Are your analytical weighing procedures compliant with the new chapter 2.1.7 of the European Pharmacopoeia?

What is the European Pharmacopoeia and to whom does the new chapter 2.1.7 "Balances for analytical purposes" apply?

The European Pharmacopoeia is a set of expert texts describing quality standards for ingredients, dosage forms and methods of analysis for medicinal products for human and veterinary use. These standards are defined to ensure the quality of pharmaceutical products. Ph.Eur. is a legally binding reference for all pharmaceutical companies that place pharmaceutical products on the market of European Member States, as well as all manufacturers of medicines and/or substances for pharmaceutical use that export to the European market. Chapter 2.1.7 affects companies in these industries if they use “balances for analytical purposes”.

What areas does Article 2.1.7 cover and what is new in it?

Article 2.1.7 covers good practice in the installation and use of instruments and emphasizes that calibration should be mandatory and documented, together with measurement uncertainty and calibration certificate. It also describes two performance test checks that need to be performed between two calibrations:

• Random measurement error estimation test (repeatability estimation)
• Systematic error estimation test (sensitivity estimation).

What are the requirements of article 2.1.7 regarding balance calibration?

During calibration, a relationship is established between the known values of the test weights and the associated indicated values of the balance. Section 2.1.7 requires that "... instruments must be periodically calibrated by […] the user or the appropriate competent authority".

Therefore, in Chapter 2.1.7 Ph.Eur. three basic calibration requirements are prescribed:

1. Calibration must determine the traceability of measurement results to SI units.
2. Calibration results must include associated measurement uncertainty.
3. It is recommended that calibration is performed before any maintenance procedure that significantly alters the measurements and that a second calibration is performed thereafter. Significant operations according to article 2.1.7 include repairs, relocation of the balance or mechanical adjustments.

To ensure accurate and reproducible results and to meet the above requirements, we recommend that you calibrate your measuring instruments with trusted calibration providers, such as our accredited mass and volume calibration laboratory.

What are the requirements for repeatability and sensitivity?

For the repeatability check, a single-piece test load is used that is not bigger than 5% of the maximum capacity of the balance, but at least 100 mg. This weight is placed at least 10 times on the measuring surface. Before each measurement, the balance is set to zero. Repeatability is satisfactory if twice the standard deviation of the measured values divided by the minimum net weight defined by the user does not exceed 0.10%. In cases where the standard deviation (s) is less than 0.41 × d (where d is the actual scale interval), s is replaced by 0.41 × d.

For the sensitivity check, a one-piece test load weighing between 5% and 100% of the balance capacity is placed on the balance. The sensitivity is satisfactory if the difference between the displayed value of the balance and the nominal weight of the test load (or its conventional mass) does not exceed 0,05%.

Are Ph.Eur. Chapter 2.1.7 and Chapter <41> of the United States Pharmacopoeia (USP) similar? What are the main differences between these two chapters?

There are certain differences in the applicability of individual chapters, which is somewhat broader in Ph.Eur. ("analytical purposes") compared to the USP ("when substances must be accurately weighed"):

• Ph.Eur. explicitly requires traceability of measurement results to the SI unit
• Ph.Eur. explicitly states that the calibration of the balance must include the calculation of the measurement uncertainty
• To verify repeatability, Ph.Eur. requires a test load not exceeding 5% of the maximum capacity of the balance but at least 100 mg, while the USP does not provide any comparable limits
• Sensitivity test Ph.Eur. it is similar to the “accuracy” check of the USP, but an acceptable deviation of 0.05% in Ph.Eur. is less than 0.10% in the USP
• For both performance checks, Ph.Eur. explicitly requires one-part test loads, while this is not the case in the USP.

How often do you need to perform performance checks?

Similar to USP <41>, the frequency is not defined in chapter 2.1.7 Ph.Eur. and must be defined by the user, stating that "The frequency of qualification and performance checks is defined in each user's quality management system." We recommend defining the frequency of testing based on the risk of a particular application.

For detailed guidance, read the Frequently Asked Questions on Chapter 2.1.7 "Balances for analytical purposes" of the European Pharmacopoeia.