Hi Rajib,
As per the guidance "Bioavailability and Bioequivalence studies submitted in NDA's or IND's" Page
In vitro data can be used to compare formulations of drug products under certain circumstances. If an applicant seeks to demonstrate the BA or BE of immediate-release formulations for capsules, tablets, and suspensions using in vitro data, FDA recommends that sponsors generate dissolution profiles for all strengths using an appropriate dissolution method. If the dissolution results indicate that the dissolution characteristics of the product are not dependent on the pH and product strength, dissolution profiles in one medium are usually sufficient to support demonstrating BE. Otherwise, dissolution data in at least three media (e.g., pH 1.2, 4.5, and 6.8) are recommended. The f2 test should be used to compare profiles from the different strengths of the product (see FDA guidance for industry, Dissolution Testing of Immediate Release Solid Oral Dosage Forms). An f2 value > 50 indicates a sufficiently similar dissolution profile to support a biowaiver. For an f2 value < 50, discussion with the appropriate review division is recommended to determine whether an in vivo study is needed. The f2 approach is not suitable for rapidly dissolving drug products (e.g., > 85% dissolved in 15 minutes or less).
Based on what you mentioned, it seems like the dissolution characteristic is dependent on pH. In this case, you may need to discuss with the appropriate review division for further guidance.
Hope this helps.
Thanks,
Mehul
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Mehul Govani RAC
Regulatory Affairs Manager
Westbury NY
United States
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Original Message:
Sent: 06-Apr-2018 03:15
From: Rajib Kumar Baishnab
Subject: Biowaivers of Lower strength Drug
Dear Members,
We have conducted multimedia dissolution profile on 100, 50 & 25 mg tablet. The 100 mg is the subject of an in-vivo biostudy. All the three strength are dose proportional formulation. To claim biowaiver of other two strength we have conducted comparative dissolution profile with the higher strength & have found f2 values above 50 in all 3 media(pH 1.2, 4.5 & 6.8 ) except for pH 4.5 acetate buffer (f2 < 50).
Do we still have a chance to claim biowaiver on the other two lower strength? What is the justification we can use?
According to Guidance for Industry; Dissolution Testing of Immediate Release Solid Oral Dosage Forms, For multiple strengths of IR products with linear kinetics, the bioequivalence study may be performed at the highest strength and waivers of in vivo studies may be granted on lower strengths, based on an adequate dissolution test, provided the lower strengths are proportionately similar in composition (21 CFR 320.22(d)(2)).
Again on page 13 of that guidance, If an appropriate dissolution method has been established (see section III.D.), and the dissolution results indicate that the dissolution characteristics of the product are not dependent on the product strength, then dissolution profiles in one
medium are usually sufficient to support waivers of in vivo testing.Otherwise, dissolution data in three media (pH 1.2, 4.5, and 6.8) are recommended.
Can anyone please interpret the above condition to claim biowaiver for lower strength drug.Thanks in advance.
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Thanks & Best regards
Rajib Kumar Baishnab
Manager, Regulatory Affairs
The ACME Laboratories Ltd.
Dhamrai, Dhaka-1350, Bangladesh
Ph: +8801990-407587
Email: rbaishnab.qo@acmeglobal.com
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