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Calibration in the lab

 

Here you will find answers to the following questions:

  • What equipment has to be calibrated?
  • How and how often is calibration to be carried out?
  • What should be done if the equipment is not compliant?
  • How is the documentation to be compiled?

See also chapter 14.D Qualifying laboratory instruments.

11 Definitions

In accordance with the EU GMP Guideline, Annex 18, calibration is defined as follows:

Figure 14.E-1 Definition of calibration

Definition of calibration

Calibration is the demonstration that a particular instrument or device produces results within specified limits by comparison with those produced by a reference or traceable standard over an appropriate range of measurements (Q7a).

11.1 Persons

For each instrument, a system owner and a deputy must be named. The system owner is responsible for ensuring that the equipment is always in a faultless condition and for arranging the necessary maintenance and repair work. Finally, this person is also responsible for ensuring that the calibration is carried out at the planned times. He can also be consulted for training courses (equipment instruction).

The user is the person who works with the equipment temporarily. This person is responsible for proper operation of the equipment. In particular, he is obligated to check, before starting the analysis, that the equipment is calibrated and approved (see chapter 12 System suitability test (SST)).

11.2 Instruments

The essential functions are to be described in the instrument description. In addition, each piece of instrument is to be clearly labelled (instrument no., inventory no. etc.). If a piece of instrument consists of several components (instrument system), it must be ensured that it is possible at all times to track the individual components of which the instrument consists. This is most easily documented in the instrument log book. In practice, it has proven worthwhile to provide one component with an identification number to represent the entire system (e.g. auto-sampler in HPLC systems).

For each piece of instrument/each component, the critical parameters must be established. They form the basis for verifying proper operation (see chapter 12.1 Test intervals, test points, test instructions).

The test points are the critical functionalities of a piece of instrument, which are checked during calibration.

11.3 Working

Maintenance of analysis instrument is carried out regularly to ensure functional efficiency. Repair requires intervention in the equipment by the system owner, his deputy or a service technician, to restore functional efficiency.

Calibration of analysis instrument is the regular verification of the functional efficiency after start-up using a defined procedure. Usually, the result of this is the relationship of the measurement value to the true, known value of a standard used.

Adjusting of analysis equipment is the task of making the equipment ready for operation, with the elimination of systematic measurement deviations which could have a falsifying effect on the result. Adjusting requires intervention in the equipment.

Official verification is the operation in which the conformity of a measuring instrument with the calibration regulations is ascertained by the calibration authority. Stamping certifies that the measuring instrument complied with the verification regulations at the time of the test. This is an official operation.

12 Calibration instructions and record

Calibration of equipment is to be described in an SOP. The "umbrella SOP" basically specifies that all equipment used for GMP analyses must be calibrated.

In this SOP, it is advisable to define a generally valid calibration interval for all equipment for which there is initially no equipment-specific SOP.

Then, an individual SOP is to be compiled for each instrument or a set of instruments. Execution must be described accurately, in particular the calibrating equipment and reagents required must be listed therein. If special test techniques are used, these too must be specified.

The calibrations must be recorded and the documentation saved in the log book. In practice, the use of forms has proven useful for this purpose. It is advisable to include these in the SOP.

12.1 Test intervals, test points, test instructions

The equipment-specific SOP must contain specifications on the test interval, the test points and test instructions. For multi-component equipment, it is feasible that the test intervals for individual components will be different. The test points are derived from the description of the critical parameters (see chapter 14.D Qualifying laboratory instruments). The individual tests must be specified. Often they are already listed in the instrument manual or can be applied with slight changes. It is advantageous to describe the maintenance work in the same SOP.

In principle, calibration is always due if significant parts of a piece of equipment are replaced or if the equipment is moved to a new location. Re-qualification must also be taken into consideration (see chapter 14.D Qualifying laboratory instruments). Many calibrations can be covered by service agreements. This is a permissible procedure, for which the pros and cons must be weighed up against each other. External solution can be expensive and internal staff may lose in-depth equipment knowledge. In addition, it must be ensured that the external company implements the internal requirements. Above all, compliance with formal aspects (documentation) must be ensured.

In large companies, there are sometimes internal teams for calibration of equipment. Here, there is the risk that with this largely cost-effective solution, the individual employees will take their equipment responsibility slightly less seriously. The advantage of calibration by a system owner is justified by the better equipment knowledge and the higher level of responsibility. However, this is not always the most cost-effective solution.

13 Examples

13.1 Balance

The balances represent an essential element in the chain of analytical results. For each balance, extensive calibration must be carried out at least once a year. Parameters such as the following are checked:

  • Measuring uncertainty, gives the permissible minimum initial weight via the repeated standard deviation (N = 10) (acc. to USP <41>)
  • Analysis of the sample position
  • Analysis of the linearity

This work can be processed well via service agreements.

Depending on the balance type, different procedures can be used for short-term (daily) and longer-term (annual) verification. A distinction is also made between tests that are carried out with built-in (automatic or manual) or external, certified control weights (manual). The balance calibration types are listed in figure 14.E-2 as an example:

Figure 14.E-2 Types of balance calibration

Balance calibration

Activity

Frequency

Automatic auto-calibration with internal weights

Daily

Manual auto-calibration with internal weights
Note: These daily checks must be documented in the log book

Daily

Calibration with external weights (all balances)

Monthly

Comprehensive calibration, etc. with USP test

Annual

It must be noted that calibration with external control weights is to be planned regularly - e.g. monthly - for all balance types (Note: the FDA has also already demanded daily verification here). It must be possible to justify the established procedure. For verification, it is also necessary to establish which control weights are used, preferably in the usual weighing range.

For some current balance types by Mettler-Toledo, the control weights are listed in the following overview (figure 14.E-3).

Figure 14.E-3 Control weights by balance type  

Control weights (accuracy class E2, for precision balance F1)

Balance type

Weight

Tolerance

Micro-balance UM 3

Micro-balance M 3

Micro-balance MT 5

10 mg

10 mg

10 mg

± 0.004 mg

± 0.01 mg

± 0.04 mg

Analytical balance AE 163

100 mg

100 g

± 0.04 mg

± 0.4 mg

Analytical balance AE 260

100 mg

100 g

± 0.04 mg

± 4 mg

Analytical balance AM 100

10 g

± 0.4 mg

Analytical balance AT 261

100 mg

100 g

± 0.04 mg

± 4 mg

Analytical balance AT 460

100 mg

100 g

± 0.4 mg

± 4 mg

Precision balance PB 153

Precision balance PB 1502

Precision balance P 1200 N

100 g

100 g

1000 g

± 0.004 g

± 0.04 g

± 0.02 g

Precision balance PC 440

10 g

100 g

± 0.002 g

± 0.02 g

Precision balance PC 4400

100 g

1000 g

± 0.02 g

± 0.2 g

Taking calibration law and the recommendations of the balance manufacturer into account, many companies set tighter tolerance values than prescribed in the calibration law. For analytical balances, it is generally recommended to check the linearity with at least 2 weights. Here, only control weights for which there is a valid certificate may be used. For Mettler-Toledo control weights in accuracy class E2 and F1, the re-certification period is 5 years. For handling, the manufacturer's specifications must be followed, which prescribe, for example, special tweezers with gum mantles or suitable grease-free gloves. The control weights must be stored carefully and maintained in accordance with the manufacturer's specifications (degrease).

13.2 Volume measuring instruments

Calibrated glass pipettes and measuring flasks need not be calibrated. For automatic pipettes, a calibration interval of 6-12 months is usual. These control tests can also be assigned to third parties. Volume measuring instruments are usually checked gravimetrically. This is carried out on the Dilutor Hamilton Microlab 500, where the control test is executed once a year.

Critical parameters

  • Accuracy
  • Precision

Demineralised water, 0.01 N sulphuric acid and potassium dichromate p.a. are used (e.g. Fluka Item No. 1.04868). The dispenser function is checked gravimetrically, by weighing the aspirated and then ejected liquid volume on an analytical balance. The dilutor function is checked photometrically.

Dispenser function

The required volume is determined by weighing de-ionised water. The temperature of the water may only deviate from the ambient temperature by max. 2 °C. Calibration is carried out with a calibrated analytical balance. The temperature is measured with a certified thermometer.

5 ml of water are dosed in an Erlenmeyer flask and the atmosphere in the flask is saturated with water through repeated swivelling. The flask is placed on the analytical balance, tared and the desired volume is dosed. Here, with a variably adjustable volume, the volume of the flask/cylinder used must be checked as the full volume and as a partial volume of 50% and 10% of the full volume. Each fixed or variably adjustable volume amount must be ejected and weighed 7 times. The syringe is initially filled completely, whether or not the ejection is complete or partial. When determining partial volumes, the corresponding amounts are specified as aliquots. The displayed weight is printed out or noted. The syringe of the ejection pipe does not enter the liquid. The dispenser is operated at the standard speed (factory setting with specified parameters, e.g. syringe size).

During a measuring sequence, the Erlenmeyer flask must not be touched with bare hands. If the weighing range of the balance is exceeded during a measuring sequence, the flask is emptied, 5 ml water is dosed, it is retared and the measuring sequence is continued. For the 25 ml syringe, PE-tubes with a larger interior diameter must be used.

The following are calculated from the values measured per volume:

  • the mean value
  • the relative standard deviation (srel in%)
  • and the recovery.

For the recovery and the mean value, the density of the water at the present measuring temperature must be taken into account.

Tolerances

Srel

Recovery

Full volume 100%

Partial volume 50%

Partial volume 10%

£ 0.5%

£ 0.5%

£ 2.0%

99.0-101.0%

98.0-102.0%

95.0-105.0%

Dilutor function

Potassium dichromate solutions

Stock solution A

Accurately weigh (to within 0.1 mg)
24.0-26.0 mg potassium dichromate p.a.,
dissolve in 0.01 N sulphuric acid p.a. to 100.0 mL

Stock solution B

Accurately weigh (to within 0.1 mg)
245.0-255.0 mg potassium dichromate p.a.,
dissolve in 0.01 N sulphuric acid p.a. to 100.0 mL

From stock solution A, a dilution series A is produced with the dilutor with a 250-mL sample syringe, 1 mL diluent syringe and standard sample tube.

Dilution series A

Stock solution A

0.01 N sulphuric acid

1 + 1

250 mL

250 mL

1 + 3

125 mL

375 mL

1 + 7

75 mL

525 mL

1 + 15

62 mL

938 mL

From stock solution B, a dilution series B is produced with the dilutor with a 250-mL sample syringe, 1 mL diluent syringe and standard sample tube.

Dilution series B

Stock solution B

0.01 N sulphuric acid

1 + 19

250 mL

4750 mL

1 + 39

125 mL

4875 mL

1 + 79

62.5 mL

4940 mL

1 + 159

31.25 mL

4970 mL

1 + 199

25 mL

4975 mL

The solutions are measured against 0.01 N sulphuric acid with a UV/VIS spectral photometer at 350 nm in 0.5 cm half micro-cuvettes.

Requirements for the dilutor: For each dilution series, the fulfilment of the Lambert-Beer law is checked by determining the linearity (y = mx + b) and the regression (correlation coefficient R2), e.g. using an Excel sheet.

Figure 14.E-4 Tolerances for the dilutor function

Tolerances

 

Linearity

Intercept b must not exceed 1% of the measured maximum value of absorbance

Correlation

R2 ³ 0.99

13.3 Photometer

The procedure is illustrated using the example of the UV/VIS Uvikon 922 spectral photometer by KONTRON. The calibration standard used is, for example, the secondary standard set for calibration of spectral photometers in the VIS range by HELLMA GmbH, Cat. No. 666-000. The methods are integrated in the equipment software of the spectrometer. The equipment is checked once a year. The equipment must be operated for at least 12 hours before calibration (conditioning of the bulbs).

Critical parameters

  • Bulb intensity
  • Abscissae values
  • Ordinate values
Bulb intensity
  • Intensity mode 200 nm (deuterium lamp adjustment)
  • Intensity mode 580 nm (tungsten halogen lamp adjustment)

For the bulb intensity, the highest adjustable value is required. Setting the bulb intensity via the respective potentiometer up to the highest possible intensity (in accordance with user instructions). If the bulb intensity is too weak, it is set to the highest possible intensity via the respective potentiometer. If the intensity is still too weak, the bulb is replaced and then the bulb intensity is measured again with the new bulb.

Abscissae values

The standard filter set F1 of the secondary standard set for calibration of spectral photometers in the VIS range by HELLMA GmbH, cat. no. 666-000, is used.

The following settings are selected:

  • Method: Wavelength Scan
  • Ordinate scale: Absorption
  • Slit width: 1 nm
  • Scanning speed: 30 nm/min

Figure 14.E-5 Tolerances for the abscissae values

Standard

Approximate position of the peaks (nm) *

F1

279

361

453

536

638

Tolerance

± 0.2

± 0.2

± 0.2

± 0.2

± 0.2

* The actual position of the peaks is to be taken from the certificate.

Ordinate values

The standard filter set F2, F3 and F4 of the secondary standard set for calibration of spectral photometers in the VIS range by HELLMA GmbH, (cat. no. 666-000), is used, for example.

The following settings are selected:

  • Method: Fixed Wavelength
  • Ordinate scale: Absorption
  • Slit width: 1 nm
  • Adjustment time: 2 s

Figure 14.E-6 Tolerances for the ordinate values  

Standard

Ordinate values * (absorption) at the following wavelengths

 

440 nm

465 nm

546 nm

590 nm

635 nm

F2

0.269

0.240

0.242

0.256

0.258

F3

0.500

0.457

0.469

0.498

0.486

F4

0.989

0.920

0.948

0.991

0.947

Tolerance

± 0.002

± 0.002

± 0.002

± 0.002

± 0.002

* The actual ordinate values are to be taken from the certificate.

13.4 HPLC system

The calibration of complete systems, shown here using the example of an HP 1100 HPLC system, is more time-consuming. In such cases, the manufacturers often offer suitable software-based calibration packages. It is then up to the users to decide if the entire package should be used or only parts of it. If you are dealing with a mixed environment, i.e. equipment by different manufacturers, it may be worth determining the best procedure from all packages that covers all equipment regardless of the manufacturer.

The HPLC system consists of the following elements: pump system, degasser, autosampler with injector unit, column oven, detector unit and data analysis system.

The wavelength accuracy (Diode Array Detector = DAD or Variable Wavelength Detector = VWD), bulb intensity, temperature accuracy, temperature stability, noise, flow rates, injector precision and linearity, cross over, gradient mixer function (A/B and C/D), detector linearity and degasser function (vacuum) are checked as critical parameters.

Calibration should be performed annually and after significant changes in the system.

Before calibration, thorough maintenance of the entire system must be executed. The detector should be switched on approximately 24 hours in advance. The specifications defined for the individual tests are prescribed by the HP ChemStation software. The evaluation is carried out automatically by the software. All tests are described in detail in the "Operational Qualification/Performance Verification for Complete HP 1100 Series HPLC Systems" manual.

The tests are executed in the order shown in figure 14.E-7.

Figure 14.E-7 HPLC test order

HPLC test order

1. Intensity

2. Holmium oxide test

3. Temperature accuracy

4. Wavelength accuracy (DAD or VWD)

5. Injector precision

6. Injector linearity

7. Detector linearity and cross over

8. Background noise, flow rate, temperature stability

9. Gradient mixer function (A/B and C/D)

For calibration, the material listed in figure 14.E-8 is required.

Figure 14.E-8 Material for calibration of an HPLC

Material for calibration of an HPLC

Number

Material

1

Hypersil ODS cartridge column with holder, 125 mm * 4 mm, 5 mm
(HP part number: 798 261 8-564 and 5021-1845)

2

ZDV Unions (HP-part number 0100-0900)

1

Caffeine Standard Kit (HP part number: 8500-6762)

1.0 L

Water (HPLC quality, e.g. Fluka)

1.0 L

Acetonitrile (HPLC quality)

0.7 L

Isopropanol (HPLC quality)

0.7 L

0.5% Acetone in Isopropanol (HPLC quality)

1

Control thermometer

Preparation
  • Installation of the columns
  • Eluent A: Water, Eluent B: Acetonitrile, condition columns with A:B 85:15 v/v (approx. 30 min)
  • Switch to the "Verification" menu, select "Standard Tests" under Options and select all available tests with the "Edit" option. For each test, call up the "set up" and enter the limits and waiting time (see figure 14.E-9).
  • The VWD wavelength test is called up under the "Enhanced Test" option and executed separately (easier to execute than in the "Standard Test" option).
  • The gradient mixer function test is executed separately (see gradient composition check).
  • Time required: Around 6-7 hours per piece of equipment must be scheduled.

    Figure 14.E-9 Waiting times and limits for HP 1100  

    Test

    Limit

    Waiting time

    Intensity

    at max: 10000
    at min: 5000
    lower wavelength: 220 nm
    upper wavelength: 350 nm

    0 min

    Holmium oxide test

    Accuracy: 2 nm

    0 min

    Temperature accuracy

    left / right: 2 °C

    0 min

    Wavelength accuracy VWD

    at min (244.3 nm)
    at min (205 nm)
    at max (272.2 nm): 2 nm

    No waiting time, test is executed independently

    Wavelength accuracy DAD

    at min (244.3 nm)
    at max (272.2 nm): 2 nm

    10 min, break before start

    Injector precision

    Retention time: 1.5% RSD
    Peak area: 1% RSD
    Peak height: 2% RSD

    0 min after DAD test, otherwise 10 min, break before start

    Injector linearity

    Correlation: >0.999
    RF Linearity: 5% RSD

    0 min

    Detector linearity/cross over

    Correlation < 0.999
    RF linearity 5% RSD
    Cross over
    Area: 0.2%
    Height: 0.4%
    Quantity: 0.2%

    5 min

    Background noise, flow rate, temperature stability

    ASTM: 0.5 mAU
    Wander: 0.2 mAU
    Drift (DAD): 2.0 mAU/h
    Drift (VWD): 2.0 mAU/h
    Temperature stability: 0.5 °C
    Flow rate accuracy: 5%

    10 min

    Gradient mixer function (only for HP1100 with degasser)

    Waves: 0.5%
    Step accuracy: 0.7%
    Precision: 0.5%

    30 min system conditioning after switching to isopropanol

    Degasser function

     

    Degasser shuts down electronically in the case of a loss of power (warning light switches from green to red)

The following control tests figure 14.E-9 must be executed:

Figure 14.E-10 Test points for HP 1100  

Test points

Intensity

   

Principle:

With a built-in measuring cell, the entire spectrum is scanned and the cell is rinsed with pure water.

Implementation:

Channel A

Flow

Column

Temperature

Technique

Sequence

100 % water

1 mL/min A

Standard

36 °C

IVNOISE.M

IVNOISE.S

Interpretation and decision:

Is integrated in the technique. The results must be within the specified range

Holmium oxide test

Principle:

The accuracy of the wavelength of the DAD or VWD is checked using an installed holmium oxide test filter. The holmium spectrum shows a series of bands for a known wavelength. This check examines if the measured values match the saved values.

Implementation:

Channel A

Flow

Column

Temperature

Technique

Sequence

100 % water

1 mL/min

Standard

36 °C

IVNOISE.M

IVNOISE.S

Interpretation and decision:

Is integrated in the technique. The results must be within the specified range.

Temperature accuracy

Principle:

For good reproducibility, it must be possible to adjust the temperature exactly. The set temperature is measured in the column oven using an external, certified thermometer.

Implementation:

Channel A

Flow

Column

Temperature

Technique

100 % water

1 mL/min

Standard

36 °C

IVNOISE.M

Interpretation and decision:

Is integrated in the technique. The results must be within the specified range.

Wavelength accuracy DAD

Principle:

The spectrum of a 0.125 mg/mL caffeine solution is recorded (spectrum in range 230 to 290 nm).

Implementation:

Channel A

Channel B

Flow

Column

Temperature

Sample

100 % water

100 % ACN

0.8 mL/min 85 % A/15 % B (V/V)

Standard

36 °C

Caffeine standard #3 (0.125 mg/mL Caffeine in water) in position 3 in the autosampler

Technique

Sequence

IVWLACC.M

IVWLACC.S

Interpretation and decision:

Minimum and maximum are calculated automatically. The results must be within the specified range.

Wavelength accuracy VWD

Principle:

The spectrum of a 0.125 mg/mL caffeine solution is recorded.

Implementation:

Channel A

Channel B

Flow

Column

Temperature

Sample

100 % water

100 % ACN

0.8 mL/min 85 % A/15 % B (V/V)

Standard

36 °C

Caffeine standard #3 (0.125 mg/mL Caffeine
in water) in position 3 in the autosampler

Technique

Sequence

OQWAV1.M

OQWAV1.S

 

The test is executed independently of the others

Interpretation and decision:

The maximum and two minimums are calculated automatically. The results must be within the specified range.

Injector precision

Principle :

A caffeine standard is injected 6 times. The standard deviation of the peak areas obtained is determined (evaluation integrated in the technique).

Implementation:

Channel A

Channel B

Flow

Column

Temperature Sample

100 % water

100 % ACN

0.8 mL/min 85 % A/15 % B (V/V)

Standard

36 °C

Caffeine standard #3 (0.125 mg/mL Caffeine in water) in position 3 in the autosampler

Technique

Sequence

IVINJPRE.M

IVINJPRE.S

Interpretation and decision:

The standard deviation of peak areas, peak height and the retention time is determined automatically. The results must be within the specified range.

Injector linearity

Principle:

Different volumes are injected from a sample vial. After plotting the peak areas against the volume, the linear regression calculation including 0 gives a straight line. The correlation coefficient and the standard deviation of the response factors (RF) are determined.

Implementation:

Channel A

Channel B

Flow

Column

Temperature Sample

100 % water

100 % ACN

0.8 mL/min 85 % A/15 % B (V/V)

Standard

36 °C

Caffeine standard #2 in position 2 of the auto-sampler

Technique

Sequence

IVINJLIN.M

IVINJLIN.S

Interpretation and decision:

Is integrated in the technique. The results must be within the specified range.

Detector linearity and cross over

Principle:

For the detector linearity a concentration series is recorded and the correlation coefficient is determined through linear regression including 0. Five samples are measured with the adjusted caffeine concentration.

To determine the cross over, the quantity of substance from the injection of the first sample that is found again in the subsequent sample is determined in two consecutive measurements. The first sample is highly concentrated, while the second sample only contains the solvent of the first sample.

Implementation:

Channel A

Channel B

Flow

Column

Temperature

Sample

100 % water

100 % ACN

0.8 mL/min 85 % A/15 % B (V/V)

Standard

36 °C

Caffeine standard #1, #2, #3, #4, #5 in positions 1, 2, 3, 4, 5; blank (water) in position 6 of the auto-sampler

Technique

Sequence

IVDETLIN.M

IVDETLIN.S

Interpretation and decision:

Is integrated in the technique. The results must be within the specified range.

Background noise, flow rate, temperature stability

Principle:

Determination of background noise, flow rates, temperature stability with a flow rate of 1mL/min with water.

Implementation:

Channel A

Flow

Column

Temperature

Sample

100 % water

1 mL/min

Standard

36 °C

Caffeine standard #3 (0.125 mg/mL Caffeine in water) in position 3 in the autosampler

Technique

Sequence

IVNOISE.M

IVNOISE.S

Interpretation and decision:

Is integrated in the technique. The results must be within the specified range.

Gradient mixer function (A/B and C/D)

Principle:

According to a specified plan, specific mixtures of a pure solvent (isopropanol) and the solvent spiked with a marker (acetone in isopropanol) were produced with the gradient mixer and the pump.

Implementation:

Channel A

Channel B

(Channels C and
D can be tested
in the same way

Isopropanol (HPLC-grade)

Isopropanol/acetone 99.5%/0.5% (V/V)

Flow

Columns

Temperature

Conditioning

Technique

3 mL/min 100% A

Restriction capillary G1313-87305)

36 °C

30 min with isopropanol

IVCOQP.M

 

Three runs are executed. After completion of the test for A/B, files comp0001.d, comp0002.d and comp0003.d are renamed to comp0004.d, comp0005.d and comp0006.d (in Explorer). This is required, as otherwise the HP software would overwrite the A/B analytical results. Then "Set-up" switches to C/D and the three runs are executed for channels C and D

Interpretation and decision:

Is integrated in the technique. The results must be within the specified range.

Time intervals for maintenance

Figure 14.E-11 Time intervals for maintenance for HP 1100

Activity

Interval

Change purge valve filter

Monthly

Change frits of the eluent bottles

Monthly

Filter for electronically controlled inlet valve

As required (e.g. in case of leaks in the valve)

Rotasil in injector unit

As required (e.g. if ghost peaks are caused by contamination in the system)

Connection capillaries

As required (e.g. if ghost peaks are caused by contamination in the system)

Change seales in the pump

Annually, as required

Rinse the entire system

Always if the system remains idle for a long time after an analysis run (risk of salting out if using buffers).

Clean the equipment (remove dust)

Every 2 months

14 Decision

14.1 Requirements, tolerances, specifications

For each test point, the corresponding acceptance criteria (requirements, tolerances, specifications) must be established. In practice, it has proven worthwhile discussing these with the manufacturer. They should be established "sensibly" in order not to unnecessarily restrict the handling leeway, and on the other hand in order to be able to set selective criteria. The manufacturer's documentation often contains limits that seem implausibly generous, on the basis of which precise working under GMP would not be possible.

14.2 Equipment release

If all test points comply with the acceptance criteria, the equipment is released by the system owner or by a person authorised by him until the next test time. To this end, an easily visible label is to be applied to the equipment, which specifies the test date, the test person and the date of the next test (month/year). In practice, a green approval sticker (so-called "TÜV sticker") has proven its worth. This can easily be procured and has the advantage that its meaning is easily understood.

14.3 Out of calibration

In the event of being out of calibration, the equipment must be rejected immediately. The equipment is to be clearly labelled accordingly, e.g. with a red "Rejected" sticker, labelled with the date/signature and this is to be noted in the equipment log book. Further measures for the equipment must be stipulated accurately. This can include repeating the calibration (re-calibration), alignment or other measures such as maintenance, repair or even disposal of the equipment. The further steps to be taken must be defined specific to the equipment. It is also necessary to check which analysis results obtained with the equipment are to be re-evaluated retrospectively. The measures must be documented.

Summary

All equipment used for analytical work must be calibrated. The scope is to be defined individually for each piece of equipment.

A basic interval of e.g. once per year, applies as the test interval, but this must be adjusted according to the equipment.

The calibration status of the equipment is to be clearly labelled (e.g. green release sticker, red rejected sticker). The date of the next calibration is to be specified.

The documentation must be clean and complete (log book).



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