MMQCI INTROL^® Cystic Fibrosis Panel I Control v.02

Part Number: G106ac / Kit Contains: 3 bottles x 2mL / 1 each G106a, G106b, and G106c

Part Number: G106ac-1 / Kit Contains: 3 bottles x 1mL / 1 each G106a-1, G106b-1, and G106c-1

INTROL® CF Panel I Control v.02 DataSheet

INTENDED USE:

INTROL^® CF Panel I Control v.02 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 v.02 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 (I506V, I507V, F508C) and the 5/7/9T variants.

PRODUCT DESCRIPTION:

INTROL^® CF Panel I Control v.02 consists of synthetic CFTR DNA suspended in a matrix of carrier DNA of non-human species, preservatives, dye, and stabilizers. The synthetic DNA contains all 27 CFTR gene exons plus intronic borders, and contains specific mutations and polymorphisms which are divided among 3 bottles (bottles a, b, and c). The specific mutations present in each bottle are listed in Table 1; all other CFTR sequence is wild type. CFTR mutations that are not listed cannot be detected in the INTROL^® CF Panel I Control v.02.

CFTR DNA is stabilized in the matrix and released when processed through common extraction methods as if it were a whole blood specimen. Following extraction, the released DNA can be used in common amplification based molecular assays techniques. Because INTROL^® CF Panel I Control v.02 is designed to mimic the whole blood sample, the resulting copy number of the artificial CFTR segment, after extraction, will be similar to that found in a processed human whole blood sample (v/v).

INSTRUCTIONS FOR USE:

Extract and analyze INTROL^® CF Panel I Control v.02 as you would a whole blood specimen:

1. Allow INTROL^® CF Panel I Control v.02 to reach room temperature (18° – 25°C).
2. Thoroughly mix the controls prior to opening by inverting the bottle several times immediately before use, or by placing on an automated mixer.
3. Extract INTROL^® CF Panel I Control v.02 in the same manner as a whole blood clinical specimen. Use the same volume of INTROL^® CF Panel I Control 02 that would be used for a patient sample in your lab.

Note 1: Certain extraction methods may require additional processing of control material, such as dilution prior to analysis.

Note 2: The level of CFTR DNA present in the extracted control may not be detectable with certain quantitation methods and is not quantifiable by spectrophotometer measurements.

4. Analyze the extracted DNA as you would genomic DNA. If dilutions or other preparations of the extracted DNA are required as part of the testing procedure, handle the INTROL^® CF Panel I Control v.02 DNA according to your standard laboratory
5. Tightly recap each bottle after use and store refrigerated (2° - 8°C).
6. Controls should be tested routinely as a matter of Good Laboratory Practice and according to guidelines or requirements of local, state, and/or federal regulations or accrediting organizations. The frequency of running the control material will depend on individual laboratory practice and may vary according to the analytical system being

STORAGE:

Upon receipt and after opening, the material should be stored at 2° – 8°C. Do not freeze.

STABILITY:

Unopened INTROL^® CF Panel I Control v.02 material is stable through the expiration date printed on each bottle when stored refrigerated (2° – 8°C). Opened material returned to the refrigerator (2° – 8°C) shortly after use is stable for thirty

• days from the date of opening. Contact MMQCI if control material was inadvertently frozen or exposed to high

Table 1. Composition of INTROL^® CF Panel I Control v.02 includes the following combinations of CFTR mutations and polymorphisms (plus wild type sequence covering 27 CFTR exons). Polymorphisms are in parentheses ( ).

PRECAUTIONS AND WARNINGS:

• This product contains 23% ethanol (v/v) and could be flammable. Keep away from open
• This product does not contain any biological material of human
• The laboratory should follow Good Laboratory Practice (GLP) and establish its own performance characteristics for INTROL™ CF Panel I in demonstrating adequate system
• MMQCI CF products are not intended to be frozen and are shipped with a DO NOT FREEZE label.

LIMITATIONS:

• Interferences and cross-reactions may occur with some detection methods and confound interpretation of the test. Please refer to the kit manufacturers package insert to review possible cross-reactions and near neighbor interferences identified in the
• Recoveries may vary depending on extraction method, instrumentation, cycle time / temperature, reagents, method variation, and systematic or random

PERFORMANCE CHARACTERISTICS:

All INTROL^® CF Panel I Control v.02 products are tested by an FDA-cleared CFTR mutation detection method before being released for market distribution. Any mutations not tested by the FDA-cleared method are sequenced bidirectionally before product is released. All mutations must be detected.

Clinical Evaluation – External Sites:

The clinical study performed at the external sites evaluated reproducibility of INTROL™ CF Panel I Control material with respect to within run, between run, between sites, between lots, and between methods.

Evaluation using different extraction methods:

*Five laboratories didn't continue after DNA extraction because DNA quantitation method they used indicated that no DNA was extracted/isolated. Considering that the level of synthetic CFTR DNA present in the extracted control may not be detectable with certain quantitation methods, there is a possibility that extractions in these 5 laboratories may have been successful; however, this could not be assessed because the assays were not performed.

INTROL^® CF Panel I Control v.02 material has been tested using CFTR assays at 10 external sites, 8 of which were clinical laboratories representing intended user. Samples from 11 different manufacturing lots were tested at minimally 3 external sites in at least 3 separate runs. Results are summarized in Table 2.

Table 2. External site evaluations.

1. Each bottle is processed independently and has its own lot number.

INTROL^® CF Panel I Control v.02 is protected by patents. It cannot be cloned, sold, or transferred to other laboratories without the explicit written consent of MMQCI.

Expected Results:

Expected results with the INTROL^® CF Panel I Control v.02 using an FDA- cleared CFTR assay are presented in Table 3.

Table 3. Results with the INTROL^® CF Panel I Control v.02 using an FDA cleared CFTR assay.

1       Detected as homozygous mutant.