Regulatory Guidance
➦ PortaCellTec – the pathfinder for your drug
Transporters are membrane proteins whose primary function is to facilitate the movement of molecules—such as nutrients or endogenous substrates (e.g., sugars, amino acids, nucleotides)—into and out of cells.
However, the specificity of these transporters is not limited to physiological substrates. Drugs that share significant structural similarity with endogenous compounds can also be recognized and transported.
As a result, transporters play essential roles in determining the bioavailability, therapeutic efficacy, and pharmacokinetics of a wide range of drugs.
According to the ICH M12 guideline and recommendations from the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and Japanese Pharmaceuticals and Medical Devices Agency (PMDA), PortaCellTec Biosciences, a life science CRO, offers transporter assays to demonstrate the interaction of drugs and their metabolites with selected cellular transporter proteins. These assays include transporters responsible for the uptake of molecules into cells (SLC transporters) and those mediating efflux from cells (ABC transporters).
➦ Guidance for Industry
‣ ICH harmonization for better health: ICH harmonization guideline (2024)
‣ US Food and Drug Administration (FDA)
- FDA – In Vitro Metabolism- and Transporter- Mediated Drug-Drug Interaction Studies (2017)
- FDA – Guidance for Industry – Draft Guidance (2017)
- FDA – Drug Interaction Studies − Study Design, Data Analysis, and Implications for Dosing and Labeling Recommendations (2012)
- FDA – Major human transporters (2006)
- FDA – Drug Interaction Studies − Study Design, Data Analysis, and Implications for Dosing and Labeling – Draft Guidance For Industry (2006)
‣ European Medicines Agency (EMA)
- EMA – Guideline on the Investigation of Drug Interaction (2012)
- EMA – Guideline on the Investigation of Drug Interaction – Draft Guidance (2010)
‣ Japanese Pharmaceuticals and Medical Devices Agency (PMDA)
- Japan –Guideline on drug interaction for drug development and appropriate provision of information (2019)
- Japan – Guideline on the Investigation of Drug Interactions (2014)‣
‣ The International Transporter Consortium (ITC)
- The International Transporter Consortium – Membrane transporters in drug development: the full report from the International Transporter Consortium, March 2010, is available from Nature Reviews
➦ More Information:
- A public drug transporter database ➔ UCSF-FDA TransPortal
- SLC (Solute Carrier) transporter database ➔ Bioparadigms
| Transporter | Gene | Drug Elimination | ITC/FDA | EMA | PMDA |
|---|---|---|---|---|---|
| OAT1 ▸ | SLC22A6 | renal | + | + | + |
| OAT3 ▸ | SLC22A8 | renal | + | + | + |
| OATP1B1 ▸ | SLCO1B1 | hepatic | + | + | + |
| OATP1B3 ▸ | SLCO1B3 | hepatic | + | + | + |
| OCT1 ▸ | SLC22A1 | hepatic | propose | + | – |
| OCT2 ▸ | SLC22A2 | renal | + | + | + |
| MATE1 ▸ | SLC47A1 | hepatic/renal | + | consider | + |
| MATE2K ▸ | SLC47A2 | renal | + | consider | + |
| MDR1 ▸ | ABCB1 | hepatic/renal | + | + | + |
| BCRP ▸ | ABCG2 | hepatic | + | + | + |
| BSEP ▸ | ABCB11 | hepatic | prefer | consider | – |
