PQRI Update
For
Drug and Pharmaceutical Packaging
Committee Meeting
June 13, 2011
1
Product Quality Research Institute
(PQRI)
• Board of Directors
Steering Committee
Drug Product Technical Committee (DPTC)
Container Closure Working Group (CCWG)
Dan Malinowski, Pfizer
Dennis O’Reilly, GSK
Jim Bergum, BMS
Hugh Lockhart, MSU
Yisheng Chen, Novast
Randy Glenn, sanofi-aventis
R. Forster, Amgen
Vicki Penn, PQRI
Chris Moreton, FinnBrit
Rey Chern, Merck
Desmond Hunt, USP
Rich Hollander, Pfizer
John Bitner, Watson
2
Product Quality Research Institute
Member Organizations
• AAPS - American Association of Pharmaceutical
Scientists
• CHPA – Consumer Healthcare Products Association
• FDA/CDER – Food and Drug Administration/Center for
Drug Evaluation and Research
• HC – Health Canada
• IPAC- RS - International Pharmaceutical Aerosol
Consortium on Regulation & Science
• IPEC–Americas – International Pharmaceutical
Excipients Council of the Americas
• USP – United States Pharmacopeia
3
January 2001
DPTC to CCWG
Find a way to avoid unnecessary stability
testing if the water uptake of a new package
is the same as or better than the existing
package.
Testing to be carried out at 40o C/75% RH
and at RT/60% RH
4
December 2001
Meeting of CCWG
• Focus on supporting Post Approval
Packaging Change (PACPAC)
• Create a definition of “equivalence” for
container closure systems
• Focus on Solid Oral Dosage forms (80%
of marketed drug products)
• Formed 4 committees to review:
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December 2001
Meeting of CCWG
• Four committees to review:
Definitions of equivalence
Test methods for WVTR
Test methods for light transmission - dropped
Test methods for seal integrity - dropped
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December 2002
CCWG established five research objectives
• Establish clear definition of “equivalence”
• Develop a method of test; accuracy and
sensitivity of current USP <671> are
questionable
• Achieve differentiation among high barrier
packages
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December 2002 (Continued)
Research objectives (continued)
• Utilize WVTR/unit – problem with volume
for bottles vs dosage unit for blisters
This one became first priority
• Define when, during testing, WVTR steady
state is reached
8
December 2002: Decision Made
•
to design an experiment that would meet
the five research objectives.
– Data mining was not working.
•
•
Began DOE for bottle and blister WVTR.
WVTR/unit remains first priority.
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Jan-Feb 2005 (Slide 1 of 3)
Published in Pharmacopeial Forum, vol
31(1)
“Basis for Using Moisture Vapor
Transmission Rate per Unit Product in
the Evaluation of Moisture-Barrier
Equivalence of Primary Packages for
Solid Oral Dosage Forms”
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Jan-Feb 2005 (Slide 2 of 3)
Three points made in the paper
1. MVTR/unit is the critical parameter for
equivalence
2. Once an equivalent range is
established by stability test and
MVTR/unit, then a substitute barrier
package is an equivalent barrier if the
MVTR/unit is within the qualified
range
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Jan-Feb 2005 (Slide 3 of 3)
Three points made in the paper
3. A method with increased sensitivity is
required in order to satisfy point 2.
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September, 2006
• PQRI bottle protocol finalized.
• Experiment under way in four
laboratories to measure WVTR of bottles
and blisters
• DOE included measure of variation within
lab and between lab
13
March, 2007
Research report published internally:
Statistical Summary of HDPE Container
MVTR Measurements for Screening
Study
Edited for 2010 publication on PQRI web
site
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December 2009
Research Report published internally:
Statistical Summary of WVTR
Measurements – Blister Screening Study
Edited for 2010 publication on PQRI web
site
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2010 – 3 research reports posted
on PQRI web site
1. “Determination of Water Vapor
Transmission Rate for High Density
Polyethylene Screw-cap Bottles”
2. “Determination of Water Vapor
Transmission Rates for Various High
Barrier Blister Packs”
3. “Protocol for HDPE Container MVTR
Measurement (DOC)”
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To Obtain the Reports
•
•
•
•
Go to the web site at www.pqri.org
Click on PQRI Structure
Click on Working Groups
Click on Container Closure Systems
– In the Additional Material section, click on the
title of each report
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May, 2011
Published ASTM Standard D7709-11,
“Standard Test Methods for Measuring
Water Vapor Transmission Rate
(WVTR) of Pharmaceutical Bottles and
Blisters”
Available from ASTM International
(www.astm.org) at a cost of $39
18
To Purchase a Copy of D7709
• Go to the ASTM web site www.astm.org
– You get the home page
• Enter D7709 in the search window
– You get a page showing title, price ($39) and
the “Significance and Use” and “Scope”
sections of the method
– Instructions for completing the purchase are
included there
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Some Features of D7709
•
•
•
•
•
•
Test conditions: 40o C/75% RH
Blanks: None used
Length of test: 35 days
Weighing Interval: 7 days
Steady state: 5 data points
Analytical method: Regression
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Sensitivity and Variation
Container
Bottle Intct
WVTR
mg/day
1.21
S.D.
mg/day
0.03
C.V.
%
2.7
Bottle Bchd
8.18
0.98
12
PVC blist
3.06
0.106
3.5
PVdC blist
0.83
0.044
5.4
Aclar/PVC
0.14
0.0066
4.6
Foil/foil
0.004
0.0060
146
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June 7, 2011 Meeting of CCWG
1. Started planning to publish an article to
summarize and publicize:
(a) WVTR/unit concept
(b) bottle and blister studies
(c) ASTM Method
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June 7, 2011 Meeting of CCWG
(Continued)
(d) how to apply these concepts and
methods to reduce regulatory burden
for changes to container closure
systems.
We will publish in a scientific journal and a
trade journal
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Thank You
Questions?
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