Ancillary Materials in Cell Therapy Product Development

25 Pages·2012·1.19 MB·English

Ancillary Materials in
Cell Therapy
Product Development
Nicole M. Provost, PhD
Independent Consultant
Member of USP BB2 Expert Committee
Ancillary Material
Topics to be Covered

Common Sense Approaches

Definitions and Abbreviations

CMO Advantages and Disadvantages

Risk-based Approaches

“Big 3” Questions to Address

Relevant Examples

Take-home Messages

(Intuitively Obvious )
Common Sense Approaches
Figure out what you know, don’t know

Don’t ignore problems

Make plans

Be ready to change your plans

Definitions and Abbreviations
Ancillary Material (“AM”)

◦ Material used and removed during manufacture
of a cell or tissue product
Supplier

◦ “Off-the-shelf” manufacturer of AM
Contract Manufacturing Organization

(“CMO”)
◦ Custom manufacturer of AM
Product Development (“PD”)

Research and Development (“R&D”)

CMO Advantages
AM Manufactured by CMO

◦ No Manufacturing and Quality personnel to
hire and oversee
◦ Reduced need for additional facilities
◦ Reduced need for additional headcount
Supply Chain Managed by CMO

◦ Fewer suppliers to oversee
◦ Shipping and storage managed by CMO
◦ Multiple suppliers = more flexibility
CMO Disadvantages
AM Manufactured by CMO

◦ Ultimately, CMO issues become yours
◦ Be prepared to troubleshoot
◦ Designate a contact person on your side
Supply Chain Managed by CMO

◦ Sourcing is out of your control
◦ Shipping and storage issues can disrupt your
own manufacturing and R&D
◦ Multiple suppliers may = more variability
Risk-based Approaches to AMs
in a Nutshell
Perform Criticality Assessments

Identify the major risks to cell product:

purity, consistency, supply, stability, etc.
Determine AM & product failure mode(s)

Define product/patient impacts

Mitigate or eliminate the major risks

Decide which headaches you own, and

which you share with the CMO
Build trust with your CMO

The “Big 3” Questions for PD
What’s in the Ancillary Material?

How does the Ancillary Material affect

the cell product?
• Can the CMO make enough Ancillary
Material?
What’s in the Ancillary Material?
Is it a complex mixture?

◦ Classic examples: culture media and serum
Identify & characterize active component(s)

◦ Sometimes the impurities are active!
◦ Conduct fractionation and add-back experiments
◦ Relative component ratios may be important
Identify major impurities

◦ Common examples: fragments, endotoxin, DNA
How variable are the batches?

◦ Quantitation and characterization assays critical
How Does the AM Affect
the Cell Product?

Is the AM essential to cell product quality?

◦ Damage or omit the AM to assess its criticality
◦ Determine concentration effects, stability in use
◦ Assess many batches or sources
Do impurities affect cell product quality?

◦ Add-back experiments with known impurities
◦ Determine safety limits
Are both AM and impurities removed during cell

product manufacturing?
◦ Both can be washed out, taken up by cells, or adsorbed
onto production equipment