# Adheroza 420 mg: renewed source review, 12 September 2026

**Result: both exact-presentation cases remain `needs_evidence`.** The renewed search found a relevant US 420 mg manufacturing supplement, but no inspected document establishes its applicability to the Canadian co-pack or the specific 150 mg trial material. This is an AI source assessment, not human adjudication. No application records were changed.

The narrower relationship is already supported: Health Canada's Adheroza submission includes DIN 02550989 and cites HLX02-HV01 Part 2 and HLX02-BC01. The unresolved question is the exact presentation bridge, not whether these studies belong to Adheroza's development program. [Health Canada SBD](https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SBD1736954230750), retained normalized fields `/source_fields/15/text`, `/source_fields/123/text`, `/source_fields/159/text` and `/source_fields/162/text`.

| Case | Established evidence | Remaining gap |
|---|---|---|
| DIN 02550989 → NCT02581748 | HC cites HLX02-HV01 Part 2; the registry has that sponsor study ID; EMA describes the 150 mg HLX02 material and the Part 2 subgroup. | An applicable connection from that clinical material to the Canadian 420 mg co-pack. Do not substitute HV02 for HV01 or the 123-person registry aggregate for the 37-person HLX02 subgroup. |
| DIN 02550989 → NCT03084237 | HC cites HLX02-BC01; the registry identifies the same protocol; section 5.2 specifies 150 mg HLX02 vials. | An applicable connection from that trial presentation to the Canadian 420 mg co-pack. The 8/6 mg/kg regimen does not identify vial size. |

Trial locators: [HV01 registry](https://clinicaltrials.gov/api/v2/studies/NCT02581748), `/protocolSection/identificationModule/orgStudyIdInfo/id` and `/protocolSection/armsInterventionsModule`; [EMA initial assessment](https://www.ema.europa.eu/en/documents/assessment-report/zercepac-epar-public-assessment-report_en.pdf), physical PDF pages 46–48 and 68–69; [BC01 registry](https://clinicaltrials.gov/api/v2/studies/NCT03084237), the same JSON paths; [BC01 protocol](https://cdn.clinicaltrials.gov/large-docs/37/NCT03084237/Prot_SAP_000.pdf), physical PDF pages 35–37, especially section 5.2.

## New findings

1. FDA records a **6 September 2024** SUPPL-1 action for Hercessi under BLA 761346, categorized as a CMC new-strength supplement. The overview exposes its approved label, but no supplement assessment report or approval letter. The 18 September date in the manufacturer's announcement is its publication date, not this FDA action date. [FDA application history](https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?ApplNo=761346&event=overview.process), Supplements and Labels tables.
2. The FDA supplement label describes **420 mg multiple-dose** Hercessi and preparation with 20 mL bacteriostatic water containing 0.9–1.1% benzyl alcohol; the diluent is **not supplied**. That is a stronger lead than the EU single-dose 420 mg presentation, but it is still a different jurisdictional package. [FDA supplement label](https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761346Orig1s001lbl.pdf), physical PDF page 4, section 2.6; page 6, section 3.
3. Accord's own 420 mg approval announcement connects the Hercessi program to HV01, HV02 and BC01. It does not state that Canadian DIN 02550989 shares the covered presentation or describe a trial-to-Canadian-kit comparability study. [Manufacturer announcement](https://www.prnewswire.com/news-releases/accord-biopharma-inc-announces-us-food--drug-administration-approval-of-420mg-strength-of-hercessi-trastuzumab-strf-a-biosimilar-to-herceptin-trastuzumab-for-the-treatment-of-several-forms-of-her2-overexpressing-cance-302251163.html), About Hercessi, paragraphs describing the three studies.

## A source interpretation that can be fixed now

The apparent `KIT` versus `POWDER FOR SOLUTION` inconsistency should be represented as **packaging versus drug dosage form**, rather than treated as proof of a pharmacological difference. Keep the raw DPD value and add a cited interpretation: drug component = 420 mg trastuzumab lyophilized powder in a multidose vial; co-pack component = 20 mL bacteriostatic water with 1.1% benzyl alcohol; route = intravenous infusion. The Canadian monograph states these details directly. [Canadian monograph](https://pdf.hres.ca/dpd_pm/00084164.PDF), retained version authorized 24 March 2026, physical PDF pages 12 and 15–16, section 6.

This interpretation resolves a source vocabulary issue; it does **not** establish trial exposure or approve the exact-product connection. The US label also reports some excipient quantities using wording that differs from the Canadian monograph. Do not infer a formulation difference or equivalence from those numeric values without resolving hydrate/anhydrous conventions and the applicable manufacturing record.

## Accurate public wording

“Health Canada cites this study in the Adheroza submission. The inspected trial documents describe 150 mg HLX02 vials. The selected Canadian product is a 420 mg vial co-packed with diluent. The relationship to that exact presentation has not yet been established from the available documents.”

Present the official submission link separately from any independently reviewed exact-product link. Missing evidence should remain visible, while the verified program-level connection remains usable.

## Evidence needed to close these cases

A regulator or manufacturer document explicitly identifying the Canadian 420 mg co-pack and connecting it to the 150 mg clinical material or a clearly applicable development/manufacturing comparability program, followed by independent human review of the frozen packet. Useful next document targets are the supporting review for FDA BLA 761346/SUPPL-1 and the Canadian submission's presentation-comparability section. Public access to those specific records was not established here; no request or outreach was sent.

## Audit limits and retained material

- Six retained primary source files were rehashed successfully; exact paths, hashes and pointers are in `retained-source-integrity.json`.
- Four newly inspected public sources were archived successfully with request times, final URLs, byte counts and SHA-256 in `acquisition-receipts.json`.
- Current HC SBD and RDS page requests returned **403**; the DPD product page returned **502**. They were not retried through another client. This assessment uses the explicitly identified retained HC versions; it makes no fresh-HC-source claim.
- No full public-web completeness claim, patient-level commercial-pack exposure claim, human approval, or production update is made.
- Search coverage and access outcomes are in `search-and-access-log.json`; output assessment is also available in `assessment.json`.