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The President of the United States, released on March 13, 2020, a “Memorandum of Expanding State-Approved Diagnostic Tests” (Memorandum) . This Memorandum allowed the Department of Health and Human Services to promulgate policies that enable other states to authorize testing for COVID-19. Under this policy, other States have oversight responsibility, “notification of SARS-CoV-2 test validation is not submitted to the FDA, and the laboratory does not submit a EUA request to FDA”. However, the states or territories must notify the FDA if they decide to choose this pathway for enabling test access.

Accordingly, the FDA issued a “Coronavirus Disease 2019 (COVID-19) Emergency Use Authorizations for Medical Devices” with emphasis on in vitro diagnostics. In line with the “Policy for Diagnostic Tests for Coronavirus Disease-2019 during the Public Health Emergency, Immediately in Effect Guidance for Clinical Laboratories, Commercial Manufacturers, and Food and Drug Administration Staff” issued on the web on March 16, 2020, and the Memorandum issued by the President of the United States, States were allowed to authorized laboratories within the State to develop and perform tests used to detect COVID-19.

[1] https://www.whitehouse.gov/presidential-actions/memorandum-expanding-state-approved-diagnostic-tests/
[2] https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations#coronavirus2019

About the Commission

The ​Puerto Rico Diagnostic Test Evaluation Commission (PRoDTEC) is a panel of experts coordinated by the Puerto Rico Department of Health to expedite the revision and approval of the use of in vitro diagnostic testing to detect the SARS-CoV-2 virus, responsible for the COVID-19 illness.

Members of the Committee

Marcos López Casillas, PhD

Federico Goodsaid, Ph.D.

Lcda. Agnes A. Rodríguez Soto,MT,MS,ASQ/CMQ/OE/CFSQA

Guidelines

Currently, we are enduring a public health emergency in the Commonwealth of Puerto Rico due to the novel coronavirus SARS-Cov-2. Accordingly, it is imperative to take proactive measures to prepare and act to the public health threat involving COVID-19. Diagnostic tests are critical for the prompt clinical management of affected individuals and the epidemiologic monitoring, control, and prevention of the pandemic. Accordingly, a diagnostic test must be robustly validated to safeguard that results obtained from the test meet the expected performance criteria. Then, the reliability of the diagnostic test is essential, as its results will have significant implications in clinical care and public health practice.

Based on the policies outlined in the Immediately in Effect Guidance for Clinical Laboratories, Commercial Manufacturers, and Food and Drug Administration Staff: Policy for Coronavirus Disease-2019 Tests during the Public Health Emergency (Revised), Section IV.B Puerto Rico has chosen to authorize laboratories in the Archipelago to develop and perform testing for COVID-19. This opportunity enacted the formation of the Puerto Rico Diagnostics Testing Commission, PRoDTEC. Now, laboratories within the jurisdiction of Puerto Rico must submit their emergency use authorizations (EUA) directly to PRoDTEC for evaluation and authorization of molecular, antigen, and serological SARS-CoV-2 testing.

PRoDTEC, as part of their oversight process, will require laboratories developing SARS-CoV-2 tests to validate those tests before use. As stated by the FDA, in vitro diagnostic (IVD) devices are tests performed on samples taken from the human body, such as swabs of mucus from inside the nose or back of the throat, or blood taken from a vein or fingerstick. IVDs can detect diseases or other conditions and can be used to monitor a person’s overall health to help cure, treat, or prevent diseases.

The PRDoTEC will locally authorize the emergency use of laboratory-developed tests of the following types:

  • Diagnostic Tests – Tests that detect parts of the SARS-CoV-2 virus can be used to diagnose infection with the SARS-CoV-2 virus. These include molecular tests and antigen tests.
  • Serology/Antibody Tests – Tests that detect antibodies (e.g., IgM, IgG) to the SARS-CoV-2 virus. Serology/antibody tests cannot be used to diagnose a current infection.
  • Tests for Management of COVID-19 Patients – Beyond tests that diagnose or detect SARS-CoV-2 virus or antibodies, there are also tests that are authorized for use in managing patients with COVID-19, such as to detect biomarkers related to inflammation. Once patients are diagnosed with COVID-19 disease, these additional tests can inform patient management decisions.

Commercial manufacturers looking to distribute their SARS-CoV-2 diagnostic tests in other states of the US should follow the traditional EUA submission to the FDA route as these policies only applied to Laboratory Developed Tests.

PRoDTEC will follow the same established guidelines described by the FDA described in the Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised) – Immediately in Effect Guidance for Clinical Laboratories, Commercial Manufacturers, and Food and Drug Administration Staff. PRoDTEC has adapted the following templates, that are part of the policy established by the FDA.

Laboratories wishing to obtain an emergency use authorization for their LBTs should use the following templates to help facilitate the preparation, submission, and authorization of a EUA:

Laboratories are encouraged to contact PRoDTEC to discuss the use of alternative approaches to any specific concerns and questions at approvals@prodtec.org. The formal EUA should be submitted through approvals@prodtec.org.

These guidelines and any recommendations for approval of use will only be valid during the COVID-19 outbreak declared by the Secretary of Health and Human Services until termination of the HHS EUA declaration.

Who Can Submit a Request for Accelerated Approval?

Requests of approval of use of LDTs or RUO kits for detection of SARS-CoV-2 is limited to laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) that meet the CLIA regulatory requirements of 1988 (CLIA), 42 U.S.C. §263a to perform high complexity testing. Interested laboratories must submit evidence of CLIA-certification and any other pertinent information that will support your application (e.g., CAP, JC, or NY State certifications) to PRoDTEC.

LDTs or RUO kits for detection of SARS-CoV-2 must be validated prior to use. Evidence of the validation must be submitted for revision to PRoDTEC. The following minimum testing is required to be performed to ensure the clinical and analytical validity of the tests:
Laboratories must document and submit the limit of detection (LoD) of the assay for the detection of SARS-CoV-2. In order to determine the LoD of the assay, either the inactivated virus or RNA spiking into the artificial or real clinical matrix (e.g., Bronchoalveolar lavage [BAL] fluid, sputum, etc.). Also, laboratories should test a dilution series of three replicates per concentration and confirm the final concentration with 20 replicates. The LoD is defined as the lowest concentration at which 19/20 replicates are positive. In the case in where multiple clinical matrices are going to be tested, results from the most challenging matrix is only required.
An in silico analysis should be performed to establish the percent identity matches against publicly available SARS-CoV-2 sequences detected by the tests. All the published SARS-CoV-2 sequences must be detectable with the primers and probes selected. Sequences can be downloaded from NCBI or GISAID databases.
In silico analysis of the assay primer and probes against common respiratory flora and viral pathogens must be performed for initial clinical use. In silico cross-reactivity is defined as greater than 80% homology between one of the primers/probes and any of the sequence present in the targeted microorganism. Sequences can be downloaded from NCBI or GISAID databases. Alternatively, wet testing can be performed at concentrations of 106 CFU/ml or higher for bacteria and 105 pfu/ml or higher for viruses. The recommended microorganisms that should be included in the analysis are the following:

  • Human coronavirus 229E – Haemophilus influenzae
  • Human coronavirus OC43 – Legionella pneumophila
  • Human coronavirus HKU1 – Mycobacterium tuberculosis
  • Human coronavirus NL63 – Streptococcus pneumoniae
  • SARS-coronavirus – Streptococcus pyogenes
  • MERS-coronavirus – Bordetella pertussis
  • Adenovirus (e.g. C1 Ad. 71) – Mycoplasma pneumoniae
  • Human Metapneumovirus (hMPV) – Pneumocystis jirovecii (PJP)
  • Parainfluenza virus 1-4 – Candida albicans
  • Influenza A & B – Pseudomonas aeruginosa
  • Enterovirus (e.g. EV68) – Staphylococcus epidermis
  • Respiratory syncytial virus – Staphylococcus salivarius
  • Rhinovirus – Pooled human nasal wash – to represent diverse microbial flora in the human respiratory tract
  • Chlamydia pneumoniae

Clinical Evaluation

This test can be performed with known positive samples or contrived clinical specimens. A minimum of 30 positive/contrived reactive specimens and 30 non-reactive specimens blinded and randomized must be tested to confirm the performance of the test. Contrived reactive specimens can be created by spiking RNA or inactivated virus into leftover individual clinical specimens representing unique patients; most of these specimens can be leftover respiratory specimens such as NP swabs, sputum, etc. Twenty of the contrived clinical specimens should be spiked at a concentration of 1x-2x LoD, with the remainder of specimens spanning the assay testing range. Acceptance criteria for the performance are 95% agreement at 1x-2x LoD, and 100% agreement at all other concentrations and for negative specimens.

Application Process

PRoDTEC will follow the same established guidelines described by the FDA described in the Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised) – Immediately in Effect Guidance for Clinical Laboratories, Commercial Manufacturers, and Food and Drug Administration Staff. PRoDTEC has adapted the following templates, that are part of the policy established by the FDA.

Laboratories wishing to obtain an emergency use authorization for their LBTs should use the following templates to help facilitate the preparation, submission, and authorization of a EUA:

Laboratories are encouraged to contact PRoDTEC to discuss the use of alternative approaches to any specific concerns and questions at approvals@prodtec.org. The formal EUA should be submitted through approvals@prodtec.org.

Application Requirements

Laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) to perform high-complexity testing are eligible to submit a EUA.

Laboratories seeking a EUA must follow the following steps to apply:

  • Validation – all tests must be validated before use. Recommendations regarding testing should be performed to ensure analytical and clinical soundness and are included in each of the submission templates provided.
  • Notification – After validation, laboratories should notify PRoDTEC about the validation of the assay. The notice should include all the laboratory information and must be performed via email to approvals@prodtec.org. From the time of notification, laboratories will have 15 business days to submit a full EUA application. If an application is not received within that timeframe, it will not be considered.
  • EUA application – laboratories must use the templates provided in the “Application Process” link to facilitate EUA preparation and submission. Any different approaches should consider requesting PRoDTEC’s advice to enable them through the pre-EUA and EUA route. PRoDTEC fosters laboratories to consider any alternative technological approaches to validating their test via email at approvals@prodtec.org. Paper or in mail applications will not be considered.
Validation Report (DOWNLOAD PDF)

Documents

Guidelines and Requirements

Contact Us / Contacto

Puerto Rico Science, Technology & Research Trust
PO Box 363475
San Juan, Puerto Rico 00936-3475

105 Carr. #21, Km. 0.8 Bo. Monacillo
San Juan, PR 00927



Dr. Martín Montoya
Director de Operaciones
(Operations Director)
Cel: 787-469-7926
Tel: 787-523-5651

mmontoya@prsciencetrust.org