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PQRI Update

ForDrug and Pharmaceutical Packaging

Committee MeetingJune 13, 2011

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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 Chris Moreton, FinnBrit

Hugh Lockhart, MSU Rey Chern, Merck

Yisheng Chen, Novast Desmond Hunt, USP

Randy Glenn, sanofi-aventis Rich Hollander, Pfizer

R. Forster, Amgen John Bitner, Watson

Vicki Penn, PQRI

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Product Quality Research InstituteMember 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

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January 2001DPTC 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

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December 2001Meeting 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 2001Meeting 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

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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 VaporTransmission Rate per Unit Product inthe Evaluation of Moisture-BarrierEquivalence of Primary Packages forSolid Oral Dosage Forms”

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Jan-Feb 2005 (Slide 2 of 3)

Three points made in the paper1. MVTR/unit is the critical parameter for

equivalence2. 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

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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

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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 WVTR

mg/day

S.D.

mg/day

C.V.

%

Bottle Intct 1.21 0.03 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?