📚 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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Module 1 — Container/Carton/Patient Labeling (TILA-278)

Document ID: M1-LBL
Version: 1.0
Change History: 1.0 — Initial issue.
Standard(s): 21 CFR 201/208; SPL

Container, Carton & Patient Labeling — TILA-278

The submission labeling set for TILA-278 beyond the prescribing information: immediate-container and carton labels (proprietary/nonproprietary name, strength, route [subcutaneous], storage, lot/expiry), a Medication Guide / Patient Package Insert, and, for the device presentation, Instructions for Use. In a US submission these are also provided as Structured Product Labeling (SPL) XML. 21 CFR 201; 208; SPL R8.

Scope and regulatory framework

TILA-278 (proposed proprietary name TILVARA; proposed nonproprietary name tilazumig, an anti-TL1A antagonist / IL-22R agonist bispecific IgG1 monoclonal antibody produced in a Chinese hamster ovary [CHO] cell line) is a licensed biological product; its container and package labeling are therefore governed by the biologics labeling provisions of 21 CFR 610.60–610.62 in addition to the prescription-drug labeling requirements of 21 CFR 201.100 and the content/format rules of 21 CFR 201.56/201.57. The labeling artifacts filed at eCTD 1.14 are internally consistent with, and derived from, the draft Prescribing Information (eCTD 1.14.1.3) and the annotated labeling (eCTD 1.14.1.2). As a licensed biologic, the finished-product labels bear the U.S. License Number of Virtual Biopharma Inc. and the FDA-designated four-letter suffix appended to the proper name in accordance with the Agency's nonproprietary-naming policy for biological products. 21 CFR 601; 610.60–610.62; 201.100.

Two commercial presentations are labeled, each a single-dose combination product (21 CFR Part 4): a single-dose prefilled syringe and a single-dose prefilled autoinjector, both delivering 450 mg/3 mL (150 mg/mL) for subcutaneous administration. Storage, strength, route, container-closure, and device-performance statements on the labels are traceable to Module 3.2.P (drug product and container-closure system), Module 3.2.P.7 / device documentation, and the stability program.

Immediate-container labels (prefilled syringe and autoinjector)

The immediate containers are small-volume prefilled devices; abbreviated content is applied under the small-container provisions of 21 CFR 201.10(i) and 610.60(b), retaining only the information essential to safe use while directing the user to the carton and enclosed labeling for the full content. Each immediate-container label carries:

Element	Content on immediate container
Proprietary / proper name	TILVARA (tilazumig) injection
Strength / fill	450 mg/3 mL (150 mg/mL)
Route	For subcutaneous use only
Dosing units	Single-dose; discard unused portion
Legend	Rx only
Sterility / preservative	Sterile; preservative-free
Traceability	Lot number; Expiration date (MMM YYYY)
Storage	Store 2°C–8°C; do not freeze; do not shake
Responsible firm	Virtual Biopharma Inc.; U.S. License No. [to be assigned]
Machine-readable identifier	Linear/2D bar code encoding the NDC per 21 CFR 201.25

Because label real estate on the syringe barrel and the autoinjector body is limited, the proper name (with suffix), strength, route, lot, and expiry are prioritized so the drug can be identified and its integrity verified at the point of administration; the plunger-rod flag and needle-cap components are labeled consistent with the device design outputs. 21 CFR 610.60(b); 201.10(i); 201.25.

Carton (outer package) labels

Each presentation is supplied as a carton of 1. The carton (package) label carries the full complement of biologics package-label content required by 21 CFR 610.61, together with the prescription-drug content of 21 CFR 201.100:

• Identity: proprietary name TILVARA and proper name tilazumig (with FDA-designated suffix); dosage form (injection); strength 450 mg/3 mL (150 mg/mL); route "For subcutaneous use only."
• Contents/quantity: one single-dose prefilled syringe, or one single-dose prefilled autoinjector.
• Codes: NDC [to be assigned]; U.S. License No. [to be assigned]; lot number and expiration date.
• Legend and dispensing statement: Rx only; a prominent statement directing the pharmacist to dispense the enclosed Patient Information and Instructions for Use to each patient.
• Storage and handling: Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light; do not freeze; do not shake. A single room-temperature excursion up to 25°C (77°F) in the original carton is permitted for the period established by the drug-product stability program, after which the product is discarded if unused. Keep out of the reach of children.
• Composition statements: preservative-free; a statement that the device components (including the needle cap) are not made with natural rubber latex, consistent with the container-closure/device characterization.
• Responsible firm: Manufactured for / distributed by Virtual Biopharma Inc.
• Serialization and security: a DSCSA product identifier (serialized 2D Data Matrix encoding NDC, serial number, lot, and expiry) per the Drug Supply Chain Security Act, and tamper-evident carton features.

Storage statements on the carton reconcile exactly with the "How Supplied/Storage and Handling" section of the Prescribing Information and with the stability-derived shelf life and excursion allowances. 21 CFR 610.61; 201.100; 201.25.

Patient labeling — Medication Guide determination and Patient Information

A determination under 21 CFR Part 208 was made as to whether a Medication Guide is warranted, evaluating the product against the Part 208 criteria (patient labeling could help prevent serious adverse effects; the product carries serious risks of which patients should be informed; and adherence to directions is essential to effectiveness). The clinically important risks of an immunomodulatory bispecific antibody in this class — infections (including consideration of tuberculosis and hepatitis B reactivation), hypersensitivity and immunogenicity, injection-site reactions, and the need to avoid live vaccines — are conveyed through routine labeling (Prescribing Information Sections 5.1–5.4) and patient counseling. Consistent with the REMS assessment (M1-REMS), no important identified risk requiring elements to assure safe use was identified; accordingly, the sponsor proposes FDA-approved Patient Information under 21 CFR 201.57(a)(17) rather than a Medication Guide, while deferring to the Agency's determination on whether Part 208 patient labeling is required.

The Patient Information is written in plain, non-technical language and covers: what TILA-278 is and its mechanism in ulcerative colitis (blocking TL1A-driven intestinal inflammation while supporting mucosal-barrier healing through the IL-22 receptor); the approved use (induction of clinical remission in adults with moderately to severely active UC); what to tell the healthcare provider before starting (signs of infection, tuberculosis exposure, hepatitis B status, planned vaccinations, pregnancy or breastfeeding); how the medicine is given (subcutaneous injection at Weeks 0, 2, 4, and 8, with response assessed at Week 12); possible side effects, with instructions to seek care for serious infection or allergic reactions; how to store the product refrigerated and protected from light; and general information on safe use. 21 CFR 208; 201.57(a)(17).

Instructions for Use (device presentations)

Because both commercial presentations are drug-device combination products (21 CFR Part 4), a presentation-specific Instructions for Use (IFU) accompanies each of the prefilled syringe and the autoinjector. The IFU content was developed and validated under a usability-engineering process (IEC 62366-1 and FDA human-factors guidance), with a use-related risk analysis and a human-factors validation study in representative users (patients and caregivers) performing simulated self-injection; the supporting design controls, use-related risk analysis, and validation results are provided in the device/combination-product documentation (M3-DEV) and Module 3.2.P.7. The IFU reconciles with Dosage and Administration (Section 2.3) of the Prescribing Information and includes:

• an annotated diagram of the device parts (needle cap, viewing window, plunger/activation button);
• removal from refrigeration to reach room temperature for approximately 30 minutes before injection, without other warming methods and without removing the needle cap during this time;
• visual inspection (the solution is clear to slightly opalescent, colorless to pale yellow) and instructions not to use if cloudy, discolored, particulate-containing, or damaged;
• selection and rotation of injection sites — the abdomen (avoiding the 2-inch area around the navel), the front of the thigh, or the outer upper arm (caregiver administration only) — and avoidance of tender, bruised, hard, or scarred skin;
• the step-by-step injection sequence, including the autoinjector hold time until the injection is complete;
• single-use handling and disposal of the device in a sharps container.

21 CFR Part 4; 4/820.30; IEC 62366-1; ISO 11608.

Structured Product Labeling (SPL)

All content of labeling is provided in SPL R8 XML per the FDA SPL Implementation Guide and submitted within eCTD Module 1.14. This comprises the Content of Labeling SPL (the full Prescribing Information rendered with LOINC-coded sections), the product/indexing SPL carrying the structured product data elements (NDC package and product codes, proprietary and proper name with suffix, dosage form [injection], route [subcutaneous], strength [150 mg/mL], and packaging descriptions for each presentation), and the establishment registration and drug-listing SPL identifying the manufacturing, testing, packaging, and labeling establishments consistent with FDA Form 356h and Module 3.2.A.1. The SPL files provide the machine-readable, exchange-ready representation of the human-readable container, carton, and patient labeling described above, and are maintained under version control across the product lifecycle. SPL R8; 21 CFR 207 (registration and listing).

Consistency, cross-references, and lifecycle control

Every quantitative and qualitative statement across the immediate-container labels, carton labels, Patient Information, Instructions for Use, and SPL is reconciled against a single source: strength, fill volume, route, and presentation trace to Module 3.2.P; storage conditions and the room-temperature excursion allowance trace to the drug-product stability program; container-closure integrity and device essential performance trace to Module 3.2.P.7 and M3-DEV; and the naming and license statements trace to 21 CFR 610.62 and the biologics naming policy. Placeholders (NDC, U.S. License No., initial approval and revision dates) are finalized in the approved labeling. Any post-approval change to the labels or SPL is managed under the applicable reporting category (annual report, CBE-30, or prior-approval supplement) per 21 CFR 601.12. 21 CFR 601.12; 610.62.