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Dear Friends,
What should be minimum sample size for pivotal bioequivalence study
for EU & US FDA submission?
Regards,
Nikunj Bhatt
Sr. Research Associate - Biostatistics
Veeda Clinical Research Pvt. Ltd.
Ahmedabad, India
Web: www.veedacr.com
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That would be 12 completed subjects. Best, -Dave
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Minimum of 12 subjects.
Ref: FDA Guidance for Industry-Bioavailability and Bioequivalence
Studies for Orally Administered Drug Products - General Considerations
Regards
Dr. M. Joseph
Lambda
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1) FDA, WH0, ANVISA, CANADA -Minimum of 12 subjects
2) EMEA, TGA - Not less than 12 unless justified.
3) MCC -12, Minimum 20 for MR Dosage forms
4) CDSCO- Not less than 16 unless justified for ethical reasons
Regards,
Viresh
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Dear Nikunj,
Sample size for pivotal study depends on your ratio% estimates and CV
% of pilot study for a specified power.
FDA and EU genearly ask for at least 2X2 crossover study with minimum
of 12 volunteers.
I hope this one helps.
Regards,
Ravi Pandey
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That is for pilot study and the number specified (12) is not clearly
mentioned in the said guidance. The sentence in the guidance under
SECTION 3.A.2 related to number of subjects is as follows: "A pilot
study that documents BE may be acceptable, provided that its design
and execution are suitable and a sufficient number of subjects (e.g.
12) have completed the study."
My interpretation is
1. The required number of subjects is not specified, and has to be
decided by the statistician on the basis of data from the pilot study
or the literature available.
2. Even the mentioned number is to be considered, it is specifically
for pilot study, not for pivotal study.
Regards,
Sanjay Kumar
Sr. Scientist- DRA
Alkem Laboratories Ltd
Mumbai
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Dear All,
Even though it is not clear as rightly pointed out by Mr. Sanjay, we
can assume that a Pilot study planned just like a pivotal study as two
way, cross over, fasting study with 12 subjects and fortunately if the
drug passes the bioequivalence criteria, then we can submit the same
data to FDA for its approval.
Correct me if I am wrong.
Regards
Dr. M. Joseph
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Forum:
For what it's worth, when Graham Mould and I ran Guildford Clinical
Pharmacology for 14 years we evolved the rule of thumb that the FDA
wants 24 per group and Europe 12 (assuming within subject comparisons
and reasonable variances.
I remember we had discussions about the FDA 24 being more likely to
detect outliers, and slow metabolisers in particular who would
accumulate the compound in clinical practice. However, as 24 is only
a step in that direction we assumed that Europe concludes that it's
not worth doubling the numbers.
Andrew Sutton
Consultant in Clinical Pharmacology
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