The Clinical Chemistry and Clinical Toxicology Devices Panel met on November 13-14, 2000 at the Gaithersburg Hilton to provide advice and recommendations to the Agency. On November 13, 2000, the Panel discussed the "Guidance for Prescription Use Drugs of Abuse Assays Premarket Notifications" during the morning session and "Over the Counter (OTC) Screening Tests for Drugs of Abuse: Guidance for Premarket Notifications" during the afternoon session.
FDA clarified the scope of the revised prescription use guidance including providing examples of study design formats and characterizing performance around the cutoff.
FDA asked for comment on the proposed study designs. The Panel’s responses included the following:
- The study designs are appropriate, but some definitions need clarifying.
- Modify the guidance to include testing under various light conditions for visual read devices, use other mass spectrometry (e.g., LC/MS) as comparative methods, address sample storage, allow comparison to a predicate, elaborate on quality control for point of care devices, address cocaine metabolites, and include information on cigarette smokers and dietary supplements in cross reactivity studies.
- Consider alternatives to clinical specimens.
FDA asked for comment on the appropriate methods for establishing cutoffs and assessing accuracy in the absence of SAMHSA guidelines. The Panel noted that the draft guidance might be a reasonable starting point but encouraged working with sponsors to determine the appropriate method.
Public comments on the prescription guidance addressed
- Difficulty in meeting requirements regarding clinical sample cutoff
- Confusion with detection limit and cutoff descriptions
- Justification for selection of cutoffs
- Inability to obtain perfect agreement to the reference method
- Difficulty in testing multiple lots at external sites
- Concern about limiting guidance to SAMHSA cutoffs
- Comments regarding FDA’s legal jurisdiction (these were deferred)
FDA clarified the scope of the revised OTC guidance including ways to encourage confirmation testing, description of study designs, types of claims FDA considers OTC, and plans for regulating OTC alcohol devices.
FDA asked for comments on mandatory confirmation testing as part of the design of screening tests. The Panel’s responses included the following:
- Support for mandatory confirmation testing
- Comment that confirmation testing itself should not be regulated by the FDA
- Suggestion to handle confirmation testing for alcohol tests differently
FDA asked for comments on whether the proposed studies and labeling guidelines were appropriate for the proposed OTC settings. The Panel commented as follows:
- Limit the guidance to assays used at home.
- The guidance should be applied to all stated settings (i.e., home, workplace, sports, and insurance).
- The consumer study design was appropriate for demonstrating performance by lay users. (No additional studies were recommended.)
- Regarding the consumer study design: incorporate quality control, replace the term "uncertain" (results), include an 800 number, and revisit the intended use as this will depend on the setting of intended use.
FDA asked for comments on whether the same studies were appropriate for OTC alcohol testing devices. The opinions of the panelists were as follows:
- Alcohol tests requirements should be separate from drugs of abuse.
- The DOT model may be adequate.
- Confirmatory testing is recommended in settings where consequences would be severe (e.g., workplace, sports, and insurance).
FDA asked for comments about performance around the cutoff. Panelists responded as follows:
- The performance criterion at ± 50% of the cutoff is too tight.
- The performance criterion at ± 50% of the cutoff is too liberal.
- Certain performance criteria need to be established to support the cutoff for visual read devices.
- Consider the European standard for qualitative tests.
FDA asked whether performance data should be included in OTC labeling. The Panel commented as follows:
- Some performance data should be included.
- Sponsors should consider referring users to a website discussing interpretation of results and other performance information.
- Sponsors should test a population to make sure the labeling is understandable.
FDA asked whether only those devices with SAMHSA cutoffs should be eligible for OTC use. The panelists felt that OTC use should not be restricted to those with SAMHSA cutoffs.
Public comments on the OTC guidance addressed
- Including the cost of confirmation testing increasing the cost of the device
- Performance requirements around the cutoff
- Confirming negatives
- Confirming positives because of cross reactivity with other drugs and dietary supplements
- Mandatory confirmation testing as recommended in the guidance potentially conflicting with certain state regulations
- Importance of consumer feedback
- Lack of utility of including performance data in consumer labeling
- Handling OTC alcohol test devices differently from drugs of abuse
- FDA’s legal jurisdiction (these were deferred)
On November 14, 2000, the meeting began with a thirty-minute closed session at which the FDA presented confidential information on pending and future device submissions. This was followed by the open session at which the Panel discussed and made recommendations on a premarket notification (510(k)) for the Psychemedics Corporation Opiate Assay. This product is a radioimmunoassay intended for use in the qualitative and semiquantitative analysis of heroin in human hair with a cutoff of 2 ng/10 mg hair. This assay provides only a preliminary positive test result, which must be confirmed, with the preferred confirmatory method being mass spectrometry.
The sponsor presented an overview of the current use of hair testing, an overview of their analytical procedures, responses to the FDA questions for panel deliberations (including a statistical examination of hair color bias), and hair testing and federal efforts.
FDA asked for comments on whether data from research reports and other sources as opposed to a prospective, controlled clinical trial could establish and characterize assay performance. The Panel commented that
- Research reports were not sufficient alone.
- The data in the application are sufficient as is.
- A controlled, clinical trial with heroin would be problematic and is not practical.
- Demographic data are needed.
FDA asked for comment on the use of urinalysis and self-reporting of use/non-use to establish drug status. The Panel responded that
- A negative urinalysis plus a negative self-report might be acceptable, but a positive urinalysis lacking confirmed results might be suspect.
- Self-reporting is not reliable.
FDA asked for comments about the minimum dose to produce a positive result. The Panel commented as follows:
- Minimum dose is not important information.
- The importance of this information depends on the intended use.
- The relationship of drug use pharmacokinetics and incorporation into hair is not necessary.
- Focus on whether the sample is collected in the appropriate timeframe.
FDA asked for comments on whether the potential for bias by individual differences (e.g., race, age, sex, hair color, etc.) in the incorporation and retention of drug in the hair should be evaluated. The Panel responded as follows:
- Bias should be evaluated, particularly with respect to women and melanin content.
- Studies to evaluate bias could be conducted post-market.
FDA asked for comment on whether the sponsor adequately addressed the issue of retention of drug in the hair from environmental exposure. The Panel’s responses included the following:
- The wash procedure adequately addressed this question.
- Smoke exposure or powder on hair may not have been adequately addressed in the wash procedure.
- Wash-to-wash and sample-to-sample variability needs to be established.
- The sponsor adequately addressed the effect of various washing or hair treatment procedures on the internally incorporated/bound drug.
- Any additional studies addressing the environmental exposure could be done post-market.
Public comments on the Psychemedics Corporation Opiate Assay addressed
- The criticality of drug testing in the workplace because of chronic use detection, easy collection, and difficulty adulterating sample as compared to urine
- The need for prompt clearance
- Hair testing experiences in diversionary programs and in high school settings
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