Manufacturers of prequalified in vitro diagnostics (IVD) must submit change reports to the World Health Organization or risk having their product de-listed from the compendium of prequalified IVDs.
Reportable changes, according to new WHO draft guidance issued late last week, include:
- Changes to the IVD or how it’s manufactured that have the potential to impact an IVD’s function, performance, usability or safety
- Changes to a company’s quality management system (QMS), ie., a change in the ISO 13485:2003 certification status
- And some administrative changes
“Reporting of reportable changes should occur prior to implementation of a substantial change to allow WHO to assess the change,” WHO says. “Manufacturers are encouraged to contact WHO early in the process of designing and validating the change, to allow sufficient time for assessment before the change is implemented.”
In order to initiate WHO’s assessment, companies will have to pay a non-refundable $3,000 fee for the costs associated with change documentation review, manufacturing site(s) inspection and dissemination of change information.
“Failure to report changes in accordance with the requirements set in this document may result in the delisting of the product from the list of prequalified IVDs,” WHO says, noting how to determine if a change will impact the IVD’s overall residual risk/benefit evaluation.
Reportable changes can be linked to an IVD’s manufacturing, particularly with the relocation of a product’s manufacturing site or to critical raw materials/components, software, labelling; or a product’s QMS, such as change of ownership or legal status; design and intended use; or even a change to the intended testing population.
A change in the regulatory status of the prequalified IVD also must be brought to WHO’s attention. For example, WHO says, a license suspension in Canada, receipt of a warning letter from the US Food and Drug Administration, suspension of registration in Australia, or suspension of a CE mark certification in the EU all must be reported. Changes to a product name, product code(s) or manufacturer name must also be reported.
In some cases, changes will have an impact on the safety and performance of the IVD and result in a product that’s substantially different from the product originally prequalified, which means a company would need to submit a new application to the Prequalification Program, according to WHO.
Examples of changes that require submission of a new application for prequalification include: A change to what is detected (i.e. the analyte or measurand); changes in antigens, antibodies, primers or solid phase; a change to the specific disorder, condition or risk factor of interest that it is intended to detect, define or differentiate; a change in the test result format from a qualitative or quantitative or vice versa; a change in biological or chemical principle of the test; and/or a change in design of test technology.
And as far as what WHO considers to be non-reportable changes, the organization points to:
- Simple changes to the product labelling documentation, such as: rewording or expanding for clarification; translating from one language to another; correcting typographical errors; and/or replacing (or complementing) written text by internationally recognized symbols;
- Minor software changes that do not impact the safety or performance of the product;
- Minor QMS changes such as increased post-market surveillance activity or regular updates of controlled QMS procedures (such as control of documents, management review, etc.);
- Minor manufacturing, additional in-process quality control criteria or test methods for manufacturing processes to provide equivalent or better assurances of reliability, as determined by the manufacturer but which do not affect safety or performance.
WHO Draft Guidance on Reportable Changes to a Prequalified In Vitro Diagnostic
Status of active applications to the prequalification of in vitro diagnostics
WHO list of prequalified in vitro diagnostic products
WHO Overview of the Prequalification of IVD Assessment from 2014
More information from WHO