Good Weighing Practices in QC Laboratories . Balances & USP requirements

1. Good Weighing Practices
At QC Laboratory
Dr. A. Amsavel M.Sc., B.Ed., Ph.D.

2. Content
• Significance of balances in the QC Laboratories
• Types of Balances
• Definition
• Minimum weight
• Location for installation Balances
• USP requirement
• Performances test
• Calibration
– Repeatability
– Linearity
– Eccentricity
– Sensitivity
• Factor influence the accuracy of weight
• Types of samples and handling
• Precaution to be taken while weighing

3. Impact of Weighing in Analysis
• Weighing is a one of key activities in all the QC laboratories
• Most of the time, our understanding is not at sufficient level
• Its importance or complexity is underestimated.
• Quality of weighing determines the Quality & Accuracy of final• Quality of weighing determines the Quality & Accuracy of final
test result.
• The USP specifically requires highly accurate results when
weighing analytes for quantitative measures
• Right choice of balances (Analytical/semi-micro/micro ) with
desired resolution, accuracy & repeatability is essential to
reduce the error and meet the compliance

4. Type of balances
Balance name Resolution Quantity of
decimal digits (gm)
Ultra-microbalances 0.1 µg 0.0000001
Microbalances 1 µg 0.000001
Semi-microbalances 0.01mg 0.00001
Analytical balances 0.1mg 0.0001
Precision balances 1g ÷ 1mg 1g ÷ 1mg

5. Balance Selection for Minimum Weight
Resolution Repeatability
（ S.D.）
Minimum weight
(typical)*3
0.001 mg 2.5 μg 3.0 mg
0.01 mg
0.03 mg 20 mg
0.02 mg 30 mg
0.1 mg 0.2 mg 120 mg

6. Requirement of Balances

7. What is minimum weight ?
• Minimum weight is the minimum sample quantity required to
perform an accurate quantitative analysis is based on the
measurement error of the balance used
• In order to satisfy the required weighing tolerance, when
samples are weighed the amount of sample mass (i.e., the net
weight) must be equal to or larger than the minimum weight.
• The minimum weight applies to the sample weight, not to the
tare or gross weight.
• If the sample quantity is too small, the measurement error will be
huge and result of the analysis will be unreliable.

8. Calculation of Minimum Mass
Minimal mass value of balance can be established based on
repeatability
- analysis required precision 0,1%,
- standard deviation (Balance specification)
Eg Max 220g; d=0.01mg/0.1mg; s = 0,025mg; k = 2; A = 0.1%
• Minimal weighing for the balance is 50mg, if analysis is supposed to
be performed with precision 0.1%.

9. Definition:
Accuracy
• Closeness of agreement between a measured quantity value and a
true quantity value of a measurand. VIM *
• Difference between measurements average value and the real value
according to USP
PrecisionPrecision
• Closeness of agreement between indications or measured quantity
values obtained by replicate measurements on the same or similar
objects under specified conditions. VIM
Trueness
closeness of agreement between the average of an infinite number
of replicate measured quantity values and a reference quantity value
(*) VIM – International Vocabulary of Terms in Legal Metrology
(**) USP – United States Pharmacopeia

10. Accuracy & Precision

11. USP General Chapters
• Measurement is stated to be 'accurately measured' or
'accurately weighed',
– (41) Balances
– (1251) Weighing On An Analytical Balance– (1251) Weighing On An Analytical Balance

12. Understand the USP Requirement
USP General Chapter <1251>:
"In order to satisfy the required weighing tolerance, when
samples are weighed, the amount of sample mass (i.e.,
the net weight) must be equal or larger than the minimumthe net weight) must be equal or larger than the minimum
weight.
The minimum weight applies to the sample weight, not to
the tare or gross weight.

13. Requirement of Balances
Select the appropriate balance based on the accuracy,
repeatability, stability, access control, printout or connect to
other instrument or LIMS etc.
 URS
 Select Correct accuracy and repeatability Select Correct accuracy and repeatability
 Qualification
 Installation at right place / location
 Operation qualification
 Performance qualification / Calibration
 Password protection, Access control , printer, etc

14. Balances Requirement - USP
REPEATABILITY USP General Chapter <41>
Repeatability tolerance 0.10%
Expansion factor, K 2
Acceptance criteria 2 x SD/N ≤ 0.10%
Smallest possible sample
weight/lowest starting point
820 d (in optimal conditions)
weight/lowest starting point
Operating Range (2 x SD x 1000) to max capacity or
(2 x 0.41d x 1000) to max capacity (if SD < 0.41d)
ACCURACY USP General Chapter <41>
Tolerance Satisfactory if its weighing value is within 0.10% of
the test weight value
Test weight Between 5% and 100% of the balance's capacity
Calibration uncertainty of the
weight
Must be ≤ 1/3 of 0.10%

15. Location : Installation of Balances
• Install the balance on anti- vibration table &
• non-magnetic surface and grounded to prevent static
electricity
• Room should be temperature and humidity controlled
• vibration, air currents,
• Should be free of drafts and away from air conditioner or fans
or windows to avoid strong air current or direct sunlight
• Away from magnetic fields (magnetic stirrer), electromagnetic
radiation eg RF generators/communication devices and
electric motors,
• Away from Corrosive materials are used nearby.

16. Operational Qualification
OQ has to cover following, but not limited to;
• Control of stable indication
• Mechanical mobility of all moveable parts
• Manually triggered or automatic adjustment by means of• Manually triggered or automatic adjustment by means of
built-in weights.
– Automatic adjustment reduce the drift of the balance.
• Operation of ancillary equipment
• Tare function
• Calibration part of OQ

17. Performance Test
Prop-
erty
Definition Acceptance
Criteria
ExamplesSensitivity
Change in weighing value divided by
the change in load, usually measured
between zero and the capacity of the
balance.
NMT 0.05% deviation
where 〈41〉 is
applicable. For other
uses, respective
tolerance requirement
divided by 2.
The test load at or
sufficiently close
to the capacity of
the balance.
Sensitivity
divided by 2.
Repeat-ability
Ability of a weighing instrument to display
identical measurement values for repeated
weighings of the same objects under the
same conditions, e.g.,
the same measurement procedure,
operator, measuring system, operating
conditions, and same location over a short
period of time. Repeatability usually is
expressed as the standard deviation of
multiple weighings.
Requirement from 〈41〉
where applicable. For
other uses, user
specified requirements
will apply.
10 replicate
weighings (test
weight -few
percent of the
nominal capacity
of the balance).

18. Performance Tests
Pro
perty
Definition Acceptance
Criteria
Examples
Linearity
Ability of a balance to follow the linear
relationship between a load and the
indicated weighing value. Nonlinearity
usually is expressed as the largest
magnitude of any linearity deviation
within the test interval.
NMT 0.05% deviation
where 〈41〉 is
applicable. For other
uses, respective
tolerance
requirement divided
From 3 to 6 points
over the range of the
balance.
Linearity
within the test interval. requirement divided
by 2.
Eccentricity
Deviation in the measurement value
caused by eccentric loading—in other
words, the asymmetrical placement of
the center of gravity of the load relative
to the load receiver. Eccentricity usually
is expressed as the largest magnitude of
any of the deviations between an off-
center reading and the center reading
for a given test load.
NMT 0.05% deviation
where 〈41〉 is
applicable. For other
uses, respective
tolerance
requirement divided
by 2.
Performed in the
center of gravity & 4
quadrants (
Test load usually
should be 30% of the
capacity of the
balance or higher

19. Accuracy <41>:
Accuracy:
• The accuracy is satisfactory if its weighing value, is within 0.10%
of the test weight value.
• A test weight is suitable if it has a mass between 5% and 100% of• A test weight is suitable if it has a mass between 5% and 100% of
the balance's capacity.
• maximum permissible error (mpe) or uncertinity shall 1/3 of the
applied test ie 0.03%. (ASTM E617)
Note: A readability of 0.1 mg of balance is believed as “accurate to 0.1 mg” as
misconception.

20. Balance Calibration
According to USP General Chapter <41> “Balances”, for
substances to be accurately weighed, the balance used must
be calibrated over the operating range
The most important are ;
 Repeatability (RP),
 Eccentricity (EC),
 Linearity (L) and
 Sensitivity (SE),

21. Repeatability
• Why Repeatability is so important?
• It will have significant impact on all the quantitative analysis
• Ability of a weighing instrument to display identical
measurement values for repeated weighings of the same
objects under the same conditions, e.g., the sameobjects under the same conditions, e.g., the same
measurement procedure, same operator, same measuring
system, same operating conditions, and same location over a
short period of time.
• Systematic deviations normally can be prevented if
Repeatability is performed.

22. Repeatability :
Repeatability :
Individual measurement deviation from average value does not exceed
standard deviation, that is ~ 0,0003g with probability 68,5%.
Individual measurement deviation does not exceed three standard
deviations, that is ~ 0,0009g with probability higher than 99,7%, so very close
to certainty.

23. Repeatability test <USP 41>
• Perform 10 measurements with the same reference weight
• Calculate the Standard Deviation [SD]
Repeatability is satisfactory if
– 2 x SD/Nominal reference weight used is ≤ 0.10 %
• If the standard deviation obtained is less than 0.41d, (d-is the scale interval),• If the standard deviation obtained is less than 0.41d, (d-is the scale interval),
replace this standard deviation with 0.41d.
– 2x SD x 1000 If SD < 0.41d,
• In this case, repeatability is satisfactory if two times 0.41d, divided by the
nominal value of the weight used, does not exceed 0.10%.
– 2x SD (0.41d) x 1000 = 820d
– analytical balance with a readability of 0.1 mg, this means the
starting point yielded is 82 mg.

24. Linearity test
• Linearity: To ensure that balance is
accurate at the desired level in the
operating range
• Ability of a balance to follow the linear
relationship between a load and the
indicated weighing value.
• Non-linearity usually is expressed as the
largest magnitude of any linearity deviation
within the test interval.
• Perform 3 to 6 points over the range of the
balance.
• Limit: NMT 0.05% deviation where 〈41〉 is
applicable. For other uses, respective
tolerance requirement divided by 2.
It is a deviation of balance real curve
from straight line joining two points
A:B – ideal weight.

25. Eccentricity Test
• Deviation in the measurement value caused by eccentric loading— in other
words, the asymmetrical placement of the center of gravity of the load
• Eccentricity usually is expressed as the largest magnitude of any of the
deviations between an off-center reading and the center reading for a given
test load.
• In practice, a difference is defined between indication when mass standard is• In practice, a difference is defined between indication when mass standard is
put at central point of weighing pan and indication when the same mass
standard is located at another place on the weighing pan.
• Performed in the center of gravity and the four quadrants
• Test load usually should be 30% of the capacity of the balance or higher.
Limit: NMT 0.05%
Deviation where (41) is applicable.

26. Sensitivity Test
• Change in weighing value divided by the change in load,
usually measured between zero and the capacity of the
balance.
• Use certified weights with an appropriateUse certified weights with an appropriate
weight class
• Perform as performed for repeatability test
• Limit: NMT 0.05% deviation where 〈41〉 is applicable. For
other uses, respective tolerance requirement divided by 2.

27. Testing of Balance parameters
• How often balance parameters should be tested?
Intervals defining balance calibration/testing shall be based on
range of operation, their intensity, balance stability in time
and expected weighing process measurement precision.
• Assuming that external conditions are stable, following• Assuming that external conditions are stable, following
balance parameters control periods can be fixed:
– Calibration annually
– Repeatability & centricity monthly
– Sensitivity change weekly
– Verification/ adjustment daily

28. Factors affects the weighing Accuracy
There are several external factors influence the accuracy of weighing;
• Ambient area and people influence result of weight measurement;
• Major balance external factors are ;
– Oscillations, vibrations
– Breeze of air
– Temperature drifts– Temperature drifts
– Electrostatics
– Evaporation and absorption phenomena (hygroscopicity)
– Magnetism
• Other factors is nature of sample ,
• Both balance and the sample will influence the accuracy of results
• To prevent any such issue , need to identify the reason properly
– Is it due to Balance – external factor or sample – external factor?

29. Impact of Vibration & Strong Air
• Oscillations – vibrations are transmitted by the ground and
walls that are generates and affects weighing balance
– Effect is longer measurement time and higher indication
dispersion.
– Prevent vibrations by keep away from vibration area
– Keep on anti-vibration table. Anti vibration double rubber– Keep on anti-vibration table. Anti vibration double rubber
console, to suppress vibrations
• Breeze of air influence to instability and long weighing time.
– Balance workstation should not be located close to doors or
windows.
– Closeness to devices such as air-conditioning, fans, should be
avoided.

30. Impact due to Temperature
How Temperature affect the weighing;
• Weighing room temperature should be maintained at constant
level. Eg variation must not more than 0.5°C/hour.
• Equilibrate the sample to room temperature before weighing ,
will give error due to heat convection ( hot sample will be lesswill give error due to heat convection ( hot sample will be less
than true value)
• Precaution/ aspects for weighing process:
 pick up the samples with use of tweezers or other holders
 should not put their hands into weighing chamber
 Touched with hands, samples –may change their
temperature

31. Hygroscopic samples
Sample nature influence the weighing accuracy:
 Hygroscopic samples absorbs the moisture from ambient
air and steadily gain the weight
 Measured weight will have higher mass than actual
 Weighed promptly Weighed promptly
 Use the hermetic vessels or a gas-tight enclosure.
 Weighing vessel should be clean & dry and easily
transferable
 Add the desired amount of sample, and replace the
enclosure

32. Volatile or hygroscopic samples
Sample nature influence the weighing accuracy:
Volatile liquids (low boiling solvents or solid with volatile
solvents ) can undergo evaporation during weighing
Balance indicates fluctuation / drift; ie weighing continuously
decrease while measurement
Use appropriate weighing vessels, like bulbs with narrow necksUse appropriate weighing vessels, like bulbs with narrow necks
or vessels with top cover.
Weighing of Volatile samples:
 Weighing of low boiling liquid point in a vessel with a gas-tight
enclosure of small diameter.
 Close immediately after transfer of material
 After the balance display stabilizes, the analyst records the
specimen weight

33. Corrosive and Bio-hazardous Samples
Aseptic or Biohazardous Samples
• Weighing the samples in the confines area / bio-safety cabinet
/isolator, or similar containment device.
• Care should be taken if airflow in the hood may cause balance
instabilityinstability
Corrosive Materials
• Extra care is essential when materials of this nature are
weighed.
• Use sealed containers such as weighing bottles or syringes

34. Samples with Electrostatics
Effect of electrostatic presence.
o Slow drift of weighing result,
o Large dispersion of weighing results in a series of measurements,
and
o No return to zero if a load is taken off the weighing pan.
Possible source:
– Dry, finely divided powders may be charged with static electricity– Dry, finely divided powders may be charged with static electricity
– The static charge may develop due to low relative humidity, clothing
worn and gloves used
How to prevent:
 Antistatic weigh boats, antistatic guns, and antistatic screens
 Placing the container in a metal holder
 Balances with a built-in antistatic device is available (piezoelectric
components or low amount of a radioactive polonium) to generate a
stream of ions that dissipate

35. Magnetism as interfering factor
• If magnetic load is measured, electromagnetic field of a
balance is disturbed or weighed sample is influenced by
magnet installed in a balance.
• It will lead to incorrect mass reading of a weighed
sample.sample.
• High resolution balances are constructed on basis of
electromagnetic sets which include a force-motor and
magnet.
• How to avoid: Increasing a distance between a sample
and balance mechanism. Use under-hook weighing with
application of special racks or hooks made of aluminum.

36. Precaution while weighing
• All receivers must be clean, dry, and inert.
• weighing uncertainty for small samples, i.e., net weights with a
mass determined around repeatability.
• Receivers should be nonmagnetic used at ambient
temperature
• Weighing dishes should be polymer or aluminum. Antistatic
and compatible with the liquid sample.
Safety measures:
• Use proper PPEs gloves , mask, goggles etc during a weighing to avoid exposure
• Hazardous materials should be handled in an enclosure that has appropriate air
filtration.
Many toxic— and possibly allergenic— substances are present as liquids or finely
divided particles.

37. Reference
• US Pharmacopeia- 42
• General Chapter <41> Balances,
• General Chapter <1251> Weighing on an Analytical
Balance,Balance,
• Reichmuth, A., Weighing Small Samples on Laboratory
Balances, 13th International Metrology Congress, Lille
(F), 2007

38. Thank youThank you