For accredited biobanks, a path to CLIA equivalence

Charna Albert

October 2019—The requirement revisions in the new edition of the Biorepository Accreditation Program checklist, published last month, are aimed at accommodating a growing overlap between clinical diagnostic activity and biomedical research. And effective with the release of the 2019 edition, biorepositories accredited by the CAP will be inspected every two years instead of three.

The CAP’s decision to make CAP-accredited biobanks more consistent with CLIA was the main driver of the checklist revisions.

“As the research sphere and clinical sphere are overlapping more and more,” says Philip Branton, MD, consulting pathologist to the Biorepositories and Biospecimen Research Branch of the National Cancer Institute, “it’s become evident that a lot of what even five years ago was ‘research only’ is now becoming both research and clinical.” And biobanks involved potentially in clinical treatment, even indirectly, need to follow CLIA requirements.

Biorepository Accreditation Program Committee members didn’t fully consider CLIA regulations when developing the program, says Dr. Branton, chair of the CAP’s BAP Committee. The program’s original focus was to help biorepositories align their processes with Laboratory Accreditation Program requirements—“standardizing SOPs, maintaining personnel records, and developing quality management plans,” for instance.

But more recently, Dr. Branton says, CLIA compliance has emerged as an issue.

It came to the committee’s attention when a biorepository director and member of the committee informed the group that the clinical lab at the research university hospital where she works wouldn’t accept samples back from the biobank without evidence of CLIA equivalence. “We started hearing similar anecdotal stories,” Dr. Branton says. “One is an anecdote, two is interesting, three it really becomes a trend.”

Having CLIA alignment of the biorepository is a safeguard, says Shannon McCall, MD, vice chair of the BAP Committee and director of the Biorepository and Precision Pathology Center, Duke University Medical Center. “It makes our diagnostic clinical laboratories feel more comfortable if they have to accept tissue back from the biobank when the sample is needed to finalize patient care.”

If a biobank is not CLIA equivalent, Dr. Branton says, samples that get recalled for further clinical diagnostic testing technically shouldn’t be used in patient care. Once samples are out of a CLIA-compliant space, “there’s no guarantee that all the standards that apply in a clinical pathology lab are being followed.” CLIA equivalence, he says, will enable “free passage of patient specimens back and forth from the clinical to the research space.”

Biobanks hold and collect paired small samples, such as needle core biopsies, and it’s here that Dr. McCall has seen an increase in specimen recall requests at Duke.

“The pathologist might want to take that needle core biopsy and do multiple immunohistochemical stains, the clinician might need biomarker assays like PD-L1 or HER2 or microsatellite instability, and then ultimately the oncologist might want next-generation sequencing, which would require eight or potentially 10 unstained slides from that same needle core,” she says. “In those cases, often what happens is they just run out of tissue on the clinical side” and may turn to biobanks.

“If the clinical team is aware that the biobank has paired material from that sample, then we’ll get requests to either release that back to the clinical laboratory in-house or send that biobank material out to a reference lab for next-generation sequencing,” for example.

At Duke, Dr. McCall has seen the number of requests increase “maybe 50 percent over the last five years,” and she expects to see more. “As we get even more newer types of diagnostic assays, including RNA sequencing, or more in situ hybridization, it’s going to require more tissue.”

Another factor is greater recognition of the importance of preanalytic variables in clinical testing, says Dr. McCall, citing as an example the ASCO/CAP guidelines for preanalytic variables in HER2 testing.

Like the clinical community, the research community is becoming aware that how tissue samples are procured, processed, and stored can affect assay results, she says. “That’s influenced a focus on quality in biorepositories.”

The checklist revisions, Dr. Branton says, “shouldn’t have any significant effect on the end user’s experience.” However, biorepository directors should take note that the BAP will be transitioning from a three-year to a two-year inspection cycle.

During the development of the BAP, three years was thought to be appropriate for biobanks, “especially because a lot of them had never gotten any kind of inspection before,” Dr. Branton says. But moving to a two-year cycle now will allow institutions that have both CAP-accredited clinical laboratories and biorepositories to be inspected at the same time, optimally with the same personnel team performing both inspections. For these institutions, “the prospect of having just one grand inspection every two years is great,” he says. All biorepositories in the program, including storage-only facilities, will be moving to a two-year inspection cycle, “primarily for ease of record-keeping” on the CAP’s part, Dr. Branton says.

Until now, biorepositories have been inspected with two checklists—the biorepository checklist and laboratory general checklist. With the release of the 2019 edition, four checklists will be used for biorepository inspections: biorepository, laboratory general, director assessment, and all common, with the latter two customized to include only requirements relevant to biorepositories. The former edition of the laboratory general checklist contained a special section for biorepository inspection; the new edition reduces duplicate requirements within the laboratory general checklist by eliminating the biorepository section and instead incorporating biorepository-specific requirements throughout. The CAP will customize the laboratory general checklist for laboratories that have biorepositories.

A range of requirements taken from three accreditation program checklists—molecular pathology, anatomic pathology, and laboratory general—have been added to the biorepository checklist.

Broadly speaking, the requirements taken from the molecular pathology checklist address molecular extractions, molecular specimen processing, target amplification and PCR, and electrophoresis. The requirements taken from the anatomic pathology checklist address in situ hybridization, IHC and immunofluorescence, digital image analysis, and CLIA-related quality control, among others. Biorepository checklists will continue to be customized according to the menu of services biobanks self-report to the CAP during the accreditation application process.

Biobanks embedded in large pathology departments that do extensive research “function almost like clinical laboratories in that they do a considerable amount of on-site testing and specimen manipulation,” says Dr. Branton. These biorepositories will “obviously have a much more sophisticated and involved checklist” than biobanks that only “receive and hold,” he says. But since CAP checklists are now customized, “they can be as short or as long as needed.”