Post on 29-Jul-2020
transcript
Contact: Joke De Gelder, joke.degelder@anacura.com presentation Tuesday June 19th, 3 pm
Eddy Ruijter, eddy.ruijter@anacura.com BOS CMC Basel, booth 27
Standardized approach
Risk mitigation
Knowledge
GMP prospectExpectations
Product
Timelines Customise
You
typical DS trackValidation
Forced degradation
Method optimisation
Solubility
Validation
Forced degradation
Method optimisation
Solubility Stability modelling
Pre-validation
anacura DS track
Time
All aboard! Analytical Insights fast track your Time to Market
Stability modelling: DP tablet example
Applications
• DS/DP stability indication
• Formulation selection
• Packaging selection (performance/cost)
• Avoid reformulations
• Extended shelf-life claim in filing
Theory
• Humidity corrected Arrhenius equation: a
kinetic understanding of degradation
ln k = ln A – (Ea / RT) + (B * RH)
• Isoconversion time = time needed to reach
the specification limit
• Identical pathways to failure
Efficient and effective drug development starts with sharing goals, expected timelines, product
information and with creating customized solutions.
Stability of formulations is an important aspect throughout product development. The stability
modelling using the ASAP technology is employed at several points throughout the drug
development phases, supporting quick DS stability checks, formulation selection, packaging
selection and extended shelf-life claims.
At anacura we have developed a process with smart
integration of forced degradation studies, solubility testing,
method optimisation, stability modelling using ASAP studies
and pre-validation. The integrated approach results in higher
quality and avoids rework.
An ASAP stability study takes 4-10 weeks from protocol design
to report, which is significantly shorter than traditional
development stability studies. The outcome is a shelf life
prediction, which allows fast descisions on needed revisions
in the production process. This risk mitigation pays off in the
next phases of drug development.
Creating the model
In ASAPprime® software:
Data of the major degradant:
Model evaluation:
R² > 0.9
Q² > 0.7
Study setup
Early DS development track
Predicted shelf-life
• At 25°C/60%RH for 0.4 years with 97%
probability at a degradant specification of
0.30%w_w
• At 5°C for 2 year with 98% probability at a
degradant specification of 0.30%w_w
Excipients Predicted water uptake
In ASAPdesignTM software:
• Broad range of T and RH conditions
(min. 5)
• Determine ‘the plane’
Stress testing
Packaging HDPE bottles selected
as preferred packaging (cost-related)
Excipient composition table
combined with database
information on excipient water
uptake.
• RH: use of saturated salt
• Continous logging of T and RH
in proximity of the samples
• Immediate appearance
evaluation after pulling
• Storage of pulled samples at
5°C, protected from moisture
• Comparative appearance of all
conditions
• Combined LC runs to minimize
inter-day variability
Packaging selection
Humidity of the packaging headspace
Water uptake of the formulation
Development stability
Viewpoint