General Safety and Performance Requirements (GSPRs) under IVDR 2017/746

General Safety and Performance Requirements laid out in Annex I of IVDR 2017/746 represent the baseline for the safety and performance requirements applicable to all IVDs. These replace "Essential Requirements" for IVDs and apply to all classes of IVDs (Classes A-D). For manufacturers and authorised representatives, compliance involves demonstrating traceability between the design, manufacturing, performance testing, risk management and labeling to the GSPRs.

Structure Of Annex i General Safety And Performance Requirements  Overview

Annex I is subdivided into three Chapters:

• Clauses I: General requirements (1 to 8) including general requirements of safety, performance and risk based approach.

• Clauses II: Requirements on performance, design & manufacture (9 to 19) concerning the device design, material, performance, manufacture and conditions of use.

• Clauses III: Requirements on the information supplied with the device (20) concerning the labeling, IFU, packaging and information provided to users. 

This structure will help you to organize your technical documentation and to link all requirements to relevant evidence (risk files, test reports, IFUs etc).

Chapter I: General requirements

Suitability of devices for their intended purposes

• All the devices have to be designed and manufactured in a way that makes them suitable for their intended purposes, be safe and effective, without affecting the clinical condition and safety of the patients, users and others. (Annex I, 1)

• This means the manufacturer must define the intended purpose and ensure that the design/validation demonstrates the suitability of the device for that purpose.

Risk reduction "as far as possible"

• The requirement for risk reduction means reduction as far as possible without having an adverse effect on the benefit risk ratio. (Annex I, 2)

• This requires a documented risk management approach involving state of the art measures and trade offs must be justified.

Risk management system

• Manufacturers shall establish, implement, document and maintain a comprehensive risk management system through the whole device lifecycle. (Annex I, 3)

• Risk management shall be performed in an iterative manner and updated with production and post market data.

Design/manufacture risk control

Risk control shall be done in line with established safety principles taking into account the state of the art at the time. Residual risks should be assessed as acceptable. The users should be informed of residual risks. (Annex I, 4)

Use error considerations

• The risks related to use error should be reduced through ergonomic features, the conditions of use, the user knowledge/training and the characteristics of the users (lay, professional, disabled, etc.). (Annex I, 5)

• This highlights the importance of human factors engineering for IVDs which are intended for near patient testing or self testing.

Performance over lifetime

• The devices should be designed and manufactured so that the characteristics and performance during its lifetime (indicated by the manufacturer) remain safe and effective. (Annex I, 6)

• This includes durability, maintenance, calibration, etc.

Packaging, storage, transport

• The device shall be designed, manufactured and packaged in such a way that its characteristics and performance are not negatively influenced during transport and storage (considering instructions for use from the manufacturer). (Annex I, 7). Therefore, conditions such as extreme temperatures/humidity should be assessed.

Benefit risk assessment

• All known and foreseeable risks, as well as undesirable effects must be reduced and must be considered acceptable in relation to the assessed potential benefits of the device during normal use. (Annex I, 8)

• It is up to manufacturers to record the benefit risk analysis proving that residual risk is justified by the benefit.

Chapter II: Requirements regarding performance, design & manufacturers

Performance characteristics (analytical + clinical)

• The device shall be designed and manufactured in such a way that they are fit for their intended use and meet performance as declared by the manufacturer considering state of the art. (Annex I, 9.1)

• Analytical performance (such as sensitivity, specificity, limits) and clinical performance (such as diagnostic sensitivity/specificity, predictive values) should be taken into account. (Annex I, 9.1(a/b)) .The performance should remain stable throughout the lifetime of the device. (Annex I, 9.2)

• When using calibrators/control materials, the metrological traceability should be provided. (Annex I, 9.3)

• In case of self testing or near patient testing devices, the performance should be verified under relevant conditions or lay persons. (Annex I, 9.4)

Chemical, physical & biological properties

• The device shall be designed and manufactured in such a way that all requirements of Chapter I are met. Pay special attention to incompatibility between materials/substances and specimens, analyte/marker, body fluids, etc. (Annex I, 10.1)

• Packaging and manufacturing processes should minimize the risk related to contaminants/residues, especially attention should be paid to CMR (carcinogenic, mutagenic, reproductive toxicity) substances and endocrine disrupting substances. (Annex I, 10.2-10.4)

• The device should reduce the risk of substance entry and risks related to particle release including nanomaterials. (Annex I, 10.5-10.6) 

Infection/microbial contamination

• Design, manufacture and packaging should eliminate or reduce as much as possible the risk of infection to users/patients/others. (Annex I, 11.1)

• If the device is labelled sterile or has a specific microbial state, then the device should keep this state during transport, storage until the moment of use. (Annex I, 11.2-11.4)

Materials of biological origin

• If applicable, this clause requires special attention to the devices which contain materials of human or animal origin, ensuring proper sourcing, processing, documentation, traceability and minimizing risks of infection/transmission. (Annex I, 12)

Construction & interaction with environment

• The device should be constructed in such a way that it can perform safely under the intended conditions of use and in the environment where it will be used – including compatibility with other devices if applicable. (Annex I, 13)

Measuring functions

• For devices which have measuring functions, accuracy, calibration, influence of the environment, drift and reference intervals should be considered. (Annex I, 14)

Protection against radiation

• If the device emits or is exposed to the radiation (ionising or non ionising) then the design/manufacture should provide protection of users/patients/others. (Annex I, 15)

Software / electronic programmable systems

• If the device incorporates software, or is software, then design lifecycle, validation, security, reliability, and updateability should be considered. (Annex I, 16)

Devices connected to energy source

• If the device is connected to or equipped with the energy source (electrical, hydraulic, pneumatic, etc.) then the risk from this source should be minimized - including shielding, insulation, and safe design. (Annex I, 17)

Protection against mechanical/thermal risks

• The device should be designed and manufactured in such a way that mechanical and thermal risks (heat, pressure, vibration, sharp edges, unstable parts) should be considered and minimized. (Annex I, 18)

Self‑testing / near‑patient testing risks

• The devices intended for self testing or near patient testing should be designed in such a way that lay persons or use in a non laboratory environment will not affect safety or performance; instructions should consider the environment. (Annex I, 19)

Chapter III: Requirements Regarding The Information Supplied With The Device

General information requirements

• The manufacturer shall provide information allowing identification of the device and manufacturer and any relevant safety and performance information for users or others. (Annex I, 20.1) 

Labelling information

• Labels shall include information such as device name, manufacturer, intended purpose, CE marking, UDI, warnings/precautions, storage conditions, batch/serial number, etc. (Annex I, 20.2)

Packaging of sterile devices

• In case of sterile devices or devices having particular microbial state, packaging shall indicate clearly this state, instructions how to keep this state and warnings if the packaging integrity is compromised. (Annex I, 20.3)

Instructions for use (IFU)

• IFUs should have information for the safe and correct use of the device: intended purpose, user type, specimen requirements, performance characteristics, contraindications, warnings, storage/handling, interpretation of results, residual risks, disposal, symbols, and much more (Annex I, 20.4)

GSPR Mapping In Technical Documentation

Each GSPR clause in your technical documentation (conformity assessment under IVDR) needs to be mapped in a checklist (GSPR matrix), showing: applicability (yes/no), location of the evidence (risk file, test reports, IFU, design verification, etc.) The mapping of GSPRs helps in demonstrating conformity.

Linking of GSPRs to the risk management (e.g., ISO 14971), performance evaluation (Annex XIII), post market performance follow up, and labelling is vital.

Key Implementation Tips For IVD Manufacturers

• Define and document the intended purpose of the device properly: user type (lay or professional), use environment (lab, home, POC), specimen types, analyte/marker.

• Implement and/or improve risk management systems that will cover the entire life cycle and will connect to design and post market surveillance.

• With regard to software/device connected to other devices – make sure that your software lifecycle management (development, validation, update and cybersecurity) is covered by GSPR 16

• Make sure that labeling and IFU have all the necessary elements (GSPR 20), residual risks disclosed and usage limitations stated

• Implement procedures of transport and storage stress testing and validation of device performance during those conditions (GSPR 7)

• Maintain material traceability, especially with biological origin materials (GSPR 12) or materials that wear and shed debris (GSPR 10).

• Use the GSPR checklist in your QMS, link evidence, cross link to design verification and performance evaluation documentation.

• With regard to analytical and clinical performance, make sure that the validation/verification will cover lay use or near patient use, if needed (GSPR 9.4)

Common Pitfalls And Audit Focus Areas

• Viewing the GSPRs as a fixed checklist, instead of a life cycle oriented system. (As mentioned in commentary)

• Claiming that the particular GSPR clause "is not applicable" without reasonable justification and evidence.

• Lack of documented evidence of performance maintenance during lifetime (GSPR 9.2) or actual use environment (GSPR 9.4).

• Failure to address the risk of use error, especially for lay / self testing devices (GSPR 5 & 19)

• Lack of labeling/IFU, especially residual risks, limitations, user training, or language issues

• Omitting packaging/transportation/storage impact on the performance (GSPR 7)

• In software devices or connected IVDs - lack of documentation of cybersecurity, updates or algorithm change (GSPR 16)

Conclusion

General Safety and Performance Requirements (GSPRs) listed in Annex I of IVDR constitute the foundation of the IVD safety and performance in the EU market. GSPR compliance requires not only addressing individual clauses, but integrating them into your design, manufacturing, risk management and post market systems. Mapping each clause to evidence, cross linking documentation and ongoing monitoring are critical for audit ready submission.

How Morulaa Can Help With GSPR Compliance

Morulaa helps to ensure that your devices comply with General Safety and Performance Requirements (GSPR) according to IVDR. Morulaa helps to implement each of the GSPRs throughout the life cycle of your product. Morulaa assists in creation of technical documentation and GSPR matrices that will map each requirement to the design and manufacturing process.