Pharmaceutical Development for ADCs - Baxter BioPharma Solutions

57 Pages·2013·3.42 MB·English

by  Donna Abear

Pharmaceutical Development
for ADCs
Presenters
Lisa Hardwick
Wendy Saffell-Clemmer
Antibody Drug Conjugates (ADCs)
2
!  Consist of:
–  a Monoclonal Antibody
–  Chemical linker and
–  Cytotoxic
!  Monoclonal antibody
–  Typically targets tumor-associated antigens on the surface
of cancer cells
–  Effectiveness requires internalization of the ADC in the cell
Antibody Drug Conjugates (ADCs)
3
!  Linker cleavable vs. non-cleavable
–  Cleavable linkers rely on internal cellular processes to
release the cytotoxin
–  Non-cleavable linkers require degradation of the
conjugate
!  Cytotoxin – must be highly potent
–  Calicheamicin
–  Duocarmycins
–  Auristatins
–  Myotansinoids
Image from http://www.adcetris.com
Current ADC Platforms
4
ADC – Surge in INDs
5
Source- S. Miksinski, presented at AAPS NBC, May 23, 2012
What Makes an Optimal ADC?
6
Source: Current Cancer Drug Targets, 2009, 9, 982-1004
What Makes an Optimal ADC
Drug Product Formulation? 7
!   Stability of Linkage !   Stability of Mab
–  Aggregation
–  Fragmentation
–  Deamidation
Because of

stability concerns
related to the Mab,
all ADCs we have
worked with have
been lyo products.
Liquid Formulations
8
•  Advantages of Liquid •  Disadvantages of Liquid
Formulation Formulation
–  Ease of use –  Usually more unstable
formulation
–  Less expensive
manufacturing –  Drug product is often
frozen at -80°C
–  Complicated cold chain
management
Lyo Formulations
9
•  Advantages of Lyo •  Disadvantages of Lyo
Formulation Formulation

–  Higher probability of –  More complicated
technical success development
–  Better stability –  More expensive
manufacturing
–  Frozen storage not
required –  Specialized capabilities
.
required
The Pharmaceutical Development Process
10
!  Timing: Clients come to us for formulation
development in two different scenarios:
–  Preclinical
–  Manufacturing scale-up optimization (Phase I +)
!  Clients often desire an aqueous solution formulation
instead of lyo but this is not always possible
!  Common to pursue dual path where the goal is to
develop drug product formulation suitable for either a
sterile solution or a freeze-dried solid presentation.
–  The formulation is designed with lyophilization in mind,
meaning that lyo-suitable buffers and stabilizers are
selected.