Demonstrating Bioequivalence of Locally Acting Orally Inhaled Drug Products (OIPs): Workshop Summary Report.
This March 2009 Workshop Summary Report was sponsored by Product Quality Research Institute (PQRI) based on a proposal by the Inhalation and Nasal Technology Focus Group (INTFG) of the American Association of Pharmaceutical Scientists (AAPS). Participants from the pharmaceutical industry, academia and regulatory bodies from the United States, Europe, India, and Brazil attended the workshop with the objective of presenting, reviewing, and discussing recommendations for demonstrating bioequivalence (BE) that may be considered in the development of orally inhaled drug products and regulatory guidances for new drug applications (NDAs), abbreviated NDAs (ANDAs), and postapproval changes. The workshop addressed areas related to in vitro approaches to demonstrating BE, biomarker strategies, imaging techniques, in vivo approaches to establishing local delivery equivalence and device design similarity. The workshop presented material that provided a baseline for the current understanding of orally inhaled drug products (OIPs) and identified gaps in knowledge and consensus that, if answered, might allow the design of a robust, streamlined method for the BE assessment of locally acting inhalation drugs. These included the following: (1) cascade impactor (CI) studies are not a good 2 predictor of the pulmonary dose; more detailed studies on in vitro/in vivo correlations (e.g., suitability of CI studies for assessing differences in the regional deposition) are needed; (2) there is a lack of consensus on the appropriate statistical methods for assessing in vitro results; (3) fully validated and standardized imaging methods, while capable of providing information on pulmonary dose and regional deposition, might not be applicable to the BE of inhaled products mainly due to the problems of having access to radiolabeled innovator product; (4) if alternatives to current methods for establishing local delivery BE of OIPs cannot be established, biomarkers (pharmacodynamic or clinical endpoints) with a sufficiently steep dose-response need to be identified and validated for all relevant drug classes; and (5) the utility of pharmacokinetic studies for evaluating "local pulmonary delivery" equivalence deserves more attention. A summary of action items for seminars and working groups to address these topics in the future is also presented.
Food and Drug Administration, Center for Drug Evaluation and Research , Office of Pharmaceutical Science, Office of Generic Drugs, Rockville, Maryland, USA.
Wallace P
WP
Adams
Richard C
RC
Ahrens
Mei-Ling
ML
Chen
David
D
Christopher
Badrul A
BA
Chowdhury
Dale P
DP
Conner
Richard
R
Dalby
Kevin
K
Fitzgerald
Leslie
L
Hendeles
Anthony J
AJ
Hickey
Günther
G
Hochhaus
Beth L
BL
Laube
Paul
P
Lucas
Sau L
SL
Lee
Svetlana
S
Lyapustina
Bing
B
Li
Dennis
D
O'Connor
Neil
N
Parikh
David A
DA
Parkins
Prasad
P
Peri
Gary R
GR
Pitcairn
Michael
M
Riebe
Partha
P
Roy
Tushar
T
Shah
Gur Jai Pal
GJ
Singh
Sandra Suarez
SS
Sharp
Julie D
JD
Suman
Marjolein
M
Weda
Janet
J
Woodcock
Lawrence
L
Yu
D000280:Administration, Inhalation; D000284:Administration, Oral; D000336:Aerosols / Q000493:pharmacokinetics*; D006801:Humans; D013810:Therapeutic Equivalency
D000336:Aerosols