FDA Compliance

&

SOLVO Biotechnology provides all the definitive in vitro P-gp assays that comply with the 2006 FDA Draft Guidance on assessing drug-drug interactions.

Why is P-gp important?

• P-gp drug efflux transporter is present in all pharmacological barriers influencing the ADMETox properties of drugs
• drugs that are substrates or inhibitors of P-gp may participate in drug-drug or drug-nutrient interactions, leading to modified bioavailability of the drug and to serious side effects such as morbidity in case of drugs with narrow therapeutic index

What are the main characteristics of SOLVO's FDA-compliant P-gp services?

• studies can be conducted using human Caco-2, or MDCKII-MDR1 cell lines according to your request
• the general protocol applies two P-gp inhibitors in the Caco-2 assay recommended by the FDA: Verapamil and Ketoconazole
• it can identify P-gp substrate and inhibitory properties of your NCE, IND or NDA
• it can provide IC₅₀ data for the inhibition of digoxin transport
• it is a flexible design for optimal cost and quick turn-around time
• a clear and consistent flow-chart with decision points describes SOLVO's FDA-compliant P-gp studies

Additional P-gp studies are also available at SOLVO Biotechnology:

• SOLVO has the most comprehensive P-gp technology platform from HT in-vitro assays to in-vivo studies
  • in-vitro assays
    • Caco-2 and MDCKII-MDR1 monolayer assays are available at different levels of complexity: basic, custom besides the FDA setup. Transporter specific interactions can also be investigated with the use of P-gp substrates and inhibitors
    • P-gp PREDIVEZ^TM Kit: this vesicular transport assay is a unique HT SOLVO technology that identifies all the compounds that interact with P-gp
    • P-gp PREDEASY^TM Kit: SOLVO's HT ATPase assay is able to distinguish substrates and inhibitors
    • P-gp Calcein assay: SOLVO's proprietary cellular dye efflux assay
  • in-vivo services
    • rat brain microdialysis uses quinidine as reporter substrate, and PSC833 as a specific P-gp inhibitor
• SOLVO suggest tailor-made solutions to optimize study design and the right combination of the appropriate assays
• you can save money and time by choosing the most appropriate SOLVO P-gp assays for the different stages of your drug development

Recommendations by pharma, academic and regulatory experts (International Transporter Consortium) are introduced in Nature Reviews Drug Discovery (2010) Volume 9 /March: 215:236

SOLVO Biotechnology provides all major assays that comply with the Transporter Working Group recommendations.

SOLVO Biotechnology

• continuously expands its portfolio based on the latest results in transporter science, the needs of the pharmaceutical industry and the various regulatory agencies such as FDA and EMEA
• has the widest range of transporter assay systems that satisfies all the upcoming requirements for efflux and uptake transporters
• has unparalleled knowledge on transporters, and has the biggest drug transporter R&Ð department publishing regularly in peer-reviewed journals.

Which additional drug transporters are under consideration?

• Efflux transporters: BCRP
• Uptake transporters: OATP1B1/OATP-C, OATP2B1/OATP-B, OATP1B3/OATP8, OCT2, OAT1, OAT3

Recommended assays for these transporters:

Efflux transporter assays:

• BCRP: MDCKII-BCRP monolayer assay
  

• OATP1B1: cellular assay
• OATP2B1: cellular assay
• OATP1B3: cellular assay
• OCT2: cellular assay
• OAT1: cellular assay
• OAT3: cellular assay

For additional information please contact SOLVO at sales@solvo.com.

A wide range of related products, licenses and services are also available. See our Products and Services catalogues for more details.