TIPS FOR THE INDUSTRY TO LEVERAGE PHARMACOMETRIC REVIEW OF
ANTIMICROBIAL AGENTS
Pharmacometrics is apparently important in drug R&D. The manufacturers
with an intention to develop antimicrobial agents should take advantage
of pharmacometrics to understand the PK-PD profile of the drug under
study and build physiologically based PK (PBPK) and population PK models
at early stage of drug development. The in vitro susceptibility
testing data of clinical pathogenic isolates (bacteria or fungi) can be
combined with PK data to inform trial design and the dosing regimens in
clinical trials, to identify the optimal dosing regimen, and accelerate
new drug launch. As drug R&D advances, real-time modeling is
recommended by dynamic update of the predefined model to better
understand which physiological, pathological, concomitant medication or
other factors of patients are the significant covariates affecting the
PK profile of the drug, and provide adequate data to support drug safety
and efficacy. The following measures may be helpful for relevant
entities to benefit from pharmacometrics.
- Recruit dedicated pharmacometricians, provide professional training,
build specialized pharmacometrician team or assign the pharmacometrics
responsibility to a clinical pharmacology team. The research-based
pharmaceutical companies should make the size of their
pharmacometrician team appropriate to their product pipeline.
- Actively encourage the staff members to attend pharmacometric training
program. Pharmacometrics is developing rapidly as an emerging
discipline with ever-changing research hot spots. The concerned
pharmaceutical companies are recommended to keep an eye on the latest
training information and develop a customized training plan according
to the background knowledge and experience of pharmacometric staff.
- Integrate pharmacometric strategy and study into Company’s Target
Product Profile (TPP), Clinical Development Plan (CDP), and
Pharmacology Development Plan (PDP) to boost product development.
Innovative pharmacometric methods should also be considered in the
development of generic drugs to conduct modeling analysis of key
parameters for bridging the safety and efficacy of the generic drug
with the original brand drug, improving the quality of generic drugs,
and shortening the development cycle.
- Actively communicate the strategy of pharmacometric study and
development milestones with the regulatory agencies for guidance and
advice from the regulator.
- Include the data of pharmacometric study in the clinical trial
application and NDA package submitted to Chinese regulatory agency and
to standardize the wording of package leaflet.
- Actively attend pharmacometric meetings held regionally or globally to
communicate scientific findings and advance pharmacometric research.
The pharmaceutical companies should also pay attention to the following
issues when applying the pharmacometric strategy and approaches to new
drug development:
- The requirement for pharmacometric study may vary with the stage of
new drug development and evaluation. Pharmaceutical companies should
plan scientifically with reference to current guidelines. During the
development of innovative antimicrobial agents, PK data should be
combined with in vitro bacteriostatic results. Population PK
data should be combined with PK-PD analysis to optimize the dosing
regimen. The clinical and microbiological efficacy data should be
collected in clinical studies for dynamic pharmacometric analyses.
- At each stage of new drug development, the industry should work with
the investigator and regulator to conduct analysis and employ the
strategy of pharmacometric study for an individual drug.
- The results of pharmacometric study should be confirmed in subsequent
clinical trials or practice.
In conclusion, pharmacometrics is an intricate emerging discipline
involving clinical pharmacology, physiology, pharmacology, toxicology,
clinical medicine, microbiology, biology, and statistics. Pharmaceutical
companies should strengthen pharmacometric team building via systematic
professional education and training to meet the requirements of
increasingly complicated new drug
development.