Ann Griswold, PhD
August 2013—At CAP ’11, then president-elect Stanley Robboy, MD, sat at a table in a conference room. He didn’t know those seated with him but he and they started to chat. The conversation turned to Dr. Robboy’s goals for his upcoming presidential term, and a member from Saudi Arabia, Amal Saadallah, MD, PhD, proposed that newborn screening requirements be created for accreditation.
Dr. Saadallah knew well the limitations of the CAP’s clinical biochemical genetics checklist. She is professor of clinical pathology and section head of the quality improvement and safety task force at the National Laboratory for Newborn Screening, King Faisal Specialist Hospital and Research Centre. The checklist was a big advance but inadequate given the needs of her country. “She wanted to see something more,” Dr. Robboy recalls. “What she said made sense. Medicine is global. It’s no longer about U.S. medicine or Saudi Arabian medicine or Chinese medicine.”
By the time CAP ’11 ended, he had wide support for a newborn screening project. Now, less than two years later, those much-needed requirements are part of the latest edition of the Laboratory Accreditation Program checklists, released July 29. So too are requirements for the use of MALDI-TOF mass spectrometry in microbiology laboratories.
“MALDI-TOF mass spec is new technology, so we tried to come up with reasonable advice for individuals who might be utilizing it as an identification system or who are planning to use it as an identification system in their laboratories,” says Julie Ribes, MD, PhD, a member of the CAP Microbiology Resource Committee and an associate professor, director of clinical microbiology, and associate director of hospital laboratories, University of Kentucky College of Medicine.
[dropcap]T[/dropcap]he newborn screening requirements that constitute a new section of the clinical biochemical genetics checklist are aimed at collection, specimen quality monitoring, consent, out-of-range results, reporting, and followup.
“Our working group tried to encompass the holistic view that newborn screening is a process—a public health process to lessen the morbidity and mortality of infants,” says Devin Oglesbee, PhD, a member of the CAP Newborn Screening Working Group and an assistant professor of laboratory medicine, pathology, and medical genetics and co-director of the biochemical genetics reference laboratory, Mayo Clinic, Rochester, Minn. The reference laboratory performs screening for all infants born in Minnesota.
At Mayo Clinic, all infants receive a heel stick after the first 24 hours of life and their blood is spotted on a newborn screening, or “Guthrie,” card. One sheet from the card is sent by courier to the Minnesota Department of Health Laboratory in St. Paul. The remaining blood sample is subjected to technical analyses, including tandem mass spectrometry. “Our tandem mass spec experience has been quite extensive,” Dr. Oglesbee says. “We basically have the capacity to do high-throughput newborn screening for about 90,000 births a year.”
In developing the new CAP requirements, he says, the Newborn Screening Working Group considered each step in the process: type of screening paper, temperature of specimen storage, protocols and timelines for shipping and processing specimens—everything down to the diameter of blood spots obtained from infant heel sticks. The group’s goal: Reinforce the need for timely results so that infants can be followed appropriately, especially if they are at risk for a condition that could compromise their health.
The group reached above and beyond current state and federal newborn screening recommendations. “One of the things that came out of our discussions was that current requirements were focused only on a subsection of newborn screening,” Dr. Oglesbee explains. “Some of the preanalytical variables are extremely important for a newborn screening program but aren’t necessarily included in current clinical chemistry or biochemistry requirements.”
One such variable, he says, is the quality of filter paper used to collect newborn blood spots. The CAP checklist includes language about the use of ID numbers to track the cards, which are themselves FDA-approved devices, and the importance of adhering to the expiration date. “At this point, every laboratory in the U.S. has a method to track the screening paper. In the U.S., many of our newborn screening cards contain expiration dates and a lot ID, though this may be new to international laboratories. So including these regulations in the checklist was important for our international participants.”
The working group opted to provide laboratories with the authority to dictate the size of blood spots, the type of screening paper, and how specimens should be labeled and shipped. “Some issues that the group explored were whether one would want to designate the ordering physician or another individual to receive positive results from a newborn screening card,” Dr. Oglesbee says. “Many of these things are going to be state-specific. But the CAP requirements provide the impetus for these requirements to exist, and give labs flexibility in setting parameters for newborn screening protocols.”
He expects the CAP screening requirements to remain fluid, noting that newborn screening activities change often. Earlier this year, for example, the federal Health Resources and Services Administration suggested expanding the recommended panel for newborn screening targets to include critical congenital heart disorder, a condition detected by point-of-care pulse oximetry and defined as congenital heart disease requiring invasive intervention or resulting in death in the first 30 days of life. States that decide to screen for this disorder will rely on infrastructure not addressed in the 2013 checklist.
Current and future members of CAP resource committees and working groups will likely be busy keeping up with changes in the field so the checklist doesn’t fall behind. “I won’t be surprised if the technologies available for molecular genetic diagnoses become cheap enough to be used by newborn screening laboratories,” Dr. Oglesbee says.
[dropcap]F[/dropcap]or use of MALDI-TOF, the CAP Microbiology Resource Committee created six checklist requirements that describe use of the technology, its validation for clinical use, and quality control in the laboratory setting.
The committee began by examining the mass spectrometry requirements in the chemistry checklist, then explored how a few relevant items might be adapted to the operation of MALDI-TOF instruments in microbiology. But it quickly became apparent that each committee member’s lab operated a bit differently, and most erred on the side of abundant caution. “We saw a great deal of variation from laboratory to laboratory, as far as the number and types of organisms that labs were running on a daily basis for their QC. In many places, it was pretty excessive,” Dr. Ribes says. “So we tried to indicate an appropriate blend of organisms that should be assessed daily without imposing an unnecessary burden.”
The new requirements—all phase II—will encourage microbiology labs to run daily quality control checks on at least one control bacterium, a representative yeast, and a mycobacterium if the laboratory is using the instrument for these identification purposes. The choice of organisms must conform to the manufacturer’s recommendations in labs that are using FDA-approved platforms for MALDI-TOF mass spec, once FDA approval is obtained for these platforms.
The committee focused on what needed to be documented to demonstrate that the instrument is working correctly. In addition to using the standards that come with the platform, Dr. Ribes says, additional organisms, including one or more representative gram-positive and gram-negative organisms, should be tested, as well as an extraction control organism, which for her laboratory is a yeast.
“I’m a customer of the CAP checklists, too,” she notes. “My laboratory has a MALDI-TOF, and I can say that the checklist requirements have right-sized the number of organisms that are being tested daily to demonstrate that the system is operating correctly.”
The new requirements emphasize the need to follow the manufacturer’s recommendations, particularly when it comes to the grade of solvents, type of consumables, and instrument maintenance schedule. Deviations from the manufacturer’s recommendations are allowed but must be validated and documented and may represent “off-label” use of what is soon anticipated to be FDA-approved testing platforms.
The new MALDI-TOF section has a preemptive feel, considering the newness of the technology. But as more institutions adopt MALDI-TOF—and as the first platforms gain FDA approval for clinical use—the section will become an increasingly valuable tool. “Laboratories will need to decide what to do as they bring in these new instruments,” Dr. Ribes says. “Our checklist will grow as more laboratories utilize MALDI-TOF, and as they develop applications that are not necessarily purchased from the manufacturer.” Issues like specimen extraction from blood culture bottles and early identification of pathogens will likely be addressed as technologies related to MALDI-TOF mass spec evolve.
[dropcap]T[/dropcap]he objective in this year’s edition was to construct a checklist framework to address unmet needs, says Gerald A. Hoeltge, MD, chair of the Checklists Committee and a retired clinical pathology consultant for the Cleveland Clinic. “We have new language for telepathology and telecytology, better language for test method validation in molecular pathology, and the new requirements for MALDI-TOF in microbiology. The new checklists also address, for the first time, newborn screening on filter paper, next-generation sequencing of maternal plasma [see next month’s CAP TODAY], and Mohs-only surgery labs.”
Some of the phase assignments have changed too, Dr. Hoeltge says. The Checklists Committee reviewed every requirement with an eye to consistency and identified 58 that were previously phase II and are now phase I. About 54 phase I requirements are now phase II.
One of the reclassified requirements was ANP.11713, in the anatomic pathology checklist, which requires that pathologists perform daily reviews of the technical quality of histologic preparations. “This is a really good idea, and absolutely something that a laboratory should do if it hopes to get that CAP accreditation stamp,” Dr. Hoeltge says. “But this requirement is not regulatory. Whether the quality is reviewed by a pathologist every day or not, it’s not going to affect anyone’s health or safety.” As a result, it’s now considered a phase I requirement.
The language used in the requirements has been revised for clarity. “This year’s edition adds a number of definitions to the checklists’ glossaries so that everyone knows how the checklists use familiar terms,” Dr. Hoeltge says. Validation and verification, for example, are terms that are often confused and were not used consistently in previous editions, he adds. Validation applies to test methods developed in and by the laboratory, including any modification to the manufacturer’s instructions. Verification refers to conformance to a manufacturer’s stated claims. “For example, you verify that a test kit performs in your lab as it’s supposed to before you begin to use it. Change some aspect of that same test kit and you have to validate the change,” he explains.
Each laboratory’s checklists can be downloaded to a computer, customized to that laboratory’s activity menu. Alternatively, labs can download a “Change” document that reveals every revision, even the editorial ones. A third option is to download each checklist in a spreadsheet format. “That’s a handy way to manage the changes—what needs to be done, who’s responsible, and so on,” Dr. Hoeltge says.
This year’s checklist changes are not just specific to biochemical or microbiological issues. Dr. Robboy says the idea behind all checklist revisions is to ask how through the checklists patient care can be made safer. “How can we look at the entire hospital and improve medicine for everyone?”
That some of the latest improvements began with a stranger and a simple exchange of words is a plus.
“By happenstance, I sat next to someone who in my normal daily life I would never meet,” he says. “This was the perfect example of why we have a national meeting. Throw many people into a room, each with different interests, and they will connect. It is as simple as that.”
Ann Griswold is a writer in Annapolis, Md.