Sartorius Weighing Seminars · Regulations in the pharmaceutical laboratory and Weighing related regulations 24. September 2013 36 Which weighing related regulations are relevant

Sartorius Weighing Seminars

Regulations and Procedures to ensure best Weighing Accuracy in your Laboratory

Modules

2

• Terminology - Avoid errors and understand their daily impact on your

weighing accuracy (Uncertainty)

• Regulations in the pharmaceutical laboratory

• Accurate sample weighing to 0.10% uncertainty according to USP

• Qualification of your laboratory balance

• Monitoring your laboratory balance

Optional:

• Calibration weights - selection, storage and correct handling

• Product presentation Secura, Quintix and Practum

24. September 2013

Qualified Accurate weighing

324. September 2013

Qualified Accurate weighing requires:

• Trained competent personnel

• Defined appropriate equipment and

conditions

• Testing facility designed to minimise

problems

424. September 2013

Qualified Accurate weighing requires:

• Regular calibration of measuring

equipment

• According to accepted methods

• Use of Appropriate test & reference

standards – Calibration Weights

524. September 2013

Qualified weighing requires you to:

• Keep your balance clean

• Position the balance on firm surface

• Level the balance

• Protect the balance from drafts

• Especially air conditioning

• Never position in direct sunlight

• Keep well away from all heat sources

24. September 2013 6

Avoid hazards that impact on your weighing resultsThe correct place of installation?

• Mechanically and climatically stable

− stable temperature and humidity

− better on the first floor than on

upper floors

• No vibrations

− especially low frequencies

< 10Hz should be avoided

− better to be closer to a wall, than

in the middle of the room

724. September 2013

Aircondition Open doors

Open windows

Sunlight

Air draft

unstabletable

Humidity

Hustleand Bustle

Vibrations

Avoid hazards that impact on your weighing resultsThe correct place of installation?

• Avoid installation in the exhaust area

of an air conditioner (disturbances and

temperature)

• Not near to a window, no direct sunlight

− avoid infrared radiation;

no direct light e.g.... a desk lamp

• Quiet place without hustle and bustle

824. September 2013

Aircondition Open doors

Open windows

Sunlight

Air draft

unstabletable

Humidity

Hustleand Bustle

Vibrations

Terminology

• Readability

• Maximum capacity

• Response time

• Repeatability

• Linearity

• Sensitivity drift

• Accuracy

• Uncertainty


Readability

The smallest change in weight

that can be measured


Readability



1124. September 2013

Readability



• 9.99g �10.00g

• Readability = 0.01g (d)


Weighing capacity

The maximum amount that can be

weighed out before overloading occurs


Weighing capacity

The maximum amount that can be

weighed out before overloading occurs

8,200 maximum capacity – 5,000 load

= 3,200g remaining weighing capacity

A fill guide prevents overload after taring


Stabilisation Time

The time taken for the balance to become

stable after the load is applied

A stable reading is indicated by showing

the „g“


Repeatability

Repeatability, or test-retest reliability,

is the variation in measurements taken

by a single person or instrument on the

same item and under the same

conditions.


Repeatability of a balance


± 0.01g

Linearity

Deviation from the theoretical linear slope


± 0.01g

± 0.0001g

Sensitivity DriftDrift associated with temperature change

• ± 1x10-6 per degree Celsius or:

• ± 1 part per million per degrees Celsius

• Relating to a 200g Calibration Weight

• 200.0000g x 10-6

• or

• 200.0000g ÷ 1,000,000

• 0.0002g drift per degree Celsius


Accuracy

• Is the extent to which the readout

approaches the true value of the object.

• Accuracy is subject to local random and

systematic influences therefore cannot

be specified

• Accuracy can only be determined at the

place of use


Uncertainty of measurement


• Any measured value is only meaningful when presented together with it’s

determined uncertainty

• Uncertainty indicates the range above and below the measured value,

in which it will lie

• e.g.

• 20.0003g ± 0.0005g

• with 95% confidence

• Meaning: a 95% certainty the true value is within the range 19.9998g - 20.0008g

Avoid external errorsElectrostatic charges


• Electrostatic charges create an acting force in addition to the weight of the sample

and container.

− This force is not constant. It’s influenced by humidity, the user and handling of

samples and containers.

− The weight readout drifts in one direction. Values are non-repeatable.

• Static electricity occurs on:

− substances or containers with low electrical conductivity

− large surfaces (plastic or glass containers, filters)

• The reasons are:

− internal friction in powders, external friction

− transfer of electrical charges by persons

− problem increases with decreasing humidity (<40%)

Avoid errorsElimination of electrostatic Charges

Internal solutions:

• Built-in ionizer inside the draft shield of

semi-micro, analytical and 1mg-balances

External solutions

• Ionizer cube YIB01

• Stat Pen YSTP01 for small sample

containers and membrane filters


Avoid errorsMagnetic and magnetisable samples

The problem:

Magnetic materials in samples or containers, such as

nickel, iron, steel, generate force fields that act against

the permanent magnet of the weighing system.

• Weight values are stable, but non-repeatable.

• Different values are displayed depending on theposition of the sample on the weighing pan.

How to avoid:

• Do not weigh with magnetic stirrer inside the vessel

• Perform demagnetisation before weighing. Use a nonmagnetic object to distance the sample from theweighing pan.

• Use Mu-metal (81% Ni and 19% Fe) foil as shielding.

• Use below balance weighing


Avoid errorsNon-level balance

One of the worst errors that occurs during

weighing is caused when the balance is

out of level.


αααα

400µm

Avoid errorsNon-level balance

Example:

If the balance is inclined only 400µm

(Thickness of a business card) on one side

an incorrect measurement is produced:

• That means, the mass of 200g is displayed 0.37mg too low

• The resulting error is greater than the allowable tolerance of a 200g ± 0.3mg E2 calibration weight for an analytical balance.

Error calculation:

md = m · cos α = 200g · cos (0,11°)

= 199,99963g

α = arctan (0.4mm/200mm)

∆m = -0.00037g


αααα

400µm

Avoid errors – due tochanges in regional gravity, influenced by changes in elevation andlatitude

• Ground floor 200.00000g

• First floor 199.99974g

• Difference 0.00026g


Avoid errors:Balance warm-up period

Balances need to be warmed up

(after new installation)

• Precision Balances (d >1 mg)approx. 30 min

• Analytical Balances (d> 0.1 mg)approx. 4 h

• Semimicro Balances (d> 0.01 mg)approx. 12 h

• Ultramicro/Micro Balances (d> 0.001 mg)approx. 24 h

To avoid subsequent warm up periods :

• do not disconnect from power

• Always leave balance in the standby-mode


Avoid errorsCritical samples

Hygroscopic substances:

• Moisture absorption of powders

Efflorescent substances

• evaporation from the sample

• both cause a real weight change

• different results when weighing the

sample at different times

• weighing value is drifting

How to avoid?

• use narrow-necked or covered vessels

• stabilise sample humidity in a desiccator

• work quickly24. September 2013 29

Avoid errorsNon acclimatised samples and tare containers

Sample containers are very often not

sufficiently acclimatised:

• temperature differences betweenweighing chamber and sample/samplevessels

• weighing results are varying

• weighing value is drifting:

− sample too cold: “weight increasing”

− sample too warm: “weight decreasing”

How to avoid?

• acclimatisation of sample/samplecontainers

• place weighing containers and sample inside weighing chamber beforeweighing


Avoid errorsHandling of samples, vessels and calibration weights

• handling the sample with hands raises

temperature and causes “gain-weight”

effects

• this temperature effect can still be

recognised after 10 minutes

• fingerprints falsify the real mass approx.

50 to 100µg

• additionally fingerprints can be

hygroscopic

• using the hand inside the draft shield

causes additional turbulence and

temperature effects

• weighing values are different, not stable

and drifting


Avoid errorsHandling of samples, vessels and calibration weights

How to avoid?

• never handle the sample without

tweezers or some other suitable gripping

device

• always use gloves

• avoid working inside the draft shield, use

a spatula which is long enough to keep

the hand outside


Modules

33

• Terminology - Avoid errors and understand their daily impact on your weighing

accuracy (Uncertainty)





Optional:



24. September 2013

Following Regulations in the pharmaceutical laboratoryWhat should you expect from your balance supplier

• Manufacturers expertise

• Reliable, highly precise products

• Adaptible to meet pharmaceutical

regulations

• Global service and support

• Feel safe factor


Following Regulations in the pharmaceutical laboratoryWhat can you expect from Sartorius

Help and advice from experts in all

weighing related questions

Local weighing specialist - Worlwide

This mainly includes the expertise of the

practical handling of the pharmaceutical

related standards and regulations.

Plus: help in selecting the correct

balance based on your weighing needs


Regulations in the pharmaceutical laboratory andWeighing related regulations


Which weighing related regulations are relevant in pharmaceutical Laboratories

• Quality Control

• GLP/GMP

• FDA

• ISO 17025 (government lab, accredited)

• Legal Metrology - verified balances in Europe subject to local differences

• R&D

Regulations in the pharmaceutical laboratoryGLP/GMP

GLP

• in labs that work on preclinical studies

GMP

• in Labs that work in the clinical phase

and beyond (includes QC)

General demands:

• control of inspection, measuring and test

equipment (e.g. calibrations)

• instrument qualification (IQ, OQ, PQ)

• documentation of measured values

• standardised procedures (SOP)

• Four eyes principle


Regulations in the pharmaceutical laboratoryFDA

FDA –Food and Drug Administration

• General Demands

− process validation

− 21CFR Part 11 electronic data handling

− electronic signatures

− audit trails

• Special Demand:

− USP (United States Pharmacopeia)

− determination of the Operating Range


Regulations in the pharmaceutical laboratoryLegal Metrology

• Legally required and controlled quality

assurance system to protect consumers

• acc. international guidelines

(e.g. OIML R76)

• translated into national law

• globally large differences


Regulations in the pharmaceutical laboratoryWhere must a verified balance be used in Europe?


• determination of mass for commercial transactions;

• determination of mass for the calculation of a toll, tariff, tax, bonus, penalty,

remuneration, indemnity or similar type of payment;

• determination of mass for the application of laws or regulations; expert opinion

given in court proceedings;

• determination of mass in the practice of medicine for weighing patients for the

purposes of monitoring, diagnosis and medical treatment;

• determination of mass for making up medicines on prescription in a pharmacy and

determination of mass in analyses carried out in medical and pharmaceutical

laboratories;

• determination of price on the basis of mass for the purposes of direct sales to the

public and the making-up of pre-packages

Verified balances are marked with M

Renewing is subject to local regulations

Regulations in the pharmaceutical laboratory


... a lot of different regulations with different demands

BUT

... there is one similarity :

Not all regualtions are not defined specifically for balances –

specifics given in general terms (so as to fit all lab measuring equipment)

Regulations in the pharmaceutical laboratoryMeasurement and test equipment acc. DIN ISO 10 012


Target

• To ensure that measurements are made with the intended accuracy

• To specify the features of a system which ensures that measuring equipment

meets the requirements for its use.

Regulations in the pharmaceutical laboratoryRequirements for measuring and test equipment acc. DIN ISO 10 012


• The required metrological characteristics must be established, e.g. accuracy,

stability, range and resolution.

• Accuracy: Essentially, the accuracy of measuring equipment should be preferably

1/10 of the permissible error in your process. However, for economic reasons, an

accuracy of 1/3 of this error is still acceptable.

• An additional requirement is to establish and maintain a documented system for

managing, confirmation and use of measuring equipment, including measurement

standards.

Regulations in the pharmaceutical laboratoryRequirements for measuring and test equipment acc. DIN ISO 10 012


• When measurements are performed, all significant identified uncertaintiesin the measurement process, including those contributed by personnel, procedures and

environment, must be taken into account.

• Calibrations and adjustments are to be performed at prescribed

intervals using measuring and test equipment, including measurement standards, that

has been cross-checked against other standard in an officially recognised procedure to

demonstrate and confirm the traceability of this equipment to the standard.

• Written procedures (Standard Operating Procedures) must be

provided and used for all important aspects concerning the use of measuring and test

equipment.

Page 1

United States Pharmacopeia – Chapter 41 New Release

Have you heard about

the new USP?

24. September 2013

...it is easier than you think!...it is easier than you think!...it is easier than you think!...it is easier than you think!

US Pharmacopeia Chapter 41 „Balances“ – New Release USP39Operational Range

USP no longer mentions „Minimum

Sample Weight“

New:

User defines the „Opeartional Range“


Displayed W

eighing Value

OperationalRange

Operational

range

Displayed W

eighing Value

200g

US Pharmacopeia Chapter 41 “Balances” – it is easier than you think!

... it is all about measuring uncertainty (accuracy)!

0.1%

• USP dictates a maximum uncertainty error of 0.10%

measuringuncertaintyerror (rel)

sample weight

• as smaller the sample, as larger the effect of the measuring uncertainty error (relatively)

• a balance always has a measuring uncertainty error

X mgmaxcapacity

Operating Range

not allowed

• this demand specifies the usable weighing range (operating range) of the balance

0g 1g 10g 100g

0%

1%

US Pharmacopeia Chapter 41 “Balances” – Why?

• FDA inspects customers on USP regulations

• USP Chapter 41 is mandatory

• Minimum accuracy of 0.10% for important

weighings is dictated

24. September 2013

Please note:

• Near its zero point, a balance is very inaccurate.

• The higher you go in a balance’s weighing range,

the more accurate it becomes (relatively)

US Pharmacopeia Chapter 41 “Balances” – New Release

• From the 1st of December 2013 on, the new

USP release will be available

• After 20 years, USP Chapter 41 will be

significantly changed

• e.g. renamed from Weights and Balances

to Balances

• It does not reference minimum sample

weight anymore, it defines Repeatability and

Accuracy, which specifies the Operating

Range

24. September 2013


• Defines the starting point of the

operating range of the balance

• Calculation from 10 measurements

• 2 x Standard Deviation / nominal value

≤ 0.10 %

• The starting point of the operational

weighing range

• When SD < 0.41d, it must be replaced

by 0.41 digits

24. September 2013

%10.0W

SD 2≤

1000**2min SDOR =

dOR 8201000*41.0*2min ==

OR = Operating RangeSD = Standard Deviationd = DigitW = Weight

1. Repeatability:

US Pharmacopeia Chapter 41 “Balances” – Repeatability

September 24, 2013

What does this mean?

1. The new USP does not refer to minimum sample weight anymore. It specifies the

operating range. The operating range is specified by the capacity and a “starting point”

(formally known as minimum sample weight) – so this starting point needs to be defined

according to the Repeatability determination routine.

0 g 100 g 200 g displayed weight value

weight on balance

100 g

200 g

max capacity, e.g. 220 g

starting pointwith min accuracy of 0.10%

Please note:

The higher you get in the

weighing range of a

balance, the more

accurate (%) it becomes!



2. The determination parameters are modified:

old: 3 x SD (three times standard deviation)

new: 2 x SD (two times standard deviation) - 30%

old: 0.1 % (which means 0.149%)

new: 0.10% (not possible to enlarge) + 30 %

• So the result will be in a similar range

• No significant changes expected!

September 24, 2013



3. The absolute minimum is defined new

old: 1000 d (acc. Sartorius interpretation)

new: 820 d (2 x 0.41d x 1000 = 2 x 410d)

• This means that the maximum operating range for a Sartorius balance goes from

820d to max capacity:

Balance Type Readability Operating Range

optimal typical*

MS*2.7S 0.1 µg 0.082 mg – 2 g 1 mg – 2 g

MS*6.6S* 1 µg 0.82 mg – 6 g 2 mg – 6 g

MS*225S* 10 µg 8.2 mg – 220 g 20 mg – 220 g

MS*224S* 0.1 mg 82 mg – 220 g 100 mg – 220 g

MS*623S* 1 mg 820 mg – 620 g 900 mg – 620 g

September 24, 2013

Please note:

d = Digit

A digit is one displayed

step on a balance

****based on Sartorius’ experience

US Pharmacopeia Chapter 41 “Balances” – Accuracy

• Defines the test weight and the weight

class

• Weight must be within 5% to 100% of

capacity

• Deviation of measured value compared to

weight value ≤ 0.10% of weight value

• The measuring uncertainty of the weight

must be 1/3 of 0.10%

September 24, 2013

WtVm %10.0≤

%10.0*3/1≤Mw

Wt = Test WeightMw= measuring uncertainty of weightVm = Mw - Wt

2. Accuracy:

US Pharmacopeia Chapter 41 “Balances” – Accuracy


1. The USP describes the quality of the weights, used for this test

e.g. 100 g Accuracy ≤ 0.1 g 99.9000 ... 100.1000 g

Measuring uncertainty ≤ 0.03 g

• Calibrated weights must be used to be able to show the uncertainty.

• No need to use higher class weights, F1 or F2 is absolutely enough!

24. September 2013


Additional Information:

• The USP now defines that customers must use “calibrated balances”.

• There are different ways to calibrate a balance.

• A well accepted method is according to ISO 17025

• Sartorius offers the service to perform ISO 17025 calibrations.

24. September 2013

US Pharmacopeia Chapter 41 “Balances” – Summary

24. September 2013

Chapter 41 Old New

Scope of validity

Applies only to assays of substances Applies to all sample weights

Determination of the minimum sample weight

Determination of the operating range

Repeatability (around the starting point)

Repeatability tolerance 0.1(49)% 0.10%

Expansion factor K 3 2

Number of weighing values for the repeatability test

10 10

Acceptance criterion 3 x std. dev./m ≤ 0.1% 2 x std. dev./m ≤ 0.10%

Smallest possible sample weight/lowest starting point

1,000 d 820 d

Accuracy

Tolerance None specified ≤ 0.10%

Test weight None specifiedBetween 5% and 100% of the balance’s capacity

US Pharmacopeia Chapter 41 “Balances” – Summary

24. September 2013

Chapter 41 Old New

Scope of validity

Applies only to assays of substances Applies to all sample weights

Determination of the minimum sample weight

Determination of the operating range

Repeatability (around the starting point)

Repeatability tolerance 0.1(49)% 0.10%

Expansion factor K 3 2

Number of weighing values for the repeatability test

10 10

Acceptance criterion 3 x std. dev./m ≤ 0.1% 2 x std. dev./m ≤ 0.10%

Smallest possible sample weight/lowest starting point 1,000 d 820 dAccuracy

Tolerance None specified ≤ 0.10%

Test weight None specifiedBetween 5% and 100% of the balance’s capacity


0.01000g

0.1000g

1.000g

0.00820g

0.0820g

0.820g

What we mean by Digits

USP Chapter 1251 “Weighing on an Analytical Balance”

Chapter 1251 is “only” a recommendation, not mandatory!

It describes methods on:

• Balance qualification and calibration

• Risk analysis for balances

• Description of applications (e.g. differential weighing)

Argumentation:

• The recommendations in 1251 is only a suggestion.

• There are other approaches available which are even better!

24. September 2013

Accurate sample weight according to USP My sample weight is 10 mg. Which balance should I use?

• 10 mg is the absolute limit for a 5

decimal balance in “perfect” conditions

• The minimum sample weight is based

on the reproducibility of a balance and

is significantly influenced by ambient

conditions at the place of installation.

• Specifying minimum weight to the

absolute limit it is not recommended

since performance is not guaranteed

over a balances complete life time.

Recommendation:

Use a microbalance with a readability

of 1 µg.


Accurate sample weight 0.10% according to USP Typical* Sample Weights achieved by Sartorius Balances

Readability/Balance Type

0.1µg

1 µg

2 µg

0.01mg

0.1 mg

1 mg

* typical = based on Sartorius experience

Smallest Sample Weight

1 mg

2 – 5 mg

5 – 15 mg

15 – 100 mg

100 mg

1 g


Modules

64







Optional:



24. September 2013

Equipment QualificationValidation - Qualification


• Validation is the documented evidence that a process fulfills the defined needs in

practical use.

• Qualification is the evidence that the equipment is able to fulfill it´s part in this

validated process

• Therefore a balance is never validated – it is qualified to be used in a validated

process

Equipment QualificationAny equipment qualification needs 4 steps


DQ = Design Qualification

IQ = Installation Qualification

OQ = Operational Qualification

PQ = Performance Qualification

Technical specification forequipment (specification meet the user requirements)

Equipment is delivered and installed in accordance with the qualified design

Test of operational functions

Test of specified application

Ongoing performance tests and preventive maintenance

Before

Purchasing

At

installation

After

installation

At regular

intervals

Equipment QualificationDesign Qualification (DQ)


• DQ is the documented collection of activities that define the functional and

operational specifications of the instrument and criteria for selection of the vendor,

based on the intended purpose of the instrument

• It documents the design of the system and include :

− Functional specification

− Technical / performance specification for equipment

• A thoroughly executed DQ ensures that:

− Specification meet the user requirements

− Design is compliant with GMP and other regulatory requirements

− Details all equipment that must be ordered

Equipment QualificationInstallation Qualification (IQ)


• IQ is the documented collection of activities necessary to establish that an

instrument is delivered as specified, is properly installed in the selected

environment, and that this environment is suitable for the instrument

• Parts of the IQ

− Comparison of the equipment received with the purchase order

− Equipment check for any damage.

− Documentation check for completeness

− Installation of hardware

− Initial cleaning

− SQ-min-Identification

Good to know:

Responsibility for IQ lies, as the whole EQ, with the user but activities can be

supported and carried out by the vendor.

Equipment QualificationOperational Qualification (OQ)


• OQ is the documented collection of activities necessary to demonstrate that an

instrument will function according to its operational specification in the selected

environment

• OQ tests verify that the instrument

− meets manufacturer or users specification

− operating within established limits and tolerances

• Parts of the OQ

− Basic function check and check if the instrument powers up after it is switched on

− Calibration

− Operator training

Equipment QualificationPerformance Qualification (PQ)


• PQ is the documented collection of activities necessary to demonstrate that an

instrument consistently performs under ‘full operational‘ conditions, and is

appropriate for the intended use

• PQ tests using production materials

• Tests include a condition or set of conditions encompassing upper and lower

operating limits

• PQ is ongoing

Good to know:

PQ is described as a separate activity, for balances it is appropriate to perform it in

conjunction with OQ

IQ/OQ-Service

• IQ/OQ documentation is based on a

generic risk analysis

• Documentation consists of the IQ and

OQ planning and of protocols for the IQ

and OQ tests

• Documentation supports GLP, GMP and

FDA guidelines

• Accredited calibration certificates for our

balances

• All documentation could easily be

integrated in existing QM systems


Equipment Qualification


One main question remains:

• What should be tested during a IQ|OQ?

− Is it important to test the right colour of the equipment housing?

− Is it important to test if the right power supply was delivered?

− Is it important to issue a calibration certificate?

• How is the scope of test defined?

Failure mode and effects analysis (FMEA)


• Sartorius IQ|OQ Documents are based on a generic risk analysis

• Potential risks that are connected with the installation and operation of a laboratory

balances where evaluated with an FMEA .

• Equipment and application specific risks had not been taken into account.

Modules

74







Optional:



24. September 2013

Monitoring the balance


Two things are important in daily work with the balance in a pharmaceutical lab:

• Monitoring the test equipment –

making sure that the balance always is working within the defined tolerance limits

• Avoiding weighing errors caused by the user, the environmental conditions and the

sample or sample container influences

Routine testing for constant safety – test equipment monitoring


Every Lab, which is accredited according to ISO/IEC 17025 or works according to the

GLP/GMP guidelines must regularly calibrate its testing equipment, and adjust as

necessary.

• Minimize the risk of erroneous measurements

• Fulfill the required process accuracy at any time

But, when and how often should calibration/adjustment be carried out on regular

basis?

• The length of the inspection interval depends on the risk of weighing, that means:

The customer has to clarify “how critical is the weighing value in the complete

process”

• Based on that evaluation „warning levels“ and „action levels“ are determined

Page 5

Monitoring test equipment– how often ?

Simple rule:• Daily, weekly or monthly in case the weight values are not critical• If weighing values are critical in the whole process, than

calibration should be done before every series of measurement

Perhaps Better:• Dynamic verification and adjustment of intervals based on

calibration results and defined warning and action thresholds

Page 6

Monitoring test equipment

Dynamic verification of calibration intervals

Time

Mea

suring Value

Upper intervention limit

Target Value

Upper warning limit

Lower intervention limit

Lower warning limit

Time

Mea

suring Value


Target Value

Upper warning limit


Lower warning limit

Increase IntervalIncrease Interval

Time

Measuring Value


Target Value

Upper warning limit


Lower warning limit

Time

Measuring Value


Target Value

Upper warning limit


Lower warning limit

Decrease IntervalDecrease Interval

Time

Mea

suring Value


Target Value

Upper warning limit


Lower warning limit

Time

Mea

suring Value


Target Value

Upper warning limit


Lower warning limit

case 1: increase intervals

case 3: call service

case 2: decrease intervals

Monitoring test equipmentHow many and which weights to use ?

Often calibration is done only at one point

of the whole weighing range.

Better:

• Calibration should be performed at three

prominent points of the characteristic

balance curve

• Near the minimum weight, to fulfill the

regulatory requirements of USP

• In the working range, where the balance

is finally used; typically this is 10 to 20%

• Near the maximum load, because at that

point the absolute error is the highest


Monitoring test equipmentThe balance is monitoring itself - isoCAL

• Sartorius Cubis and Secura series

balances are designed for

Pharmaceutical labs and include

functions, which make monitoring easier

for the user

• Automatic calibration/adjustment function

isoCAL

• isoCAL maintains the accuracy of the

balance within an narrow tolerance band

without testing efforts


It corrects:

• deviations regarding to the sensitivity

of the balance

• temperature influence

(temperature limits can be set)

• compensates the influence of gravitation

(location, differences in altitude)

• air pressure, air density and humidity

fluctuations (but it‘s not a compensation)

• aging effects of mechanic and electronic


Monitoring test equipmentThe balance is monitoring itself - isoCAL

One of the worst errors that occurs during

weighing is caused when the balance is

unleveled.


αααα

400µm

Monitoring test equipmentThe balance is monitoring itself – Q-Level


αααα

400µm


Example:

If the balance is inclined only 400µm ( thickness of a

businesscard) on one side an incorrect measurement is

produced:

md = m · cos α = 200g · cos (0,11°) = 199,99963g

α = arctan (0.4mm/200mm)

∆m = -0.00037g

That means, the mass of 200g is displayed 0.37mg too

less

The resulting error is greater than the allowable

tolerance of a 200g ± 0.3mg E2 calibration weight for

an analytical balance.

The automatic motorised leveling featured

on some balances controls that the

balance is correctly leveled and performs

the time

consuming alignment of the balance.

It is activated by pressing a start key or

fully automatically in conjunction with the

isoCAL function



Modules


• Qualified weighing

• Terminology

• Avoid errors – and understand their daily impact on your weighing accuracy

• Uncertainty determination


• Minimum sample weight according to USP



• Calibration and servicing of your laboratory balances


• Health and safety during weighing

Calibration and servicing of your laboratory balances

Would you hang up your life on bungee

which was not

regularly checked?

• How can you be sure that the bungee

has the right length for your weight

• Would you trust a balance that is not

calibrated


Calibration and servicing of your laboratory balancesMaintenance


• Qualification is not a one time event.

• The user needs to demonstrate and document with regular testing and regular

preventive maintenance that an instrument consistently performs and is appropriate

for the intended use

• Maintenance and test procedures should be in place to detect and fix problems

before they can have a negative impact on analytical data.

Calibration and servicing of your laboratory balancesCalibration


• Who has the responsibility to define the maintenance frequency?

• What is the right maintenance frequency?

• Who defines the required maintenance work?

• How should maintenance activities be documented?

The auditor is only interested in two things

PROTOCOL

How and

Where is it

documented

PLAN

Why and

How are

things done

Calibration and servicing of your laboratory balancesCalibration vs. Adjustment


Calibration:

• Calibration in metrological meaning is a measuring process for the determination

and documentation of the deviation of a measuring instrument, incorporated by a

reference standard.

• The frequency of calibration should depend on the frequency of use, and the

importance of the measuring instrument in the manufacturing process

• Calibration does not make any changes within the balance

Adjustment:

• Correction of the measurement error to within an allowable level

Calibration and servicing of your laboratory balancesTraceability

Traceability:

A calibration is traceable if the used

standard is related to a national or

international standards by a uninterrupted

chain of comparisons all having stated

uncertainties.


Calibration and servicing of your laboratory balancesAccreditation


The trust placed in calibration certificates depends on the competence of the

calibration laboratory. The accreditation of a calibration laboratory is the verification

of a independent accreditation body that the calibration is done with technical

competence and with an internationally comparative standard.

Accreditation:

• Ensures traceability to a national standard

• Documents measurement results, deviations and uncertainty of measurement

• Creates trust in the quality and safety of products and services.

Modules

92







Optional:



24. September 2013

Calibration weightsselection, storage and correct handling


Calibration Weights


• Calibration weights

• International Measurement Standards

• The International Prototype

• Design

• Class of weights

• Tolerences

• Correct handling and storage of weights

Calibration weights - selection, storage and correct handlingWeight Units


Unit Unit Symbol Relation to Base

Unit

Nanogram ng ÷ µg 1000

Microgram µg ÷ mg 1000

Milligram mg ÷ g 1000

Gram g ÷ 1000

Kilogram kg Base Unit

Ton t x 1000

Calibration weights - selection, storage and correct handling Metrology and standards - all scientifically defined?


m meter

s second

A Ampere

K Kelvin

cd candela

kg kilogram

Length

Time

Electric Current

Temperature

Luminous Intensity

Mass

Calibration weights - selection, storage and correct handling The international prototype kilogram is defined as:

• The mass of the international prototype

which is held at the BIPM in Paris

• Cylinder of Platinum Iridium - 90%

Platinum 10% Iridium 39mm diameter

and density 21.5gcm-3


Calibration weights - selection, storage and correct handling All certified weights are connected to the international 1 kg prototype


BIPM

international

NIST

USA

LNE

France

NMI

e.g. Netherlands

PTB

Germany

No. 52, 1,000 000 125 kg +/- 28 µg

90% platinum10% iridium

1 kg internationalprototype

National Metrological Institutes

Calibration weights - selection, storage and correct handling OIML

Organisation International de

Metrology Legale specifies:

• Design,

• Material,

• Surface,

• Quality,

• Tolerances

• Permissible Markings


Calibration weights - selection, storage and correct handling Classes of calibration weights


E1 Solid Stainless Steel No markings 1kg +/- 0.5mg

E2 Solid stainless Steel No markings 1kg +/- 1.5mg

F1 Stainless Steel with adjustment cavity 1kg +/- 5.0mg

Calibration weights - selection, storage and correct handling Shape of weights


• Construction and shape defined

• Designed to minimise surface area

• Convenient to handle

• Especially so for the “milligram”

weights

• Convenient to handle

• Minimum risk of physical damage

• F1 leaf weights

• E2/E1 wire weights

Calibration weights - selection, storage and correct handling Handling and care of weights

store in boxes supplied


suitable for clean room conditions

Calibration weights - selection, storage and correct handling Handling and care of weights

Use lifting devices:

• Plastic forks or tipped forceps –

keep them clean!

• Cotton or chamois gloves


Handling and care of weights

• Remove dust with (camel hair) brush

• Never touch weights

• Fingerprints are acidic and greasy

• Polish your weights with cotton or

chamois

• Ethyl Alcohol is to remove absorption

layer or grease - during recalibration

• Weights become heavier with deposits

• Weights become lighter with wear and

tear

• Regular calibration and cleaning is

recommended – After 3 performed

recertifications it is possible to give

recommendations for future calibration

intervals


Calibration of weights


• Class E1 & E2 Weights can´t be

adjusted but only calibrated.

• The calibration certificate of a weight

states the uncertainty of the weight.

Thank you very much foryour kind attention