Cromos Pharma Regulatory Radar | 2026 Mid-Year Update

Clinical trial regulation is moving quickly in 2026.

Since January, the FDA has opened the door wider to Bayesian trial designs, started testing real time data sharing, updated its approach to master protocols and oncology eligibility criteria, and proposed new ways to accelerate early clinical development.

In Europe, attention is shifting from implementing the Clinical Trials Regulation to making the system work better, while the next major update to Good Clinical Practice is already approaching.

Here are seven developments worth knowing and, more importantly, what they could mean for sponsors.

FDA

• FDA encourages broader oncology trial eligibility

The FDA’s Oncology Center of Excellence finalized three guidance documents addressing performance status, laboratory values, and washout periods and concomitant medications in cancer trials.

The direction is clear. Eligibility criteria should protect participants without unnecessarily excluding patients who could safely participate. FDA encourages sponsors to reconsider restrictive washout periods, concomitant medication exclusions, laboratory thresholds and performance status criteria when they are not scientifically justified.

Why it matters: Overly restrictive criteria can slow recruitment, reduce the available patient population and produce trial populations that are less representative of patients seen in clinical practice.

Sponsor takeaway: Do not carry eligibility language forward automatically. Review whether each exclusion criterion is justified by the actual safety profile, pharmacology and objectives of the current study.

• FDA provides clearer direction on Bayesian trial designs

FDA published new draft guidance on the use of Bayesian methodology in clinical trials, providing a clearer framework for incorporating prior information into the design and analysis of clinical trials.

The guidance covers the use of Bayesian methods for primary inference, adaptive designs and decisions such as dose selection.

Why it matters: Sponsors may have more flexibility to use relevant existing evidence rather than treating every new study in isolation.

Sponsor takeaway: Consider Bayesian approaches early when scientifically appropriate, with clear justification and early FDA alignment.

• FDA gives sponsors more flexibility around substantial evidence

FDA published revised draft guidance on demonstrating substantial evidence of effectiveness, clarifying circumstances in which one adequate and well controlled clinical investigation, supported by confirmatory evidence, may satisfy the substantial evidence standard.

The guidance reflects a broader move toward generating rigorous evidence more efficiently and recognizes that the total evidence package can include different types and sources of confirmatory evidence.

Why it matters: For some programs, this could materially change development timelines and the evidence package needed to support approval.

Sponsor takeaway: Programs still in development should reassess whether two traditional pivotal trials are always necessary and discuss alternative evidence strategies with FDA early. We explored the implications in more detail in our recent article FDA Signals Shift Toward a One-Trial Default for Drug Approval

• FDA targets the path to first in human

As part of Operation TrialBlazer, FDA is targeting one of the less visible sources of development delay: the period between candidate selection and first patient dosed.

The agency issued new draft guidance on Quantitative Systems Pharmacology based dose selection for MABEL calculations in first in human trials and proposed an Expedited IND Pilot Program intended to shorten the path to Phase I development.

FDA has also introduced supporting resources for early IND development, including the Phase 1 IND Navigator and additional CMC resources.

Why it matters: Earlier modeling and regulatory interaction could help identify development issues before they become delays or clinical holds.

Sponsor takeaway: Consider whether QSP can strengthen FIH dose selection when a MABEL based approach is appropriate, and bring regulatory, nonclinical and CMC planning together earlier.

• FDA starts testing real time clinical trials

FDA has begun testing a very different model of regulatory interaction through its real time clinical trials initiative.

Two proof of concept studies are sharing endpoints and data signals with the agency as the trials progress. FDA is also exploring a broader pilot around the approach.

The concept challenges the traditional sequence in which a trial is completed, data are analyzed, a package is prepared and regulators review it before the next major development decision.

Why it matters: Continuous data exchange could eventually enable earlier decisions based on emerging safety and efficacy signals and reduce some of the waiting periods between development stages.

Sponsor takeaway: No immediate operational change is required, but this is an important model to watch as FDA explores ways to make regulatory review more continuous.

EMA and EU

• EMA signals a leaner path for biosimilars

EMA adopted a reflection paper on a tailored clinical approach to biosimilar development, aiming to reduce the amount of clinical data required for the development and approval of certain biosimilar medicines.

The approach reflects the increasing ability of analytical, functional, pharmacokinetic and other evidence to establish biosimilarity without relying on the same clinical development model for every product.

Why it matters: A reduced need for comparative efficacy studies in appropriate programs could meaningfully lower the cost and duration of biosimilar development.

Sponsor takeaway: Sponsors with strong analytical and PK comparability packages should consider whether a more tailored clinical program is scientifically justified and discuss the strategy through regulatory scientific advice.

• ICH E6(R3) Annex 2 sets the next GCP deadline

ICH E6(R3) Annex 2 addresses GCP considerations for trials incorporating decentralized elements, pragmatic approaches and real world data.

The update builds on the broader E6(R3) principles of quality by design and proportionate, risk based approaches to clinical trial conduct. Following adoption in 2026, Annex 2 becomes effective in the EU on January 15, 2027.

Why it matters: Modern trial models create different challenges around data reliability, participant protection, technology and sponsor oversight.

Sponsor takeaway: Sponsors planning decentralized approaches, real world data use or complex data flows in 2027 should review systems, vendor oversight and data governance now.

What the regulatory direction tells us

These developments look different on the surface, but several common themes are emerging.

• FDA is looking for ways to make clinical development more efficient through flexible evidence strategies, modern statistical and modeling approaches, broader trial populations and closer interaction between development and regulatory review.
• Europe is also moving toward greater proportionality, with potentially leaner biosimilar development and a GCP framework designed for studies that increasingly use decentralized methods, real world data and more complex data flows.

None of this means lower regulatory standards. Greater flexibility places more responsibility on sponsors to demonstrate why a particular approach is scientifically justified, operationally feasible and capable of generating reliable evidence.

For clinical development teams, the practical message is simple: regulatory strategy needs to move earlier.

Trial design, statistics, regulatory planning, clinical operations and feasibility increasingly need to be considered together rather than sequentially.

On our radar for the rest of 2026

Several developments will be worth following closely through the end of the year.

• FDA’s Operation TrialBlazer, real time clinical trial initiative and Expedited IND proposal could provide more clarity on how far the agency is willing to rethink traditional development timelines.
• In Europe, sponsors should watch the formal adoption of the new pharmaceutical legislation and prepare for ICH E6(R3) Annex 2, which becomes effective in the EU on January 15, 2027.

The next Cromos Pharma Regulatory Radar will look at which proposals moved into practice, what changed for sponsors and what clinical development teams should prepare for in the months ahead.