Comment from Anonymous

## COMMENT TO DOCKET: FORMAL NOTICE OF ADMINISTRATIVE DEFICIENCY Dockets: FDA-2021-P-1601; FDA-2021-N-1088; FDA-2020-N-1898 Re: BLA 125742 (COMIRNATY) & BLA 125746 (SPIKEVAX) To: Commissioner of Food and Drugs; Office of Biological Product Review (OBPR) Subject: Demand for Urgent Information Request (IR) and Stay of Expansion Pending Resolution of Preclinical Data Gaps I. PREFACE: THE EVIDENTIARY VOID This filing serves as formal notice that the administrative record for the licensed mRNA LNP biologics (Comirnaty and Spikevax) contains material, unresolved preclinical deficiencies. The FDA is currently in violation of its statutory duty to ensure safety under 42 U.S.C. § 262. Authorizations based on this incomplete record constitute "arbitrary and capricious" agency action under the Administrative Procedure Act (5 U.S.C. § 706). II. MATERIAL DEFICIENCIES IN PRECLINICAL OVERSIGHT The Agency has accepted truncated datasets that fail to meet established Good Laboratory Practice (GLP) and Pharmacokinetic (PK) standards: 1. Failure of Kinetic Resolution (Study R-20-0072): Radiolabeled LNP concentrations in ovarian tissue rose from 0.001 %ID/g to 0.095 %ID/g at 48 hours. Because uptake was still ascending at termination, peak concentration (Cmax) and elimination half-life (t1/2) remain unknown. The total Area Under the Curve (AUC) for reproductive tissues is unquantified. 2. Tissue Persistence of Novel Excipients (Study 083334): Cationic lipids (ALC-0315 and SM-102) demonstrate a liver half-life of 6–8 days. The FDA’s failure to demand 56-day or 90-day longitudinal biodistribution studies for these novel chemical entities is an indefensible dereliction of the Precautionary Principle. 3. Reproductive Toxicity Obfuscation (Studies 20-2054 & 20-2130): Recovery cohorts were limited to 5 rats per sex and terminated at Day 38. Data shows increased pre-implantation loss, yet F1 follow-up was curtailed at lactation day 21, preventing any scientifically valid conclusion regarding oocyte depletion or F1 sexual maturity. III. COMPULSORY ADMINISTRATIVE ACTIONS REQUESTED (WITHIN 14 DAYS) To cure these deficiencies, the FDA must initiate the following: 1. Issue an Enforceable Information Request (IR): Compel the BLA holders to produce prioritized raw biodistribution/TK datasets for R-20-0072 and 083334 (individual animal data, radiolabel stability controls, assay validation) and complete reproductive-toxicity raw data for 20-2054 and 20-2130 (individual histopathology, follicle counts, hormone assays, and F1 records). 2. Stay of Expansion: Temporarily pause new lot releases and any expansion of indications (including seasonal or age-group updates) pending an expedited review of the produced data. 3. Mandated GLP Longitudinal Studies: Order new IM biodistribution studies with later timepoints (7, 14, 28, 56, and 90 days minimum) and an extended female reproductive study following the F1 generation to sexual maturity. 4. Independent Expert Audit: Convene an expedited panel of experts in reproductive toxicology and biostatistics, free of conflicts of interest, to conduct a De Novo review of the raw data. IV. LEGAL NOTICE The FDA is hereby put on notice that permitting the distribution of these biologics while possessing actual knowledge of these preclinical uncertainties constitutes a failure of reasoned decision-making. The Agency cannot claim a "Benefit-Risk" balance when the "Risk" side of the ledger remains intentionally unquantified. Respectfully submitted, Anonymous Consumer