On Demand Webinar Slides Ensuring USP Compliance en
On Demand Webinar Slides Ensuring USP Compliance en
Webinar
Speakers
Moderator:
Patricia Van Arnum
Executive Editor
Pharmaceutical Technology
Speakers:
"Recent Revisions to USP Chapters <41> and <1251>"
Gregory Martin
President, Complectors Consulting
Chair of the USP Expert Panel on Balances
"Practical Guidance on how to Achieve USP & GMP Compliance"
Martin Huber, Ph.D
Good Weighing Practice Competence Center
Mettler-Toledo AG
"Introducing Gravimetric Sample Preparation"
Joanne Ratcliff, Ph.D
Laboratory Weighing
Mettler-Toledo AG
Gregory P. Martin
President, Complectors Consulting
[email protected]
484-942-3200
Chapter <41>
Chapter <1251>
Major overhaul
Focus on Qualification and Operation
Chapter <41>
Chapter <1251>
Scope
Requirements
Is 2 x s / m < 0.10 % ?
Where:
2 = k, coverage factor
s = standard deviation of not less than 10
determinations
m = desired smallest net weight
Example:
s = 0.007 mg, m = 20 mg
2 x 0.007 / 20 x 100 = 0.07%, which is < 0.10%
Balance is suitable for weighing 20 mg
Summary of Changes
Major overhaul
Focus on Qualification and Operation
Qualification
IQ, OQ, PQ
Balance checks, minimum weight
Operation
Receivers
Types of weighing
Problem Samples
10
Air currents
the buildup of static electricity
Excessive temperature variations
Humidity extremes (very low or very high)
Adjacent operations cause vibration
The balance is located within a fume hood or near corrosive
materials
The balance is adjacent to equipment that produces a
magnetic field (e.g. a magnetic stirrer)
Direct sunlight strikes the balance
12
13
Property
Examples
Acceptance
Criteria*
Sensitivity
NMT 0.05%
deviation
Linearity
NMT 0.05%
deviation
14
min
m min = 2000 s
16
Receivers
Types of Weighing
17
Problem Samples
Electrically charged samples and receivers (static electricity)
Volatile samples
Warm or cool samples
Hygroscopic samples
Aseptic or biohazardous samples
Air flow within the biosafety cabinet, isolator or similar device potentially
can cause balance instability
After the balance has been installed under a hood, a rigorous qualification
should be performed to assess balance performance in this environment
Safety Considerations
Analysts may be exposed to high concentrations of materials
which may be toxic or allergenic during the weighing process
18
Practical Guidance on
how to Achieve USP & GMP Compliance
Dr. Martin Huber
Good Weighing Practice
Competence Center
Mettler-Toledo AG
3.
Minimum Weight
GC <41> "Balances"
Requirements
22
23
24
25
2 s
m
0.10%
m = desired smallest
net weight
0.10%
2
27
CL
Accuracy:
5% mTW 100%
mTW = mass of test weight
CarePac
Weights for
Routine Testing
Sensitivity
Non-linearity
"Systematic
Error"
~ USP <41>
"Accuracy"
Eccentricity
Repeatability
"Random Error"
"Table 1 provides a list of the most important balance properties that should be
assessed during performance qualification.
Depending on the risk of the application and the required weighing process
tolerance, some of these tests may be omitted."
30
0.1
U_tot
U_RP
U_EC
U_NL
U_SE
0.01
0.001
0.0001
0.00001
0.01
0.1
10
100
1000
Nonlinearity
Not dominant with samples of small mass; generally not
dominant throughout the entire sample mass range
Calibration
U=(
)
Simplified formula
34
Measurement uncertainty [g or %]
U = U0 + C x l
Weight [g or kg]
Max.
35
Weight [g or kg]
Max.
Minimum weight
37
0.10%
Impact
39
40
mmin
k s
required weighing tolerance
42
"The performance of the balance and thus the minimum weight can vary over
time because of changing environmental conditions []
For these reasons, when possible, weighings should be made at larger values
than the minimum weight."
USP newly stipulates the application of a "safety factor".
43
SAFETY
FACTOR
e.g. 30 mg
adjustment
(by service)
21 mg
16mg
Minimum weight
determined
14 mg
calibration period
calibration period
time
Calibration
at Installation
As-found
calibration
44
As-left
calibration
3.
Minimum Weight
Scientific, risk-based
methodology
Applicable to all
weighing equipment
of any manufacturer
47
52
53
54
Manual /Volumetric
Automated /Gravimetric
Manual /Volumetric
Automated /Gravimetric
Published accuracy/tolerance
Amount of diluent
calculated automatically
Labels printed
automatically
Eliminates selection of
Eliminates manual
Eliminates data
calculation errors
transcription errors
QB5
Automated system: 6 mg
Safety factor of 1.5 9 mg
Max
1
AmountofSolid
(mg)
100
100
0.8
AmountofSolvent
(mLorg)
80
0.6
60
50
0.4
40
0.2
18
20
9
2.1
4.2
0
0
ManualVolumetric
(MW14mg)
QuantosQB5
(MW6mg)
QuantosQX7
(MW1.4mg)
59
Quantos QX7
120%
100%
AmountofSolid
(mg)
80
80%
AmountofSolvent
(mLorg)
60
60%
Substancesavings
(%)
100
100
96%
82%
50
40
40%
18
20
20%
0%
2.1
4.2
0%
ManualVolumetric
(MW14mg)
QuantosQB5
(MW6mg)
QuantosQX7
(MW1.4mg)
Quantos QX7
Method:
Results:
Method
Solid
amount
Diluent
amount
Time
Precision
(% RSD)
Manual
Volumetric
20 mg
50 mL
35 mins operator
(50 mins total)
1.67%
Automated
Gravimetric
5 mg
12.5 g
10 mins operator
(30 mins total)
0.49%
Reduce RISK
63
Reduce COST
Lower minimum
weight & safety
factor
Reduces substance
& solvent use by
>80%
Supports Green
Chemistry