PQRI Update

1. PQRI Update For Drug and Pharmaceutical Packaging Committee Meeting June 13, 2011

2. 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

3. 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

4. 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

5. 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:

6. 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

7. 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

8. 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

9. 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.

10. 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”

11. Jan-Feb 2005 (Slide 2 of 3) Three points made in the paper • MVTR/unit is the critical parameter for equivalence • 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

12. 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.

13. 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

14. March, 2007 Research report published internally: Statistical Summary of HDPE Container MVTR Measurements for Screening Study Edited for 2010 publication on PQRI web site

15. December 2009 Research Report published internally: Statistical Summary of WVTR Measurements – Blister Screening Study Edited for 2010 publication on PQRI web site

16. 2010 – 3 research reports posted on PQRI web site • “Determination of Water Vapor Transmission Rate for High Density Polyethylene Screw-cap Bottles” • “Determination of Water Vapor Transmission Rates for Various High Barrier Blister Packs” • “Protocol for HDPE Container MVTR Measurement (DOC)”

17. 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

18. 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

19. 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

20. 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

21. Sensitivity and Variation

22. 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

23. 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

24. Thank You Questions?