Scientific considerations of pharmaceutical solid polymorphism in abbreviated new drug applications.
OBJECTIVE
This commentary is intended to provide a scientific perspective on pharmaceutical solid polymorphism in Abbreviated New Drug Applications (ANDAs).


METHODS
This report proposes recommendations for monitoring and controlling drug substance polymorphs and describes scientific considerations of pharmaceutical solid polymorphism in the determination of drug substance sameness.


RESULTS
It presents three decision trees for solid oral dosage forms or liquids containing undissolved drug substances to provide a process for evaluating when and how polymorphs of drug substances are monitored and controlled in ANDA submissions.


CONCLUSIONS
It is scientifically concluded that differences in polymorphic composition of drug substances in generic drug products and reference-listed drugs are not directly relevant in the determination of drug substance sameness in ANDAs.
Food and Drug Administration, Center for Drug Evaluation and Research, Office of Generic Drugs, Rockville, Maryland 20855, USA. yul@cder.fda.gov
Lawrence X
LX
Yu
M Scott
MS
Furness
Andre
A
Raw
Kathy P Woodland
KP
Outlaw
Nashed E
NE
Nashed
Edwin
E
Ramos
Stephen P F
SP
Miller
Richard C
RC
Adams
Florence
F
Fang
Rashmikant M
RM
Patel
Frank O
FO
Holcombe
Yuan-yuan
YY
Chiu
Ajaz S
AS
Hussain
D002626:Chemistry, Pharmaceutical; D003663:Decision Trees; D017277:Drug Approval / Q000379:methods*; D013678:Technology, Pharmaceutical; D014481:United States; D014486:United States Food and Drug Administration