News in Phase I trial reform (‼️) The HHS and the FDA are making strides. The latest development: new reforms on manufacturing standards and implementing an expedited Phase I pathway are in the agency’s Unified Agenda and RINs have been assigned. Important signals, because it means these ideas are moving from aspiration toward binding regulation (RINs are regulation identification numbers, meaning the reforms have been assigned "codes"). But first, why does this matter? As I've argued many times, accelerating Phase I trials is one of the highest-leverage things the US can do to speed up biomedical innovation. Phase I is the first time a drug is given to humans. It's where scientific promise meets clinical reality, and where the most valuable evidence in all of drug development, real in-human data, first gets generated. It's also the point where small biotechs live or die, since crossing successfully from preclinical to clinical is what unlocks the next round of investment and starts the flywheel turning. The problem is that the US is slow at this. Getting to a first-in-human trial here takes 18 months to two years and several million dollars before a single patient is dosed. Australia does the same work 6 to 12 months faster and roughly twice as cheaply, with no loss of safety. And it has been doing this for three decades! How is this possible? Again and again, the US picks process over efficiency. Chemistry, manufacturing and controls (CMC) requirements are a clear example: because the regulatory guidance is vague, sponsors overengineer their manufacturing to stay safe, which for some complex products like cell therapies can leave a drug ten times more expensive than it needs to be. This is the backdrop behind Operation TrialBlazer, the department-wide push HHS launched on June 22. It includes proposals for phase-appropriate CMC expectations and an Expedited Phase I pilot built around Qualified Research Institutions. Now, the promise of this initiative seems to be materializing in the form of formal regulatory process, which hopefully means these changes will stick around. It’s an important step toward a durable regulatory framework to give industry stakeholders certainty. So what are the two proposed regulatory actions? 0910-AJ30 (amending 21 CFR Parts 56 and 312) is the expedited-IND and Phase I piece: the IRB and IND changes that would let eligible trials start on a faster timeline, much closer in spirit to Australia's model. 0910-AJ31 (amending Parts 210 and 211) modernizes good manufacturing practice for advanced, distributed, and point-of-care manufacturing. These are the flexible, small-batch production requirements that early-stage and personalized therapies would most benefit from. The full text isn’t out yet but keep an eye on the NPRM under RIN 0910-AJ30 for Phase I changes. There will be a chance to comment soon. In the meantime, the Operation TrialBlazer RFI is open now: comments on the Expedited-IND pilot are due July 22, 2026 (Docket FDA-2026-N-4699), so weigh in. federalregister.gov/document…