INTROL CF PANEL I CONTROL, MODEL: G106

K083171 · Maine Molecular Quality Controls, Inc. · NZB · Dec 16, 2008 · Microbiology

Device Facts

• Record ID: K083171
• Device Name: INTROL CF PANEL I CONTROL, MODEL: G106
• Applicant: Maine Molecular Quality Controls, Inc.
• Product Code: NZB · Microbiology
• Decision Date: Dec 16, 2008
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5910
• Device Class: Class 2

Indications for Use

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 the American College of Obstetricians and Gynecologists (ACOG). The INTROL™ CF Panel I Control also monitors 3 polymorphisms (I506V, I507V, F508C) and the 5/7/9T variants.

Device Story

Introl™ CF Panel I Control is an assayed quality control material; consists of synthetic CFTR DNA suspended in a matrix of synthetic DNA targets, non-human carrier DNA, preservatives, dye, and stabilizers. Used in clinical laboratories to monitor analytical performance of CFTR mutation detection assays; processed through extraction, amplification, and detection steps alongside patient samples. Modified version includes 679 additional base pairs of wild-type CFTR sequence to support detection of specific alleles (711+1G>T and 2789+5 G>A). Healthcare providers use control results to verify assay run validity; ensures accurate identification of CFTR mutations/variants for patient diagnosis. Benefits include standardized quality assurance for genetic testing workflows.

Clinical Evidence

No clinical data. Bench testing only. Three batches of modified control were tested using xTAG® (Luminex/TmBioscience), eSensor® CFCD (Osmetech), and InPlex® (Third Wave) assays. Results demonstrated correct genotype calls for all mutations and variants, including successful detection of 711+1G>T and 2789+5 G>A alleles. Lot-to-lot reproducibility was verified across multiple manufacturing builds.

Technological Characteristics

Synthetic recombinant DNA in matrix with non-human carrier DNA, preservatives, dye, and stabilizers. Ready-to-use liquid in polypropylene bottles. Storage at 2-8°C. Modification adds 679 base pairs of wild-type CFTR sequence (Exon 3, 5, and 14b flanking regions).

Indications for Use

Indicated for use as an in vitro diagnostic quality control material to monitor the analytical performance of extraction, amplification, and detection steps in assays identifying CFTR gene mutations and variants in patients undergoing cystic fibrosis testing.

Regulatory Classification

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.

Special Controls

*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.

The device is classified as Class II under regulation 21 CFR 866.5910 with special controls. The special control guidance document "Class II Special Controls Guidance Document: Quality Control Material for Cystic Fibrosis Nucleic Acid Assays" is available at http://www.fda.gov/cdrh/oivd/guidance/1614.html.

Predicate Devices

• INTROL™ CF Panel I Control (k060070)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
K083171

B. Purpose for Submission:
Addition of 679 base pairs of wild type CFTR sequence to previously cleared Introl™ CF Panel I Control (k060070)

C. Measurand:
Controls for assays detecting Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene mutations and variants

D. Type of Test:
Assayed quality control material

E. Applicant:
Maine Molecular Quality Controls, Inc. (MMQCI)

F. Proprietary and Established Names:
Introl™ CF Panel I Control

G. Regulatory Information:

1. Regulation section:
21 CFR 866.5910 DNA quality control material for genetic testing

2. Classification:
Class II

3. Product code:
NZB, Quality Control material, genetics, DNA

4. Panel:
Immunology (82)

H. Intended Use:

1. Intended use(s):
The intended use is the same as the previous cleared Introl™ CF Panel I Control (k060070) which states:

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 the American College of Obstetricians and Gynecologists (ACOG). The INTROL™ CF Panel I Control also monitors 3 polymorphisms (I506V, I507V, F508C) and the 5/7/9T variants.

2. Indication(s) for use:
Same as the intended use

3. Special conditions for use statement(s):
For prescription use only

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4. Special instrument requirements:
Not applicable

I. Device Description:
The formulation of the modified and cleared INTROL™ CF Panel I Control is the same: INTROL™ CF Panel I Control consists of synthetic CFTR DNA suspended in a matrix of synthetic DNA targets, carrier DNA of a 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 modifications from the cleared panel:
CFTR DNA has been modified as follows:
1. Exon 3: additional 106 nucleotides 3'
2. Exon 5: additional 184 nucleotides 3'
3. Exon 14b: additional 100 nucleotides 5' and additional 289 nucleotides 3'

Table I: Number of Intronic Bases Flanking Each Exon of INTROL™ CF Panel I Control

| Cleared INTROL™ CF Panel I Control | | | Modified INTROL™ CF Panel I Control | | |
| --- | --- | --- | --- | --- | --- |
| EXON | 5' | 3' | EXON | 5' | 3' |
| 1 | 312 | 91 | 1 | 312 | 91 |
| 2 | 97 | 273 | 2 | 97 | 273 |
| 3 | 144 | 125 | 3 | 144 | 231* |
| 4 | 222 | 150 | 4 | 222 | 150 |
| 5 | 307 | 86 | 5 | 307 | 270* |
| 6A | 205 | 109 | 6A | 205 | 109 |
| 6B | 255 | 100 | 6B | 255 | 100 |
| 7 | 126 | 99 | 7 | 126 | 99 |
| 8 | 198 | 134 | 8 | 198 | 134 |
| 9 | 495 | 402 | 9 | 495 | 402 |
| 10 | 339 | 246 | 10 | 339 | 246 |
| 11 | 146 | 235 | 11 | 146 | 235 |
| 12 | 160 | 289 | 12 | 160 | 289 |
| 13 | 92 | 128 | 13 | 92 | 128 |
| 14A | 385 | 250 | 14A | 385 | 250 |
| 14B | 265 | 259 | 14B | 365* | 548* |
| 15 | 142 | 133 | 15 | 142 | 133 |
| 16 | 312 | 259 | 16 | 312 | 259 |
| 17A | 235 | 315 | 17A | 235 | 315 |
| 17B | 191 | 154 | 17B | 191 | 154 |
| 18 | 244 | 211 | 18 | 244 | 211 |
| 19 | 150 | 89 | 19 | 150 | 89 |
| 20 | 186 | 251 | 20 | 186 | 251 |
| 21 | 443 | 313 | 21 | 443 | 313 |
| 22 | 585 | 235 | 22 | 585 | 235 |
| 23 | 178 | 181 | 23 | 178 | 181 |
| 24 | 178 | 222 | 24 | 178 | 222 |

*modification

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J. Substantial Equivalence Information:

1. Predicate device name(s):
INTROL™ CF Panel I Control
2. Predicate 510(k) number(s):
k060070
3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | PREDICATE | MODIFIED |
| Intended Use | Monitor analytical performance of extraction, amplification, and detection steps of CFTR mutation detection assays. | Same |
| Formulation | Synthetic (recombinant) DNA with non-human carrier DNA, preservatives, dye and stabilizers | Same |
| Physical Format | Ready-to-use liquid | Same |
| Packaging | Polypropylene bottles | Same |
| Assay Steps Monitored | Extraction, Amplification and Detection | Same |
| Recommended Storage | 2-8°C | Same |
| Directions for Use | Handle control in the same manner as the patient sample | Same |
| Method to Validate CFTR Sequence | Bi-directional sequencing | Same |
| Method to Verify each Lot | FDA-cleared CFTR detection assay, Bi-directional sequencing | Same |
| Differences | | |
| --- | --- | --- |
| Item | Predicate | Modified |
| Gene Segment SNPs | CFTR (38 mutations; 4 variants) | Additional 679 base pairs of wild type CFTR sequence to the existing SNPs |

K. Standard/Guidance Document Referenced (if applicable):
Class II Special Controls Guidance Document: Quality Control Material for Cystic Fibrosis Nucleic Acid Assays

L. Test Principle:
Not applicable

M. Performance Characteristics (if/when applicable):
1. Analytical performance:
a. Precision/Reproducibility:
Lot-to-lot reproducibility
Three builds of CF Panel I were manufactured using the same SOPs as for FDA-cleared

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CF panel I with calculations adjusted for the new size plasmids. The first two builds are comprised of five bottles each. Each bottle contained specific clones, independently manufactured. The third build is comprised of three bottles, each containing different clones independently manufactured. All lots were tested using the xTAG™ Cystic Fibrosis Kit, eSensor and other amplification methods and found to give the correct calls.

Table 3: Modified INTROL™ CF Panel 1, Build 1

| Lot Number /bottle | Method (s) | Results |
| --- | --- | --- |
| K08JUN06/ a | Other Amplification Methods | All calls correct |
| | xTAG™ Cystic Fibrosis Kit | All calls correct |
| L08JUN06/ b | Other Amplification Methods | All calls correct |
| | xTAG™ Cystic Fibrosis Kit | All calls correct |
| | eSensor | All correct except 2 transcription errors |
| A09JUN06/ c | Other Amplification Methods | All calls correct |
| | xTAG™ Cystic Fibrosis Kit | All calls correct |
| | eSensor | All calls correct |
| B09JUN06/ d | Other Amplification Methods | All calls correct |
| | xTAG™ Cystic Fibrosis Kit | All calls correct |
| C09JUN06/ e | Other Amplification Methods | All calls correct |
| | xTAG™ Cystic Fibrosis Kit | All calls correct |

Table 4: Modified INTROL™ CF Panel 1, Build 2 and 3

| Lot Number /bottle | Method (s) | Results |
| --- | --- | --- |
| B16JAN07/ a | All Amplification Methods | All calls correct |
| C16JAN07/ b | All Amplification Methods | All calls correct |
| D16JAN07/ c* | All Amplification Methods | All calls correct |
| E16JAN07/ d | All Amplification Methods | All calls correct |
| F16JAN07/ e | All Amplification Methods | All calls correct |
| A05OCT07/ a | All Amplification methods | All calls correct |
| B05OCT07/ b | All Amplification methods | All calls correct |
| C05OCT07/ c* | All Amplification methods | All calls correct |

*Bottle c contains same set of plasmids as found separately in bottles d and e

b. Linearity/assay reportable range: Reference:
Not applicable

c. Traceability, Stability, Expected values (controls, calibrators, or methods):
Same as k060070

d. Detection limit:
Not applicable

e. Analytical specificity:
Not applicable

f. Assay cut-off:
Not applicable

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2. Comparison studies:
The three batches of modified INTROL CF Panel I Control were tested in the following CFTR detection assays: xTAG® (Luminex/ TmBioscience), eSensor® CFCD (Osmetech), and InPlex® (Third Wave) which require the additional CFTR sequence of the modified INTROL CF Panel I Control in order to detect Control alleles 711+1G>T and 2789+5 G>A. All genotype calls were the same as for the predicate INTROL CF Panel I Control with the exception that 711+1G>T and 2789+5 G>A were detected by all assays.

Risk analysis
A risk analysis using Failure Modes and Effects Analysis (FMEA) was performed to assess the impact of the modifications. Results showed that the design outputs of modified INTROL CF Panel I meet design inputs in conformance with design control requirements as specified in 21 CFR 820.30.

3. Clinical studies:
Not applicable

4. Clinical cut-off:
Not applicable

5. Expected values/Reference range:
Not applicable

N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.