Comment from Anonymous

TECHNICAL MEMORANDUM IN SUPPORT OF CITIZEN PETITION: FDA-2025-P-0335-0001 RE: MANDATORY STAY OF ACTION AND REVOCATION OF BLA 125742 (COMIRNATY / TOZINAMERAN) – ADULTERATION VIA NON-CONFORMING MOLECULAR IDENTITY PROPOSITION: This information is offered in support of the petition filed by PJ O’Brien & Associates. The FDA’s application of a 10 ng DNA impurity threshold is an error of engineering regarding the biological product licensed under BLA 125742. In the manufacturing of Comirnaty, residual DNA acts as a structural participant that creates Non-Conforming Species. This constitutes Structural Adulteration, rendering the biological activity or potential toxicity of the specific sequences irrelevant to the legal necessity of a Stay. 1. NON-CONFORMING MOLECULAR IDENTITY (21 USC § 351) The FDA’s "10 ng limit" is a legacy standard for extracellular, naked DNA. It is technologically inapplicable to the high-energy microfluidic assembly used for BLA 125742, as it fails to account for the Physical Identity of the delivery vehicle: Kinetic Co-Encapsulation: Cationic lipids utilize electrostatic affinity to neutralize negatively charged nucleic acids. During LNP assembly, the lipids do not discriminate between the intended modRNA and residual plasmid DNA. Structural Deviation: Any DNA present during this phase is physically co-encapsulated into the lipid matrix. This is a departure from the Licensed Identity of an mRNA-LNP; it creates a structural constituent that was not authorized in the BLA. Identity Failure: This process produces a Heterogeneous Admixture of particles (DNA-LNP and DNA-RNA-LNP). These are Non-Conforming Species because they do not match the Master Specification defined and licensed under BLA 125742. The drug is therefore Adulterated under 21 USC § 351. 2. VOIDANCE OF ANALYTICAL COMPARABILITY (21 CFR 601.12) Evidence indicates that the Agency lacks safety data for the commercial "Process 2" product distributed under BLA 125742: Process 1 clinical trials utilized high-purity methods that did not produce these structural admixtures. Under 21 CFR 601.12, a manufacturing change that alters the Physical Identity of the drug product requires new clinical validation. The transition from a pure mRNA-LNP to a chimeric admixture constitutes a material change in product identity that voids previous comparability assumptions. 3. STATUTORY VIOLATION REGARDLESS OF TOXICITY Under 21 USC § 351, a drug is Adulterated if its "strength, quality, or purity" falls below that which it purports to possess: The biological effect of the contaminating DNA—oncogenic or otherwise—is legally moot. If the BLA specifies an mRNA-LNP, but the manufacturer distributes an mRNA-DNA-LNP Admixture, the product is non-compliant. The inclusion of any structural DNA violates the Physical Identity of the licensed biological product and constitutes a breach of the BLA contract. ADMINISTRATIVE DEMAND FOR REMEDY The FDA should immediately STAY BLA 125742 and require the manufacturer to: A. Cease distribution of all lots manufactured using the "Process 2" method; B. Submit a manufacturing supplement with real-time analytical audits proving that the kinetic assembly process successfully excludes structural DNA integration; C. Demonstrate that current commercial lots match the Master Specification and are Physically Identical to the high-purity "Process 1" clinical trial material. Until the Agency can demonstrate that commercial-scale lots of Comirnaty are structurally identical to the high-purity "Process 1" clinical material, the product remains an unlicensed, adulterated drug product.