification of preclinical study sites.
Design & Development
Process development, characterisation, formulation, analytical validation. Biosimilar comparability exercise design. COI/COC systems and potency assay development for ATMPs. Drug-device integration where applicable (delivery device selection, human factors, MDR Annex I planning). Scientific Advice (EMA, FDA, or joint) before committing to the pivotal programme.
Clinical
CTA/IND preparation including IMPD authoring. PK, immunogenicity, and (where needed) efficacy study design. For ATMPs, clinical trial applications should follow the July 2025 EMA guideline, with long-term follow-up planning built in from the start. Pharmacovigilance setup for clinical phase. Clinical supply chain and cold chain qualification.
Late Phase Clinical
Scale-up to commercial scale prior to Phase III studies, process validation, completion of analytical validation and finalisation of characterisation. Pharmacovigilance system establishment and risk management plan. Establishment of commercial supply chain and qualification of vendors.
Regulatory Submission & Approval
CTD Modules 1 to 5, including complete Module 3 with process, characterisation, and specification data. Biosimilar comparability argumentation. CAT/CHMP coordinated assessment for ATMPs. Notified Body opinion on the device component for combination products (MDR Article 117). GMP readiness for pre-approval inspection. Market access and HTA strategy in parallel.
Launch & Market Access
Pricing, reimbursement, and HTA submissions. ATMPs may require outcomes-based or managed entry agreements. Product information and labelling compliance. Device vigilance for combination products.
Post-Market & Lifecycle Management
Post-approval variations including manufacturing process changes with comparability assessment. Ongoing similarity demonstration for biosimilars. PSURs, signal detection, risk management plan updates. GMP/GDP audits. Due diligence support for acquisitions and divestitures.
Example Projects
Illustrative Example
Positive CHMP opinion within standard timeline
Biosimilar Monoclonal Antibody: EU Centralised Submission
A mid-sized biosimilar developer needed to bring a monoclonal antibody biosimilar from analytical comparability design through to MAA. We designed the analytical similarity programme, prepared the PK study protocol and immunogenicity strategy, authored CTD Modules 1 to 5, and managed the CHMP procedure including Day 120 responses.
Positive CHMP opinion within standard timeline
Illustrative Example
CTA approved without clinical holds
ATMP Gene Therapy: CTA Preparation and CAT Scientific Advice
An academic spin-out developing a lentiviral gene therapy for a rare metabolic disorder needed first-in-human CTA preparation and EMA engagement. We prepared the IMPD, coordinated the CTA sections, and managed the Scientific Advice procedure with CAT.
CTA approved without clinical holds
Illustrative Example
Approved on first assessment cycle
Biologic in Autoinjector: Integrated Drug-Device Programme
A pharma company transitioning a marketed IV biologic to a subcutaneous autoinjector needed parallel drug and device development. We ran both as one programme: reformulation and stability for the SC presentation, human factors and usability engineering for the autoinjector, MDR Annex I compliance, and the Type II variation application.
Approved on first assessment cycle
Developing a Biologic, Biosimilar, Blood Product, or ATMP?
Tell us about your product, your target markets, and where you are in development. We will assess the regulatory pathway and outline how we can support.
Speak with an ExpertFrequently Asked Questions (FAQ)
Where do vaccines fit?
Traditional vaccines and mRNA vaccines against infectious diseases are biologics and follow the centralised procedure. mRNA therapeutics for non-infectious indications fall under the ATMP framework as gene therapy medicinal products. The indication determines the classification, not the technology platform.
Can a biosimilar be approved without a comparative efficacy study?
The regulatory landscape is moving this way. EMA's draft reflection paper (April 2025) proposes waiving comparative efficacy studies where robust analytical, functional, and PK similarity is demonstrated. Implementation expected 2026. The MHRA already allows it. We assess feasibility case by case and prepare the scientific justification. The practical implication is that the analytical comparability programme carries more weight than ever. Developers who try to shortcut the analytics in hopes of saving on the clinical side will run into problems.
What is chain of identity and why does it matter?
COI is the permanent, bidirectional traceability link between a patient and their cell or gene therapy product, maintained from cell collection through manufacturing, transport, and administration. For autologous therapies, where each batch is manufactured from one patient's cells and must be returned to that exact patient, a failure in COI can result in patient harm or death. COI systems, including tamper-proof labelling, digital tracking at every handover point, and dual-verification protocols, need to be designed into the QMS from the start. They cannot be retrofitted.
Why does the delivery device matter?
Most biologics are injected, making the final product a drug-device combination under EU and US regulation. MDR Annex I requirements and the Notified Body opinion (Article 117) apply for EU. We run drug and device development as one integrated programme.
How early should we engage regulators for an ATMP?
For ATMPs, regulators should be involved as early as possible but in all cases prior to the first-in-human study. EMA offers ATMP classification requests, certification of quality and non-clinical data (valuable for SMEs and academic spin-outs), and Scientific Advice through CAT. For programmes targeting both EU and US, joint EMA/FDA Scientific Advice is available and worth considering at the end-of-Phase II stage or earlier if the clinical development plan is complex.