1. (a) An Applicant laboratory seeking approval from the Department to perform prenatal cytogenomic and/or cytogenetic tests on amniotic fluid and/or chorionic villus samples from State-approved Comprehensive or Satellite Prenatal Diagnosis Centers for California Prenatal Screening Program referrals, shall submit an application to the Department by mail. Each application shall contain the following information:

   1. (1) A Laboratory Director Statement shall:

      1. (A) Affirm the Director of the Applicant laboratory is a physician or holds a doctorate degree, has training and experience as a Clinical Cytogeneticist directing a cytogenetics laboratory, and is certified by the American Board of Medical Genetics and Genomics or Canadian College of Medical Genetics in Clinical Cytogenetics.
      2. (B) State the name, address, telephone, and facsimile number of the Applicant laboratory.
      3. (C) Include the Clinical Laboratory Improvement Amendments (CLIA) certificate number and the California Laboratory License number of the Applicant laboratory.
      4. (D) Include the Laboratory Director's signature, full name, and date of signing.
      5. (E) Include the California License Number of the Laboratory Director, licensed in California as a Clinical Cytogeneticist.
      6. (F) Affirm the Applicant laboratory has the capacity to meet the annual test volume requirements in the Prenatal Diagnosis Center Standards and Definitions 2022, incorporated by reference.
      7. (G) Affirm the Applicant laboratory has participated in, and successfully completed, the State of California-provided or approved laboratory inspection proficiency testing and/quality control program.

      8. (H) Affirm the Applicant laboratory has resources for the determination of alpha fetoprotein and acetylcholinesterase concentrations in amniotic fluid for diagnosis of neural tube defects. If resources are to be provided by another facility, an Alpha Fetoprotein/Acetylcholinesterase Concentration Determination Statement must be attached and include the following information:

         1. 1. Name of the Applicant laboratory.
         2. 2. Affirm Applicant laboratory has access to resources for the determination of alpha fetoprotein and acetylcholinesterase concentrations in amniotic fluid for diagnosis of neural tube defects.
         3. 3. Name of the laboratory providing these resources.
         4. 4. CLIA certificate number of the laboratory providing these resources.
         5. 5. California Laboratory License number of the laboratory providing these resources.
         6. 6. Address, telephone, and facsimile number of the laboratory providing these resources.
         7. 7. Name, signature, and date of signing by the Laboratory Director of the laboratory providing these resources.
         8. 8. California License number of the Laboratory Director of the laboratory providing these resources.
      9. (I) For chorionic villus sampling laboratory Applicants, affirm the Applicant laboratory has the capacity for cultures to include tissue culture of villus core.

   2. (2) Evidence of quality assurance and quality control policies enacted for the implementation of each prenatal cytogenetic test (karyotyping of amniotic fluid or chorionic villi cells) the Applicant laboratory is applying to be authorized to perform on prenatal specimens from California Prenatal Screening Program referrals. Applicant Laboratories must establish a consultative affiliation with a laboratory that is approved by the Department to perform the relevant cytogenetic test on prenatal specimens from California Prenatal Screening Program referrals, and is financially independent of the Applicant laboratory, to split and proficiently analyze consecutive samples for clinical diagnosis, as outlined in the Prenatal Diagnosis Center Standards and Definitions 2022, incorporated by reference. Evidence of quality assurance and quality control policies must include:

      1. (A) An affirmation that the Applicant laboratory has performed the tests in accordance with the requirements of the Prenatal Diagnosis Center Standards and Definitions 2022, incorporated by reference, has enacted quality assurance/quality control policies for the ongoing monitoring of prenatal testing, and acknowledges the documentation submitted is open to public inspection.
      2. (B) The name of the Applicant laboratory.
      3. (C) The Applicant laboratory's CLIA certificate number.
      4. (D) The Applicant laboratory's California Laboratory License number.
      5. (E) The name, signature, and date of signing by the Director of the Applicant laboratory.
      6. (F) The name of the laboratory approved by the Department to perform cytogenetic tests on prenatal specimens from California Prenatal Screening Program referrals and with which the Applicant laboratory established a consultative affiliation.
      7. (G) The CLIA certificate number of the laboratory with which the Applicant laboratory established a consultative affiliation.
      8. (H) The California Laboratory License number of the laboratory with which the Applicant laboratory established a consultative affiliation.
      9. (I) The name of the Laboratory Director of the laboratory with which the Applicant laboratory established a consultative affiliation.
      10. (J) The signature of the Laboratory Director of the laboratory with which the Applicant laboratory established a consultative affiliation.
      11. (K) The date signed by the Laboratory Director of the laboratory with which the Applicant laboratory established a consultative affiliation.
      12. (L) A comparison of the test results of samples analyzed by both the Applicant and the consultative affiliate laboratories, itemizing the cases.

   3. (3) Evidence that the Applicant laboratory has access to cytogenomic testing (prenatal microarray testing) with the enactment of appropriate quality assurance and quality control policies. The evidence must include:

      1. (A) For Applicant laboratories applying to be authorized to perform prenatal microarray testing and analysis, an application that includes:

         1. 1. An affirmation of the accuracy and completeness of the information provided in the application and the validation study, and an acknowledgement that the documentation submitted is a public document open to public inspection.
         2. 2. The name of the Applicant laboratory.
         3. 3. The address of the Applicant laboratory.
         4. 4. The Applicant laboratory's CLIA certificate number.
         5. 5. The Applicant laboratory's California Laboratory License number.
         6. 6. The name, signature, and date of signing by the Clinical Cytogenetics Laboratory Director/Technical Supervisor of the Applicant laboratory.
         7. 7. The Clinical Cytogenetics Laboratory Director's/Technical Supervisor's California License Number.
         8. 8. A description of the platform, including vendor, type of array, and the number of probes.
         9. 9. The criteria for designating copy number changes, including minimum number of affected probes and/or minimum aberration size.
         10. 10. The specimen type(s) to be tested (cultured/uncultured).
         11. 11. The criteria to accept and reject individual specimens.
         12. 12. Quality assurance (QA) parameters monitored to ensure reliability of data.
         13. 13. Details of the types of information reported (with reportable levels, such as size cut-offs) for copy number changes; absence of heterozygosity (loss of heterozygosity, regions of homozygosity, and long contiguous stretches of homozygosity); and mosaicism.
         14. 14. A summary of the criteria to classify aberrations as clinically relevant, benign, or of unknown clinical relevance.
         15. 15. Details on target turnaround times (TAT) and actual TAT on prenatal samples.
         16. 16. A statement as to when abnormal results are confirmed and by what method (a statement of Standard Operating Procedure).
         17. 17. A statement as to when testing for maternal cell or sibling contamination is performed and by what method (a statement of Standard Operating Procedure).
         18. 18. A narrative statement describing validation studies that includes specimen types and clinical features for validation specimens.
         19. 19. Validation and precision studies that demonstrate the proficient analysis of previously characterized samples by microarray, as outlined in the Prenatal Diagnosis Center Standards and Definitions 2022, incorporated by reference.
         20. 20. A copy of relevant contents from the laboratory's Standard Operating Procedure specifying criteria to classify aberrations as clinically relevant, benign, or of unknown clinical relevance.
         21. 21. Sample reports for abnormal finding/s, and variant/s of unknown significance.
         22. 22. Evidence of participation in an external proficiency testing program for microarray (CAP Surveys); or

      2. (B) For Applicant laboratories applying to perform only cytogenetic tests, a Prenatal Microarray Statement that includes:

         1. 1. The name of the Applicant laboratory.
         2. 2. Affirmation the Applicant laboratory has access to prenatal microarray testing.
         3. 3. The name of the laboratory approved by the Department to perform cytogenomic tests on prenatal specimens from California Prenatal Screening Program referrals and will provide this testing.
         4. 4. The CLIA certificate number of the laboratory providing this testing.
         5. 5. The California Laboratory License number of the laboratory providing this testing.
         6. 6. The address, telephone and facsimile numbers of the laboratory providing this testing.
         7. 7. The name, signature, and date of signing by the Laboratory Director of the laboratory providing this testing.
         8. 8. The California License number of the Laboratory Director of the laboratory providing this testing.
   4. (4) A copy of the Applicant laboratory's CLIA certificate.
   5. (5) A copy of the Applicant laboratory's California Laboratory License.
   6. (6) If an Applicant laboratory holds a license or permit as a clinical laboratory, with approval to perform prenatal cytogenomic and/or cytogenetic test/s, issued by a state in which the clinical laboratory standards, including standards for validation studies for prenatal cytogenomic and/or cytogenetic test approval, are equal to or exceed the Department's standards, as determined by the Department, the Applicant laboratory may submit these validation studies to the Department as evidence of meeting the validation requirements of this section.
2. (b) A laboratory that is approved by the Department to perform a prenatal cytogenetic test on amniotic fluid and/or chorionic villus samples from State-approved Comprehensive or Satellite Prenatal Diagnosis Centers for California Prenatal Screening Program referrals, and is seeking approval to perform an additional prenatal cytogenetic or cytogenomic test(s), shall submit an application to the Department that contains the information required in subsection (a) pertaining to the test(s).

Note: Authority cited: Sections 124977, 124980, 124996, 125000, 125065 and 131200, Health and Safety Code. Reference: Sections 124975, 124980, 124990, 125000, 125001, 125050, 125055 and 125065, Health and Safety Code.

History

1. New section filed 12-20-2019 as an emergency; operative 12-20-2019 pursuant to Health and Safety Code section 124977(d). Submitted to OAL for filing and printing only pursuant to Health and Safety Code section 124977(d) (Register 2019, No. 51). Pursuant to Health and Safety Code section 124977(d)(2), these regulations shall remain in effect until revised or repealed by the department.

2. Statement of Compliance pursuant to Health and Safety Code section 124977(d)(1) as to 12-20-2019 order filed 12-11-2020. Exempt from OAL review pursuant to Health and Safety Code section 124977(d)(2). Submitted to OAL for filing and printing only pursuant to Government Code section 11343.8 (Register 2020, No. 50).

3. Amendment of subsections (a)(2)-(a)(2)(A) and (a)(3)(A)19. filed 7-18-2022 as an emergency; operative 7-18-2022 pursuant to Health and Safety Code section 124977(d). Submitted to OAL for filing and printing only pursuant to Health and Safety Code section 124977(d) (Register 2022, No. 29). Pursuant to Health and Safety Code section 124977(d)(2), these regulations shall remain in effect until revised or repealed by the department.

4. Amendment of subsections (a)(2)-(a)(2)(A) and (a)(3)(A)19. refiled 9-9-2022 as an emergency; operative 9-9-2022 pursuant to Health and Safety Code section 124977(d) (Register 2022, No. 36). Pursuant to Health and Safety Code section 124977(d)(2), these regulations shall remain in effect until revised or repealed by the department.