Biopharmaceutics classification system: the scientific basis for biowaiver extensions.
The current BSC guidance issued by the FDA allows for biowaivers based on conservative criteria. Possible new criteria and class boundaries are proposed for additional biowaivers based on the underlying physiology of the gastrointestinal tract. The proposed changes in new class boundaries for solubility and permeability are as follows: 1. Narrow the required solubility pH range from 1.0-7.5 to 1.0-6.8. 2. Reduce the high permeability requirement from 90% to 85%. The following new criterion and potential biowaiver extension require more research: 1. Define a new intermediate permeability class boundary. 2. Allow biowaivers for highly soluble and intermediately permeable drugs in IR solid oral dosage forms with no less than 85% dissolved in 15 min in all physiologically relevant dissolution media, provided these IR products contain only known excipients that do not affect the oral drug absorption. The following areas require more extensive research: 1. Increase the dose volume for solubility classification to 500 mL. 2. Include bile salt in the solubility measurement. 3. Use the intrinsic dissolution method for solubility classification. 4. Define an intermediate solubility class for BCS Class II drugs. 5. Include surfactants in in vitro dissolution testing.
Yu
Lawrence X
LX
Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Science, Rockville, Maryland 20857, USA. yul@cder.fda.gov
Amidon
Gordon L
GL
Polli
James E
JE
Zhao
Hong
H
Mehta
Mehul U
MU
Conner
Dale P
DP
Shah
Vinod P
VP
Lesko
Lawrence J
LJ
Chen
Mei-Ling
ML
Lee
Vincent H L
VH
Hussain
Ajaz S
AS
D001702:Biopharmaceutics / Q000145:classification* / Q000331:legislation & jurisprudence*; D017277:Drug Approval / Q000331:legislation & jurisprudence; D010539:Permeability; D012995:Solubility; D013810:Therapeutic Equivalency; D014481:United States
Non-programmatic