






  
  2006D-0344
  
   Guidance for Industry on Drug Interaction Studies--Study Design, Data Analysis, and Implications for Dosing and Labeling

  

  
  
  

  
  

  
  

  
  FDA Comment Number : 
  
  EC6
  


  
  Submitter : 
  
  Dr. David Stresser
  
  Date & Time: 
  
  11/13/2006 11:11:23
  


  
  Organization : 
  
  BD Biosciences
  


  
  Category : 
  
  Device Industry
  


  
  Issue Areas/Comments 
  

  
  

  
  GENERAL
  

  
  


  
  GENERAL
  

  
  


  
   Division of Dockets Management (HFA-305)

Food and Drug Administration

5630 Fishers Lane, Rm. 1061

Rockville, MD

20852

 

Re: Docket No. 2006D-0344, CDER 20051

 

Dear Sir/Madam:

We would like to submit comments to the draft guidance document entitled: Guidance for Industry on Drug Interaction Studies - Study Design, Data Analysis, and Implications for Dosing and Labeling.

 

The guidelines contain parameters to determine a properly functioning PGP-containing cell model system. We believe these should be the primary determinants in the guidance - as opposed to type of membrane used to culture the cells.  For example, PC and PET are functional equivalents and there are several references in the literature to support this (see references below).  However, the guidance indicates PC membranes are preferred. 

 

Allowing multiple sources of membranes assures a more stable supply (e.g., the sole source high quality polycarbonate film which was the basis for the TC membranes was discontinued).   

 

As this is in the interest of all parties we respectfully suggest the guidance be modified to reflect acceptance of PET membranes.

 

Kind regards,

 

Charles L Crespi, Ph.D.

David Stresser, Ph.D.

Marshall Kosovsky, Ph.D.

BD Biosciences Discovery Labware

Woburn, MA USA

 

 

References using PET membranes:

1. Lau, Y., et al. Evaluation of a Novel In Vitro Caco-2 Hepatocyte Hybrid System For Predicting In Vivo Oral Bioavailability. Drug Metab.

  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  







  
   Dispos. 32: 937 (2004).

 

2. Cummins, C., et al. CYP3A4-Transfected Caco2 Cells as a Tool for Understanding Biochemical Absorption Barriers: Studies with Sirolimus and Midazolam. J. Pharmacol. Exp. Ther. 308:143 (2004).

 

3. Paine, M., et al. Identification of a Novel Route of Extraction of Sirolimus in Human Small Intestine: Roles of Metabolism and Secretion. J. Pharmacol. Exp. Ther. 301:174 (2002).

 

4. Harrison, A., et al. Nonlinear Oral Pharmacokinetics of the  -Antagonist 4-Amino-5-(Fluorophenyl)-6,7-Dimethoxy-2-[4- (Morpholinocarbonyl)-Perhydro-1,4-Diazepin-1-YL] Quinoline in Humans: Use of Preclinical Data to Rationalize Clinical Observations. Drug Metab. Dispos. 32:197 (2004).

 

5. Furfine, E., et al. Preclinical Pharmacology and Pharmacokinetics of GW433908, a Water-Soluble Prodrug of the Human Immunodeficiency Virus Protease Inhibitor Amprenavir. Antimicrob. Agents Chemother. 48:791 (2004).

 

6. Xu, Y., et al. Intestinal and Hepatic CYP3A4 Catalyze Hydroxylation of 1 , 25-Dihydroxyvitamin D3: Implications for Drug-Induced Osteomalacia. Mol. Pharmacol. 69:56 (2006).

 

7. Sasabe, H., et al. Differential Involvement of Multidrug Resistance-Associated Protein 1 and P-Glycoprotein in Tissue Distribution and Excretion of Grepafloxacin in Mice. J. Pharmacol. Exp. Ther. 310:648 (2004).

 

8. Letschert, K., et al. Vectorial Transport of the Peptide CCK-8 by Double-Transfected MDCKII Cells Stably Expressing the Organic Anion Transporter OATP1B3 (OATP8) and the Export Pump ABCC2.  J. Pharmacol. Exp. Ther. 313:549 (2005).

  

References using PET or PC membranes:

1. Rosmann, S., et al. Activation of Human Meprin-  in a Cell Culture Model of Colorectal Cancer Is Triggered by the Plasminogen-activating System. J. Biol. Chem. 277:40650 (2002).

 

2. Rothen-Rutishauser, B., et al. Formation of Multilayers in the Caco-2 Cell Culture Model: A Confocal Laser Scanning Microscopy Study. Pharm. Res. 17:460 (2000).

 

3. Yamashita, S., et al. New and Better Protocols for a Short-term Caco-2 Cell Culture System. J. Pharm. Sci. 91:669 (2002).

 

4. Schmiedlin-Ren, P., et. al. Expression of Enzymatically Active CYP3A4 by Caco-2 Cells Grown on Extracellular Matrix-Coated Permeable Supports in the Presence of 1,25-Dihydroxyvitamin D3. Mol. Pharm. 51:741 (1997).  

 

5. Sergent-Engelen, T., et al. Improved cultivation of polarized animal cells on culture inserts with new transparent polyethylene terephthalate or polycarbonate microporous membranes. J. Bio.Tech. 4:89 (1990).

 

  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  

  
  


  
    2006D-0344-EC6-Attach-1.pdf



	Dispos. 32: 937 (2004). 2. Cummins, C., et al. CYP3A4-Transfected Caco2 Cells as a Tool for Understanding Biochemical Absorption Barriers: Studies with Sirolimus and Midazolam. J. Pharmacol. Exp. Ther. 308:143 (2004). 3. Paine, M., et al. Identification of a Novel Route of Extraction of Sirolimus in Human Small Intestine: Roles of Metabolism and Secretion. J. Pharmacol. Exp. Ther. 301:174 (2002). 4. Harrison, A., et al. Nonlinear Oral Pharmacokinetics of the -Antagonist 4-Amino-5-(Fluorophenyl)-6,7-Dimethoxy-2-[4- (Morpholinocarbonyl)-Perhydro-1,4-Diazepin-1-YL] Quinoline in Humans: Use of Preclinical Data to Rationalize Clinical Observations. Drug Metab. Dispos. 32:197 (2004). 5. Furfine, E., et al. Preclinical Pharmacology and Pharmacokinetics of GW433908, a Water-Soluble Prodrug of the Human Immunodeficiency Virus Protease Inhibitor Amprenavir. Antimicrob. Agents Chemother. 48:791 (2004). 6. Xu, Y., et al. Intestinal and Hepatic CYP3A4 Catalyze Hydroxylation of 1 , 25-Dihydroxyvitamin D3: Implications for Drug-Induced Osteomalacia. Mol. Pharmacol. 69:56 (2006). 7. Sasabe, H., et al. Differential Involvement of Multidrug Resistance-Associated Protein 1 and P-Glycoprotein in Tissue Distribution and Excretion of Grepafloxacin in Mice. J. Pharmacol. Exp. Ther. 310:648 (2004). 8. Letschert, K., et al. Vectorial Transport of the Peptide CCK-8 by Double-Transfected MDCKII Cells Stably Expressing the Organic Anion Transporter OATP1B3 (OATP8) and the Export Pump ABCC2. J. Pharmacol. Exp. Ther. 313:549 (2005). References using PET or PC membranes: 1. Rosmann, S., et al. Activation of Human Meprin- in a Cell Culture Model of Colorectal Cancer Is Triggered by the Plasminogen-activating System. J. Biol. Chem. 277:40650 (2002). 2. Rothen-Rutishauser, B., et al. Formation of Multilayers in the Caco-2 Cell Culture Model: A Confocal Laser Scanning Microscopy Study. Pharm. Res. 17:460 (2000). 3. Yamashita, S., et al. New and Better Protocols for a Short-term Caco-2 Cell Culture System. J. Pharm. Sci. 91:669 (2002). 4. Schmiedlin-Ren, P., et. al. Expression of Enzymatically Active CYP3A4 by Caco-2 Cells Grown on Extracellular Matrix-Coated Permeable Supports in the Presence of 1,25-Dihydroxyvitamin D3. Mol. Pharm. 51:741 (1997). 5. Sergent-Engelen, T., et al. Improved cultivation of polarized animal cells on culture inserts with new transparent polyethylene terephthalate or polycarbonate microporous membranes. J. Bio.Tech. 4:89 (1990).





















































	2006D-0344-EC6-Attach-1.pdf