A Look Ahead in Life Sciences: What We Are Tracking in Q4 2023 and Beyond

How companies develop their products:

• The Food and Drug Administration (FDA) released a draft guidance, “Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products,” with added sections on Type D and INTERACT meetings. Importantly, Type D meetings can occur on a shorter timeline than Type C meetings and can be leveraged for a “general question about an innovative development approach that does not require extensive, detailed advice.” Regarding industry desire for more in-person and virtual interactions with the FDA, the FDA stands its ground in the guidance that it will determine when a “written response only” approach is “most appropriate” but notes that a sponsor may explain its rationale for holding a meeting, which the FDA will consider. Comments may be submitted to the docket through December 21, 2023.
• The FDA recently announced the availability of final guidance intended to assist institutional review boards, investigators, and sponsors in complying with the FDA’s informed-consent regulations for clinical trials. The guidance does not address possible future changes to the FDA’s informed-consent regulations that may be developed as part of the FDA’s harmonization efforts with the Common Rule, which are still underway.
• The FDA will host a virtual public meeting, “Mitigating Clinical Study Disruptions During Disasters and Public Health Emergencies,” on October 18 and 19, 2023. The meeting will bring the clinical research community together to discuss a variety of topics, including recommendations provided by the FDA during the COVID-19 emergency period; the actions sponsors took to adopt such recommendations; the characteristics of the sponsors, studies, and patient populations affected by such recommendations; recommendations for incorporating certain recommendations for mitigating disruption of clinical studies into current or additional guidance; and strategies for advanced planning to mitigate disruption of clinical research during future disasters and public health emergencies (PHEs). The FDA also issued a 34-page final guidance, “Considerations for the Conduct of Clinical Trials of Medical Products During Major Disruptions Due to Disasters and Public Health Emergencies,” intended to be an enduring guidance now that the COVID-19 PHE has concluded.
• We continue to watch for the FDA’s implementation of its new clinical trial Diversity Action Plan authority for Phase 3 or pivotal study drug and biologic developers and device developers conducting clinical trials (whether under investigational device exemptions or not), pursuant to section 3601 of the Food and Drug Omnibus Reform Act of 2022 (FDORA). Related to increasing diversity in clinical trials, the FDA issued draft guidance to describe FDA requirements and recommendations for obtaining safety and effectiveness information on drugs, when appropriate, in the post-marketing setting in historically underrepresented patient populations in clinical trials. Comments on the draft guidance are due to the docket by October 10, 2023.
• We continue to watch for the FDA’s implementation of a new provision of the Federal Food, Drug, and Cosmetic Act that allows the FDA to designate a “platform technology” that has the potential to be incorporated in or utilized by more than one drug. Under section 2503 of FDORA, the FDA may expedite the development and review of a subsequent application for a drug that incorporates or utilizes a designated platform technology and must issue draft guidance on the new designation program within one year of enactment of FDORA. The head of the FDA’s Office of Therapeutic Products recently noted the potential opportunity the designation can offer cell and gene therapy sponsors.
• The FDA issued a request for information to stakeholders regarding “critical scientific challenges and opportunities to advance the development of individualized cellular and gene therapies (CGTs).” The request for information focuses on three areas: manufacturing, nonclinical development, and clinical studies. The FDA intends to use the feedback obtained by stakeholders to assist in planning future town halls, workshops, or discussion papers, which could further facilitate the development of regulatory science tools, standards, or guidance. Comments are due to the docket by November 20, 2023.
• We continue to monitor a new bill (H.R. 1117) introduced to Congress in February, with a growing list of cosponsors, that would address inclusion of pregnant and lactating women in clinical research.
• We are monitoring the Medicines and Healthcare products Regulatory Agency’s (MHRA) implementation of legislation to reform the regulatory framework for clinical trials in the UK. On March 21, 2023, the MHRA published its response to the public consultation that it conducted at the beginning of 2022 on legislative proposals concerning the regulation of UK clinical trials. The MHRA has confirmed that the new legislation will ensure that patients and their safety are at the focus of all clinical trials, bring the benefits of clinical trials to everyone, create a proportionate and flexible regulatory environment, cement the UK as a destination for international trials, and provide a framework that is streamlined, agile, and responsive to innovation.

Deciding whether a company can market or sell a specific product:

Pharmaceuticals and Biologics

• The FDA recently published a draft guidance, “Demonstrating Substantial Evidence of Effectiveness With One Adequate and Well-Controlled Clinical Investigation and Confirmatory Evidence,” to complement its December 2019 draft guidance, “Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products,” and its May 1998 final guidance, “Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products.” This latest guidance supplements and expands the recommendations in the 2019 draft guidance by providing further detail on the use of data drawn from one or more sources to substantiate the results of one adequate and well-controlled clinical investigation. The latest guidance also describes factors to consider when assessing whether a single adequate and well-controlled trial and confirmatory evidence are sufficient to demonstrate substantial evidence of effectiveness. The guidance further emphasizes the need for early engagement with the FDA for sponsors that intend to establish substantial evidence of effectiveness with one adequate and well-controlled study and confirmatory evidence. Comments on the draft guidance are due to the docket by December 18, 2023.
• We are following a new bill (S. 2780) introduced in the US Senate that would require sponsors of drug applications and holders of approved applications to provide certain submissions and communications to the FDA and the US Patent and Trademark Office.
• We continue to follow reintroduced bipartisan legislation that would create a regulatory pathway for the provisional approval of drugs in certain cases. The Promising Pathway Act would require the FDA to establish a “rolling, real-time, priority review pathway for drugs intended to treat, prevent, or diagnose serious or life-threatening diseases or conditions.” Drugs approved under this proposed pathway would be granted time-limited approval and would be required to track usage through patient registries.
• We continue to follow substitute language in the Preserve Access to Affordable Generics and Biosimilars Act (S. 142), which was introduced in January 2023 with 10 bipartisan cosponsors and reported to the Senate Committee on the Judiciary with an amendment to “prohibit brand name drug companies from compensating generic drug companies to delay the entry of a generic drug into the market, and to prohibit biological product manufacturers from compensating biosimilar and interchangeable companies to delay the entry of biosimilar biological products and interchangeable biological products.”
• We will monitor any forthcoming publicly announced outcomes from sponsors that were selected as first participants in the FDA’s Advancing Real-World Evidence (RWE) Program, which provides those sponsors with four program meetings geared toward creating a path forward with the FDA for the use of RWE in indication expansion and approvals. On a related note, the FDA finalized its guidance about the use of RWE to help support approval of a new indication for an already approved drug or to help support post-approval study requirements.
• We are monitoring the European Commission’s implementation of its legislative proposals — Regulation 2023/0131 and Directive 2023/0132 — to replace the current EU regulatory framework for all medicines (including those for rare diseases and for children). The proposals were announced on April 26, 2023, and they aim to reduce costs, expedite the introduction of new medicines, and prevent medicine shortages. Read our summary of these proposals here. Members of the European Parliament held discussions on the legislative proposals on September 20, 2023, in relation to the modulation of regulatory protection, orphan-drug provisions, antimicrobial resistance, and medicine shortages.
• We are monitoring the implementation of the Windsor Framework that will apply as of January 1, 2025, in the UK. On February 27, 2023, the UK government and the European Commission announced a political agreement in principle to replace the Northern Ireland Protocol with a new set of arrangements, the Windsor Framework. This new framework fundamentally changes the existing system under the Northern Ireland Protocol, including the regulation of medicines in the UK. In particular, the MHRA will be responsible for approving all medicines destined for the UK market (that is, Great Britain and Northern Ireland), and the European Medicines Agency (EMA) will no longer have a role in approving medicines destined for Northern Ireland. The MHRA will grant a single UK-wide marketing authorization for all medicinal products sold in the UK, enabling medicines to be sold in a single pack and under a single authorization throughout the UK. The Windsor Framework was approved by the EU-UK Joint Committee on March 24, 2023, meaning the UK government and the EU will enact legislative measures to bring it into law.
• We are monitoring the implementation of the International Recognition Procedure (IRP), starting January 1, 2024, in the UK, which will replace the European Commission Decision Reliance Procedure. The IRP will allow the MHRA to consider the expertise and decision-making of medicines regulators in Australia, Canada, the EU, Japan, Singapore, Switzerland, and the US when approving a new medicine. The decentralised and mutual recognition reliance procedure (MRDCRP), which allows the MHRA to have regard for approvals in the EU, will be incorporated under the umbrella of the IRP. See our summary of the IRP here.

Medical Devices and Medtech

• The FDA recently published a trio of draft guidances related to its efforts to “strengthen and modernize” the 510(k) Program. The draft guidances address two foundational issues of concern with the 510(k) process — best practices for selecting a predicate device and when clinical data is needed in a 510(k) — in addition to providing updated performance testing recommendations for manufacturers of 510(k) implant devices. See our summary of these guidances here. Comments on the draft guidances are due by December 6, 2023.
• The FDA Digital Health Center of Excellence recently issued frequently asked questions (FAQs) for digital health products, available here. The FAQs provide quick links to key information for digital health product developers, including links to FDA’s device lists for artificial intelligence (AI) and machine learning (ML)–enabled devices and augmented reality (AR) and virtual reality (VR) devices (though the FDA is due to update both lists). We note that the FDA also recently published Questions to Consider for AR/VR devices, with a focus on informing patients and healthcare professionals of benefits, risks, and limitations, among other things.
• We continue to monitor the FDA’s ongoing focus on the use of digital health technology to advance health equity following the Patient Engagement Advisory Committee meeting on September 6, 2023. The meeting materials are now available (along with the webcast link for those who missed it).
• We continue to monitor how the FDA is applying their September 2022 final guidance on clinical decision support software, with an eye toward potential “software as a medical device” (SaMD) definitional changes stemming from the reopening of the International Medical Device Regulators Forum SaMD working group.
• We are continuing to monitor the FDA’s Total Product Life Cycle Pilot, designed to help reduce time from concept to commercialization for medical devices going through the FDA approval and clearance processes, which the FDA recently announced will be expanded as of October 1, 2023, to include devices reviewed in the Office of Neurological and Physical Medicine Devices. We also continue to monitor the Voluntary Alternative Pathway, a potential new regulatory pathway for novel products, including digital health products, referenced by Center for Devices and Radiological Health (CDRH) Director Jeffrey Shuren at the Food and Drug Law Institute’s annual conference in May 2023.
• We are evaluating the FDA’s recently published final guidance, “Fostering Medical Device Improvement: FDA Activities and Engagement with the Voluntary Improvement Program [VIP].” The VIP is a voluntary program facilitated through the Medical Device Innovation Consortium that evaluates the capability and performance of a medical device manufacturer’s practices using third-party appraisals. The VIP is intended to guide improvement to enhance the quality of devices and builds on the framework piloted through the 2018 Case for Quality program.
• We continue to monitor the implementation of new cybersecurity authorities for software-containing or internet-connected devices, enabling the FDA to require sponsors to develop cybersecurity plans for post-market implementation, as mandated in section 3305 of FDORA. The FDA issued its guidance on its “refuse to accept” policy for cyber devices and related systems earlier this year.
• We are following stakeholder input to the FDA’s recently issued draft guidance on predetermined change control plans for AI/ML-enabled devices.
• We are monitoring the implementation of the FDA’s final guidance, “Content of Premarket Submissions for Device Software Functions.”
• We are analyzing the FDA’s recent pair of draft guidances, “Medical Devices with Indications Associated with Weight Loss - Non-Clinical Recommendations” and “Medical Devices with Indications Associated with Weight Loss - Clinical Study and Benefit-Risk Considerations.”
• We are monitoring the impact of Regulation (EU) 2017/745 (the European Medical Device Regulation, or MDR) which has been applicable since May 26, 2021, in the EU. There have been recent calls for action from MedTech Europe and for 34 national associations to reform the MDR, including the removal of certificate expirations, an innovative device pathway, and more central processes.
• We are monitoring the implementation of the Innovative Devices Access Pathway (IDAP), which will launch later in 2023 in the UK and be run by the MHRA, the National Institute for Health and Care Excellence, and other partners, including the devolved administrations in the UK. The aim of IDAP is to enable and improve patient access to innovative and transformative medical devices by providing an integrated and enhanced regulatory and access pathway to developers. The MHRA launched a pilot of IDAP on September 25, 2023, which will run until October 29, 2023. The pilot is open to UK and international commercial and noncommercial developers with new health technology solutions.

In Vitro Diagnostic and Laboratory Testing

• On September 29, 2023, the FDA posted and scheduled for publication a proposed rule to make explicit that laboratory developed tests (LDTs) are devices regulated by FDA. At the same time, FDA is proposing a policy to, upon finalization of the proposed rule, phase out its current general enforcement discretion approach so that LDTs would generally fall under the same enforcement approach as in vitro diagnostic (IVD) tests that FDA currently actively regulates. Comments on the proposed rule are due 60 days after the date of publication of the proposed rule.
• We are monitoring the Verifying Accurate Leading-edge IVCT Development Act of 2023, which was introduced in the US House of Representatives by Reps. Larry Bucshon (R-IN) and Diana DeGette (D-CO) in March 2023.
• We continue to monitor the FDA Oncology Center of Excellence’s recently launched voluntary pilot program, the Oncology Dx Pilot, which focuses on the use of certain LDTs with oncology products to identify cancer biomarkers. Through this program, the FDA will request performance information for the tests used to enroll patients in a sponsor’s clinical trials that support drug approval. Based on an assessment of that information, the FDA will post to its website the minimum performance characteristics recommended for similar tests that may be used to select patients for treatment with the approved drug. Laboratories may use this information to guide development of their LDTs to identify specific biomarkers used for selecting cancer treatment and help facilitate better and more consistent performance of LDTs and overall better drug selection and improved care for patients with cancer.

How companies manufacture, promote, and monitor their approved products:

• The FDA, together with the Product Quality Research Institute, held a virtual public workshop on September 26 – 27 to discuss critical topics related to the use of AI in pharmaceutical manufacturing. This workshop aimed to facilitate interaction among AI stakeholders on critical areas for development, implementation, and regulatory considerations including uses in process development and control, operation of Pharmaceutical Quality Systems, life cycle approaches, and Current Good Manufacturing Practice. The workshop follows the FDA’s discussion paper “Using Artificial Intelligence and Machine Learning in the Development of Drug and Biological Products,” published earlier this year.
• The FDA extended the comment period for a recent draft guidance, “Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products,” which provides guidance to assist sponsors of CGTs in determining whether certain types of manufacturing changes to their products would necessitate the filing of aninvestigational new drug application or biologics license application (BLA). Comments to the draft guidance can be submitted to the docket through November 13, 2023.
• The FDA recently announced a one-year stabilization period, until November 27, 2024, to allow trading partners to implement, troubleshoot, and mature their electronic interoperable systems to meet the requirements of the Drug Supply Chain and Security Act (DSCSA). This stabilization period is intended to avoid disruption to the supply chain and ensure continued patient access to drug products as trading partners work to fully implement the enhanced drug security requirements of the DSCSA. The FDA also issued an immediately effective compliance policy guidance regarding the enforcement of requirements for enhanced drug distribution security. It also issued a revised final compliance policy guidance that describes the FDA’s policies regarding enforcement requirements for wholesale distributors and dispensers to verify a product’s identifier in certain circumstances.
• The FDA recently issued a draft guidance intended to help applicants develop draft labeling for proposed biosimilar and interchangeable biosimilar products for submission in a 351(k) BLA. When finalized, the guidance will revise and replace the FDA’s July 2018 final guidance and includes recommendations on labeling for interchangeable biosimilar products, product identification when the reference product labeling describes a clinical study conducted with a non-US-approved biological product, pediatric use statements, and incorporating relevant immunogenicity data and information from the reference product labeling in the biosimilar or interchangeable biosimilar product labeling. Comments on the draft guidance can be submitted to the docket through November 17, 2023.
• The FDA has issued a long-awaited proposed rule to amend its human prescription-drug labeling regulations to require a new type of Medication Guide — "Patient Medication Information” — for prescription drug products used, dispensed, or administered on an outpatient basis. This new Medication Guide would be an FDA-approved, one-page document that highlights essential information that patients need to know about a prescription drug product. Comments on the proposed rule can be submitted to the docket through November 27, 2023.
• We are digesting the recent FDA draft guidance, “Regulatory Considerations for Prescription Drug Use-Related Software,” which outlines how FDA intends to apply its drug-labeling authorities to certain software outputs that are disseminated by or on behalf of a drug sponsor for use with a prescription drug or a prescription drug–led, drug-device combination product.
• The FDA Office of Prescription Drug Promotion (OPDP) has increased its activity in the second half of 2023 with untitled and warning letters. Notably, the OPDP’s recent untitled letter relating to social media posts follows its June 2023 final guidance, “Presenting Quantitative Efficacy and Risk Information in Direct-to-Consumer Promotional Labeling and Advertisements.”
• We are awaiting a final rule by which the FDA will align its quality system regulation with ISO 13485 and are digesting CDRH’s recent International Harmonization Draft Strategic Plan, which outlines how CDRH will meet its Medical Device User Fee Amendments (MDUFA) V commitments.
• Section 3611 of FDORA codifies the FDA’s authority over medical device inspections to allow the FDA to collect “records or other information” from facilities “in advance of, or in lieu of,” inspections of manufacturing establishments. We will be monitoring for FDA’s guidance on this topic.
• As of August 14, 2023, the FDA updated the AccessGUDID database and the openFDA Unique Device Identifier endpoint to include the field for Global Medical Device Nomenclature Code along with the status of the code.

Whether government or commercial payers are willing to pay for a product, how much they are willing to spend, and under what circumstances:

Pharmaceuticals and Biologics

• We continue to follow how the Inflation Reduction Act of 2022 (IRA) will affect reimbursement for pharmaceutical and biologic products (such as price caps, required discount program for all drugs, mandatory rebates if a drug’s price increases at a rate that outpaces inflation, a redesign of the Medicare Part D benefit, and an increase in biosimilar pricing). The Centers for Medicare & Medicaid Services (CMS) has selected the first 10 drugs subject to the negotiation program. Additional lawsuits have been filed by pharmaceutical manufacturers challenging the constitutionality of the drug price negotiation program, alleging that the IRA’s drug price negotiation program and excise tax punishment violate the First Amendment’s prohibition on compelled speech; the Fifth Amendment’s prohibition on government taking of property without just compensation; the Fifth Amendment’s prohibition on the government depriving private parties of property without due process; and the Eighth Amendment’s ban on excessive fines and penalties. In addition, lawsuits assert that the IRA violates the Constitution’s separation of powers. Each suit requests declaratory and injunctive relief, including a delay in the implementation of the IRA’s drug price negotiation provisions. Manufacturers of the first 10 drugs selected for the drug price negotiation program have until October 1 to submit the required Medicare Drug Price Negotiation Program Agreement. CMS has also issued its first request for the public to identify therapeutic alternatives for the first 10 selected drugs, which will be used to set the initial offer and ultimately set the IRA’s price caps.
• We continue to monitor the Department of Health and Human Services’ (HHS) proposed rule that would modify the current alternative-dispute-resolution process under the 340B Drug Pricing Program, which has been the subject of much scrutiny and disagreement among pharmaceutical manufacturers (who are obligated to cap prices significantly for patients of qualified covered 340B public health entities) and the public health entities whose patients benefit from reduced 340B pricing. The proposed rule was open for comments until January 30, 2023, and would simplify and expedite the process by which covered entities and drug manufacturers resolve disputes about overcharging, duplicate discounts, or drug diversion.
• We are monitoring legislation introduced in Congress earlier this year (H.R. 3290) that would amend the 340B statement to require covered entities to include additional information disclosures regarding who is receiving 340B drugs and how covered entities are using the money saved by participation in the 340B Program.
• Congress is considering numerous proposed pharmacy benefit manager (PBM) reforms in both the House and the Senate. Legislative proposals include but are not limited to: eliminating rebates; divorcing service fees from the price of a drug, discount, or rebate; prohibiting spread pricing; limiting administrative fees; requiring PBMs to report formulary placement rationale; promoting transparency; and many others. PBM reform and transparency measures have become a key policy topic in Washington and could be on the close horizon (as of fourth-quarter 2023).
• CMS issued a proposed rule, “Misclassification of Drugs, Program Administration and Program Integrity Updates Under the Medicaid Drug Rebate Program (MDRP)” (or “Proposed Rule”). Among other topics, the Proposed Rule focuses on enhancing MDRP administration by incorporating policies that would facilitate more accurate and consistent drug information reporting, data collection, and operations. One of the most significant proposals is to revise the definition of “best price” to provide that manufacturers must aggregate cumulative discounts, rebates, or other arrangements to determine the final price realized by the manufacturer for a particular unit of a drug. The CMS fact sheet is available here. Comments on the Proposed Rule were due by July 25, 2023.
• We are monitoring the implementation of Regulation (EU) 2021/2282 (or the “HTA Regulation) on health technology assessment (HTA), which came into force on January 11, 2022, in the EU and will apply through January 12, 2025. An HTA is a multidisciplinary process that summarizes information about the medical, social, economic, and ethical issues relating to the use of a health technology in a systematic, transparent, unbiased, and robust manner. Currently, and until the applicability of the HTA Regulation ends in 2025, a manufacturer, after obtaining the respective authorization for health technologies, must apply to different HTA agencies in various EU member states before new health technologies are broadly accessible. The HTA Regulation aims to harmonize various procedures and standards by ensuring health technology developers can submit only once, at the EU level, any information, data, analyses, and other evidence required for the contemplated joint clinical assessment.

Medical Devices and Medtech

• We continue to monitor developments related to CMS’s recently released new proposed coverage procedures that would permit earlier coverage of medical technology that has received FDA breakthrough designation. The new program, the Transitional Coverage of Emerging Technology pathway (TCET), will leverage existing national coverage determination and coverage with evidence development processes to help ensure earlier coverage for advanced technology and to address the so-called medtech valley of death (i.e., the period after FDA market authorization and before Medicare coverage). Comments on the proposal were due by August 28, 2023. Goodwin Procter hosted a webinar on the TCET proposal in July 2023.

Companies’ interactions with their customers and other stakeholders:

• On July 3, 2023, the HHS Office of the Inspector General (OIG) published a final rule that amends the agency’s civil monetary penalty regulations to add new information-blocking penalties. The rule allows OIG to investigate information blocking and to apply penalties of up to $1 million. This creates a mechanism for OIG to enforce the prohibitions on information blocking contained in the 21st Century Cures Act.
• We anticipate the release of two proposed rules from the HHS Office of the National Coordinator for Health Information Technology. The first, anticipated in September 2023, would address healthcare providers who have committed information blocking. The second, anticipated in November 2023, would address patient engagement, information sharing, and public health interoperability.

Companies’ interactions with patient data:

• With companies collecting patient data on a global basis, we closely follow the latest privacy law developments around the world. In the EU, the UK, and Switzerland, we are tracking evolving case law and guidance surrounding the EU and UK General Data Protection Regulation and the Swiss Federal Act, as well as implications for companies collecting and handling patient data. In the US, the post-Dobbs era is marked by intense regulatory focus on health data. This includes state consumer privacy legislation protecting sensitive health information, health data–specific laws such as the state of Washington’s My Health My Data Act, and a wave of Federal Trade Commission enforcement actions against digital health providers.
• On July 10, 2023, the European Commission adopted an adequacy decision for the new EU-US Data Privacy Framework (DPF), the revamped transatlantic framework designed to support transfers of personal data from the EU to US companies that self-certify compliance with the DPF’s privacy requirements. This has replaced the prior, invalidated Privacy Shield Framework. See Goodwin’s blog post for more information. This is an important update for life science companies because the previous Privacy Shield Framework excluded key-coded patient data from its scope, which prevented sponsors, clinical research organizations (CROs), and other parties involved in transfers of patient data to the US from certifying to the old framework. However, the new DPF has extended its framework’s protection to key-coded patient data processed under a clinical trial, allowing sponsors, CROs, and researchers to certify to the DPF. Separately, the UK and the US have finalized a UK-US adequacy agreement, which will take effect on October 12, 2023. The UK-US adequacy agreement opens up transatlantic data flows between the UK and the US.