Updated: 6th August 2026
Reviewed by: David Small BSc (Hons), MSc, MTOPRA (Founder and CEO)
What Is Drug Stability in Medical Devices?
Drug stability is a critical consideration for medical devices that store, deliver or come into direct contact with medicinal products. While pharmaceutical manufacturers are responsible for demonstrating the stability of the medicinal product itself, medical device manufacturers must also consider whether the device’s materials, design and intended use could alter the safety, quality or performance of the drug. This assessment, often referred to as drug-device compatibility, helps ensure that patients receive the intended dose of medication without unacceptable changes to its chemical, physical or biological properties.
Medical devices such as syringes, prefilled syringes, infusion sets, extension lines, administration bags, drug reservoirs and infusion pumps may all interact with medicinal products during storage or clinical use. These interactions can include the adsorption of active pharmaceutical ingredients onto polymer surfaces, absorption into device materials, chemical degradation, oxidation, hydrolysis, the migration of extractable or leachable substances from the device into the drug product and changes in pH, particulate levels or overall formulation stability. Even small interactions may affect the efficacy, safety or shelf life of sensitive medicinal products, particularly biologics and complex injectable therapies.
Drug stability assessments are therefore closely linked to the wider Biological Evaluation of medical devices. As part of a risk-based approach under ISO 10993-1:2025, manufacturers should consider whether the materials used within the device could introduce chemical constituents or otherwise influence patient exposure. Where appropriate, Extractables and Leachables (E&L) studies performed in accordance with ISO 10993-18 help identify chemical substances that may migrate from device materials, while toxicological risk assessments undertaken in accordance with ISO 10993-17 determine whether those substances present an acceptable biological risk. Together, these activities support the overall demonstration of biological safety and compatibility.
Drug stability has become increasingly important with the rapid growth of biologics, biosimilars, monoclonal antibodies, cell and gene therapies, and other highly sensitive pharmaceutical products. Unlike many conventional small-molecule drugs, these complex medicines can be particularly susceptible to material interactions, protein adsorption, aggregation, oxidation and other subtle changes that may affect therapeutic performance. As a result, regulators increasingly expect manufacturers to adopt a scientifically justified, risk-based approach when evaluating the compatibility of medical devices with the medicinal products they are intended to store or deliver.
This guide explains the principles of drug stability and drug-device compatibility, the mechanisms by which medical devices can influence medicinal products, the types of devices that commonly require compatibility assessments, the laboratory testing methods used to evaluate stability and how these studies support Biological Evaluation, Technical Documentation and regulatory compliance for medical devices.
New to Biological Evaluation?
Drug stability and drug-device compatibility are important considerations within a risk-based Biological Evaluation. If you're looking for a complete introduction to ISO 10993, Biological Evaluation Plans (BEPs), Biological Evaluation Reports (BERs), biocompatibility testing, chemical characterisation, toxicological risk assessment and biological endpoints, explore our Complete Guide to Biological Evaluation of Medical Devices.
Understanding Drug Stability
Drug stability refers to the ability of a medicinal product to maintain its physical, chemical, microbiological and therapeutic properties throughout its intended shelf life, storage, transportation and clinical use. Maintaining stability is essential to ensure that patients receive a product that remains safe, effective and performs as intended from the point of manufacture through to administration.
For medical devices that store, prepare or deliver medicinal products, drug stability extends beyond the pharmaceutical formulation itself. Manufacturers must also consider whether contact with device materials could influence the quality or performance of the medicinal product. This broader assessment, often referred to as drug-device compatibility, evaluates whether interactions between the drug and the medical device could result in unacceptable changes that affect patient safety or therapeutic efficacy.
Drug stability assessments may consider several aspects of the medicinal product, including:
- Chemical stability – ensuring the active pharmaceutical ingredient (API) does not degrade or react with device materials.
- Physical stability – confirming there are no unacceptable changes such as precipitation, aggregation, colour changes, phase separation or increased particulate matter.
- Microbiological stability – demonstrating that the product maintains sterility or remains protected from microbial contamination throughout its intended use.
- Biological stability – particularly important for biologics, ensuring proteins, peptides, antibodies and other complex molecules retain their structure and biological activity.
- Therapeutic stability – confirming that the medicinal product continues to deliver its intended clinical performance and dosage throughout storage and administration.
A comprehensive drug stability assessment helps manufacturers identify potential compatibility issues before products reach patients. It also provides important evidence supporting Biological Evaluation, risk management, Technical Documentation and regulatory submissions, particularly for devices intended to store or administer injectable medicines, biologics and other sensitive pharmaceutical products.
Why Is Drug Stability Testing Important?
Drug stability testing is essential because interactions between a medical device and a medicinal product can influence the safety, quality and therapeutic performance of the drug throughout storage and clinical use. Medical devices such as syringes, prefilled syringes, infusion sets, administration bags, extension lines and infusion pumps often remain in prolonged contact with medicinal products, creating opportunities for physical or chemical interactions that may not be apparent during routine product development.
A scientifically designed drug stability study helps manufacturers demonstrate that these interactions do not adversely affect the medicinal product or introduce unacceptable risks to patients. This evidence supports product development, Biological Evaluation, risk management activities and regulatory submissions.
Drug stability testing is performed to demonstrate that:
- Patient safety is maintained by confirming that no harmful degradation products, contaminants or excessive levels of extractable or leachable substances are introduced during storage or administration.
- Drug efficacy is preserved by ensuring that the active pharmaceutical ingredient (API) retains its intended potency, biological activity and therapeutic performance throughout the product’s shelf life and clinical use.
- Product quality remains consistent by confirming that important characteristics such as pH, particulate levels, appearance, concentration, sterility and formulation integrity remain within acceptable specifications.
- Device compatibility has been demonstrated by evaluating whether contact with polymers, elastomers, lubricants, adhesives, coatings or other device materials causes adsorption, absorption, degradation or other interactions that could affect the medicinal product.
- Regulatory expectations are met by generating scientific evidence that supports Biological Evaluation, Technical Documentation and risk management activities, while demonstrating compliance with applicable international standards and regulatory guidance.
As pharmaceutical products become increasingly complex, particularly biologics, biosimilars, antibody-based therapies and other advanced medicinal products, robust drug stability and drug-device compatibility studies are becoming an increasingly important component of medical device development. These studies help ensure that both the medical device and the medicinal product continue to perform safely and effectively throughout their intended lifecycle.
Challenges in Drug Stability and Drug–Device Compatibility Testing
Drug stability and drug–device compatibility studies can be technically challenging because they must demonstrate that both the medicinal product and the medical device continue to perform safely and effectively throughout storage, preparation and clinical use. The complexity of these assessments has increased significantly with the growing use of biologics, combination products and advanced drug delivery systems, requiring manufacturers to consider multiple scientific, analytical and regulatory factors.
Material Compatibility
Medical devices used to store or administer medicinal products are manufactured from a wide range of polymers, elastomers, adhesives, lubricants and coatings. Materials such as polypropylene, polyethylene, polyvinyl chloride (PVC), cyclic olefin polymers (COP), cyclic olefin copolymers (COC), silicone and rubber components may interact differently with pharmaceutical formulations. These interactions can result in adsorption of the active pharmaceutical ingredient, absorption into device materials, chemical degradation or the migration of extractable and leachable substances that could affect product quality or patient safety.
Complex Pharmaceutical Formulations
Modern medicinal products are becoming increasingly complex. While conventional small-molecule drugs are generally well understood, biologics, monoclonal antibodies, peptides, vaccines and cell and gene therapies may be highly sensitive to environmental conditions and material interactions. Even minor changes in pH, temperature, light exposure, agitation or contact with device materials can lead to protein aggregation, denaturation or loss of biological activity, making compatibility studies particularly important for these products.
Simulating Clinical Use
One of the greatest challenges in drug stability testing is reproducing realistic storage and administration conditions within a laboratory environment. Manufacturers should consider factors such as storage duration, transportation, temperature fluctuations, infusion times, flow rates, contact duration, light exposure and the intended method of administration when designing stability studies. Testing should reflect both the labelled conditions of use and reasonably foreseeable worst-case scenarios to ensure that compatibility has been adequately demonstrated.
Sensitive Analytical Testing
Detecting subtle changes in pharmaceutical products often requires multiple complementary analytical techniques. Manufacturers may use high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), gas chromatography-mass spectrometry (GC-MS), inductively coupled plasma-mass spectrometry (ICP-MS), particulate analysis, pH measurement and visual inspection to identify degradation products, impurities, changes in potency and interactions between the medicinal product and device materials. Selecting appropriate analytical methods is therefore a critical part of any drug stability programme.
Regulatory Expectations
Drug stability assessments should be scientifically justified and integrated into the wider Biological Evaluation and risk management process. Manufacturers should demonstrate that compatibility studies have been appropriately planned, that potential chemical interactions have been investigated where necessary and that the available evidence supports the intended clinical use of the medical device. This may include consideration of extractables and leachables, toxicological risk assessment, ISO 14971 risk management and the overall Biological Evaluation documented within the Technical Documentation.
Drug Stability Testing Strategy
1. Drug Stability Testing Strategy
A well-designed drug stability study begins long before laboratory testing is performed. Manufacturers should develop a scientifically justified testing strategy that reflects the intended use of the medical device, the characteristics of the medicinal product and the potential interactions that may occur throughout storage, preparation and clinical administration. The study should generate sufficient evidence to demonstrate that the medical device does not adversely affect the quality, safety or therapeutic performance of the medicinal product under normal and reasonably foreseeable conditions of use.
Define the Study Objective
The first step is to clearly define the purpose of the stability study. The study objectives should reflect the intended clinical use of the medical device and identify the compatibility questions that need to be answered.
Typical objectives may include:
- Demonstrating that the medicinal product remains stable throughout its intended shelf life.
- Assessing compatibility between the drug and medical device materials.
- Evaluating the potential impact of storage and administration conditions.
- Identifying any degradation products or impurities that may develop over time.
- Confirming that the medical device does not adversely affect the quality or therapeutic performance of the medicinal product.
A clearly defined objective helps ensure that the study design, analytical methods and acceptance criteria are appropriate for the intended application.
Select Representative Medical Devices
Drug stability studies should use medical devices that accurately represent the finished product placed on the market. Wherever possible, testing should be performed using finished, sterilised production-equivalent devices rather than prototype components.
Manufacturers should consider:
- Finished and sterilised devices.
- Patient-contacting materials.
- Fluid-path components.
- Adhesives, lubricants and coatings.
- Manufacturing and sterilisation processes.
- Worst-case material combinations where multiple configurations exist.
Testing representative devices helps ensure that the study reflects the actual product that will be used by healthcare professionals and patients.
Choose the Medicinal Product
The medicinal product selected for testing should represent the intended clinical application of the medical device. Where a device is designed for use with multiple drugs, manufacturers may adopt a scientifically justified worst-case approach by selecting formulations that present the greatest compatibility challenge.
Factors influencing product selection may include:
- Small-molecule pharmaceuticals.
- Biologics and biosimilars.
- Monoclonal antibodies.
- Protein and peptide therapeutics.
- Highly concentrated formulations.
- Products with extreme pH values.
- Lipid emulsions or solvent-based formulations.
The rationale for product selection should be documented within the study protocol.
Define Storage and Environmental Conditions
Storage conditions should reflect both the labelled storage requirements and any reasonably foreseeable environmental conditions that the device and medicinal product may experience before administration.
The study should consider factors such as:
- Storage temperature.
- Relative humidity.
- Light exposure.
- Transportation conditions.
- Shelf-life duration.
- Freeze-thaw cycles where applicable.
Where appropriate, accelerated stability studies may also be performed to evaluate long-term performance within a shorter timeframe.
Simulate Clinical Use
Laboratory testing should reproduce the intended conditions of clinical use as closely as possible. This helps ensure that any observed interactions between the medicinal product and medical device are representative of real-world patient exposure.
Depending on the device, manufacturers may evaluate:
- Contact time between the drug and device materials.
- Infusion duration.
- Flow rates.
- Priming procedures.
- Administration temperatures.
- Multiple-dose or prolonged infusion scenarios.
- Worst-case clinical conditions where appropriate.
Simulating clinical use provides confidence that laboratory results are relevant to the intended application of the device.
Select Sampling Time Points
Drug stability should be evaluated throughout the period during which the medicinal product remains in contact with the medical device. Sampling should be planned to detect both immediate and delayed changes in product quality.
Typical sampling points may include:
- Initial baseline measurements.
- Intermediate storage intervals.
- End-of-shelf-life assessments.
- Immediately before administration.
- During prolonged infusion or use.
- At the completion of administration.
The frequency of sampling should be justified according to the anticipated stability profile of the medicinal product.
Establish Acceptance Criteria
Before testing begins, manufacturers should define objective acceptance criteria against which the study results will be evaluated. These criteria should be based on scientific evidence, product specifications and applicable regulatory expectations.
Acceptance criteria may include:
- Active pharmaceutical ingredient (API) potency.
- Chemical purity.
- Absence of significant degradation products.
- Acceptable pH range.
- Appearance and colour.
- Particulate levels.
- Sterility where applicable.
- Biological activity for biologics.
Predefined acceptance criteria help ensure that study conclusions are objective, reproducible and scientifically defensible.
Perform Statistical Evaluation
Where appropriate, study data should be analysed using suitable statistical methods to demonstrate that observed changes are not clinically or scientifically significant. Statistical evaluation can help distinguish genuine trends from normal analytical variation and provides greater confidence in the overall conclusions.
The final assessment should integrate analytical results, compatibility observations and scientific interpretation to determine whether the medicinal product remains stable and suitable for use with the medical device throughout its intended lifecycle. This evidence can then be incorporated into the manufacturer’s Biological Evaluation, Risk Management File and Technical Documentation to support regulatory compliance.
Want to Learn What’s New in ISO 10993-1:2025?
Drug stability and drug-device compatibility should be considered within a risk-based Biological Evaluation. Learn how ISO 10993-1:2025 strengthens the requirements for Biological Evaluation Plans (BEPs), Biological Evaluation Reports (BERs), chemical characterisation, toxicological risk assessment and scientific justification for testing in our Guide to ISO 10993-1:2025.
2. Laboratory Testing Methods
Following study design and sample preparation, a range of analytical techniques may be used to evaluate the stability of medicinal products after contact with medical devices. The choice of laboratory methods depends on the characteristics of the pharmaceutical product, the materials used within the device and the potential interactions being investigated. In many cases, manufacturers employ multiple complementary analytical techniques to provide a comprehensive assessment of chemical, physical and biological stability.
| Laboratory Method | Primary Purpose | Typical Assessment |
|---|---|---|
| High-Performance Liquid Chromatography (HPLC) | Assess potency and chemical degradation | Quantifies the active pharmaceutical ingredient (API) and detects degradation products formed during storage or administration. |
| Liquid Chromatography-Mass Spectrometry (LC-MS) | Identify degradation products and impurities | Detects and characterises degradation products, impurities and compounds that may migrate from medical device materials. |
| Gas Chromatography-Mass Spectrometry (GC-MS) | Detect volatile organic compounds | Identifies volatile organic compounds, residual solvents and other volatile contaminants that may affect product quality. |
| Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) | Identify elemental impurities | Measures trace metals and elemental contaminants that may originate from device materials or manufacturing processes. |
| UV-Visible Spectroscopy | Monitor concentration changes | Assesses changes in drug concentration and monitors degradation of light-sensitive pharmaceutical products. |
| pH Measurement | Detect formulation changes | Confirms that contact with the medical device has not significantly altered the acidity or alkalinity of the formulation. |
| Osmolality Testing | Confirm solution integrity | Evaluates changes in solution concentration that may indicate evaporation, dilution or formulation instability. |
| Visual Inspection | Assess physical appearance | Detects changes in colour, clarity, precipitation, phase separation or other visible signs of instability. |
| Particulate Testing | Detect visible and sub-visible particles | Identifies particulate contamination, aggregation or material shedding that could compromise product quality or patient safety. |
No single analytical method can evaluate every aspect of drug stability. Manufacturers therefore combine complementary analytical techniques to assess the chemical, physical and, where applicable, biological stability of medicinal products while identifying potential interactions between the medicinal product and the medical device. This orthogonal analytical approach provides greater confidence that changes in product quality have been appropriately detected, characterised and scientifically evaluated.
The selection of laboratory methods should always be scientifically justified based on the characteristics of the medicinal product, device materials, route of administration, intended clinical use and the objectives of the stability study. The resulting analytical data should then be interpreted alongside Biological Evaluation, Extractables and Leachables (E&L) studies, toxicological risk assessments and ISO 14971 risk management activities to demonstrate that the medical device remains suitable for its intended purpose throughout its lifecycle.
What Happens if Drug Stability Testing Identifies a Compatibility Issue?
A drug stability study that identifies changes in the medicinal product does not necessarily mean that the medical device is unsafe or unsuitable for its intended purpose. Instead, the results should be carefully investigated to determine the underlying cause, evaluate the potential impact on patient safety and product performance, and identify appropriate corrective actions. The objective is to establish whether the observed changes are scientifically acceptable or whether additional risk control measures are required before the device can be placed on the market.
Investigate the Root Cause
The first step is to determine why the medicinal product has changed during storage or administration. Manufacturers should review all aspects of the study to identify the most likely source of the interaction.
Potential causes may include:
- Adsorption of the active pharmaceutical ingredient (API) onto device materials.
- Absorption of drug constituents into polymer components.
- Chemical degradation caused by material interactions.
- Migration of extractable or leachable substances.
- Changes in pH or formulation chemistry.
- Inappropriate storage or environmental conditions.
- Manufacturing or sterilisation-related effects.
Understanding the root cause allows manufacturers to determine whether the issue is related to the medical device, the medicinal product or the study design itself.
Assess the Potential Risk
Once the cause has been identified, manufacturers should evaluate whether the observed changes are likely to affect patient safety, medicinal product quality or therapeutic performance. This assessment should consider the extent of degradation, patient exposure, clinical use and any available toxicological or pharmaceutical evidence.
Where migrated chemical constituents are identified, manufacturers may perform additional chemical characterisation and toxicological risk assessments in accordance with ISO 10993-18 and ISO 10993-17 to determine whether patient exposure remains within acceptable limits.
Consider Design or Material Changes
If the compatibility issue is linked to the medical device, changes to the device design or material selection may be necessary. Depending on the findings, manufacturers may consider:
- Selecting alternative polymers or elastomeric materials.
- Modifying lubricants, coatings or adhesives.
- Reducing contact time between the medicinal product and device materials.
- Improving manufacturing or sterilisation processes.
- Optimising packaging or storage conditions.
Any design changes should be assessed through the manufacturer’s ISO 14971 risk management process before implementation.
Perform Additional Testing Where Necessary
Following design modifications or additional risk assessments, further testing may be required to confirm that the identified issue has been resolved. This may include repeat drug stability studies, extractables and leachables investigations, additional analytical testing or other biological endpoints identified within the Biological Evaluation Plan (BEP).
The extent of further testing should always be proportionate to the identified risk and supported by scientific justification.
Update the Biological Evaluation
The results of all investigations, risk assessments and additional testing should be incorporated into the manufacturer’s Biological Evaluation Report (BER), Risk Management File and Technical Documentation. This ensures that the overall evidence continues to demonstrate that the medical device remains suitable for its intended purpose and does not adversely affect the quality, safety or therapeutic performance of the medicinal product throughout its intended lifecycle.
Could Drug-Device Interactions Affect Cell Safety?
Where drug stability studies, chemical characterisation or toxicological assessment identify a potential biological concern, cytotoxicity may require further evaluation. Learn how ISO 10993-5 testing assesses whether medical device materials or extracts have the potential to damage living cells in our Complete Guide to Cytotoxicity Testing.
Could Patient-Contacting Materials Cause Skin Irritation?
Drug-contacting medical devices may also contain components that contact the patient’s skin and require evaluation for irritation risk. Learn how ISO 10993-23 uses reconstructed human epidermis (RHE) models to assess irritation potential within a risk-based Biological Evaluation in our Complete Guide to In Vitro Skin Irritation Testing.
Need to Understand Extractables and Leachables?
Drug stability and drug-device compatibility are closely linked to substances that may migrate from medical device materials into medicinal products. Learn how manufacturers perform chemical characterisation, identify extractables and leachables, assess patient exposure and evaluate toxicological risk under ISO 10993-18 and ISO 10993-17 in our Complete Guide to Extractables and Leachables Testing.
Worked Example: Drug Stability Assessment for a Prefilled Syringe
A manufacturer develops a single-use prefilled syringe intended to deliver a monoclonal antibody for subcutaneous injection. The syringe consists of a cyclic olefin polymer (COP) barrel, a silicone-lubricated stopper and an elastomeric plunger seal. Because the medicinal product will remain in contact with the syringe components throughout its shelf life, the manufacturer identifies drug stability and drug-device compatibility as key considerations during product development.
As part of the Biological Evaluation Plan (BEP) and overall risk management process, a comprehensive drug stability study is designed to determine whether prolonged contact with the syringe materials could affect the quality, safety or therapeutic performance of the monoclonal antibody. The study protocol includes long-term storage under labelled conditions, accelerated ageing, simulated transportation and in-use evaluations representative of normal clinical practice.
Representative finished, sterilised syringes are filled with the medicinal product and stored under controlled environmental conditions. Samples are collected at predefined intervals throughout the study and analysed using complementary laboratory techniques including HPLC to monitor potency and degradation, LC-MS to identify degradation products and impurities, GC-MS and ICP-MS to investigate potential chemical migration from syringe materials, together with pH measurement, particulate analysis and visual inspection to assess formulation stability.
In parallel, Extractables and Leachables (E&L) studies are performed to determine whether any chemical constituents migrate from the syringe materials into the medicinal product during storage. Identified compounds are evaluated through a toxicological risk assessment in accordance with ISO 10993-17, while the overall chemical characterisation strategy follows the principles of ISO 10993-18.
The study demonstrates that the monoclonal antibody maintains its potency, structural integrity and biological activity throughout the intended shelf life. No clinically significant adsorption to device materials is observed, no unacceptable degradation products are detected and the concentration of any extractable or leachable substances remains within scientifically acceptable limits. Visual appearance, pH and particulate levels also remain within predefined product specifications.
Based on the complete body of evidence, the manufacturer concludes that the syringe is compatible with the medicinal product for its intended use. The findings are incorporated into the Biological Evaluation Report (BER), the ISO 14971 Risk Management File and the Technical Documentation, providing robust scientific evidence that the medical device does not adversely affect the safety, quality or therapeutic performance of the medicinal product throughout its intended lifecycle.
Key Takeaways
- Drug stability studies evaluate whether a medical device affects the safety, quality or therapeutic performance of a medicinal product throughout storage and clinical use.
- Drug-device compatibility assessments consider interactions such as adsorption, absorption, chemical degradation and the migration of extractable or leachable substances from device materials.
- A scientifically justified testing strategy should reflect the intended clinical use, device materials, medicinal product characteristics and relevant worst-case conditions.
- Multiple complementary analytical techniques, including HPLC, LC-MS, GC-MS and ICP-MS, are typically required to assess chemical, physical and biological stability comprehensively.
- Drug stability evidence supports Biological Evaluation, ISO 14971 risk management, Technical Documentation and regulatory compliance by demonstrating that the medical device remains compatible with the medicinal product throughout its intended lifecycle.
When Is Additional Biocompatibility Testing Required?
Drug stability or compatibility concerns do not automatically mean that new biological testing is required. Manufacturers should first review existing evidence, chemical characterisation, toxicological risk assessments and identified biological risks. Learn how these decisions are made in our Guide to When Biocompatibility Testing Is Required.
Conclusion
Drug stability and drug-device compatibility are fundamental considerations for medical devices that store, prepare or administer medicinal products. Whether evaluating syringes, prefilled syringes, infusion sets, administration bags or other drug-contacting devices, manufacturers should demonstrate that contact with device materials does not adversely affect the medicinal product’s chemical, physical or biological stability throughout its intended shelf life and clinical use.
A robust drug stability programme combines careful study design, representative testing conditions and scientifically justified analytical methods to identify potential compatibility issues before products reach patients. These studies frequently complement Biological Evaluation activities by providing evidence that material interactions, extractables and leachables, degradation products and other compatibility risks have been appropriately investigated and controlled.
As pharmaceutical products become increasingly complex, particularly biologics, biosimilars and other advanced therapies, the importance of comprehensive drug stability assessments will continue to grow. By integrating drug stability studies with Biological Evaluation, ISO 14971 risk management and Technical Documentation, manufacturers can generate the evidence needed to demonstrate regulatory compliance while ensuring that medical devices continue to deliver medicinal products safely, effectively and consistently throughout their intended lifecycle.
Frequently Asked Questions
Drug stability in medical devices refers to the ability of a medicinal product to maintain its chemical, physical, microbiological and therapeutic properties while stored or administered using a medical device. Drug stability studies evaluate whether contact with device materials affects the quality, safety or effectiveness of the medicinal product throughout its intended shelf life and clinical use.
Drug-device compatibility ensures that the medical device does not adversely affect the medicinal product during storage, preparation or administration. Compatibility assessments investigate potential interactions such as adsorption, absorption, chemical degradation, extractables and leachables, particulate formation and changes in formulation characteristics that could compromise patient safety or therapeutic performance.
Drug stability studies are commonly performed for medical devices that come into prolonged contact with medicinal products, including prefilled syringes, infusion sets, intravenous (IV) administration sets, extension lines, infusion bags, drug reservoirs, infusion pumps and drug delivery catheters. The extent of testing depends on the intended use, contact duration, device materials and characteristics of the medicinal product.
Several factors can influence drug stability, including the composition of device materials, adsorption of active pharmaceutical ingredients, migration of extractable or leachable substances, temperature, light exposure, storage duration, pH changes, oxygen exposure, agitation during transport and the chemical properties of the medicinal product. Biologics and protein-based therapies are often particularly sensitive to these factors.
Drug stability studies typically use multiple complementary analytical techniques. These may include High-Performance Liquid Chromatography (HPLC) to assess potency and degradation, Liquid Chromatography-Mass Spectrometry (LC-MS) to identify impurities, Gas Chromatography-Mass Spectrometry (GC-MS) for volatile compounds, Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) for elemental impurities, together with pH measurement, osmolality testing, particulate analysis and visual inspection to evaluate overall product quality.
Extractables and leachables (E&L) studies support drug stability assessments by identifying chemical substances that may migrate from medical device materials into the medicinal product. These studies help determine whether migrated compounds could affect product quality, patient safety or therapeutic performance and form an important part of chemical characterisation and Biological Evaluation under the ISO 10993 series.
If a stability study identifies unacceptable changes to the medicinal product, manufacturers should investigate the underlying cause. This may involve reviewing device materials, manufacturing processes, sterilisation methods, storage conditions or product formulations. Additional analytical testing, toxicological risk assessment or design modifications may be required before the device can be considered suitable for its intended use.
Drug stability studies provide valuable scientific evidence for the Biological Evaluation of medical devices by demonstrating that contact with device materials does not adversely affect the medicinal product. The results may be considered alongside chemical characterisation, extractables and leachables studies, toxicological risk assessments and ISO 14971 risk management activities to support the overall demonstration of biological safety.
Drug stability assessments are particularly important for biologics, biosimilars, monoclonal antibodies, peptides and other advanced medicinal products because these therapies are often more sensitive to material interactions than conventional small-molecule drugs. Manufacturers should consider factors such as protein adsorption, aggregation, oxidation and compatibility with device materials when designing stability studies.
Patient Guard supports manufacturers in planning and reviewing drug stability and drug-device compatibility programmes for medical devices used with medicinal products. Our consultants assist with Biological Evaluation Plans (BEPs), risk management, chemical characterisation strategies, Extractables and Leachables (E&L) assessments, Technical Documentation and Biological Evaluation Reports (BERs), helping manufacturers demonstrate compliance with ISO 10993, ISO 14971, EU MDR and UK MDR requirements.
References
This guide is based on the following legislation, international standards and official regulatory guidance relating to drug stability, drug-device compatibility, chemical characterisation, toxicological risk assessment and the safe storage and administration of medicinal products using medical devices.
| Organisation | Reference | Why it's relevant |
|---|---|---|
| European Union | Regulation (EU) 2017/745 on Medical Devices (MDR) | Provides the legal framework for medical devices placed on the European Union market. It requires manufacturers to demonstrate that devices are designed and manufactured to achieve their intended performance without compromising patient safety, including where devices administer, transport or come into contact with medicinal products. |
| International Council for Harmonisation (ICH) | ICH Q1A(R2) – Stability Testing of New Drug Substances and Products | Establishes internationally recognised principles for pharmaceutical stability testing, including the assessment of how drug quality changes over time under environmental influences such as temperature, humidity and light. It supports the establishment of shelf life, storage conditions and appropriate stability-testing programmes. |
| International Council for Harmonisation (ICH) | ICH Q5C – Quality of Biotechnological Products: Stability Testing of Biotechnological and Biological Products | Provides stability-testing guidance for biological and biotechnological medicinal products. It is particularly relevant to monoclonal antibodies, proteins, peptides and other biologics that may be sensitive to adsorption, aggregation, degradation and interactions with medical device materials. |
| U.S. Food and Drug Administration (FDA) | Container Closure Systems for Packaging Human Drugs and Biologics | Explains the FDA's expectations for information supporting the suitability of packaging and container-closure materials used with human drugs and biologics. The principles are relevant to prefilled syringes, drug reservoirs and other devices that remain in direct contact with medicinal products during storage. |
| International Organization for Standardization (ISO) | ISO 10993-1:2025 – Biological Evaluation of Medical Devices – Part 1: Requirements and General Principles for the Evaluation of Biological Safety Within a Risk Management Process | Provides the overarching risk-based framework for evaluating the biological safety of medical devices. Although it is not a pharmaceutical stability standard, it supports consideration of device materials, chemical constituents and patient exposure where a medical device stores or administers a medicinal product. |
| International Organization for Standardization (ISO) | ISO 10993-18:2020 – Biological Evaluation of Medical Devices – Part 18: Chemical Characterisation of Medical Device Materials Within a Risk Management Process | Defines the framework for identifying and quantifying chemical constituents associated with medical device materials. It supports extractables, leachables and simulated-use assessments used to investigate whether substances may migrate from syringes, infusion sets, bags or other drug-contacting devices. |
| International Organization for Standardization (ISO) | ISO 10993-18:2020/Amd 1:2022 – Amendment 1: Determination of the Uncertainty Factor | Amends ISO 10993-18 by addressing the analytical uncertainty factor used when establishing and applying reporting thresholds during chemical characterisation and extractables and leachables assessments. |
| International Organization for Standardization (ISO) | ISO 10993-17:2023 – Biological Evaluation of Medical Devices – Part 17: Toxicological Risk Assessment of Medical Device Constituents | Specifies the process for determining whether estimated patient exposure to chemical constituents released from medical device materials presents an acceptable toxicological risk. It supports the assessment of leachables identified in medicinal products following contact with device components. |
| International Organization for Standardization (ISO) | ISO 10993-17:2023/Amd 1:2025 – Amendment 1 | Provides the published amendment applicable to ISO 10993-17:2023 and should be considered when planning, performing and documenting toxicological risk assessments of medical device constituents. |
| International Organization for Standardization (ISO) | ISO 14971:2019 – Medical Devices – Application of Risk Management to Medical Devices | Provides the internationally recognised framework for identifying, evaluating, controlling and monitoring risks associated with medical devices. It supports the assessment and management of drug-device compatibility risks throughout product development and the device lifecycle. |
Drug stability and drug-device compatibility studies should be designed according to the medicinal product, medical device materials, duration and conditions of contact, intended clinical use and identified risks. Pharmaceutical stability guidance, chemical characterisation, toxicological assessment and medical device risk management should be applied together where relevant, with the scientific rationale and conclusions documented within the appropriate pharmaceutical and medical device Technical Documentation.
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