translating the requirements of thermal cycling / excursion guidelines through … ·...
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Translating the Requirements of Thermal
Cycling / Excursion Guidelines Through the
Use of a Comprehensive Risk Management
Matrix for Time and Temperature Sensitive Pharmaceutical Products
Curtis Strother, Senior Technical Services Scientist & Project Manager Alyson Norrick
BioConvergence®
1.) Problem
2.) Risk
3.) Solution
4.) Case
Studies
5.) Benefit
©2011 - Property of BioConvergence LLC 18 May 2011
Review and highlight existing guidance documents that address pharmaceutical
stability and supply chain issues
2
• TRS 953, Annex 2
• TRS 937, Annex 5 World Health Organization
• Q1A(R2) International Conference
on Harmonisation
• <1079> U.S. Pharmacopeia
• Technical Report 39
• Technical Report 46
Parenteral Drug
Association
• Good Practice Guide International Society
Professional Engineers
©2011 - Property of BioConvergence LLC 18 May 2011 3
There is a wealth of available guidance; for some companies there may be a lack of resources to understand and apply it.
The question of how to apply the guidance is a complex one, involving a number of inter-related variables.
18 May 2011 ©2011 - Property of BioConvergence LLC 4
Potential loss of pharmaceutical product
Increased Quality deviations & investigations
Delayed clinical timelines
Compromised clinical data
Compromised efficacy and/or patient safety
©2011 - Property of BioConvergence LLC 18 May 2011 5
18 May 2011 ©2011 - Property of BioConvergence LLC
Parameter Low Risk Medium Risk High Risk
Storage / shipping temperature Ambient 15° to 25°C 2° to 8°C /
Frozen materials
Shipping destination Local, ≤24h
(ground) Contiguous US, >24h
(ground / air / combo) OUS
Type of molecule Raw material / excipient Small molecule Large molecule /
Vaccine
Type of formulation Tablets / capsules Lyophilized product Solution / suspension
Extent of stability data (may include TC/TE data)
Long term & accelerated stability data available
Short term stability data available
No stability data
Relative stability of molecule Stable Moderately stable Not stable
Material's Quality status Non-GMP GMP, pre-clinical GMP, clinical or
commercial
Material's intended use Research Toxicology /
clinical trial distribution Commercial distribution
6
Profile the use of the risk matrix with two different products (“real life” examples)
For each matrix parameter, we will assign a risk rating using scale from 1-20, with 1 being low risk
Summarize the supply chain and stability solutions that we proposed using the matrix
Present the post-matrix result
18 May 2011 ©2011 - Property of BioConvergence LLC 7
18 May 2011 ©2011 - Property of BioConvergence LLC
Parameter Product ABC Risk Rating
Storage / shipping temperature 2° to 8°C 10
Shipping destination Domestic, air & ground 10
Type of molecule Large molecule 10
Type of formulation Parenteral solution 10
Extent of stability data (may include TC/TE data)
Accelerated stability No TC/TE Studies
10
Relative stability of molecule Stable under normal
conditions, aggregates form under sheer force stress
15
Material's Quality status GMP 5
Material's intended use Phase 1 Clinical Trial 20
8
Product ABC ◦ 48 Hr passive shipper
◦ Logistics Services Provider, overnight
◦ Temp monitoring
◦ Temperature Excursion Study
18 May 2011 ©2011 - Property of BioConvergence LLC 9
18 May 2011 ©2011 - Property of BioConvergence LLC
Parameter Product ABC Original Risk Rating Post-Matrix Results
Storage / shipping temperature
2° to 8°C 10 5
Shipping destination Domestic, air &
ground 10 5
Type of molecule Large molecule 10 10
Type of formulation Parenteral solution 10 10
Extent of stability data (may include TC/TE data)
Accelerated stability No TC/TE Studies
10 5
Relative stability of molecule
Stable under normal conditions, aggregates
form under sheer force stress
15 15
Material's Quality status GMP 5 5
Material's intended use Phase 1 Clinical Trial 20 10
10
18 May 2011 ©2011 - Property of BioConvergence LLC
Parameter Product XYZ Risk Rating
Storage / shipping temperature
15° to 25°C
5
Shipping destination OUS 20
Type of molecule Small molecule 5
Type of formulation Lyophilized 10
Extent of stability data (may include TC/TE data)
Accelerated & Limited Long term
10
Relative stability of molecule Moderately stable 5
Material's Quality status GMP 5
Material's intended use
Phase 3 Clinical Trial
20
11
Product XYZ ◦ 72 Hr passive shipper
◦ Clinical Material Freight Forwarder
◦ Temp monitoring
◦ Thermal Cycling/Temperature Excursion Study
18 May 2011 ©2011 - Property of BioConvergence LLC 12
18 May 2011 ©2011 - Property of BioConvergence LLC
Parameter Product XYZ Risk Rating Post-Matrix Results
Storage / shipping temperature
15° to 25°C 5 1
Shipping destination OUS 20 5
Type of molecule Small molecule 5 5
Type of formulation Lyophilized 10 10
Extent of stability data (may include TC/TE data)
Accelerated & Limited Long term
10 5
Relative stability of molecule Moderately stable 5 5
Material's Quality status GMP 5 5
Material's intended use Phase 3 Clinical Trial 20 5
13
More predictable cost of developing a transportation control strategy
More predictable product availability
Clinical study/data/timeline minimally affected by temperature excursion issues
Increased patient safety
©2011 - Property of BioConvergence LLC 18 May 2011 14
Aug-2009, FDA Warning Letter to a clinical study sponsor, related to Temperature Excursion study
Proper risk management can ensure that your project will not become a statistic such as this
◦ The Risk Matrix is a new tool
◦ Has been in use since Q3 2010
◦ Currently in use at BioC with Supply Chain clients
◦ Scope of the matrix could be expanded to include formulation development
©2011 - Property of BioConvergence LLC 18 May 2011 15
QUESTIONS?
©2011 - Property of BioConvergence LLC 18 May 2011 16
Curtis Strother
+1 812 961 1751
curtis.strother@bioc.us
For additional information:
www.bioc.us/2011MHSCC
©2011 - Property of BioConvergence LLC 18 May 2011 17
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