FDA Releases Two Draft Guidance Documents on Proposed Laboratory Developed Test (LDT) Regulatory Oversight

This post was written by Jennifer Pike and Vicki Morris.

On September 30, 2014, the Food and Drug Administration (FDA) announced the availability of two draft guidances intended to implement a new regulatory oversight framework for LDTs, which are defined by the FDA as "a type of in vitro diagnostic test that is designed, manufactured and used within a single laboratory" and which are intended for clinical use. Release of the documents follows on the heels of FDA’s notification to Congress in late July of its intent to issue draft guidance in this area. The first draft guidance, "Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs)" (Framework Guidance), describes a risk-based framework for addressing the regulatory oversight of LDTs. The Framework Guidance also describes FDA’s priorities for enforcing pre- and post-market requirements for LDTs, and the process by which FDA intends to phase in enforcement of FDA regulatory requirements for LDTs over time. The second draft guidance, "FDA Notification and Medical Device Reporting for Laboratory Developed Tests (LDTs)" (Notification and Reporting Guidance), describes the process for clinical laboratories to notify FDA of the LDTs they manufacture as well as the Medical Device Reporting (MDR) requirements for clinical laboratories that manufacture LDTs. Both draft guidances reflect the FDA’s effort to take steps to encourage the advancement of personalized medicine by helping to ensure the reliability of certain diagnostic tests. The guidances are neither final nor in effect at this time.  

The following is an overview of the specific issues addressed in the draft guidances:

  • Low-Risk LDTs (Class 1 Devices), LDTs for Rare Diseases, LDTs for Unmet Needs and Traditional LDTs: FDA proposes to continue to exercise enforcement discretion for premarket review and quality system requirements, but will enforce other regulatory requirements, including registration and listing (or notification) and adverse event reporting for Low-Risk LDTs (Class 1 Devices), LDTs for Rare Diseases, Traditional LDT Oversight, and LDTs for Unmet Needs.
    • LDTs used for rare diseases are tests that meet the both the definition of LDT and the definition of a Humanitarian Use Device (HUD). FDA proposes factors to balance the need to mitigate the risks associated with these tests and their potential benefit for patients, and invites feedback on the proposed factors. FDA also seeks feedback as to whether a factor other than the HUD definition should be considered in defining these tests.
    • LDTs used for unmet needs are tests used when no FDA-cleared or -approved alternative exists. FDA proposes factors to determine whether an LDT is an “LDT for Unmet Needs,” and notes that the Agency does not intend to consider factors such as whether the LDT is comprised of only legally marketed components and instruments or whether the LDT is interpreted by qualified laboratory professionals, without the use of automated instrumentation or software for interpretation. FDA believes that greater flexibility is appropriate for LDTs for Unmet Needs because there is no FDA-cleared or approved alternative for the device on the market.
    • Traditional LDTs refer to in vitro devices that reflect the types of LDT available when FDA began its policy of generally exercising enforcement discretion over LDTs in 1976. FDA’s policy of enforcement discretion is based on a number of existing factors that the FDA believes appropriately mitigate risks associated with Traditional LDTs being used on patients. In the Framework Guidance, FDA also proposes, and requests feedback on, three new factors it believes mitigate risk for Traditional LDTs.
  • High and Moderate Risk LDTs: FDA intends to enforce all applicable regulatory requirements for these LDTs.
  • Forensic LDTs and LDTs for Transplant: FDA proposes to continue to exercise enforcement discretion for all regulatory requirements for these types of LDTs.
  • Defining Healthcare System: With respect to Traditional LDTs and LDTs for Unmet Needs, FDA proposes that enforcement discretion should be limited to those LDTs that are both manufactured and used by a healthcare facility laboratory, which are defined in the guidances as a collection of hospitals that are owned and operated by the same entity and that share access to patient care information for their patients, such as, but not limited to, drug order information, treatment and diagnosis information, and patient outcomes. FDA seeks public feedback on which types of facilities would or would not be considered within a healthcare system, or an alternative description of healthcare system for Agency consideration.
  • Timing on Quality System (QS) Enforcement: FDA proposes continued enforcement discretion over QS regulation requirements until a manufacturer of a given LDT submits a Premarket Approval (PMA) or FDA issues a 510(k) clearance order for the LDT. Under this enforcement policy, the clinical laboratory manufacturing and using the LDT will be responsible for having a quality system in place that meets certain requirements either at the time of PMA submission or prior to market launch for cleared devices, as applicable. FDA proposes a timeframe for phase-in enforcement of QS regulation requirements, including enforcement of premarket review requirements for high-risk LDTs 12 months following publication of the final Framework guidance, and enforcement of design control requirements 24 months after publication of the final guidance.
  • Notification: FDA proposes that the Agency will collect information regarding LDTs currently being used by laboratories through a notification process. Specifically, laboratory owners/operators with LDTs currently being used in their labs should begin to notify FDA no later than 6 months after publication of the final Notification and Reporting Guidance. Starting 6 months after the publication of the final Notification and Reporting Guidance, laboratories that intend to offer new LDTs should provide notification to FDA prior to offering the LDT. FDA notes that when laboratories make a significant change to the marketed intended use of an LDT for which they have previously provided notification, the LDT will be considered a new LDT subject to a new notification. FDA intends to continue to exercise enforcement discretion for laboratories manufacturing only LDTs (and no other medical device) with respect to registration and listing requirements provided that such laboratories notify FDA of their LDTs. FDA will consider laboratories that do not notify the Agency that they are manufacturing LDTs within the required timeframes to have opted not to be within the scope of FDA’s enforcement discretion policy with respect to the registration and listing requirements.
  • Multiple Site Test Notification: FDA seeks comments on its proposal to allow a single notification from laboratory networks (i.e., more than one laboratory under the control of the same parent entity) that offer the same test in multiple laboratories throughout their network.

FDA will hold a webinar on October 23, 2014 on the Framework Guidance. For more information on accessing the webinar and its materials, click here.

Comments to the draft guidances should be submitted by February 2, 2015. FDA also intends to hold a public meeting in early January 2015 to collect additional input during the comment period.

About the Authors: Jennifer Pike (associate) and Vicki Morris (Law Clerk) are members of the firm’s Life Sciences Health Industry Group and is based in our Washington, D.C. office.

FDA Releases "Purple Book," Including Biosimilar Products

The FDA’s new “Purple Book” lists biological products licensed by FDA under the Public Health Service Act (the PHS Act). The publication includes information on whether FDA evaluated the biological product for reference product exclusivity under section 351(k)(7) of the PHS Act, and whether the FDA has determined a biological product to be biosimilar to or interchangeable with a reference biological product.

FDA Releases Final Medical Device Cybersecurity Guidance, Schedules Workshop on Topic

Yesterday the FDA issued final guidance entitled “Content of Premarket Submissions for Management of Cybersecurity in Medical Devices,” which includes recommendations for medical device manufacturers on cybersecurity management and information that should be included in a pre-market submission. The recommendations are intended to supplement previous FDA guidances, “Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices,” and “Guidance to Industry: Cybersecurity for Networked Medical Devices Containing Off-the-Shelf (OTS) Software.”

In a related development, on October 21-22, 2014, the FDA is holding a public workshop on “Collaborative Approaches for Medical Device and Healthcare Cybersecurity.” Through the workshop, FDA seeks to encourage collaboration among stakeholders, identify challenges, and discuss strategies and best practices for promoting medical device cybersecurity.

Upcoming House Hearings to Address ACA Implementation, Accelerating Medical Innovation

On September 9, 2014, the House Energy and Commerce Subcommittee on Health is holding a hearing entitled “21st Century Cures: Examining the Regulation of Laboratory Developed Tests.” The hearing will focus on the FDA’s recent guidance on the regulation of lab developed tests and its “impact on innovation and the practice of precision medicine.” The panel will also host a “roundtable” discussion September 10 at which HHS Secretary Burwell, NIH Director Collins, FDA Commissioner Hamburg, and other experts will address opportunities to accelerate the discovery, development, and delivery of new cures and treatments. In addition, two hearings are scheduled on ACA implementation. On September 10, the House Ways and Means Subcommittee on Health will review ACA Marketplace administration, including verification of tax credit eligibility. On September 18, the House Oversight and Government Reform Committee will address Healthcare.gov transparency, accountability, and information security.

House Panel to Examine FDA Lab-Developed Test Policy

On September 9, 2014, the House Energy and Commerce Subcommittee on Health is holding a hearing entitled “21st Century Cures: Examining the Regulation of Laboratory Developed Tests.” The hearing will focus on the FDA’s recent guidance on the regulation of lab developed tests and its “impact on innovation and the practice of precision medicine.”

FDA Seeks Comments to Updated Guidance on Informed Consent in Clinical Trials

This post was written by Jennifer Pike and Vicki Morris.

Earlier this summer, the Food and Drug Administration (FDA) issued a draft 42-page "Informed Consent Information Sheet" that provides guidance for institutional review boards (IRBs), clinical investigators, and clinical trial sponsors on complying with the Agency’s informed consent regulations. Once finalized, the draft guidance will supersede FDA’s previous Information Sheet on this topic, "A Guide to Informed Consent," which was last updated over 15 years ago, in 1998.  The guidance, which is a compilation of FDA’s regulations and past guidances on informed consent, also reflects the Agency’s coordinated efforts with the Department of Health and Human Services (HHS) to facilitate consistency across informed consent requirements and policies among federal government agencies.

Broadly, the new guidance indicates FDA policy shifting towards enhanced informed consent processes. More narrowly, the draft guidance explains the various and often caveated elements of informed consent (including providing patients with a description of the trial, its risks, benefits, alternative treatments, confidentiality and compensation in the event of injury), depicts the detailed responsibilities of IRBs, clinical investigators and sponsors of clinical trials (including compliance with the process, elements and documentation of informed consent), and provides examples of recommended language to assist industry parties in complying with FDA’s informed consent regulations. FDA accomplishes this task by clarifying some aspects of existing guidance and creating additional guidance in new areas.

The following provides an overview of some of the draft guidance’s notable new and revised provisions.

  • Risks and discomforts: In a new policy, FDA states that “all possible risks do not need to be described in detail in the informed consent form, especially if it could be overwhelming for subjects to read.” Instead, FDA states that only risks that are more likely to occur and those that are serious should be included. This is a change from the 1998 information sheet in which FDA stated that “[a]ny procedures relating solely to research…should be explained to the subjects.”
  • Alternative procedures: Like FDA’s new stance on risks and discomforts, the Agency does not require that all alternative treatments be explained. Unlike the 1998 information sheet, which stated that “subjects should be aware of the full range of options available to them,” now the Agency states that “it may be appropriate to refer the subject to a healthcare professional who can more fully discuss the alternatives.” Although FDA clarifies that such a referral should be completed before the subject signs and dates the informed consent form, the question remains as to how an investigator should document the referral.
  • Off-label use disclosure: FDA clarifies in the guidance that disclosures of alternative treatment, as required under 21 C.F.R. 50.25(a)(4), must include a description of medically recognized standards of care, which may include off-label uses of approved products. FDA’ position on the disclosure of off-label uses is likely to create a new burden for investigators and sponsors to determine when an off-label use of a product has become a “standard of care.”
  • Impaired consent capacity: The guidance introduces a new section on obtaining informed consent of patients with impaired consent capacity, ranging from minor or temporary impairments to complete or permanent impairments. In these cases, FDA suggests that clinical trial enrollment forms may require modification, and that investigators should consider if including patients with impaired consent capacity is “ethically appropriate and scientifically necessary.”
  • Alternative methods of obtaining informed consent: In this new section, FDA recognizes that new technologies (e.g., fax or email) may be used as part of the consent process and may serve as an alternative to the traditional paper consent form. FDA encourages those interested in pursuing alternative methods of obtaining informed consent to contact the Agency and provide comments on these alternative methods.
  • Reviewing patient records: The guidance indicates that sponsors and investigators may seek to review patient medical records for a variety of reasons related to a clinical investigation, such as to determine if a patient is eligible for a clinical trial or to retrospectively review the records of a previously enrolled patient. Whether consent or “reconsent” of the patient is necessary is determined on a case-by-case basis. Apart from a potential need for consent, sponsors and investigators must also consider the need to comply with federal and state privacy laws, such as HIPAA.
  • Multiple trial participants: FDA “strongly discourages” the practice of individual patients participating in multiple and simultaneous clinical trials or enrolling in a single clinical investigation multiple times. The Agency’s rationale is partly due to medical safety reasons for the patient, and also due to the high likelihood of trial subjects not fully understanding all the risks, proposed benefits and demands of multiple trial protocols, thereby delegitimizing informed consent.
  • Affirmative right to compensation for injury: Expanding FDA regulation that requires informed consent documents to include a “statement that compensation or medical treatment are or are not available if unanticipated injuries occur and of what they consist,” the draft guidance encourages sponsors to include in informed consent forms an affirmative statement that subjects are “not precluded from seeking to collect compensation for injury related to malpractice, fault or blame on the part of those involved in the research.”

In addition to the above new and expanded sections, the guidance also offers additional insight into topics such as “assent” to research by children, informed consent of non-English-speaking clinical trial participates, and when to disclose to subjects when an investigator conflict of interest exists or when a study has been suspended or terminated.

The new guidance raises many questions and considerations for clinical trial sponsors, investigators and IRBs and provides an important opportunity for these industry parties to provide comments to FDA. Comments on the draft guidance are due to FDA by September 15, 2014 and can be submitted here.

About the Authors: Jennifer Pike (associate) and Vicki Morris (Law Clerk) are members of the firm’s Life Sciences Health Industry Group and is based in our Washington, D.C. office.

FDA Public Hearing on the Implementation of Generic Drug User Fee Amendments (Sept. 17)

This post was written by Jennifer Pike and Vicki Morris

On September 17, 2014 the Food and Drug Administration (“FDA”) is holding a public hearing at the College Park Marriot Hotel and Conference Center, in Hyattsville, MD, to discuss the Agency’s implementation of the Generic Drug User Fee Amendments of 2012 (GDUFA) and its obligations under GDUFA as set forth in the GDUFA Commitment Letter accompanying the legislation. The central purpose of GDUFA is to help speed the delivery of safe and effective generic drugs to the public and to reduce costs to industry. GDUFA requires manufacturers to pay a user fee to supplement FDA’s costs of reviewing generic drug applications and inspecting facilities. Per the GDUFA Commitment Letter, the user fees enable the Agency to reduce a backlog of pending applications, cut the average time required to review generic drug applications for safety, and increase risk-based inspections.

At the public hearing, FDA will focus on two particular aspects of GDUFA: (1) soliciting public comment on the five draft guidance documents that FDA has issued to facilitate implementation of the law, and (2) recommending future policy priorities, including recommendations for additional guidance topics to facilitate GDUFA implementation (e.g., 180-day generic drug exclusivity, and potential first generics). The meeting will provide an opportunity for public input from all interested parties, including regulated industry, consumers, patients, caregivers, health care professionals, and patient groups, on future FDA policy priorities.

To register for the hearing or to make a request to make an oral presentation at the hearing, send an email to GenericDrugPolicy@fda.hhs.gov, by September 3, 2014, that includes the complete contact information for each attendee, including name, title, affiliation, address, email address and telephone number. FDA will accept electronic and written comments on this topic after the hearing until October 13, 2014. Electronic comments may be submitted at www.regulations.gov

About the Authors: Jennifer Pike (Associate) and Vicki Morris (Law Clerk) are both members of the firm’s Life Sciences Health Industry Group and are based in our Washington, D.C. office.

FDA Meeting on Biomarker Development (Sept. 5)

On September 5, 2014, the FDA is holding a public meeting at the Washington Plaza Hotel, in Washington DC, to discuss current scientific and regulatory approaches to biomarker development, acceptance, and utility in the development of therapeutic products (e.g., drugs and biologics). Specifically, FDA will focus on (1) identifying challenges for biomarker applications in early- and late- phase clinical trials, and (2) emerging best practices for successful biomarker-based programs (including codevelopment of in vitro diagnostic devices and use of biomarkers as outcome measures in clinical trials). Public input from the meeting will be used to identify opportunities for biomarker-related regulatory guidance, improve understanding and consistency in regulatory review of therapeutic product applications that incorporate biomarkers in clinical trial designs, and identify potential strategies to facilitate scientific exchanges in regulatory and non-regulatory contexts. For more information on the meeting, which is being held in collaboration with Brookings Institution, and for early registration deadlines to attend the live meeting, see the FDA announcement.  FDA will also accept comments on this topic through November 5, 2014.

FDA Will Not Enforce Compliance for Mobile Device Data Systems and Other Low Risk Devices, Agency Reports

This post was written by Jennifer Pike.

In a new draft guidance document, the Food and Drug Administration (FDA) has announced that it does not intend to enforce compliance with general regulatory controls that apply to Medical Device Data Systems (MDDS), medical image storage devices and medical image communications devices.

MDDS refers to hardware and software that transfers, stores, converts format and displays medical device data, but that does not modify the data or control the functions or parameters of any connected medical device. In 2011, MDDS were classified by FDA as Class I medical devices subject to general regulatory controls under the Federal Food, Drug and Cosmetic Act. FDA has since determined that MDDS pose a low risk to the public and play an important role in advancing health.  The agency has therefore decided not to enforce compliance with the controls that apply to MDDS, medical image storage devices and medical image communications devices (e.g., registration and listing, premarket review, postmarket reporting and quality system regulation).

The draft guidance also proposes changes to FDA’s draft guidance titled “Mobile Medical Applications” issued on September 25, 2013 to conform with the new draft guidance.

Comments regarding the draft guidance should be submitted to FDA by August 25, 2014.

FDA Releases Drug/Device Industry Social Media Guidance Documents

The FDA released two draft social media guidance documents last week, describing how manufacturers, packers and distributors of prescription drugs and medical devices may: (1) communicate both benefit and risk information on Internet/social media platforms with character space limitations, and (2) correct independent third-party misinformation about a firm’s products.  For details, see Reed Smith's Client Alert posted on our Life Sciences Legal Update blog.

FDA Issues Draft Guidance on Communicating New Risk Information about an Approved Drug Product - Comment Opportunity

This post was written by Jillian W. Riley.

On June 6, 2014, the US Food and Drug Administration (FDA) issued a draft guidance addressing the distribution of new risk information to health care providers (HCPs) and health care entities (HCEs). The draft guidance defines “new risk information” as “information that becomes available after a drug is marketed that rebuts or mitigates information about a risk already identified in the approved labeling or otherwise refines risk information in the approved labeling in a way that does not indicate great seriousness of the risk.” The draft guidance is not intended to address risk information that is newly identified, but that which was not available at the time FDA approved the labeling. Acknowledging the evolving nature of a drug’s safety profile, the draft guidance is aimed at helping sponsors better communicate “new risk information” in order to allow HCPs and HCEs make the best decision for each patient.

Through the guidance, FDA lays out criteria for determining the appropriate circumstances under which to distribute “new risk information” to HCPs and HCEs. FDA does not intend to object to the distribution of new risk information as long as the distribution is consistent with the criteria established in the draft guidance.

The criteria are broken into two categories, those governing the data source and those governing the distribution. Both criteria categories must be met in order for a drug company to distribute new risk information that rebuts, mitigates, or refines risk information in the approved labeling.

Data source criteria include the following:

  • The study or analysis should meet accepted design and other methodologic standards and be sufficiently well-designed and informative;
  • If the data rebuts a prior determination about a causal connection between the drug and an adverse event, the study or analysis should be at least as persuasive as the data it is rebutting;
  • The conclusions should give appropriate weight and consideration to all relevant information in the safety database, including contrary or otherwise consistent findings; and
  • The study or analysis should be published in an independent, peer-reviewed journal.

Distribution criteria include the following:

  • The reprint or digital copy should be accompanied by a cover sheet that clearly and prominently discloses:
    • The study design, critical findings, and significant methodology
    • That the information is NOT consistent with certain risk information in the approved labeling
    • That FDA has not reviewed the data; and
    • Any financial interests or affiliations between the study author(s) and the drug company;
  • The reprint or digital copy should be accompanied by the approved product labeling;
  • The reprint or digital copy should be separate from any promotional material; and
  • Any statements made by a drug company representative to a HCP or HCE concerning the reprint should be consistent with the content and the disclosure information.

Comments on the draft guidance should be submitted by August 20, 2014.

FDA Initiative Opens Door to Easily Accessible, User-Friendly Data

This post was written by Jennifer Pike.

Yesterday, the U.S. Food and Drug Administration (FDA) made available data on millions of reports of drug adverse events and medication errors made to FDA between 2004 and 2013. The release of the data is part of FDA’s new data sharing initiative, openFDA, which is designed to make it easier for developers, researchers and the public to access data collected by FDA. OpenFDA organizes large amounts of publicly-available data in a structured, computer-readable format and makes it possible for users to instantaneously search and pull the data for their own use. . According to Walter Harris, FDA’s chief operating officer and acting chief information officer, “openFDA is a valuable resource that will help those in the private and public sectors use FDA public data to spur innovation, advance academic research, educate the public, and protect public health.”

For now, openFDA will begin as a pilot program with data involving the drug adverse event and medication error reports. FDA will later expand openFDA to include data on product recalls and product labeling.

Expedited Drug Development and Review: New FDA Resource Now Available

This post was written by Jennifer Pike.

A new guidance entitled “Expedited Programs for Serious Conditions – Drugs and Biologics” is now available from the Food and Drug Administration (FDA). The 40-page guidance is intended to serve as a single resource for information on FDA’s policies and procedures related to its four expedited drug development and review programs: (1) fast track designation, (2) breakthrough therapy designation, (3) accelerated approval, and (4) priority review designation. The guidance also defines the threshold criteria generally applicable to each program, including when a condition is considered “serious,” when a therapy is “available therapy,” and when a medical need is “unmet.”   The guidance follows the 2012 passage of the Food and Drug Administration Safety and Innovation Act, which called for FDA to expand its efforts to expedite the development and review of drugs intended to treat serious conditions.  Comments regarding the guidance may be submitted at any time.

FDA Workshop to Focus on 3-D Printing of Medical Devices

According to the Food and Drug Administration (FDA), additive manufacturing, also known as 3-D printing, is entering mainstream use in medical devices, both as an alternative device production method for traditional components and as a method to create patient-matched devices. FDA has begun to receive submissions using additive manufacturing for medical devices, and the agency sees “many more on the horizon.” As the use of additive manufacturing becomes more widespread, the FDA wants additional information on scientific and technical challenges associated with the use of such technology for medical devices, particularly with regard to process verification and validation to ensure patient safety. To that end, the FDA is hosting a public workshop on October 8 and 9, 2014 entitled “Additive Manufacturing of Medical Devices: An Interactive Discussion on the Technical Considerations of 3-D Printing.'' The meeting is intended to provide a forum for FDA, medical device manufactures, additive manufacturing companies, and academia to explore this issue in detail, including ways to provide a transparent evaluation process for future submissions. The workshop discussion may facilitate development of new draft guidances and/or standards for additive manufacturing of medical devices. Comments on the workshop topic will be accepted until November 10, 2014.

Hundreds of Drugs and Biologics Face Labeling Changes under New FDA Plan

This post was written by Jennifer Pike.

In a notice published in the Federal Register on May 7, 2014, the U.S. Food and Drug Administration (“FDA”) announced its intent to incentivize manufacturers to voluntarily update their prescription drug and biologics labels by using a government contractor.

FDA’s announcement stems from a January 2006 final rule in which FDA established revised content and format requirements for prescription drugs and biologics (the “Physician Labeling Rule” or “PLR”). The PLR required drugs and biologics approved after June 30, 2001 to adopt the new labels. A detailed implementation schedule under the PLR, which only resulted in only 15% of all drug and biologics being labeled in the PLR format, expired in November 2013. Therefore, moving forward, the only products which will be labeled in the PLR format will be new drugs and biologics and drugs that are voluntarily updated. To address this lack of labeling conversion, on February 6, 2013, FDA proposed the Prescription Drug Labeling Improvement and Enhancement Initiative. As part of the initiative, and as explained in detail in FDA’s notice, FDA plans to use a government contractor to provide PLR conversion resources and services, including preparation of draft PLR format labeling, in hopes of facilitating voluntary conversion.

The number of drugs and biologics affected by FDA’s initiative is staggering. FDA estimates that 375 manufacturers will be contacted over a 5 year period regarding 750 products. FDA will select the products for labeling conversion based on criteria that would maximize the benefit to public health, including volume of prescriptions, clinical relevance, and risk-based  considerations. Beyond the 750 products selected for PLR conversion, FDA further estimates that over 1,800 generic products will require labeling updates to reflect changes made to the corresponding brand-name products.

FDA is seeking public comment on its collection of information related to the initiative. Comments should be submitted in writing, or electronically at www.regulations.gov, on or before July 7, 2014.

Busy Week for FDA's Center for Devices and Radiological Health

This post was written by Jillian W. Riley

Earlier this week, FDA’s Center for Devices and Radiological Health (CDRH) published two separate draft guidance documents to advance the dual goals of FDA and industry to provide pathways for medical devices to reach the market quickly while ensuring the safety and efficacy of the product.

The first guidance, entitled Balancing Premarket and Postmarket Data Collection for Devices Subject to Premarket Approval, clarifies FDA’s current thinking on creating an effective means to achieve “the right balance of premarket and postmarket data collection facilitates timely access to important new technology without undermining patient safety.” Greater reliance on postmarket data collection can help a new product reach the market – and patients – sooner. One key factor FDA considers when determining whether postmarket data collection is appropriate is the device’s potential impact on public health. For example, and as discussed more thoroughly in the separate guidance discussed below, FDA may accept greater pre-approval uncertainty regarding specific benefits and risks of devices where there is demonstrated potential to address unmet medical needs.

The second guidance, Expedited Access for Premarket Approval Medical Devices Intended for Unmet Medical Need for Life Threatening or Irreversibly Debilitating Diseases or Conditions, proposes a new expedited review program for medical devices that address unmet medical needs and are subject to premarket approval (PMA) applications. The program laid out in the draft guidance establishes opportunities for earlier and more active engagement between sponsors and FDA staff, including earlier involvement of senior management to ensure more consistency in messaging to industry. The early interactions aim to establish better plans for efficient collection of the scientific and clinical data necessary to support FDA’s approval determinations. The guidance also describes the criteria an applicant must meet in order to obtain an expedited access PMA designation.

FDA will be accepting comments regarding the draft guidances until July 23, 2014.

Will Physician Payment Sunshine Act Data Usher in a New Era of False Claims Act Litigation?

This post was authored by Scot Hasselman, Elizabeth Carder-Thompson, Katie Pawlitz and Jillian Riley.

While attention has been focused on Medicare physician payment data released by CMS yesterday, upcoming Sunshine Act data will shine a new spotlight on financial relationships between physicians and pharmaceutical and medical device companies – with potential FCA implications.

Last week marked the deadline for pharmaceutical and medical device manufacturers and group purchasing organizations (GPOs) to register with and submit aggregate 2013 payment and investment interest data to the Centers for Medicare & Medicaid Services (CMS) on certain financial relationships between themselves and physicians and teaching hospitals, as required by the Physician Payment Sunshine Act.1 In May, manufacturers and GPOs will be required to submit to CMS detailed 2013 payment data. With some exceptions, CMS will be making these data public by September 1, 2014. While the publicly available data are intended to provide more transparency for patients – to allow them to have a better understanding of the financial relationships between physicians and pharmaceutical and medical device companies – patients will certainly not be the only group interested in this public information. The Department of Health and Human Services (HHS) Office of the Inspector General (OIG), Department of Justice (DOJ), and relators’ attorneys will likely utilize these data to initiate investigations and support complaints under the federal False Claims Act (FCA). As with the recent release of the 2012 Medicare Part B Physician Fee Schedule data, members of the media will likely make inferences about certain financial relationships.

The U.S. government recovered $3.8 billion in settlements and judgments from civil cases involving fraud against the government in the fiscal year ending Sept. 30, 2013.2 Fiscal 2014 looks to be a record-breaking year, with ever-increasing civil settlements by major pharmaceutical companies.3

As the reporting deadlines approach, it is worth considering an interesting, and largely unknown, potential implication of the public availability of these data: How will it affect future FCA litigation? The publically available Sunshine Act data could become relevant to FCA litigation in a variety of ways; two in particular are discussed below.

Anti-Kickback Statute Violations

The data could give rise to suspicions of violations of the federal Anti-kickback Statute (AKS). The AKS makes it a criminal offense to knowingly and willfully offer or pay remuneration to induce the referral of, or arrange for the provisions of, federal health care program business.4 In other words, the law prohibits any person or entity from giving, receiving – or offering to give or receive – anything of value in return for or to induce referrals for businesses covered by Medicare, Medicaid, or any other federally funded health care program. Violators of the AKS face imprisonment, criminal, and civil fines, as well as exclusion from federal health care programs.5

It is easy to see how publishing information regarding payments from pharmaceutical and medical device manufacturers to physicians and teaching hospitals could implicate the AKS, and by extension, the FCA. The Patient Protection and Affordable Care Act (ACA) made explicit that violations of the AKS are also violations of the FCA.6 Any payment from a pharmaceutical or medical device manufacturer to a physician who prescribes a product manufactured by the company providing the payment could be viewed as potentially inappropriate remuneration intended to influence prescribing behavior.

Off-Label Promotion

Publically available information reported as a result of the Sunshine Act may also have off-label promotion implications. Notably, reports to CMS must include the name of the drug or the type of device that forms the basis of the payment.7 Tying the payment to a particular drug or type of device could raise suspicions of off-label promotion. A pharmaceutical or medical device manufacturer that promotes its products for uses for which the product has not yet been approved by the United States Food and Drug Administration (FDA), i.e., off-label uses, is at risk of FCA liability. A false claim can arise when a manufacturer promotes a product for off-label, non-covered uses (that is, for a use that both has not been approved by FDA and is not covered by the federal health care programs). Payments going to physicians who specialize in an area that is outside the scope of a pharmaceutical or medical device’s approved indication could necessarily raise suspicions that the manufacturer is promoting the product for unapproved uses.

Potential Limits

Besides the risk of government identifying potential issues for further investigation and prosecution as a result of reported Sunshine Act data, private parties may also mine the publically available data. One substantial impediment to relators’ attorneys using Physician Sunshine Payment data in FCA litigation is the limitation that publicly available data cannot form the basis of a whistleblower claim.8 This is known as the public disclosure bar, although the effectiveness of this defense has been diminished with recent FCA amendments.

That said, the Sunshine Act data, even if not the basis of a claim, could nonetheless impact the litigation in many ways. For example, it could provide additional evidence for the government to review in reaching its decision whether to intervene in a qui tam action. Both OIG and DOJ could review the data before it is publicly available to assist in the determination that a given matter warrants intervention. Additionally, the publicly available data – beyond providing flavor in support of an FCA claim and assisting with meeting the heightened pleading standard associated with fraud allegations9 – could be a potential mine for plaintiff attorneys to locate areas of focus. Relators’ attorneys will no doubt track the data to ascertain potential problem drugs or companies about which they can then dedicate efforts to uncovering fraud and abuse in the federal health care system.

Going Forward

It remains to be seen how all of these risks will play out going forward. Courts will have to decide how these new data will fit into FCA litigation. OIG and DOJ will have to determine how much to rely on the new information. And relators’ attorneys will need to make decisions about how many resources to dedicate to mining the Sunshine Act data.

One potential consequence that we are already starting to see occur is that pharmaceutical and medical device manufacturers may halt or limit payments to physicians, and/or that physicians themselves will be reluctant to accept such payments, e.g., for research, for expenses associated with training on a device, and the like. Companies may decide to do so for a variety of reasons, including avoiding the administrative burdens associated with tracking and reporting such payments for purposes of the Sunshine Act, fear of FCA litigation, or for public relations reasons. Many physicians simply do not want their names publicized. It remains to be seen how these trends will evolve.
 

1 42 C.F.R. § 403.908(a).
2 DOJ Press Release, available at: http://www.justice.gov/opa/pr/2013/December/13-civ-1352.html. 3 See, e.g., DOJ Press Release, available at: http://www.justice.gov/opa/pr/2013/November/13-ag-1170.html.
4 42 U.S.C. § 1320a-7.
5 Id.
6 42 U.S.C. § 1320a-7b(g). Note that manufacturers may submit “assumptions documents” as part of Sunshine reporting. Although CMS stated in the preamble to the Sunshine regulations its belief that the contents of such documents “should not be made public,” it acknowledged that it could provide access to the documents during an audit or investigation by other HHS divisions, the Office of Inspector General, or the Department of Justice.
7 42 C.F.R. 403.94(c)(8).
8 31 U.S.C. § 3730(e)(4).
9 Fed. R. Civ. P. Rule 9(b).

April Congressional Hearings

Recent Congressional hearings on health policy issues include the following:

  • House Energy and Commerce Committee hearings on the “Helping Families in Mental Health Crisis Act”; the FDA’s proposed changes to generic drug labeling; and legislation intended to improve predictability and transparency in Drug Enforcement Agency and FDA regulation (H.R. 4299, H.R. 4069, and H.R. 4250).
  • House Ways and Means Health Subcommittee hearing on final Treasury Department regulations implementing the employer mandate and employer information reporting requirement provisions of the ACA..

In addition, on April 9, 2014, the Senate Health, Education, Labor and Pensions Committee is holding a hearing on “Addressing Primary Care Access and Workforce Challenges: Voices from the Field.”

FDA Proposal Amends Medical Device Classification Rules

This post was written by Jennifer Pike.

On March 25, 2014, the Food and Drug Administration (FDA) published a proposal to amend its regulations governing the classification and reclassification of medical devices. In addition to conforming the regulations to recent changes made by the 2012 Food and Drug Administration Safety and Innovation Act (FDASIA), the proposed rule makes changes unrelated to FDASIA. Among other changes to 21 CFR Part 860, FDA proposes to:

  • Amend several definitions at 21 CFR § 860.3, including the definitions of Class I, Class II and Class III to reflect the key principle underlying device classification that a reasonable assurance of safety and effectiveness is necessary for all three classes, but that the level of regulation necessary to provide such assurance is specific to the level of risk.
  • Amend the definition of Class III to clarify which devices fall in this category.
  • Establish special controls for Class II devices by replacing the term “performance standards” in 21 CFR § 860.7.
  • Amend 21 CFR § 860.84 to remove from the classification process the requirement to answer the classification questionnaire and provide information using the supplemental data sheet.
  • Revise the procedure at 21 CFR § 860.130 to reflect the FDASIA requirement that devices reclassified under 513(e) of the Food, Drug and Cosmetic Act be reclassified using an administrative order procedure.
  • Revise the process under 21 CFR § 860.133 for the filing of a premarket approval for Class III preamendment devices to conform to FDASIA.

Comments to the proposed rule may be submitted in writing, or at www.regulations.gov, on or before June 23, 2014.

March Congressional Health Policy Hearings

Congressional panels continue to hold hearings to address various health policy issues, including the following:

Older Entries

March 14, 2014 — Drug Companies are Reminded - FDA is Following Facebook

February 27, 2014 — There are HOW many calories in that? FDA Seeks Comments on Proposal to Update Nutrition Facts Food Label

February 24, 2014 — FDA to Overhaul an OTC System That "Isn't Working"

February 24, 2014 — Coming to a TV Near You? FDA Seeks Public Input on Limiting Risks Presented in Direct-to-Consumer Television Ads

January 28, 2014 — FDA Provides Direction on "Dear Doctor" Letters

January 20, 2014 — FDA Seeks Comments on Drug Company Social Media Guidance

January 7, 2014 — CMS, FDA Extend Pilot Program for Parallel Review of Medical Products

January 7, 2014 — FDA Releases Final Guidance on Qualification Process for Drug Development Tools

December 10, 2013 — Drug Distribution Security Legislation Signed into Law

November 14, 2013 — Congressional Hearings Focus on HealthCare.gov Enrollment, Other Policy Issues

August 2, 2013 — FDA Proposes New Rule to Exercise its Administrative Detention Authority for Drugs

August 2, 2013 — New Draft Guidances from FDA Address Expedited Review, Safety Labeling and More

June 20, 2013 — Draft FDA Guidance Recommends Cybersecurity Risk Assessments and Management Plans for Premarket Medical Device Submissions

June 20, 2013 — FDA Amends Orphan Drug Regulations

June 5, 2013 — House Approves Drug Distribution Security Plan

May 28, 2013 — FDA Issues New Draft Guidance Documents on Access to Investigational Drugs

April 15, 2013 — April Congressional Health Policy Hearings & Markups

April 15, 2013 — FDA Draft Guidance on Biosimilar Product Development Now Available

March 12, 2013 — FDA Issues New Guidance Documents

January 29, 2013 — FDA Issues Final Rule on Current Good Manufacturing Practice Requirements for Combination Products

January 29, 2013 — FDA Announces 2013 Generic Drug Active Pharmaceutical Ingredient and Finished Dosage Form Facility User Fee Rates

January 29, 2013 — New FDA Draft Guidance Addresses Combination Product Postapproval Modification Submissions

January 14, 2013 — Obama Administration's Regulatory Agenda Points to Busy 2013 for HHS

January 11, 2013 — FDA Requests Comments on Review of Medical Device Submissions

January 11, 2013 — FDA Issues Final Guidance Documents on Drug and Medical Device Submissions

January 11, 2013 — FDA Releases Draft Guidance Documents on Providing Submissions in Electronic Format

January 11, 2013 — FDA Draft Guidance Addresses Clinical Trial Enrichment

January 11, 2013 — FDA Issues Two Final Guidances on Safety Reporting Requirements

January 11, 2013 — FDA To Hold Workshop on Accessible Standardized Medical Device Labeling (April 29-30)

December 18, 2012 — FDA Issues Two New Draft Guidance Documents Related to the Conduct of Clinical Trials

December 18, 2012 — New FDA Draft Guidance Documents Address Product Safety and Risk Minimization

November 28, 2012 — FDA Addresses Food and Drug Administration Safety and Innovation Act (FDASIA) Implementation

November 28, 2012 — Upcoming FDA Public Meeting: Framework for Pharmacy Compounding/State and Federal Roles (Dec. 19)

November 12, 2012 — November Congressional Health Policy Hearings

October 31, 2012 — FDA Issues Generic Drug User/Backlog Fee Notices

October 16, 2012 — GAO Flags Concerns about Implantable Medical Device Information Security

October 16, 2012 — OIG Examines Dietary Supplement Claims, Registration with FDA

October 15, 2012 — Short-Term Government Funding, FDA User Fee & Safe Doses Bills Signed into Law

September 27, 2012 — Generic Drug User Fee Fix Cleared by Congress

September 27, 2012 — FDA Meetings on Patient-Focused Drug Development Initiative

September 6, 2012 — FDA Final Rule Implementing Device Registration and Listing Requirements

September 6, 2012 — Draft Guidance Regarding Self-Identification of Generic Drug Facilities and Q&A on Generic Drug User Fee Amendments

September 5, 2012 — FDA Establishes FY 2013 User Fee Rates for Biosimilars and Prescription Drugs

September 5, 2012 — FDA Guidance on FY 2013 Medical Device User Fee Small Business Qualification and Certification

September 5, 2012 — FDA Issues Guidance for Comment on Refuse to Accept Policy for 510(k)s

July 31, 2012 — Medical Device User Fee Rates for FY 2013

July 31, 2012 — FDA Issues Draft Guidance Regarding Acceptance & Filing Review for PMA Applications

July 16, 2012 — FDA Proposes Unique Device Identification System for Medical Devices

July 16, 2012 — FDA Draft Guidance the Medical Device Pre-Submission Program/Meetings with FDA Staff

July 16, 2012 — FDA Small Entity Compliance Guidance: Toll Free Number Labeling for Drugs

July 16, 2012 — FDA Draft Guidances Describe Product-Specific Bioequivalence Recommendations

July 16, 2012 — FDA Draft Guidance Document on Transferring Clinical Investigation Oversight to Another IRB

July 16, 2012 — FDA Guidance Addresses Genotoxicity Testing and Data Interpretation for Human Drugs

June 28, 2012 — Congress Clears FDA Safety & Innovation Act

June 18, 2012 — OIG Examines Scientific Disagreements at CDRH Regarding Medical Device Reviews

May 31, 2012 — House, Senate Approve FDA User Fee/Drug Safety Bills

May 11, 2012 — House Panel Unanimously Approves FDA User Fee Act

May 11, 2012 — FDA Final Rule on Disqualification of Clinical Investigators

May 11, 2012 — FDA Issues Final Rule on Sterility Testing of Biological Products

May 11, 2012 — FDA Guidance on Medical Device Pre-market Approval

May 11, 2012 — FDA Seeks Information on Risks, Benefits of Metal-on-Metal (MoM) Hip Replacements

May 11, 2012 — FDA Reports on Post-Approval Drug Safety Monitoring

May 11, 2012 — International Collaboration Highlighted in FDA Global Engagement Report

April 23, 2012 — GAO Examines FDA Device Review Process

April 2, 2012 — House Approves IPAB Repeal/Medical Liability Reform Legislation

March 30, 2012 — FDA Announces Delayed Enforcement of ACA Drug Sample Distribution Reporting Requirement

March 29, 2012 — Congressional Health Policy Hearings

March 29, 2012 — FDA Draft Guidance on Classifying Significant Postmarket Drug Safety Issues

March 29, 2012 — FDA Issues Guidance Update on Communication to the Public about Drug Safety

March 29, 2012 — Draft FDA Guidance Targets Direct-to-Consumer Television Marketing

March 14, 2012 — FDA Issues Three Draft Guidance Documents on Biosimilar Product Development; Announces May 11 Public Hearing

March 14, 2012 — FDA Draft Guidance on Safety Data Collection for Late Stage Premarket & Postmarket Investigations

March 14, 2012 — Congressional Hearings on Drug Issues.

March 14, 2012 — FDA Public Hearing Regarding Regulation of Clinical Trials (April 23-24)

February 13, 2012 — FDA Issues Guidance on New Informed Consent Requirements

February 10, 2012 — Final Rule Regarding Labeling Requirements for Products Held in Strategic National Stockpile

February 10, 2012 — FDA and Industry Reach Agreement in Principle on Medical Device User Fees

February 10, 2012 — FDA Q&A/Draft Guidance for Industry Related to PET Drug Products

February 10, 2012 — FDA Report on Exploratory Program to Increase Access to Agency Compliance and Enforcement Data

February 10, 2012 — February Congressional Health Policy Hearings

January 25, 2012 — Fall 2011 Regulatory Agenda (Belatedly) Released

January 25, 2012 — FDA Seeks Comments on Prescription Drug Promotion Survey

January 25, 2012 — FDA Completes Work on Three Drug User Fee Programs

January 25, 2012 — FDA Guidance on Product Name Placement in Advertising and Promotional Labeling

January 25, 2012 — E&C Health Subcommittee Plans FDA User Fee Hearings in February

January 23, 2012 — E&C Health Subcommittee Plans FDA User Fee Hearings in February

January 5, 2012 — GAO Report on Pediatric Medical Devices

January 4, 2012 — FDA Rule Expands Drug Manufacturer Notification Requirements for Potential Drug Shortages

December 29, 2011 — FDA Guidance Regarding Responding to Unsolicited Requests for Off-Label Information

December 29, 2011 — FDA Issues Draft Guidance Regarding Evaluation of Sex Differences in Medical Device Clinical Studies

December 29, 2011 — FDA Provides Draft Guidance on Evaluating Substantial Equivalence in Premarket Notifications

December 29, 2011 — FDA Guidance Regarding CDRH Appeals Process

December 13, 2011 — FDA Publishes Notice on Biosimilar Biological Product User Fees

December 13, 2011 — FDA Draft Guidance on Artificial Pancreas Device Systems, Hepatitis B Screening of Blood/Blood Components

December 12, 2011 — FDA Public Meeting on Generic Drug User Fees (Dec. 19)

November 10, 2011 — FDA Announces Review of Bar Code Final Rule

November 10, 2011 — President Issues Executive Order Regarding Drug Shortages

October 28, 2011 — Correction Notice on CMS/FDA Parallel Review Pilot Program

October 25, 2011 — FDA Proposes Amendments to Orphan Drug Rules

October 14, 2011 — FDA Issues Final Guidance on Risk Labeling for Prescription Drugs and Biological Products