roody
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2005-10-04 17:10

Posting: # 36
Views: 15,692
 

 Only fed study [Design Issues]

With reference to ANDA submission for US FDA, If the prescribing information says that the drug has to be taken under fed condition then whether it is necessary to conduct both fasted and fed studies? Can we only submit the fed study for immediate release formulation?
Helmut
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Vienna, Austria,
2005-10-04 17:45

@ roody
Posting: # 38
Views: 11,744
 

 Only fed study

Dear Roddy!

http://www.fda.gov/cder/guidance/5356fnl.pdf The general Guidance (2003) states for IR products:
'…, we recommend that where the focus is on release of the drug substance from the drug product into the systemic circulation, a single-dose, fasting study be performed.'

http://www.fda.gov/cder/guidance/5194fnl.pdf The Food Effect Guidance (2002) states for IR ANDAs:

'In addition to a BE study under fasting conditions, we recommend a BE study under fed conditions for all orally administered immediate-release drug products, with the following exceptions:

  • When both test product and RLD are rapidly dissolving, have similar dissolution profiles, and contain a drug substance with high solubility and high permeability (BCS Class I) (see footnote 3), or
  • When the DOSAGE AND ADMINISTRATION section of the RLD label states that the product should be taken only on an empty stomach, or
  • When the RLD label does not make any statements about the effect of food on absorption or administration.'

Therefore unless you have a BCS Class I compound, IMHO you will have to perform both a fasting and a fed study.

Anyhow, if the food effect documented in the reference's SmPC is safety-related (i.e., AEs due to GI-disturbances), you may start an argument.

Remark: in such a case European Guidelines call only for a fed study.


Edit: Links corrected for FDA’s new site. [Helmut]

Cheers,
Helmut Schütz
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Jaime_R
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Barcelona,
2005-10-04 18:42

@ Helmut
Posting: # 39
Views: 11,657
 

 Only fed study

Hi Helmut!

The reasoning behind is that although you write something in the SPC, there is no guarantee, that patients act accordingly, i.e. swallow your drug together with food. Maybe they 'know' that any drug acts 'faster'/'better' if adminstered on an empty stomach, or they don't even read the SPC.

» Anyhow, if the food effect documented in the reference's SmPC is
» safety-related (i.e., AEs due to GI-disturbances), you may start an
» argument.

Yes, but: see above ;-)

» Remark: in such a case European Guidelines call only for a fed
» study.

Again yes, but: I've heard of an application where the Dutch regulators wanted to see a fasting study - after the submitted fed study (which showed BE).
Regulators have all post approval data of the inovator's product on file; maybe that's the reason.

Regards, Jaime
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