The ABCA is a continuous flow Gas Isotope Ratio Mass Spectrometer (GIRMS) System intended for use in the measurement of stable isotopes of carbon, nitrogen, and oxygen in gas samples. For this purpose, the system is comprised of a gas sampling module, a gas purification module, and an isotope ratio mass spectrometer which are synchronously coupled by means of an external personal computer which also collects and archives data.

Device Description

The ABCA is an acronym for a configuration of modules intended for use in analysis ${}^{13}$C and ${}^{18}$O in CO${}_2$ and ${}^{15}$N in N${}_2$ and N${}_2$O gas samples. The ABCA System includes:

The Europa 20-20 continuous flow IRMS
A gas purification module (Gas Chromatograph)
An autosampler
An IBM (or compatible) personal computer for system control, data analysis and data storage

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the ABCA Gas Isotope Ratio Mass Spectrometer System, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance	Study Reference
Systematic Difference (Accuracy)	Not explicitly stated	0.06 DOB	NCCLS EP9-A
Within-Run Precision	≤ 0.1%	0.056%	NCCLS EPS-A
Linearity Range (Response Function)	Not explicitly stated	-22%o to 232%o	Not specified

Explanation of Implied Acceptance Criteria:

Systematic Difference: While no explicit acceptance criterion is given, the reporting of "0.06 DOB" suggests that this value was considered acceptable for demonstrating substantial equivalence. The method of measurement (comparison to predicate device) implies the new device should perform similarly.
Within-Run Precision: The statement "The claimed imprecision at this level is 0.1%" directly indicates the acceptance criterion for precision. The reported value of 0.056% is well within this claimed (and implicitly accepted) limit.
Linearity Range: The statement "The ABCA test system response function was determined to be linear throughout the range -22%o to 232%o" implies that linearity across this range was established and considered satisfactory.

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

Sample Size:
- Systematic Difference: 102 breath samples
- Within-Run Precision: Triplicate analyses of stable gas samples in each of 10 daily sample runs (total of 30 analyses).
- Linearity: Not specified, but likely involved multiple measurements across the specified range.
Data Provenance: Retrospective, as the systematic difference study used "102 breath samples from the ${}^{13}$C-urea breath test." The origin of these samples (e.g., country) is not specified. The precision study used "stable gas samples," implying controlled lab samples rather than clinical patient data.

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

Not Applicable. This device is a measurement instrument, not a diagnostic imaging or AI-driven interpretive device that requires human expert review for ground truth in the traditional sense. The "ground truth" for its performance is its physical and chemical measurement capabilities and comparison to a predicate device.

4. Adjudication Method for the Test Set

Not Applicable. See point 3. The performance is based on direct measurements and comparisons to known reference values or a predicate device.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No. An MRMC study was not conducted as this is a measurement device and does not involve human readers interpreting results in the way an AI diagnostic tool would.

6. Standalone (Algorithm Only) Performance Study

Yes, effectively. The "Analytical Performance Data" describe the standalone performance of the device itself (the algorithm in the broad sense of its operational principles and calculations), even though it's a physical instrument. The metrics reported (systematic difference, precision, linearity) directly assess the instrument's capability without human intervention in the primary measurement process.

7. Type of Ground Truth Used

Systematic Difference: Performance of a legally marketed predicate device (ABCA-NT Gas Isotope Ratio Mass Spectrometer System, K974322) on the same samples. Implicitly, the predicate device's performance defined an acceptable "ground" or reference for the comparison.
Within-Run Precision: Comparison against the device's own measurements over time on stable gas samples. The "ground truth" here is the expected consistency of the measurements.
Linearity: Comparison against known concentrations/ratios of reference gases across a range, although not explicitly detailed. The "ground truth" is the established linearity of the physical and chemical principles the device relies upon.

8. Sample Size for the Training Set

Not Applicable/Not Explicitly Stated. This device is a measurement instrument, not an AI model that undergoes a "training" phase with a large dataset. Its "training" or calibration involves using reference gases of known isotopic composition (as mentioned in section 2. Calibration). The sample size for this calibration process is not specified, but it would involve a limited number of analyses with these reference gases.

9. How the Ground Truth for the Training Set Was Established

Reference Gas of Known Isotopic Composition. As stated in section 2. Calibration, "The system is calibrated with reference gas of known isotopic composition." These reference gases are likely certified standards whose isotopic abundances are precisely determined through highly accurate measurement techniques.

Summary

{0}------------------------------------------------

KQ Gi 2163

Attachment 4

510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is:

Type of Submission: Special 510(k): Device Modification A.

Applicant's Name, Address, Contact Person and Date of Preparation B.

PDZ Europa Limited Europa House, Electra Way Crewe, Cheshire CW1 6ZA United Kingdom

Note that the predicate device 510(k), K974322, was submitted under the name Europa Scientific Limited. Effective November 3, 1998, Europa Scientific Limited (Europa House, Electra Way, Crewe, Cheshire, UK) became PDZ Europa Limited at the same address. PDZ Europa Limited has assumed manufacturing operations and distribution rights for all Europa Scientific's products and services. The Device Establishment Registration Number, Owner/Operator number and Device Listing information has been transferred from Europa Scientific Limited to PDZ-Europa Limited.

Please direct any requests for information to:

Clive Workman Chief Executive PDZ Europa Limited Europa House, Electra Way Crewe, Cheshire CW1 6ZA United Kingdom

Phone: +44-1270-589398 Fax: +44-1270-589412

This 510(k) was prepared June 12, 1999

Trade Name of the Device: ABCA Gas Isotope Ratio Mass Spectrometer System C.
D. Common Name of the Device: Gas Isotope Ratio Mass Spectrometer System

E. Classification

Product Code:	91DOP
Name, Class:	Mass Spectrometer, Clinical Use, Class 1
Reg. Number:	21CFR 862.2860

{1}------------------------------------------------

F. The Predicate Device

Trade Name: ABCA-NT Gas Isotope Ratio Mass Spectrometer System 510(k) number: K974322 510(k) clearance date: December 16, 1997

G. Description of the Device

The ABCA is an acronym for a configuration of modules intended for use in analysis ${}^{13}$C and ${}^{18}$O in CO${}_2$ and ${}^{15}$N in N${}_2$ and N${}_2$O gas samples. The ABCA System includes:

The Europa 20-20 continuous flow IRMS �
A gas purification module (Gas Chromatograph) �
� An autosampler
An IBM (or compatible) personal computer for system control, data analysis and data � storage

1. Principle of Operation

Gas samples for analysis are contained in tubes which may be either pre-evacuated or flushed with air or helium. Most commonly, pre-evacuated tubes such as Exetainers® or Vacutainers® are used and are placed in the holding rack of the autosampler of the System. During operation, the sample probe moves over each tube in turn and either aspirates an aliquot of sample or sweeps the entire gas sample tube to the gas purification module with purified helium. Prior to injection, the probe is purged with helium to rid it of any air.

The helium carrier gas plus sample gases pass through a solid desiccant to remove water vapor, then into a gas chromatographic (GC) column which separates sample gas components. When carbon dioxide is the species of interest. it is undesirable for nitrogen and oxygen to enter the Isotope Ratio Mass Spectrometer. To prevent this, a secondary helium flow moves into the IRMS module while oxygen and nitrogen are directed to waste by a Diverter Valve. As the CO2 emerges from the column, the valves switch to direct the pure CO2 into the IRMS with the secondary helium flow directed to waste.

Once in the IRMS, the neutral molecules, e.g., ${}^{12}$CO${}_2$ and ${}^{13}$CO${}_2$, are ionized in the ‘Source’
producing positively charged ions, e.g., ${}^{13}$CO${}_2$${}^+$ and ${}^{12}$CO${}_2$${}^+$. The charged molecules are then given a precise amount of energy by an electric field and directed into a magnetic field where they follow curved paths dependent on the mass to charge ratio. The separated 'beams' of molecules are focused on three different Faraday 'bucket' collectors, thus generating independent electrical currents corresponding to masses 44, 45, and 46 amu. The ratio of currents generated at the 45 and 44 amu collectors corresponds to the ratio of ${}^{13}$CO${}_2$ to ${}^{12}$CO${}_2$ in the original gas sample. The current generated at the 46 amu collector corresponds to the ${}^{12}$C${}^{16}$O${}^{18}$O${}^+$ ion and is used to correct for contributions of ${}^{12}$C${}^{16}$O${}^{17}$O${}^+$ to the 45 amu current using the Craig correction since the ${}^{17}$O/${}^{18}$O ratio is constant.

{2}------------------------------------------------

2. Calibration

The system is calibrated with reference gas of known isotopic composition. The reference gas may be contained in sample tubes in the autosampler or may be introduced directly from a gas cylinder.

Calculation of Results 3.

For a given gas specimen, the ratio of the electrical current signals from the ${}^{13}CO_2^+$ and ${}^{12}CO_2^+$ ions is compared to that obtained when a reference CO2 sample of known isotopic abundance is introduced into the GIRMS system under identical conditions. The result of this differential measurement is expressed as the "delta per mil" difference between the (${}^{13}CO_2/{}^{12}CO_2$) ratio of the sample (RB) and the reference (RS):

$$\text{So } ^{13}\text{C} = \frac{R_B - R_S}{R_S} \text{ * 1000, *\text{@}}$$

The symbol for the "delta per mil" unit is %0.

Intended Use E.

F. Summary of Modifications to the Predicate Device

Hardware Modifications

a) The gas purification (gas chromatograph) module, gas sampling module and the sample injector are housed in a single cabinet to reduce counter space requirements.
b) A redesigned gas sampling module allows sampling an aliquot of gas samples instead of using the entire sample. This permits re-sampling if necessary.
c) A re-sized gas chromatographic column and reduced helium carrier gas flow allow smaller samples and improved chromatographic resolution.
d) An option for direct reference gas injection from a reference gas cylinder eliminates the need to occupy patient sample or QC tube positions in the autosampler with reference gas tubes.

{3}------------------------------------------------

Software Modifications

The Microsoft Visual Basic compiler was upgraded from VB 3.0 to VB 5.0. Software a) was revised to compile under VB 5.0.
b) New program code was introduced for mass spectrometer operation and control of the new gas sampler.
c) Addition of a macro language enables automation of routine operations, provides easier code maintenance and facilitates research applications.
d) A modified graphical user interface facilitates data entry and data storage.

G. Substantial Equivalence

The modified ABCA GIRMS System has the following similarities to the ABCA-NT System which previously received 510(k) clearance:

1. Has the same intended use
Uses the same fundamental scientific technology 2.
1. Incorporates the same basic Europa GIRMS design
Calibrates using the same principle 4.
1. Calculates final results identically
1. Has substantially equivalent technical specifications

In summary, the ABCA Gas Isotope Ratio Mass Spectrometer described in this submission is substantially equivalent to the predicate device.

H. Analytical Performance Data

Using calculations recommended in NCCLS EP9-A, the mean systematic difference 1. between the predicate device and the modified device at 2.4 Delta Over Baseline (DOB) on 102 breath samples from the "C-urea breath test was determined to be 0.06 DOB.
1. Using calculations recommended in NCCLS EPS-A, within-run precision at a level of -22% was determined to be 0.056% based on triplicate analyses of stable gas samples in each of 10 daily sample runs. The claimed imprecision at this level is 0.1%.
1. The ABCA test system response function was determined to be linear throughout the range -22%o to 232%o.

{4}------------------------------------------------

Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle with its wings forming three curved lines.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUL 1 3 1999

PDZ Europa Limited c/o Dr. Robert F. Martin MarChem Associates, Inc. 325 College Road Concord, Massachusetts 01742

K992163 Re:

Trade Name: ABCA-NT Gas Isotope Ratio Mass Spectrometer System Regulatory Class: I reserved Product Code: DOP Dated: June 24, 1999 Received: June 25, 1999

Dear Mr. Workman:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

{5}------------------------------------------------

Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597, or at its internet address "http://www.fda.gov/cdrl/dsma/dsmamain.html".

Sincerely yours.

Steven Sutman

Steven I. Gutman, M.D. M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

{6}------------------------------------------------

Attachment 1

Indications for Use Statement

Device Name:

ABCA Gas Isotope Ratio Mass Spectrometer System

Indications for Use:

Prescription Use: No

Hencooper
(Division Sign-Off)

ision of Clinical Labo oratory Devices 510(k) Number

Regulation Number and Section

§ 862.2860 Mass spectrometer for clinical use.

(a)
Identification. A mass spectrometer for clinical use is a device intended to identify inorganic or organic compounds (e.g., lead, mercury, and drugs) in human specimens by ionizing the compound under investigation and separating the resulting ions by means of an electrical and magnetic field according to their mass.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.