If you work in quality control in the pharmaceutical industry and your company is located in Europe or exports to it, the requirements of General Chapter 2.1.7 ("Balances for analytical purposes") of the European Pharmacopoeia (Ph.Eur.) is relevant to you. The new General Chapter 2.1.7 became effective on 1 January 2022, and relates to balances used for analytical purposes. One of the highlighted features relates to the requirements for checking instruments between calibrations (during routine use). Performance checks include repeatability and sensitivity checks, as two critical parameters to ensure proper operation of analytical balances. Read below to see if your analytical weighing procedures comply with this regulation.
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”.
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:
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:
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.
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%.
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"):
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.