Test Approval

FDA-Approved assays include those cleared (510k), approved (PMA), exempted, or with Emergency Use Authorization (EUA) by the United States Food and Drug Administration (FDA) that have not been modified to change the procedure or the intended use. Investigational Use Only (IUO)-labeled tests are ONLY included when utilized under a specific FDA Investigational Device Exemption (IDE).
 

A standard method is defined as an assay that has an established record of reliability and clinical validity, and which employs a standardized protocol that is universally applied in laboratories that employ the method for the analyte, such application being consistent with industry standards recognized by leading authorities in laboratory science. These are, in general, methods in use prior to FDA’s 1976 Medical Device Amendments.
 

A legacy assay is an assay that was in use in the laboratory prior to April 24, 2003. Laboratories are required to verify or establish performance specifications for any test system. However, submission for review of Standard Operating Procedures Manuals and validation for any test system used by the laboratory prior to April 24, 2003 is not required, unless specifically requested. This is in accordance with the CLIA interpretive guidelines published by the Centers for Medicare and Medicaid Services (CMS) for the establishment and verification of performance standards (§493.1253(a)).

CLEP has determined that the use of digital imaging of slides in pathology will not be subject to submission requirements as a laboratory-developed test. This includes digital imaging of slides with subsequent use of artificial intelligence/machine learning.  As required in CLEP’s Clinical Laboratory Standards, a licensed pathologist must examine and report out all histopathology cases and all non-gynecologic cytopathology cases; a licensed pathologist must examine and report out all gynecological cases with epithelial cell abnormalities. These standards also apply to any digital pathology using artificial intelligence/machine learning. Digital imagining systems and algorithms used in pathology may require approval from the Food and Drug Administration.
 

How to Apply

• Laboratories holding a permit in the test appropriate category: no further action required, test can be offered.
• Laboratories applying for the category: Submit the request for the category under the Permit Category/Tests tab in eCLEP. Testing on NYS specimens cannot begin until an amended NYS permit is issued.
• Laboratories initially applying for a permit: We will send you a Test Menu form after we receive your permit application. Complete and return the form as directed. Testing on NYS specimens cannot begin until a NYS permit is issued.
   

Additional Information

• FDA clearance or approved status can be found at the FDA’s Medical Devices Databases website.
• A list of FDA approved donor screenings assays can be found at the FDA’s Infectious Disease Tests website.
   

Examples of Standard Methods

• Immunohistochemical (IHC) stains and classic in-situ hybridization (ISH) probes used for tissue pathology are considered standard methods when used as part of MD pathologist-guided processes under cytopathology and histopathology. 
• Culture-based and biochemical -based identification of microorganisms are considered standard methods in microbiology.
• Short-tandem repeat analysis is considered a standard method in parentage testing.
• Protein electrophoresis is considered a standard method in clinical chemistry and hematology.
• Metaphase chromosome karyotyping is considered a standard method in cytogenetics.
• Manual differentials are considered a standard method in hematology.

Modifications are changes to the intended use and/or the testing procedure for FDA-approved, NYS-approved assays, and legacy assays. Modifications to an assay that utilizes a standard method that incorporates a newer technology/method are considered to be a new LDT and not a modification. A full method validation submission would be required. 
 

Modifications that change the intended use include a change to the specimen type; the type of analysis (e.g., qualitative vs. quantitative); the purpose of the assay (e.g., screening, diagnosis, prognosis, monitoring, and /or confirmation); or the target population(s) as specified in the NYS approval letter or FDA-approved package insert.
 

In clinical and forensic toxicology, adding further drug targets to a previously approved assay using the same matrix (e.g., urine or oral fluid), extraction and injection parameters (e.g. “dilute and shoot” in negative mode; “dilute and shoot” in positive mode, or solid-phase extraction) is considered a modification. The introduction of a new specimen matrix requires a comprehensive LDT method validation submission.
 

How to Apply

• This is considered a laboratory-developed test and is subject to the Tiered Evaluation of Laboratory Developed Tests Policy described below.
• All laboratories:
  • Complete and submit Assay Modification Form for the category and test/assay being proposed.
  • Complete and submit the Risk Attestation Form for the test/assay. 
     

Additional Information

• A risk assessment will be conducted, and the laboratory will be notified of the test classification.
• Supporting documentation in addition to those requested in the Assay Modification Form may be requested at the discretion of the Department.
• Explicit approval by the Department, as determined by risk assignment, is required before patient testing may commence.

Variously labeled commercial kits or reagents (e.g., RUO, IUO) or those without labeling, require review by the Department prior to use.
 

How to Apply

• This is considered a laboratory-developed test and is subject to the Tiered Evaulation of Laboratory Developed Tests Policy described below.
• All laboratories:
  • Complete and submit the appropriate submission checklist for the category and test/assay being proposed.
  • Complete and submit the Risk Attestation Form for the test/assay.
     

Additional Information

• A risk assessment will be conducted, and the laboratory will be notified of the test classification.
• Explicit approval by the Department, as determined by risk assignment, is required before patient testing may commence.

LDTs are non-FDA cleared or approved assays that are developed by the laboratory offering the assay. LDTs may include a combination of reagents and/or kits prepared by the laboratory, labeled as Analyte Specific Reagents (ASR), Research Use Only (RUO), or Investigational Use Only (IUO) that are NOT covered under an explicit FDA Investigational Device Exemption (IDE). 
 

How to Apply

• Subject to the Tiered Evaluation of Laboratory Developed Tests Policy described below.
• Laboratories holding a permit in the appropriate permit category(ies):
  • Complete and submit the appropriate submission checklist for the category and test/assay being proposed.
  • Complete and submit the Risk Attestation Form for the test/assay.
  • A risk assessment will be conducted, and the laboratory will be notified of the test classification.
  • Explicit approval by the Department, as determined by risk assignment, is required before patient testing may commence.
• Laboratories applying for a permit or a permit category:
  • Complete and submit the appropriate checklist from the "Making a Submission" section below for the category and test/assay being proposed.
  • A permit or amended permit and explicit approval for the method validation submission is required before patient testing may commence.

Laboratories performing tests on specimens from trial participants for participant management under Institutional Review Board (IRB) approved research or clinical trial protocols, where the results are reported and are used for clinical decision making, are required to obtain a NYS clinical laboratory permit. Examples of testing performed for participant management include those that influence enrollment (exclusion or inclusion), assignment to treatment arms, safety, toxicity, or dosing.
 

How to Apply

• Subject to the Tiered Evaluation of Laboratory Developed Test Policy described below
  • Submit the Risk Attestation Form.
  • Submit a narrative summary of the purpose of testing
  • Submit the validation summary
  • Submit sample reports for all possible outcomes
  • Submit one of the following:
    • the IRB approval letter that includes language that the assay poses no significant risk to the trial participant,
    • the clinicaltrials.gov identified for the study protocol of the clinical trial, or
    • the FDA letter indicating that the assay poses no significant risk. 
       
• Assays that receive Investigational Device Exemption (IDE) from the FDA are considered equivalent to an FDA-approved assay as described above.

CLEP may determine, based upon a submitted LDT package, that certain tests do not require evaluation of analytical and clinical validity. For example, certain tests where there is no clinical claim or direct reference to a recognized disease(s) or condition(s) may not require such evaluation. Laboratories wishing to perform any LDT, whether or not evaluation of analytical and clinical validity is ultimately required, must submit a full method validation package in accordance with the appropriate submission checklist and a Risk Attestation Form. Relevant documentation from the method validation submission may be shared with the Centers for Medicare and Medicaid Services (CMS) for a determination on whether the proposed testing is subject to Clinical Laboratory Improvement Amendments (CLIA) regulations. We reserve the right to change our determination and assess this method for analytical and clinical validity should any new information arise. 
 

Laypersons should review our Tests Not Evaluated by DOH webpage for more information about the risks of tests that claim to be for ‘wellness’ or ‘healthy lifestyle’.
 

How to Apply 

• Subject to the Tiered Evaluation of Laboratory Developed Tests Policy described below.
• Submit a full method validation package according to the appropriate submission checklist
• Submit the Risk Attestation Form.

Research testing is exempt from the requirement for a clinical laboratory permit per Public Health Law Article 5, Title V, Subsection 580(2) where no patient specific results are reported to a health care provider or the subject of the tests. The possibility for the need to report patient-specific results should be considered during the design and Institutional Review Board (IRB) approval of the research study protocols. 
 

If patient-specific results will be reported, a NYS clinical laboratory permit and test-specific approval is required prior to reporting. See method validation submission for LDTs above.

Once acceptable method validation performance has been demonstrated by the NYS approval of a representative sampling of tests that utilize a methodology that is common across many analytes/targets, the laboratory may request an exemption from the requirement to submit full method validation documentation for future test/assays that utilize the same methodology (e.g., FISH analysis, Sanger sequencing, LC/MS/MS). This allows for more streamlined submissions, as noted below under Adding LDTs Under an Approved Exemption.
 

How to Apply

Submit the following:

• A completed Exemption Request Form. 
• a standardized protocol for method validation to include a description of the laboratory’s principles and practices for assay development and initial validation. Note that the protocol must address all the criteria for method validation set forth in the relevant category-specific Submission Guidelines document, where one exists for the category of testing.
• laboratory-specific protocols for on-going validation, including quality control procedures and quality assurance indicators.
   

Additional Information

• Laboratories will be notified of exemption approval via letter with a specific Project ID (PID) which must be referenced in all future submissions under the exemption.
• The Department reserves the right to rescind an exemption approval at any time. 

Maintaining an Exemption

Exemptions are valid for five years; this policy is retroactive to exemptions approved prior to 2024. An exemption renewal request must include a comprehensive method validation submission for a previously unsubmitted representative assay in the permit category, methodology and specimen type(s). Exemption renewal requests should not be submitted more than one month in advance of the exemption expiration date. The exemption renewal request may be submitted at any time after the expiration, whenever the laboratory is prepared to submit a previously unsubmitted assay validation. 

To renew an exemption, submit the following:

• A completed Exemption Request Form
• A complete method validation submission for a previoiusly unsubmitted representative assay, including the appropriate submission checklist for the category. 
• Laboratory-specific protocols for on-going validation, including quality control procedures and quality assurance indicators.
• A standardized protocol for method validation to include a description of the laboratory’s principles and practices for assay development and initial validation. Note that the protocol must address all the criteria for method validation set forth in the relevant category-specific Submission Guidelines document, where one exists for the category of testing.

Additional Information

• Laboratories will be notified of exemption renewal approval via letter.
• Additional assays submitted while the exemption renewal is being reviewed/processed will be subject to the Tiered Evaluation of Laboratory Developed Tests Policy. 

Laboratories that have been granted an exemption from the requirement to submit comprehensive method validation packages for new LDTs using a given methodology are required to notify the Department of additions to their test menu. Additions under exemption are subject to the Tiered Evaluation of Laboratory Developed Tests Policy described below.
 

How to Apply

Submit the following:

• a completed Add Under Exemption Form to include the Project ID (PID) of the approved exemption and the name and description of the assay to be added.
• a summary of the validation performed.
• sample reports for all possible outcomes.
• a Risk Attestation Form for the test(s)/assay(s) being added under the exemption.
• For the categories of Genetic Testing – Molecular, Cytogenetics -Prenatal and Cytogenetics - Restricted, also submit the Informed Consent education materials to be provided to clinicians.

Guidance for laboratory developed tests that include at-home specimen collection

Access to clinical testing is an important public health tool, particularly for communicable disease. Traditionally, access to testing requires an in-person visit to a healthcare provider and/or a specimen collection site, which are potential barriers for a person who needs testing. At-home testing and at-home specimen collection may help eliminate these barriers. At-home testing allows the patient to collect the specimen, perform the test, and obtain a result. At-home testing may only be performed when the testing device is appropriately authorized for at-home, over-the-counter use by the federal Food and Drug Administration (FDA). In contrast, at-home specimen collection allows the patient to collect a clinical specimen outside a clinical setting and send it to a laboratory for testing. Clinical tests that use at-home specimen collection may be offered in NYS but must meet applicable NYS requirements. This guidance document addresses only at-home specimen collection and subsequent testing by a laboratory holding a New York clinical laboratory permit in the relevant category of testing, highlighting certain clinical laboratory requirements, test ordering, business practice, and healthcare practice.
 

The department is aware of several at-home specimen collection models. Each includes a clinical laboratory that performs testing and a healthcare provider who orders the test and manages patient care. Certain models include a third party that coordinates interactions among the patient, provider, and laboratory. Each party must comply with applicable NYS requirements. Any of these parties may provide specimen collection kits to patients.
 

Clinical laboratory requirements

Clinical laboratories testing at-home collected specimens must have appropriate NYS approvals (NYS Public Health Law, Article 5, Title 5; Subpart 58-1 of 10 NYCRR). These laboratories must have a NYS clinical laboratory permit that includes the applicable category of testing and FDA or NYS approval for the test. 
 

NYS does not review or approve at-home collection kits, though these kits may require FDA approval or clearance. Modifications to FDA or NYS approved assays solely to use an at-home specimen collection process for the same specimen type do not require NYS review or approval. However, if the modification to use an at-home specimen collection process changes the nature of the specimen (e.g., whole blood vs. dried blood spots), submission to NY is required to determine that the change in specimen type does not alter assay performance.
 

Test ordering

Clinical laboratories may test a specimen only at the request of a NYS-licensed physician or other person authorized by law (see Subpart 58-1 of 10NYCRR). In the context of at-home specimen collection, a patient may request a test directly from a laboratory or indirectly through a third party. However, the laboratory may not perform the test until a licensed healthcare provider acting within their scope of practice has evaluated the request and, if appropriate, issued a test order. The patient’s regular healthcare provider or a provider affiliated with the laboratory or other party may perform this function.
 

Business practices of laboratories and health care services purveyors

Clinical laboratories and healthcare providers must comply with business practice requirements described in NYS Public Health Law, Article 5, Title 6 and Part 34 of 10NYCRR. These requirements broadly prohibit a clinical laboratory or its agent, employee or fiduciary from providing financial incentives to a health services provider to secure referral of services to the clinical laboratory. In the context of at-home specimen collection where the patient/client initiates the request for testing from a specific laboratory using a web-based platform, this is not considered to be any incentive provided to the health services provider for authorizing the test order. 
 

Patient care

Healthcare providers must meet certain practice requirements established by the State Education Department and the Office of Professional Medical Conduct. For example, the provider ordering the test must meet record keeping requirements for each patient, including the provider’s evaluation of the patient. The evaluation may be in person, via telehealth, or by reviewing health information provided by the patient. These record keeping requirements apply no later than the time the provider issues the test order. In addition, the provider must ensure that patients receive appropriate care based on the testing results. It is important, given that at-home specimen collection may not require an in-person visit with a healthcare provider, that patients receive appropriate care before and after testing.

1. All LDT submissions must include a Risk Attestation Form containing a succinct summary of the assay and responses to the questions listed on the Form. 
2. A classification assignment (high, moderate, low, clinical trial, or lifestyle) will be made as part of the existing CLEP LDT validation review and approval process described on this webpage. Laboratories will be notified of the risk assignment within three weeks of the submission of a complete package.
3. Questions about completing the Risk Attestation form can be submitted to clepval@health.ny.gov. The department is unable to perform pre-submission risk determinations.

• High risk: LDTs assessed as High risk will NOT receive Conditional Approval and testing cannot be offered on specimens from NYS until the review has been completed and full approval has been granted. Review of LDTs assessed as High risk will be prioritized. High risk will apply to all packages submitted by laboratories that are pending a permit or the appropriate permit category unless the package qualifies for either a Clinical Trial or Lifestyle classification.
• Moderate risk: LDTs assessed as Moderate risk will receive Conditional Approval if the laboratory holds a permit in the appropriate category of testing. Laboratories may offer the test once notified by CLEP of the moderate risk classification and conditional approval. The department reserves the right to withhold or withdraw conditional approval at its discretion.
• Low risk: LDTs assessed as Low risk will receive full approval and will not be subject to review, provided the laboratory holds a permit in the appropriate category of testing. Laboratories will be able to offer the test once notified by CLEP of the low risk classification and approval. The department reserves the right to withhold approval and/or require review of the test at its discretion.
• Clinical Trial: LDTs assessed as being solely performed under a Clinical Trial will receive notification from CLEP recognizing that the proposed test is part of a clinical trial and may be offered to clients. The trial for which the LDTs are performed must be approved by the National Institutes of Health (NIH) or another relevant independent Institutional Review Board. For additional information, please visit: https://clinicaltrials.gov/ct2/manage-recs/fdaaa.
• Not Evaluated: Laboratories with LDTs assigned this classification will receive notification from CLEP that the test may be offered to clients with the disclaimer that it has not been evaluated by the NYS Department of Health. Relevant documentation from the method validation submission may be shared with the Centers for Medicare and Medicaid Services (CMS) for a determination on whether the proposed testing is subject to Clinical Laboratory Improvement Amendments (CLIA) regulations. If not, CLEP will make a separate, independent assessment on the necessity for a NYS clinical laboratory permit. If the assay is subject to CLIA or NYS law requiring a clinical laboratory permit, CLEP/CLRS will make an independent assessment for the determination of the Not Evaluated classification.