1. Quality /
Compliance
Supply
Reliability
Cost /
Cash /
Value
Compromise to quality and compliance is not an option
A peek into lyophilization
at Pfizer
Jim Searles, Ph.D.
Technical Fellow
Global Technology Services, Pfizer Global Supply
Pfizer CentreOne Symposium, AAPS National Meeting, Denver, CO 15 Nov 2016

2. • Pfizer Lyo Network overview
• A new mechanism for vial breakage elucidated using
strain gauges
2
Outline

3.  The main goal is to deliver business value in
freeze-drying
– Support process transfer and optimization
– Develop and implement cost-sparing and process
enabling PAT tools, formulations, and freeze-drying
alternatives
– Provide high-value training
– Enhance communications across the Network
• Company-wide including R&D as well as
manufacturing globally
3
Pfizer Lyo Network charter

4. Over 270 colleagues
 United States – Andover, Collegeville, Groton, Kalamazoo, McPherson,
Pearl River, Peapack, San Diego, Sanford, St. Louis, Lake Forest
 Australia – Melbourne
 Belgium - Puurs
 Canada - Montreal
 China – Wuxi, Hsinchu,
 India – Chennai, Vizag, Ahmedabad
 Ireland – Grange Castle
 Italy – Catania, Liscate
 Spain – Algete
 United Kingdom – Sandwich
4
Where are PLN colleagues located?

5. • Monthly seminar (anyone can listen/watch, speakers can
be from anywhere)
• Subteams
• Email forum
• Best practices
• Problem solving
• Advanced technologies
• LyoSchool
• Bridge R&D and MFG
5
Major activities

6.  Contributions to:
− Lyo Hub (Lyo Consortium):
 Develop a technology roadmap – activity initiated with
industry, FDA, and academia colleagues
 Draft a Best practices document on process instrumentation
− BioPhorum (LyoPAT team) – Implement current technologies
(PAT tools implementation, Modeling in process design and
scale up)
6
External memberships and
conference contributions

7.  Conferences
− AAPS National Meeting
− AAPS National Biotechnology Conference
− Freeze-Drying of Pharmaceuticals and Biologicals (Breckenridge
and Garmisch)
− CHI PepTalk
− CHI Bioprocessing Summit
− ECA Lyophilization Conference
− ISL-FD
− PDA Europe
− SMi Lyophilization USA Conference
− SP Scientific Webinar Series
7
External memberships and
conference contributions

8. Quality /
Compliance
Supply
Reliability
Cost /
Cash /
Value
Compromise to quality and compliance is not an option
Elucidating vial breakage
mechanisms during lyo cycle
optimization using strain gauges
Jim Searles, Ekneet Sahni and Dina Lyne
Global Technical Services, Pfizer Global Supply, McPherson, KS
8

9. • Problem: Extensive vial breakage while attempting to
optimize a lyo cycle
• Approach: Implement strain gauges in the lab to confirm
the breakage mechanism
• Published works:
– Craig et al. (2004 presentation): Strain gauges during
lyophilization (first published/presented work)
– Milton et al. (2007): Strain due to crystallization of NaCl
– Jiang et al. (2007a):Strain due to mannitol crystallization
– Jiang et al. (2007b): Strain due to “break-free” event during
freezing
9
Background

10. 10
Example Lyo Cycle
Pressure(mTorr)
Temperature(C)
Time
SHELF INLET T
SHELF_SP
TC04
TC05
TC06
TC07
TC08
CHAMBER_CM
CHAMBER PIRANI
CONDENSER P
VACUUM_SP
Sridhar Aravapalli

11. 11
Extreme Breakage
0
5
10
15
20
25
30
35
40
45
50
-30 -25 -20 -15 -10 -5 0
#BrokenVials(50totalperrun)
Product Temperature Early in Primary Drying (C)
Thinner Vials, Processed
Thicker Vials, Processed
Thinner Vials, Not Processed
with Mark Nachtigall

12. • Stress (σ) = Force/ Area (units of pressure)
• Strain (Ɛ)= Dimension Change/Original Dimensions
(dimensionless)
12
Strain vs. Stress
Pfizer Confidential. For Internal Use Only.

13. Strain gauge
Strain gauges purchased from Micro Measurements and Kyowa. Instrument
purchased from Micro Measurements

14. Freeze Thaw: 0.1 C/min to -45 ⁰C,
3 breakages

15. Freeze Thaw ̶ Comparison of Horiz SG for
freezing temps: 0.1 C/min, -25 ⁰C and -45 ⁰C

16. • Strain gauged vials can be used in development of
formulations and process cycles to insure acceptably low
levels of strain and reduce or eliminate vial breakage.
• Strain gauged vials are useful for troubleshooting and
remediation of manufacturing issues.
• For this product, vial breakage occurred during re-
warming, not freezing.
Conclusions

17. • Hirakura Y, Kojima S, Okada A, Yokohama S, Yokota S. (2004) Int J Pharm
286:53–67.
• Gordon D. Craig, Mark Moreno, Dinesh Mishra, Nathaniel Milton, Michael
Roy, Lian Yu (2004) Presentation at Breckenridge Protein Stability
Conference, Breckenridge, CO, July 28 – 31
• Milton, N., Gopalrathnam, G., Craig, G.D., Mishra, D.S., Roy, M.L. and Yu,
L. (2007) J. Pharm. Sci., 96: 1848–1853.
• Ge Jiang, Mike Akers, Manish Jain, Jeremy Guo, Adrian Distler, Rob Swift,
Manpreet-Vick S. Wadhwa, Feroz Jameel, Sugu Patro, and Erwin Freund
(2007a) PDA J Pharm Sci Technol 61:441-451
• Ge Jiang, Mike Akers, Manish Jain, Jeremy Guo, Adrian Distler, Rob Swift,
Manpreet-Vick S. Wadhwa, Feroz Jameel, Sugu Patro, and Erwin Freund
(2007b) PDA J Pharm Sci Technol 61:452-460
17
References