Welcome to the State of California 

About The Genetic Disease Laboratory

Accurate Laboratory Testing

Mission Statement

Public-Private Partnership

Screening and Confirmatory Tests

Quality and Test Volume

Test Management

Screening Laboratories

Central Laboratory (GDL)

Methods of Assessment

New Test Methods

Objectives of GDL

Accurate Laboratory Testing

California statutes provide for universal access to quality genetic medical services. Accurate laboratory testing is a key component of these services. GDL has the responsibility to assure that laboratory tests are conducted with uniform standards of high quality.

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Mission Statement

The Genetic Disease Laboratory conducts a statewide program of adult, prenatal and newborn testing of persons for detection of genetic diseases in support of the clinical initiatives of the Genetic Disease Screening Program. The mission of the Genetic Disease Laboratory is to ensure that these tests are reliable, accurate and cost-effective.

GDL is mandated to serve as a laboratory testing facility or to contract with other qualified laboratories. The statutes authorize GDL to perform laboratory services, including quality control, confirmatory testing, and emergency testing.

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Public-Private Partnership

Most of the Genetic Disease Branch's genetic testing for birth defects and congenital disorders is performed in the private sector by laboratories who work under contract to GDL. This method of "contracting out" takes advantage of the efficiency of business and the economy of competitive bidding while preserving the State's mandated control of test quality. Contracting, as opposed to government approval or licensure, affords the most stringent control of quality and the maximum assurance that the laboratories perform uniformly according to established standards. Since the current statutes were signed into law in 1979, GDL has maintained a productive public-private partnership with the laboratories that carry out the testing as well as with the vendors of test instruments that provide reagents and equipment.

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Screening and Confirmatory Tests

Genetic Disease Laboratory Branch (GDLB), contracts with both screening laboratories and confirmatory laboratories. Screening laboratories ascertain the possible presence of a birth defect or congenital disorder. When a screening test result is a presumptive positive, the patient is referred for a definitive clinical evaluation that includes diagnostic testing at a confirmatory laboratory. Confirmatory laboratories perform a battery of diagnostic tests to help determine with certainty if a birth defect or congenital disorder is actually present.

GDLB itself serves as a screening laboratory for phenylketonuria (PKU) disease for testing patients that were identified PKU positives by the newborn screening program and they are on PKU diet. The laboratory also performs newborn screening for congenital adrenal hyperplasia disease.

Screening tests are performed on dried-blood-spot specimens collected from newborns. Genetic Disease laboratory is certified by the State and CLIA.

GDLB oversees the testing of seven contract laboratories that perform newborn and prenatal screening testing. GDLB is responsible for quality assurance, data review and release, method validations, chemical research and training, supply of equipment and reagents to contract laboratories, maintain blood spot specimen bank, vendor services, and inspections for compliance.

California newborn screening program, a leader in genetic screening tests newborns for 76 genetic disorders including sickle-cell disease and other hemoglobinopathies, primary congenital hypothyroidism,   galactosemia (transferase deficiency), biotinidase deficiency, cystic fibrosis (immunoreactive trypsin), amino acid, organic acid, and fatty acid disorders.

Prenatal screening is performed on maternal serum specimens collected in the first and second trimester for prenatal screening program. Maternal serum specimens are tested for open neural tube defects, Down syndrome, trisomy 18, and other defects.

Confirmatory testing is carried out at designated diagnostic reference laboratories that employ a variety of specialized procedures.

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Quality and Test Volume

Any laboratory performing a test must have a sufficient number of samples to process daily, so that accuracy can be achieved at an acceptable cost. For this reason, the California statutes and regulations limit the number of newborn and prenatal screening laboratories. Screening tests are carried out at five area laboratories located throughout the state and at two laboratories at Northern and Southern Kaiser Permanente Medical Group. This helps to assure that the laboratories have the experience necessary to perform the work accurately. At a previous time, when screening was carried out at a large number of clinical laboratories, many of whom had only a few samples to test in a year, approximately ten percent of the cases of phenylketonuria were not detected. Now that most states restrict testing to one or a few sites, the percentage of missed cases is less than one percent.

GDLB contracts with seven screening laboratories and with six confirmatory laboratories. The average test volume processed daily at the screening laboratories ranges from 1000 to 1200 dried-blood-spot specimens from newborns and 100 to 400 maternal serum specimens for prenatal screening.

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Current Screening Laboratories

Western Clinical Laboratory, Inc.; Roseville

GDL; Richmond

The Permanente Medical Group, Inc., Regional Laboratory; Berkeley

Allied Laboratories, Inc.; Mountain View

Fresno Community Hospital Laboratory; Fresno

Quest Laboratory; West Hills

Memorial Medical Center of Long Beach; Long Beach

Southern California Permanente Regional Endocrinology Laboratory; Carson

 Current Confirmatory Laboratories

Galactosemia Confirmatory Testing Laboratory, ARUP

Biopterin Testing Laboratory, Children's Hospital of Los Angeles

Hemoglobin Reference Laboratory, Children's Hospital of Oakland

MS/MS Disorders Confirmatory Testing Laboratory, Quest Diagnostics Inc

Biotinidase Testing Laboratory, Stanford University Hospital & Clinic Stanford

Cystic Fibrosis Testing Laboratory, Stanford University Hospital & Clinic Stanford

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Test Management

Prevention, assessment and correction are three essential elements of test management. GDL builds preventive measures that include laboratory contracts, specifications for the reagent-instrument test systems, and test protocols. For assessment, GDL performs daily review of test results, weekly proficiency testing, periodic special studies, site visits and monitoring of clinical results and interesting cases. Corrective measures include technical troubleshooting and consultation as well as the possibility of contract termination.

GDL supplies screening laboratories with identical equipment obtained through a master reagent-instrument agreement with the vendor. Potential contract laboratories need not invest their own capital in equipment, and therefore more laboratories in the private sector are able to compete for the award of contracts. Also, if one of the contract laboratories fails to continue testing, the equipment can be moved to a new laboratory.

Standard methods are promulgated by GDL for use at the contract laboratories. The standard methods include protocols for test methods, sample collection, quality control, and the reporting of results. GDL specifies the calibrators to be used and defines the dose-response relationship. GDL provides training to the testing personnel at the contract laboratories. GDL, in collaboration with the Genetic Disease Branch, promulgates the cutoff rules to be used to identify presumptive positive test results. The cutoff rules are identical at all testing sites. Test results from the contract laboratories are electronically transmitted to GDL. Quality control officers at GDL review the results for accuracy before the results are released to physicians.

Through management from the central laboratory at GDL, the State is assured of uninterrupted screening. GDL monitors potential problems that, without intervention, could lead to a delay in the reporting of results. GDL maintains inventories that can be used to supply laboratories in the event of unforeseen shortages. GDL manages the reassignment of supplies and equipment between laboratories when needed to meet urgent demands.

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Screening Laboratories

The GDL contracts that govern the screening laboratories specify the following conditions:

Financial payments

Test methodology

Turnaround time

Equipment

Calibrators and controls

Accession of specimens

Methods for reporting results

Back-up arrangements

Proficiency testing

Equipment maintenance

Specimen handling and storage

Record keeping

Standards of performance

Source of specimens

Actions for inadequate specimens, presumptive positives and repeat specimens

Space allocation

Job titles

Overload capacity, the ability to absorb the workload of another contract laboratory if needed.

Matters under direct control of each contract laboratory are:

Personnel -- hiring, salaries, assignments, training, scheduling, supervision, evaluation, continuing education, licensure or certification

Facilities -- layout, environmental quality, maintenance

Supplies -- water, consumables (but not equipment, specified reagents, calibrators, controls)

Standard laboratory practices -- safety and health, general procedures

Specimen transport -- mail or courier.

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Central Laboratory (GDL)

As the central laboratory of the test system, GDL has certain duties, which include the following specific tasks:

Review bids and award contracts

Develop, evaluate, establish and revise test methods and equipment

Write specifications for reagent-instrument test systems, and select vendors

Verify the uniformity of different lots of reagents

Maintain technical expertise, provide consultations to contract laboratories, and review test results and interesting clinical cases

Prepare, evaluate and supply calibrators and controls; determine acceptability limits

Maintain matched laboratory performance

Perform site inspections

Prepare proficiency testing samples, score weekly results obtained by the contract laboratories, direct corrective measures if needed

Perform quality control monitoring of blood collection paper used in newborn screening

Provide emergency testing

Enforce State-promulgated guidelines

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Methods of Assessment

GDL evaluates test performance at each of the contract laboratories to assure that test results reported by the different laboratories are matched.

Data Review: Test measurements (including raw data) made at the contract laboratories are telecommunicated to GDL daily. Using computerized algorithms, quality control officers examine the data before results are reported to physicians. The review includes a sampling of raw data (e.g., chromatograms), calibration curves, quality control results, performance checks, individual test values and statistical parameters. When needed, GDL staff counsel the personnel at the contract laboratories and direct corrective action. The use of a telecommunications network assures rapid turnaround time and timely corrective action. QC rules are programmed to automate the data review process and facilitate the rapid release of acceptable data.

Quality Control: Contract laboratories assay surrogate specimens at predetermined intervals. Acceptability limits are set by GDL and are the same for all laboratories. GDL directs corrective action when needed.

Performance Checks: Specified measurements are made at each of the contract laboratories to assure that instruments are functioning correctly and that reagents are satisfactory. Acceptability limits are set by GDL and are the same for all laboratories. GDL directs corrective action when needed.

Individual Test Values: Statewide limits are set for patient test results. GDL initiates an evaluation whenever results are either unusually high or low and undertakes corrective action if needed.

Statistical Parameters: A departure from an expected pattern of results in an indication for evaluation and possible corrective action. GDL examines trends, shifts, and drifts in quality control, proficiency testing and the incidence of presumptive positives.

Proficiency Testing: A proficiency test is the analysis by the contract laboratories of special samples provided by GDL. GDL fabricates the samples to be surrogates for patient specimens. The GDL samples have expected target results that are known to GDL but not to the laboratory testing persons. GDL conducts an open proficiency test weekly. Open testing is carried out in such a way that the contract laboratory knows that the samples they are analyzing are proficiency test samples. (Blind tests can also be carried out. In a blind test the specimens are submitted to the contract laboratories in such a way that the laboratories are not aware that the specimen is a surrogate sample with known target values.) Weekly scores are evaluated by GDL. When scores are unsatisfactory, GDL directs the contract laboratory to undertake corrective action. By distributing samples and scoring results every week, GDL is able to direct corrective actions on a timely basis.

Clinical Review: In collaboration with GDSP, GDL reviews clinical history to assure that test results are consistent with clinical outcome. The contract laboratories report approximately 6000 newborn screening test results daily and 3600 prenatal test results daily. Some patterns of results may appear to be unusual. These are evaluated. Results must be found to be consistent with clinical outcome.

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New Test Methods

GDL serves as the hub connecting different laboratory components of the newborn and prenatal screening programs. GDL seeks to maintain relationships with academic and commercial research laboratories, reference laboratories, prenatal diagnostic centers and regional networks. GDL staff collaborate with these other institutions on the selection and development of applicable new test methods. Methodology must meet standards of clinical efficacy, cost-effectiveness, turnaround time, reliability and test performance. Pilot projects are carried out to determine the applicability of methods to genetic testing.

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Objectives of GDL

Remain in the forefront of scientific knowledge in this rapidly developing field of clinical diagnostics in order to provide consultation to the Department on the biochemical and molecular characteristics of genetic diseases.

Develop and apply laboratory methods for identifying, confirming and monitoring genetic diseases in humans.

Maintain the central State genetics laboratory through which the Department meets its mandated responsibilities to test the population for preventable genetic diseases which cause disabilities, mental retardation and death.

Establish and administer a statewide network of non-governmental laboratories that provide the public with screening and confirmatory testing for genetic diseases under contract to the Department.

Perform continuous monitoring and evaluation of the quality of laboratory services in genetics which are provided to the public by local clinical and public health laboratories.

Train laboratory personnel in the accurate performance of tests for genetic diseases.

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Last modified on: 11/13/2013 5:11 PM