FDA considers establishing a new ‘Office of Patient Affairs’

The FDA announced that it is establishing a public docket to solicit public input on ongoing efforts to enhance mechanisms for patient engagement at the agency. In addition, to achieve a more transparent, accessible, and robust experience for patient communities, the FDA is considering establishing a new Office of Patient Affairs.

On November 4, 2014, the FDA established a docket (FDA-2014-N-1698) for the public to submit information related to the FDA’s implementation of the Food and Drug Administration Safety and Innovation Act (FDASIA) (P.L. 112-144), Patient Participation in Medical Product Discussions under FDASIA section 1137.

Based on the comments received, the FDA identified objectives for its patient engagement activities. First, to develop a nuanced understanding of the patient experience of disease by: (1) gathering patient perspective on what is clinically meaningful; (2) assessing attitudes towards benefit-risk and tolerance of uncertainty; and (3) enhancing the science of eliciting and integrating patient input.

Second, to support patients and their advocates in understanding regulatory processes and navigating the FDA by: (1) communicating relevant FDA positions, procedures, and activities; (2) connecting patients and their advocates with the appropriate resources; and (3) resolving discrete challenges and needs.

To achieve these objectives, the FDA is considering establishing a central “Office of Patient Affairs.” The responsibilities of this central office would include:

  • offering a single, central entry point to the FDA for the patient community;
  • providing triage and navigation services for inbound inquiries from patient stakeholders;
  • hosting and maintaining robust data management systems that would incorporate and formalize knowledge shared with the FDA by patient stakeholders and the FDA’s relationships with patient communities; and
  • developing a scalable and forward-looking platform for communicating with patient stakeholders, particularly online channels.

The Office of Patient Affairs would be directly accountable to the medical product Centers. A regular evaluation of this central office and of FDA’s overall patient engagement efforts are also proposed.

 

 

Life sciences industry groups ask for indefinite stay, say FDA strayed

The Final rule titled Clarification of When Products Made or Derived From Tobacco Are Regulated As Drugs, Devices, or Combination Products; Amendments to Regulations Regarding “Intended Uses” (82 FR 2193, January 9, 2017) violates the Administrative Procedures Act (APA) (P.L. 79-404) and constitutes an overstep of the FDA’s authority, according to a petition for an indefinite stay of the rule’s implementation, filed by the industry groups, Medical Information Working Group (MIWG), the Pharmaceutical Research and Manufacturers of America (PhRMA), and the Biotechnology Innovation Organization (BIO). The petition focuses primarily on the second part of the Final rule, asking the FDA to indefinitely halt implementation of the Final rule’s new “intended use” policy.

Petition

The petition asserts, by not adequately informing the public of changes to the “intended use” doctrine, the FDA’s final rule violates the APA.  The substance of the petition argues by not including the “intended use” changes prior to the publication of the Final rule, on January 9, 2017, the industry groups were deprived of the fair notice and hearing required by the APA. Instead of being a permissible “logical outgrowth” of the proposed rule, the industry groups assert that the FDA strayed too far beyond the Proposed rule (80 FR 57756) and engaged in “a fundamental change to the regulatory scheme for drugs and devices.”

Intended use

Section 502(f)(1) of the Food, Drug, and Cosmetics Act (FDC Act) requires that drug and device labeling contains “adequate information” regarding any “use for which [the drug or device] is intended.” The doctrine was codified at 21 C.F.R. Sec. 201.128 (for drugs) and at 21 C.F.R. Sec. 801.4 (for medical devices). The FDA doctrine includes the following provision: “if a manufacturer knows, or has knowledge of facts that would give him notice, that a drug or device introduced into interstate commerce by him is to be used for conditions, purposes, or uses other than the ones for which he offers it, he is required to provide adequate labeling for such a drug which accords with such other uses to which the article is to be put.”

The petitioners object to the above, the FDA’s pre-rule regulatory position, and were, instead, supportive of the position set out in the Proposed rule, which would have established a position where the FDA would no longer “regard a firm as intending an unapproved new use for an approved or cleared medical product based solely on that firm’s knowledge that such product was being prescribed or used by doctors for such use.”

Totality of the evidence

The industry groups challenge what they call the totality of the evidence standard, which, they say, the FDA presented for the first time in the Final rule, a doctrine under which a manufacturer would be required to provide adequate labeling for all intended uses, if the “totality of the evidence” indicates the manufacturer intends for a drug to have off-label uses. The petition asserts that by establishing such a requirement, the Final rule will violate the First Amendment to the U.S. Constitution, chilling truthful and non-misleading promotional speech.

Review

The petition is currently under FDA review. There are currently no pending resolutions to disapprove the rule in Congress.

 

Bloodstream infection detection test approved for marketing

In a first of its kind, the FDA has approved the marketing of the PhenoTest BC Kit, which is the first test to identify organisms that cause bloodstream infections. The test kit, manufactured by Accelerate Diagnostics Inc., can provide information to health professionals about which antibiotics the organism is sensitive to and potentially reduce the amount of time to provide this information. As a result, antibiotic treatment recommendations can be formulated much quicker. Unlike traditional identification and antibiotic susceptibility tests that may take 24 to 48 hours after detection in a positive blood culture to provide test results, the PhenoTest BC Kit can identify bacteria or yeast from a positive blood culture in approximately 1.5 hours. The test can identify 14 different species of bacteria and two species of yeast that cause bloodstream infections, while also providing antibiotic sensitivity information on 18 selected antibiotics for a subset of the identified organisms as appropriate.

Bacterial or yeast blood infections can occur in individuals of all ages, but are particularly severe in infants, the elderly, and those with weakened immune systems. If not treated rapidly, such bloodstream infections can lead to severe complications, such as septic shock and death. The PhenoTest BC Kit can also provide treatment recommendations within 6.5 hours of organism detection in blood cultuers.

The FDA reviewed the data for the PhenoTest BC Kit through its de novo premarket review pathway, a regulatory pathway for devices of a new type with low-to-moderate-risk that are not substantially equivalent to an already legally marketed device and for which special controls can be developed, in addition to general controls, to provide a reasonable assurance of safety and effectiveness of the devices. Although some risks with the kit included false positive findings, the FDA’s decision was based on Accerlerate’s clinical study of 1,850 positive blood cultures.  In the study, bacteria or yeast in positive blood culture was identified correctly more than 95 percent of the time.

Too much ‘noise’ in system at root of device recall delays

Postmarket surveillance of medical devices, which includes device manufacturers’ investigations of complaints about their devices, are generally not logged in the FDA’s adverse event report system. In a study sponsored by the University of Minnesota and published in the journal Production and Operations Management, the researchers found that the more adverse event reports there are for a ­particular device, the more likely it was a company would have “under-reaction” bias in deciding whether a recall was appropriate.  In other words, device manufacturers, when presented with multiple adverse event reports for a specific device, actually took longer to react on the recall decision.

Each year, the FDA receives several hundred thousand medical device reports (MDRs) of suspected device-associated deaths, serious injuries, and malfunctions. The FDA uses MDRs to monitor device performance, detect potential device-related safety issues, and contribute to benefit-risk assessments of these products. A Manufacturer and User Facility Device Experience (MAUDE) database houses these MDRs submitted to the FDA by mandatory reporters (manufacturers, importers, and device user facilities) and voluntary reporters, such as health care professionals, patients and consumers.

Although MDRs are a valuable source of information, they provide only a passive surveillance system. Limitations include the potential submission of incomplete, inaccurate, untimely, unverified, or biased data. In addition, the incidence or prevalence of an event cannot be determined from this reporting system alone due to potential under-reporting of events and lack of information about frequency of device use. Because of this, MDRs comprise only one of the FDA’s several important postmarket surveillance data sources. As the researchers applied digital analytics to millions of medical device product reports and recall records for their study, they found a high “signal to noise” ratio correlated with the delays. Not only did these indicators create detection issues, older and widely used devices tended to have multiple adverse event reports in MAUDE, making safety-signal detection difficult.

In 2012, the FDA announced plans to develop a National Evaluation System for Health Technology (NEST) to generate better evidence for regulation and agency decisions throughout the lifespan of a device. Whether the system will provide a better way for both the agency and industry to monitor postmarket safety of medical devices is indeterminate, but the FDA is counting on the system providing more collaboration than the current one.