📚 Part of the TILA-278 Regulatory Dossier — Reader's Guide. This article shows the live document; edits to the source appear here automatically.

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Governance & RACI (TILA-278)

Document ID: PM-002
Version: 1.0
Change History: 1.0 — Initial issue.
Standard(s): Program management

Governance & RACI — TILA-278

Decision rights and accountabilities for the TILA-278 programme: the steering committee, the core team roles, escalation paths, and a RACI matrix across clinical, nonclinical, CMC, regulatory, biostatistics, and operations.

1. Purpose and scope

This document defines the governance model and the decision-rights framework for the TILA-278 development programme (Virtual Biopharma Inc.), a recombinant humanized immunoglobulin G1 (IgG1) bispecific monoclonal antibody that couples anti-TL1A (TNFSF15) antagonism with IL-22 receptor (IL-22R) agonism, produced by Chinese hamster ovary (CHO) cell culture and administered subcutaneously (SC) for the treatment of moderate-to-severe ulcerative colitis (UC). It establishes the governance bodies and their remits, the accountable core-team roles, the delegation of authority for stage-gate decisions, the escalation paths, the oversight of the Sponsor's outsourced (virtual) operating model, and a Responsible/Accountable/Consulted/Informed (RACI) matrix spanning the clinical, nonclinical, CMC, regulatory, biostatistics, and operational domains.

The framework governs the transition of the programme from the completed Phase 2b induction study (Protocol TILA278-201) toward a confirmatory Phase 3 programme and marketing application, anchored to the End-of-Phase-2 (EOP2) interaction with health authorities and to a Biologics License Application (BLA) filed under 21 CFR Part 601. It is written to be consistent with the risk-based quality-management and oversight expectations of ICH E6(R3), the quality risk-management principles of ICH Q9(R1), and the biotechnology-specific technical standards that apply to the product (ICH S6(R1) for nonclinical assessment; ICH Q5A(R2), Q5C, and Q6B for viral safety, stability, and specifications). It is the companion governance instrument to the Project Charter (PM-001), the Program Risk Register (PM-004), the Vendor/CRO Management plan (PM-006), and the Clinical Development Plan (PM-007), and it does not restate their content but assigns the decision rights that operate over them.

2. Governance framework

Governance is structured as a four-tier model that separates executive/investment authority from programme-level integration, functional execution, and independent oversight. The tiers are deliberately kept distinct so that benefit-risk and investment decisions are made with the appropriate separation from day-to-day execution, and so that independent safety and data-integrity judgements are insulated from programme advocacy.

• Tier 1 — Executive and Board (investment authority). Approves programme continuation at major stage gates, authorizes the confirmatory-programme investment, and owns portfolio, financing, and partnering decisions for a capital-intensive first-in-class programme. Chaired by the Chief Executive Officer (CEO) with the Chief Business Officer (CBO).
• Tier 2 — Development Governance Committee (DGC) — the steering committee. The standing cross-functional decision body for the programme. It integrates clinical, nonclinical, CMC, regulatory, biostatistics, safety, and operational inputs; endorses the integrated development plan, the target label, and the health-authority strategy; approves benefit-risk positions for external interactions; and is the escalation destination for any risk crossing into the High band of the Program Risk Register. Chaired by the Chief Medical Officer (CMO).
• Tier 3 — Program Team (core team). The operational engine that executes the plan endorsed by the DGC. Led by the Program Director (PMO), it comprises the functional leads and is accountable for delivery to scope, timeline, budget, and quality, and for surfacing risks and decisions to the DGC.
• Tier 4 — Independent oversight. An independent Data Safety Monitoring Board (DSMB) and independent central endoscopy reading provide judgements that are structurally separated from the Program Team. The DSMB reviews unblinded safety data against a pre-agreed charter; central readers apply blinded, adjudicated endoscopy scoring so that the primary and key secondary endpoints are not subject to site-level or Sponsor influence.

Beneath the Program Team, standing functional sub-teams (working groups) execute defined workstreams and report into the core team: a Clinical Sub-team, a Clinical Pharmacology/PK-immunogenicity Sub-team, a CMC/Technical Operations Sub-team (including the combination-product/device workstream), a Nonclinical Sub-team, a Regulatory Sub-team, a Biostatistics and Data Management Sub-team, and a Safety Management Team (SMT) for ongoing signal detection and benefit-risk maintenance.

3. Governance bodies

Table 3-1. Governance bodies, remit, and cadence

Body	Chair	Core membership	Primary remit	Cadence	Decision authority
Executive / Board	CEO	CEO, CBO, CMO, CFO/Finance, non-executive directors	Investment gates, financing, partnering, portfolio	Quarterly and on stage-gate	Approve/decline programme continuation and funding
Development Governance Committee (DGC)	CMO	CMO, HCD, HCP, HPV, HBS, VPRA, VPCMC, HNC, HQA, CPL, PMO, CBO	Integrated plan, target label, benefit-risk, health-authority strategy, High-band risk oversight	Quarterly and on trigger	Endorse plan and external positions; direct mitigation
Program Team (core team)	PMO	PMO plus all functional leads	Execution to scope/time/budget/quality; risk surfacing	Monthly	Operational decisions within DGC-endorsed plan
Safety Management Team (SMT)	HPV	HPV, CMO, HCD, HCP, medical monitor, HBS	Signal detection, RMP, aggregate safety review, benefit-risk maintenance	Monthly and ad hoc	Recommend safety actions; escalate to DGC/DSMB
Data Safety Monitoring Board (DSMB)	Independent chair	Independent physicians and an independent statistician (voting); non-voting Sponsor liaison	Unblinded safety oversight against charter	Per charter (scheduled and triggered)	Recommend continue/modify/pause/stop
Central Endoscopy Reading	Independent reader panel	Blinded central readers with adjudication	Independent endpoint scoring (endoscopy)	Continuous during conduct	Adjudicated endpoint reads binding for analysis

Quorum, voting, and conflict-of-interest rules are defined in each body's terms of reference or charter. DGC and Board decisions are minuted with a documented rationale and are traceable to the supporting technical modules of the dossier (Modules 2, 3, and 5). The DSMB operates under an independent charter with a firewalled unblinded statistician; the Sponsor does not access unblinded comparative safety data outside the pre-specified process.

4. Core team roles and responsibilities

Accountable owners are the functional leaders empowered to direct execution within their domain and to escalate. The role key below is used consistently in the RACI matrix (Section 6) and aligns with the ownership taxonomy of the Program Risk Register (PM-004).

Table 4-1. Core team role key and accountabilities

Abbreviation	Role	Principal accountabilities for TILA-278
CEO	Chief Executive Officer	Investment and continuity decisions; Board interface; ultimate corporate accountability
CBO	Chief Business Officer / Alliance Management	Partnering/financing; alliance governance; competitive positioning of the dual-mechanism profile
CMO	Chief Medical Officer	Programme medical leadership; DGC chair; benefit-risk ownership; medical sign-off on external positions
HCD	Head of Clinical Development	Confirmatory design, endpoints, and clinical strategy; clinical study reports
HCO	Head of Clinical Operations	Study execution, site management, enrollment delivery, and CRO operational oversight
HCP	Head of Clinical Pharmacology	Population PK/TMDD modelling, exposure-response, dose/interval selection, immunogenicity (ADA) interpretation
HPV	Head of Pharmacovigilance / Drug Safety	Signal detection, RMP, aggregate safety, SMT leadership, DSMB liaison
HBS	Head of Biostatistics	Estimands, Statistical Analysis Plan, unblinding controls, analysis integrity
VPRA	VP Regulatory Affairs	Health-authority strategy and interactions; BLA (21 CFR 601) filing and lifecycle
VPCMC	VP CMC / Technical Operations	CHO drug-substance and drug-product process, comparability, specifications, and supply
HNC	Head of Nonclinical Safety	ICH S6(R1) nonclinical package; cynomolgus toxicology; nonclinical waiver justifications
HQA	Head of Quality Assurance	GxP quality systems, audits, inspection readiness, vendor quality oversight
CPL	Combination-Product / Device Lead	Prefilled-syringe/autoinjector design control and human-factors dossier
PMO	Program Director (PMO)	Cross-functional integration, plan/timeline/budget, risk register, governance reporting

5. Decision rights and delegation of authority

Decision rights are assigned so that each stage-gate has a single accountable authority, a designated recommending body, and defined consulted functions. Recommendations originate in the Program Team and its sub-teams; endorsement of externally facing or benefit-risk-bearing positions rests with the DGC; investment and continuity decisions rest with the Executive/Board.

Table 5-1. Stage-gate decision authority

Decision / stage gate	Recommending body	Accountable authority	Key consulted functions
Transition from Phase 2b to confirmatory programme (EOP2 go/no-go)	Program Team	Executive / Board (on DGC endorsement)	CMO, HCD, VPRA, HBS, VPCMC, CBO
Confirmatory dose and dosing-interval selection	Clinical Pharmacology Sub-team	DGC	HCP, HCD, HBS, HPV
Confirmatory protocol design, endpoints, and estimands	Clinical Sub-team	DGC	HCD, HBS, VPRA, CMO
Nonclinical package scope and waiver rationale (no genotoxicity, carcinogenicity, hERG, or thorough-QT studies for a monoclonal antibody, per ICH S6(R1))	Nonclinical Sub-team	HNC (endorsed by DGC)	VPRA, CMO, HPV
Commercial CHO process lock and comparability strategy (ICH Q5E)	CMC Sub-team	VPCMC (endorsed by DGC)	HQA, VPRA
Drug-substance/drug-product specifications, including dual potency (ICH Q6B)	CMC Sub-team	VPCMC	HQA, HCP, VPRA
Health-authority interaction strategy and meeting positions	Regulatory Sub-team	VPRA (endorsed by DGC)	CMO, HCD, VPCMC, HNC, HBS
BLA submission readiness and filing (21 CFR 601)	Program Team	Executive / Board (on DGC endorsement)	VPRA, VPCMC, HCD, HBS, HQA
Safety action (continue/modify/pause) on a signal	SMT / DSMB	CMO (DSMB recommendation binding on conduct)	HPV, HCD, HBS
Vendor selection, qualification, and material contract change	CMC/Clinical Sub-teams	PMO with VPCMC/HCO (per spend authority)	HQA, CBO
Programme budget and investment gate	Program Team	Executive / Board	CBO, PMO

6. RACI matrix

6.1 Legend and conventions

R — Responsible performs the work. A — Accountable is the single owner who signs off (exactly one A per row). C — Consulted provides input before the decision. I — Informed is notified of the outcome. Governance bodies (DGC) and the PMO appear as columns because they hold integration and endorsement roles distinct from functional execution. The matrix spans the six programme domains named in the scope; where a deliverable is externally facing, the DGC holds an endorsement role and the accountable function retains technical A.

Table 6-1. Programme RACI matrix

Deliverable / decision	DGC	PMO	CMO/HCD	HCP	HPV	HBS	VPRA	VPCMC	HNC	HQA	CPL	CBO
Clinical
Confirmatory protocol design and endpoints	C	I	A/R	C	C	C	C	I	I	I	I	I
Clinical study execution and site/enrollment delivery	I	C	A/R	I	I	I	I	I	I	C	I	I
Integrated benefit-risk assessment (Module 2.5)	C	I	A/R	C	C	C	C	C	C	I	I	I
Pharmacovigilance, RMP, and safety signal management	C	I	C	C	A/R	C	C	I	C	I	I	I
Clinical pharmacology
Population PK/TMDD modelling and dose/interval selection	C	I	C	A/R	C	C	I	C	I	I	I	I
Immunogenicity (ADA) strategy and interpretation	C	I	C	A/R	C	C	C	C	I	I	I	I
Biostatistics
Estimands and Statistical Analysis Plan	C	I	C	C	C	A/R	C	I	I	I	I	I
Data integrity and unblinding controls	I	I	C	I	C	A/R	I	I	I	C	I	I
Nonclinical
Cynomolgus toxicology and ICH S6(R1) package	C	I	C	C	C	I	C	C	A/R	I	I	I
Nonclinical waiver rationale (genotoxicity/carcinogenicity/hERG/TQT not warranted)	C	I	C	I	C	I	C	I	A/R	I	I	I
CMC
CHO process, Protein A + polishing, and comparability (ICH Q5E)	I	I	I	I	I	I	C	A/R	I	C	I	I
Specifications and dual potency release (ICH Q6B)	I	I	I	C	I	I	C	A/R	I	C	I	I
Viral safety and stability (ICH Q5A(R2)/Q5C)	I	I	I	I	I	I	C	A/R	I	C	I	I
Combination-product/device (prefilled syringe/autoinjector)	I	C	C	I	I	I	C	C	I	C	A/R	I
Regulatory
Health-authority engagement and meeting strategy	C	I	C	C	C	C	A/R	C	C	I	I	I
BLA preparation and filing (21 CFR 601)	C	C	C	C	C	C	A/R	C	C	C	C	I
Operations / business
Vendor/CRO/CDMO governance and oversight	I	A/R	C	I	I	I	I	C	I	C	I	C
Program budget, funding, and portfolio decisions	C	R	I	I	I	I	I	I	I	I	I	A
Risk register maintenance and governance reporting	C	A/R	C	C	C	C	C	C	C	C	C	C
Quality systems, audits, and inspection readiness	I	C	I	I	I	I	I	C	I	A/R	I	I

7. Escalation

Escalation is triggered by defined thresholds rather than by discretion alone, so that material issues reach the accountable authority without delay. The path runs sub-team → Program Team → DGC → Executive/Board, with independent safety judgements routed through the SMT and DSMB.

Standing escalation triggers include: any Program Risk Register item crossing into the High band or any new Critical-impact risk (to the DGC); a DSMB recommendation to modify, pause, or stop (binding on conduct, with CMO/DGC action); an adjudicated malignancy or proliferative-histopathology safety signal relevant to the IL-22R-agonist mechanism (SMT → DSMB → DGC); a confirmed neutralizing-ADA incidence or exposure attenuation above the pre-specified threshold affecting dose/interval assumptions (HCP → DGC); a CMC comparability-protocol deviation or a specification/stability failure that could affect bridging of the CHO process to commercial scale (VPCMC → DGC); a critical vendor audit finding or GCP data-integrity event (HQA/PMO → DGC); and enrollment or funding shortfalls threatening programme timeline or continuity (PMO/CBO → Executive/Board). Each triggered escalation carries a corrective-action plan with an accountable owner and a defined closure date, and is minuted at the receiving body.

8. Vendor and alliance governance

Virtual Biopharma Inc. operates a largely outsourced model, executing clinical, nonclinical, and manufacturing work through CROs and CDMOs while retaining in-house medical, regulatory, biostatistical, and technical accountability. Governance of this model is therefore explicit: the PMO owns the vendor-governance framework (defined in PM-006), including risk-based monitoring, quality and technical agreements, defined key performance indicators, and a QA audit and inspection-readiness program aligned to ICH E6(R3). CDMO oversight is weighted to the risks specific to a bispecific produced in CHO culture — heterodimer fidelity and product-related impurity control, Protein A capture plus polishing performance, viral safety per ICH Q5A(R2), and comparability across scale — with single-source dependencies tracked as governed risks. Alliance-level decisions (partnering, financing, second-source strategy) are owned by the CBO under Executive/Board authority. Decision rights are never delegated to vendors: recommendations may originate with a CRO or CDMO, but accountability (the A in the RACI matrix) remains with the named Sponsor function.

9. Meeting cadence and reporting

Table 9-1. Governance cadence and reporting flow

Forum	Frequency	Standing inputs	Standing outputs
Program Team	Monthly	Functional status, risk deltas, decision log	Actions, escalations, updated integrated plan
Safety Management Team	Monthly and ad hoc	Aggregate safety, ADA and signal data	Safety actions, RMP updates, DGC/DSMB escalations
DGC (steering)	Quarterly and on trigger	Integrated plan, benefit-risk, High-band risks	Endorsed positions, external strategy, mitigation direction
DSMB	Per charter	Unblinded safety review	Continue/modify/pause/stop recommendations
Executive / Board	Quarterly and on stage-gate	Investment case, portfolio, risk profile	Funding and continuity decisions

Reporting flows upward from the sub-teams through the Program Team to the DGC and Executive/Board, and the risk profile is reconciled by the PMO against the Program Risk Register (PM-004) and the integrated Clinical Development Plan (PM-007) at each cycle. The programme status reflected in this framework corresponds to the completed Phase 2b induction readout from Study TILA278-201, in which clinical remission (modified Mayo ≤ 2, no subscore > 1) at Week 12 was 37.3% (106/284) in the High-dose arm, 16.2% (46/283) in the Low-dose arm, and 0.7% (2/273) on placebo, with dose-ordered key secondary endpoints (endoscopic improvement 48.9% / 27.9% / 6.2%; modified-Mayo LS-mean change −3.36 / −2.76 / −1.00). These results anchor the EOP2 governance decision to advance to the confirmatory programme.

10. Records, interfaces, and document control

Governance records — terms of reference, charters, minutes, decision logs, and the RACI matrix — are maintained under the Sponsor's controlled document system and filed to the Trial Master File and the programme records where GxP-relevant. This framework interfaces directly with the Project Charter (PM-001), the Program Budget and Cost Model (PM-003), the Program Risk Register (PM-004), the Vendor/CRO Management plan (PM-006), and the Clinical Development Plan (PM-007), and it provides the decision-rights layer over the technical assessments held in Modules 2, 3, and 5 of the dossier. It is a living instrument, reviewed at each DGC cycle and updated as the programme advances through the confirmatory phase and marketing-application preparation; changes are version-controlled and reflected in the Change History above.