Use of IVIVC Data to Support Biowaiver - PQRI

Use of IVIVC Data to Support
Biowaiver
Group E
Jim Polli

Topics
• Biowaiver opportunities
• IVIVC vs IVIVR
• Clarifying topics

Biowaiver opportunities
• 2003 BE/BE guidance
– IR requires
• Biostrength acceptable (e.g. BE shown for high strength)
• Formulations proportionally similar
• Acceptable dissolution testing (e.g. e.g. F2 OK using
compendial method)
– MR requires [Note: ANDA for MR not use biowaiver as
a term (legal issue)]
• As above, but three different pH media and compendial
media
– Previously for MR
• BE for all strengths
• BE in multiple dose testing

Biowaiver opportunities
• NDAs and ANDAs
– SUPAC IR, SUPAC MR, and IVIVC MR (plus other dosage
forms)
• Biowaivers for ANDAs using IVIVC
– Any level 3 SUPAC MR (not IR)
– Change dissolution specs
• 505b(2)
– Lower strengths
• > 10X dose range possible if IVIVC
– Plus/minus external validation
– Versus rule of at most 3-4 strengths max

IVIVC vs IVIVR
• IVIVC = FDA level A method
– Biowaiver-focused
• IVIVR = method other than FDA level A
– Not biowaiver-focused
• In some firms, need POC before do IVIVC
• Do (a little more) earlier
• Not BE, ask why.
• Formulation-driven

IVIVC vs IVIVR
• FDA level A method (#1 use) [from n=24
votes]
– QbD 0 votes
– Diss spec justification 1 vote
– Biowaivers 23 votes
• IVIVR (#1 use) [from n=24 votes]
– QbD 23 votes
– Diss spec justification 1 vote
– Biowaivers 0 votes
Time-dependent, $ issue, product-specific

Clarifying topics
• Nomenclature and methods
– Sandra Suarez-Sharp’s slides
• Level A vs non-Level A
• Convolution-base vs deconvolution-based
• Slope
• Rank-order
– Mean vs ind
• QbD design space vs SUPAC vs IVIVC