owing to criticality of the segment.
Yet another challenge in procurement of animal models
is disruptions resulting from the animal rights extremist activities, which target the transit of animals from supplier to
buyers. These disruptions also portray a negative image of
The procurement of RMS is largely through transactional
or preferred partnerships, as the volume of animals procured
varies with the number of projects actively running in the
pipeline. Understanding the demand for RMS is achieved
through refinement as well as reduction of animal models
used per procedure. This further helps in projection of future requirement of animal models.
The management of demand for animal testing, therefore,
emerges as one of the solutions to the issues discussed
above; it is achievable through
Refining the conventional procedures through adoption of technology – This can be achieved through refining
the traditional procedures through new technologies.
The use of imaging techniques like MRI, CT, SPECT, provide
an alternate to vivisection and complex procedures like intubation, which causes stress in animals tested. Additionally
they reduce the number of animals required by 70-80%.
DNA based screening refines the process of developing a
GM line in research models. The technique involves screening the gametes of animals to be bred and thereby reducing
the number of animals required. A large pharma adopted this
refinement in selection of GM line to propagate rodents and
reported a 70% reduction in number of rodents used.
Dried blood spotting is yet another technique that helps
in reducing the research models used in an experiment. This
technique uses drops of blood spotted and dried on special
absorbent paper, rather than collection of fluid blood in vials. Therefore, it results in reduction of research animals by
~50%, blood volume requirements by ~75% and reduces the
sample handling as well as storage costs!
Replace the traditional models with new research
models – With increasing prevalence of cardiovascular disorders, the requirement of complex traditional models like
non-human primates increases, this in turn results in a significant rise in cost of animal models.
However, replacing such complex and costly animal models
with simple, cost effective and yet highly predictive animal
models like zebra fish can result in significant cost savings.
A large Pharma replaced rodents (GM) with zebra fish for
screening of toxicology. This resulted in a 16% reduction in
rodents used in research per year.
Use of alternates to animal testing – There are several
technologies that claim to replace the need of animals for
toxicology testing of drugs, cosmetics, chemicals as well as
agrochemicals. Few popular technologies and their impact
on cost are explored in the following sections.
In vitro techniques that mimic tissues/organs of hu-
man – In vitro techniques use cells, tissues and organs derived
from human and/or animals result in cost saving across various
arenas of animal testing.
The cost savings achieved below are attributable to the animal model and labor (animal model handling and testing expertise) related activities. Thus on an average, 50 - 70% of cost can
be saved by switching to in vitro testing. This can be done in initial stages of drug development (like lead optimization, primary
and secondary screening, etc.).
New technological developments like 3D tissue chips and
use of stem cells (iPSC cells) instead of the cell lines that have
2D matrix and have fixed functions, offer better correlation to
organs and organ systems in humans. Although they require additional validations, these technologies can nevertheless, predict
toxicology effects better! (Figure 2)
In silico techniques that predict the toxicology profile of
drug – In silico modelling is a virtual solution to predict the
toxicology profile of a molecule. These technologies are broadly
based on the tenet that molecules having similar structures have
similar functions – Structure Activity Relationship (SAR) (Figure 3)
Microdosing technique – Microdosing utilizes injecting miniscule doses of the drug in humans that elicits response at cellu-
PHARMACEUTICAL PROCESSING | MARCH 2014 65 ■
Parameters Microdosing Conventional
Duration (months) 6-8 12-18
Cost (million USD) 0.3 - 0.5 1. 5-5.0
Amount of drug <100 mg ~100 gm.
Regulations Few Many
Special requirements C14 labeling and AMS Not required
Some Prominent Software to Predict ADMET
Software Application Supplier
DEREK Prediction of toxicology Lhasa Ltd
METAPC Metabolism & Biodegradation Expert System Multicase Inc
Leadscope QSAR Toxicology Prediction through QSAR Leadscope
Alternates to animal
Combination with in
Replace animal testing
Adoption (%) 80 10-20
Cost Savings 20-30 30-50
Advantages More data relevant to
humans rather than animals
Allows an early stop in
Limitations Still missing the human
Complexities in mammals
not yet repeatedly
Reduction of preclinical timelines by 7- 8 months and cost by ~80%