Routine Testing with Test Weights

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FDA – Questions and Answers on cGMP‘s

http://www.fda.gov/cder/guidance/cGMPs/

Supplier`s Question“Many leading analytical balance manufacturers provide built-in "auto calibration" features in their balances. Are such auto-calibration procedures acceptable instead of external performance checks? If not, then what should the schedule for calibration be?”

FDA AnswerExternal performance checks still have to be carried out, but less frequently. Risk analysis (criticality and tolerance of the process) and frequencyof use determine the frequency of performance checks. The calibration of an “auto-calibrator” should be periodically verified –usual frequency is once per year - using […] traceable standards.

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Our Experience put into Practice

Higher Risk

⇒More Testing

Impact (for business and for consumer)

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low medium high

1 %

0.1 %

0.01 %

10 %

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Which tests should I carry out to minimize my risk ?

Risik Management

Let us look at the parameters that reallyinfluence your weighing results. Werecommend that you test only therelevant parameters.

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Repeatability (RP)

Sensitivity Offset (SE)

Linearity Deviation „Nonlinearity“ (NL)

Eccentric Load Deviation (EC)

Readability

Parameters influencing Weighing Accuracy

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Rel

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Wei

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]Influence of Weighing Parameters on Accuracy

0.00001

0.0001

0.001

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0.01 0.1 1 10 100 1000

U_totU_RPU_ECU_NLU_SE

Model XP204: Individual Uncertainty Contributions (@k=2)

Sample Mass [g]

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Repeatability: Dominant influencing factor near the lowend of the measurement range

Sensitivity and eccentricity:Dominant influencing factors near the upperend of the measurement range

Nonlinearity:Not dominant throughout the wholemeasurement range

Influence of Weighing Parameters on Accuracy

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All User Tests can be done with 2 Weights

Weight 1: Largest OIML/ASTM weight which isbelow the balance capacity

Weight 2: Largest OIML/ASTM weight whichequals or is below 5% of the capacity

XP205: XP4002S:2000 g and 200 g200 g and 10 g

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Sensitivity [SE]

Indication

Load

• Ideal characteristic curve

• Characteristic curve withsensitivity deviation

Example: XP205

The calibration of sensitivity is most efficient if done near the upperend of the measurement range

Weight 1:200g F2

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Sensitivity [SE]For even smaller test weights, sensitivity calibration is useless

- The absolute sensitivity deviation is very small and very difficult if impossible to detect- Near the lower end of the measurement range, the effect of repeatability is dominant

See e.g. USP <41>: For small loads, the determination of measurementuncertainty is executed by means of a repeatability test

Indication

Load

• Ideal characteristic curve

• Characteristic curve withsensitivity deviation

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Sensitivity TestsTest sensitivity with a test weight close to nominal capacity (1).

Using a smaller test weight (a) results in a smaller offset, which is partially disturbed by repeatability (pink band).

Using an even smaller test weight (b) results in the sensitivity offset being buried entirely in the deviations of repeatability.

Load

• Ideal characteristic curve

• Characteristic curve withsensitivity deviation

1ab

Best

Feasible

Wrong

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Repeatability Test at 5% of weighing range

Indication

Load

Standard deviation of the repeatability

Lower end (< 5%) of measurementrange: Repeatability almost constantWeight 2

Repeatability is almost constant at the lower end of the measurement range. That is why the weight 2 can be used to determine the minimum weight, which is of course much smaller than weight 2.

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Repeatability is constant at the lower end

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Nonlinearity [NL]

Nonlinearity normally doesnot play a dominant role foranalytical and low-loadprecision balances and isnegligible for small netloads, so that the usernormally does not have to test nonlinearity.

Nonlinearity is assessed in the framework of theservice by an accreditedservice technician.

Indication

Load

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Eccentricity [EC]

Eccentricity errors can be minimized by use of specialaccessories as e.g. ErgoClips

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Frequency of User Tests

Higher Risk

⇒More Testing

Impact (for business and for consumer)

Wei

ghin

gac

cura

cy

low medium high

1 %

0.1 %

0.01 %

10 %

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Test weights for User Tests

Weight 2 Weight 1Weight 1 Weight 2

( )If required

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CarePacs for Routine Testing

User BenefitsCost savings – only two weights rather than entire weight set

Time savings – easy and quick tests supported by METTLER TOLEDO SOP’s

Option to add 3rd weight for specific testing

Ergonomically designed weight handling accessories included

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Frequency of User Tests: Sensitivity

Sensitivity calibration is an integral part of the functional control of a measurement device

Sensitivity tests are very simple and fast

For a balance with activated FACT, sensitivity calibrations withexternal weights can be carried out less frequently

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Frequency of User Tests: Repeatability

The repeatability is important for the determination of the minimumweight

In many cases, economic and safety reasons play an important rolefor the determination of the minimum weight (weighing of precioussubstances; flavor of food, etc.)

Some regulations as e.g. USP explicitely require the determinationof minimum weight

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Frequency of User Tests: Eccentricity

Eccentricity may play a role if the tare vessel is removed for filling;The tare may be placed on a different location of the weighing pan

Eccentricity may also be important when larger amounts are weighed in, with the tare vessel being placed non-centric on the pan

The use of accessories such as ergo clips minimizes eccentricity errors, in that case it is enough if eccentricity tests are carried out by the MT service technician.

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Frequency of User Tests: Nonlinearity

The influence of nonlinearity on the weighing result is often negligible

The determination of nonlinearity is time consuming, since not onlyone or two weights but a whole set of weights have to be used

For almost all of the cases, it is justified to leave the determination of nonlinearity to the service techician

For higher risk, the calibration performed the service technician shallbe carried out more frequently; this calibration includes nonlinearity

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Example of a GWP® Recommendation

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Test Tolerances

Control limit exceeded: Balance has to be markedas „out of control limits“ and shall not be usedanymore. MT has be contacted.

Warning limit exceeded: No immediate actionnecessary, but balance has to be kept undersurveillance

GWP SOP‘s for Routine Testingprovide more information for the user

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SOP‘s for Routine Testing

GWP SOP‘s for Routine Testingprovide more information for the user

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Example of a GWP® Recommendation

The weight classes are chosen so that theuncertainty of the weights can be neglectedcompared to the process accuracyrequirements.

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Straightforward routine testing with GWP®

Routine Testing with Test Weights