Page 86 - Binder2

Regulators: Mandated for Safety and Efficacy,
Not Immunologic Harmony

Regulatory agencies like the FDA and EMA are guardians
of public safety, but their frameworks are shaped by
specific, historically bounded mandates: prove that a drug
is safe and effective—often over a span of months, not
years. Immunogenicity is measured, yes. But it's rarely
central to the approval decision, and it’s almost never
grounds for rejection unless it triggers overt safety
concerns.

Regulators lack validated standards for what constitutes
unacceptable tolerization. ADA testing protocols vary.
Thresholds for concern are inconsistent. And there are no
clear, enforceable benchmarks for immune durability over
time. Long-term outcomes are left to post-marketing
surveillance, which—when it comes to tolerization—is
fragmented, inconsistent, and often industry-controlled.

Until regulators redefine efficacy to include sustained
immune response, drug developers have little reason to
prioritize it.

Clinicians: Adapting Within Constraints

Doctors aren’t ignoring tolerization—they’re working
around it. Faced with incomplete data, shifting formularies,
and limited treatment options, clinicians are forced to
manage around failure rather than prevent it. The typical
clinical response to biologic failure is pragmatic: increase
the dose, shorten the interval, switch therapies, or add an
immunosuppressant.

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