Model-informed services
across the drug lifecycle
From early-phase studies to regulatory submissions, we apply the F.A.T. framework at every stage. In all stages of drug & generics development we analyze the data utilizing the Finite Time Pharmacokinetics (FTPK) Software, which replaces time-consuming PBPK modeling work. Population PK studies are analyzed with NONMEM using the F.A.T.-based models as structural models, which are embedded in the FTPK software.
Early Drug Development
We do not follow the classical development based on bottom-up PBPK models, since no time-consuming and controversial PBPK modeling is required (see rationale, PBFTPK models — PubMed & top-down FTPK vs. bottom-up PBPK). We perform an oral study with six volunteers and analyze data with the FTPK Software, obtaining the detailed PK profile: number of drug input stages, their duration and input rates, and elimination/disposition rate constants. Most importantly, we estimate — uniquely from an oral study alone — a lower boundary of absolute bioavailability, LAB; for the simplest case, a one-compartment model with one input stage,
where kel and τ are the estimates for the elimination rate constant and the duration of drug absorption, respectively, derived from the fitting of the PBFTPK model to the C,t data using the FTPK software.
Phase I–III Clinical Studies
We provide model-informed design and analysis of Phase I, II, and III clinical studies using the FTPK software platform. In addition, we conduct population pharmacokinetic (PopPK) analyses using the PBFTPK models embedded in the FTPK software. The optimization work is facilitated since the LAB and F/Vd estimates bracket the true volume of distribution:
Besides, population analysis free of the wrong estimates of the absorption rate constant is accomplished.
Clinical · PK/PDDevelopment of Generics
Prior to any in vitro study for the development of a generic formulation, we analyze the published in vivo data of the Reference formulation using the FTPK software. We then construct the % Absorbed versus time curve following our novel methodology. We then follow our revised IVIVC strategy coupled with comparative dissolution studies of the reference formulation carried out under sink conditions (e.g. USP 4). This approach reveals the IVIVs, if any, for the Reference formulation and guides the rational development of the generic formulation. Our approach aligns with the latest EMA/FDA guidance and F.A.T.-informed science.
IVIVC · DevelopmentAssessment of Generics: Bioequivalence Studies
Prior to the study, innovator and generic products are examined in the spirit delineated in the "Development of Generics" section. Rigorous BE studies are performed to deliver accurate, FDA and EMA regulatory-compliant assessments. Apart from the classical BE report, we provide an additional analysis based on a F.A.T. model-dependent methodology using meaningful parameters, (FD/Vd, in concentration units) and (FD/τVd, in concentration/time units), for the extent and rate of absorption, respectively, for both formulations. In addition, the lower boundary of absolute bioavailability LAB will be provided for both formulations. Needless to say, we re-analyze failed BE studies using the FTPK software.
Generics · RegulatoryAnalysis with the FTPK software
We utilize FTPK software for the analysis of pharmacokinetic data. Six PBFTPK models are currently employed, comprising one- and two-compartment disposition models with one, two, or three input stages. In all cases, the number of input stages is determined, and parameter estimates — along with their associated uncertainties — are obtained for the duration and input rates of each stage, as well as for the elimination rate constant or disposition constants. Most importantly, an estimate of the concentration corresponding to the fraction of dose absorbed is derived, allowing the estimation of a lower bound of absolute bioavailability based solely on oral data, through comparison with the observed maximum concentration.
We conduct population pharmacokinetic (PK) analysis using NONMEM based on PBFTPK structural models.
FTPK Software · Population Analysis · NONMEM
Model-Informed, F.A.T.-Based Development of Modified-Release Formulations
The analytical power of FTPK software enhances the rational design of modified-release formulations. This is because sustained-release formulations are typically designed to exhibit an initial immediate-release phase followed by a prolonged sustained-release phase. Consider a company aiming to develop a 20 mg once-daily formulation to replace an existing 10 mg tablet administered twice daily. Analysis of the in vivo published data for the 10 mg tablet using FTPK software can reveal not only the two absorption phases but also the duration of each phase and their corresponding input rates. The targeted release profile of the new formulation is derived from this analysis and optimized according to the company’s specifications.
PK · DevelopmentClinical Studies
We perform clinical studies involving human volunteers to explore new ways to diagnose, treat, prevent or understand diseases and health conditions. We carry i) Phase I studies to test safety and dosage, ii) Phase II studies to explore efficacy and side effects in a larger group, iii) Phase III studies to confirm effectiveness and monitor side effects, and iv) Phase IV post-marketing studies to gather additional information on long-term effects. We participate in clinical trials approved in the European Union or Internationally. We collaborate with NKUA's hospitals and private hospitals and local CROs for the registration aspects of the study, monitoring of the patients etc of the clinical trial.
Clinical · PK-PDPharmaceutical Analysis — Organic Synthesis Lab
Analytical characterization of drug substances and products, supporting formulation development and quality assessment for regulatory filings. The analytical work is also extended to identification of drug metabolites using mass spectrometry. The organic synthesis laboratory can carry the synthesis of metabolites. Also, this laboratory utilizes advanced techniques and methodologies to design and execute synthetic routes for a wide range of organic compounds.
Analysis · QA · SynthesisDermopharmaceutics Lab
In a GLP-certified animal laboratory, studies on skin pharmacology, skin toxicity, oxidative stress, antioxidants, and topical preparations are conducted. Examples of studies carried out in the past include the assessment of the healing potential of various compounds, the evaluation of dermatological effects of acute and long-term UV-C exposure, and the in vitro assessment of the effects of portable, domestic UV-C disinfection devices on skin fibroblasts.
Skin · Regulatory