Comment from Anonymous

To: Members, Vaccines and Related Biological Products Advisory Committee (VRBPAC) Docket No: FDA-2026-N-4162 Subject: Statutory Non-Prescribability of BLA STN 125869/0 (MFLUSIVA) Due to Indeterminate Dosing Esteemed Committee Members, This submission presents critical pharmacological and statutory facts demonstrating that the implementation of an in vivo cellular transfection architecture for routine seasonal prophylaxis under BLA STN 125869/0 (MFLUSIVA) introduces a fatal regulatory conflict regarding standardized pharmaceutical dosing. Under federal law, this product is structurally unprescribable. The core of this issue is a fundamental pharmacological contradiction: 1. The Prodrug Classification: Unlike conventional biologicals where the administered mass is the active immunogen, MFLUSIVA functions as a Type IA intracellular prodrug. The vial contains only an exogenous delivery vehicle (lipid nanoparticle) and an inactive precursor (synthetic mRNA). The actual active drug substance—the translated influenza antigen—does not exist until the recipient's somatic cells execute metabolic conversion. 2. Violation of 21 CFR 201.57(c)(3): Federal labeling law explicitly mandates that a prescription drug's Full Prescribing Information state the exact quantitative dosage of the active substance. Because host conversion relies entirely on individual tissue-specific ribosomal capacity, cellular uptake speed, variable intracellular half-life, and unpredictable enzymatic degradation, the precise microgram yield of the active viral protein is structurally unknowable at the time of injection. 3. Dosing Blindness and Misbranding: A clinician cannot measure, adjust, or control the final therapeutic payload. The physician is left completely blind, injecting a vehicle with no capacity to determine if they are administering an underdose or a toxicological overdose. Under 21 U.S.C. 352(f), a product is legally misbranded if its labeling cannot define a standardized pharmacokinetic profile and clear parameters for dose calibration. Because the sponsor can only declare the mass of the inactive vehicle and precursor, not the resulting active biological substance, the product fails the statutory labeling thresholds required to execute a legal prescription. Authorizing an annual, routine biological platform where the active therapeutic dose is an unquantifiable, unknowable variable establishes an illegal regulatory loophole. VRBPAC must reject BLA STN 125869/0 and restrict routine seasonal biologicals to the established paradigm of passive, verifiable antigen exposure. Respectfully submitted, Anonymous