The Complete Guide to Pharmacokinetics Studies in ADC Development

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The Complete Guide to Pharmacokinetics Studies
in ADC Development
www.creative-biolabs.com/adc
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Pharmacokinetics (PK) studies
Analysis Process
Content
ATA Uses
Conclusion
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Pharmacokinetics (PK) studies provide critical
information regarding the behavior of a drug in
circulation and its ultimate form after extensive
in vivo metabolism. Results from PK studies often
serve as guidelines for clinical trials designs,
especially in the development of an antibody-drug
conjugate ( ADC). Due to the heterogeneous nature
of ADCs, multiple analytes have to be assessed to
reveal the ADC characterization, making these
studies more complex.
Pharmacokinetics (PK) studies
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First, a positive sample was screened from a
screening test (verification experiment) in a
sample from a clinical study and a competition
with ADO-mAb antibody emtansine. Its ATA
specificity is characterized by a competitive
binding curve with trastuzumab ADO-emtansine and
trastuzumab, confirming that the positive sample
is serially diluted to obtain the titer. A
confirmatory test is a necessary test for
determining the method used to confirm that the
anti-therapeutic antibody-positive sample is
truly positive, and to eliminate the second-level
immunogenicity assay effect of the false positive
sample. The most commonly used verification tests
use a competitively-bound test procedure that
incorporates a therapeutic ADC into the sample
before screening the test sample in the test.
Analysis Process
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The use of alternative sources of ATA and the
inclusion of monoclonal antibody-conjugated drugs
from cynomolgus monkey samples prove that their
stratified immunogenicity strategy is useful.
This includes the detection of all ATA bridging
detection methods for different component ADCs.
The determination of titer levels from
non-clinical study samples may be useful for the
next level of ATA action and for pharmacokinetic
studies. In addition, for an ADC, due to the
specificity of the ATA components, an appropriate
competitor can be evaluated by adding competitive
binding test samples before the same screening
test.
ATA Uses
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ADC is known as a complex drug system because of
its conjugation in chemistry with a complex in
vivo processes, and are affected by a wide range
of membrane effects and metabolic enzymes during
transport. It is expected that in vivo, due to
the circulation over time, this may not only
affect its safety and efficacy, but also present
an increased bioanalysis challenge to prematurely
disassociate the drug. It is important to
understand the changes in the composition of the
ADC in vivo. Therefore, extra care must be taken
when analyzing in vitro results.
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When studying the pharmacokinetics of novel ADCs,
it is important to establish the bioassay methods
for assays that reflect their functional
characteristics because ADCs have a complex
molecular structure with features that combine
small molecule drugs with protein therapies.
Compared to small molecule drugs and protein
therapies, biological ADC analysis can be
challenging. It has many difficult research
works, such as the establishment of bioanalytical
methods for the differential determination of
carrier materials and drug delivery systems (such
as targets, spacers, linkers, and drugs) in
biological samples, the clarification of
mechanisms for releasing free drugs, the analysis
of plasma protein binding drugs, metabolism, and
the elimination of the pharmacokinetics
characteristics.
ATA Uses
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Established in 2004, Creative Biolabs is highly
specialized in advanced antibody biochemistry and
engineering. With more than a decade of
exploration and expansion, our current research
and service capacity covers the entire new drug
discovery and development pipeline, ranging from
early discovery, antibody design, pre-clinical
evaluations, cGMP manufacturing, to clinical
trials. As an international cooperation, we have
established offices all around the globe with
more than 200 well-trained full-time scientists
and technicians, who work closely with our
customers and research partners to develop new
medicines for a better, healthier world. After
years of pursuit for perfection, Creative Biolabs
has established our leadership in targeted
immunotherapy and antibody-drug conjugate (ADC)
development.
Creative Biolabs
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