Sartorius Weighing Seminars Qualified Weighing in Pharmaceutical - PowerPoint PPT Presentation

Sartorius Weighing Seminars Qualified Weighing in Pharmaceutical Labs Regulations and Procedures to ensure best Weighing Accuracy in your Laboratory

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

Qualified weighing requires: • Trained competent personnel • Defined appropriate equipment and conditions • Testing facility designed to minimise problems 5. Februar 2013 3

Qualified weighing requires: • Regular calibration of measuring equipment • According to accepted methods • Use of Appropriate test & reference standards – Calibration Weights 5. Februar 2013 4

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 • Never position in direct sunlight • Keep well away from all heat sources 5. Februar 2013 5

Avoid errors The correct place of installation? • Mechanically and climatically stable Air − Open doors condition stable temperature and humidity − Sunlight better on the first floor than on upper floors Open • No vibrations windows Air − − especially low frequencies especially low frequencies draft draft Humidity < 10Hz should be avoided − better to be closer to a wall, than unstable Hustle Vibrations table in the middle of the room and Bustle • Avoid installation in the exhaust area of an air conditioner (disturbances and temperature) 5. Februar 2013 6

Avoid errors The correct place of installation? • Not near to a window, no direct sunlight Air − avoid infrared radiation; Open doors condition no direct light e.g.... a desk lamp Sunlight • Quiet place without hustle and bustle Open windows Air draft draft Humidity unstable Hustle Vibrations table and Bustle 5. Februar 2013 7

Avoid errors Electrostatic 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%) 5. Februar 2013 8

Avoid errors Elimination of electrostatic Charges Internal solutions: • Built-in ionizer inside the draft shield of semi-micro, analytical and 1mg-balances External solutions • Ionizer cube YIB01 • Ionizer cube YIB01 • Stat Pen YSTP01 for small sample containers and membrane filters 5. Februar 2013 9

Avoid errors Magnetic 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 the • Different values are displayed depending on the position of the sample on the weighing pan. How to avoid: • Do not weigh with magnetic stirrer inside the vessel • Perform demagnetization before weighing. Use a nonmagnetic object to distance the sample from the weighing pan. • Use Mu-metal (81% Ni and 19% Fe) foil as shielding. • Use below balance weighing 5. Februar 2013 10

Avoid errors Non-level balance One of the worst errors that occurs during weighing is caused when the balance is unlevel. 400µm α α α α 5. Februar 2013 11

Avoid errors Non-level balance Example: If the balance is inclined only 400 � m (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: 400µm α α α α m d = m · cos α = 200g · cos (0,11° ) = 199,99963g α = arctan (0.4mm/200mm) ∆ m = -0.00037g 5. Februar 2013 12

Avoid errors – due to changes in regional gravity influenced by changes in elevation and latitude • Ground floor 200.00000g • First floor 199.99974g • Difference 0.00026g 5. Februar 2013 13

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 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 Was passiert wann • leave balance always in the standby- konkrete Empfehlungen mode 5. Februar 2013 14

Avoid errors Critical 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 Bilder Tauschen How to avoid? • use narrow-necked or covered vessels • stabilise sample humidity in a desiccator • work quickly 5. Februar 2013 15

Avoid errors Non acclimatized samples and tare containers Sample containers are very often not sufficiently acclimatised: • temperature differences between weighing chamber and sample/sample vessels • weighing results are varying • weighing results are varying • weighing value is drifting: − sample too cold: “weight increasing” − sample too warm: “weight decreasing” How to avoid? • acclimatisation of sample/sample containers • place weighing containers and sample inside weighing chamber before weighing 5. Februar 2013 16

Avoid errors Handling 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. • fingerprints falsify the real mass approx. 50 to 100 � g • 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 5. Februar 2013 17

Avoid errors Handling 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 • avoid working inside the draft shield, use a spatula which is long enough to keep the hand outside Bilder Tauschen 5. Februar 2013 18

Avoid errors Filling containers Ergonomic aspects: • sometimes it’s difficult to weigh in the sample into small vessels, flasks or tubes • the greatest problem is “spilling sample on the weighing pan” on the weighing pan” • the sample weight is displayed correctly but the sample is not inside the container How to avoid: • Use special vial holder (Q-Grip) 5. Februar 2013 19

• Minimum sample weight according to USP

Minimum sample weight according to USP Weighing in the Pharmaceutical Laboratory USP Minimum Sample Weight Determination 12,6 Kg divided by 3! 5. Februar 2013 21

Minimum sample weight according to USP United States Pharmacopeia – Chapter 41 USP 34 NF Chapter 41 Weights and Balances • determination of the minimum sample weight • the measuring uncertainty must be known – three times the standard known – three times the standard deviation out of min. 10 replicant weighings = 3 * U SD • measuring uncertainty (U) must not exceed 0.1% of the minimum sample U ≤ weight (M): 0 . 001 1000 * ≤ M U M • the factor can be extended up to 0.00149 U ≤ 0 . 001 ( 49 ) M 5. Februar 2013 22

Minimum sample weight according to USP United States Pharmacopeia - Interpretation • the USP demands the practical determination of the minimum sample weight on site • sample containers (vessels, flasks, ...) must be tared • the smalest minimum sample weight • the smalest minimum sample weight is = 1000 digits • the minimum sample weight is only applicable for „assays“!! 5. Februar 2013 23

Minimum sample weight according to USP • there are different interpretations of the USP, Chapter 41 • Sartorius determins if a mass is applicable vs • OTHERS calculates the minimum weight to measured on the balance to measured on the balance OTHERS • both procedures are globally used • BUT, important is the interpretation of the local FDA inspector... 5. Februar 2013 24

Minimum sample weight according to USP Sartorius method to determine if appropriate OTHERS calculates * 1000 = = 14 mg Sartorius has verified a 15mg weight from a Sartorius USP Certificate 5. Februar 2013 25