RN Collins: Series 2 No.2 of 20 Articles Regulatory Clarity vs. Innovation Tension in Emerging Drug Classes

R.N. Collins has written a series of 20 new articles for cannabis law report on 2026 Psychedelics & Legal Issues.

This is the second

Regulatory Clarity vs. Innovation Tension in Emerging Drug Classes 2/20

Author RN Collins

Contact: https://www.linkedin.com/in/rn-collins/

 

I. Introduction

The drug approval framework built over the past half-century was designed around a stable model: a single chemical entity with a defined mechanism of action, tested in a randomized controlled trial against a placebo or active comparator, producing an endpoint measurable by a validated scale. That model continues to function well for the vast majority of pharmaceutical products. For psychedelic-assisted therapies — where the pharmacological compound interacts with a structured psychotherapeutic intervention in ways that neither component fully explains — it functions poorly. Not because regulators are obstructionist, but because the epistemological assumptions embedded in the existing approval framework are not satisfied by the evidence structures that psychedelic therapy trials can generate.

The tension between regulatory clarity and therapeutic innovation in this space is real and bilateral. Sponsors cannot confidently design trials without knowing what evidence standards will be applied. Regulators cannot define evidence standards without knowing what the therapy actually is — pharmacological, psychotherapeutic, or both. The resolution of this tension is not a matter of one side accommodating the other. It requires structural reform of how regulatory agencies conceptualize evidence adequacy for genuinely novel therapeutic modalities.

II. The Epistemological Mismatch: When Pathway Design Assumptions Fail

FDA’s expedited approval pathways — Breakthrough Therapy Designation, Fast Track, Accelerated Approval, and Priority Review — were designed to accelerate the development and review of therapies that address serious conditions with unmet medical need. Breakthrough Therapy Designation, authorized under 21 U.S.C. § 356(a), is granted when preliminary clinical evidence indicates that a drug may demonstrate substantial improvement over available therapies on one or more clinically significant endpoints.¹ The designation triggers intensive FDA guidance, rolling review, and organizational commitment from senior agency leadership. It does not, however, modify the evidentiary standard for approval — the statutory requirement under 21 U.S.C. § 355(d) for “substantial evidence of effectiveness,” generally understood as adequate and well-controlled clinical trials.²

MDMA received Breakthrough Therapy Designation for the treatment of PTSD in August 2017, based on pooled results from MAPS-sponsored Phase 2 trials.³ The designation was a recognition that the available evidence was promising. It was not a guarantee that the existing approval framework could process the evidence that Phase 3 trials would ultimately generate. When FDA issued a Complete Response Letter to Lykos Therapeutics on August 9, 2024, declining to approve midomafetamine (MDMA) capsules for PTSD, the agency identified concerns that are better understood as epistemological than as simply evidentiary.⁴

The distinction matters: an evidentiary problem is a problem of insufficient data that more data can solve. An epistemological problem is a problem with the framework through which data is generated and evaluated — a problem that more data of the same kind cannot resolve. FDA’s concerns about functional unblinding, the inseparability of drug and psychotherapy effects, and the durability of treatment response are epistemological in this sense. Functional unblinding — the near-universal participant awareness of whether they received active MDMA or placebo, attributable to MDMA’s pronounced subjective effects — is not a design flaw that better randomization can correct. It is a structural feature of any trial involving a pharmacologically active psychedelic compound.⁵ The attribution problem — the impossibility of cleanly separating MDMA’s pharmacological contribution from the psychotherapy’s therapeutic contribution when the sponsor’s design thesis is that they are jointly necessary — cannot be resolved by adding more trial arms. And the durability question — whether 18-week endpoint assessments adequately capture the persistence of therapeutic gains from a modality whose mechanisms may include lasting neuroplastic changes — requires a different theory of evidence sufficiency, not simply longer follow-up.⁶

The lesson is not that accelerated pathways are inadequate. It is that the assumptions embedded in those pathways — that blinding is achievable, that pharmacological and psychotherapeutic effects are separable for purposes of attribution, and that post-treatment endpoints can be assessed in a standardized timeframe — must be made explicit and examined before trials are designed, not after an NDA is submitted.

FDA took a significant step toward addressing these structural features in June 2023, when CDER issued its first psychedelic-specific draft guidance: Psychedelic Drugs: Considerations for Clinical Investigations, Docket No. FDA-2023-D-1987.⁷ The guidance acknowledges that functional unblinding may be unavoidable given the “intense perceptual disturbances” caused by psychedelic drugs, recommends use of blinding questionnaires for both subjects and independent raters to assess its impact, recommends a factorial design separating drug from psychotherapy effects in clinical trials, and addresses dose-response characterization and durability monitoring for chronic conditions.⁸ These are precisely the epistemological challenges this article identifies as requiring structural reform. The 2023 guidance represents a meaningful beginning — but it is draft guidance only, is non-binding, and was issued after the MAPP1 and MAPP2 Phase 3 trials had already been completed under the prior SPA agreement. The MDMA CRL demonstrates that acknowledged challenges in draft guidance do not, without more, translate into advance clarity for sponsors about what evidentiary standards will actually be applied at the approval stage.

The SPA process itself is the most instructive case study. FDA and MAPS reached a Special Protocol Assessment agreement on MAPP1 and MAPP2 design — an agreement that, under 21 U.S.C. § 505(b)(5)(B), is binding and may only be changed through written agreement or upon FDA’s identification of a substantial scientific issue essential to product safety or efficacy.⁹ The PDAC’s June 2024 advisory committee meeting and FDA’s subsequent August 2024 CRL raised concerns — including functional unblinding, the contribution of psychotherapy, and durability — that post-dated the SPA agreement and that MAPS had understood to have been resolved by it.¹⁰ This is not evidence of bad faith on either side. It is evidence that the SPA process, as currently structured, is capable of producing agreement on trial design without producing agreement on evidence sufficiency standards — because sufficiency standards are applied at review, not at the SPA negotiation stage. A prospectively negotiated framework adequate to psychedelic therapies would need to close this gap.

III. Accelerated Pathways Analysis: What Each Pathway Can and Cannot Do

Breakthrough Therapy Designation (21 U.S.C. § 356(a)) provides enhanced FDA engagement and guidance but does not modify evidentiary standards.¹¹ For psychedelic therapy, its primary value is in enabling early and intensive dialogue about trial design — a value that was not fully realized in the MDMA/PTSD program, where disagreements about blinding and endpoint assessment were not resolved prior to Phase 3 trial initiation.

Fast Track Designation (21 U.S.C. § 356(b)) is available for drugs intended to treat serious conditions and designed to fill an unmet medical need.¹² Its principal benefit is rolling review of completed sections of the NDA/BLA, allowing sponsors to submit data as it becomes available rather than waiting until the entire package is complete. For psychedelic therapies with long integration periods and complex postmarket monitoring requirements, rolling review could meaningfully reduce time-to-approval — but only if the underlying evidentiary issues are resolved.

Accelerated Approval (21 U.S.C. § 356(c)) permits approval based on a surrogate or intermediate clinical endpoint that is reasonably likely to predict clinical benefit.¹³ The pathway has been extensively used in oncology, where surrogate endpoints like tumor response rate predict survival outcomes. The 2023 Omnibus spending bill made significant changes to the Accelerated Approval framework — codified at 21 U.S.C. § 356(c)(3) — requiring FDA to initiate withdrawal proceedings if sponsors fail to fulfill required postmarket confirmatory trials on a timely basis, substantially tightening the conditions under which confirmatory obligations can be deferred or modified.¹⁴ For psychedelic therapies, this is a material consideration: Accelerated Approval conditioned on postmarket confirmatory trials might address the durability concern FDA raised in the MDMA CRL, but the tightened confirmatory trial requirements mean sponsors can no longer rely on extended flexibility in meeting them. A sponsor that accepts Accelerated Approval with confirmatory trial conditions faces real enforcement risk if the confirmatory trial timeline is not met.

The fundamental problem across all pathways is that they were designed for therapies within established drug categories — oncology, cardiology, infectious disease — where the evidentiary framework is settled. Psychedelic-assisted therapies sit outside those categories. The pathways provide procedural acceleration; they do not provide the epistemological clarity that sponsors need to design trials with confidence that the resulting evidence will satisfy approval standards.

IV. Global Regulatory Divergence: Different Evidentiary Frameworks, Different Approval Logic

International comparison reveals that the evidentiary difficulties FDA has identified in psychedelic therapy trials are not treated as insurmountable by peer regulatory agencies. Three regulatory developments are particularly instructive.

Australia’s Therapeutic Goods Administration (TGA) announced on February 3, 2023, that psilocybin and MDMA would be rescheduled from Schedule 9 (Prohibited Substances) to Schedule 8 (Controlled Drugs) in the Poisons Standard, effective July 1, 2023.¹⁵ Under the rescheduling, authorized psychiatrists may prescribe psilocybin for treatment-resistant depression and MDMA for PTSD, subject to approval under the TGA’s Authorised Prescriber scheme and ethics committee oversight.¹⁶ Australia’s reclassification constitutes a controlled access pathway rather than a full marketing approval in the sense FDA would recognize — there is no approved product on Australia’s Register of Therapeutic Goods, and the Authorised Prescriber scheme requires individual ethics committee authorization for each prescribing psychiatrist.¹⁷ What makes it analytically significant is the risk-benefit determination it represents: the TGA concluded, on the basis of Phase 2 evidence and clinical judgment about unmet need, that controlled access under enhanced oversight was justified before Phase 3 evidence was complete. FDA has not made an equivalent determination for any psychedelic compound.

Canada’s Special Access Program (SAP) offers a second model. Effective January 5, 2022, regulatory amendments to the Food and Drug Regulations — Regulations Amending Certain Regulations Relating to Restricted Drugs (Special Access Program), SOR/2021-271 — permitted licensed health care practitioners to request access to restricted drugs, including psilocybin and MDMA, through the SAP for patients with serious or life-threatening conditions where other therapies have failed, are unsuitable, or are unavailable.¹⁸ By February 2024, Health Canada had authorized 176 Canadians to access psilocybin through the SAP.¹⁹

The European Medicines Agency’s (EMA) PRIME designation — Priority Medicines, launched in March 2016 — offers a third model.²⁰ PRIME provides enhanced regulatory support for medicines targeting unmet medical needs, including early dialogue with EMA scientific committees and accelerated assessment pathways. Unlike FDA’s Breakthrough Therapy Designation, PRIME is explicitly designed to accommodate products that may require adaptive or unconventional evidentiary approaches — making it a more flexible tool for the epistemological challenges that psychedelic therapies present. No psychedelic compound had received PRIME designation as of the time of writing, but the designation’s design principles — early adaptive engagement, acceptance of unconventional evidence structures in defined contexts — offer a model that FDA’s Breakthrough Therapy framework could incorporate.

The contrast among Australian, Canadian, and U.S. regulatory approaches does not straightforwardly establish that FDA’s evidentiary standards are excessive — safety concerns about blinding, selection bias, and durability are legitimate. What it does establish is that the assumptions embedded in FDA’s approval framework are not the only possible assumptions: different agencies, applying different risk-benefit frameworks and different access models, have reached different conclusions about what evidence is sufficient for therapeutic use under controlled conditions. Systematic engagement with these comparative models — with attention to the safety surveillance outcomes they are generating — should inform FDA’s evolution of its approach to psychedelic therapies.

V. Real-World Evidence Integration and Regulatory Sandboxes

Two structural mechanisms offer pathways toward regulatory frameworks better calibrated to convergent psychedelic therapies: real-world evidence (RWE) and regulatory sandboxes.

FDA published its Framework for the Real-World Evidence Program in December 2018, pursuant to Section 3022 of the 21st Century Cures Act, which added 21 U.S.C. § 355g to the FD&C Act.²¹ The RWE framework enables sponsors to use data derived from clinical practice — including electronic health records, patient registries, and insurance claims — to support approval of new indications for already-approved drugs or to satisfy postapproval study requirements. The framework’s primary development has been in oncology, rare disease, and cardiovascular medicine, where large patient registries and established biomarkers provide high-quality RWD.

Oregon’s licensed psilocybin services program, which began accepting license applications on January 2, 2023, under Oregon Administrative Rules Chapter 333, Division 333, and opened service centers to clients in summer 2023, is generating what may become the first large-scale post-use dataset from a real-world psychedelic therapeutic context in the United States.²² Oregon’s SB 303, signed June 6, 2023, created a centralized data collection system for safety-related information from psilocybin service centers, with mandatory reporting requirements effective January 1, 2025. This data does not constitute clinical trial evidence and would face significant methodological challenges before FDA could treat it as RWE in the statutory sense. But it represents an emerging dataset whose systematic analysis could inform both the safety profile and the durability questions that FDA has identified as central to the psychedelic approval challenge.

The most advanced pending NDA package for a psychedelic therapy now comes from Compass Pathways. In June 2025, Compass reported that its Phase 3 COMP005 trial of COMP360 psilocybin for treatment-resistant depression met its primary endpoint — a statistically significant reduction in MADRS score at Week 6 following a single 25 mg dose compared to placebo, with a mean treatment difference of -3.6 points (p<0.001).²³ In February 2026, Compass reported that its second Phase 3 trial, COMP006, also met its primary endpoint, with a -3.8 point mean treatment difference between two doses of 25 mg COMP360 and two doses of 1 mg COMP360 administered three weeks apart (p<0.001), making COMP360 the first classic psychedelic to achieve highly statistically significant results in two independent Phase 3 trials.²⁴ Compass has submitted a request for FDA meetings to discuss a rolling NDA submission, targeting an NDA filing in Q4 2026.²⁵ The regulatory handling of the Compass NDA will be the first test of whether FDA applies the evidentiary framework developed through the MDMA program or develops a new approach responsive to the epistemological critiques this article identifies. The distinction matters: Compass’s Phase 3 program was designed after the MDMA CRL and with awareness of the blinding, attribution, and durability concerns FDA raised — making it a more direct test of whether the 2023 draft guidance, when translated into a Phase 3 design, produces an approvable evidence package.

Regulatory sandboxes offer a complementary mechanism. The concept — borrowed from financial services regulation, where the UK Financial Conduct Authority’s sandbox programme has provided a controlled space for testing innovative products under temporary regulatory permission — has been proposed for pharmaceutical innovation contexts.²⁶ Two existing FDA programs are partial domestic analogues. The Digital Health Technologies (DHT) for Drug Development program, established under PDUFA VII commitments, provides a structured framework for early engagement on the use of digital health technologies — including AI monitoring tools — in clinical drug development, with a DHT Steering Committee spanning CDER, CBER, and CDRH to promote review consistency.²⁷ The Emerging Technology Program (ETP), established in 2014 under CDER’s Office of Pharmaceutical Quality, provides early collaborative engagement between sponsors and an interdisciplinary Emerging Technology Team to resolve technical and regulatory challenges for novel technologies prior to NDA submission.²⁸ Neither program was designed for psychedelic-specific evidentiary challenges — the DHT program focuses on digital tool validation for drug development generally, and the ETP focuses on manufacturing innovation — but both represent existing institutional infrastructure through which psychedelic sponsors could seek early guidance on novel trial design questions before full Phase 3 investment, reducing the gap between guidance and approval standard that the MDMA program exposed.

VI. The Path Forward: Modular and Dynamic Frameworks

The regulatory frameworks needed for psychedelic-assisted therapies are neither categorically more permissive nor categorically more restrictive than existing frameworks. They are differently structured. They need to be modular — capable of addressing pharmacological, psychotherapeutic, and digital components under a unified evidentiary framework rather than sequentially under separate frameworks. A modular framework would specify, in advance: what blinding alternatives are acceptable when full blinding is technically impossible (active placebo designs, expectancy correction methodologies, and open-label crossover structures are candidate approaches that FDA has not yet formally addressed in psychedelic-specific guidance); how therapeutic and pharmacological effect attribution will be handled when the sponsor’s design premise is joint necessity; and what evidence of durability is sufficient when the long-term natural history of psychedelic therapy response is still being established. They need to be dynamic — capable of incorporating accumulating real-world evidence over time rather than requiring that all evidence be generated prior to approval, with structured protocols for integrating data from Oregon’s operational psilocybin services program and from international controlled access frameworks as it matures. And they need to be prospectively negotiated — meaning that FDA, sponsors, and patient representatives engage in formal Special Protocol Assessment discussions that address the epistemological structure of the evidence package, not merely its statistical design, before Phase 3 trials begin.

The FDA’s Complete Response Letter to Lykos in August 2024 was a signal that the existing framework, applied as designed to a psychedelic therapy NDA, produced an outcome that dissatisfied all parties — the sponsor, the patient advocacy community, and, by the FDA’s own subsequent transparency initiative releasing 89 previously unpublished CRLs, arguably the agency itself.³⁰ The lesson is not that one side was wrong. It is that the framework needs development adequate to the product class. That development is the work that lies immediately ahead.

Endnotes

1. 21 U.S.C. § 356(a) (breakthrough therapy designation criteria and enhanced FDA engagement), https://www.law.cornell.edu/uscode/text/21/356.
2. 21 U.S.C. § 355(d) (new drug approval standard requiring substantial evidence of effectiveness from adequate and well-controlled clinical trials), https://www.law.cornell.edu/uscode/text/21/355.
3. MAPS, Press Release: FDA Grants Breakthrough Therapy Designation for MDMA-Assisted Psychotherapy for PTSD (Aug. 2017), https://maps.org/news/media/press-release-fda-grants-breakthrough-therapy-designation-for-mdma-assisted-psychotherapy-for-ptsd-agrees-on-special-protocol-assessment-for-phase-3-trials/; see also FDA, Briefing Document NDA/BLA # 215455, at 1 (confirming breakthrough therapy designation granted Aug. 15, 2017), https://www.fda.gov/media/178984/download.
4. MAPS, Statement on FDA’s Public Release of Complete Response Letter for MDMA-Assisted Therapy (Sept. 4, 2025), https://maps.org/2025/09/04/fda-public-release-of-crl/; MAPS, Statement on FDA Complete Response Letter on MDMA-Assisted Therapy for PTSD New Drug Application (Aug. 9, 2024), https://maps.org/2024/08/09/maps-statement-on-fda-complete-response-letter-on-mdma-assisted-therapy-for-ptsd-new-drug-application/.
5. See HCPLive, FDA Releases CRL Detailing Safety Concerns for MDMA-Assisted Therapy in PTSD (Sept. 4, 2025), https://www.hcplive.com/view/fda-releases-crl-detailing-safety-concerns-mdma-assisted-therapy-ptsd.
6. See Psychedelic Alpha, Breaking: FDA Publishes Lykos Therapeutics’ MDMA Complete Response Letter (Sept. 4, 2025), https://psychedelicalpha.com/news/breaking-fda-publishes-lykos-therapeutics-mdma-complete-response-letter-crl.
7. FDA, CDER, Psychedelic Drugs: Considerations for Clinical Investigations, Draft Guidance for Industry, Docket No. FDA-2023-D-1987 (June 2023), 88 Fed. Reg. 41257 (June 26, 2023), https://www.federalregister.gov/documents/2023/06/26/2023-13428/psychedelic-drugs-considerations-for-clinical-investigations-draft-guidance-for-industry.
8. Id. (recommending blinding questionnaires for both subjects and independent clinical raters to assess functional unblinding; recommending factorial designs separating drug and psychotherapy effects; addressing durability monitoring for chronic conditions).
9. 21 U.S.C. § 505(b)(5)(B) (Special Protocol Assessment agreements binding on FDA absent written agreement or identification of substantial scientific issue essential to safety or efficacy), https://www.law.cornell.edu/uscode/text/21/355.
10. See Clinical Trial Vanguard, Guided, Then Penalized: A Deep Dive into the FDA’s MDMA Ruling and What It Means for Psychedelic Clinical Trials (May 5, 2025), https://www.clinicaltrialvanguard.com/opinion/guided-then-penalized-a-deep-dive-into-the-fdas-mdma-ruling-and-what-it-means-for-psychedelic-clinical-trials/.
11. 21 U.S.C. § 356(a); FDA, Breakthrough Therapy Designation: Guidance for Industry (Dec. 2018), https://www.fda.gov/regulatory-information/search-fda-guidance-documents/breakthrough-therapy-designation.
12. 21 U.S.C. § 356(b), https://www.law.cornell.edu/uscode/text/21/356.
13. 21 U.S.C. § 356(c), https://www.law.cornell.edu/uscode/text/21/356.
14. Consolidated Appropriations Act, 2023, Pub. L. No. 117-328, div. FF, tit. III, § 3208 (2022) (amending 21 U.S.C. § 356(c)(3) to require FDA to initiate withdrawal proceedings when sponsors fail to fulfill confirmatory trial requirements, substantially tightening prior flexibility), https://www.congress.gov/bill/117th-congress/house-bill/2617/text.
15. TGA, Change to Classification of Psilocybin and MDMA to Enable Prescribing by Authorised Psychiatrists (announced Feb. 3, 2023; effective July 1, 2023), https://www.tga.gov.au/news/media-releases/change-classification-psilocybin-and-mdma-enable-prescribing-authorised-psychiatrists.
16. TGA, Re-scheduling of Psilocybin and MDMA in the Poisons Standard: Questions and Answers, https://www.tga.gov.au/resources/publication/scheduling-decisions-final/notice-final-decision-amend-or-not-amend-current-poisons-standard-june-2022-acms-38-psilocybine-and-mdma/re-scheduling-psilocybin-and-mdma-poisons-standard-questions-and-answers.
17. A New Era of Psychedelic Medicine in Australia, Regulatory Rev. (Apr. 23, 2024), https://www.theregreview.org/2024/04/23/perkins-a-new-era-of-psychedelic-medicine-in-australia/.
18. Health Canada, Notice to Stakeholders: Requests to the Special Access Program (SAP) Involving Psychedelic-Assisted Psychotherapy (citing SOR/2021-271, in force Jan. 5, 2022), https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/announcements/requests-special-access-program-psychedelic-assisted-psychotherapy.html.
19. Michael Polito et al., Expanded Access to Psychedelic Treatments: Comparing American and Canadian Policies, PMC (2025), https://pmc.ncbi.nlm.nih.gov/articles/PMC11840896/.
20. European Medicines Agency, PRIME: Priority Medicines (launched Mar. 7, 2016), https://www.ema.europa.eu/en/human-regulatory-overview/research-development/prime-priority-medicines.
21. FDA, Framework for the Real-World Evidence Program (Dec. 2018), issued pursuant to 21 U.S.C. § 355g, https://www.fda.gov/science-research/science-and-research-special-topics/real-world-evidence; 83 Fed. Reg. 63395 (Dec. 7, 2018), https://www.federalregister.gov/documents/2018/12/07/2018-26546/framework-for-a-real-world-evidence-program-availability.
22. Or. Health Auth., Oregon Psilocybin Services — Administrative Rules, Or. Admin. R. ch. 333, div. 333, https://www.oregon.gov/oha/ph/preventionwellness/pages/psilocybin-administrative-rules.aspx; Or. Rev. Stat. §§ 475A.372, 475A.374 (2023), https://www.oregon.gov/oha/PH/PREVENTIONWELLNESS/Pages/Psilocybin-SB303-and-Data-Collection.aspx.
23. Compass Pathways plc, Compass Pathways Successfully Achieves Primary Endpoint in First Phase 3 Trial Evaluating COMP360 Psilocybin for Treatment-Resistant Depression (June 23, 2025) (reporting COMP005 primary endpoint: mean MADRS treatment difference -3.6 points, 95% CI [-5.7, -1.5]; p<0.001 at Week 6; comparison: 25 mg COMP360 versus placebo), https://ir.compasspathways.com/News–Events-/news/news-details/2025/Compass-Pathways-Successfully-Achieves-Primary-Endpoint-in-First-Phase-3-Trial-Evaluating-COMP360-Psilocybin-for-Treatment-Resistant-Depression/default.aspx.
24. Compass Pathways plc, Compass Pathways Successfully Achieves Primary Endpoint in Second Phase 3 Trial Evaluating COMP360 Psilocybin for Treatment-Resistant Depression (Feb. 17, 2026) (reporting COMP006 primary endpoint: mean MADRS treatment difference -3.8 points, 95% CI [-5.8, -1.8]; p<0.001 at Week 6; comparison: 25 mg COMP360 versus 1 mg COMP360; 26-week COMP006 data expected second half of 2026), https://ir.compasspathways.com/News–Events-/news/news-details/2026/Compass-Pathways-Successfully-Achieves-Primary-Endpoint-in-Second-Phase-3-Trial-Evaluating-COMP360-Psilocybin-for-Treatment-Resistant-Depression/default.aspx.
25. Compass Pathways plc, supra note 24 (stating company has submitted request for FDA meeting to discuss rolling NDA submission, targeting NDA filing Q4 2026).
26. See UK Fin. Conduct Auth., Regulatory Sandbox, https://www.fca.org.uk/firms/innovation/regulatory-sandbox.
27. FDA, CDER and CBER, Digital Health Technologies (DHTs) for Drug Development, PDUFA VII Framework, https://www.fda.gov/science-research/science-and-research-special-topics/digital-health-technologies-dhts-drug-development.
28. FDA, CDER, Emerging Technology Program (ETP) (est. 2014), https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/emerging-technology-program-etp; see also FDA, Advancement of Emerging Technology Applications for Pharmaceutical Innovation and Modernization: Guidance for Industry (2021), https://www.fda.gov/regulatory-information/search-fda-guidance-documents/advancement-emerging-technology-applications-pharmaceutical-innovation-and-modernization-guidance.
29. Polito et al., supra note 19; FDA, Expanded Access to Investigational Drugs for Treatment Use, https://www.fda.gov/patients/learn-about-expanded-access-and-other-treatment-options/expanded-access.
30. Labiotech, With Lykos CRL Now Public, FDA Opens New Era of Accountability (Sept. 8, 2025), https://www.labiotech.eu/trends-news/lykos-crl/.