Dorsey Health Law

On January 7, 2019, FDA Commissioner Scott Gottlieb announced significant updates to the FDA’s pilot Software Pre-Certification Program, sometimes referred to more broadly as a Digital Health Pre-Certification Program (“Pre-Cert”). Pre-Cert was originally announced in 2017 as part of the FDA’s Digital Health Innovation Action Plan. The FDA envisions the program as a streamlined process for bringing digital health technologies to market. More specifically, the FDA hopes to develop Pre-Cert into a program by which certain digital health developers can become precertified as part of an “Excellence Appraisal.” Excellence-appraised developers could then take advantage of streamlined premarket submission processes for their digital devices. To date, the FDA has been working with a variety of stakeholders, including nine companies “represent[ing] a wide range of companies and technology in the digital health sector,” in developing the program. In connection with the announcement earlier this week, the FDA issued “three documents that, together, launch us into the next phase of the agency’s vision of Pre-Cert.” The first of the three documents is a Regulatory Framework for Conducting the Pilot Program within Current Authorities (the “Framework”). This document builds out the regulatory framework within which the FDA will implement Pre-Cert.  Here are some highlights: At least to start, Pre-Cert is limited to software as a medical device (“SaMD”), defined as software intended to be used for one or more medical purposes that perform these purposes without being part of a hardware medical device. The FDA hopes eventually to expand the program to review all medical device software products, including software in a medical device (“SiMD”) and other software that could be considered accessories to hardware medical devices. The FDA intends to utilize the De Novo classification process (section 513(f)(2) of the FD&C Act), an existing pathway for certain new types of low to moderate risk devices to obtain marketing authorization as a Class I or Class II device as opposed to automatic Class III designation, for the next phase of Pre-Cert. Here is an overview of the proposed process: Participants with a SaMD product may participate in an Excellence Appraisal, as well as an optional Review Determination Pre-Submission. When submitting a product for De Novo Review, an excellence-appraised developer would submit a streamlined “Pre-Cert De Novo Request,” in which it would not need to re-submit information reviewed during the Excellence Appraisal or the optional Pre-Submission. Assuming premarket requirements are met, the FDA would classify the device by written order and, if the device is Class II, establish special controls, which may include Excellence Appraisal elements and postmarket data collection elements. Following a De Novo order, an excellence-appraised developer would also be able to take advantage of a streamlined “Pre-Cert 510(k)” process, in which the developer can again leverage submission requirements already documented during the Excellence Appraisal and optional Pre-Submission process. The FDA expects review of a Pre-Cert 510(k) to be more efficient than the review of a traditional 510(k). The Pre-Cert 510(k) can also be used for modifications to devices, assuming a 510(k) is required for the modification.  The second document is a 2019 Test Plan (the “Test Plan”). The Test Plan lays out the scope and approach of the Pre-Cert pilot in 2019.  The primary purpose of the Test Plan “is to assess whether the Excellence Appraisal and Streamlined Review components together produce an equivalent basis for determining reasonable assurance of safety and effectiveness for a SaMD product… as compared to the traditional paradigm.” Here are some highlights: Consistent with the Framework, the scope of the Test Plan is limited to: (i) selected SaMD with De Novo Requests, and (ii) selected 510(k) submissions, which would be tested as if they were follow-on 510(k)s for devices classified through a Pre-Cert De Novo Request. The FDA plans to prioritize selection of submissions that will enable evaluation and testing of all four components (Excellence Appraisal, Review Pathway Determination, Streamlined Review, and Real-World Performance plan) outlined in the Working Model (discussed below), and to focus on cases representing a broad spectrum of software developers (e.g., small and large firms, low- and high-risk products, companies not traditionally considered medical device manufacturers). During the Test Plan, the FDA will apply both the proposed Pre-Cert pathway and the traditional review process to each test case, enabling it to refine Pre-Cert and confirm the validity of the overall program. Developers participating in the Pre-Cert pilot, after an Excellence Appraisal and optional Pre-Submission, will still need to submit full traditional marketing submissions. Internally, the FDA will then create a “mock Streamlined Review package” and review the submission on parallel paths, traditional and “mock Streamlined.” Similarly, the FDA will also be internally conducting retrospective tests of SaMD regulatory submissions previously reviewed. Finally, the third document released is an updated Working Model (currently v1.0). The Working Model, which has been updated over time with continuous public input, describes in greater detail the goal, vision, scope, and process for Pre-Cert. It also includes summaries of public comments that have been received and FDA responses to them. Pre-Cert, if implemented and successful in accomplishing FDA’s stated goals, could have a significant impact on the healthcare industry beyond the software developers it promises to impact directly. Digital health is increasingly becoming an important tool for healthcare businesses. Streamlining processes for bringing digital health technology to market and modifying existing technology will in turn increase the rate at which providers are able to utilize updated digital health technologies in practice. As this technology continues to garner the focus and support of regulatory bodies, it will be important not only for developers to understand the FDA’s streamlined approval process, but also for providers to prepare for the potential transformative effect digital health tools can have on the care they provide.

On June 12, the FDA issued guidance that clarifies its recommendations for certain product communications made by medical product manufacturers, packers, and distributors (collectively “firms”). The guidance, “Medical Product Communications That Are Consistent With the FDA-Required Labeling” (the “Guidance”), explains the FDA’s views on firms’ communication of information that is not contained in the FDA-required labeling for their drugs or medical devices, but that is consistent with that labeling. As explained in a statement by FDA Commissioner Scott Gottlieb introducing the Guidance, FDA-required labeling “is the primary tool that communicates the essential information needed for the safe and effective use of a medical product [and it is] subject to content requirements and limitations.” That being said, FDA-required labeling does not address all that is known about a product, such as data from post-market studies and surveillance of a product’s approved uses or additional information obtained from pre-market studies. Firms may want to communicate this information to help inform decision-making regarding patient care, and payors want this information to inform their purchasing decisions or negotiation of value-based contracts. However, firms may be wary of communicating such information for fear of being deemed to have communicated information that is inconsistent with FDA-approved labeling, that is false or misleading, and/or that establishes a new intended use. In response to a number of questions from firms on these issues, the Guidance seeks to clarify what types of information are considered consistent with FDA-required labeling. It also provides general recommendations for conveying that information in a truthful and non-misleading way, along with examples to illustrate these concepts. The Guidance makes clear that the FDA does not view communications consistent with required labeling alone as evidence of a new intended use, though it does caution that such communications will not necessarily be excluded altogether from assessing a firm’s conduct if there is other evidence of a new intended use. When determining whether a communication is consistent with the required labeling for the product, the FDA considers three factors. A communication must satisfy all three factors in order to be consistent with the required labeling: Comparing to Conditions of Use: First, the FDA considers how the information in the product communication compares to the information about the conditions of use in the product’s required labeling. More specifically, a product communication is not consistent with the FDA-required labeling if the representations/suggestions in the communication relate to a different indication than the ones reflected in the product’s required labeling, if the patient population represented/suggested in the communication is outside of the approved/cleared patient population in the required labeling, if the representations/suggestions in the communication conflict with the use limitations or directions for handling, preparing, and/or using the product reflected in the required labeling, or if the representations/suggestions about the product conflict with the recommended dosage or use regimen, route of administration, or strengths set forth in the required labeling.   Evaluating Effect on Potential for Harm: Second, the FDA considers whether the product communication increases the potential for harm to health relative to the labeling. If a communication alters the risk-benefit profile of a product in a way that may result in increased harm to health, this indicates the communication is not consistent with the required labeling. For example, if the representations/suggestions in a communication may introduce new risks not included in FDA-required labeling or increase the rate of occurrence or severity of existing risks, the communication may fail this test.   Evaluating Effect on Safe and Effective Use: Finally, the FDA considers whether the directions for use in the labeling enable the product to be used safely and effectively under the conditions represented/suggested in the product communication under consideration. Here, firms should examine any unique considerations associated with the use suggested by a product communication and whether the FDA-required labeling furnishes appropriate context.   The Guidance acknowledges the potential for overlap in these three factors, but emphasizes that all must be satisfied for a communication to be consistent with the required labeling. It also gives examples of communications that may satisfy one factor but fail others. The Guidance also outlines recommendations for truthful and non-misleading promotional communications of information consistent with required labeling, including recommendations regarding evidentiary support. To be truthful and non-misleading, representations or suggestions made by firms about their products need to be grounded in fact and science and presented with appropriate context. Any data, studies, or analyses relied on should be scientifically appropriate and statistically sound to support the representations or suggestions made. While sufficient evidentiary support must be presented, the FDA will not consider representations or suggestions in a communication consistent with required labeling to be false or misleading based only on the lack of evidence sufficient to satisfy the applicable approval/clearance standard. In the same statement introducing the Guidance, Commissioner Gottlieb also introduced accompanying guidance, “Drug and Device Manufacturer Communications With Payors, Formulary Committees, and Similar Entities - Questions and Answers,” which we covered in more detail in a previous post. Commissioner Gottlieb explained that the ultimate goal of the two guidances “is to help facilitate a market that is more competitive, based on the outcomes that matter most –the benefit to patients.” Authors’ Note: Summer Associate Margaret Fitzpatrick provided substantial assistance with the drafting of this blog post.

On June 12, the FDA issued guidance that clarifies its recommendations for certain medical product communications. The guidance, “Drug and Device Manufacturer Communications With Payors, Formulary Committees, and Similar Entities - Questions and Answers” (the “Guidance”), provides answers to common questions about the communications between medical product manufactures, packers, and distributors (“firms”), and insurance companies, formulary committees and similar entities (“payors”). In particular, it addresses communications by firms to payors regarding approved or cleared products as well as unapproved products and unapproved uses of approved or cleared products. In a statement, FDA Commissioner Scott Gottlieb acknowledged the sophistication of payors as an audience and recognized their need for access to a range of information on the effectiveness, safety, and cost-effectiveness of approved/cleared products. The Guidance is therefore designed to enable truthful, non-misleading and appropriate company communications to promote public health benefits such as increased cost savings from informed and appropriate coverage and reimbursement decisions. The FDA similarly seeks to give companies clear guidelines for providing payors with truthful and non-misleading information about unapproved products and unapproved uses of approved/cleared products. Through the Guidance, the FDA aims to help facilitate communications that can allow payors to provide coverage for these new products and new uses more quickly after FDA approval or clearance as well as help companies and payors to establish pricing structures that benefit patients as well as health plans. First, the Guidance addresses the communication of health care economic information (“HCEI”) regarding both approved drugs and approved/cleared devices. HCEI is defined in section 502(a) of the Food, Drug, and Cosmetics Act (“Section 502(a)”) as “analysis… that identifies, measures, or describes the economic consequences… of the use of a drug.” As noted in the Guidance, HCEI generally pertains to economic consequences related to the clinical outcomes of treating, preventing, or diagnosing a disease. The Guidance clarifies Section 502(a), which provides that the FDA will not consider dissemination of HCEI to an appropriate audience to be false or misleading if the HCEI relates to an approved indication and is based on competent and reliable scientific evidence (the “CARSE” standard). Specifically, the Guidance expounds on the FDA’s thinking as to what it means to “relate to an [approved] indication,” the type of evidentiary support needed for HCEI, and the components of HCEI to which the CARSE standard applies, among other topics. Notably, although the language in Section 502(a) addressing HCEI applies to drugs, not devices, the FDA states that its recommendations are also applicable to firms’ communications of HCEI regarding approved/cleared devices. The Guidance also describes information that should be included when disseminating HCEI. While recognizing not all categories of information will be applicable to particular HCEI presentations, the Guidance provides that, when relevant, the HCEI presentation should also clearly and prominently include appropriate background and contextual information, including study design and methodology, generalizability, limitations, sensitivity analysis, and additional information for a balanced and complete presentation. The disclosure of this information may be concise, so long as all material information is provided. In response to indications from payors that they need to plan for and make coverage and reimbursement decisions far in advance of the effective date of such decisions, the Guidance also discusses types of information about unapproved products or unapproved uses of approved/cleared/licensed products that a firm may communicate to a payor. Provided that the information is “unbiased, factual, accurate, and non-misleading,” communications may include product information, information about the indication sought, anticipated timeline for possible FDA approval/clearance/licensure of the product or new use, product pricing information, patient utilization projections, product-related programs or services, and factual presentations of results from studies including clinical studies of drugs or devices or bench tests that describe device performance. Additionally, the communication must be accompanied by additional information, including a clear statement that the product or use is not approved/cleared/licensed, and that the safety or effectiveness of the product or use has not been established. In the same statement introducing the Guidance, Commissioner Gottlieb also introduced accompanying guidance, “Medical Product Communications That Are Consistent With the FDA-Required Labeling - Questions and Answers,” which we will cover in more detail in Part II of this post.   Authors' Note: Summer Associate Margaret Fitzpatrick provided substantial assistance with the drafting of this blog post.

All eyes are on the federal government as top officials have recently signaled upcoming actions which could impact the prices of prescription drugs. In the past two weeks, leaders from both the FDA and HHS have made statements signaling that the agencies are focused on reducing prescription drug prices. In remarks at the Food and Drug Law Institute conference held on May 3, 2018, U.S. Food and Drug Administration Chief Scott Gottlieb suggested that by reexamining the current safe harbor under the anti-kickback statute for drug rebates, list prices for drugs would be closer to negotiated prices and competition may increase. Mr. Gottlieb stated that, while “[t]here’s a range of reasons why drug prices are too high” one reason “that’s driving higher and higher list prices, is the system of rebates between payers and manufacturers. And so what if we took on this system directly, by having the federal government reexamine the current safe harbor for drug rebates under the Anti-Kickback Statute?” (The transcript of Mr. Gottlieb’s remarks can be found here). Mr. Gottlieb appears to be siding with critics of drug rebates who have argued that the practice leads to higher prices for patients because the rebates do not make their way down to patients, and instead, patients pay list prices for the drugs as they meet their out-of-pocket obligations. Mr. Gottlieb also mentioned some additional upcoming actions to reduce drug prices, including a Biosimilars Action Plan that is similar to the FDA’s Drug Competition Act Plan (DCAP); additional policies under DCAP to promote generic competition; a comprehensive framework for the regulation of gene therapy; and prioritizing the review of low competition products for generic product applications. Additionally, Mr. Gottlieb alluded to changes that may be introduced by Secretary of Health and Human Services, Alex Azar, including policies that “will dismantle many of the provisions that shield parts of the drug industry from more vigorous competition” and “a series of changes to the pricing mechanism in [Medicare] Part D.” Days later, on May 9, Alex Azar told members of the American Hospital Association that “HHS is focused on solving a number of the problems that plague drug markets. These include the high list prices set by manufacturers; seniors and government programs overpaying for drugs due to the lack of the latest negotiating tools; rising out-of-pocket costs for consumers; and foreign governments free-riding off of American investments in innovation.” Mr. Azar’s full speech can be watched here. President Trump is schedule to deliver a speech on Friday, May 11, 2018 addressing the steps that the administration plans to take to address drug pricing in the United States. Mr. Azar noted that President Trump wants to go “much, much further” in addressing drug prices than the proposals initially set forth in the President’s 2019 Budget. We will continue to closely monitor these activities which may have a significant impact on all involved in the prescription drug market.

Last week, Dr. Scott Gottlieb, Commissioner of the FDA, touched on two issues that have frequented headlines in the past two years. First, in remarks made on November 28, 2017, Commissioner Gottlieb expanded on plans to finalize guidance related to complex generic drugs, a broader issue that received specialized focus during coverage of EpiPen’s price hike that began in 2016 and has continued in 2017. Then, on November 30, 2017, Commissioner Gottlieb stated plans to leverage accelerated approval processes for promising drugs, using targeted cancer drugs as an example. Innovative cancer treatments, especially recently approved cancer treatments using gene alteration techniques, which the Commissioner specifically discussed later in the session when discussing the progress of the Oncology Center of Excellence, have also grabbed headlines of late. While these topics, and efforts to address them, are not entirely novel, each statement provided understanding into the FDA’s ongoing efforts to remove regulatory barriers to drug access and gave additional insight as to concrete changes the FDA may be implementing in the foreseeable future. On the complex generic drug issue, Commissioner Gottlieb started by noting steps the FDA has taken to address lack of competition due to branded drug makers using tactics to block generic drug makers from running bioequivalence studies, as well as opportunistic behavior by speculators who acquire off patent drugs with little competition and raise prices sharply. He then went on to expand on plans to improve the process for developing and approving complex generic drugs. Without mentioning EpiPen by name, Commissioner Gottlieb used an example of a drug delivered through a complex device, such as an auto-injector, and went on to explain that “the branded drug maker may still hold IP on certain features of the device. In such a circumstance, the drug can be an old medicine, but the device can be hard to copy since new patents protect its key features.” According to Commissioner Gottlieb, the FDA will aim to address this and similar issues in guidance it is working to finalize under which, among other things, generic products will be allowed “to have certain labeling differences from the branded product – if such labeling changes stem from permitted design differences.” As long as differences in design will not affect the clinical effect or safety profile, the generic product can be approved. This relaxation of rigorous “sameness” standards may prove to have a significant effect on the availability of generic products in situations such as that presented by EpiPen. Similar to the complex generics, the accelerated approval discussion was also part of a larger discussion of steps the FDA is taking to address issues in its approval process. Commissioner Gottlieb and Dr. Francis Collins, Director of NIH, addressed the House Committee on Energy and Commerce to discuss progress in implementing the 21st Century Cures Act nearly a year into its existence. The Cures Act is sweeping legislation that, among other things, aims to streamline the drug and device approval process. For earlier discussion of the Cures Act and its treatment of certain medical software, see this post from my colleague, Ross D’Emanuele. Although Commissioner Gottlieb and Dr. Collins discussed progress under the Cures Act broadly, the Commissioner used his opening statement to specifically mention his view of a potential path for accelerated approval of promising drugs such as targeted cancer treatments. Specifically, Commissioner Gottlieb discussed the potential for using a process, similar to existing accelerated approval processes, for drugs like targeted cancer treatments that may show an “outsized benefit on overall survival” in small trials. Such drugs would ordinarily require further evidence as to how to use the drug in clinical setting, but Commissioner Gottlieb said earlier approval with post-market approval studies to collect further information could often be beneficial. As explained by the Commissioner, accelerated approval is ordinarily granted in situations where drugs show benefits on a surrogate endpoint, such as tumor shrinkage; however, he suggested in his prepared statement it may also be appropriate in these circumstances where outsized benefit is shown on a clinical endpoint, such as survival. It remains to be seen if and how these plans will be finalized and implemented. However, it is clear that the FDA plans to continue to address issues in the drug and device approval process that have come under public scrutiny as of late.