In Vitro Diagnostic Devices: Guidance for the Preparation of 510(k) Submissions - Appendix L - In Vitro Diagnostic Devices Triage Review Procedures - Letter To All Manufacturers Of In-Vitro Diagnostic (IVD) Devices Signed By Dr. Steve Gutman, Director, DCLD - 5/31/96
LETTER TO ALL MANUFACTURERS OF IN-VITRO DIAGNOSTIC (IVD) DEVICES SIGNED BY DR. STEVE GUTMAN, DIRECTOR, DCLD - 5/31/96
This letter describes revisions in the Tier/Triage Program for premarket submissions that are about to be implemented by the Division of Clinical Laboratory Devices (DCLD) in the Office of Device Evaluation (ODE).
The tier/triage program is an ODE initiative introduced in 1993 as part of a comprehensive management action plan for improving the efficiency of its administrative work process. This program is designed to allow levels of review of premarket submissions to be adjusted according to device risk. The lowest risk devices are assigned the lowest intensity of review, tier 1 review, and the highest risk devices the highest level of review, tier 3 review. Products of moderate risk are assigned tier 2 review.
When implemented by ODE in 1993, DCLD made the decision to limit assignment of tier 1 category to those devices for which review of standard performance characteristics (accuracy, precision, analytical sensitivity and specificity, etc.) would not be necessary. As a result only a handful of devices were reassigned to this low level review category and the workload impact of the program was minimal. In 1995 the Health Industry Manufacturers Association (HIMA) provided the agency with a proposal to expand the menu of devices assigned to the tier 1 category using a series of flowcharts incorporating a variety of device features including classification, analyte, matrix, methodology, technology, familiarity, and intended use. This flowchart approach was evaluated by DCLD and a simplified version taken to an FDA sponsored Tier/Triage workshop on October 1995. FDA staff, representatives of the IVD industry, academia, the clinical laboratory community, clinicians, and other HHS agencies all provided useful comments during this open public meeting.
The revised DCLD Tier/Triage Program consists of the following elements:
- FDA will pilot the DCLD tier/triage program for one year using the DCLD flow chart (Enclosure-1) proposed at the November 1995 Tier/Triage Workshop; starting date: June 1, 1996.
- DCLD has prepared a checklist for use in making the tier/ triage decision (Enclosure-2). Manufacturers have the option of including a suggested tier determination in their 510(k) submission using the DCLD tier decision chart and checklist. The manufacturer's tier determination will be taken into consideration by DCLD when assigning the tier level of review for each individual product submission.
- All IVD premarket submissions will have an up-front tier/triage by the branch chief of the DCLD branch to which the submission is assigned.
- Tier 1 review will consist of a submission completeness evaluation and a labeling review by the scientific reviewer to whom the submission is assigned. The review will consist of checking the labeling for conformity to 21 CFR 809.10. If the labeling content is the expected for a specific type of device, 510(k) clearance will be performed as a tier 1 review. If a deviation/omission from the usual labeling content for a specific type of device is noted, the level of review will be upgraded to tier 2. This will initiate a formal review of the data supporting the submission.
- Tier 2 review will be performed by a scientific reviewer and will consist of a labeling review similar to the one applied to the tier 1 review plus scientific evaluation of the data generated by the manufacturer to substantiate product labeling claims.
- Tier 3 review like the tier 2 review will consist of both a labeling review and a scientific evaluation of the data generated by the manufacturer to substantiate product labeling claims. Because these products are associated with high risk to the patient or with novel technical features, this review will be conducted by a team of scientific reviewers and will frequently require advisory panel review and comment either through "home work" assignments or through formal panel meetings.
- The IVD manufacturers have the option of including a suggested tier determination in their 510(k) submission using the DCLD tier decision chart. The manufacturer's tier determination will be taken into consideration by DCLD when assigning the tier level of review for each individual product submission. However, the final tier determination will be made by DCLD. All submissions regardless of their proposed tier status should include supporting information and data within the submission for all labeling claims.
- Tier 1 submissions will be reviewed in a unique review queue.
- In order to assess the appropriateness of the tier 1 review, for a limited period of time, a subset of the tier 1 IVD devices (about 10%) will be subject, randomly, to a tier 2 review.
- DCLD managers have identified which IVD devices would be subject to tier 1 review based solely on the last criterion described in the DCLD decision chart Ä major determinant in diagnosis and treatment (Enclosure-3). The ability to triage a product into the tier 1 category according to this risk assessment is predicated on the finding that the device meets all previous criteria of the decision flowchart, i.e., it involves a familiar analyte, methodology, and technology, is used in a clinical laboratory setting, and FDA has knowledge and experience in review of similar devices.
- The tier/triage program will be evaluated after one year by comparing the average overall review time following implementation of the tier triage program with the current average overall review time. Analysis will include evaluation of review times for each tier and will allow the division to assess the impact of the program on workload and on the submission turnaround time. In addition, results of the internal audit of tier 1 products will be evaluated to determine the impact of this program on the assessment of device performance and substantial equivalence to its predicate.
- The evaluation of the tier/triage program will be discussed in an open forum, similar to the one provided during the tier/ triage workshop. At this time, interested parties will have an opportunity to comment on the results of the program.
We believe that this revised program will thus streamline the review of premarket submissions and will bring more consistency and predictability to the IVD review process. If you have questions related to the content of this letter, please contact me or Clara A. Sliva at (301) 594-3084.
|Steve Gutman, MD, MBA|
|Division of Clinical Laboratory Devices|
|Office of Device Evaluation|
INTERPRETATION OF THE DCLD'S TIER TRIAGE DECISION CHART AND DEFINITION OF TERMS
- The first three criteria in the chart are taken from the ODE decision tree which is routinely used to determine whether a device can be reviewed as a 510(k) or whether the device must be reviewed as a premarket approval application (PMA). The same interpretation of terms used for the ODE 510(k) chart applies to the DCLD Tier Triage Chart.
- Criterion #1 determines if there is a legally marketed predicate device. In the absence of such a predicate, the device is automatically a class III device and is subject to a PMA.
- Criterion #2 is an assessment of whether the new device has the same intended use or indications for use as the predicate device. If the intended use and/or indications for use are the same as the predicate, the device qualifies for a 510(k) review. If different the impact of the differences must be assessed.
- Criterion #3 assess whether differences in the intended use or indications for use alter the intended therapeutic/diagnostic effect. If there is a potential impact on the safety and effectiveness (new issues raised), a PMA is required. If such an impact is not expected, the device qualifies for a 510(k) review.
- Criterion #4 determines the novelty of the product in terms of analyte, matrix, methodology and/or technology. If the issues of safety and effectiveness are not new but require high level scrutiny, then a tier 3 review is warranted.
New Analyte - a type of device that has not been previously cleared by FDA but with the same intended use as the predicate. Example: troponin for the diagnosis of acute myocardial infarction (with creatine kinase as the predicate device) is a tier 3 review. The first four of a kind will be considered under "new analytes" for the purpose of tier triage.
New Matrix - the device uses a type of clinical specimen not previously used in the same type of IVDs cleared by FDA. Example: sweat patches for drugs of abuse (with urine drugs of abuse as the predicate device) is a tier 3 review. The first four of a kind will be considered under "new matrices" for the purpose of tier triage.
New Methodology/Technology - the device's performance depends on a methodology/technology that has not been previously used in an IVD cleared by FDA. Example: nucleic acid amplification for the direct detection of certain infectious agents provided a predicate exists. The first four of a kind for each methodology/technology will be considered under "new methodology/technology" for the purpose of tier triage.
Criterion #6 identifies the level of professional training of the person for whom the test is intended. Since DCLD requires device performance data in the hands of persons with minimal clinical laboratory training when the test is intended for use in physician office laboratories (POLs) and point-of-care settings, these types of devices would be subject minimally to a tier 2 review. The same rationale applies for IVD tests intended for over-the-counter use. For over the counter tests for which there is little information available on how lay users may handle test results, a tier 3 review is generally necessary.
Clinical Laboratory Professionals - laboratory technologists or persons with clinical laboratory training employed by a clinical laboratory.
Criterion #8 takes into account the FDA experience in reviewing similar devices. As a rule, the first four IVD tests of the same type will be subject to tier 3 review.
- Criterion #9 takes into account the risk associated with the clinical use of the product. An IVD product which serves as a major determinant of diagnosis, therapy, or prognosis will be subject to tier 2 review because of its likelihood to lead to clinical decision making and significant medical intervention.
Major Determinant - an IVD test that will provide a result that is likely to make or cause change in diagnosis, therapy, or prognosis when used by itself or as a key element in conjunction with other tests.