Reportable Changes
All substantial changes are considered as reportable changes. A reportable change is one that is demonstrated, through risk analysis, to have a potential impact on the function, performance, usability, or safety of a prequalified IVD. A reportable change may:
- introduce new hazards that have not been previously addressed
- adversely affect risks associated with existing hazards
- alter the presentation of existing or new risks to the user (this can involve labelling changes or new indications for use).
Reportable changes therefore include:
- any changes to the prequalified product or its design, labelling or manufacture
- any changes to the QMS under which the product was designed and manufactured.
In addition, some administrative changes must also be reported.
A change to the prequalified IVD manufacturing process, facility or equipment that could affect the IVD’s quality, safety and/or performance is considered a substantial change and thus reportable. It requires submission of a completed Change Report Form to WHO.
| Examples of reportable changes to a manufacturing process |
|---|
| Physical move/relocation of finished product manufacturing, assembling or other processing equipment from one location to a different location or addition of a new facility (manufacturing facility, warehouse, etc.) within the same location. |
| Change in the manufacturing process such as the introduction of new equipment or change in workflow. |
| Changes to the manufacturing quality control procedures, such as the methods, tests or procedures used to control the quality of the materials or the product. |
| Removal of test acceptance criteria for in-process and finished product. Removal of in-process inspections or final inspections without replacement of these activities. |
| Addition of in-process inspection steps in response to post-market product issues. |
| Change of a supplier, or sub-tier supplier of reagents, antigens, antibodies, preservatives, anticoagulants, primers or solid phase. |
| Move of manufacturing, processing or packaging from a supplier to the manufacturer's facility. |
| Move of manufacturing, processing or packaging from the manufacturer's facility to a supplier. |
Changes to a product may range from minor changes to the design of the product to substantial changes in operating principles. All changes must be evaluated, verified and validated according to the accepted procedures recorded in the quality management system documentation. Changes to the design specifications, physical attributes, user interface, software or hardware may be substantial if they potentially have an impact on the intended use, test procedure or interpretation of results for the IVD. Additionally, changes to claims relating to the intended use must be reported, even if they do not impact on design.
| Examples of reportable changes to the product design and intended use |
|---|
| A change to the reagent volume or specimen volume required to perform the test. |
| A change to the reading period (minimum or maximum). |
| The acceptability of new anticoagulants for plasma and/or whole blood specimens. |
| A change to the manufacturer-defined automation process (including change to a new smaller/larger model if the IVD is an instrument) or the change from a manual procedure to an automated procedure for use. |
| A change to the operating principle of the IVD. |
| Changes to materials/components supplied with the IVD (e.g. introduction of new ancillary reagents such as quality control reagents). |
| A change to the function of the product (e.g. screening, monitoring, diagnosis or aid to diagnosis, staging or aid to staging of disease, prediction, self-testing). |
| A change to the specific disorder, condition or risk factor of interest that the IVD is intended to detect, define or differentiate. |
| A change in performance or design specifications. |
| A change in the test result format from qualitative to quantitative or vice versa. |
| Addition or removal of a specimen type (e.g. serum, plasma, whole blood, oral fluid, sputum, urine, dried blood spot). |
| A change to the intended testing population including any new or extended use (e.g. addition of neonates, antenatal women). |
| An addition or deletion of a warning or limitation for the IVD. |
| New data relating to stability impacting on the expiry date or storage conditions of the IVD. |
| Changes to the materials supplied with the IVD (e.g. accessories such as lancets). |
Changes to critical raw materials/components used in the manufacturing process of an IVD often affect its performance characteristics, for example sensitivity and specificity. These changes should be assessed as to their impact on the quality, safety and/or performance of the IVD.
| Examples of reportable changes in materials/components |
|---|
| Changes to the formulation of reagents in the IVD that result in a change (either increase or decrease) to the stability/shelf-life claims. |
| Changes in the conjugate or substrates that change the intended use. |
| Changes in specimen preparation such as a change in nucleic acid extraction method. |
| The addition or change of a preservative to a reagent of the IVD. |
| Changes to the source (supplier) or processing of biological materials. |
| Changes from liquid to lyophilized reagents or vice versa. |
| Changes to materials/components that necessitate testing of additional clinical specimens, or retesting of original specimens, to determine performance characteristics of the IVD. |
| Changes to the materials/components of an IVD that result in a change to the operating principle of the product. |
| Changes to materials/components that potentially affect the operating procedure of an IVD, including changes in reaction components or materials such as calibration materials, or changes in methods such as specimen pre-treatment, incubation times and operating temperatures. |
| Changes in power supply requirements. |
For the purposes of WHO Prequalification, labelling includes kit and kit component labels and instructions for use.
| Reportable changes to labelling |
| All changes to labelling should be reported unless the changes are made to: 1. Clarify labelling statement (e.g. clarifying instructions to make the IVD easier or safer to use) without changing the procedure 2. Correct errors (e.g. typographical errors or numerical errors). 3. Include additional languages. |
| Reportable changes to an IVD’s software |
|---|
| A software change that impacts the control of the IVD, and may alter the reporting result that is used in the diagnosis or other function. |
| A software change that modifies an algorithm impacting the test result. |
| A software change that impacts the way data is read, analyzed or interpreted by the user, such that the diagnosis or other function may be altered when compared to the previous version of the software. |
| A software change that replaces previously required user input. |
| A software change to correct an error that presents a safety risk to the patient. |
| Addition of a new feature to the software that may affect the diagnosis or other software driven function. |
| A software change that incorporates a change to the operating system on which the software runs. |
| Examples of changes to the quality management system |
|---|
| Changes in the ISO 13485 certification status of the manufacturer, of the prequalified IVD, such as suspension of the ISO 13485 certificate, obtaining a new certification, or change in the scope of certification. |
| Change in Notified Body or certification body. |
Changes to the legal manufacturer including:
|
| Changes to the regulatory status |
|---|
| Change in the regulatory status of the prequalified IVD in any of the member nations or regions of the International Medical Device Regulators Forum) (e.g. licence suspension in Canada, receipt of a Warning Letter from the US Food and Drug Administration, suspension of registration in the Australian Register of Therapeutic Goods, or suspension of a CE mark certification in the European Union). |
Changes limited to the product name, product code(s) and/or manufacturer name must be reported to WHO.
| Reportable administrative changes |
|---|
| Changes only to the product name. |
| Changes only to the product codes(s). |
| Changes only to the manufacturer name. |