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CLIA & GCLP standards for clinical trial support

Posted on: June 25, 2020

Providing laboratory support testing for a clinical trial by meeting trial sponsors’ growing needs, all while meeting stringent regulatory requirements? It’s possible.

Flow cytometry-based assays serve as valuable tools for various aspects of the drug development process ranging from target discovery and characterization to evaluation of responses in a clinical setting [1]. Clinical core laboratories are becoming more and more of an integral component of modern research and clinical trial support. The possibility for laboratories being able to support clinical trial testing and maintain GCLP standards, all while concurrently meeting the stringent regulatory requirements required by CLIA (Clinical Laboratory Improvement Amendment of 1988), is becoming a reality.

 

What are GCLP (Good Clinical Laboratory Practice) standards?

The GCLP (Good Clinical Laboratory Practice) standards were developed to bring together multiple guidance and regulatory information as they apply to clinical research. These standards fill a void of a single GCLP reference for global clinical research laboratories with regard to laboratories that support clinical trials. Before reporting study-participant results, each laboratory that introduces a non-waived (a CLIA designation) test such as a lymphocyte subset enumeration, must demonstrate performance specifications comparable to those established by the manufacturer (as found in manufacturer’s publications such as user manuals or package inserts) to ensure the assay is performing optimally within the proposed testing environment [2]. 

 

What is CLIA accreditation?

Stringent regulations require these laboratories to develop and meet requirements spanning a number of categories. Laboratories holding CLIA accreditation are responsible for maintaining requirements that include regulations governing standards that include:

CLIA regulations

  • Standards for Organization and Personnel
  • Standards for Laboratory Equipment
  • Standards for Test Facility Operation
  • Document Control Plan
  • Quality Control Program
  • Standards for Verification of Performance Specifications
  • Standards for Records and Reports
  • Standards for Physical Facilities
  • Standards for Specimen Transport and Management
  • Standards for Personnel Safety
  • Standards for Quality Management

 

How to meet CLIA & GCLP standards for clinical trial support

There is a growing market need for clinical trial support. Meeting all of these critical CLIA regulated requirements, alongside the GCLP standards, is highly desirable in a laboratory providing testing support for clinical trials. Contract Research Organizations (CROs) that can provide routine laboratory testing for clinical trial support only adds to their appeal for potential customers. 

Being able to select a niche CRO that specializes in quality flow cytometry while providing the highest level of control to minimize variability and enhance data quality should be a top priority to an organization with clinical trial needs. Having the benefit of receiving the most comprehensive menu of scalable solutions, covering the spectrum from large-scale clinical trial testing to custom assay development, instills that sense of clinical confidence companies is looking for. 

Selecting a company that can support your biomarker efforts and manages parallel companion diagnostic development from concept to clinic is a utopia. It is important for contract companies to develop new testing services to proactively address evolving needs [2].

 

Who requires CLIA certification?

Laboratories in the United States that perform tests on human specimens for the purpose of providing information for the diagnosis, prevention, or treatment of a disease or for the assessment of the health of an individual are regulated by CLIA and are required by the Centers for Medicare & Medicaid Services (CMS) to be CLIA certified through a process that ensures that certain quality control assurances and requirements are in place. 

CLIA, and its associated regulations, were put in place to protect patients from harm resulting from inaccurate laboratory testing [3]. If laboratories report individual results that could be used for clinical decision making, CMS has interpreted the regulations to mean that those laboratories must be CLIA certified [3] CLIA certification assures the clinical trial customer they are receiving regulated, quality laboratory testing services.

Today's laboratories are charged with providing harmonized clinical diagnostic testing and a consolidated database for clinical trial sponsors. It is imperative to continue to evolve against the backdrop of an increasingly complex clinical trial environment. Today the industry balances the demands of complicated laboratory testing requirements, budget restrictions, and geographical challenges while maintaining a constant focus on the deliverables sponsors require [4].

Central laboratories

Current central laboratories maintain strict CLIA regulations while streamlining clinical trial diagnostic testing. CLIA licensed lab necessity is growing, in part, from the need to efficiently and accurately process high volumes of specimens as clinical trials grew larger and more global in scope. Laboratory service providers now turn their attention to standardizing collection kits and consolidating laboratory results into a single database, thereby, enhancing consistency and reducing costs [4].

A supporting, central laboratory, will need to combine the rapid response and diagnosis offered by select tests with its own ability to find and measure disease in minutes and early stages. The result will be greater speed and diagnostic certainty for specific patients and their current clinical state. This style of laboratory practice evolves out of necessity, as regulatory agencies govern many change pathways with their patient safety requirements and, secondarily, oversee data, and study integrity. Support labs must strike a delicate balance of meeting trial sponsors’ growing demands while upholding regulatory standards and requirements [4].

 

How Flow Metric can help

We have a vision to provide a supporting, central-type laboratory that can provide the same service to a small, niche CRO in the same way that a larger central laboratory does. The central lab industry has evolved in a number of directions due to several influencing factors, including global trial requirements, analytical complexity, and broad testing requirements. At the core of the many sponsor requirements is global consistency of service, with support laboratories required to provide validated, consistent, and dependable test results regardless of whether the sample was collected from across the country or right in the laboratories local community [4]. 

TBNK testing

TBNK testing performed on the BD FACSCanto II, under the validated BD Biosciences single platform assay, has proven to be a reliable, reproducible test that can provide valuable data for select studies. TBNK testing reliability has been confirmed by comparison testing alongside the BD FACSLyric. For equivalency between methods, data (n = 362) were analyzed with Deming regression for absolute count and percentage of lymphocytes. 

Results gave R2 ≥0.98, with slope values ≥0.96, and slope ranges between 0.90-1.05. The percent (%) bias values were <10% for T- and NK cells and <15% for B- cells. The between-site (n = 4) total precision was tested for 5 days (2 runs/day) and gave %coefficient of variation below 10% for absolute cell counts. The stability claims were confirmed (n = 186) using the two reagents associated with the test.  the BD FACSLyric and the BD FACSCanto II systems generated comparable measurements of T-, B-, and NK-cells using BD Multitest assays [5]. FlowMetric Diagnostics performs this test on a qualified BD FACSCanto II flow cytometer.

An accredited, regulated, support clinical laboratory can provide testing support to clinical trial services for virtually all of the well-known biopharmaceutical companies that are diligently working towards successful key testing grounds for determining the effectiveness and safety of new treatments and drugs for cancer and other diseases. 

 FlowMetric specializes in delivering high-quality laboratory testing services designed to optimize clinical trial outcomes for our customers. FlowMetric Diagnostics can provide regulated, high-quality clinical testing to support this endeavor. 

 

Learn More

Looking for a niche, quality CRO that can provide you with CLIA licensed clinical testing support such as lymphocyte subset enumeration? Contact us to discuss your clinical testing needs for your clinical trial platform. We can assist you in finding the ideal “one-stop-shop” which can prove to be an arduous task for many promising clinical-stage, biopharmaceutical companies looking to gain success for their investigational product candidates. 

While FlowMetric provides not only a niche contract research organization that fulfills all regulatory requirements and provides high-quality support of clinical trials, we can now also provide support clinical laboratory testing with the addition of a CLIA certified laboratory on site.

 

1. J Immunol Methods. 2011 Jan 5;363(2):120-34. doi: 10.1016/j.jim.2010.09.036. Epub 2010 Oct 11. Recommendations for the validation of flow cytometric testing during drug development: II assays. O'Hara DM1, Xu Y, Liang Z, Reddy MP, Wu DY, Litwin V.

https://www.ncbi.nlm.nih.gov/pubmed/20946898/

 

2. Guidelines on Good Clinical Laboratory Practice. Bridging Operations between Research and Clinical Research Laboratories. J. Ezzelle, I. R. Rodriguez-Chavez, J. M. Darden, M. Stirewalt, N. Kunwar, R. Hitchcock, T. Walter, and M. P. D’Souza.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213906/

 

3. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington (DC): National Academies Press (US); 2018 Jul 10. 6, Reshaping the Legal and Regulatory Landscape to Support Return of Individual Research Results.

National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Sciences Policy; Committee on the Return of Individual-Specific Research Results Generated in Research Laboratories

https://www.ncbi.nlm.nih.gov/books/NBK525078/

 

4. Inside the Central Laboratory Model For Clinical Trials Diagnostic Testing. Contributed by:

Mark Engelhart, Chief Commercial Officer and Jerry Boxall, Managing Director, ACM Europe and Asia, ACM Global Laboratories.https://www.pharmavoice.com/article/2016-06-diagnostic-testing/

 

5. Accurate and reproducible enumeration of T-, B-, and NK lymphocytes using the BD FACSLyric 10-color system: A multisite clinical evaluation. Omana-Zapata, Mutschmann, Schmitz J, Gibson S, Judge K, Aruda Indig M, Lu B1, Taufman D, Sanfilippo AM, Shallenberger W, Graminske S, McLean R, Hsen RI, d'Empaire N, Dean K, O'Gorman M.

PLoS One. 2019 Jan 28;14(1):e0211207. doi: 10.1371/journal.pone.0211207. eCollection 2019.

https://www.ncbi.nlm.nih.gov/pubmed/30689658

 

1-3 Authored by: Kathleen Schroeder

 

 

Clinical Laboratory Manager / Technical Supervisor, FlowMetric Diagnostics. 

Prior to integrating into the GxP environment, Kathleen spent 30+ years in the clinical laboratory testing environment under CLIA/CAP regulations. After completing college, Kathleen worked as Medical Technologist in a Hematology laboratory that specialized in testing for leukemia patients and obtained expertise in diagnostic flow cytometry and gained experience monitoring patients enrolled in clinical trials. After 20+ years specializing in diagnostic flow cytometry for Leukemia and Lymphomas for the Oncology team and Bone Marrow Transplant Physicians, Kathleen moved to a large CRO\GMP organization testing manufactured cells for clinical trials under GLP/GMP regulations, first in the role of Study Director / Technical Reviewer and then Manager of Flow Cytometry for the Quality Control Testing group. After joining the FlowMetric team as Clinical Laboratory Manager and Technical Supervisor for FlowMetric Diagnostics, Kathleen has become a highly regarded SME for the company’s clinical flow cytometry.

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