Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Quality Assurance and Standardization of Cell-Free DNA-Based Prenatal Testing Laboratory Procedures
Cell-Free DNA-Based Prenatal Testing as a Genetic Test in Laboratories
Cell-free DNA-based prenatal testing is a screening test that estimates the risk of fetal aneuploidy (trisomy 21, 18, and 13) by analyzing cell-free DNA (cfDNA) circulating in the maternal plasma . The requirements for cfDNA tests are similar as for other screening and diagnostic tests in the medical domain . This includes all steps from blood collection, transport and storage to DNA extraction and analysis, and interpretation of results .
Standardization
Harmonization of procedures is needed to obtain reproducible and comparable results and minimize the risk of individual deviations and unexpected events. The term “standardization” refers to “standards.” Standards are a published set of minimum requirements for the execution of processes, designed for harmonization and to ensure safety . They are developed, written, and subsumed by experts representing all relevant parties. As standards are very often international, referral to national regulations is not made. A list of harmonized standards used to demonstrate compliance with relevant EU legislations has been published at http://ec.europa.eu/growth/single-market/european-standards/harmonised-standards_en .
ISO 15189
ISO 15189 is an international standard that specifies the quality management system requirements particular to medical laboratories. The standard is provided by the International Organization for Standardization and covers all steps relevant for laboratory tests done to obtain information about the health of a patient in relation to diagnosis, treatment, or prevention of disease.
Laboratories that implement a quality management system according to ISO 15189 must fulfill management as well as technical requirements. Management requirements include, for instance, specifications for personnel, facilities, and equipment. Technical requirements include preanalytical steps, analytical procedures, and postanalytical steps. Furthermore, ISO 15189 identifies the needs and expectations of customers. Through corrective and preventive actions, it focuses on continuous quality improvement and addresses prevention of errors and nonconformities. Some of the most important parts of ISO 15189 are discussed later.
Documents, Document Control, and Documentation
Written “standard operating procedures” (SOP) have to be in place and accessible for each staff member for their respective field. They have to be updated or reconfirmed at agreed points in time (“lifecycle” check; “document control”). Laboratories have to guarantee that the content of the SOP is correct during their development, implementation, and revision.
All working steps, from sample to report, must be documented.
Internal Audits
A laboratory is required to perform internal audits in each section at least once a year. An audit aims at controlling compliance to the ISO guidelines and to the specified procedures, and at providing information about eventual actions needed to improve processes and quality.
Validation
The validation process ensures that the results a laboratory issues are compared to a “standard” and are thus trustworthy. A framework for validation of clinical molecular genetic tests has been described by Mattocks et al. . There are different possibilities for validating a method/process. The most common ways are to compare the results with an already validated method, to perform a cross-validation of results with another laboratory or reference institute, and to participate in an external quality assessment scheme ( Chapter 11 ).
Validation studies should comprise all stages of a method or process and should especially focus on critical steps. In cfDNA-based testing preanalytical steps, which are operator dependent, and evaluation of results with bioinformatics programs, are part of the validation process.
Qualification
Almost all methods in laboratories require special instruments. These instruments must be qualified, which means that their functioning has been proven.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here