Overview of international PCR standardization efforts.

N u m e r o u s variables are associated with PCR, and modifications in technique exist from laboratory to laboratory for any one type of PCR format. Consequently, variation in results among different laboratories can easily occur when PCR is used in experiments or diagnostic assays. In addition, the possibility of false-positive results attributable to contamination and false-negative reactions caused by enzyme inhibition are potential problems for PCR use in clinical diagnostic laboratories. (1~ Therefore, standardized PCR procedures are needed to ensure reliable results. Standardized procedures can help to avoid confusion, mistakes, and complications, and they encourage efficiency, reproducibility, and quality control. The objective of this overview is to describe a number of efforts presently under way by national and international organizations to standardize PCR procedures. The overview does not tabulate or compare specific requirements or recommendations from different standards organizations, because most of the PCR standards are presently still in development and, consequently, are unavailable to the public. What is a laboratory standard? There are different types of standards and different definitions of standards, depending on the organization that established the definition. The two general types of standards that are described in this overview are written laboratory standards (standardized procedures) and laboratory standard solutions or reagents. The latter type of standard is well known and does not require clarification. A written laboratory standard is essentially a written description of a particular laboratory procedure on which a group of individuals agreed. If a standard for a particular laboratory procedure has been developed properly and has been well written, then individuals working in different laboratories should be able to use the standardized procedure and obtain comparable results. There are different types of written laboratory standards, depending on the organization that developed them and the purpose of the standards. They range from voluntary consensus standards to mandatory government regulatory standards. Consensus standards are generally prepared by standards organization committees of representatives, for example, from industry, universities, and government. Some consensus standards are only a set of recommendations that offer guidance but do not establish a fixed procedure, that is, "guidelines" or "guides." Others are definitive procedures that produce test results such as "test methods." Government regulatory standards are usually developed by government employees with government and nongovernment input obtained through a formal notification and response process. In some cases, government agencies adopt voluntary consensus standards and convert them to mandatory regulatory standards. Most of the PCR written standards discussed in this overview are voluntary consensus guidelines. Readers should be made aware of the date of completion of this overview (December 1993), because the pace of PCR technology advancement and standards development is so rapid. This overview represents my own viewpoints and not the views, opinions, or endorsements of the U.S. Food and Drug Administration, the U.S. Public Health Service, or the U.S. Department of Health and Human Services. MULTICENTER COLLABORATIVE TRIALS