The development of “in house” methodologies by Molecular Biology laboratories, in many cases, requires the application of reagents and substances that are not subject to approval by the National Health Surveillance Agency (ANVISA), including materials called Research Use Only (RUO) , because they are tests that require specialized technology with less prevalence or that do not have a substitute technique, either for tests of the spectrum of infectious or genetic diseases. After the standardization of these exams using its own methodology, it is necessary to validate them.
Importance of the validation process
The validation process of standardized tests aims to prove, through tests, documents and calculations that these tests used in a laboratory are performing their functions as expected and in a safe manner. The laboratory must make a document containing the entire standardization process and then the validation process and its respective criticality assessments. In RUO tests, they must be evaluated as “in house” tests.
The exams processed with RUO and “in house” kits are allowed to be used in clinical diagnostics as long as they follow the recommendations of the legislation RDC 302/2005 [1] and technical note nº001/2016 GEVIT / GGTPS / Anvisa [2].
Performance characteristics
These tests must have the following performance characteristics determined, recorded and approved before being placed in the laboratory routine:
- Analytical sensitivity (detection limit);
- Precision;
- Accuracy;
- Analytical specificity;
- Reportable interval (for quantitative tests);
- Reference intervals (when applicable);
- Diagnostic sensitivity;
- Diagnostic specificity.
The document must also contain other performance characteristics, such as reagent validity, cross reaction, sample stability, among others. And in the end the approval of the person in charge of the laboratory or the sector.
It is important to cover a representative number of samples, containing all possible results, with a few exceptions. Matrix validation is also necessary.
A commercial test with ANVISA registration if modified also has to go through a validation process, whether it is the inclusion of a matrix that is not included in the package insert, or changing the volume, or even an equipment within others.
In this context, clinical laboratories that use “in house” methodologies have this excellent alternative, but are fully responsible for the qualification of the materials and inputs used, validation of the method and information to the patient or user, as determined by RDC nº 302/2005, no therefore, there is a restriction on the use of products, labeled or not as RUO, for this type of methodology.
About the author:
Alexandra Reis has an undergraduate and master’s degree in Biological Sciences and a PhD in Infectious and Parasitic Diseases from the University of São Paulo (USP). He held a post-doctoral degree from CNPQ in the field of Molecular Biology. Has experience in Microbiology, focusing on Applied Microbiology and on infectious and parasitic diseases. Currently works in consultancy in the Molecular Biology sector for several companies and laboratories.
References:
[1] RESOLUÇÃO DE DIRETORIA COLEGIADA – RDC Nº 302, DE 13 DE OUTUBRO DE 2005
[2] NOTA TÉCNICA CONJUNTA N° 001/2016 GEVIT/GGTPS/ANVISA e GRECS/GGTES/ANVISA
[3] RESOLUÇÃO – RDC Nº 36, DE 26 DE AGOSTO DE 2015
[4] Edição eletrônica: Lista de Orientação em Diagnóstico Molecular – Segunda versão – 2018 Páginas: 56
