As discussed on our Life Sciences Legal Update blog, the FDA has released draft guidance clarifying its acceptance of medical device clinical data from studies conducted outside of the United States. The draft guidance highlights special considerations that apply when using foreign clinical data, including applicability to populations within the US, and provides recommendations to assist sponsors in ensuring their data are adequate under applicable FDA standards. Comments on the guidance are due by July 20, 2015.
CMS and FDA are establishing an interagency task force to reinforce their collaboration regarding the oversight of laboratory-developed tests (LDTs), which are tests intended for clinical use and designed, manufactured, and used within a single lab. According to an FDA blog post, the goals of the FDA/CMS task force include: (1) identifying areas of similarity between the FDA quality system regulation and requirements under the Clinical Laboratory Improvement Amendments (CLIA); (2) working together to clarify responsibilities for laboratories that fall under the purview of both agencies; and (3) leveraging joint resources to avoid duplication and maximize efficiencies.
On March 10, 2015, the Senate Health, Education, Labor and Pensions (HELP) Committee held a hearing on “Continuing America’s Leadership in Medical Innovation for Patients,” featuring testimony from NIH Director Francis Collins, MD, PhD, and FDA Commissioner Margaret Hamburg, MD.
On March 17, the HELP Committee has scheduled a hearing on “America’s Health IT Transformation: Translating the Promise of Electronic Health Records into Better Care.” The Senate Finance Committee is holding a hearing on the “Affordable Care Act at Five Years” on March 19.
The Energy and Commerce has not yet rescheduled a previously-announced hearing on the 340B drug pricing program that was cancelled due to weather.
On April 1, 2015, the FDA is hosting a workshop entitled “Clinical Outcomes Assessment Development and Implementation: Opportunities and Challenges.” The workshop will update the public on ongoing efforts in the use of clinical outcome assessments (COAs), and plan for the future of COA development and utilization in drug development programs. The workshop will also discuss how to incorporate patient-centered outcome measures, standards for COA use, and collaborative processes for COA development and dissemination. Interested parties may participate in person or via webcast. The registration deadline is March 27, 2015.
As discussed on our sister blog, Life Sciences Legal Update, the FDA has published a notice soliciting comments on a draft guidance document on the use of electronic media and processes to obtain informed consent for FDA-regulated clinical investigations of medical products. The HHS Office for Human Research Protections (OHRP) also is considering whether to adopt the policy for research regulated under HHS protection of human subjects regulations.
On January 27, 2015, the House Energy and Commerce Committee released its “21st Century Cures Act” discussion draft, the product of a year-long, bipartisan effort by the Committee to accelerate the pace of medical cures in the United States. The nearly 400-page bill addresses a wide range of topics, including, among many other things: the drug and device approval processes; clinical trials; Medicare coverage, payment, and coding; drug safety; and other proposals intended to streamline medical technology regulations across government. The Committee invites interested stakeholders to submit specific suggestions about how to improve the legislation; no deadline is specified.
In a related development, on January 29, the Senate Health, Education, Labor and Pensions (HELP) Committee launched its own initiative to examine and reform public policies in order to speed patient access to safe and effective medical products and treatments. To kick off this effort, the HELP Committee released a report entitled “Innovation for Healthier Americans: Identifying Opportunities for Meaningful Reform to Our Nation’s Medical Product Discovery and Development.” The report seeks feedback on a series of questions on ways to decrease the time and costs associated with bringing medical products to patients, including questions related to: more effectively targeting government resources; evaluating public-private partnerships; promoting biomedical research; streamlining clinical trial requirements; modernizing Food and Drug Administration medical product approval processes; and harmonizing US regulations with international standards. Feedback is requested by February 23, 2015. The Committee also intends to hold a series of hearings on issues raised in the report.
The FDA published a proposed rule on December 18, 2014 that would require electronic distribution of the prescribing information intended for health care professionals, which is currently distributed in paper form on or within the prescription drug or biological product packaging. FDA also is proposing that prescribing information intended for health care professionals will no longer be permitted to be distributed in paper form with the package from which a prescription drug or biological product is dispensed, except as provided by this regulation. According to the FDA, its proposal is intended to facilitate the distribution of updated prescribing information as new information becomes available or prescribing information changes are made, and to ensure that “the most current prescribing information for distributed prescription drugs will be available and readily accessible to health care professionals at the time of clinical decisionmaking and dispensing.” Comments on the proposed rule will be accepted until March 18, 2015.
This post was written by Jennifer Pike.
Last February, the Food and Drug Administration (FDA) asked for public feedback on a proposed research study related to prescription drug television advertisements. In a notice published in the Federal Register on January 13, 2015, FDA announced its intention to continue to move forward with the proposed study. Specifically, the notice announced that the Agency had submitted a proposed collection of information to the Office of Management and Budget (OMB) for review and approval. The notice describes the general framework for the study, entitled “Disclosure Regarding Additional Risks in Direct-to-Consumer (DTC) Prescription Drug Television (TV) Advertisements (Ads),” and it provides FDA’s response to the 55 comments it received regarding its February 2014 notice.
Current FDA regulations (21 CFR § 202.1) require that TV and radio ads present a product’s major risks in audio, or audio and visual parts of the ads (“major statements”). FDA is concerned that these major statements are too long, resulting in reduced consumer comprehension, minimization of important risk information, and, potentially, therapeutic noncompliance due to fear of side effects. At the same time, and in conflict with the above, FDA is concerned that DTC TV ads do not include adequate risk information. FDA believes that providing limited risk information in ads will promote improved consumer perception and understanding of serious and actionable drug risks.
OMB is accepting comments on the collection of information until February 12, 2015.
On February 20, 2015, the FDA is hosting a public workshop on “Optimizing FDA’s Regulatory Oversight of Next Generation Sequencing Diagnostic Tests.” The purpose of the workshop is to receive feedback from the community on FDA’s regulatory approach to diagnostic tests for human genetics or genomics using Next Generation Sequencing (NGS) technology. As pointed out in an FDA preliminary discussion paper, “NGS tests are unique among existing [in vitro diagnostics] in the amount of data that can be generated, the lack of an a priori definition of what will be detected, and the number of clinical interpretations that can be made from a single patient sample.” The FDA is considering several regulatory approaches to regulating NGS tests, including a standards-based approach to analytical performance of NGS tests and the use of centralized curated databases containing up-to-date evidence to support clinical performance.
This post was written by Kevin M. Madagan.
Time to pop the bubbly a little early! FDA announced today that the Drug Supply Chain Security Act (DSCSA) deadline of January 1, 2015 for product tracing (i.e., the new federal pedigree standards) will not be enforced until May 1, 2015. This means manufacturers, wholesale distributors, and repackagers have an additional four months to work with trading partners to determine how best to comply with the DSCSA pedigree standards. Although we are not surprised by this development, it is still cause to celebrate, given the potential adverse impact of enforcing the requirements before industry is prepared for compliance.
The new DSCSA Compliance Policy – DSCSA Implementation: Product Tracing Requirements – Compliance Policy Guidance for Industry – announces that FDA “recognizes” that some manufacturers, wholesale distributors, and repackagers “may need additional time to work with trading partners” to ensure that all of the product tracing information required under the DSCSA is provided to and captured by the recipient trading partner. It also acknowledges the very real concern that enforcing the January 1, 2015 deadline could disrupt the supply chain and impact patients’ access to needed prescription drugs.
The DSCSA Compliance Policy is clear: FDA “does not intend to take action against trading partners (manufacturers, wholesale distributors, and repackagers) who do not, prior to May 1, 2015, provide or capture the transaction information, transaction history, and transaction statement required by section 582 of the FD&C Act (product tracing information) associated with each transaction of certain human, finished prescription drugs, as defined in section 581 of the FD&C Act (21 U.S.C. 360eee).” The policy is limited only to the DSCSA requirements that trading partners provide and capture product tracing information; it does not extend to other DSCSA requirements, such as verification related to suspect and illegitimate product (including quarantine, investigation, notification and recordkeeping) and requirements related to engaging in transactions only with authorized trading partners.
Congress Approves Bill to Incentivize Ebola Treatment/Vaccine Developments; Congressional Hearings Address Ebola Response
In light of the recent Ebola outbreak and concerns over health safety, Congress has approved a bill (S. 2917) that would add Ebola to the Food and Drug Administration’s (FDA) priority review voucher program, which is designed to incentivize the development of treatments and vaccines for neglected tropical diseases. The legislation was approved by the Senate on December 2, 2014, followed by the House on December 3, and is now awaiting the President’s signature.
The Ebola outbreak has also been the subject of several recent Congressional hearings. For instance, the Senate Homeland Security and Governmental Affairs Committee recently held a hearing entitled "Preparedness and Response to Public Health Threats: How Ready Are We?” In addition, the House Energy and Commerce Committee has held hearings on medical product development in the wake of the Ebola epidemic and the U.S. public health response to the Ebola outbreak.
The FDA has scheduled a public workshop on the “Framework for Regulatory Oversight of Laboratory Developed Tests'' on January 8 – 9, 2015. The purpose of the workshop is to discuss FDA's proposal for a risk-based framework for addressing the regulatory oversight of “laboratory developed tests,” a subset of vitro diagnostic devices intended for clinical use and designed, manufactured and used within a single laboratory. Among other things, the FDA will address LDT labeling considerations; clinical validity and intended use; enforcement discretion; adverse event reporting; quality system regulation; and procedural issues. The workshop registration deadline is December 12, 2014. FDA will accept comments related to the public workshop until February 2, 2015.
NIH Releases Proposed Rule on FDAAA Requirements for ClinicalTrials.Gov Registration and Results Submission
NIH has just released a proposed rule that would clarify and expand requirements for the submission of clinical trial registration and results information, including adverse event information, to the ClinicalTrials.gov database in conformance with the Food and Drug Administration Amendments Act of 2007 (FDAAA). The rule would implement the statutory requirement for the submission of summary results information for trials involving drugs, biological products, and devices that are approved, licensed, or cleared by FDA, and it proposes to extend such requirements to clinical trials of drugs, biological products, and devices that are not approved, licensed, or cleared by FDA. Among other things, the proposed rule would require the responsible party (i.e., the trial sponsor or principal investigator) to register an applicable clinical trial no later than 21 days after enrolling the first participant, and results generally would be required to be submitted no later than 1 year after the completion date of the clinical trial (the date of final data collection for the primary outcome measure studied). Results submission could be delayed for up to two additional years with certification that either an unapproved, unlicensed, or uncleared product studied in the trial is still under development by the manufacturer or that approval will be sought for a new use of an approved, licensed, or cleared product that is being studied in the trial. Extension requests also could be submitted for “good cause.” With regard to adverse events reporting, the proposed rule would require the responsible party to submit information summarizing the number and frequency of adverse events experienced by participants enrolled in a clinical trial, by arm and organ system, and it specifies the form of that reporting. The proposed rule would require submitted information to be updated at least annually if there are changes to report, with provisions for more rapid updating in certain circumstances. The proposed rule does not impose requirements on the design or conduct of clinical trials or on the data that must be collected during clinical trials. The proposed rule is scheduled to be published on November 21, 2014, and comments will be accepted for 90 days after publication.
This post was written by Vicki Morris.
The Food and Drug Administration (FDA) recently issued a notice announcing the Agency’s revised guidance for industry defining the types of action, inaction, and circumstances that FDA considers to constitute delaying, denying, or limiting inspection, or refusing to permit entry or inspection for the purposes of making a drug adulterated. The revised guidance, entitled “Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection,” follows the enactment of the 2012 Food and Drug Administration Safety and Innovation Act (FDASIA), which added a provision (and teeth) to the Food, Drug, and Cosmetic Act (the FD&C Act) concerning inspections that render a drug “adulterated” – a new term used by the FDA in this context. Specifically, a drug adulterated under FDASIA “has been manufactured, processed, packed, or held in any factory, warehouse, or establishment and the owner, operator, or agent of such factory, warehouse, or establishment delays, denies, or limits an inspection, or refuses to permit entry or inspection.” FDA issued the revised guidance in response to comments on the Agency’s draft guidance for industry of the same title issued in July 2013.
The revised guidance clarifies FDA’s expectations regarding the types of action, inaction, and circumstances that make a drug adulterated under FDASIA and the FD&C Act. FDA also provides examples that constitute reasonable explanations for actions, inactions, or circumstances that could otherwise be considered delaying, denying or limiting inspection, or refusing to permit entry or inspection, as discussed below.
Delays of Inspections: While the guidance acknowledges that delays may occur for many reasons – some of which are beyond the control of the facility – it explicitly states that where an owner, operator or agent causes the delay of an inspection, this may cause the drugs to be deemed adulterated. FDA provides examples of delaying a pre-announced inspection that include, but are not limited to:
- A facility will not agree to a proposed inspection start date and does not give a reasonable explanation for its failure to do so
- A facility, after scheduling an inspection, requests a later start date without giving a reasonable explanation
- A facility fails to respond following the FDA’s attempt to contact the facility’s designated contact(s)
Delay During an Inspection: The guidance suggests that actions by a facility’s owner, operator, or agency before or after the beginning of an inspection, that impede an FDA investigator at the inspection site from performing the inspection in a reasonable manner, may be considered delaying the inspection. However, FDA notes that it will recognize minor delays from good faith efforts by the facility to comply with FDA requests as not unreasonable. FDA provides examples of delays during an inspection that may cause drugs to be adulterated:
- A facility does not allow the FDA investigator access to an area of the facility until a specific future date or time, even though the area is operational and is an area of the inspection site that FDA has authority to inspect, without giving a reasonable explanation
- A facility leaves the FDA investigator in a conference room without access to necessary documentation or responsible individual for an unreasonable period of time that interferes with the investigator’s ability to complete the inspection
Delays in Producing Records: FDA emphasizes the importance of the Agency’s preparation for inspecting drug facilities in collecting and reviewing hardcopy and electronic records, files and papers. The guidance offers examples of delays in producing records that may cause drugs to be deemed adulterated that include, but are not limited to:
- The FDA investigator, during an inspection, requests, within a specific, reasonable timeframe, records that it has authority to inspect, but the facility fails to produce the requested records within the timeframe requested by the Agency, without reasonable explanation
- The FDA requests records under its legal authority to do so, but the facility fails to produce the requested records in a timely manner, without reasonable explanation
FDA emphasizes that in instances where the facility provides a reasonable explanation for delaying production of records, the facility should also ensure that the resulting delay is of a reasonable duration.
Limiting of Inspection: The guidance explains four circumstances where an owner, operator, or agent of a drug facility prevents an authorized FDA representative from conducting an inspection that constitutes a limitation that may cause drugs to be deemed adulterated:
- Limiting access to facilities and/or manufacturing processes
- Limiting photography
- Limiting access to or copying of records
- Limiting or preventing collection of samples
While the guidance suggests that impeding or resisting photography by an FDA investigator may be considered a limitation if such photographs are determined by the investigator to be necessary to effectively conduct that particular inspection, there is no mention of the Agency’s authority to regulate this activity in MAPPs, FDA’s internal guidelines.
Refusal to Permit Entry or Denials of Inspection: FDA interprets the term “refuses to permit entry or inspection” to include not only active, but also passive behavior and non-action by the owner, operator or agent of a drug facility, to prevent an authorized representative of the FDA from conducting an inspection, or to prevent the FDA from completing an inspection. Denials of inspection also include statements or physical actions intended to avoid inspection, or to mislead, deceive or impede the investigator. FDA provides examples that may constitute denying an inspection that may cause drugs to be adulterated:
- A facility ignores or rejects the FDA’s attempt to schedule a pre-announced inspection
- The facility does not allow the FDA investigator, upon arrival at the facility, to enter the facility or begin the inspection
- A facility does not allow the FDA investigator to inspect the facility because certain staff members are not present, without a reasonable explanation, or
- A facility sends staff home for the day and tells the FDA investigator that the facility is not producing any product
Although neither the FDA’s revised guidance nor the FD&C Act specifically define “reasonable,” FDA has long maintained that the inspectional authority under section 704 of the Act “extends to what is reasonably necessary to achieve the objective of the inspection.” Further, FDA contends that it will consider reasonable explanations for behavior that may otherwise be considered to be delaying, denying, limiting, or refusing an inspection under the revised guidance. The guidance’s vagueness reinforces the importance of taking the following key steps to ensure FDA inspection compliance:
- Review FDA rules and guidance on how to conduct a good inspection
- Assess facility’s existing plans for FDA inspection
- Develop written internal procedures and systems that specifically address inspectional issues
- Consider rationale for any delays, limits, or denials of inspection
- Train and prepare staff for FDA inspections, including understanding the company’s positions and employees’ roles before, during, and after FDA investigations
- Track what is stored at the facility and what is provided to the authorized FDA representative at inspection
Vicki Morris (Law Clerk) is a member of the firm’s Life Sciences Health Industry Group and is based in our Washington, D.C. office.
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.
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.
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.
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.
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.”
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.