INTROL™ CF Panel I Control is intended for in vitro diagnostic use as a quality control to monitor analytical performance of the extraction, amplification and detection steps of diagnostic assays used in the detection of the Cystic FibrosisTransmembrane Regulator (CFTR) gene mutations and variants. This product is intended to be extracted and analyzed routinely with each CFTR assay run. The INTROL™ CF Panel I Control is designed to monitor the detection of 38 CFTR mutations associated with cystic fibrosis, including the 23 mutations recommended for testing by American College of Medical Genetics (ACMG) and American College of Obstetricians and Gynecologists (ACOG). The INTROL™ CF Panel I Control also monitors 3 polymorphisms (1506V, I507V, F508C) and the 5/7/9T variants.

Device Description

Modified INTROL™ CF Panel I Control consists of synthetic (recombinant) CFTR DNA suspended in a matrix of carrier DNA of non-human species, preservatives, dye, and stabilizers. CFTR DNA is stabilized in the matrix and released when processed through common extraction methods as if it were a whole blood specimen. INTROL™ CF Panel I Control was modified to contain additional wild type CFTR DNA required for primer annealing of some CFTR detection assays.

AI/ML Overview

The provided document is a 510(k) Summary for a Quality Control Material for Cystic Fibrosis Nucleic Acid Assays, not a medical device in the typical sense of providing diagnostic feedback based on patient data. Therefore, many of the requested criteria related to device performance on patient data, such as sensitivity, specificity, MRMC studies, or ground truth established by experts/pathology/outcomes data, are not applicable in this context.

This document describes a modification to an existing quality control product (INTROL™ CF Panel I Control) and asserts its substantial equivalence to the predicate device (K060070). The acceptance criteria for such a product would primarily revolve around its ability to perform consistently and as intended when used with diagnostic assays.

Here's an analysis based on the provided text, addressing the applicable criteria:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Implied for a Quality Control Material)	Reported Device Performance
Intended Use: Consistent performance as a quality control for extraction, amplification, and detection steps of CFTR diagnostic assays.	"INTROL™ CF Panel I Control is intended for in vitro diagnostic use as a quality control to monitor analytical performance of the extraction, amplification and detection steps of diagnostic assays used in the detection of the Cystic FibrosisTransmembrane Regulator (CFTR) gene mutations and variants." "Verification and validation testing performed as needed according to risk analysis showed that modified INTROL™ CF Panel I Control performed as well or better than INTROL™ CF Panel I Control (K060070)."
Monitoring Capability: Designed to monitor detection of 38 CFTR mutations, including 23 ACMG/ACOG recommended mutations, 3 polymorphisms, and 5/7/9T variants.	"The INTROL™ CF Panel I Control is designed to monitor the detection of 38 CFTR mutations associated with cystic fibrosis, including the 23 mutations recommended for testing by American College of Medical Genetics (ACMG) and American College of Obstetricians and Gynecologists (ACOG). The INTROL™ CF Panel I Control also monitors 3 polymorphisms (1506V, I507V, F508C) and the 5/7/9T variants."
Equivalence to Predicate: Performance is as good as or better than the predicate device.	"Verification and validation testing performed as needed according to risk analysis showed that modified INTROL™ CF Panel I Control performed as well or better than INTROL™ CF Panel I Control (K060070)." "Test methods were the same as those used for 510(k) submission of the predicate." "Based on analysis and performance testing, we conclude that modified INTROL™ CF Panel I Control is substantially equivalent to INTROL™ CF Panel I Control (K060070), is as safe and effective as the predicate, and performs better than the predicate in certain CFTR detection assays."
Conformance: Meets design inputs in accordance with design control requirements (21 CFR 820.30).	"Design outputs of modified INTROL CF Panel I Control meet design inputs in conformance with design control requirements as specified in 21 CFR 820.30."

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

The document states: "Verification and validation testing performed as needed according to risk analysis showed that modified INTROL™ CF Panel I Control performed as well or better than INTROL™ CF Panel I Control (K060070). Test methods were the same as those used for 510(k) submission of the predicate."

Sample Size: The specific sample sizes for the "verification and validation testing" are not provided in this 510(k) summary.
Data Provenance: Not explicitly stated. Given that MMQCI is a US-based company, the testing was likely conducted in the US, but this is not confirmed. The document does not specify if the data was retrospective or prospective, though performance testing of a quality control would typically be prospective for new runs.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This question is not applicable. For a quality control material, there isn't a "ground truth" established by experts in the context of diagnostic interpretation. The "ground truth" for the control material itself is its known genetic composition (synthetic CFTR DNA with specific mutations/polymorphisms), which is validated during manufacturing and characterization.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable. Adjudication methods are typically used for interpreting results from diagnostic devices based on patient samples, often involving multiple human readers or expert panels. This is a quality control material, not a diagnostic device.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. This is a quality control material, not an AI-powered diagnostic device, and therefore MRMC studies with human readers are irrelevant.

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

Not Applicable. This is a physical quality control material for laboratory assays, not an algorithm.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The "ground truth" for the INTROL™ CF Panel I Control is the known, manufactured genetic composition of the synthetic (recombinant) CFTR DNA it contains, including the specific 38 mutations, polymorphisms, and variants it is designed to monitor. This is intrinsic to the product design rather than being derived from external data sources like expert consensus or patient outcomes.

8. The sample size for the training set

Not applicable. This product is a quality control material, not a machine learning algorithm that requires a training set.

9. How the ground truth for the training set was established

Not applicable. This product is a quality control material, not a machine learning algorithm that requires a training set.

Summary

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SECTION 12

INTROL CF Panel I Control Special 510(k)

CONFIDENTIAL

6 of 8

APPENDIX 4

10 Southgate Road, Suite 170 Scarborough, Maine 04074 Phone: 207-885-1072; Fax: 207-885-1079 · www.mmqci.com

083171

510 (k) Summary

DEC 1 6 2008

Applicant Contact Information:

Applicant:	Maine Molecular Quality Controls, Inc. (MMQCI)
Address:	10 Southgate Road, Suite 170
	Scarborough, Maine 04074

Contact Person:	Joan H. Gordon, President
Phone Number:	207-885-1072
Fax Number:	207-885-1079

October 19, 2008

Preparation Date:

Device Trade Name:

INTROLTM CF Panel I Control

Device Regulatory Information:

Regulation No .: Common name: Classification Name:

Regulatory Class: Product Code: Panel:

21 CFR 866.5910 Quality control, genetic, DNA control Ouality Control Material for Cystic Fibrosis Nucleic Acid Assays Class II NZB Immunology (82)

Predicate Device:

K060070

INTROL™ CF Panel I Control

Device Description (same as predicate):

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Image /page/1/Picture/0 description: The image shows a logo for MMQCI, which stands for Maine Molecular Quality Controls, Inc. The logo is black and white and features the letters "MMQCI" in a large, bold font. Below the letters, the full name of the company is written in a smaller font. To the left of the letters, there is a graphic that appears to be a stylized representation of a strand of DNA.

10 Southgate Road, Suite 170 Scarborough, Maine 04074 Phone: 207-885-1072; Fax: 207-885-1079 www.mmqci.com

" "

510(k) Summary (Cont.)

Device Intended Use (same as predicate):

Substantial Equivalence:

In view of technical, physical, and performance characteristics, MMQCI believes modified INTROL™ CF Panel I Control is substantially equivalent to INTROL™ CF Panel I Control (K060070) as to intended use and fundamental scientific technology.

Summary of Performance Nonclinical Data

Verification and validation testing performed as needed according to risk analysis showed that modified INTROL™ CF Panel I Control performed as well or better than INTROL™ CF Panel I Control (K060070). Test methods were the same as those used for 510(k) submission of the predicate. Design outputs of modified INTROL CF Panel I Control meet design inputs in conformance with design control requirements as specified in 21 CFR 820.30.

Conclusions

Based on analysis and performance testing, we conclude that modified INTROL™ CF Panel I Control is substantially equivalent to INTROL™ CF Panel I Control (K060070), is as safe and effective as the predicate, and performs better than the predicate in certain CFTR detection assays.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the Department of Health & Human Services U.S.A. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES U.S.A." arranged around the perimeter. Inside the circle is a stylized eagle-like symbol with three curved lines representing the body and wings.

ood and Drug Administration 2098 Gaither Road Rockville MD 20850

Maine Molecular Quality Controls, Inc. c/o Ms. Joan H. Gordon President 10 Southgate Road, Suite 170 Scarborough, Maine 04074

EC 1 6 2008

Re: K083171

Trade/Device Name: INTROLTM CF Panel I Control Regulation Number: 21 CFR 866.5910 Regulation Name: DNA quality control material for genetic testing Regulatory Class: Class II Product Code: NZB Dated: October 19, 2008 Received: October 27, 2008

Dear Ms. Gordon:

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

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Page 2 - MMOCI

requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). 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 advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (240) 276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at (240) 276-3464. 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 http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Josephine Bautista
for Maria M. Chan, Ph.D.

Acting Division Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use Statement

K083171 510 (k) Number:

Device Name:

INTROL™ CF Panel I Control

Indications for Use:

The intended use for the cleared and modified INTROL™ CF Panel I Controls is the same. The INTROL™ CF Panel I Control is intended for in vitro diagnostic use as a quality control to monitor analytical performance of the extraction, amplification and detection steps of diagnostic assays used in the detection of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene mutations and variants. This product is intended to be extracted and analyzed routinely with each CFTR assay run.

The INTROL™ CF Panel I Control is designed to monitor the detection of 38 CFTR mutations associated with cystic fibrosis, including the 23 mutations recommended for testing by American College of Medical Genetics (ACMG) and American College of Obstetricians and Gynecologists (ACOG). The INTROL CF Panel I Control also monitors 3 polymorphisms (1506V, I507V, F508C) and the 5/7/9T variants.

For in vitro diagnostic use.

Prescription Use X

(Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use

(21 CFR 807 Subpart C)

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

H/NEEDED)

Stephanie Bautista

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K08317

SECTION 12

INTROL CF Panel I Control Special 510(k) CONFIDENTIAL

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Regulation Number and Section

§ 866.5910 Quality control material for cystic fibrosis nucleic acid assays.

(a)
Identification. Quality control material for cystic fibrosis nucleic acid assays. A quality control material for cystic fibrosis nucleic acid assays is a device intended to help monitor reliability of a test system by detecting analytical deviations such as those that may arise from reagent or instrument variation in genetic testing. This type of device includes recombinant, synthetic, and cell line-based DNA controls.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9. The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Quality Control Material for Cystic Fibrosis Nucleic Acid Assays.” See § 866.1(e) for the availability of this guidance document.