PharmPK Discussion - 90% Confidence Interval for Tmax

• On 24 Sep 2007 at 16:24:44, muthuswamy chinnaiah (muthuswamy_23.-a-.yahoo.co.in) sent the message
  

  
  DEAR MEMBERS,
  
  I just want to know that is it necessary to have 90% confidence
  intervals for Tmax  for an immediate release dosage formulation to
  establish bioequivalence.
  The guidelines says 90% confidence intervals
  of the geometric mean ratio of three PK parameters i.e AUC(0-t) ,
  AUC(0-infinity)  and Cmax between the test and the reference fall
  within 80-125%.
  Kindly suggest,
  
    Regards,
  
  MUTHUSWAMY.C
  EX.RESEARCH ASSISTANT
  GVK BIOSCIENCE PVT.LTD.,
  HYDERABAD.
  
  

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• On 25 Sep 2007 at 12:59:24, Helmut Schuetz (helmut.schuetz.aaa.bebac.at) sent the message
  

  
  The following message was posted to: PharmPK
  
  Dear Muthuswamy!
  
  You wrote:
   > I just want to know that is it necessary to have 90% confidence
   > intervals for Tmax  for an immediate release dosage formulation to
   > establish bioequivalence.
   > The guidelines says 90% confidence intervals
   > of the geometric mean ratio of three PK parameters i.e AUC(0-t) ,
   > AUC(0-infinity)  and Cmax between the test and the reference fall
   > within 80-125%.
  
  If asking questions concerning regulatory requirements, I would suggest
  adding the country you are referring to in your request.
  There more than 30 different guidelines in operation worldwide; for a
  collection see:
  http://bebac.at/Guidelines.htm
  
    From your quote I guess you are are talking about the FDA ;-)
  http://www.fda.gov/cder/guidance/5356fnl.pdf
  
  Comparison of 'early exposure' is only neccessary based on clinical
  grounds (i.e., rapid onset of effect claimed in the label, or to avoid
  adverse events). See Section III A 8 a:
  'In this setting, the guidance recommends use of partial AUC as an early
  exposure measure. We recommend that the partial area be truncated at the
  population median of Tmax values for the reference formulation. We also
  recommend that at least two quantifiable samples be collected before the
  expected peak time to allow adequate estimation of the partial area.'
  
  In other countries (European Union, ASEAN States, Australia, New
  Zealand, South Africa,...) Tmax is compared (only if clinically
  necessary) by a nonparametric method (untransformed data; according to
  some guidelines the aceptance range has to be set based on clinical
  grounds, some guidelines call for 80%-120% of the reference).
  
  Best regards,
  Helmut
  
  --
  Ing. Helmut SchA\0x00tz
  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 28 Sep 2007 at 03:30:17, "Hiren Mehta" (hirenpharm.at.gmail.com) sent the message
  

  
  HPFB / FDA asks comparision of AUCreftmax with AUCtest(truncated) for
  drugs which require rapid onset of action. e.g. Pain-killers.
  
  NZ asks for 90% CI for Tmax also.
  
  Hope this suffice
  
  

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