translating the requirements of thermal cycling / excursion guidelines through … ·...

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


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



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


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



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


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


Parameter Product XYZ Risk Rating


15° to 25°C

5

Shipping destination OUS 20

Type of molecule Small molecule 5

Type of formulation Lyophilized 10


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



Parameter Product XYZ Risk Rating Post-Matrix Results


15° to 25°C 5 1

Shipping destination OUS 20 5

Type of molecule Small molecule 5 5

Type of formulation Lyophilized 10 10


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


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


QUESTIONS?


Curtis Strother

+1 812 961 1751

[email protected]

For additional information:

www.bioc.us/2011MHSCC


mailto:[email protected]

http://www.bioc.us/2011MHSCC

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