Available at, CDC. When possible, laboratories should establish their own reference ranges by evaluating an appropriate number of samples to verify the reference ranges provided in literature or textbooks or by manufacturers. No professional practice guideline specifically recommends informed consent for biochemical genetic tests. Accessed February 2, 2012. Silver Spring, MD: Food and Drug Administration; 2007. Laboratories must comply with applicable requirements and follow professional practice guidelines in establishing policies and procedures to ensure confidentiality of patient information, including information and test results on biochemical genetic testing and newborn screening. The laboratory director is responsible for ensuring that the laboratory policies and procedures for specimen retention comply with applicable federal, state, and local requirements (including laboratory accreditation requirements, if applicable) and are consistent with the laboratory quality assurance and quality assessment activities. J Am Med Inform Assoc 2010;17:13–8. Available at, National Newborn Screening & Genetics Resource Center. However, when informed consent for patient testing is recommended or required by law or other applicable requirements as a method for documenting the process and outcome of informed decision making, laboratories should ensure that certain practices are followed. Collaborative efforts by many federal agencies, advisory groups, and the private sector have led to the development of standards and mechanisms for electronic reporting of newborn screening results (36–38). Available at, De Jesús VR, Lim TH, Meredith NK, et al. Publication no. Although the recommended practices are primarily intended for laboratories performing biochemical genetic testing and newborn screening, many recommendations reflect general good laboratory practices for ensuring the quality of laboratory services. Both disease prevalence and sample characteristics might influence sample availability, thus the availability of samples and reference materials also should be considered. Establish or verify test performance specifications and determine quality control parameters for the test. Written procedures addressing specimen-related issues, such as the preferred and necessary specimens and the timing of specimen collection, should be consistently applied. Clinical and Laboratory Standards Institute. Personnel who perform biochemical genetic testing or newborn screening must meet these requirements. Publication no. The calibration and control procedures also must be determined based on each test's performance specifications. Clinical consultants for biochemical genetic testing should have any one of the following additional sets of qualifications, which are more specific than those required by CLIA: CLIA regulations require clinical consultants for high-complexity testing to be responsible for providing consultation to laboratory clients regarding the appropriateness of the testing ordered and the interpretation of test results (42 CFR §493.1457) (13). Newborn screening test reports must comply with the CLIA general test report requirements (42 CFR §493.1291) and applicable state requirements. Therrell BL, Hannon WH, Pass KA, et al. Clinical and Laboratory Standards Institute. Evaluation of precision performance of quantitative measurement methods; approved guideline, 2nd ed. To help ensure the quality of laboratory testing, CDC collaborated with the Centers for Medicare & Medicaid Services, the Food and Drug Administration, the Health Resources and Services Administration, and the National Institutes of Health to develop guidelines for laboratories to meet CLIA requirements and apply additional quality assurance measures for these areas of genetic testing. CDC has collaborated with the Centers for Medicare & Medicaid Services (CMS), the Food and Drug Administration (FDA), and other federal agencies; state programs; professional organizations; standard-setting institutions; and federal advisory committees to promote the quality of genetic testing and provide guidance for appropriate use of genetic tests in clinical and public health practices. For each quantitative test, the laboratory is responsible for determining the ability of the test method to produce accurate results. 263a) that amended the Clinical Laboratory Improvement Act of 1967 and required HHS to establish regulations to ensure the quality and reliability of laboratory testing on human specimens for disease diagnosis, prevention or treatment, or health assessment purposes (12). These documents compared existing CLIA regulations with other relevant federal requirements, state regulations, accreditation standards, professional guidelines, and other voluntary national and international standards and guidelines. Public Health Informatics Institute. For example, the National Library of Medicine (NLM) and Health Resources and Services Administration (HRSA) have developed guidelines for standardized terminology, coding, and electronic messaging for ordering newborn screening tests and reporting test results to facilitate complete and accurate data collection, prompt results delivery and communication, and improved patient management (37,38). Publication no. app (1972). Inherited metabolic diseases, often referred to as inborn errors of metabolism, comprise a large class of genetic diseases involving disorders of metabolism; collectively, these diseases have an incidence of at least one in 1,500 persons in the United States (1). Management and quality assurance in the biochemical genetics laboratory. Other means of assessing and correcting unacceptable control values have failed to identify and correct the problem. Sheffield, UK: ERNDIM. Available at, Public Health Informatics Institute. Interim report on biochemical genetic testing in Europe: deficits and needs and EQA. These laboratories may be accredited by a deemed-status accreditation program approved by CMS to meet the CLIA certification requirements (13). Arch Pathol Lab Med 2003;127:71–6. Available at, Cowan TM, Strovel ET. CLIA regulations require laboratories that perform nonwaived testing to develop and follow written policies and procedures for specimen submission and handling, specimen referral, and test requests (42 CFR §493.1241 and §1242) (13). CLIA requires laboratories to establish and follow written policies and procedures for patient preparation, specimen collection, specimen labeling (including patient name or unique patient identifier and, when appropriate, specimen source), specimen storage and preservation, conditions for specimen transportation, specimen processing, specimen acceptability and rejection, and referral of specimens to another laboratory (42 CFR §493.1242) (13). Although samples might be available from various sources, such as tested patient specimens, reference materials, proficiency testing materials, and control materials, laboratories should consider using samples that have the same dried blood spot matrix as that used for specimen collection from newborns (72). Silver Spring, MD: Food and Drug Administration, 2011. Additional state requirements also might be applicable to newborn screening laboratories. External proficiency testing programmes in laboratory diagnoses of inherited metabolic disorders. Laboratories should consider these factors and define test performance specifications and limitations based on the samples that are available and included in the performance establishment. For each biochemical genetic test, the following information should be provided to facilitate appropriate test selection and requests, specimen collection and handling, and submission of patient specimens together with relevant information to the laboratory: Laboratories should review the biochemical genetic tests they perform and the procedures they use to provide and update the recommended test information. Genet Med 2006;8(Suppl 1):1S–252S. 2. Additional specimens might be needed when testing unstable analytes to verify that the initial specimen quality was not compromised. Sources: Raghuveer TS, Garg U, Graf WD. Organized proficiency testing programs do not exist for many tests performed for inherited metabolic diseases, including biochemical genetic tests and, occasionally, new tests for newborn screening. Ann Acad Med Singapore 2006;35:688–93. Patient specimens should be retained until after the final reporting of results for quality assurance and any need for additional testing of the same specimen, with adequate provisions for specimen stability.