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Navigating risk in biological quality testing: A guide for emerging laboratories
For correspondence: Ms. Shalini Tewari, Quality Management Unit, National Institute of Biologicals, Noida 201 309, Uttar Pradesh, India e-mail: stewari69@gmail.com
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Received: ,
Accepted: ,
How to cite this article: Shrivastava R, Goel S, Trivedi N, Mishra N, Tewari S. Navigating risk in biological quality testing: A guide for emerging laboratories. Indian J Med Res. 2026;163:611-7. doi: 10.25259/IJMR_3513_2025
Abstract
Biological products are inherently complex and highly sensitive to variations in testing conditions, rendering quality control (QC) testing laboratories particularly vulnerable to high-impact operational, analytical, and biosafety risks. Despite the emphasis on risk-based thinking in international standards, a structured laboratory-specific framework for identifying, assessing, and mitigating risks in biological product QC testing remains insufficiently articulated. This article presents a simplified approach for proactive identification of testing-related and occupational health risks, along with their mitigation and conversion into opportunities. The concept aligns with internationally accepted standards, including ISO/IEC Guide 51, ISO 31000:2018, ISO/IEC 17025:2017, and ICH Q9 guidelines. Implementation of this framework enhances the reliability of results, strengthens regulatory compliance, and improves patient and occupational safety. By addressing the gap in structured risk assessment for biological QC laboratories, the article provides practical guidance for implementing ISO/IEC 17025:2017 Clause 8.5 and enables continuous improvement through systematically converting identified risks into opportunities.
Keywords
Biological products
ICH Q9
ISO/IEC 17025
Risk assessment
Risk priority number
Quality control laboratories
Biopharmaceuticals, or biological drugs- including vaccines, plasma-derived products, recombinant proteins, and monoclonal antibodies- constitute a highly effective, targeted, and often life-saving class of therapeutics widely used in rheumatology, oncology, cardiology, dermatology, gastroenterology, neurology, and diabetes management.1 These products have emerged as therapies of choice in conditions where conventional chemically synthesised drugs display limited efficacy.1 Biological products are derived from living systems such as bacteria, yeast, plants, or animal cells, either through extraction or recombinant DNA technology. These are inherently sensitive to environmental and process-related variables.2
Unlike chemically synthesised small-molecule pharmaceuticals, which are structurally well-defined and highly reproducible, biological products are large, structurally complex, and heterogeneous. Variability arising from post-translational modifications and manufacturing conditions means that even minor process changes can significantly alter critical quality attributes, including potency, stability, and immunogenicity.3 Therefore, stringent control throughout the product life cycle- spanning production, transport, storage, and distribution- is essential.
Testing of biological products, therefore, poses challenges distinct from those encountered in conventional pharmaceutical or clinical analytical laboratories. Quality evaluation often relies on complex bioassays, cell-based assays, and functional tests that are inherently variable, operator-dependent, and highly sensitive to environmental conditions. Unlike routine physicochemical tests used for small-molecule drugs, biological assays often lack absolute measurement endpoints and depend on reference standards that may themselves exhibit limited stability.4 Moreover, laboratories testing biological products must address biosafety risks associated with live organisms, cell cultures, or biologically active materials.5
Taken together, these factors render the risks associated with biological product testing distinct in terms of assay variability, reproducibility, biosafety, reference standard management, and environmental control. This underscores the need for a structured, laboratory-specific risk assessment framework tailored to biological product quality control laboratories, rather than reliance on conventional risk management approaches used for small-molecule or routine clinical testing.6
For mitigating potential risks in the context of laboratories, risk management has been prescribed via various global guidelines related to biosafety, manufacturing of biopharmaceuticals, occupational safety, and patient safety, wherein false testing results could lead to a wrong diagnosis. Risk management needs the involvement of every sphere of the organisation in a structured and comprehensive manner for consistent and comparable quality outcomes.7-11 Significant challenges have been highlighted previously for the need to implement risk management procedures methodologically and technically in laboratories following global regulatory, biosafety, and quality norms.12-13 The importance of risk assessment in laboratory test results related to clinical laboratories, mechanical product testing laboratories, or in general, accredited testing laboratories has been deliberated earlier.14-16 However, in the field of biological product testing, a crucial gap still exists with respect to such methodologies and ways for risk management.
Importance of biological product QC testing laboratory and its compliance with ISO/IEC 17025:2017
National Control Laboratories play a key role in bolstering the country’s healthcare system since they ensure the quality of Biopharmaceuticals, a critical class of medicines mostly classified as life-saving medicines.17 An exceptionally well-maintained quality system has to be in place for the testing of such medicines to ensure that no false results let any substandard product get released in the Indian market. Thus, a well-accredited system in conformance with ISO/IEC 17025:2017 is recommended for laboratories.
As per the requirement of the ISO/IEC 17025:2017 standard, which prescribes requirements for competence of testing and calibration, testing laboratories are required to plan and implement actions to address risks and opportunities that may affect the validity and quality of their test results. Addressing both risks and opportunities forms the basis for improving management system efficiency, achieving better outcomes, and mitigating adverse impacts.
To contextualise the subsequent risk assessment framework, an overview of routine biological QC laboratory workflows aligned with ISO/IEC 17025:2017 requirements is presented below in Figure.
Risk assessment process
The laboratory should prepare a risk assessment plan to identify potential hazards and determine controls to prevent or minimise the undesired impacts and potential failures in its activities. It is to ensure the management system for achieving its objective, intended results, and opportunities for improvement. The process entails three key phases:
Phase 1: Identifying hazards
The first step in risk management involves the retrospective or prospective identification of potential hazards. This includes a thorough examination of the laboratory environment, processes, and equipment to pinpoint sources of risk. Hazard identification serves as the foundation for subsequent risk assessment and risk mitigation efforts.
Phase 2: Perform risk assessment
Risk assessment involves a systematic evaluation of identified hazards based on their probability of occurrence and the severity of potential consequences. Laboratories employ risk matrices to classify risks by combining Probability (P) and Severity (S), with the overall risk level expressed as the Risk Priority Number (RPN), calculated as RPN = P × S. Based on RPN values, risks are categorised into low, medium, or high levels, enabling prioritisation of risk mitigation measures. The residual risk level following implementation of controls must be lower than the initial assessed risk.
Risk assessment represents a snapshot in time and therefore requires periodic review. Reassessment is essential when new products, test parameters, chemicals, reagents, or equipment are introduced, when changes occur in laboratory processes, or when trends indicate reduced effectiveness of existing controls.
A laboratory has the flexibility to adopt a risk matrix with dimensions of 3x3, 4x4, or 5x5, depending on its operational complexity. As a minimum, a 3×3 matrix defines distinct risk levels, with the vertical axis representing likelihood of occurrence (probability) and the horizontal axis representing impact (Severity), as shown in Table I. Higher RPN values indicate greater priority for control and mitigation actions.18
| Likelihood of occurrence (Probability; P) | Intensity of risk (Severity; S) | ||
|---|---|---|---|
| Low (1) | Medium (2) | High (3) | |
| Low (1) | Minimum risk (1) | Tolerable Risk (2) | Moderate Risk (3) |
| Medium (2) | Tolerable risk (2) | Moderate Risk (4) | Substantial Risk (6) |
| High (3) | Moderate Risk (3) | Substantial Risk (6) | Substantial Risk (9) |
Risk score = P×S; higher scores indicate higher priority for control and mitigation
Laboratories prioritise actions based on the RPN
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(i)
Low risk (RPN 1-2; minimum-tolerable risk): RPN 1 risk, highly improbable shortly, and deemed acceptable, requiring no immediate action beyond maintaining existing controls. For RPN 2 risk, consideration should be given to reducing these risks to an acceptable level, factoring in costs. Risk mitigation strategies should be implemented within a specified timeframe while ensuring current controls are upheld.
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(ii)
MEDIUM Risk (RPN 3–4 - moderate risk): Reasonably improbable or probable, requiring significant efforts to mitigate.18 Urgent implementation of risk reduction measures is advised, potentially including suspension or restriction of activities or interim controls, while maintaining existing measures.
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(iii)
HIGH Risk (RPN 6–9 - substantial risk): Highly probable or significant in likelihood, these risks are intolerable and demand immediate action.18 Activities should cease until risks are mitigated to an acceptable level. If reduction is not feasible, work must remain prohibited.
Phase 3: Action plan
Deploy control measures and establish standard operating procedures (SOPs) and training protocols. Upon identifying a control measure, analysts or researchers should integrate it into their workflow before commencing work. A concise SOP must be developed to outline the correct procedures for the process, equipment, or substance involved.18 Employees should have easy access to the SOP for reference and undergo documented training to ensure adherence to the correct procedures.
Biological product QC testing laboratory: Risk and opportunities
The Probability × Severity (P×S) model is recommended to evaluate risks in biological QC testing laboratories due to its simplicity, clarity, and practical applicability. Likelihood (probability) and Consequence (severity) scores allow semi-quantitative prioritisation of critical risks, facilitating timely mitigation and informed decision-making.18 A 3×3 risk matrix, which balances simplicity and decision-making clarity, was chosen to provide sufficient granularity for distinguishing low, medium, and high-risk events without overcomplicating the assessment process.
While alternative approaches, such as Failure Mode and Effects Analysis (FMEA), multi-criteria decision analysis, or weighted scoring systems, provide more detailed risk characterisation, they are often resource-intensive and require extensive data, which may not be feasible for all biological testing laboratories.7 The P×S model strikes a balance between methodological rigor and operational practicality, making it particularly suitable for emerging and resource-constrained laboratories.
The Supplementary Table outlines risk identification, analysis (probability and severity), evaluation, and associated mitigation and improvement opportunities for each function of a biological product QC testing laboratory, thereby supporting objective evidence of risk-based thinking during accreditation assessments.
Among the identified risks, those associated with sample handling, testing, and analysis, quality systems, documentation control, resource management, training, and customer pressure exhibited the highest Risk Priority Numbers, i.e. ≥6. These risks pose direct threats to data integrity, regulatory compliance, and accreditation. These risks require immediate mitigation through strengthened aseptic practices, robust method validation, effective QC review, preventive maintenance, competency-based training, and reinforced QMS and document control. Concentration of high risks in these functions clearly guides laboratory management to prioritise resources, corrective actions, and oversight where impact on quality and compliance is the greatest. The prioritisation of high-risk areas enables laboratories to allocate resources strategically, focusing first on risks with both high probability and severe impact on test validity and personnel safety.13 For example, variability in cell-based potency assays can be mitigated through enhanced analyst qualification and trend analysis.
Table II outlines the biological product QC testing activities that may pose occupational safety risks. It identifies specific hazards associated with each activity, describes the potential harm to personnel, and lists control measures implemented to mitigate risks.
| Function | Risk description | Likelihood (Probability) | Consequences (Severity) | RPN¥ (P×S) | Risk level | Risk evaluation | Control measures |
|---|---|---|---|---|---|---|---|
| 1. Handling of blood and blood products | Exposure to bloodborne pathogens (Needle prick, contact with the mucus membrane) | Low (1) | High (3) | 3 | Medium | Risk of transfusion-transmitted infection (HIV, HBV, HCV, Syphilis, etc.) | Biosafety practices, prophylactic immunisation (HBsAg), adherence to SOPδ, biosafety manual, in-house training, safe disposal, and an IBSC¯ in place |
| 2. Handling of control standard endotoxin | Exposure to bacterial endotoxins | Low (1) | Low (1) | 1 | Low | Fever risk | Biosafety practices, adherence to SOPδ, biosafety manual, in-house training, safe disposal, IBSC¯ in place |
| 3. Vaccine testing | Exposure to the Rabies challenge virus strain | Low (1) | High (3) | 3 | Medium | Rabies infection risk | Prophylactic vaccination, biosafety practices, PPE† use, SOPδ adherence, in-house training, differential air pressure, and IBSC¯ in place |
| 4. In vivo testing - lab animal handling | Exposure to infection (Bites) | Low (1) | Low (1) | 1 | Low | Risk of injury | Prophylactic vaccination, biosafety practices, PPE† use, SOPδ adherence, in-house training, differential air pressure, safe disposal, IBSC¯ in place |
| Exposure to zoonotic diseases | Low (1) | Medium (2) | 2 | Medium | Risk of zoonotic infections | ||
| 5. Packing of biological material | Exposure to dry ice/coolants/tools | Low (1) | Medium (2) | 2 | Low | Frostbite and injury risk | Use of gloves, PPE†, and handling procedures |
| 6. Transport and handling of biological material | Exposure to infectious material | Low (1) | High (3) | 3 | Medium | Infection risk from spills/breakages | Adherence to SOPδ, declaration certificate, courier services with data loggers, and spill kit availability |
| 7. Handling of bacterial vaccines | BCG culture exposure (needle prick, spills, aerosol) | Low (1) | Medium (2) | 2 | Low | Infection risk | Health monitoring, biosafety practices, PPE† use, SOPδ adherence, exposure control plan, differential air pressure, safe disposal, IBSC¯ in place |
| 8. Handling of bacterial and fungal culture | Exposure to bacteria and fungi | Low (1) | Low (1) | 1 | Low | Infection risk | Biosafety cabinet use, PPE†, SOPδ adherence, biosafety manual, differential air pressure |
| 9. Handling of cell lines | Exposure to continuous cell lines (carcinomas) | Low (1) | Medium (2) | 2 | Medium | Cancer risk | Biosafety cabinet use, PPE†, SOPδ adherence, biosafety manual |
| 10. Handling of chemicals and reagents; spillage of chemicals | Exposure to toxic chemicals | Low (1) | Medium (2) | 2 | Medium | Irritation/toxicity risk | Emergency showers, PPE† use, spill kits |
| Exposure to acids | Low (1) | High (3) | 3 | Medium | Acid burns | Eye wash station, emergency shower, acid-handling gloves, spill kit, fume hoods, PPE†, MSDS‡, SOPδ, biosafety manual, safe disposal, IBSC¯ in place | |
| Exposure to flammable liquids | Low (1) | High (3) | 3 | Medium | Fire risk | Fire extinguishers, proper storage, and ventilation | |
| Exposure to carcinogens/irritants | Low (1) | High (3) | 3 | Medium | Cancer, skin disease | MSDS‡ adherence, PPE† use, and safe handling training | |
| 11. Handling of liquefied gases | Exposure to liquid nitrogen spills | Low (1) | Medium (2) | 2 | Medium | Cryogenic injury risk | Cryogloves, cryogenic pump, in-house training |
| 12. Handling of sharps | Needle pricks, injuries with broken glass | Low (1) | High (3) | 3 | Medium | Injury risk | Needle destroyer, puncture-proof storage, ampoule/bottle openers, safe disposal, IBSC¯ in place, first aid box |
| 13. Cleaning of lab ware material | Exposure to detergent | Low (1) | Low (1) | 1 | Low | Irritation/allergy risk | PPE† use, biosafety practices, eye wash station, emergency shower, IBSC¯ in place |
| Exposure to acids | Low (1) | Medium (2) | 2 | Medium | Acid burns | ||
| Exposure to biological material | Low (1) | Medium (2) | 2 | Medium | Infection risk | ||
| 14. Sterilisation and decontamination of lab ware | Exposure to steam, boiling water bath, and dry heat | Low (1) | Medium (2) | 2 | Medium | Burn risk | Heat-resistant gloves, PPE† use, waste segregation, biomedical waste disposal, in-house training, IBSC¯ in place |
| 15. Operation of equipment | Exposure to UV radia tion in a biosafety cabinet | Low (1) | Low (1) | 1 | Low | Skin disease risk | Front shield with sensors |
| Explosion of autoclave, centrifuge, vacuum pump, gas cylinder | Low (1) | High (3) | 3 | Medium | Injury risk | Timely maintenance, safety protocols | |
| 16. Use of cold rooms | Exposure to -20°C | Low (1) | Medium (2) | 2 | Medium | Frostbite risk | Cryogloves, gowns, emergency alarm, logbook |
| Slippery floor | Low (1) | Medium (2) | 2 | Medium | Injury due to a slip/fall | Non-slip flooring, hazard markings | |
| Suffocation due to trapping | Low (1) | High (3) | 3 | Medium | Hypothermia risk | Emergency alarm, buddy system |
Source: The table has been developed based on cumulative institutional experience of over 3 decades in biological product QC testing at the National Institute of Biologicals (NIB), supported by established biosafety guidelines and risk management principles (e.g., WHO Laboratory Biosafety Manual, ISO/IEC 17025:2017, and ICH Q9)
The occupational safety risk assessment shows that most hazards associated with biological product QC testing fall within the low to medium risk range, with no high-risk (RPN ≥ 6) scenarios identified. Medium-risk areas are mainly linked to exposure to bloodborne pathogens, live viruses (e.g., rabies), infectious materials during transport, sharps, hazardous chemicals, cryogenic liquids, and equipment operation. These risks are effectively controlled through biosafety practices, prophylactic vaccination, use of personal protective equipment, engineering controls, strict SOP adherence, training, and oversight by the Institutional Biosafety Committee.19 The findings support a preventive safety strategy, guiding laboratories to sustain vigilance in medium-risk activities while maintaining robust training, infrastructure, and monitoring systems to protect personnel and ensure safe operations.
Overall, this article provides a practical framework to support biological product testing laboratories in meeting ISO/IEC 17025:2017 Clause 8.5 requirements through systematic risk identification and risk mitigation. By integrating internationally accepted risk management principles with empirical laboratory data from historical deviations, non-conformities, equipment failures, biosafety incidents, and expert judgment based on long-term operational experience, the framework enables proactive control of critical operational and biosafety risks across the testing workflow. While inherent risks cannot be eliminated, the structured risk-based approach enables systematic identification, prioritisation, and mitigation of critical risks across the testing workflow, with direct implications for test validity, personnel safety, product quality, regulatory compliance, and public health outcomes. Importantly, the framework bridges accreditation standards with real-world laboratory practices, making it adaptable, implementable, and particularly valuable for emerging and resource-constrained laboratories seeking sustainable, globally aligned quality systems.
Author contributions
RS: Formal analysis, resources, manuscript writing; SG, NT: Resources, data curation; NM: Supervision, manuscript writing; ST: Conceptualisation, supervision, resources, manuscript writing. All authors have read and approve the final edited printed version of the manuscript.
Financial support and sponsorship
None.
Conflicts of Interest
None.
Use of Artificial Intelligence (AI)-Assisted Technology for manuscript preparation
The authors confirm that there was no use of AI-assisted technology for assisting in the writing of the manuscript and no images were manipulated using AI.
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