Manufacturing & Controls for Advanced Therapy Medical Products

Advanced Therapy Medicinal Products (ATMPs)

According to the European Medicines Agency (EMA), ATMPs are medicines for human use that are based on genes, tissues or cells. They are medicines for human use with an active therapeutic substance based on at least one of the following: 1) technology to modify patient genome, 2) recombinant nucleic acid or genes, 3) substantially manipulated cells, 4) cells intended for a different essential function in the patient versus the donor, 5) engineered tissue.

They offer new opportunities for the treatment of diseases and injuries with unmet medical needs.

ATMPs are classified into three main categories: 

• Gene Therapy Medicinal Products (GTMPs),
• Somatic cell therapy medicinal product (sCTMPs) and,
• Tissue-engineered products (TEPs).

In addition, combined ATMPs contain one or more medical devices as an integral part of the medicine. (See "Therapy Classification” on EuroGCT)

Before these therapies are offered to patients, the products must complete a development phase that adheres to the guidance of regulatory bodies such as the EMA. At the beginning of drug development, developers of Gene Therapy Medicinal Products (GTMPs) and Cell-Based Medicinal Products (CBMPs) need to navigate regulatory requirements related to non-clinical studies (See “Non-clinical Development Flowchart” on EuroGCT).

At this early stage, developers have to address key questions such as “what is the mechanism of action?”, “what is the efficacy?” and “what are the potential toxicological concerns?”. At later development stage, they also need to comply with various standards, including Good Laboratory Practice (GLP), Good Manufacturing Practice (GMP) (See “Good Manufacturing Practice for ATMPs” on EuroGCT), and Good Clinical Practice (GCP). (See “Clinical trials” on EuroGCT). The assessment of the quality, safety and efficacy of ATMPs is conducted by the EMA’s Committee for Advanced Therapies (CAT).

The CAT provides scientific recommendations on the classification of ATMPs (See “CAT scientific recommendations on classification” on EuroGCT) and is responsible for preparing a draft opinion on each ATMP marketing authorisation application submitted to the EMA. This draft is then reviewed by the Committee for Medicinal Products for Human Use (CHMP), which adopts the final opinion on the marketing authorization of the medicinal product (See “Market Access for ATMPs” on EuroGCT). The CAT also participates in procedures that deliver advice on the conduct of efficacy follow-up, pharmacovigilance or risk-management systems for ATMPs (See “Support for innovative medicines’ development at the EMA level” on EuroGCT). 

More information can be found in Regulation (EC) 1394/2007 and in the CAT Work Plan 2025.

Manufacturing and control are key steps in drug development. They are involved in the production and the characterisation of the medicinal substance (also called drug substance or DS) which is then formulated to become the medicinal product (also called drug product or DP). This product is released according to well-defined criteria and it may be stored before being administered to patients. The terms “manufacturing, control and formulation” are collectively referred to as “CMC” which stands for “Chemistry, Manufacturing and Control”. CMC along with preclinical and clinical activities are necessary to transition a potential medicine from discovery phase to clinical trials. Clinical trial applications in Europe (See “Clinical trials” on EuroGCT) and Investigational new drug applications in the USA are reviewed by regulatory agencies and have to be cleared before initiating clinical trials. These applications must include information related to non-clinical pharmacology and toxicology studies, manufacturing and control, clinical protocols and investigator information. The figure 1 below titled “CMC in drug development” provides further details on this process. Guidance documents help developers in the rapidly evolving field of ATMPs in which scientific achievements often translate quickly into therapeutic innovations. The mapping of the European landscape and specificity of ATMPs guidance has been published in June 2025 by Aurélie Mahalatchimy et al.  

The EMA is a decentralized agency of the European Union responsible for the scientific evaluation, supervision and monitoring of the safety of medicines. It operates across all Member States of the European Union, as well as in the countries of the European Economic Area. Founded in 1995, EMA plays a vital role in ensuring that more than 450 million people have access to reliable, effective and high-quality medicines. The EMA works closely with scientific experts and the national regulatory authorities of its member countries. It coordinates the efforts of thousands of European experts while maintaining the independence of its scientific advice. Its primary function is to provide scientific recommendations regarding the marketing of therapies and medicines on the European territory. After receiving these recommendations, the European Commission makes the final legal decision on whether to approve the marketing of a therapeutic product (See “Standard Marketing Authorisation Pathway: Centralised Procedure for ATMPs” on EuroGCT). 

The ANSM is a public agency established by the French State to guarantee access to health products in France and ensure the safety of medicines throughout their life cycle. ANSM plays a crucial role at all stages of medicines development (also referred to as drug development) by assessing the benefit-risk ratio of products. Its primary objective is to ensure that the benefits of taking a medicine outweigh the risks for patients. The ANSM plays a key role in coordinating clinical trials within France and in assessing the safety of medicines marketed in the country. Meanwhile, the EMA provides scientific opinions on the marketing of medicines and is responsible for the scientific evaluation and supervision of the medicines marketed at the European level. Although their responsibilities differ, both bodies work closely to ensure the safety of patients. And more generally, the EMA works closely with all National medicines agencies to ensure the safety of patients.

Figure 1: CMC in drug development

CMC, non-clinical and clinical activities toward IND and CTA filing

A Regulatory Risk-Based Approach to ATMP/CGT Development: Integrating Scientific Challenges With Current Regulatory Expectations

Source : Laura I. Salazar-Fontana, Front. Med., Sec. Regulatory Science, 13 May 2022

CMC is one of the most important activities in medicinal product development and encompasses process development, manufacturing, quality control and generate data on investigational medicinal product (IMP) for clinical trial applications (CTA).

See the figure 2 below “The CMC elements of ATMP manufacturing process development”

Figure 2: The CMC elements of ATMP manufacturing process development

Manufacturing process development of ATMPs within a regulatory framework for EU clinical trial & marketing authorisation applications

Source: Giulia Detela & Anthony Lodge, Cell & Gene Therapy Insights 2016

Legend of the figure: “The development of a manufacturing process for a medicinal product (including an ATMP) can be considered to involve, first, manufacture of the drug substance from the starting materials and raw materials, and second, manufacture of the drug product from the drug substance and raw materials and/or excipients. The starting materials for ATMP manufacture include donated cells or tissues, banked cell lines and banked viral vectors expressing cloned genes (other types of vectors may also be used). Raw materials may include cell culture medium, serum and cell dissociation agents, while excipients (non-pharmaceutical ingredients of the final product) may include stabilizers or cryopreservatives. The drug substance is the active substance/active pharmaceutical ingredient responsible for a medicinal product’s therapeutic effect, and the drug product is the drug substance in its final formulation for administration to patients. The drug substance and drug product should be fully characterized during the development phase using appropriate analytical methods to identify the product-specific quality attributes (see text for details). The critical quality attributes that correlate with safety and efficacy in patients are typically used to define a release specification and stability profile for drug substance and/or drug product. Some of the quality attributes included in the release specification and stability profile (e.g., potency, product-related impurities) will be defined and justified as ranges based on data obtained during process and product characterization. The steps of the manufacturing process should be controlled through process parameters and in-process controls to ensure that the specifications can be achieved. Together, all activities involved in manufacturing process development (inputs, process steps, analytical methods, characterization, outputs, validation) are referred to as CMC (chemistry, manufacturing and controls)”. 

Acronyms of the figure 2: PPs stands for Process Parameter IPCs stands for In Process Control CQAs stands for Critical Quality Attributes

The selection and the sourcing of the raw material (such as culture media) and the starting material (such as cells from healthy donors) is the first activity to be implemented. Then the process development step takes care of material, instruments and methods to develop consistent, scalable and cost-effective solution to manufacture and control the quality attributes of the intended product defined in the Target Product Profile (TPP). The Critical Process Parameters (CPPs) are carefully defined before Process Validation (PV) according to the Process Validation Master plan (PVM). The manufacturing step consists in the production of the targeted amount of medicinal product with a sufficient level of purity and quality. For clinical applications, the product must be produced according to GMP. 

Manufacturing is usually divided in three parts: the upstream processing, the downstream processing and the fill & finish.

• Upstream processing: the production step aiming at generating enough active substance with a level of quality compatible with future use. Key parameters for the upstream processing are the scale, the yield and the robustness.
• Downstream processing: purification and concentration of the active substance.  The purified and concentration of the active substance (called drug substance by Food and Drug Administration, FDA) is obtained after the downstream processing and is characterized in terms of quantity, viability (for cell products), potency, identity, content, purity, sterility and mycoplasma.
• Fill & finish: formulation and aseptic repartition for future storage and utilization. The finished medicinal product (called drug product by FDA) is obtained after formulation of the active substance and is characterized in terms of quantity, viability (for cell products), potency, identity, content, purity, sterility, mycoplasma.

Quality controls are essential to assess the performance of the process and the product manufactured. They consist in assays performed to assess the Critical Quality Attributes (CQAs) of the product and to reach the Quality Target Product Profile (QTPP). In process controls are performed at different steps of the manufacturing process. Release assays are performed to assess the quality attributes of the medicinal product before delivering it. Analytical methods have to be validated before being used for release testing.

Stability studies are conducted to assess how long the product can be kept in the defined conditions of storage (e.g. temperature) while maintaining critical quality attributes in the range defined for the product. 

Figure 3: Examples of controls for the manufacturing a mesenchymal stem cell product

Manufacturing process development of ATMPs within a regulatory framework for EU clinical trial & marketing authorisation applications

Source: Giulia Detela & Anthony Lodge, Cell & Gene Therapy Insights 2016

Legend of the figure: In this example of somatic cell therapy medicinal product manufacture from donated tissue starting material, Mesenchymal Stem Cells (MSCs) are isolated from a bone marrow aspirate and expanded in culture. These process operations represent an intermediate stage that generates an Intermediate Cell Batch (ICB). All steps involved in cell expansion should be controlled via MSC-specific IPCs, for example doubling time, population doubling level, morphology and surface marker profile analysis, cell yield, viability and confluence. Additionally, cryopreservation of the ICB enables the MSCs isolated and expanded from the starting material to be fully characterized to ensure their suitability for further product manufacture. The non-continuous nature of this process illustration also allows a full set of release tests to be performed on the active substance also called drug substance (DS), which is defined as the cells at the end of the final expansion phase (note that additional ICBs may therefore be introduced before the active substance if considered necessary).

GMP productions are performed in clean rooms with environmental monitoring. Particle counters are used to monitor airborne particles in the manufacturing areas. According to the current GMP guidelines, the maximum permitted airborne particle concentrations in areas are as follows:

Figure 4: Maximum permitted number of particles within a given volume according to EU and WHO guidelines 

For EU guidelines, please see guidelines on good manufacturing practices for ATMPs. The classification of clean rooms/clean air devices is done according to ISO14644-1 (https://www.iso.org/standard/53394.html). The recommended maximum limits, in operations, for particles egal or larger than zero point five micrometers per meter square is 3 520 for a grade A clean room, 352 000 for a grade B and 3 520 000 for a grade C. The maximum limit for grade D is based on risk assessment. For particles equal or larger than five micrometers per meter square, the limits in operations are respectively for 20, 2 900 and 29 000 for grade A, B, C.

Source: Page 25 Guidelines on Good Manufacturing Practice specific to ATMPs

The maximum permitted number of particles for each grade has been established in accordance with WHO guidelines: WHO good manufacturing practices for sterile pharmaceutical products.

This number is the same for ATMPs as for other medicines in the EU (page 12 of the  EudraLex - Volume 4 - "The rules governing medicinal products in the European Union" - Good Manufacturing Practice.

The rules governing medicinal products in the European Union can be found here.

Grade A: The critical zone for high-risk operations (e.g. aseptic processing line, filling zone, stopper bowl, open primary packaging or for making aseptic connections under the protection of first air). Normally, such conditions are provided by a localised airflow protection, such as unidirectional airflow workstations within restricted access barrier systems or isolators. The maintenance of unidirectional airflow should be demonstrated and qualified across the whole of the grade A area. 

Grade B: For aseptic preparation and filling, this is the background cleanroom for grade A (where it is not an isolator). Air pressure differences should be continuously monitored. Cleanrooms of lower grade than grade B can be considered where isolator technology is used

Grades C and D: These are cleanrooms used for carrying out less critical stages in the manufacture of aseptically filled sterile products or as a background for isolators.

ATMPs can be manufactured in open systems (cleanroom, A in B) or in closed systems (isolators, A in C) depending on the configuration and the organization of the manufacturing facility. A laminar flow cabinet can achieve a Class A cleanliness rating if the surrounding air is classified as Class B. An isolator can achieve a Class A cleanliness rating even if the surrounding air is classified as Class C.

Airlock systems contribute to prevent contamination and to limit the risk of dissemination. 

An Air-lock is “An enclosed space with two or more doors, and which is interposed between two or more rooms, e.g. of differing class of cleanliness, for the purpose of controlling the air-flow between those rooms when they need to be entered. An airlock is designed for and used by either people or goods”. (Guidelines on Good Manufacturing Practice specific to Advanced Therapy Medicinal Products, European Commission, Brussels, 22.11.2017, C(2017) 7694 final, Glossary, p.85)

Figure 5: Different airlock systems

Source: Types Of Airlocks Used In The Pharmaceutical Industry | GMP Insiders

Legend of the figure: A cascade airlock operates on the principle of pressure differentials, where each connected room has progressively lower air pressure as one moves from a cleaner to a less clean area. A bubble airlock is designed to create a zone of positive pressure, ensuring that the air pressure inside the airlock is higher than in both adjacent rooms. A sink airlock is a type of airlock that operates with a lower internal pressure than the adjacent rooms, creating a “sink” effect that draws air into the airlock.

More information can be found in Volume 4 EU Guidelines for Good Manufacturing Practice for Medicinal Products as well as in Guidelines on Good Manufacturing Practice specific to Advanced Therapy Medicinal Products, European Commission, Brussels, 22.11.2017, C(2017) 7694 final.

Cell banks are essential for cell and gene therapies. For allogeneic cell therapies, they are usually produced from healthy donors. They can be genetically modified by gene editing tools or with viral vectors. They can be based on immature cells like Induced Pluripotent Stem Cells (iPSCs). Cell banks are also used as packaging cell lines and producer cell lines for the production of viral vector particles. Bacterial cell banks are used for plasmid production. Master Cell Bank (MCB) and Working Cell Bank (WCB) development are critical elements in the production of many ATMPs and are carefully characterized before use. MCBs are prepared for long-term storage. WCB is prepared from one or more MCB vials. WCB is used for the manufacturing of the intended product: plasmid, viral vector particles, allogeneic cells … The EMA provides guidance on standards for the derivation of human and animal cell lines and microbial cells to be used in biotechnological/biological products. 

ICH Q5D Derivation and characterisation of cell substrates used for production of biotechnological/biological products - Scientific guideline

These guidance documents are based on International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidance and are thus generally similar at the global level. For example, ICH Q5A(R2) Guideline provides guidance on viral safety evaluation of biotechnology products derived from cell lines of human or animal origin.

Figure 6: Example of master and working cell banks of HEK293T cells

HEK293T cells are human embryonic kidney cells widely applied in industrial biotechnology, toxicology, and cancer research. These immortalized cells are used to produce a variety of therapeutic proteins and viral vectors. 

Cell Banking of HEK293T cell line for clinical-grade lentiviral particles manufacturing

Source: Perpina et al., Translational Medicine Communications 2020

Legend of the figure: “A) MCB workflow. MCB was composed of 3 independent batches containing 20 or more cryotubes. The HEK293T cell line cryovial was thawed and expanded until reaching 200·106 cells. Two cell passages were needed to obtain the final number of 200·106 cells. B) MCB HEK293T were thawed and expanded to reach 1000·106 cells. Only one cell passage was needed to obtain 1000·106 cells. Cells were transferred into cryotubes at a concentration of 20·106 cells per tube and frozen using a ramp program that lowers the temperature 1 °C/minute […]. WCB cryotubes were transferred to a gas phase nitrogen tank […]”

Engineering runs are performed under GMP at the scale intended to be used for clinical trials and generate necessary data for clinical trial applications (CTA). The common technical information to be provided is detailed in the figure 7 “Outline structure of Module 3” below.

Clinical manufacturing is performed under GMP and generate DP used in clinical trials.

Developers of ATMPs should follow the ICH guidelines on pharmaceutical development published by EMA and detailing the elements to be considered for pharmaceutical development such as QTPP, CQA and risk assessment, DS, excipients, DP…

ICH Q8 (R2) Pharmaceutical development - Scientific guideline | European Medicines Agency (EMA)

The Common Technical Document (CTD) describes the format for MAA submissions in the EU. 

Figure 7: Outline structure of Module 3

Source: Manufacturing process development of ATMPs within a regulatory framework for EU clinical trial & marketing authorisation applications, Giulia Detela & Anthony Lodge, Cell & Gene Therapy Insights 2016

A risk assessment is performed to determine which process parameters have a significant impact on CQAs. The assessment consists of 3 steps: risk identification, risk analysis, risk evaluation. A plan for risk control is implemented in order to reduce the risk and to bring it to an acceptable level. A quality risk management process is implemented for risk assessment and risk control. EMA/CAT published a Guideline on the risk-based approach according to Annex I, part IV of Directive 2001/83/EC applied to Advanced Therapy Medicinal Products. According to this guideline, the risk-based approach is based on the identification of various risks associated with the clinical use of an ATMP and risk factors inherent to the ATMP with respect to quality, safety and efficacy. The risk is defined as a “potential unfavorable effect that can be attributed to the clinical use of ATMP” and is of concern to the patient and/or to other populations. The risk factor´ is defined as a “qualitative or quantitative characteristic that contributes to a specific risk following handling and/or administration of an ATMP”. The risk profiling is defined as a methodological approach to systematically integrate all available information on risks and risk factors in order to obtain a profile of each individual risk associated with a specific ATMP.

Figure 8: Overview of a typical Quality Risk Management: 

Source: Quality Risk Management System and Advanced Therapy Medicinal Products | American Pharmaceutical Review - The Review of American Pharmaceutical Business & Technology, August 1, 2024

ATMP Sweden has summarised information regarding the legal classification for ATMPs. The schema can be found with the following link: Therapy Classification | EuroGCT.

The guideline on safety and efficacy follow-up and risk management of ATMP medicinal products is proposed by the EMA:

• Risks to patients in relation to quality characteristics, storage and distribution of the product are discussed including the risk of transmission of a disease: origin of cells and tissues, the characteristics of the cell type used for the manufacturing of the medicinal product
• Rick of tumorigenicity : characteristics of the product that may affect the differentiation capacity of the cells, the risk related to mutations when gene editing techniques are used
• Risk related to the storage, transport and distribution of the medicinal product, for instance the risks of breaking the cold chain. This could impact on the biological activity of the ATMP potentially leading to treatment failure.

(EMA/149995/2008 Guideline on Safety and Efficacy Follow-up and Risk Management of Advanced Therapy Medicinal Products) 

Other guidelines related to the quality and safety of ATMPs can be found following the links below:

• EMA/CAT/80183/2014: Guideline on the quality, non-clinical and clinical aspects of gene therapy medicinal products
• CHMP/GTWP/671639/2008: Guideline on quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells
• EMA/CHMP/410869/2006: Guideline on Human Cell-based Medicinal Products
• EMA/CHMP/BWP/271475/2006 Rev.1: Guideline on potency testing of cell based immunotherapy medicinal products for treatment of cancer
• CAT/CPWP/686637/2011: Guideline on the risk-based approach according to Annex I, part IV of Directive 2001/83/EC applied to Advanced Therapy Medicinal Products
• CHMP/CPWP/83508/09: Guideline for Xenogeneic cell-based medicinal products
• CPMP/BWB/2458/03: Guideline on Development and Manufacture of Lentiviral vector
• CHMP/GTWP/125459: Guideline on the Non-Clinical Studies Required before First Clinical Use of Gene Therapy Medicinal Products
• EMEA/273974/05: Guideline on non-clinical testing for inadvertent germline transmission of gene transfer vectors
• CHMP/GTWP/60436/07: Guideline on follow-up of patients administered with gene therapy medicinal products
• CHMP/GTWP/125491/06: Guideline on Scientific Requirements for the Environmental Risk Assessment of Gene Therapy Medicinal Products

Cell therapies represent a promising medical advance, offering potential solutions for many serious and currently incurable diseases. To ensure the safety, efficacy and high quality of these treatments, rigorous processes known as CMC are essential for their design and implementation.

Example of the manufacturing of stem cell-based therapies

Stem Cell Therapy Production Steps

The CMC strategy for stem cell therapies involve several crucial steps. Stem cells can be enriched form the collected starting material and grown under strictly controlled conditions in a laboratory, where temperature, nutrients, and humidity are precisely regulated to promote their optimal growth. Once they have sufficiently proliferated, these cells undergo a differentiation process. Through this process, stem cells can differentiate into various types of specialized cells, such as heart cells, neurons, or blood cells, depending on the therapeutic needs. This differentiation may occur in culture or be completed in vivo.

After the expansion and differentiation in culture (upstream processing), cells are purified to remove impurities and formulated according to intended route of administration to the patients (downstream processing). Following this, rigorous testing is conducted to ensure the cells meet high quality standards required for clinical applications. Often, they are frozen (cryopreserved) for safe storage and transportation, ensuring their viability for future use.

Different Types of Stem Cell Therapies

There are two main approaches for stem cell therapies: autologous and allogeneic. Autologous therapies involve the collection of cells from the patient, which are subsequently processed and reinfused into the same patient. This approach significantly minimizes the risk of immune rejection, as the cells originate from the patient's own body. Conversely, allogeneic, also referred to as heterologous therapies, utilize stem cells sourced from a donor who is not the patient. While this approach offers the possibility to manufacture “off-the-shelf” product immediately available at reduced cost per dose, it is associated with an increased risk of immune rejection and typically necessitates a match of main Human Leukocyte Antigens (HLA) between the donor and the recipient or after hypoimmune engineering of cells aims to avoid immune recognition by innate and adaptive immune cells.

Challenges associated with stem cell therapies

The advancement of stem cell therapies encounters several significant challenges. The complexities involved in the cell culture process, along with the purification and the formulation steps, necessitate a high level of technical expertise. Furthermore, the inherent heterogeneity in stem cell quality across different donors or patients can result in variability between batches, thereby impacting the consistency and efficacy of treatments. Stem cell therapies are also subjected to strict regulatory requirements to ensure their safety and effectiveness, which can complicate and prolong the development process. The substantial costs associated with the technologies and equipment needed for the production of these therapies can restrict their accessibility to the patients.

Advantages related to the development of CMC processes

The implementing CMC processes in the development of stem cell therapy products allows stringent quality controls and validated manufacturing protocols. It ensures the production of therapies that maintain high quality standards.

Furthermore, these therapies can be tailored to individual patient profiles, often utilizing cells taken directly from the patient for autologous therapies, which minimizes the risk of immune rejection.

Conclusion on cell therapies

In conclusion, CMC plays a crucial role in the development of stem cell therapies. Although the challenges are many, the potential benefits for medicine and patients are considerable. With rigorous controls and continued innovation, cell therapies could transform the healthcare landscape and provide solutions for many diseases with unmet medical need.

1. Methods for the characterization of stem cells:

• Reference: Forced aggregation of defined numbers of human embryonic stem cells into embryoid bodies fosters robust, reproducible hematopoietic differentiation - ScienceDirect, Ng, E. S., Davis, R. P., Azzola, L., Stanley, E. G., & Elefanty, A. G. (1st September 2005). Blood, 106(5), 1601-1603.
• Summary: This article describes methods for culturing and differentiating human embryonic stem cells to promote robust and reproducible hematopoietic differentiation.

2. Challenges in stem cell therapy:

• Reference: Stem Cell Therapies in Clinical Trials: Progress and Challenges, Trounson, A., & McDonald, C., Cell Stem Cell (2 July 2015), 17(1), 11-22.
• Summary: This review examines the challenges faced in the development of stem cell therapies, including issues of cell variability and strict regulations.

3. Advantages of autologous and allogeneic stem cell therapies:

• Reference: Clinical Trials with Mesenchymal Stem Cells: An Update, Squillaro, T., Peluso, G., & Galderisi, U., Cell Transplantation (1st May 2016), 25(5), 829-848.
• Summary: The article provides an update on clinical trials using mesenchymal stem cells, highlighting the advantages and disadvantages of autologous and heterologous therapies.

4. Quality control in stem cell manufacturing:

• Reference: Human embryonic stem cells: origins, characteristics and potential for regenerative therapy, Mountford, J. C., Transfusion Medicine, (February 2008). 18(1), 1-12.
• Summary: This article discusses quality controls in the manufacturing of human embryonic stem cells, highlighting the rigorous requirements necessary to ensure the safety and efficacy of therapies.

5. Economic aspects and accessibility of stem cell therapies:

• Reference: A Brief Definition of Regenerative Medicine, Mason, C., & Dunnill, P., Regenerative Medicine (21 December 2007), 3(1), 1-5.
• Summary: The authors discuss the economics and accessibility of stem cell therapies, highlighting the high costs associated with the necessary technologies and equipment.

6. Regulatory bodies and guidelines impacting CMC activities:

• Food and Drug Administration
• European Medicines Agency
• International Organization for Standardization (ISO)
• International Council for Harmonisation (ICH)
• Compliance with Good Manufacturing Practice

The EMA publishes scientific guidelines on human medicines that are harmonised by the ICH.

Published: 22/09/2025

Authors:

Manon Chauveau Sarlandie de la Robertie, Biotechnology Engineer, Industrialisation Assistant engineer in Biotechnologies at CarbonWorks

Andrii Podliesnyi, Biotechnology Engineer, Medical Information Officer at MEDADOM

Léo Cavarec, Biotechnology Engineer, Clinical Research, Clinical Research Associate at Lille University Hospital

Minodora Brimpari, EuroGCT ELSI Group 1 member, Project Leader in Cell Therapy at Helmholtz Zentrum München

Olivier Nègre, Member of The General Committee Management Group at EuroGCT, Board Member of the French Society of Cell and Gene Therapy, Paris, France; Co-President of the Gene and Cell Therapy Institute, Expert in Cell and Gene Therapy at Biotherapy Partners, Paris, France

Reviewed by:

Aurélie Mahalatchimy, EuroGCT WP4 Convenor, UMR 7318 DICE CERIC, Aix-Marseille University, CNRS, Aix-en-Provence, France