Absorption Systems has performed dozens of BCS classification studies over the past ten years, many of which have resulted in successful BCS biowaiver submissions. Eight of the ten largest generic drug companies have conducted in vitro BCS biowaiver studies with Absorption Systems. It was our permeability data that supported some of the very first in vitro BCS biowaivers.
Our extensive experience continues to facilitate innovative solutions and enable in vitro classification for a broader range of drugs. This, combined with our 10-day turnaround for pre-qualification and our cost effective designs, saves you time and money. Just a few reasons why Absorption Systems averages more than 30 BCS studies each year.
Avoid expensive and time consuming clinical bioequivalence studies with in vitro solubility, permeability, and dissolution data. It is a critical optimizer in time and money for drug developers.
Our validated 3-step study design allows for early identification of BCS biowaiver candidates and optimization of protocol elements. These steps include:
Pre-qualification and determination of the eligibility of test compound for BCS biowaiver. Your go/no-go decision point.
Protocol optimization and conduct of FDA-required experiments to establish protocol for pivotal studies.
GLP BCS classification of permeability and/or solubility
BCS Biowaivers Background Information
A Decade of BCS History
Translating Cellular Science into Human Outcomes
Redefining the Threshold for Permeability Classification
Welcome to the BCS Zone
|Simplified with Exemplary Service
Absorption Systems provides a clear advantage with results you can trust. Research managers are dedicated to your project, acting as your personal Data Concierge™ — delivering projects on time and on budget.
Recent enhancements to our study design enable favorable classification of a broader range of compounds, including cytotoxic and highly variable drugs. Such improvements include use of a novel high permeability standard, test system validation at multiple pH levels, and alternative designs for low-recovery compounds. We take a 3-step approach to BCS classification.
Phase 1A: BCS Pre-Qualifying Screen
Bidirectional permeability of test compound is evaluated at a single concentration across Caco-2 cell monolayers. Test compound is co-dosed with minoxidil (high permeability) and atenolol (low permeability) reference standards. This pre-qualifying screen allows for comparison of test compound permeability vs. control compounds and determination of passive transport (bidirectional symmetry). It also confirms the suitability of test conditions for classification of the compounds.
Phase 1B: Non-GLP Protocol Optimization
This protocol optimization step prior to GLP study includes non-specific binding assessment, tolerability evaluation, bidirectional permeability assessment in the absence of control compounds and optional solubility evaluation.
Phase 2: Pivotal GLP BCS Study
The definitive classification study includes GLP validation of analytical method and permeability assessment at three concentrations of test compound.
EA901 Preliminary BCS Solubility
EA902 GLP BCS Solubility
EA903 Preliminary BCS Permeability
EA904 GLP BCS Permeability
EA202 Express Bidirectional Caco-2
EA814 Rat Closed Loop Intestinal Perf
EA815 Rat Single Pass Intestinal Perf
EA816 Rat Recirculating Intestinal Perf
EA232 BCRP Interaction Assessment Lev 2
EA233 BCRP Interaction Assessment Lev 3
EA234 BCRP Interaction Assessment Lev 1
EA240 P-gp Interaction Assessment
EA250 Express P-gp Substrate in CPT-B1
EA251 Express BCRP Substrate in CPT-B1
EA252 Express P-gp Substrate in CPT-P1
EA820 Express Rodent Brain to Plasma Ratio
Fabre G, et al., Correlation between oral drug absorption in humans, and apparent drug permeability in TC-7 cells, a human epithelial intestinal cell line: comparison with the parental Caco-2 cell line. Pharm Res. 1998 May; 15(5):726-33.
Sambuy Y, et al., The Caco-2 cell line as a model of the intestinal barrier: influence of cell and culture-related factors on Caco-2 cell functional characteristics. Cell Biol Toxicol. 2005 Jan;21(1):1-26.
Which compounds are eligible for BCS-based biowaivers?
BCS biowaivers may apply for both generics and NCE’s. According to the FDA Guidance (2000), immediate release solid oral dosage forms that exhibit high solubility (over the pH range 1-7.5), high permeability (as qualified in a validated test system with internal standard) and high dissolution, are eligible for BCS-based biowaivers of clinical BA/BE studies. The EMA permits biowaivers for both Class I (high solubility/high permeability) and Class III (high solubility/low permeability) compounds. Some argue that biowaivers should be permitted for some Class II compounds as well.
Which methods are acceptable for permeability classification?
The FDA Guidance (2000) permits the use of human PK studies (absolute bioavailability or mass balance studies) and intestinal permeability methods (in vivo human intestinal perfusion, in vivo or in situ animal intestinal perfusion, excised human or animal intestinal tissue, or in vitro cultured epithelial cell monolayers) as methods to determine permeability classification.
Which studies can be bypassed with a BCS-based biowaiver?
After initial bioavailability studies, additional bioavailability or bioequivalence studies may be waived. Requests for biowaivers can be made in one of three types of regulatory submissions to the FDA:
• Investigational New Drug (IND) applications, for drugs under development
• New Drug Applications (NDAs) to market new drug products
• Abbreviated New Drug Applications (ANDAs) to market generic drug products
The following studies may be waived: clinical drug-drug interaction studies, bioequivalence studies for line extensions based on dose proportionality, formulation changes, approval of generic drug products, post-approval changes in manufacturing formula, manufacturing process, excipients, manufacturing site/equipment.
Absorption Systems is the world leader in biopharmaceutics classification system. We have been performing BCS studies for over a decade, and we supported the very first in vitro BCS-based biowavier.
For us, BCS is routine. Our experienced staff perform, on average, more than 30 studies per year and have uniquely classified more than 100 compounds.
We are innovators in the field and utilize an internal HPIS, minoxidil, which has a Papp value of approximately 7-fold less than metoprolol, leading to more accurate compound classifications.
Our proven track record with the FDA, including successful site audits and training sessions, can't be matched by any of our competition.