DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
Food and Drug Administration
1401 Rockville Pike
Rockville, MD 20852-1448
December 23, 2003
Trinity Biotech plc
IDA Business Park
Southern Cross Road
Bray Co., Wicklow
Product: Trinity Biotech Uni-Gold Recombigen HIV, Uni-Gold Recombigen HIV Positive and Negative Controls
Device Code: MZF
Date Received: 08-APR-2003
Dear Ms. Campbell:
The Center for Biologics Evaluation and Research (CBER) of the Food and Drug Administration (FDA) has completed its review of your premarket approval application (PMA) for the Trinity Biotech Uni-Gold Recombigen HIV test. This device is indicated for the detection of antibodies to HIV-1 in human serum, plasma or whole blood (venipuncture) specimens. We are pleased to inform you that the PMA is approved. You may begin commercial distribution of the device in accordance with the conditions described below and in the "Conditions of Approval" (enclosed).
In order to ensure the safe and effective use of this device, the sale, distribution, and use of this device are restricted within the meaning of section 520(e) of the Federal Food, Drug, and Cosmetic Act (the Act) under the authority of section 515(d)(1)(B)(ii) of the Act, as follows:
(1) The labeling must specify that
(a) sale of the Trinity Biotech Uni-Gold Recombigen HIV test is restricted to clinical laboratories that have an adequate quality assurance program, including planned systematic activities to provide adequate confidence that requirements for quality will be met; and where there is assurance that operators will receive and use the instructional materials;
(b) the Trinity Biotech Uni-Gold Recombigen HIV test is approved for use only by an agent of a clinical laboratory;
(c) test subjects must receive the "Subject Information Leaflet" prior to specimen collection, and appropriate information when test results are provided;
(d) the Trinity Biotech Uni-Gold Recombigen HIV test is not approved for use to screen donors of blood, plasma, cells or tissues.
(2) You must provide a letter to all purchasers advising them of these restrictions.
We remind you that the sale, distribution, and use must not violate sections 502(q) and (r) of the Act. Further, no advertisement or other descriptive printed material issued by the applicant or private label distributor with respect to this device shall recommend or imply that the device may be used for any use that is not included in the FDA-approved labeling for the device.
As agreed upon in your Letter of Commitment dated December 19, 2003 the following post-approval commitments must be fulfilled:
1. Trinity Biotech commits to provide FDA with results from studies investigating sequence data for peptide fragments generated by Skatole treatment on an additional 2 lots ------------- . These data will be provided to FDA within 12 months from the date of the pre-market approval for this device.
2. Trinity Biotech commits to provide FDA with results from studies investigating the identity of a protein in the ----------------- that has a molecular weight greater than 36kD on the SDS-PAGE. These data will be provided to FDA within 12 months from the date of the pre-market approval for this device.
3. Trinity Biotech commits to producing a plan to detail how it will track and monitor false-positive Trinity Biotech Uni-Gold Recombigen HIV results (negative by western blot) and investigate the possibility of cross-reactivity of minor bands of the antigens with these same false-positive samples. Trinity Biotech will collaborate with 3 high throughput end users in the USA to obtain 100 such samples. Trinity will submit the results of this study to FDA when 100 samples have been collected or 12 months from the date of the pre-market approval for this device, whichever occurs first.
Expiration dating for the Uni-Gold Recombigen HIV test has been established and approved at 12 months at 2 - 27°C and dating for the Uni-Gold Recombigen HIV Positive and Negative Controls is 12 months at 2-8°C.
CBER does not evaluate information related to contract liability warranties, however you should be aware that any such warranty statements must be truthful, accurate, and not misleading, and must be consistent with applicable Federal and State laws.
CBER will notify the public of its decision to approve your PMA by making available a summary of the safety and effectiveness data upon which the approval is based. The information can be found on the FDA CBER Internet website. Written requests for this information can also be made to the Dockets Management Branch, (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. The written request should include the PMA number or docket number. Within 30 days from the date that this information is placed on the Internet, any interested person may seek review of this decision by requesting an opportunity for administrative review, either through a hearing or review by an independent advisory committee, under section 515(g) of the Act.
Failure to comply with the conditions of approval invalidates this approval order. Commercial distribution of a device that is not in compliance with these conditions is a violation of the Act.
If you have any questions concerning this approval order, please contact Michael Wiack at (301) 827-5307.
--- signature ---
Hira L. Nakhasi, Ph.D.
Division of Emerging and Transfusion
Office of Blood Research and Review
Center for Biologics Evaluation and Research
CONDITIONS OF APPROVAL
APPROVED LABELING. As soon as possible, and before commercial distribution of your device, submit three copies of an amendment to this PMA submission with copies of all approved labeling in final printed form to Document Control Center (HFM-99), Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, Rockville, Maryland 20852-1448
ADVERTISEMENT. No advertisement or other descriptive printed material issued by the applicant or private label distributor with respect to this device shall recommend or imply that the device may be used for any use that is not included in the FDA approved labeling for the device. If the FDA approval order has restricted the sale, distribution and use of the device to prescription use in accordance with 21 CFR 801.109 and specified that this restriction is being imposed in accordance with the provisions of section 520(e) of the Act under the authority of section 515(d)(1)(B)(ii) of the Act, all advertisements and other descriptive printed material issued by the applicant or distributor with respect to the device shall include a brief statement of the intended uses of the device and relevant warnings, precautions, side effects and contraindications.
PREMARKET APPROVAL APPLICATION (PMA) SUPPLEMENT. Before making any change affecting the safety or effectiveness of the device, submit a PMA supplement for review and approval by FDA unless the change is of a type for which a "Special PMA Supplement-Changes Being Effected" is permitted under 21 CFR 814.39(d) or an alternate submission is permitted in accordance with 21 CFR 814.39(e). A PMA supplement or alternate submission shall comply with applicable requirements under 21 CFR 814.39 of the final rule for Premarket Approval of Medical Devices.
All situations which require a PMA supplement cannot be briefly summarized, please consult the PMA regulation for further guidance. The guidance provided below is only for several key instances.
A PMA supplement must be submitted when unanticipated adverse effects, increases in the incidence of anticipated adverse effects, or device failures necessitate a labeling, manufacturing, or device modification.
A PMA supplement must be submitted if the device is to be modified and the modified device should be subjected to animal or laboratory or clinical testing designed to determine if the modified device remains safe and effective.
A "Special PMA Supplement - Changes being Effected" is limited to the labeling, quality control and manufacturing process changes specified under 21 CFR 814.39(d)(2). It allows for the addition of, but not the replacement of previously approved, quality control specifications and test methods. These changes may be implemented before FDA approval upon acknowledgment by FDA that the submission is being processed as a "Special PMA Supplement - Changes Being Effected." This procedure is not applicable to changes in device design, composition, specifications, circuitry, software or energy source.
Alternate submissions permitted under 21 CFR 814.39(e) apply to changes that otherwise require approval of a PMA supplement before implementation of the change and include the use of a 30-day PMA supplement or annual post-approval report. FDA must have previously indicated in an advisory opinion to the affected industry or in correspondence with the applicant that the alternate submission is permitted for the changes. Before such can occur, FDA and the PMA applicant(s) involved must agree upon any needed testing protocol, test results, reporting format, information to be reported, and the alternate submission to be used.
POST-APPROVAL REPORTS. Continued approval of this PMA is contingent upon the submission of post-approval reports required under 21 CFR 814.84 at intervals of 1 year from the date of approval of the original PMA. Post-approval reports for supplements approved under the original PMA, if applicable, are to be included in the next and subsequent annual reports for the original PMA unless specified otherwise in the approval order for the PMA supplement. Two copies identified as "Annual Report" and bearing the applicable PMA reference number are to be submitted to the Document Control Center (HFM-99), Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, Rockville, Maryland 20852-1448. The post-approval report shall indicate the beginning and ending date of the period covered by the report and shall include the following information required by 21 CFR 814.84:
- Identification of changes described in 21 CFR 814.39(a) and changes required to be reported to FDA under 21 CFR 814.39(b).
Bibliography and summary of the following information not previously submitted as part of the PMA and that is known to or reasonably should be known to the applicant:
- Unpublished reports of data from any clinical investigations or nonclinical laboratory studies involving the device or related devices ("related" devices include devices which are the same or substantially similar to the applicant's device); and
- Reports in the scientific literature concerning the device.
If, after reviewing the bibliography and summary, FDA concludes that agency review of one or more of the above reports is required, the applicant shall submit two copies of each identified report when so notified by FDA.
ADVERSE REACTION AND DEVICE DEFECT REPORTING. As provided by 21 CFR 814.82(a)(9), FDA has determined that in order to provide continued reasonable assurance of the safety and effectiveness of the device, the applicant shall submit 3 copies of a written report identified, as applicable, as an "Adverse Reaction Report" or "Device Defect Report" to MedWatch (HF-2), Food and Drug Administration, 5600 Fishers Lane, Rockville, Maryland 20852-9787 within 10 days after the applicant receives or has knowledge of information concerning:
- A mixup of the device or its labeling with another article.
Any adverse reaction, side effect, injury, toxicity, or sensitivity reaction that is attributable to the device and
- Has not been addressed by the device's labeling or
- Has been addressed by the device's labeling, but is occurring with unexpected severity or frequency.
- Any significant chemical, physical or other change or deterioration in the device or any failure of the device to meet the specifications established in the approved PMA that could not cause or contribute to death or serious injury but are not correctable by adjustments or other maintenance procedures described in the approved labeling. The report shall include a discussion of the applicant's assessment of the change, deterioration or failure and any proposed or implemented corrective action by the applicant. When such events are correctable by adjustments or other maintenance procedures described in the approved labeling, all such events known to the applicant shall be included in the Annual Report described under "Post-approval Reports" above unless specified otherwise in the conditions of approval to this PMA. This post-approval report shall appropriately categorize these events and include the number of reported and otherwise known instances of each category during the reporting period. Additional information regarding the events discussed above shall be submitted by the applicant when determined by FDA to be necessary to provide continued reasonable assurance of the safety and effectiveness of the device for its intended use.
REPORTING UNDER THE MEDICAL DEVICE REPORTING (MDR) REGULATION. The Medical Device Reporting (MDR) Regulation became effective on December 13, 1984. This regulation was replaced by the reporting requirements of the Safe Medical Devices Act of 1990, which became effective on July 31, 1996, and requires that all manufacturers and importers of medical devices, including in vitro diagnostic devices, report to the FDA whenever they receive or otherwise become aware of information, from any source, that reasonably suggests that a device marketed by the manufacturer or importer:
- May have caused or contributed to a death or serious injury; or
- Has malfunctioned and such device or similar device marketed by the manufacturer or importer would be likely to cause or contribute to a death or serious injury if the malfunction were to recur.
The same events subject to reporting under the MDR Regulation may also be subject to the above "Adverse Reaction and Device Defect Reporting" requirements in the "Conditions of Approval" for this PMA. FDA has determined that such duplicative reporting is unnecessary. Whenever an event involving a device is subject to reporting under both the MDR Regulation and the "Conditions of Approval" for a PMA, the manufacturer shall submit the appropriate reports required by the MDR Regulation within the time frames as identified in 21 CFR 803.10 (c) using FDA Form 3500A, i.e., 30 days after becoming aware of a reportable death, serious injury, or malfunction as described in 21 CFR 803.50 and 21 CFR 803.52 and 5 days after becoming aware that a reportable MDR event requires remedial action to prevent an unreasonable risk of substantial harm to the public health. The manufacturer is responsible for submitting a baseline report on FDA Form 3417 for a device when the device model is first reported under 21 CFR 803.50. This baseline report is to include the PMA reference number. Any written report and its envelope is to be specifically identified, e.g., "Manufacturer Report," "5-Day Report," "Baseline Report," etc.
Any written report is to be submitted to:
Center for Devices and Radiological Health
Medical Device Reporting
P. O. Box 3002
Rockville, MD 20847-3002
Copies of the MDR Regulation (FOD # 336 & 1336) and FDA publications entitled "An Overview of the Medical Device Reporting Regulation" (FOD #509) and "Medical Device Reporting for Manufacturers" (FOD #987) are available on the CDRH WWW Home Page. They are also available through CDRH's Fact-On-Demand (F-O-D) at 800-899-0381. Written requests for information can be made by sending a facsimile to CDRH's Division of Small Manufacturers Assistance (DSMA) at 301-443-8818.