Certara’s Simcyp PBPK Modeling and Simulation Technology Achieves First FDA Virtual Bioequivalence Approval for ‘Complex’ Generic Drug

In-silico bioequivalence approach using Simcyp’s Multi-Phase
Multi-Layer Mechanistic Dermal Absorption model successfully replaced in-vivo,
clinical studies in FDA ANDA approval

PRINCETON, N.J.–(BUSINESS WIRE)–Certara® the global leader in model-informed drug
development, regulatory science, real-world evidence and market access
services, today announced that its Simcyp®
physiologically-based pharmacokinetic (PBPK) modeling and simulation
technology was used to demonstrate bioequivalence (BE) for the US Food
and Drug Administration (FDA) approval of a complex generic drug on the
agency’s abbreviated new drug application (ANDA) pathway.

“This drug approval represents a breakthrough for the industry and will
help usher in a new era in which complex generic drugs and treatments
with alternative delivery methods and formulations can be brought to
patients more quickly, without compromising their safety. This approach
also benefits patients by supporting the FDA’s mission to provide
affordable quality products through increasing competition and extending
the playing field,” said Simcyp President and Managing Director Steve
Toon, PhD.

“Virtual bioequivalence represents an ideal application for Simcyp’s
PBPK modeling and simulation capabilities. It is also an excellent
addition to the many scientific and regulatory accomplishments that the
Simcyp team has achieved during the past 20 years,” said Certara Chief
Scientific Officer Professor Amin Rostami. “This approval demonstrates
the boundless opportunities for innovation using PBPK across the entire
spectrum of new, alternative and reformulated drug products.”

BE studies are conducted to ensure that the rate and extent of
absorption of test drug products are not significantly different from
that of the comparable reference drug products. Changes in the
manufacturing process/site, raw material supplier or minor adjustments
to the drug formulation, also require evaluation of BE to demonstrate
that such changes do not substantially change its in vivo

Virtual bioequivalence leverages advanced modeling and simulation to not
only demonstrate BE, but also provide additional insight into drug
performance. These in silico studies are safer (removing the need
for drug administration to, often, young healthy volunteers), faster and
less expensive to conduct than clinical BE studies and represent an
important advance for generic and innovator drug companies alike.

Certara’s innovative research into the in-silico evaluation of
bioequivalence and bioavailability has been actively encouraged by the
FDA. For example, Certara’s Simcyp division was awarded an FDA grant in
2014 to further develop and verify the Simcyp Simulator’s Multi-Phase
Multi-Layer Mechanistic Dermal Absorption model, MPML MechDermA,
specifically to assess the bioequivalence of drugs absorbed through the
skin, while also factoring in variability in specific populations. In
2016, Simcyp was awarded an additional FDA grant to create and verify a
PBPK modeling and simulation framework to predict the behavior of
complex, supersaturating drug products in the human body.

In 2018, the FDA awarded Simcyp two additional virtual BE grants, one of
which focused on the inclusion of skin disease states in PBPK models to
help pharma companies develop non-Q1/Q2/Q3 formulations and simulate in-vivo
performance in patient populations to further support their
substitutability in diseased skin. When evaluating BE, the FDA uses Q1
to define qualitative equivalence (test and reference products contain
the same active and inactive ingredients), Q2 for quantitative
equivalence (test and reference products contain the same amounts of
active and inactive ingredients), and Q3 for physicochemical attributes
of a specific dosage form.

In addition to the grants, Simcyp’s Senior Principal Scientist and Head
of the Dermatological Research Group Professor Sebastian Polak was
invited to present at the FDA’s topical dermatological generic drug
products workshop in October 2017 on the “Development and Validation of
Dermal PBPK Model towards Virtual Bioequivalence Assessment.” MPML
MechDermA was featured as the result of an FDA-supported research
initiative that created an alternative approach to evaluate
bioequivalence for topical dermatological generic drug products that was
more efficient and reproducible.

Certara’s Simcyp Simulator is the most sophisticated platform for
determining first-in-human dose selection, designing more efficient and
effective clinical studies, evaluating and advancing new drug
formulations, and predicting drug-drug interactions and PK outcomes in
numerous virtual clinical populations. These include vulnerable
populations, such as pediatric patients, pregnant women, and patients
with impaired organ function. The Simcyp Simulator has now been used to
inform drug label claims, removing the need for specific clinical
investigation, for more than 50 new drugs approved by FDA, the European
Medicines Authority, and Japan’s Pharmaceuticals and Medical Devices

About Certara

Certara enables superior drug development and patient care
decision-making through model-informed drug development, regulatory
science, real-world evidence solutions and knowledge integration. As a
result, it optimizes R&D productivity, commercial value and patient
outcomes. Its clients include hundreds of global biopharmaceutical
companies, leading academic institutions, and key regulatory agencies
across 60 countries. For more information, visit www.certara.com.


Certara Contact:
Ellen Leinfuss, 609-216-9586
Corporate Affairs Officer

Media Contact:
Lisa Osborne, 206-992-5245
Healthcare Solutions