PharmPK Discussion - Tightening of BE limits for NTI

• On 14 Jul 2012 at 16:30:33, narasimha reddy (r.nara.simha.reddy123.-at-.gmail.com) sent the message
  

  
  Hi,
  
  Whether we need to tighten the BE limits for Narrow Therapeutic Index drug
  intended for US submission and MCC.?
  
  Regards,
  Narasimha Reddy
  
  

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• On 15 Jul 2012 at 09:57:29, "Gobburu, Joga" (jgobburu.aaa.rx.umaryland.edu) sent the message
  

  
  The following message was posted to: PharmPK
  
  You will need to consult Guidance for Industry for BE requirements (if any) for
  your specific product. If not, you need to check if your product qualifies as
  High Variability Product - the BE criteria might be different for them. Else,
  the regular BE criteria would apply.
  
  Joga Gobburu, PhD, FCP, MBA |  Professor | School of Pharmacy  |  School of
  Medicine
  Executive Director |Center for Translational Medicine
  N407, 20 N Pine, Baltimore, MD-21201
  

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• On 15 Jul 2012 at 18:03:02, Helmut Schuetz (helmut.schuetz.at.bebac.at) sent the message
  

  
  The following message was posted to: PharmPK
  
  Dear Narasimha,
  
  EMA: See the BE GL (2010), Section 4.1.9.
  The limits may have to be tightended to 90.00-111.11 but there is no list of
  NTDIs (like e.g. in Canada), the decision must be done on a case by case basis.
  In doubt go for a scientific advice. Only tacrolimus and ciclosporine were taken
  through a referral procedure and a decision was already made by the PK working
  party. See the Q&A document from Feb 2012:
  http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002963.pdf
  Tacrolimus: 90-111% for AUC and 80-125% for Cmax.
  Ciclosporine: 90-111%, both for AUC and Cmax.
  
  FDA: See the general BE guidance (2003), Section VI. F.
  Check the product specific guidances at:
  http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm075207.htm
  Currently FDA is considering a scaling approach narrowing the acceptance range
  based on the intra-subject CV of the reference (requires a replicate design).
  For details see the 'Slides for the July 26, 2011 Meeting of the Advisory
  Committee for Pharmaceutical Science and Clinical Pharmacology' at:
  http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AdvisoryCommitteeforPharmaceuticalScienceandClinicalPharmacology/ucm266768.htm
  
  Best regards,
  Helmut
  
  -
  Ing. Helmut Schuetz
  BEBAC - Consultancy Services for
  Bioequivalence and Bioavailability Studies
  Neubaugasse 36/11
  1070 Vienna, Austria
  e-mail  helmut.schuetz.at.bebac.at
  web     http://bebac.at/
  forum   http://forum.bebac.at/
  
  

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• On 15 Jul 2012 at 19:11:34, Andrew Sutton (drasutton.aaa.gmail.com) sent the message
  

  
  I think it is right to take cases individually as Helmut says it is in the US.
  
  What would be the purpose of tightening these limits? =46rom a regulatory point of
  view it would have to be to stop inadequate formulations getting to the market.
  But if they are inadequate I would not expect them to be put onto the market
  anyway...the dose response would be too erratic; by which I mean poor efficacy
  in some patients and excess adverse effects in others.  So what company would
  take on such a product?
  
  It raises the question of whether we are satisfied with the current limits.  Do
  they really mean that absorption is as predictable as it should be?
  
  It's interesting that the Canadians haven't left it to industry ... to make this
  mistake?
  
  Andrew Sutton
  
  

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