House Energy and Commerce Committee Unanimously Approves 21st Century Cures Bill

Today the House Energy and Commerce Committee approved H.R. 6, the “21st Century Cures Act,” by a bipartisan, unanimous 51-0 vote. This major legislation is intended to accelerate the pace of medical cures in the United States through a variety of reforms addressing drug and device development and approval, clinical trial design, research funding, interoperability of health technology, and other issues  It also would exclude journals, reprints, and other education-related items and payments from Physician Payment Sunshine Act reporting.

During markup, the panel approved an amendment offered by Chairman Upton making a number of policy revisions and offsets, including, among other things, provisions that:

  • Limit Medicaid durable medical equipment reimbursement rates to Medicare fee-for-service rates applicable in the state, effective January 1, 2020;
  • Make various changes to Medicare imaging reimbursement policy, including modification of Medicare physician fee schedule and outpatient prospective payment system payments to incentivize the transition from traditional x-ray imaging to digital radiography (with payment reductions for the use of non-digital technology) and a requirement that the Secretary conduct an empirical analysis before applying the multiple procedure payment reduction to the professional component of imaging services;
  • Implement OIG recommendation to delay certain Medicare Part D prescription drug plan prepayments;
  • Establish a Cures Innovation Fund equal to $110 million for each of fiscal years 2016 through 2020; and
  • Exempt certain FDA user fees from sequestration.

The bill now moves on to the full House.

FDA Issues Three Biosimilar Final Guidances

This post was written by Vicki Morris and Jennifer Pike.

On April 28, 2015, the federal Food and Drug Administration (FDA) finalized three guidances for industry on developing biosimilar drugs. The guidances, which follow the FDA’s first approval of a biosimilar drug in March, are intended to clarify both scientific and regulatory considerations for a broad range of stakeholders, including drug companies, in manufacturing biosimilars. The guidances include: Scientific Considerations in Demonstrating Biosimilarity to a Reference Product; Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product; and Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009.

Scientific Considerations

The guidance on scientific considerations provides an overview of FDA’s approach to determining biosimilarity. Specifically, this guidance purports to assist sponsors in demonstrating that a proposed therapeutic protein product is biosimilar to a reference product for the purpose of submitting a marketing application through an abbreviated licensure pathway under section 351(k) of the Public Health Service Act. Under the guidance, FDA highlights the Agency’s intention to consider the totality of the evidence submitted in a 351(k) application. FDA also notes the importance of particular scientific considerations in demonstrating biosimilarity, including a stepwise approach to demonstrating biosimilarity and general scientific principles in conducting comparative structural analyses, functional assays, animal testing, human pharmacokinetics and pharmacodynamics studies, clinical immunogenicity assessment, and comparative clinical trials, including clinical study design issues.

Quality Considerations

The guidance on quality considerations provides sponsors with an overview of analytical factors that are relevant to assessing whether a proposed biosimilar product (i.e., a therapeutic protein product) and the reference product are highly similar for the purpose of submitting a marketing application through the 351(k) abbreviated licensure pathway. By way of background, biosimilarity is defined to mean that the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components and that there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product. In making this highly similar determination, FDA deemed the following factors important: expression system, manufacturing process, assessment of physiochemical properties, functional activities, receptor binding and immunochemical properties, impurities, reference product and reference standards, finished drug product, and stability.

Questions and Answers

Lastly, FDA issued answers to common questions from sponsors interested in developing proposed biosimilar products, biologic license application (BLA) holders, and other interested parties regarding FDA’s interpretations of the Biologics Price Competition and Innovation Act of 2009, which created the abbreviated licensure pathway for biosimilar products. The Q&A’s cover biosimilarity vs. interchangeability, provisions related to requirement to submit a BLA for a “biological product,” and exclusivity. FDA also noted that an alternative approach may be used if such approach satisfies the requirements of the applicable statutes and regulations.

OIG Assesses FDA Progress on Oversight/Inspections of Generic Drug Manufacturers

In a recent report, the HHS OIG concludes that FDA has made progress in improving oversight of generic drug manufacturers, including greater parity in inspections of foreign and domestic generic drug manufacturers. A summary of the report, FDA Has Made Progress on Oversight and Inspections of Manufacturers of Generic Drugs, is available on our Life Sciences Legal Update blog. 

FDA Draft Guidance on Acceptance of Medical Device Clinical Data from Studies Conducted Abroad

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, FDA Establishing Interagency Task Force on LDT Quality Oversight

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.

March Congressional Health Policy Hearings

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.

FDA to Host Clinical Outcome Assessments Public Workshop (April 1)

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.

FDA,OHRP Considering Guidance on Use of Electronic Informed Consent In Clinical Investigations

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.

Congressional Panels Take Steps to Speed Patient Access to Medical Innovation

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. 

Electronic Distribution of Prescribing Information for Prescription Drugs & Biologicals

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.

FDA One Step Closer to New Direct-To-Consumer Television Ad Requirements

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.

Upcoming FDA meeting on Next Generation Sequencing Technology (Feb. 20)

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.

Happy New Year! FDA Helps Industry Ring in New Year with Generous DSCSA Compliance Policy

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.

FDA Public Meeting on Regulatory Oversight of Laboratory Developed Tests (Jan 8-9)

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 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.

FDA Revises Guidance Defining Delays, Denials, Limits and Refusals of a Drug Inspection

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.

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.

Older Entries

September 5, 2014 — Upcoming House Hearings to Address ACA Implementation, Accelerating Medical Innovation

September 4, 2014 — House Panel to Examine FDA Lab-Developed Test Policy

August 26, 2014 — FDA Seeks Comments to Updated Guidance on Informed Consent in Clinical Trials

August 19, 2014 — FDA Public Hearing on the Implementation of Generic Drug User Fee Amendments (Sept. 17)

July 22, 2014 — FDA Meeting on Biomarker Development (Sept. 5)

July 2, 2014 — FDA Will Not Enforce Compliance for Mobile Device Data Systems and Other Low Risk Devices, Agency Reports

June 23, 2014 — FDA Releases Drug/Device Industry Social Media Guidance Documents

June 12, 2014 — FDA Issues Draft Guidance on Communicating New Risk Information about an Approved Drug Product - Comment Opportunity

June 3, 2014 — FDA Initiative Opens Door to Easily Accessible, User-Friendly Data

May 29, 2014 — Expedited Drug Development and Review: New FDA Resource Now Available

May 22, 2014 — FDA Workshop to Focus on 3-D Printing of Medical Devices

May 8, 2014 — Hundreds of Drugs and Biologics Face Labeling Changes under New FDA Plan

April 25, 2014 — Busy Week for FDA's Center for Devices and Radiological Health

April 10, 2014 — Will Physician Payment Sunshine Act Data Usher in a New Era of False Claims Act Litigation?

April 8, 2014 — April Congressional Hearings

April 2, 2014 — FDA Proposal Amends Medical Device Classification Rules

March 24, 2014 — March Congressional Health Policy Hearings

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 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