Module 9 2021

ATMPs & Biologics are different

Manufacturing

Biologics

ATMPs

Structure and characterization

Produced by host cells Cell or virus is the product Process product specific Can be patient specific

Biologics High M.W.

ATMPs

No M.W. defined

Mass activity Balance (μg, IU)

Cell/kg, MOI, Viability

Large batches

Small batches

Product degradation

Unwanted cell population

Terminal sterilization

No terminal sterilization

In vivo behavior

Clinical development

Biologics

ATMPs

Biologics

ATMPs

Large, blind, randomized pivotal trial

Unblind (non-randomized) pivotal trial

MABEL

Effective dose

Standard design

Adaptative design

p450 degradation system

Long time resident

FiH  Ph I  Ph II  Ph III  MA

FiH

 (Ph I/II  (Ph III))  MA

PK and TK

Biodistribution

Healthy volunteers for FiH Patient only enrolled

Carcinogenicity, mutagenesis Tumuorigenicity and insertional mutagenesis Developmental toxicity Vertical transmission

Conditional , Exception MA PASES , Registry establishment

Full MA

Novartis Pharma AG- Business use only- not for further distribution

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