Regulatory Focus™ > News Articles > FDA Overhauls Controls for Device, Citing Need to Avoid Risks for MS and Crohn's Patients

FDA Overhauls Controls for Device, Citing Need to Avoid Risks for MS and Crohn's Patients

Posted 27 January 2014 | By Alexander Gaffney, RAC

US device regulators have released a new regulation outlining special controls for serological reagents intended to detect the presence of the John Cunningham Virus (JCV) and prevent the spread or development of progressive multifocal leukoencephalopathy (PML).


As FDA's Federal Register notice explains, JCV is a common but typically asymptomatic virus that is generally harmless. For immunocompromised individuals, however, the virus can cause PML, a disease which attacks the brain and most often results in death.

Luckily for patients, PML is "very rare," even among immunosuppressed individuals. Unluckily for patients, the disease remains poorly understood, even as it is correlated with the use of some FDA-approved biologics.

In August 2013, for example, FDA issued a warning about Novartis' drug Gilenya (fingolimod) after it was associated with just a single case of PML in a patient in Europe. Other drugs, such as Tysabri (natalizumab) have also been associated with cases of PML, FDA said. Both drugs are used to treat multiple sclerosis, and Tysabri is also used to treat Crohn's disease.

Risk Control Strategy

Despite the serious risks and the lack of insight into the mechanisms by which the virus progresses into PML, regulators say they have a strategy they hope can prevent future harm to patients.

Because PML is dependent upon infection with JCV, FDA says that any tool that can identify the presence of JCV would be useful in stratifying those patients from therapy with Tysabri or other biologics associated with PML.

Luckily, such tools exist, and function by detecting JCV antibodies in the blood. Now FDA has moved to reclassify those products under a Class II - Special Controls regulatory scheme. Under the Federal Food, Drug and Cosmetic Act (FD&C Act), Class II products are those that need special controls (i.e. beyond Class I general controls) in order to assure their safety and efficacy.

Because failure of a reagent to detect the presence of the JCV virus could conceivably kill a patient, just as a false positive could lead a patient to forgo necessary treatment, FDA said manufacturers of any device intended to detect JCV will have to meet enhanced standards for safety and efficacy.

New Requirements

As explained by FDA, federal regulations require any manufacturer who intends to market a Class II device to do the following:

  1. conform to the general controls of the FD&C Act, including the premarket notification requirements described in 21 CFR 807 Subpart E
  2. address the specific issues of safety and effectiveness identified in this guideline
  3. obtain a substantial equivalence determination from FDA prior to marketing the device

In the case of FDA's new guideline, Classification of John Cunningham Virus Serological Reagents, FDA primarily focuses on the second of those three requirements: specific issues of safety and effectiveness.

Manufacturers will need to conduct a "risk analysis prior to submitting a premarket notification to identify any other risks specific to their device." Premarket notifications are more commonly referred to as 510(k) submissions.

Manufacturers will, among other things, need to include a detailed description of the device, its components, its ancillary reagents, tests used to validate the device, and extensive information about the device's performance characteristics.


Guideline: Class II Special Controls Guideline: John Cunningham Virus Serological Reagents

Federal Register

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