Title: Calibration and use of Balances in a Quality System
1Calibration and use of Balances in a Quality
System
2Calibration and Daily use of Balances
- Tony Kowalski
- Sartorius Lab Weighing
3Calibration and Daily use of Balances
- Balances and Scales in Quality Systems
- Equipment Qualification
- Terminology
- Good weighing Practice
- Calibration
- Calibration Weights
4Calibration and Daily use of Balances
- Balances under 90/384/EEC
- Choosing the right balance acc. to USP
- Uncertainty of measurement
- Setting appropriate pass fail criteria
- Summary and Open Question Session
5Why do we need a quality System like GLP
- To avoid Litigation Claims
- To build purchaser-supplier confidence
- To maintain marketability
- To optimise costs/profitability
6Good Laboratory Practice (GLP) Requires
- Qualified and competent personnel
- Defined appropriate equipment and conditions
- Testing facility designed to minimise problems
- Record management/Archive
7Good Laboratory Practice (GLP) Requires
- Suitable Test and Reference Standards and
Internal Audit System - Documented SOPs
- Regular Calibration of Measuring Equipment
According to Accepted Methods
8 For GLP Balances have printouts to identify
- Model Manufacturer
- Serial number
- Software version number
- All adjustment routines
9For GLP Premium Balances have these features
- Internal Adjustment Weights
- Real Time Clock
- Alpha Numeric Data Input
- Bar Code Scanner Connectivity for sample IDs
10Typical GLP/GMP Compliant Printout
- 13.11.1998 11.45.23
- Sartorius AG
- Model LP6200S
- Ser. no. 60419914
- Ver. no. 01-30-01
- ID QCLab 22
- -----------------------------------------------
- Internal Calibration
- Start isoCAL/temp
- Diff. 0.07g
- Internal adjustment completed
- Diff. 0.00g
- -----------------------------------------------
- 13.11.1998 11.46.23
- Name Joe Bloggs
11Typical GLP/GMP Compliant Printout
- 13.11.1998 11.45.23
- Sartorius AG
- Model LP6200S
- Ser. no. 60419914
- Ver. no. 01-30-01
- ID QCLab 22
- -----------------------------------------------
- Internal Calibration
- Start isoCAL/temp
- Diff. 0.07g
- Internal adjustment completed
- Diff. 0.00g
- -----------------------------------------------
- 13.11.1998 11.46.23
- Name Joe Bloggs
12Typical GLP/GMP Compliant Printout
- 13.11.1998 11.45.23
- Sartorius AG
- Model LP6200S
- Ser. no. 60419914
- Ver. no. 01-30-01
- ID QCLab 22
- -----------------------------------------------
- Internal Calibration
- Start isoCAL/temp
- Diff. 0.07g
- Internal adjustment completed
- Diff. 0.00g
- -----------------------------------------------
- 13.11.1998 11.46.23
- Name Joe Bloggs
13Typical GLP/GMP Compliant Printout
- 13.11.1998 11.45.23
- Sartorius AG
- Model LP6200S
- Ser. no. 60419914
- Ver. no. 01-30-01
- ID QCLab 22
- -----------------------------------------------
- Internal Calibration
- Start isoCAL/temp
- Diff. 0.07g
- Internal adjustment completed
- Diff. 0.00g
- -----------------------------------------------
- 13.11.1998 11.46.23
- Name Joe Bloggs
14Hardware Validation or IQ/OQ
- Equipment Qualification EQ
- What is it?
- Why?
- Description!!
15Installation Qualification or IQ
- Completeness Check
- Record Serial
- Software Version
- Location
- Accessories
- Appropriate Safety Standards
16Operational Qualification or IQ
- Testing against Specification
- Subject to Environmental conditions
- Testing Functionality of Balance
- Essentially a Full Calibration
17Performance Qualification PQ
- Performed by the Operator
- Daily or Weekly
- User Defined
- One or Two Calibration Weights
- Outlined in the SOP
18Design Qualification DQ
Design Qualification DQ
- Confirmation that the Equipment is Suitable for
the Application - Can include Copies of Quality/Safety Certificates
19Finally The Maintenance Log
1 Tonne
- Record of Service Visits
- Calibration Results
- Any Repairs Done
- Modifications
- Date of Next Visit
20Calibration and Daily use of Balances
- Terminology
- Weight Units
- Basic Principle of an Electronic Balance
- Care in the use of balances
- Hazards to avoid
21Terminology
Is this you?
- Accuracy
- Readability
- Sensitivity
- linearity Error
- Repeatability
- Uncertainty
Then order your copy of The Fundamentals of
weighing - Now!
22Accuracy
- Is the extent to which the readout approaches the
true value of the object.
23Readability
- The smallest difference that can be measured.
- Resolution or Discrimination
24Reproducibility of a Balance
0.01g
25Reproducibility of a Balance
0.03g
26Linearity - Deviation from Theoretical Strait Line
27Linearity - Deviation from Theoretical Strait Line
28Linearity - Deviation from Theoretical Strait Line
0.01g
29Sensitivity Drift
- Quantitative measure of drift per degree Celsius.
- (2x10-6) x (5C) x 10g 0.1mg
- 1 Error!
- Defined Temperature Range between 10-30C
- isoCal
30Errors - out of level weighing
- Balance table 1m x 1m
- Raise one side 5mm
- Before 200.00000g
- After 199.99850g
- Difference 0.00150g
31Errors - changes in regional gravity
- Ground Floor 200.00000g
- First Floor 199.99974g
- Difference 0.00026g
32Weight Units
33(No Transcript)
34Good Weighing Practice
- Keep Balance Clean
- Site Balance on Firm Surface
- Level the balance
- Free from Drafts
- Not in Direct Sunlight
- Not near a Radiator
35Good Weighing PracticeHazards to Accuracy
- Electro Static Influences from
- Plastic Containers
- Oven Dried Glassware
- Some Samples
- Magnetic/ Electromagnetic Effects
- Stirring Bar!
- Steel Containers
36Calibration and Daily use of Balances
- Calibration weights
- Design
- Class of weights
- How to Adjust a Balance
- Internal v External Weights
- Daily Calibration Checks
37Metrology and Standards(which is the odd one
out?)
- m Meter
- s Second
- A Ampere
- K Kelvin
- cd Candela
- kg Kilogram
- Length
- Time
- Electric Current
- Temperature
- Luminous Intensity
- Mass
38Metrology and Standards(which is the odd one
out?)
- m Meter
- s Second
- A Ampere
- K Kelvin
- cd Candela
- kg Kilogram
- Length
- Time
- Electric Current
- Temperature
- Luminous Intensity
- Mass
39The International Prototype kilogram
Definition
- The International prototype kilogram is-
The mass of the international prototype which is
held at the BIPM in Paris - Cylinder of Platinum - iridium (90Pt, 10Ir)
39mm diameter, density 21.5gcm-3
40The National Measurement System
41The National Measurement System
42The National Measurement System
43The National Measurement System
44The National Measurement System
45Calibration Weights and OIML
- Organisation International de Metrology Legale
- Specifies Design, Material,
Surface Quality, Tolerances, Markings,
Manufacture - RI 111
46Classes 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
47Conventional mass
- The certified mass of a weight is not its true
mass - but is
- The hypothetical amount of stainless steel,
density 8.00gcm-3 that it would exactly
counter-balance in air of density 0.0012gcm-3 at
20oC
48Handling and care of weights
- Construction and shape
- Designed to minimise surface area
- Convenient to handle
- Minimum risk of physical damage
49Handling and care of weights
- Primary standards are cylindrical
- Laboratory weights Knob or cylindrical
- Flat or concave base?
- OIML recommends slight concave
50Handling and care of weights
- Weight Calibration Laboratories store weights
under a Glass Dome - E2 and F1 store in Boxes supplied
- Oak boxes can be acidic
- Suitable lining material
- Free from fibres
51Handling and care of weights
- Use lifting devices
- Plastic forks
- Tipped forceps keep clean!
- Cotton or chamois gloves
52Handling and care of weights
- Remove dust with camel hair brush
- Never touch weights
- Fingerprints are acidic and greasy
- Clean weights with cotton or chamois
- Alcohol or steam cleaning removes absorption layer
53Handling and care of weights
- Weights become heavier with depositions
- Weights become lighter with wear and tear
- Regular calibration and cleaning recommended
54Handling and care of weights
- E1 and E2 intervals not exceeding 2 years
- F1 every year
- Review after some history
- Maximum change one half to one third uncertainty
55Handling and care of weights
- Calibration of weights
- Weights examined and cleaned before calibration
- Weights must be acclimatised prior to calibration
56Handling and care of weights
- Weights checked for magnetic susceptibility
surface finish - In some cases density
- Calibration made according to mass comparison
method
57Calibration of Laboratory Balances
- What is the difference between Calibration and
adjustment ?
58Calibration of Laboratory Balances
- Calibration determines the relationship between
displayed values and mass of a certified standard
No intervention takes place - Adjustment reduces any deviation to an acceptable
minimum
59Calibration of Laboratory Balances
Calibration test with 10g weight
60Adjustment of a laboratory balance
61Calibrating Laboratory Balances
- Frequency -depends influence of observed error
to the experiment or manufacturing process - Daily or before use - using a single or small
number of weights - Full Calibration - As per your SOP Once
or twice a year including linearity,
eccentric loading repeatability test
62How to Adjust Laboratory Balances
Calibrating Laboratory Balances
- Adjustment -Usually a fixed single point
- Some balances can select variable points
- Some balances allow input of certified mass the
of calibration weight - Some balances have internal weights of either the
nominal value or may be proportional
63How to Fully Calibrate Laboratory Balances
Full Calibration of Laboratory Balances
- Usually by a competent third party
- Sometimes the manufacturer
- Some small agents can seem cheaper
- ISO 9000 (ISO 2000 soon)
- UKAS not always essential
64How to Fully Calibrate Laboratory Balances
Calibrating Laboratory Balances
- The balance must be equilibrated to ambient
conditions and at operating temperature - (Adjust the balance with internal weight)
- Check the entire weighing range for departures
from linearity 6-10 equally spaced points
65How to Fully Calibrate Laboratory Balances
Calibrating Laboratory Balances
- Repeatability test
- 6-10 measurements the calculate the SD
- Off Centre load test (at half load)
- Hysterisis test
- 0.00g 500.00g 1000.00g
66Calibration Records to be kept
- Description and unique ID of Balance
- Calibration results
- Source of Calibration used
- Service/Maintenance Log
67Calibration Records to be kept
- Error limits
- Any limitations of use
- Responsible person(s)
68USP Measurement to 0.1 max Uncertainty
- United States Pharmacopoeia
- Implemented by the FDA Food and Drugs
Administration
69USP Measurement to to 0.1 max Uncertainty
- Pharmaceutical Laboratories
- All measurements to be made with intended
accuracy - 0.1 maximum uncertainty
70What is Uncertainty?
- Sum of systematic and random errors
- Systematic errors- from the balance
- Random Errors- from operators, and the
environment,
71Errors
- Random Errors
- Operators
- Off Centre Loading
- Occasional Poor conditions
- Occasional Drafts
- Occasional Vibration
72Errors
- Systematic Errors
- Inherent performance flaws
- Errors in Calibration
- Temperature change
73What is Uncertainty?
- Measured mass 20.0000g
- Determined Uncertainty 0.0003g
- Result is likely to lie between 19.9997
and 20.0003g
74Measurement to 0.1 max Uncertainty
- According to USP25 section 41
- Maximum of 0.1 uncertainty in any weighing
75Measurement to 0.1 max Uncertainty
- For USP Uncertainty is accepted as equal to 3
times the determined SD (In the place of
use)
76Measurements to 0.1 max Uncertainty
- To determine if balance is acceptable for 300mg
- Standard deviation 0.1mg
- Uncertainty 0.1 x 3
- Uncertainty 0.3mg
77Measurements to 0.1 max Uncertainty
- The Question is
- 0.3 mg lt (or equal to) 0.1 of 300mg
78Measurements to 0.1 max Uncertainty
USP statement SD /sample weight 0.001 0.3/300
0.001
79USP Minimum Weight to 0.1 max Uncertainty
- Even easier
- Minimum weight is calculated
- Measured SD x 3 x 1000
- 0.1mg x 3 x 1000
- 300mg
80Typical theoretical minimum weights
Readability
Typical Minimum weight
- 1mg balance 3000mg
- 0.1mg balance 300mg
- 0.01mg balance 45mg
- 1µg balance 3mg
81Determination of minimum weight
82USP Minimum Weight to 0.1 max Uncertainty
- Common questions
- Can I add the weight of the container
- Do I test with the actual weight of sample
- Do I test with a tare value
- What if I obtain a fluke SD
83USP Minimum Weight to 0.1 max Uncertainty
- What is uncertainty?
- Sum of Random Systematic errors
- So what is this 3x SD nonsense!
84Determination of Uncertainty
- Remember from before
- Statistically 68 results one S
- Statistically 95 results two S
85Determination of Uncertainty
- Maximum uncertainty u is defined as 2S
- 95 results lies within 2S
86Determination of Uncertainty with 10g sample
- Reproducibility 0.07mg
- Temp drift 5C
- 10g x 1 x 10-6 x 5C 0.05mg
- Max linearity 0.15mg
- E2 calibration error 0.015mg
- (200g max 0.3mg)
87Determination of Uncertainty with 10g sample
- Density is 2gcm-3 with 20 uncertainty
- Difference due to air buoyancy 2.25mg
- 2.25mg with u of 20 0.45mg
88Determination of Uncertainty with 10g sample
89Determination of Uncertainty with 10g sample
mg
90Determination of Uncertainty with 10g sample
- We can now say
- 10.0000 0.05mg with 95 confidence
91Setting pass fail limits
- You can determine what is possible from your
balance - You have a measured value for your weight
- Set limits in accordance with tolerable error in
your assays
92Summary and Open Question Session
What about balances and 21CFR part 11?