March 18, 2019
Central laboratories need to be viewed as partners in clinical trials, not simply as vendors doing routine safety work, says a veteran laboratory auditor.
“If the central laboratory understands the objectives and has the opportunity to suggest the best possible means to meet the objectives, the success rate of the study goes up. You need to have a very interactive central laboratory,” says Michelle Sceppa, founder and principal of MSceppa Consulting.
But it has to be the right lab for the trial. It’s crucial to qualify a central lab before the start of a clinical study, Sceppa says.
A qualifying audit of a central lab is somewhat different from a qualifying audit of a more traditional vendor. For one thing, the lab is subject to different regulatory, including requirements from the College of American Pathologists (CAP) and the Clinical Laboratory Improvement Amendments (CLIA) maintained by the Centers for Medicare and Medicaid Services. The CAP and CLIA rules require a laboratory to show proficiency in the various types of testing they perform.
Sceppa advises having a laboratory qualifying audit performed by an auditor with specific experience with labs, whether that’s an in-house expert or someone brought on specifically for the task.
In many cases, a lab company may have a plethora of locations, particularly as the industry has consolidated. These locations may be in the U.S. and abroad. It can be tricky, Sceppa says, to know which or how many of these locations should be evaluated. But she suggests auditors visit a lab company’s central, global offices, rather than trying to audit multiple satellite locations. She uses the example of Covance Laboratories, which has a central U.S. location in Indianapolis and a central European office in Switzerland. For a global clinical study, it would be sufficient to visit these two headquarters, rather than trying to track down the specific satellite offices that may be handling testing for the various clinical sites.
However, Sceppa says it is a good practice to inquire about the specifics of how testing samples are tracked between locations and what their chain of custody looks like. “What do they do if there’s a problem with the sample transport? How do they escalate? How do they investigate? What’s their CAPA resolution?” These are all questions that the staff at a lab company’s central office should be able to answer satisfactorily.
Another key question to ask in a laboratory audit is whether the lab has the capacity and experience to fulfill the contract. “The first thing you want to look at is how many samples come in, how they can open those samples, get those samples to the laboratory and get that work done promptly,” Sceppa says. “A lot of times, those [data] are important to look at before you can enroll a patient in the study, so most people are looking for a 24- or 48-hour turnaround on laboratory data.”
It’s also important to ask how the laboratory provides the results to the clinical site and sponsor, she says. How do hard copy records compare to electronic records? How is the electronic transfer done? How does the lab verify that transfer is done appropriately. “You have to look at that validation because [the data] is going from one system to another system.” The laboratory’s computer system must be in compliance with the FDA’s electronic systems rules at 21 CFR Part 11.
Other important questions to ask include:
- What number and type of clinical studies (including the number of sponsors) are handled by the laboratory at any one time?
- Are there any affiliations and/or contracts with third parties performing tasks on behalf of the laboratory, e.g., kit assembly, courier service, data management, service contractors for lab equipment and computer system validation;
- Is the facility and staff size adequate to perform the required testing?
- Is the lab/staff experienced in any special tests the trial may require?
- Are there other departments (pharmacy, cytology, etc.) at the site to assist in the study if required?
Sceppa says she usually allots a day and a half for the audit, including reviewing procedures and documentation, and touring the facility. “The tour will take me, depending on the laboratory, maybe two to three hours, maybe four at max.” And she always tours, even when it’s a laboratory she’s evaluated before. “There’s always something new for me to look at and new for me to see, so I never say, ‘Oh, I’ve been here before. I’m not going to tour.’ I always tour again.”
“A lot of times when I go back to the same places, I want to see if the same people are working there,” she says. “I look for that continuity in staff because I always think that’s really important no matter who you’re auditing.“
-By Leslie Ramsey