Hi Tom,
Sharing my thoughts to your questions below:
- Does this strategy make sense? - In general yes - is this a generic product and are there any literature around BCS class ? If a generic then check FDA website for BE study recommendation and dissolution method.
- Do we also need stability data on one batch of the 10mg even though bracketed by 5 an 15mg? Yes I would suggest inc 1x10mg bx
- Do you agree no BE/BA studies required? Depending on strength of dataset & position may be requested to perform BE on highest 20mg strength
- Do we need to submit solubility and/or permeability data to support BCS Class 1? Absolutely - see recent US guideline (also EU/Canadian/ICH guidance available)
"Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System Guidance for Industry"
Is dissolution profile comparison needed or is single point testing (85% in 30 min) adequate since BCS Class 1? Profile required in QC dissolution method as well as using multi-pH media as follows;
(1) 0.1 N HCl or Simulated Gastric Fluid USP without enzymes; (2) a pH 4.5 buffer; and (3) a pH 6.8 buffer or Simulated Intestinal Fluid USP without enzymes
I'm suggesting we submit this strategy proposal to FDA CMC reviewer in advance to get FDA agreement. Agree? Yes - also I believe there may be some form of FDA BCS committee that can assess categorisation
Hope the above helps.
regards,
Roy
------------------------------
Roy Jamieson
Regulatory CMC Director
AZ Gothenburg, Sweden
------------------------------
Original Message:
Sent: 31-May-2018 17:29
From: Tom Stothoff
Subject: Addition of new tablet strengths
Hoping to receive feedback on the following scenario and strategy.
We currently have approval for 5mg and 15mg IR tablets (round with white film coat). We are planning to file a sNDA to add 10mg and 20mg strengths (oval with blue film coat). All four strengths utilize common granulation so all excipients are dose proportional. Only difference is the coatings which are same w/w%. The 20mg dose was tested in clinical trials using 2 x 10mg tabs. We believe this compound is BCS Class 1 (high solubility/high permeability) but haven't submitted anything to get formal classification as BCS Class 1.
Plan is to submit a Prior Approval Supplement to include the following:
- 3M real time and accelerated stability data on one batch of 20mg. The 10mg is bracketed by the approved 5 and 15mg so need for stability data on 10mg.
- Dissolution profile comparison data comparing the new 10 and 20mg to the approved 15 mg
- Biowaiver for BE studies since BCS Class 1.
Questions:
- Does this strategy make sense?
- Do we also need stability data on one batch of the 10mg even though bracketed by 5 an 15mg?
- Do you agree no BE/BA studies required?
- Do we need to submit solubility and/or permeability data to support BCS Class 1?
- Is dissolution profile comparison needed or is single point testing (85% in 30 min) adequate since BCS Class 1?
- I'm suggesting we submit this strategy proposal to FDA CMC reviewer in advance to get FDA agreement. Agree?
Thank you.
Tom
Chicago