Human Tissues and Cells: EU Rules Biotech Teams Often Overlook

Human-derived materials sit at a complex intersection of medical science, ethics, and regulation. For biotechnology teams building advanced therapies, diagnostic platforms, or digital systems that process donor information, the regulatory landscape governing human tissues and cells is often less visible than pharmaceutical or device rules, yet it is foundational. When a product relies on human cells or tissues—whether as starting material, as an active component, or as a reference for validation—the obligations under European Union law extend beyond the familiar confines of the Clinical Trials Regulation or the Medical Device Regulation. They reach into procurement standards, donor eligibility testing, traceability requirements, and post-market vigilance that are specific to human origin. Understanding this framework is not merely a compliance exercise; it is a prerequisite for safe innovation and for maintaining public trust.

This article explains the EU framework for the donation, procurement, testing, traceability, and vigilance of human tissues and cells. It clarifies how these rules operate in practice, where they intersect with biotech product regulations, and how national competent authorities implement and enforce them. It also highlights practical implications for developers of cell therapies, biobanks, diagnostic laboratories, and digital health platforms that handle sensitive donor data. The aim is to provide a precise, operational understanding for professionals working across AI, robotics, biotech, data systems, and public or regulated institutions in Europe.

The European Framework for Human Tissues and Cells

The EU’s regulatory architecture for tissues and cells is anchored in the Tissues and Cells Directive (2004/23/EC), often referred to as the TCD. This directive sets the overarching standards for donation, procurement, testing, processing, preservation, storage, and distribution of human tissues and cells intended for human application. It is complemented by two technical directives that specify detailed requirements: Directive 2006/17/EC (implementing the TCD as regards certain technical requirements for donation, procurement, and testing) and Directive 2006/18/EC (implementing the TCD as regards traceability requirements and the reporting of serious adverse reactions and events). Together, these instruments establish a harmonized baseline across the European Union, with the notable exception of certain aspects of cord blood banking, which are addressed under a separate regulation (see below).

The TCD applies to tissues and cells, including hematopoietic progenitor cells (HPCs) derived from cord blood, peripheral blood, and bone marrow. It also covers reproductive tissues and cells (gametes and embryos) for assisted reproduction, as well as tissues such as corneas, bone, skin, and heart valves. Importantly, the TCD does not cover organs intended for transplantation, which are governed by the Organ Extraction and Transplantation Directive (2010/53/EU). The distinction matters in practice: while many procurement organizations and transplant centers have integrated processes for both organs and tissues, the regulatory obligations and quality management requirements differ. For biotech teams, understanding whether the material falls under organs, tissues and cells, or advanced therapy medicinal products (ATMPs) is a critical first step.

At the EU level, the European Commission provides policy direction and legislative oversight. However, day-to-day supervision is carried out by National Competent Authorities (NCAs) in each Member State. These authorities designate and inspect establishments involved in tissues and cells, approve quality systems, and enforce compliance. The European Directorate for the Quality of Medicines & HealthCare (EDQM) plays a key role in developing standards, publishing guides, and coordinating inspections through its Tissues and Cells (TIC) network. The European Commission’s Expert Group on Tissues and Cells supports policy development and harmonization. While the TCD sets the legal framework, implementation varies across countries, reflecting differences in organizational structures, funding models, and national health systems.

Scope and Definitions: What Counts as Tissues and Cells?

For regulatory purposes, “tissues” are defined as “groups of similar cells outside the body that are not interconnected by a structure.” The TCD explicitly includes reproductive tissues and cells. “Cells” are individual cellular units. The directive covers both somatic tissues and cells (for therapeutic use) and gametes and embryos (for reproductive medicine). It applies to materials intended for human application, whether autologous (used in the same individual) or allogeneic (used in a different individual), although the level of regulatory oversight may differ depending on the intended use and the risk profile.

It is essential to distinguish between tissues and cells used directly in human application and those that are further processed or manipulated to become Advanced Therapy Medicinal Products (ATMPs). ATMPs include gene therapies, somatic cell therapies, and tissue-engineered products. These fall under the Regulation (EC) No 1394/2007 and are centrally authorized by the European Medicines Agency (EMA). However, the starting material for ATMPs—often human tissues or cells—is subject to the TCD requirements at the procurement and testing stages. In practice, this means that a developer of a CAR-T therapy must ensure that the donor cells are procured and tested in accordance with TCD standards before they enter the manufacturing process regulated under the ATMP framework.

Interaction with Other EU Regimes: Blood, Devices, and Medicines

The TCD sits alongside the Blood Directive (2002/98/EC) and its implementing directives, which govern the collection and testing of human blood and blood components. While there is overlap in principles such as donor selection and testing, the Blood Directive focuses on transfusion, whereas the TCD focuses on transplantation and application of tissues and cells. For biobanks and research infrastructures, the General Data Protection Regulation (GDPR) imposes additional obligations when processing donor data. Furthermore, if a tissue or cell product is processed into a form that meets the definition of a medicinal product or a medical device, it may fall under the Medicinal Products Directive or the Medical Devices Regulation. The intersection is particularly relevant for products that combine human material with technology, such as scaffolds, matrices, or encapsulation devices.

There is also a specific EU instrument for cord blood: Regulation (EC) No 1394/2007 includes provisions on cord blood banking, and the Cord Blood Regulation (EU) 2023/1223 (which repealed the earlier Commission Directive 2006/86/EC) sets out detailed rules on quality and safety standards for cord blood. This regulation harmonizes requirements for collection, testing, processing, storage, and distribution of cord blood units intended for transplantation. For biotech teams working with cord blood-derived HPCs, this is the controlling legal text, rather than the TCD directives.

Donation and Procurement: Ethics, Consent, and Anonymization

Donation of tissues and cells in the EU is governed by ethical principles and strict legal requirements. The TCD mandates that donation must be voluntary and unpaid. Non-remuneration is a core principle; donors cannot receive financial compensation beyond reimbursement of verifiable expenses. This principle is designed to protect donors from exploitation and to safeguard the integrity of the system. Member States must ensure that donation processes are structured to minimize risks to both donor and recipient.

Consent is a cornerstone. For tissues and cells intended for human application, informed consent must be obtained in accordance with national law. The TCD allows for opt-out systems for certain types of donation (e.g., corneas) in some Member States, provided that robust safeguards are in place. For reproductive cells (gametes and embryos), consent requirements are particularly stringent, and donors must be provided with comprehensive information about the implications of donation, including future rights of donor-conceived individuals to access information under national rules.

Anonymization and traceability are carefully balanced. Donor and recipient anonymity must be preserved unless national law provides otherwise (for example, in the context of donor-conceived individuals’ rights to access identifying information). Establishments must maintain records that allow traceability from donor to recipient and vice versa, which is essential for vigilance and recall. In practice, this requires robust information systems that can link unique identifiers while protecting personal data under GDPR.

Donor Eligibility and Health Assessments

Donor selection is risk-based. The TCD and its implementing directives require a thorough assessment of the donor’s medical history and risk factors. The goal is to prevent transmission of infectious diseases and to ensure that donation does not pose undue risk to the donor. The assessment includes:

• A structured interview and medical history to identify risk behaviors and exposures.
• Physical examination where appropriate.
• Testing for specified infectious diseases.

The list of mandatory tests is defined in the implementing directives and includes HIV-1 and HIV-2, hepatitis B and C, syphilis, and, for certain tissues, additional pathogens as indicated by risk assessment. For gametes, there are specific requirements, including genetic screening in certain contexts, depending on national law. The tests must be performed using validated methods and in accredited laboratories. The timing of testing is critical; for example, there are windows of relevance for exposures, and repeat testing may be required depending on the donor’s risk profile and the tissue type.

For autologous donations (where the tissue or cells are intended for use in the same individual), the TCD allows for derogations from certain testing requirements, recognizing that the risk of disease transmission to another person is absent. However, quality and safety standards for processing and storage still apply to protect the patient.

Special Considerations for Post-Mortem Donations

Post-mortem donation of tissues (such as corneas or bone) is an important source of material. The TCD sets out specific timelines and conditions for procurement, including the requirement for a medical practitioner to certify death according to national law. The procurement must be performed under hygienic conditions and within defined timeframes to ensure tissue viability. Establishments must have procedures to verify the donor’s eligibility and to ensure that consent (or authorization under national law) has been obtained.

Testing and Quality Standards: From Donor to Product

Testing of tissues and cells is not limited to donor screening. The TCD framework requires that all tissues and cells undergo quality control testing appropriate to the product. This includes microbiological testing, sterility testing, and, where applicable, functional testing. For cell-based products, viability and cell count may be required. The implementing directives specify minimum requirements, but establishments are expected to perform a risk-based assessment to determine additional tests.

Processing, preservation, and storage must be performed under a Quality Management System (QMS) that meets the requirements of the TCD. This includes standard operating procedures (SOPs), staff training, equipment validation, and environmental monitoring. The EDQM publishes detailed guidance on these topics, including the Guide to the Quality and Safety of Tissues and Cells for Human Application, which is a key reference for inspectors and establishments.

For biotech teams, it is important to recognize that the TCD does not prescribe a single set of processing methods; rather, it sets outcome-based requirements. Establishments must demonstrate that their processes consistently yield safe and effective tissues or cells. This is similar in spirit to Good Manufacturing Practice (GMP) but tailored to the nature of human-derived materials. In many jurisdictions, establishments handling tissues and cells are required to be licensed or designated by the NCA, and inspections are conducted to verify compliance.

Import and Export: Third-Country Rules

When tissues or cells are imported from or exported to non-EU countries, the TCD requires that the third country’s standards are equivalent to EU requirements. The importing establishment must ensure that the material meets EU standards for donor eligibility, testing, processing, and traceability. Member States may require prior authorization or notification for imports. In practice, this means that biotech companies sourcing materials globally must map the regulatory status of each supplier and maintain evidence of equivalence. The EDQM coordinates efforts to recognize or assess third-country standards, but the ultimate responsibility lies with the importing establishment and the NCA.

Traceability and Vigilance: Detecting and Responding to Adverse Events

Traceability is a core safety feature. The TCD mandates that establishments maintain records that allow the tracing of tissues and cells from donor to recipient and vice versa. This includes unique identifiers for donations, batches, and recipients where applicable. Records must be kept for at least 30 years or longer if required by national law. Electronic systems are encouraged, but they must ensure data integrity, confidentiality, and availability in the event of a recall or safety investigation.

Vigilance involves the detection, reporting, and investigation of serious adverse events (SAEs) and serious adverse reactions (SARs). An SAE is an incident related to the procurement, processing, storage, or distribution of tissues or cells that could lead to transmission of infectious disease, death, or life-threatening injury. A SAR is a reaction in the recipient that results in death, life-threatening illness, or permanent disability. Establishments must have procedures to report SAEs and SARs to their NCA within defined timelines. The NCA investigates and may trigger recalls, suspensions, or corrective actions. Data are aggregated at the EU level to monitor trends and identify systemic risks.

For biotech teams developing digital systems that support traceability or vigilance, the requirements are specific. Systems must be capable of linking donor and product identifiers, capturing adverse event data, and supporting rapid notification to authorities. They must also comply with GDPR, ensuring that personal data are processed lawfully, with appropriate technical and organizational measures to protect confidentiality and integrity.

Reporting Timelines and Responsibilities

The TCD and its implementing acts specify reporting timelines. In general, establishments must report SAEs and SARs to their NCA as soon as possible and no later than a defined period after becoming aware of the event. The exact timelines may be set by national law but are typically aligned with EDQM guidance. Establishments must also conduct root cause analyses and implement corrective and preventive actions. NCAs may require follow-up reports and can impose restrictions on donations or establishments if risks are identified.

Under the TCD framework, traceability and vigilance are not optional add-ons; they are integral to the legal license to operate. Establishments that fail to maintain robust systems risk suspension of activities and regulatory sanctions.

Intersection with Biotech Products: ATMPs, Devices, and Research

Many biotech products rely on human tissues or cells as starting materials. The regulatory boundary between TCD and other regimes is defined by the intended use and the degree of manipulation. If the cells are minimally manipulated and intended for homologous use, they may remain under the TCD. If they are subjected to more than minimal manipulation, combined with non-cellular components, or used for non-homologous purposes, they likely qualify as ATMPs and require EMA authorization.

For example, a product consisting of autologous chondrocytes expanded in culture and seeded onto a scaffold for cartilage repair is a tissue-engineered product and an ATMP. The donor cells must be procured and tested under TCD standards, but the final product is regulated by the EMA under the ATMP framework. In contrast, cryopreserved allogeneic bone grafts that are minimally processed and used for orthopedic reconstruction typically remain under the TCD, with oversight by the NCA.

Diagnostic platforms that use human cells or tissues as reference materials or controls must also consider TCD obligations if the materials are derived from human donors. Even if the end product is a device, the source material must meet donor eligibility and testing requirements. For AI systems that analyze tissue or cell data, GDPR obligations are paramount, but the underlying data must originate from compliant donation and processing activities.

Biobanking and Research Use

Biobanks that store human tissues and cells for research are generally covered by the TCD if the materials are intended for human application. If the materials are used solely for research and not for therapeutic use, the TCD may not apply directly, but national laws often impose similar standards for quality and ethics. Many Member States require ethics committee approval and informed consent for research biobanking. The GDPR imposes strict rules on data processing, and the use of coded or pseudonymized samples does not remove the need for robust governance.

For research infrastructures that plan to share samples across borders, it is essential to verify that the donation and consent framework in the source country permits the intended research use. Cross-border transfers of human tissues and cells for research must comply with both TCD requirements (if applicable) and GDPR data transfer rules. In practice, this requires legal agreements, documented consent, and technical safeguards.

EU-Level Coordination and National Implementation

Although the TCD sets EU-wide standards, implementation is national. Each Member State designates one or more NCAs responsible for tissues and cells. These authorities may be part of the health ministry, a national medicines agency, or a specialized inspectorate. The EDQM’s TIC network facilitates harmonization through joint inspections, guidance documents, and an EU-wide vigilance database. However, differences persist in areas such as donor compensation (reimbursement policies), consent models for post-mortem donation, and the scope of authorized activities for establishments.

For example, some countries have centralized tissue banks that coordinate procurement and distribution, while others rely on hospital-based units. The governance of cord blood banks varies, with some countries maintaining public cord blood banks under strict national oversight and others allowing private banking. Biotech teams should not assume uniformity; they must map the regulatory landscape in each country where they source materials or place products on the market.

Inspections and Enforcement

Inspections are a key enforcement tool. NCAs conduct routine inspections and for-cause inspections following adverse events. Inspectors assess donor selection records, testing documentation, processing logs, equipment validation, staff training, and traceability systems. They also review vigilance procedures and corrective actions. The EDQM promotes harmonized inspection practices, but the rigor and frequency may vary. Establishments should prepare for inspections by maintaining up-to-date documentation, conducting internal audits, and ensuring that staff are trained and competent.

Non-compliance can result