Module 9 2021

19/03/2021

Examples Type of Product

Stage of Development

Type of Change

Data presented

Company

Analytical Primate PK Analytical Clinical PK Analytical Primate PK

Pre-phase 3

Formulation

Post-phase 3 , pre market

Device

Centocor

Pre-phase 2

Cell line

Analytical Animal PK/PD immunogenicity Analytical Animal PD/PK

Pre-phase 2

Cell Line

Eli Lilly

Monoclonal antibody

Cell line Fermentation conditions

Pre-phase 3

Amgen

Animal Tox Clinical PK

Pre-phase 3

Cell line

Novartis Biologics

Scale up Media Change Process change

Analytical Clinical PK Analytical Primate PK

End Phase I

Seattle Genetics

Cell line, process, scale up, site

Novartis

Analytical Animal PK Recovery Clinical PK efficacy

Site change, media change formulation change

Recombinant enzyme

Post marketing

Analytical Clinical PK/PD

Fusion protein

Phase 3 extension

Process

Table adapted from “Summary of DIA workshop: Comparability Challenges: Regulatory and Scientific Issues in the assessment of Biopharmaceutical” Drug Information Journal (2010) Vol.44 pp 485 – 504

The Organisation for Professionals in Regulatory Affairs

29

Challenging Products

• Long half lives • High immunogenicity • Limited patient population • Limited manufacturing history

The Organisation for Professionals in Regulatory Affairs

30

15