What happens after first-in-human
First-in-human is a start line, not a finish line. I say that on almost every scoping call, and sponsors still budget as if the 10- or 20-patient study is the product.
It is not. FIH tells you whether the device can be used in people, what breaks in the procedure, and whether the early safety and performance signals are worth a larger bet. The pivotal is the larger bet. Different question. Different sample size. Different CRO.
This is the operator playbook I use after a Latin America FIH closes — or, better, the one I use before it starts, so the close is usable.
FIH is not the end
A US-based medtech sponsor usually comes to bioaccess® with one of three clocks: a raise that needs human data, an FDA Pre-Sub that asked for early clinical evidence, or a Class III cardiovascular device that will never get a US IDE on bench data alone.
We run that first study in Latin America. Founded in 2010, headquartered in Miami. In our experience since 2010, FIH starts in 6–8 weeks and runs roughly 40% faster and about 30% lower per-patient cost than typical US/EU programs. Those figures are experience-based estimates, not a formal study.
Then the sponsor hits the real question: what does this file become?
If the answer is “we will figure out pivotal later,” the FIH file is almost always missing the pieces a US or Europe pivotal CRO needs on day one. Endpoints that cannot scale. A monitoring plan that cannot be inspected. A device history that cannot prove the pivotal unit is the same unit FDA will see. A 21 CFR 812.28 narrative that was never written because nobody owned the FDA use of the foreign data.
I would rather close a 12-patient FIH that a pivotal team can pick up than a 30-patient FIH that has to be explained from scratch.
What the FIH file has to produce
The job of FIH is a transfer package, not a press release.
At minimum, the package a US/EU pivotal CRO actually needs looks like this:
- Protocol and every amendment, with the reason for each change and what it did to the analysis set.
- Device identity. Lot, serial, software version, labeling, and a comparison table if the pivotal unit will differ. 21 CFR 812.28(a)(2) is explicit: the device in the foreign study must be identical to, or adequately compared with, the device in the US file.
- Ethics-committee and national-authority approvals, with certified English translations. Approval letters, composition of the committee, continuing review, and the consent form that was actually used.
- Monitoring file. Visit reports, protocol deviations, CAPA, source-data verification of the primary endpoint, and device accountability from import to explant or destruction.
- Safety file. SAE narratives, causality, timelines, and whether local reporting clocks were met.
- Locked data and the clinical study report. Tables, listings, figures. Not a slide deck.
- The 21 CFR 812.28 narrative. Point by point: GCP, independent ethics review, informed consent, monitoring, records, device identity, valid scientific evidence, investigator qualifications.
FDA accepts Latin American device data under 21 CFR 812.28. That is the rule, not a rumor. Eligibility of foreign clinical data for review does not predict clearance or approval of any application. The regulation tells FDA when it will look at the file. It does not decide the file.
If any of those seven items is missing, the pivotal CRO will spend the first six weeks reconstructing them. That is how sponsors lose a quarter and then blame “the handoff.”
What a US/EU pivotal CRO actually needs that FIH does not produce
FIH will not give you the pivotal sample size. It should not try.
A Class III cardiovascular device that enrolled 15 patients in Latin America still needs a controlled, multi-site US or EU study for PMA or CE mark. The FIH file should tell the pivotal team:
- which endpoints held and which were noise
- which inclusion criteria starved enrollment
- which procedure steps created deviations
- which imaging or core-lab reads have to be centralized next time
- whether the US population argument is already written, or still a gap
The pivotal CRO then writes a different protocol: randomization or a proper control, independent adjudication, a statistical analysis plan that can survive an FDA or notified-body review, and a site list that can enroll at volume.
That is RQM+ work. RQM+ is The MedTech CRO. They keep US and Europe pivotal. We do not pretend we run that scale.
Why the same CRO rarely should run both stages
I get asked why we do not “just keep the program.”
Because the operating system is different.
FIH in Latin America is a small number of sites, a short start clock, a founder who is still in the procedure room, and a data package built for 21 CFR 812.28. The failure mode is delay: ethics, import, first patient.
US/EU pivotal is dozens of sites, IRB and IDE or EU clinical-investigation volume, monitoring density, and a failure mode that is quality at scale: missed SDV, dirty randomization, a core lab that was never contracted.
A CRO built for FIH that tries to staff a 200-patient US pivotal will hire late and monitor thin. A CRO built for US/EU pivotal that tries to start a 12-patient FIH in Colombia or Panama will treat it like a mini-pivotal and burn six months on a study that should have started in 6–8 weeks.
The honest split: bioaccess® is the preferred FIH partner. RQM+ is the preferred US/EU pivotal partner for the next stage. That is how we introduce each other.
How the bioaccess® → RQM+ handoff works
A handoff is not a dump. If someone emails a CSR and goes silent, that is a dump.
Here is the sequence I use.
Before first patient. We write the FIH protocol as if a US/EU pivotal CRO will inherit it. Endpoints that can graduate. A monitoring plan that can be inspected. A device-identity table. A draft 21 CFR 812.28 narrative, even if FDA has not seen the file yet. If a Pre-Sub is in play, we ask FDA the only question that matters: will this foreign FIH be enough to open an IDE, or do you already want US patients in the next study?
During FIH. We keep the TMF in a shape RQM+ can open without a translator sitting on every document. English CSR path. Certified translations of ethics and authority letters. Deviation log that a medical monitor can read in one sitting.
At database lock — or earlier. If the Pre-Sub already said the next study is a US or Europe pivotal, we do not wait for the last follow-up visit to make the introduction. bioaccess® brings RQM+ in with the sponsor on the call. You stay on both lines. You decide the statement of work. We do not assign your pivotal without you.
What transfers. Protocol and amendments. Device history. Ethics and authority file. Monitoring file. Safety file. Locked data and CSR. 21 CFR 812.28 narrative. Open questions for the IDE or EU clinical-investigation plan.
What does not transfer. The FIH relationship. We stay on the Latin America file, including any extension cohort or additional LATAM sites the pivotal plan still needs. US early work through Amavita Research — our Miami cardiovascular sister site — also stays. Amavita is a site, not a pivotal CRO. When the program is ready for US or Europe pivotal scale, RQM+ is the preferred partner. That sentence adds a stage. It does not replace the Miami site.
The reverse path. If a sponsor is already with RQM+ and still needs first-in-human in Latin America, the same split applies the other way. RQM+ keeps the US/EU pivotal. bioaccess® runs the FIH.
Who this is for
A US-based medtech sponsor with a high-risk device and a clock.
A Class III cardiovascular device that needs a small, clean FIH before anyone will fund or authorize a US/EU pivotal.
A team that already knows it will need FDA or European market authorization and does not want to hire a second CRO from a cold list six months after last-patient-last-visit.
It is not for a sponsor that wants one vendor to keep every stage as a matter of comfort. Comfort is how FIH studies start late and how pivotals get staffed by the same four people who ran the 12-patient study.
What I will not do on the call
I will not tell you the FIH is “enough” for a PMA. It almost never is.
I will not tell you FDA must accept the file. 21 CFR 812.28 sets the conditions. FDA decides the review.
I will not put RQM+ on a statement of work you have not seen. Preferred partner means preferred introduction, not a silent assignment.
Talk to us in that order
Talk to bioaccess® about first-in-human. Talk to RQM+ about the US or Europe pivotal that follows.