Understanding and Reducing Analytical Error - Why Good Science Requires Operational Excellence

John McConnell, Brian K.
Nunnally, and Bernard McGarvey
Understanding and Reducing

Analytical Error
Why Good Science Requires
Operational Excellence
John McConnell, Brian K. Nunnally, and Bernard McGarvey
Analysis and Control of Variation is dedicated to

revealing weaknesses in existing approaches to understanding, reducing, and controlling variation and to
recommend alternatives that are not only based on
sound science but also that demonstrably work. Case
studies will be used to illustrate both problems and
successful methodologies. The objective of the column is to combine sound science with proven practical
advice.
Reader comments, questions, and suggestions will
help us fulfil our objective for this column. Case studies
illustrating the successful reduction or control of variation submitted by readers are most welcome. We need
your help to make Analysis and Control of Variation
a useful resource. Please send your comments and
suggestions to column coordinator John McConnell at
john@wysowl.com.au or journal coordinating editor
Susan Haigney at shaigney@advanstar.com.
KEY POINTS DISCUSSED

The following key points are discussed:
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data.
For more Author

information,
go to
gxpandjvt.com/bios
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presented.
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causal relationships in other areas.
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greatest.
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results in easier detection of causal relation
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ABOUT THE AUTHORS

John McConnell is owner and director at Wysowl Pty Ltd in Queensland, Australia. He may be
reached at john@wysowl.com.au. Brian K. Nunnally, Ph.D., is in charge of process validation
at Pfizer in Sanford, NC. He may be reached at brian.nunnally@pfizer.com. Bernard McGarvey,
Ph.D., is process modelling group leader, Process Engineering Center at Eli Lilly and Company in Indianapolis, IN. He may be reached at mcgarvey_bernard@lilly.com.
PROCESS VALIDATION Continued Process Verification
INTRODUCTION
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unchanged. It is the conduct of operations that has
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GOOD SCIENCE REQUIRES GOOD

OPERATIONS
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Some Actual Examples

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of the chart. There is no change in the science
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This is a critical understanding if we are to do
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79

Figure 1: Results of a plant trial to reduce variation.
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WHAT SHOULD BE THE INITIAL AIM?

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Polio Vaccine Clinical Supplies

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Figure 2: Reduced variation in analytical error.
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Shewhart and Deming

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81

Figure 3: Before and after results of a steady-state trial (sst).
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when in fact there exists a real difference in perfor
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82 PROCESS VALIDATION Continued Process Verification
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science.
THE FIRST PRINCIPLE

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Figure 4: The first principle; stabilize first.
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lifting a fog that hitherto had concealed the truth
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the clinic.
BIOLOGICAL ASSAYS
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controls are a good place to start.
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CONCLUSION
*OQBSU UIF'%"Guidance for Industry-Process Validation: General Principles and Practices
TUBUFT
We recommend that a statistician or person
with adequate training in statistical process control
techniques develop the data collection plan and statistical methods and procedures used in measuring
and evaluating process stability and process capability. Procedures should describe how trending and
calculations are to be performed and should guard
against overreaction to individual events as well as
against failure to detect unintended process variability. Production data should be collected to evaluate
process stability and capability. The quality unit
should review this information. If properly carried
out, these efforts can identify variability in the process and/or signal potential process improvements.
83

Figure 5: Unstable laboratory controls (for biologics).
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we understand that trying to do good science in an
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REFERENCES
+.D$POOFMM #/VOOBMMZBOE#.D(BSWFZ i#MBNFUIF
-BCPSBUPSZ6OEFSTUBOEJOH"OBMZUJDBM&SSPS wJournal of
Validation Technology 7PMVNF /VNCFS 4VNNFS
#,/VOOBMMZBOE+4.D$POOFMM Six Sigma in the
Pharmaceutical Industry $3$1SFTT
1"0GGJU The Cutter Incident :BMF6OJWFSTJUZ1SFTT

8"4IFXIBSU Economic Control of Quality of Manufactured Product 7BO/PTUSBOE
8&EXBSET%FNJOH i0O4PNF4UBUJTUJDBM"JET5PXBSE&DP
OPNJD1SPEVDUJPO wInterfaces 7PM /P "VHVTU
+.D$POOFMM #/VOOBMMZBOE#.D(BSWFZ 5IF%PT
"OE%POUTPG$POUSPM$IBSUJOH1BSU Journal of Validation Technology 7PMVNF /VNCFS 8JOUFS
'%" Guidance for Industry-Process Validation: General
Principles and Practices +BOVBSZ JVT
0SJHJOBMMZQVCMJTIFEJOUIF8JOUFSJTTVFPGThe Journal of Validation Technology
84

Understanding and Reducing Analytical Error - Why Good Science Requires Operational Excellence

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Understanding and Reducing Analytical Error - Why Good Science Requires Operational Excellence

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Droits d'auteur :

Formats disponibles

John McConnell, Brian K.

Nunnally, and Bernard McGarvey

Understanding and Reducing

Analysis and Control of Variation is dedicated to

KEY POINTS DISCUSSED

For more Author

ABOUT THE AUTHORS

PROCESS VALIDATION Continued Process Verification

John McConnell, Brian K. Nunnally, and Bernard McGarvey

GOOD SCIENCE REQUIRES GOOD

Some Actual Examples

John McConnell, Brian K. Nunnally, and Bernard McGarvey

PROCESS VALIDATION Continued Process Verification

WHAT SHOULD BE THE INITIAL AIM?

Polio Vaccine Clinical Supplies

John McConnell, Brian K. Nunnally, and Bernard McGarvey

Shewhart and Deming

PROCESS VALIDATION Continued Process Verification

John McConnell, Brian K. Nunnally, and Bernard McGarvey

THE FIRST PRINCIPLE

John McConnell, Brian K. Nunnally, and Bernard McGarvey

John McConnell, Brian K. Nunnally, and Bernard McGarvey

0SJHJOBMMZQVCMJTIFEJOUIF8JOUFSJTTVFPGThe Journal of Validation Technology

PROCESS VALIDATION Continued Process Verification

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0SJHJOBMMZQVCMJTIFEJOUIF8JOUFSJTTVFPGThe Journal of Validation Technology