The increasing complexity of large molecule development, along with the rise of personalized medicine, is driving more need for sponsors to place their large molecule projects with a CLIA-certified laboratory. Facilities that operate under CLIA have been found to adhere to established regulations for laboratory testing quality and for reporting of patient-specific results. There are additional benefits for the sponsor if the lab is also accredited by an agency such as COLA or CAP. Navigating this compliance landscape, with its many acronyms, can sometimes be confusing, so we’ve set out to bring some clarity to the topic.
The Agencies Responsible for CLIA
Clinical Laboratory Improvement Amendments (CLIA) consist of a set of federal standards that are overseen by three federal agencies: the U.S. Food and Drug Administration (FDA), the Centers for Medicare and Medicaid Services (CMS), and the Centers for Disease Control and Prevention (CDC). Any testing performed in the U.S. that yields results used to direct patient care must comply with CLIA standards. More specifically, if the results of your assay will be used to determine patient eligibility for a clinical trial, assign treatment to a specific patient, or assess individual treatment outcomes, then the test must be performed in a CLIA lab setting.
The FDA categorizes tests as waived, moderate, or high complexity based on seven categorization criteria which determine their applicable CLIA requirements. In general, the more complex the test, the more stringent the requirements. BioAgilytix, for example, is able to perform high complexity testing, which requires advanced education, training, and experience for both testing personnel and management.
The Centers for Medicare & Medicaid Services (CMS) enforces CLIA compliance. This agency ensures basic CLIA requirements are met within a laboratory, such as having an appropriate facility site, qualified lab director, and adequate description of assays being performed. Once confirmed, the CMS may issue a CLIA certificate in line with the complexity level of tests. The process of CLIA certification and accreditation is discussed in more detail in the section below.
Finally, the CDC manages the Clinical Laboratory Improvement Advisory Committee (CLIAC), which supports the CLIA program through the development of laboratory standards and guidelines, quality improvement studies, proficiency testing practices monitoring, and more.
The CLIA Certification & Accreditation Process
There are several pathways for a laboratory to obtain CLIA certification. The lab may apply for a Certificate of Waiver for “simple laboratory examinations and procedures that have an insignificant risk of an erroneous result” as defined by CLIA. If a lab performs more complex tests, they may submit an application for a Certificate of Registration. The application indicates whether the lab would like to pursue a Certificate of Compliance or a Certificate of Accreditation. Once CMS confirms basic requirements are met as described above, the lab may begin conducting clinical testing under CLIA for a specified time before the compliance or accreditation survey takes place.
Pursuit of a Certificate of Accreditation requires a lab to go above addressing the basic elements of CLIA compliance listed in Part 493 of the Federal Register, adding more stringent expectations of the lab’s quality system. The CMS has approved seven accreditation agencies with deeming authority, with the College of American Pathologists (CAP) and the Commission on Office Laboratory Accreditation (COLA) being two of the largest.
What Are the Benefits of COLA or CAP Accreditation?
If you work with a COLA- or CAP-accredited laboratory, you can be assured that they use the most comprehensive, scientifically-endorsed laboratory standards to meet or exceed CLIA requirements. The accrediting agency has evaluated the lab to ensure that its test results are of the highest quality; that assays are developed and implemented to guide accurate decision-making; and to confirm the laboratory is in compliance with CLIA standards, with the agency performing active monitoring to ensure it remains that way over time. This saves you from the potential costly loss of time and resources that could be incurred working with a lab found to be in non-compliance with CLIA, which could result in the forfeiture of their CLIA licensure and nullify the compliance of your results.
COLA accreditation is approved for core lab specialties including immunology, chemistry, microbiology, blood bank, urinalysis, and hematology. A COLA surveyor conducts an on-site inspection to issue an accreditation certificate that is valid for two years. COLA then follows the lab’s performance on a continual basis, including monitoring proficiency testing, to confirm compliance with CLIA and COLA quality requirements while also ensuring that all appropriate state licensure standards are upheld.
Specifically for CAP accreditation, detailed checklists must be completed for regulatory adherence, including both general and specialty-specific guidelines. Inspections are conducted by qualified CAP inspectors who are peers and practicing laboratory professionals from other CAP-accredited labs in that specialty. Inspections are comprised of an onsite laboratory inspection every two years and a self-inspection every other year. The Laboratory Director or Medical Director must also be qualified and hold the certificates relevant to the specific categories of testing performed by the laboratory. In general, CAP has more specialty-specific quality standards than other accreditation organizations.
While the requirements across all organizations with accreditation authority differ slightly, they all represent adherence to a higher standard of quality than with CLIA compliance alone.
BioAgilytix for Large Molecule Drug Development Under CLIA
When it comes to ensuring the safety and efficacy of your biologic candidates, there is no room for error. Our U.S. labs are CLIA-certified and we chose to request our Certificates of Accreditation to give our customers the utmost confidence that their testing will stand up to strict regulatory scrutiny.
With our CLIA-certified, CAP-accredited Boston laboratory and CLIA-certified, COLA-accredited lab in Durham, NC, BioAgilytix upholds the highest quality standards and necessary regulatory compliance to support sponsors’ studies that use patient-specific data. We invite you to speak to our scientists if you have further regulatory questions or a study you would like to discuss.