Infectious diseases range from a cold to the Ebola virus. Doctors use diagnostic tests to narrow down the causes of the various symptoms that a patient may present and, ultimately, to diagnose the cause of the patient’s symptoms and recommend appropriate treatment. The tests covered by this draft guidance represent how molecular technology in genetic sequencing can improve upon a more rudimentary diagnostic test, like a strep culture test. Particularly for severe and emerging infectious diseases like Ebola or other infections, rapid diagnosis is essential in order to act within a short time frame to benefit the patient and public health. These Infectious Disease NGS Dx devices can be developed to test the various specimens, such as blood, sputum, urine, etc., that may reveal an infectious disease agent. They can also identify markers of antimicrobial resistance and virulence, which would help the doctor select the treatment that will be the most effective.
Genetic sequencing can identify infectious disease agents by mapping their unique genetic makeup. At its most basic level, mapping an infectious disease pathogen’s DNA sequence involves taking the segment of DNA strand available in a sample and “amplifying it,” using enzymes to react with the existing segment and thereby to create millions of copies. With a complete map and millions of copies of a pathogen’s DNA sequence, scientists can fully examine and understand any individual pathogen’s potential for spreading infectious disease. That way, upon sequencing the various pathogens in a specimen, the test can identify those pathogens that are agents of infectious disease.
This guidance covers two types of approaches that an Infectious Disease NGS Dx device would use: targeted or agnostic. A targeted approach means that the device can detect the presence or absence of a particular infectious disease agent or agents (or resistance markers)—by ‘targeting’ that agent. An agnostic approach means that the device has no particular infectious disease agent in mind. The agnostic approach relies more on comparing the genetic sequences of a specimen’s microorganisms to a database or library of genetic sequences, so that the benign microorganisms can be ruled out and the infectious agents can be pinpointed. Targeted devices will already have a specific pathogen or infectious disease agent in mind, and will test specimens for the presence or absence of that particular pathogen. In contrast, agnostic devices will aim to identify which pathogen among the several pathogens in a specimen is likely to spread an infectious disease (or to resist a particular treatment).
Because Infectious Disease NGS Dx devices are complex and specialized, this Draft Guidance relies on systems science to understand and conceptualize the diagnostic process from beginning to end. “This approach will evaluate, in parallel, the system as a whole… and each individual step in the sequencing data pipeline as part of that system, from specimen collection to results report.”
CDRH classifies devices according to the level of control needed to assure their safety and effectiveness. This guidance’s Infectious Disease NGS Dx devices are considered Class II, which require the manufacturer to notify CDRH of the new device before marketing it and to meet quality controls. In contrast, Class III devices cannot be sold without pre-market application, review, and approval from CDRH; a device that diagnoses HIV, or a few other certain infectious diseases that have traditionally been treated as high-risk, would accordingly require Class III premarket approval.