United States Pharmacopeia – Chapter 41 New Release

Dirk Ahlbrecht
Director Marketing Lab Weighing • Sartorius LPS
UPS Expert Panel Member for USP Chapters 41 and 1251
May, 2015
 Have you heard about
the new USP?

...it’s easier than you think!

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

... it’s all about accurate measurements!

• A balance always has a measuring uncertainty error

• The smaller the sample, the larger the effect of the measuring uncertainty error (relatively)
• USP dictates a maximum uncertainty error of 0.10%
• This demand specifies the usable weighing range (operating range) of the balance

measuring
uncertainty
error (rel.)
1% Operating Range
not allowed

0.10%

sample
weight
0%
0g 1g 10g 100g 200g max
X mg
capacity
US Pharmacopeia Chapter 41 “Balances” – Background

• FDA inspects customers on USP regulations

• USP Chapter 41 is mandatory

• Minimum accuracy of 0.10% for important

measurements is dictated

Please note:
• Near its zero point, a balance is relatively inaccurate.
• The higher you go in a balance’s weighing range, the
more accurate it is (relatively)
US Pharmacopeia Chapter 41 “Balances” – New Release

• From December 1st 2013 on, the new USP release has
been available
• From July 1st 2014 the first revision of Chapter 41 is
active

• First significant changes of Chapters 41 and 1251

after 20 years

• 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
US Pharmacopeia Chapter 41 “Balances” – New Release

1. Repeatability:
• Defines the starting point of the operating
range of the balance

• Calculation from 10 measurements

2 SD
 0.10% • 2 x Standard Deviation / nominal value ≤
W 0.10 %

OR min  2 * SD * 1000 • The starting point of the operational

weighing range

• When SD < 0.41d, it must be replaced by

OR min  2 * 0 .41 * 1000  820 d 0.41 digits

OR = Operating Range
SD = Standard Deviation
d = Digit
W = smallest desired Net Weight
US Pharmacopeia Chapter 41 “Balances” – Repeatability

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.

weight on
balance max capacity, e.g. 220 g
starting point
200 g
with min accuracy of
0.10%
Please note:

100 g The higher you get in the

weighing range of a
balance, the more
accurate (%) it is!

0g 100 g 200 g displayed weight value

US Pharmacopeia Chapter 41 “Balances” – Repeatability

What does this mean?

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!
US Pharmacopeia Chapter 41 “Balances” – Repeatability

What does this mean?

Please note:
3. The absolute minimum is defined new d = digit
A digit is one displayed
old: 1000 d (acc. Sartorius interpretation) step on a balance
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:

Operating Range
Balance Type Readability
optimal typical*
MS*2.7S 0.1 µg 0.082 mg – 2 g 1 mg
MS*6.6S 1 µg 0.82 mg – 6 g 1- 2 mg
MS*225S 0.01 mg 8.2 mg – 220 g 20 mg
MS*224S 0.1 mg 82 mg – 220 g 90 mg
MS*623S 1 mg 820 mg – 620 g 900 mg

*based on Sartorius’ experience

US Pharmacopeia Chapter 41 “Balances” – Accuracy

2. Accuracy:

• Defines the test weight and the weight class

• Weight must be within 5% to 100% of

Vm  0.10%Wt capacity
• Deviation of measured value compared to
weight value ≤ 0.10% of weight value

Mw  1 / 3 * 0 .10 % • The measuring uncertainty of the weight must

be 1/3 of 0.10%

Wt = Test Weight
Mw= measuring uncertainty of weight
Vm = Wt ± Mw
US Pharmacopeia Chapter 41 “Balances” – Accuracy

What does this mean?

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

• Customers must use calibrated weights to be able to show the uncertainty of the
weights – an extra service we can provide!

• No need to use higher class weights, ASTM Class 2 traceable weight (OIML F1 or F2)
with certificate is often absolutely enough!
US Pharmacopeia Chapter 41 “Balances” – New Release

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
US Pharmacopeia Chapter 41 “Balances” – Summary

Chapter 41 Old New

Applies only to assays of substances Applies to all sample weights
Scope of validity Determination of the minimum sample
Determination of the operating range
weight

Repeatability (around the starting point)

Repeatability tolerance 0.1(49)% 0.10%

Expansion factor K 3 2

Number of weighing values for the repeatability

10 10
test

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

Smallest possible sample weight/lowest starting

1,000 d 820 d
point

Accuracy

Tolerance None specified ≤ 0.10%

Between 5% and 100% of the

Test weight None specified
balance’s capacity
Thank you very much for
your kind attention