--- title: "ATMPs: translating the expertise into a GMP process" description: "ATMPs are a promising new type of medicine. Learn more about the challenges in translating the expertise into a GMP process." url: https://qbdgroup.com/en/blog/atmps-translating-the-expertise-into-a-gmp-process type: "Blog post" language: en published: 2026-06-11 author: "Roberta Sgammato" category: "Pharma & Biotech" publisher: "QbD Group" citation: "QbD Group, \"ATMPs: translating the expertise into a GMP process\", https://qbdgroup.com/en/blog/atmps-translating-the-expertise-into-a-gmp-process" --- # ATMPs: translating the expertise into a GMP process > ATMPs are a promising new type of medicine. Learn more about the challenges in translating the expertise into a GMP process. In the field of regenerative medicine, **advanced therapy medicinal products** (ATMPs) represent the next generation of medicines. It is, however, not so straightforward to translate this new expertise into a **GMP process**. In this article, you'll learn more about the challenges, crucial aspects, and the most recent regulatory developments shaping the field as of mid-2026. [ATMPs comprise:](https://qbdgroup.com/en/blog/atmps-in-a-nutshell-what-you-should-know-about-classification-quality-and-go-to-market/) - **genetic therapy medicinal products (GTMPs)**, including gene editing therapies such as CRISPR-based products, - **cell-based therapy medicinal products (CTMPs)**, - **tissue-engineered products (TEPs)**, - or a combination of the above. They represent the most **promising, sometimes unique, therapeutic option** for various diseases in which traditional medicine has proven ineffective. A therapy based on ATMPs is often used for the treatment of rare diseases. It is thus targeted to a patient-specific population. ![ATMPs - translating the expertise into a GMP process - QbD - DF](https://jrtdedcfhvzaomneervp.supabase.co/storage/v1/object/public/blog-images/blog_posts/content/atmps-translating-the-expertise-into-a-gmp-process/ATMPs-translating-the-expertise-into-a-GMP-process-QbD-DF-qqeauk5pqlivo34sh0z8siexlnp3r3arw4eks64ytq-2.jpg) Figure 1 – Schematic representation of advanced medicinal therapeutic products. CAR: chimeric antigen receptor. Adapted from Goula et al. ## Preparing ATMPs: dealing with a heterogeneous product pool The first step in the development of ATMPs is **isolating the cells or tissue from human sources**. This is one of the reasons why ATMP manufacturing is considered to be strictly related to the clinical and transplantation area. Upon manipulation of the raw material, ATMPs are prepared for **autologous** (same individual) or **allogeneic** (different donor) **use**. - **CTMPs** are collected via apheresis, then modified, expanded, and administered to the patient to treat diseases or injuries at the cellular level. CAR-T cell therapies — among the most high-profile CTMPs — have become a clinical reality in Europe, with six products now carrying EMA marketing authorization: Kymriah®, Yescarta®, Tecartus®, Abecma®, Breyanzi®, and Carvykti™. - **GTMPs** consist of recombinant nucleic acid, intended for the regulation of genetic sequences directly in the patient [(in-vivo)](https://qbdgroup.com/en/blog/car-t-and-tcrs-for-the-market-current-state-and-future-perspectives/) or in cells after collection (ex-vivo). The 2024 approval of **Casgevy** — the first CRISPR/Cas9-based gene editing therapy, authorized by EMA in February 2024 for sickle cell disease and transfusion-dependent beta-thalassemia — marks a milestone for this category. - **TEPs** are based on the use of immature (e.g., stem cell) or differentiated cell populations, with the purpose of repairing structurally compromised tissues in the patient. Given the nature of ATMPs, they represent an **extremely heterogeneous pool of products** [whose preparation differs substantially from mainstream biopharmaceutical manufacturing.](https://qbdgroup.com/en/blog/qp-challenges-in-atmps/) A high degree of technical expertise and very specialized production processes are therefore required. As of mid-2026, **over 28 ATMPs** have received EMA marketing authorization, and more than **250 clinical trials** for cell and gene therapies are actively ongoing in Europe — yet the path from development to market remains demanding. ## From ATMP to GMP: a bumpy — but rapidly evolving — history ### Lack of legislation and poor harmonization For a long time, the major contribution to the development of ATMPs came from **hospitals**, **small companies**, and **academic institutions**: facilities that often have restricted financial resources and limited competencies to navigate the complex regulatory procedures required to meet GMP industrial standards. ![The ATMP landscape in Europe 2004–2010. Adopted from Maciulaitis et al - QbD - DEF](https://jrtdedcfhvzaomneervp.supabase.co/storage/v1/object/public/blog-images/blog_posts/content/atmps-translating-the-expertise-into-a-gmp-process/The-ATMP-landscape-in-Europe-2004_2010_-Adopted-from-Maciulaitis-et-al-QbD-DEF-qqeb23t5ce3fykigl6bivamxqvgw5tjennwer4uau0-2.png) Figure 2 – The ATMP landscape in Europe 2004–2010. Adopted from Maciulaitis et al For years, the **lack of an actual legislative framework** characterized ATMP development, leading to a wide variety of individual academic and hospital manufacturing settings. Poor harmonization in GMP application within EU member states, which persisted until 2009, exacerbated the issue. Nevertheless, as pharmaceutical products, ATMPs must meet manufacturing and quality standards — a complicated matter when translating ATMP development into a GMP process. ### CAT and centralized procedures: a great leap forward A major step forward was taken in January 2009 with the establishment of the [Committee for Advanced Therapies](https://www.ema.europa.eu/en/committees/committee-advanced-therapies-cat) (CAT) at the European Medicines Agency (EMA). This multidisciplinary scientific committee reviews the **quality**, **safety**, and **efficacy** **of ATMPs** according to standards established by regulatory authorities. The introduction of centralized procedures for ATMP manufacture helped pharmaceutical companies establish structured ATMP production. ### The evolving regulatory landscape: 2024–2026 The most significant regulatory shift since the creation of the CAT is now underway. In **December 2025**, the EU reached a political agreement on a comprehensive reform of its pharmaceutical legislation — a process that has direct implications for ATMPs: - **CAT-CHMP integration:** The reform proposes streamlining EMA's governance structure by integrating the CAT into the Committee for Medicinal Products for Human Use (CHMP), pending final endorsement by the European Parliament and Council. For ATMP developers, this may improve procedural consistency with broader pharmaceutical development, though it raises important questions about preserving ATMP-specific scientific expertise. - **Hospital Exemption reform:** The reform introduces new requirements for data collection and reporting under hospital exemption (HE) pathways, alongside a yearly review by national competent authorities and publication in an EMA repository — addressing the longstanding fragmentation between member states in how HE has been applied. On **1 July 2025**, the EMA's new **Guideline on quality, non-clinical and clinical requirements for investigational ATMPs in clinical trials** came into effect. It provides a comprehensive review of risk assessment processes, non-clinical and clinical documentation, and manufacturing and quality control for ATMPs at the clinical stage, with particular emphasis on early-phase, exploratory trials. Simultaneously, in **May 2025**, EMA released a concept paper proposing revisions to **Part IV** of the **EU GMP Guidelines** specific to ATMPs, with public consultation open through July 2025. Key focus areas include: - Updated expectations for clean room classifications - Use of barrier systems (isolators and RABS) - Updated legal references and definitions for starting materials of human origin Of note: **Annex 2** of the EU GMP Guidelines has been revised to exclude ATMPs entirely, which are now governed exclusively by their own dedicated GMP framework (Part IV). This separation clarifies the regulatory landscape and acknowledges the unique nature of ATMP manufacturing. ## Crucial aspects of manufacturing ATMPs in a modern GMP environment Despite regulatory progress, translating ATMP manufacture into a GMP environment still poses **significant challenges**. The intrinsic variability of the starting material and the finished product requires manufacturing procedures that necessarily deviate from those of traditional biological products. The **extreme diversity** of starting material obtained from a patient — owing to their age, health, and illness — requires **impeccable batch identity and tracking**. Moreover, ATMP therapies require a **complex trial design**, as a unique patient population is targeted. Unlike common biopharmaceuticals, flexible, well-monitored, and controlled processes are needed to cope with this complexity. ### Transport from patient to site of manipulation One of the first obstacles in ATMP production under GMP conditions is the **transportation of the collected sample** from the patient to the site of manipulation. The intraoperative environment remains at the edges of GMP regulation, which contradicts the need to avoid contamination. The industry is increasingly addressing this through **closed system technologies** — though the definition of a "closed environment" remains a subject of regulatory discussion. An emerging solution gaining traction in 2025–2026 is **decentralized manufacturing** and **point-of-care production**, which aims to reduce complex transportation networks and shorten the critical "vein-to-vein" time for autologous therapies. The UK introduced the first regulatory framework for point-of-care ATMP manufacturing in 2023; equivalent European guidance is being closely watched by the sector. ### Sterility of the final product As with CTMPs, the presence of whole live cells prevents filtration through sterilization-grade filters, meaning the final product cannot be terminally sterilized. Sterility must therefore be ensured through **routine sterility testing during manufacture and aseptic process simulations**. This requirement remains unchanged, but automation is increasingly being used to reduce the aseptic risks associated with manual interventions. ### Logistics related to ATMP manufacturing The logistics associated with ATMP production are critical: the stability of both the human sample and the final product decreases significantly with transportation duration and is strictly temperature-dependent. Cold chain management and real-time tracking systems have become essential components of a GMP-compliant ATMP supply chain. ### Automation and the future of ATMP manufacturing A defining theme in 2025–2026 is the push towards **automation and robotics** in ATMP manufacturing. Labor-intensive manual processes — long the norm in this field — are being replaced with: - **Closed process-in-a-box systems** that reduce cleanroom dependency and enable more flexible facility designs - **Robotic and cobotic technologies** that minimize operator-related batch-to-batch variability - **AI-enabled process monitoring platforms** for real-time quality oversight These advances are central to the industry's effort to reduce costs and improve scalability — the two most significant barriers to broad patient access for ATMP therapies. ### Clean rooms, risk-based approach and IPCs Developers of ATMPs have powerful tools to support GMP-compliant manufacturing. The installation of **clean rooms** and the application of a **risk-based approach** through FMEA (Failure Modes and Effects Analysis) can ensure the safe handling of processed tissues and cells at every step. **In-process controls (IPCs)** remain essential to control the safety and quality of the entire production process. The ongoing revision of GMP Part IV is expected to provide clearer guidance on clean room classifications and barrier system requirements. To structure process optimization according to the **Quality by Design (QbD) paradigm** — from CQA setting and risk assessment to experiment design and analysis — structured software platforms can be a key enabler. This approach is increasingly expected by regulators as part of a modern ATMP development dossier. [Click here to read more.](https://qbdgroup.com/en/atmp-advanced-therapy-medicinal-products/cell-by-design-cbd/) ## Monitoring quality of ATMPs: open challenges in 2026 ### Persistent gaps and new pressures Regulating the quality of ATMPs remains a hot topic for health authorities. The use of products of human origin carries inherent risks of infectious disease transmission and adverse reactions. Quality and safety must be warranted during every stage of cell and tissue manipulation. Despite regulatory progress, gaps remain. Analyses of raw starting material for identity and purity assessment of cell populations are still difficult to perform under standardized conditions — a problem that persists for both autologous and allogeneic products. There is currently **no EMA-approved cell therapy for any solid tumour**, underscoring how much clinical and manufacturing work lies ahead for one of oncology's most promising frontiers. ### Evaluation of potency or mechanism of action One of the persistent discrepancies between GMP requirements and the nature of ATMPs concerns potency assessment. The large volume of cell product required for quality testing is at odds with the scarcity of material in autologous and personalized therapies. Quality assessment tests must comply with GMP standards — meaning minimizing operator-related variability in favor of standardized, reproducible processes. The need for **automation of manufacturing and monitoring systems** is therefore not just a cost-efficiency argument; it is a regulatory imperative. Immunofluorescence analyses based on specific markers represent a solid alternative to microscopy for cell identity assessment. ### The importance of a registered Qualified Person To successfully convert ATMP production into a GMP-compliant process, a **registered Qualified Person (QP)** remains essential to certify the quality and safety of the final product prior to release. In the context of the evolving regulatory framework — with new investigational ATMP guidelines in effect, GMP Part IV under revision, and the proposed CAT-CHMP integration — the QP's role in navigating these developments and interpreting their implications for specific products has never been more demanding or more important. The ATMP regulatory and manufacturing landscape is moving faster than ever. From CRISPR-based approvals to the forthcoming reform of EMA's committee structure, developers in 2026 must combine deep scientific expertise with agile regulatory intelligence. QbD Group's life sciences experts are here to support you at every stage. ## Ready to bring your ideas to life safely and compliantly? --- Source: https://qbdgroup.com/en/blog/atmps-translating-the-expertise-into-a-gmp-process — © QbD Group. Quote freely with attribution and a link back.