Rebuttal to FDA motion 4/11/08

HiFi DNA Tech tells FDA it is “unreasonable” and should study the science of HPV DNA PCR and DNA sequencing for genotyping.

BRIDGEPORT, Conn. – HiFi DNA Tech of Trumbull, CT told a federal judge the Food and Drug Administration (FDA) “has not kept pace with the advances in molecular biology for the past 20 years, which unfortunately does not benefit women who may have HPV.”  The Memorandum in Opposition  was filed in U.S. District Court in Bridgeport, CT, April 11 in connection with a lawsuit for reclassification of a HPV genotyping device.

The FDA has been unreasonable in demanding the plaintiff to demonstrate human papillomavirus (HPV) genotyping can be used to diagnose cervical cancer in reviewing a petition to reclassify an HPV DNA PCR (polymerase chain reaction) device from a class III test to a class II virology test, said Sin Hang Lee, M.D., president of the reagent manufacturer.

“Congress has not given FDA sweeping discretion to make arbitrary medical device decisions without scientific basis and with unreasonable demands,” said attorney Anthony J. Musto for HiFi DNA.

As a reason for the denial, the FDA wrote on December 14, 2007 in its original Order “Probe design is a critical process for HPV DNA testing because of the large number of closely related HPV genotypes. Complex probe cocktails may crossreact and/or compete with one another. There is currently no standardized clinical panel of representative HPV samples available against which specific probe combinations can be evaluated for clinical effectiveness. Accordingly, it is difficult if not impossible at this time for FDA to conclude, absent well-developed clinical data, that a chosen probe design for a device of this type is reasonably safe and effective.”

HiFi DNA challenged the reasoning of the FDA in a lawsuit because neither the HPV DNA PCR device, nor the recommended HPV genotyping by DNA sequencing uses probes.

In a Motion to dismiss the lawsuit, the FDA claimed that FDA’s general definition of the term “probe” was intended to encompass PCR “primers.” This willful use of a self-fabricated definition indicates that the FDA intends to regulate the HPV testing based on what is legally permissible rather than on what is right in science, said Dr. Lee.

In the Motion, the FDA now declared “Even more fundamentally, FDA found that HiFi intends for its device to be used in conjunction with genotyping to confirm its positive test results, but HiFi did not submit any data demonstrating that an HPV genotyping test validated for diagnostic use with cervical cancer even exists” and “Congress gave FDA sweeping discretion in determining the classification of devices and therefore in judging the safety and effectiveness of medical devices.”

In the Memorandum in Opposition, attorney Anthony J. Musto of HiFi DNA told the court the HPV DNA PCR device is intended to be used to prepare clinical samples for accurate HPV genotyping by direct DNA sequencing to be performed in a certified clinical microbiology laboratory directed by a qualified medical director. The plaintiff has never claimed that HPV genotyping can diagnose cervical cancer, an impossible task the FDA set up for the plaintiff petitioner to perform. In fact, the plaintiff has requested the FDA to regulate all HPV DNA tests as virology testing device. This request is consistent with the FDA’s view that officially stated: “The HPV DNA test does not test for cancer, but for the HPV viruses that can cause cell changes in the cervix.” (FDA News Release March 31, 2003)

“All doctors know that HPV test is a virology test and does not diagnose cancer,” said Dr. Lee.

Musto compared the HPV DNA PCR device to a PCR reagent kit sold to a forensic science laboratory for “PCR-fingerprinting” in law enforcement. A forensic scientist uses the PCR reagents to amplify a small amount of DNA sample collected at the crime scene for DNA sequence determination, for example with the “short tandem repeat” (STR) analysis, a forensic science technology accepted by U.S. courts. The forensic scientist presents to the court the PCR-based DNA evidence that may link a suspect to the DNA found at the crime scene. It is up to the presiding judge of the court to decide if the evidence is acceptable and admissible for deliberation. The judge or the court, not the DNA typing, not the PCR reagent kit, finally decides if the suspect has actually committed the crime. As a physician would use HPV genotype data in evaluating a patient, the FDA’s demand of a manufacturer of an HPV DNA PCR device to demonstrate that HPV genotyping can be used to diagnose cervical cancer is arbitrary and capricious. 

HiFi DNA Tech, LLC markets a new HiFi® DNA polymerase to perform PCR at LoTemp™ cycles to prepare clinical samples to facilitate accurate HPV genotyping by direct DNA sequencing and for highly sensitive no-false-positive DNA sequencing molecular identification of Chlamydia trachomatis and Neisseria gonorrhoeae in liquid-based Pap cytology specimens. This new technology was first published in Infectious Agents & Cancer. Milford Medical Laboratory offers these clinical tests to the physicians and their patients. Visit

For Information, contact Ken Warren 203 891-9001