TDM CONTROL SET, MODEL CAT# 04521536 by ROCHE DIAGNOSTICS CORP.

The TDM Control Set is intended for use as an assayed quality control product on Roche/Hitachi and COBAS INTEGRA analyzers. Two assayed levels of serum barbiturates and three assayed levels of acetaminophen, amikacin, carbamazepine, digoxin, gentamicin, lidocaine, N-acety/procainamide, phenobarbital, phenytoin, primidone, procainamide, quinidine, salicylate, theophylline, tobramycin, valproic acid and vancomycin are provided.

Device Description

The TDM Control Set contains liquid controls based on human serum with added therapeutic drugs, preservative, and stabilizer. The adjusted concentrations and activities of the control components are usually in the normal range or at the normal/pathological threshold. Some of the methods as specified in the enclosed value sheet may not be available in all countries. The TDM Control Set contains a mixture of 17 different drugs. Drugs included are acetaminophen, amikacin, carbamazepine, digoxin, gentamicin, lidocaine, N-acetylprocainamide, phenobarbital, phenytoin, primidone, procainamide, quinidine, salicylate, theophylline, tobramycin, valproic acid and vancomycin. The concentrations and activities of the components are lot-specific. The exact values are given in the enclosed value sheet. The control set contains three levels for each drug. In addition, the TDM Control Set is value assigned for two levels (level I & II) of serum barbiturates, utilizing phenobarbital already present in the controls.

AI/ML Overview

The provided text describes a 510(k) summary for a medical device called the "TDM Control Set." This device is a quality control material intended for use with specific analyzers. The filing is for a modified version of an existing device (K060429), where the primary change is the addition of value assignments for serum barbiturates.

Acceptance Criteria and Study Information:

This 510(k) summary does not contain the typical structure for reporting acceptance criteria and a study demonstrating performance in the way one might expect for a diagnostic or therapeutic device that directly impacts patient diagnosis or treatment. This is because the device is a quality control material, not a diagnostic test itself. Its "performance" is judged by its ability to reliably provide known concentrations of therapeutic drugs for calibrating and verifying the accuracy and precision of analytical instruments.

Therefore, the study described here focuses on demonstrating the substantial equivalence of the modified device to its predicate, particularly regarding the newly added value assignment for serum barbiturates, rather than a clinical performance study with sensitivity, specificity, etc.

Here's an attempt to extract and interpret the requested information based on the provided text, while acknowledging the nature of the device:

1. Table of Acceptance Criteria and Reported Device Performance:

Given the nature of a quality control material, the "acceptance criteria" revolve around the accuracy and reliability of the assigned values for the control components. The "reported device performance" is the successful assignment of these values, particularly for the new component.

Acceptance Criteria (Inferred)	Reported Device Performance
Reliability and accuracy of value assignments for all 17 therapeutic drugs, consistent with the predicate device.	The device contains the same 17 drugs and has not changed in stability or composition compared to the predicate, implying continued reliable value assignment for these drugs. "No new analytes were added, and no drug levels have changed. Therefore, stability and composition have not changed."
Successful and accurate value assignment for two levels of serum barbiturates (Level I & II) based on the phenobarbital content.	The controls were tested using the Serum Barbiturates assay. The assay is calibrated with secobarbital, with cross-reactivity to phenobarbital of approximately 26%. "Essentially, we are using the cross-reactivity of the phenobarbital in the controls to allow us to assign targets for the Serum Barbiturates assay." This indicates successful establishment of target values for serum barbiturates through a defined methodology using existing components.
Performance of the TDM Control Set on Roche/Hitachi and COBAS INTEGRA analyzers for quality control, maintaining accuracy and precision for quantitative methods.	The device is intended for "quality control by monitoring accuracy and precision for the quantitative methods as specified in the value sheet" on "Roche/Hitachi and COBAS INTEGRA analyzers." The claim of substantial equivalence with a device that is already marketed and used on these platforms, implies continued expected performance in this role.
Equivalence to the predicate device (K060429) in all aspects except the explicit value assignment for serum barbiturates.	"The predicate device, TDM Control Set (K060429) is identical with the current TDM Control set except that it is not value assigned for two levels of serum barbiturates." This statement, along with the detailed comparison, serves as the primary "performance" metric for a 510(k) of this nature. The device is claimed to be substantially equivalent.

2. Sample Size Used for the Test Set and Data Provenance:

Sample Size: The document does not specify a "sample size" in the context of a typical clinical trial. For a quality control material, the "test set" would refer to the lots of the control material produced and tested to establish their assigned values. The description mentions "three levels for each drug" and "two levels (level I & II) of serum barbiturates." It doesn't quantify the number of units or replicates tested to establish these values.
Data Provenance: Not explicitly stated. Given that Roche Diagnostics Corporation is the submitter and the product is a control material, the data would likely originate from their internal R&D and manufacturing facilities. It would be considered prospective for the purpose of establishing the new value assignments for serum barbiturates, as these values were specifically determined for this modified device.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts:

This information is not provided in the summary. For a quality control material, the "ground truth" (i.e., the assigned values) is typically established through a rigorous internal validation process involving analytical chemists, biochemists, and metrology experts, rather than clinical experts.

4. Adjudication Method for the Test Set:

This information is not provided. Adjudication methods like "2+1, 3+1" are relevant for expert consensus in image interpretation or clinical diagnosis. For a quality control material, the "adjudication" would be through statistical analysis and adherence to established analytical validation protocols to determine the most accurate and precise assigned values for the components.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:

No, an MRMC comparative effectiveness study was not done. This type of study is typically used for diagnostic devices where human readers interpret results, often in comparison to an AI algorithm. The TDM Control Set is not a diagnostic device; it's a calibrator/quality control material for automated analyzers.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:

This concept is not directly applicable. The "device" itself is a chemical reagent. Its "performance" is in providing accurate and precise concentrations when measured by an analytical instrument. The "algorithm" here would be the analytical method on the Roche/Hitachi and COBAS INTEGRA analyzers. The control set is used with these existing algorithms to ensure their accuracy, it doesn't have an "algorithm" of its own in the AI sense.

7. The Type of Ground Truth Used:

For the TDM Control Set, the "ground truth" for each drug concentration is established through analytical reference methods and calibrated internal standards. This involves highly accurate and precise quantitative chemical analyses to determine the exact concentration of each therapeutic drug within the control material. For the serum barbiturates, the ground truth is established by correlating the known phenobarbital concentration with the existing Serum Barbiturates assay's cross-reactivity.

8. The Sample Size for the Training Set:

This information is not provided. The concept of a "training set" as understood in machine learning (where an algorithm learns from data) is not directly applicable here. For a quality control product, the "training" analogous to this would be the historical data and validation studies used to develop the manufacturing process and analytical methods that ensure the consistent production of the control material with accurate assigned values.

9. How the Ground Truth for the Training Set was Established:

As mentioned above, the concept of a "training set" for a quality control material is different from AI/machine learning. The "ground truth" for establishing the consistency and assigned values of the control material (analogous to what might be learned from a training set) would be established through:
- Validated analytical methods: Using reference assays with known traceability and accuracy.
- Statistical processes: To determine confidence intervals and assigned values for each lot of the control material.
- Manufacturing controls: Ensuring consistent formulation and production of the control material.
- For the specific addition of serum barbiturates, the ground truth was established by experimentally determining the cross-reactivity of the existing phenobarbital in the control set with the Serum Barbiturates assay, which is calibrated with secobarbital.

Summary

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K070200

510(k) Summary	MAR 19 2007
Introduction	According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.
1) Submitter name, address, contact	Roche Diagnostics Corporation9115 Hague Rd.Indianapolis, IN 46250(317) 521-7688
	Contact Person: Dimitris Demirtzoglou
	Date Prepared: January 19, 2007
2) Device name	Proprietary name: TDM Control Set
	Common name: Quality control material (assayed and unassayed).
	Classification name: Multi-analyte controls, all kinds (assayed and unassayed)
3) Predicate devices	We claim substantial equivalence to the currently marketed TDM Control Set (K060429).
4) Device Description	The TDM Control Set contains liquid controls based on human serum with added therapeutic drugs, preservative, and stabilizer. The adjusted concentrations and activities of the control components are usually in the normal range or at the normal/pathological threshold. Some of the methods as specified in the enclosed value sheet may not be available in all countries.
	The TDM Control Set contains a mixture of 17 different drugs. Drugs included are acetaminophen, amikacin, carbamazepine, digoxin, gentamicin, lidocaine, N-acetylprocainamide, phenobarbital, phenytoin, primidone, procainamide, quinidine, salicylate, theophylline, tobramycin, valproic acid and vancomycin
	The concentrations and activities of the components are lot-specific.The exact values are given in the enclosed value sheet.

Continued on next page

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510(k) Summary, Continued ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

5.) IntendedUse	The TDM Control Set is for use in quality control by monitoring accuracy andprecision for the quantitative methods as specified in the value sheet.
6.) Comparisonto the PredicateDevice	Below the similarities and differences between the modified TDM ControlSet and its predicate device [TDM Control Set (K060429)] are presented. Thedevice will continue to be sold under the same name, TDM Control Set.
	The TDM Control Set contains liquid controls based on human serum withadded therapeutic drugs, preservative, and stabilizer. The TDM Control Setcontains a mixture of 17 different drugs. Drugs included are acetaminophen,amikacin, carbamazepine, digoxin, gentamicin, lidocaine, N-acetylprocainamide, phenobarbital, phenytoin, primidone, procainamide,quinidine, salicylate, theophylline, tobramycin, valproic acidandvancomycin.The control set contains three levels for each drug. In addition, the TDMControl Set is value assigned for two levels (level I & II) of serumbarbiturates, utilizing phenobarbital already present in the controls.
	The predicate device, TDM Control Set (K060429) is identical with thecurrent TDM Control set except that it is not value assigned fo two levels ofserum barbiturates.
	No new analytes were added, and no drug levels have changed. Therefore,stability and composition have not changed. The package insert and intendeduse have not changed, but the value assignment for serum barbiturates wasadded to the value sheet. The traceability of the controls has not changed,except of course for the serum barbiturates assignment.
	Here is a summary of the TDM Control Set in relation to serum barbiturates:
	The TDM Control Set contains phenobarbital. The controls were tested usingthe Serum Barbiturates assay. The Serum Barbiturates assay is calibratedwith secobarbital, with cross-reactivity to phenobarbital of approximately26%. Essentially, we are using the cross-reactivity of the phenobarbital in thecontrols to allow us to assign targets for the Serum Barbiturates assay.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of an eagle with its wings spread, rendered in black. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular fashion around the eagle, also in black. The text is in all capital letters.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Roche Diagnostics Corp. 9115 Hague Road, PO Box 50416 Indianapolis, IN 46250-0457 ATTN: Mr. Dimitris Demirtzoglou MAR 1 9 2007

Re: K070200 Trade/Device Name: TDM Control Set Regulation Number: 21 CFR $862.1660 Regulation Name: Quality control material (assayed and unassayed). Regulatory Class: Class I (reserved) Product Code: JJY Dated: March 06, 2007 Received: March 07, 2007

Dear Mr. Demirtzoglou:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device. or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0490. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97), You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Jean m. Cooper, M.S., D.V.M.

Yean M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known):

Device Name: TDM Control Set

Indications For Use:

Prescription Use x (Part 21 CFR 801 Subpart D)

5100

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

Page 1 of

Regulation Number and Section

§ 862.1660 Quality control material (assayed and unassayed).

(a)
Identification. A quality control material (assayed and unassayed) for clinical chemistry is a device intended for medical purposes for use in a test system to estimate test precision and to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. A quality control material (assayed and unassayed) may be used for proficiency testing in interlaboratory surveys. This generic type of device includes controls (assayed and unassayed) for blood gases, electrolytes, enzymes, multianalytes (all kinds), single (specified) analytes, or urinalysis controls.(b)
Classification. Class I (general controls). Except when intended for use in donor screening tests, quality control materials (assayed and unassayed) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.