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Investigator's Brochure Update & RSI Manager

The annual investigator’s brochure update and its reference safety information, drafted, checked and ready to sign

Every investigator’s brochure updated from new data in days, its safety reference checked rule by rule.

Watch the filmBook a demo
See one case, screen by screen ↓
demo23changesdrafted as tracked changes for Veltrimab Edition 10 — every one cited to its source
target3–5daysfrom the data lock point to a full cited draft
target57 of 60safety-reference findings closed before submission; the rest kept with a reason
target1,486case assessments replayed against the RSI in force on the event date; 5 corrected
The problem

Why the annual IB update eats the weeks before the DSUR

Every investigator’s brochure is reviewed at least once a year, and it goes out with the DSUR. When the data lock point passes, the clinical scientist and the medical writer have to find everything that arrived since the last cut-off — final study reports, the DSUR draft, the integrated safety analysis, signal assessments, nonclinical reports, CMC changes, safety review committee minutes — and work out which section each one changes.

Then the reference safety information has to stand up. Grouping terms such as “serious infections”, non-serious reactions, a reaction seen once, a fatal outcome listed as expected, frequencies still on last year’s exposure: each one decides whether a case is reported as a SUSAR. And a new RSI applies only once every country with ongoing trials has approved it — so a case judged against the wrong edition is a late report waiting to happen.

target≈5weeksfrom the lock point to a full draft, by hand
demo60daysfrom the DSUR data lock point to filing the brochure with it
demo7findingsrule findings on the Veltrimab RSI, from a grouping term to a fatal reaction listed as expected
Where the days to a full draft goestimated
By hand25 days
With the solution4 days
  • Collecting new reports since the last cut-off4 → 0.5 d
  • Drafting section updates as tracked changes10 → 1.5 d
  • Checking the RSI and recalculating frequencies5 → 1 d
  • Making numbers agree across sections and the DSUR3 → 0.5 d
  • Summary of changes and cover-letter text3 → 0.5 d

Estimated split, in working days, for one annual update — by hand and with the solution.

How it works

How an update moves

Six specialist agents collect, draft, check and summarise; section owners and safety physician decide and sign.

What comes in
New data inSince the last edition · study reports, annual safety report, cases, nonclinical
Agents at work
Source collectorfiled by section
Then
Section drafter
RSI checker
Expectedness replay
Then
Consistency checkeracross sections
Then
Summary-of-changes writerready to submit
A person decides
Section owners and safety physicianaccept changes, sign the RSI
What comes out
Tracked-changes brochure
Signed safety reference
Filed with the safety report
One case, step by step

One brochure, from lock point to sign-off

Veltrimab, an IL-23 antibody in Phase 3 for plaque psoriasis and ulcerative colitis, passed its DSUR #4 data lock point on 31 August 2026. Edition 10 of its brochure is due on 30 October. Here is the update, screen by screen, in the working solution.

  1. 01Morning

    Every brochure on one shelf

    Dr. Lena Ortiz · Clinical scientist, IB owner

    Lena opens the solution to her 11 investigator’s brochures, each with its edition and its days to due. Three updates are open, 14 RSI findings wait for a decision across four brochures, and two case assessments used an RSI not yet in force. Veltrimab is due with its safety report in 23 days.

    RSI watch: “Herpes zoster · Veltrimab — Not in RSI Edition 9 → SUSAR, 15-day report due Oct 20.”

  2. 02Opened

    Fourteen new sources, already waiting

    Dr. Lena Ortiz · IB owner

    Edition 10 is ready to prepare. Fourteen documents have arrived since the Edition 9 cut-off: the DSUR #4 draft, the final CSR for VLT-201 in ulcerative colitis, the pen bioequivalence study VLT-106, a stability report, the developmental toxicity report NWB-TX-118, the population PK report, the integrated safety analysis, the serious reaction listing, signal assessment SA-2026-07, the immunogenicity report, safety review committee minutes, one CIOMS case, Edition 9 itself and a protocol amendment.

    “Nothing changes in the brochure until a person accepts it.”

  3. 03One click

    “Prepare Edition 10” — and the agents start

    The agents

    The source collector files the 14 documents by section: 3 study reports, 1 DSUR draft, 4 safety records, 2 nonclinical, 2 CMC and 2 committee records. The section drafters update Sections 1, 3, 4.3, 5.1, 5.2 and 6. The RSI checker recalculates frequencies on N = 1,846 and returns 7 findings and 1 candidate term, and the consistency checker fixes one contradiction.

    Consistency checker: “Exposure agrees in 4 places · 1 contradiction fixed: Section 6 called anaphylaxis expected.”

  4. 04Drafted

    Tracked changes, each with its source passage

    Section drafter

    Change 1 of 23, in the Summary: the lock point moves to 31 August 2026, exposure from 1,212 to 1,846 participants, five studies to seven. Beside it, the DSUR #4 exposure table with the exact passage highlighted. Each change has Accept, Edit and Reject.

    “Why. Exposure and study count taken from the DSUR #4 exposure table at the new data lock point.”

  5. 05Section 4.3

    The study Edition 9 called “ongoing”

    Nonclinical section drafter

    The final report of NWB-TX-118, the enhanced pre- and postnatal development study in cynomolgus monkeys, was signed on 2 July 2026. The new text: at up to 50 mg/kg a week, no maternal toxicity, pregnancy loss, malformations or effects on infant development up to 6 months after birth, at about 31 times the human exposure at the 100 mg maintenance dose. The sentence “Reproductive and developmental toxicity studies are ongoing” is struck.

  6. 06Summarised

    The summary of changes builds itself

    Summary-of-changes writer

    Every change by section, with its reason, its source and whether it is accepted or still open — and a plain statement at the top that a change to the RSI is a substantial change, submitted with DSUR #4 to the 14 countries with ongoing trials. The cover-letter text and the tracked-changes IB come from the same list.

  7. 07Next

    The RSI, checked rule by rule

    RSI checker

    Seven findings on Table 7-1. “Serious infections” is a grouping, not a preferred term. Injection site reaction is non-serious. Anaphylactic reaction was seen once and was life-threatening. Sepsis lists a fatal case as expected. Four rows still use N = 1,212. Each finding names the rule, what the checker found, a proposed fix and the evidence.

    “It is a grouping, so any infection — including ones never seen with veltrimab — would be treated as expected and never reported as a SUSAR.”

  8. 08Candidate

    Herpes zoster, put to the safety physician

    Dr. Maya Chen · Safety physician

    Six suspected serious reactions in three studies, five hospitalised, all recovered. The sponsor judged causality reasonably possible in five, and signal assessment SA-2026-07 proposes adding it. The checker lists the six cases and proposes the row — it never adds a term itself.

  9. 09Signed

    Signed, with the meaning and the reason

    Dr. Maya Chen · Safety physician

    Maya adds herpes zoster with an electronic signature: her password, the meaning — “I approve adding Herpes zoster to the reference safety information” — and the reason. When all seven findings are decided, she signs the RSI for Edition 10: eight expected terms, frequencies on N = 1,846. It applies to cases only after approval in all 14 countries.

    “RSI signed — ready to file with DSUR #4.”

  10. 10Sent · 23 days before due

    All 23 changes decided, sent for sign-off

    Dr. Lena Ortiz · IB owner

    Lena sends Edition 10 for sign-off. Each person signs their part: Dana Okafor Section 4, Priya Raman Section 5.1, Dr. Maya Chen Sections 5.2, 6 and the RSI, and Omar Haddad the filing with DSUR #4.

Who it’s for

Built for everyone who signs a brochure.

The same update, seen by the five people who carry it — the IB owner, the safety physician, the medical writer, a section owner and regulatory.

LO
Dr. Lena OrtizClinical scientist
IB owner
Before
Starts every annual update by hunting for what changed since the last cut-off.
Now
Opens the update to 14 sources already filed by section and 23 cited changes to accept, edit or reject.
MC
Dr. Maya ChenSafety physician
RSI signer
Before
Finds RSI problems one row at a time, often after a case has already been assessed against them.
Now
Gets each rule finding with the rule, the evidence and a proposed fix, and decides candidate terms with the case listing in front of her.
SP
Sam PatelMedical writer
Editor
Before
Rebuilds the summary of changes and the cover letter by hand from the tracked document.
Now
Edits drafts and gets the summary of changes built from the decided edits, with reason and source on every line.
DO
Dana OkaforNonclinical toxicologist
Section owner
Before
Checks that the nonclinical numbers in the brochure match the final report.
Now
Reviews Section 4.3 changes beside the highlighted passage of the report they came from.
OH
Omar HaddadRegulatory affairs lead
Filer
Before
Tracks by hand which countries have approved which RSI edition.
Now
Records each country approval and sees, per brochure, which RSI edition is in force for cases today.
Built on the engine

6 agents. Each with one job, and hard limits.

Six specialist agents collect, draft, check and summarise; section owners and safety physician decide and sign.

Source collector

Finds every document produced since the last IB data cut-off — study reports, the DSUR draft, safety analyses, signal assessments, nonclinical and CMC reports, committee records — and files each against the IB sections it affects.

  • Only approved source versions — the DSUR draft for the same lock point is the one exception
  • Read-only access to the safety database
Section drafter

Drafts each IB section as tracked changes against the current edition — the smallest set of changes that brings the text up to date, in the house IB template.

  • Every change carries a citation
  • Numbers copied, never rounded differently
  • No efficacy claims beyond the source
  • Does not change the RSI table
RSI checker

Checks every RSI row against the rules and the cumulative data — MedDRA preferred terms, serious only, seen more than once, no fatal reaction as expected, frequencies on current exposure — and lists candidate expected reactions with the case listing.

  • Proposes only; a named safety physician signs
  • Cites the rule and the evidence for every finding
  • Never adds or removes a term itself
Expectedness replay

Re-checks every case assessment in the period against the RSI version approved in every country with ongoing trials on the event date.

  • Never downgrades a SUSAR
  • Raises a 15-day or 7-day clock when a case is re-classified
Consistency checker

Makes sure exposure, frequencies and statements about expectedness agree across the Summary, Section 5, Section 6, the RSI and the DSUR draft.

  • Facts are copied from sources, never inferred
Summary-of-changes writer

Writes the summary of changes and the cover-letter paragraph from the accepted edits, by section, with reason and source — and states whether the RSI changes.

  • Only accepted changes appear
Section owners and safety physician

Decide and sign. The agents propose; a named person decides.

Ask in plain words

Ask about any brochure, in plain words

Anyone on the team can ask about a brochure, its reference safety information or the update clock — or tell it what to change. Every answer is cited.

Which brochures are due in the next 60 days?

Three, all filed with their DSUR: Veltrimab Edition 10 on Oct 30 with 23 changes drafted, NWB-2290 Edition 3 on Nov 2 with the interstitial lung disease decision open, and Corventa Edition 6 on Nov 14, in review. Talmirex Edition 5 is already filed and waits for Italy, Czechia and Hungary.

Why is herpes zoster proposed for the Veltrimab RSI?

Six suspected serious reactions in three studies — five needed hospital treatment and all recovered. The sponsor judged causality reasonably possible in five, and signal assessment SA-2026-07 concluded a causal association is reasonably possible. Dr. Maya Chen decides; adding it is a substantial change.

Which RSI version applies to a case reported today?

The RSI in force on the event date — the version approved in every country with ongoing trials. For Talmirex that is still Edition 4: Edition 5 is approved in 6 of 9 countries. A later RSI never downgrades an earlier SUSAR.

Add a check: flag consent forms when a term is added to the RSI

Done. The RSI checker now has a consent form check: when a reaction is added to an RSI, it lists the participant information sheets that must change with the substantial change. It now shows on the herpes zoster and interstitial lung disease candidates.

Every screen

The working solution, as it ships.

13 screens from the working solution, on its sample data. Pick one to see it large.

The brochure shelfEvery IB with its edition and days to due, what needs the IB owner today, and the RSI watch on new serious reactions.
Ready to prepareThe 14 documents that arrived since the Edition 9 cut-off, waiting to be read.
Agents at workSources collected, sections drafted, the RSI checked and the sections made consistent — each step with what it found.
Tracked changesEach change beside the highlighted source passage, with the reason, a confidence and Accept, Edit or Reject.
Section 4.3 ToxicologyThe developmental toxicity results replace a sentence that is no longer true.
Summary of changesEvery change by section with reason, source and status, plus the cover-letter text and the tracked-changes IB.
The RSI checkThe proposed RSI against the rules, with each finding’s rule, evidence and proposed fix.
A candidate expected reactionHerpes zoster with its six cases, the signal assessment and the decision left to the safety physician.
The RSI, signedAll seven findings decided, herpes zoster added and the Edition 10 RSI signed by the safety physician: eight expected terms on N = 1,846.
Sent for sign-offAll 23 changes decided; each section owner signs their part and regulatory files with DSUR #4.
Which RSI applies whenThe version in force for case reports, the version for the DSUR tabulation, and every assessment replayed.
The dashboardDays from lock point to a full draft, RSI findings by rule, what people did with drafted changes and the anniversary calendar.
Your cycle and rulesThe cycle anchor, due date, reminders, automatic preparation and each RSI rule with its guidance reference, switched on or off.
Governance

Built for safety reporting: cited, decided, signed.

Every change cites an approved sourceEach tracked change opens beside the highlighted passage of the report, DSUR or listing it came from. Only approved source versions are used.
People decide every changeAgents propose; the section owner accepts, edits or rejects each change, and the edition goes for sign-off only when all of them are decided.
The safety physician signs the RSIAdding a term, keeping one unexpected and signing the RSI each take an electronic signature with the meaning of the signature, a reason and a password.
The version in force, country by countryA new RSI is used for case assessments only after approval in every country with ongoing trials. Each case is judged against the RSI in force on its event date.
A SUSAR is never downgradedThe expectedness replay re-checks every assessment, never downgrades a SUSAR, and raises a 15-day or 7-day clock when a case is re-classified.
Every step on the recordEach agent step, each accepted fix and each signature is in the activity trail, and keeping a finding as it is needs a written reason.
Configuration

Your update cycle and your RSI rules

How the cycle runs, which rules the RSI checker applies and who decides are settings, not projects.

SettingDefaultChoose from
Cycle anchorDSUR data lock pointDSUR data lock point · IB anniversary date · Development birth date
Due dateLock point + 60 days (with DSUR)Lock point + 60 days (with DSUR) · + 45 days · + 30 days
Reminders to the IB owner and writer30, 14 and 7 days before45, 30, 14 and 7 · 30, 14 and 7 · 14 and 7 days
Prepare automatically at the lock pointOnOn · Off
RSI rules9 of 9 onTurn each rule on or off
Candidate threshold2 casesNumber of suspected serious reactions with reasonable causality, set with − and +
MedDRA version29.1 · September 202629.1 · 29.0
Section ownersOne per sectionAny named person on the team
Connections

Works with the systems you already run

Safety databasesuspected serious reaction listings, nightly
Document storestudy reports, nonclinical and CMC reports
Regulatory trackersubmissions and country approvals
MedDRApreferred terms and hierarchy
The current IBedited as tracked changes in your template
Submission packagetracked-changes IB and cover-letter text
What it changes

The difference, in numbers.

Every figure is labelled: a target the solution is built to, an estimate, a typical published result, or a proven one.

target
3–5days
from the data lock point to a full cited draft
By hand≈ 5 weeks
With agents3–5 days
target
57 of 60
safety-reference findings closed before submission; the rest kept with a reason
findings closed
target
1,486
case assessments replayed against the version in force; 5 corrected

“demo” = seen in the working solution, on its fictional sample data · “target” = the design goal, measured in the live solution · “estimated” = our estimate · Sources: ICH E6 (annual brochure review) · EU guidance on reference safety information (CTFG Q&A, 2017) · ICH E2F. People, companies and products named on this page are fictional — characters and sample data in the working solution.

Questions

What clinical and safety teams ask us.

What is reference safety information (RSI)?

The RSI is the list of serious adverse reactions treated as expected for safety reporting — usually Table 7-1 of the investigator’s brochure. A suspected serious reaction that is not in the RSI in force is a SUSAR and has to be reported on a 7-day or 15-day clock, so every row decides how cases are reported.

How does it draft the annual investigator’s brochure update?

At the data lock point the source collector finds every document since the last cut-off and files it by IB section. The section drafters write tracked changes against the current edition, each citing its source passage, and the consistency checker makes exposure and statements agree across sections and with the DSUR draft.

Which rules does the RSI checker apply?

Nine, each tied to the RSI guidance or a house rule: only MedDRA preferred terms, serious reactions only, seen more than once, no fatal reactions as expected, a justification for life-threatening ones, frequencies on current exposure, candidate expected reactions, IB sections that agree with the RSI, and assessment against the RSI in force. Each can be turned on or off in Settings.

Does the AI decide which reactions are expected?

No. The RSI checker proposes fixes and candidate terms with the evidence; it never adds or removes a term. The safety physician decides, with an electronic signature that records the meaning and the reason.

Will it catch a case assessed against the wrong RSI version?

Yes. The expectedness replay re-checks every assessment against the RSI approved in every country on the event date. In the working solution it flags two Talmirex syncope cases marked expected under Edition 5, which is approved in only 6 of 9 countries, and proposes re-classifying both as SUSARs on the 15-day clock.

Can we set our own update cycle and section owners?

Yes. The cycle anchor, due date, reminders, automatic preparation, each RSI rule, the candidate threshold, the MedDRA version and the owner of each section are all settings.

Do people stay in control?

Yes. Nothing changes in the brochure until a person accepts it. Section owners accept, edit or reject every change, the safety physician signs the RSI, and each section owner signs their part before regulatory files the edition.

How long does it take to go live?

The Agentic Solution Engine builds and deploys it from your requirements — your IB template, your RSI rules and a recent update cycle — and it goes live once every quality gate has passed. We will walk you through it on one of your own brochures first.

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See it on
your brochures.

We’ll run the IB & RSI Manager on one of your own brochures and its last cycle of new data.

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