Exploring the environmental exposure assessment of Advanced Therapy Medicinal Products (ATMPs) in European healthcare settings
Imagine a world where a single injection could reprogram your own cells to hunt down cancer, or where damaged heart tissue could be regenerated using engineered biological products. This isn't science fiction—it's the promise of Advanced Therapy Medicinal Products (ATMPs), a revolutionary class of treatments that include gene therapies, cell-based medicines, and tissue-engineered products 1 9 .
The first engineered cell therapy products were approved by the FDA in 2017, marking a new era in medicine 1 .
Since 2007, these groundbreaking therapies have been formally integrated into the European regulatory framework, offering new hope for treating cancer, inherited genetic diseases, and degenerative conditions 1 .
However, as these living medicines move from research labs into hospital settings, a subtle but critical challenge emerges: ensuring that during their preparation, handling, and disposal, they don't pose a risk to the environment or healthcare workers through accidental exposure. This article explores the scientific quest to secure the medication circuit of these powerful new therapies.
ATMPs represent a paradigm shift in medicine, moving beyond traditional chemical drugs to living, dynamic treatments. They are categorized into three main types:
These contain genes that lead to a therapeutic, prophylactic, or diagnostic effect. They work by inserting 'recombinant' genes into the body, which are strands of DNA created in the laboratory by bringing together DNA from different sources 9 .
These contain cells or tissues that have been manipulated to change their biological characteristics. They're used to cure, diagnose, or prevent diseases 9 .
These contain cells or tissues that have been modified to repair, regenerate, or replace human tissue 9 .
Some ATMPs combine these elements with medical devices, known as combined ATMPs, such as cells embedded in a biodegradable matrix or scaffold 9 .
The European Medicines Agency (EMA) plays a central role in evaluating all ATMPs through its Committee for Advanced Therapies (CAT), ensuring they meet strict quality, safety, and efficacy standards before reaching patients 9 .
| ATMP Type | Description | Primary Use Areas | Environmental Concerns |
|---|---|---|---|
| Gene Therapy | Contains recombinant genes | Genetic disorders, cancer, long-term diseases | Potential persistence of genetic material in environment |
| Somatic-Cell Therapy | Manipulated cells or tissues | Cancer, regenerative medicine | Cell viability outside intended environment |
| Tissue-Engineered | Modified cells/tissues for repair | Tissue repair and regeneration | Complex biological constructs requiring containment |
| Combined ATMPs | Cells combined with medical devices | Enhanced tissue regeneration | Multiple material types (biological + device) |
When a patient receives an ATMP, it undergoes a complex journey through the hospital system—from storage and thawing to preparation, administration, and eventual disposal of any waste products. Each step in this "medication circuit" represents a potential point where biological material could be released into the environment 1 .
ATMPs are often stored at ultra-low temperatures and require careful thawing before administration.
Healthcare professionals prepare the ATMP for administration, which may involve dilution or other manipulations.
The ATMP is administered to the patient through injection, infusion, or implantation.
Any remaining product, containers, or materials used in administration must be properly disposed of.
This release, known as environmental shedding, is a primary concern for regulators and healthcare institutions. While the risk might seem theoretical, assessing and managing it is crucial for the safe integration of these therapies into healthcare systems.
To understand what we know about environmental exposure risks, researchers conducted a systematic review of the literature—a rigorous scientific method that attempts to collect and analyze all available evidence that answers a specific question 7 . This particular review focused on environmental exposure assessments related to ATMP use in European healthcare settings 1 .
The systematic review followed a meticulous scientific process 1 7 :
Clearly defining what evidence was needed—specifically, data on environmental exposure from ATMP use in healthcare settings
Scanning multiple databases (PubMed, Web of Science) using precise search terms
Applying inclusion and exclusion criteria to identify the most relevant publications
Systematically gathering information and integrating findings to draw meaningful conclusions
The review uncovered several important patterns in how environmental concerns are addressed for ATMPs 1 :
Environmental contamination assessments were more frequently addressed in review articles rather than original research studies, indicating a need for more primary investigation.
Product information sections from official European assessment reports typically suggested precautions rather than strict requirements for environmental management.
Environmental considerations focused more heavily on ATMPs classified as genetically modified organisms (GMO) compared to non-GMO cellular products.
Specific instructions for waste disposal and detection of biological material on work surfaces often remained vague or elusive.
| Assessment Area | Level of Attention in Literature | Key Gaps Identified |
|---|---|---|
| Surface Contamination | Limited in primary research | Standardized detection methods needed |
| Waste Disposal Protocols | Addressed but often vague | Specific handling procedures required |
| GMO vs Non-GMO Products | More focus on GMO products | Non-GMO product guidance underdeveloped |
| Healthcare Worker Training | Rarely specifically addressed | Comprehensive safety protocols needed |
| Research Tool | Primary Function | Importance in ATMP Assessment |
|---|---|---|
| Environmental Sampling Kits | Detect biological material on surfaces | Crucial for monitoring work areas during ATMP preparation and administration |
| PCR-Based Detection Methods | Identify specific genetic sequences | Essential for tracking GMO-containing ATMPs in the environment |
| Cell Viability Assays | Measure survival of cells outside intended environment | Determine potential for ATMP cells to persist where not intended |
| Waste Tracking Systems | Monitor disposal pathway of ATMP waste | Ensure contaminated materials are properly handled and contained |
| Surface Decontamination Solutions | Eliminate biological material from work areas | Critical for maintaining safe healthcare environments during ATMP use |
Pharmaceutical oversight and strict adherence to good preparation practices and good clinical practices remain essential to ensure the safe use of these innovative therapeutic products in healthcare settings 1 .
The systematic review underscores that while ATMPs represent a medical revolution, their environmental safety profile requires further investigation 1 . The precautionary approach currently dominant in product literature suggests that regulators and developers recognize potential risks even as they work to fully characterize them.
The emergence of ATMPs represents one of the most exciting developments in modern medicine, offering potential cures for conditions previously considered untreatable. However, their complex biological nature requires equally sophisticated approaches to environmental safety.
As the systematic review reveals, the scientific community is actively working to understand and mitigate potential risks 1 . This proactive approach to environmental assessment demonstrates a commitment to responsible medical innovation—one that embraces cutting-edge treatments while carefully managing their integration into healthcare systems and the broader environment.
| Aspect | Current Status | Future Needs |
|---|---|---|
| Research Base | Limited primary research; heavy on reviews | More original studies on environmental exposure |
| Regulatory Guidance | Precautionary rather than specific requirements | More detailed, evidence-based protocols |
| Waste Management | General precautions mentioned | Specific, standardized disposal methods |
| Risk Communication | Information often elusive in product documents | Clear, accessible guidance for healthcare workers |
| GMO Considerations | Greater attention to GMO-containing products | Balanced approach for all ATMP categories |
The journey of these "living medicines" from laboratory concepts to routine treatments depends not only on their therapeutic effectiveness but also on our ability to manage their entire lifecycle safely—from manufacturing to administration and, ultimately, to disposal. It's a complex challenge, but one that the scientific and medical communities are steadily working to address as they unlock the enormous potential of these revolutionary therapies.