If your role involves the quality control of medicinal products and your company exports products into the EU, the new requirements stipulated in the European Pharmacopoeia Chapter 2.1.7 (or (Ph.Eur. Chapter 2.1.7) apply and are now in force.

Published in July 2021, Ph.Eur. Chapter 2.1.7 stipulates requirements that are very closely aligned with USP Chapter 41 in addressing the equipment’s accuracy and performance.  The Chapter introduces certain measures that must be carried out periodically to optimise the performance of analytical balances:

1. Periodic calibration including measurement uncertainty

2. Performance checks between calibration intervals to assess:

a. Random error (precision)

          b. Systematic error (accuracy).

What are the specific balance performance requirements?

1. Installation and location

Ph.Eur. Chapter 2.1.7 states that it is particularly important to ensure that the installation conditions do not adversely affect the performance of the balance. This includes both the physical and environmental conditions.

Environmental parameters affecting performance include:

  • Temperature fluctuations, including those caused by direct sunlight
  • The humidity of the location and the risk of pronounced changes in the relative humidity
  • Barometric pressure
  • Air currents and drafts from air conditioning units and ventilators, drafts from doorways, windows or placing the balance in a fume cupboard
  • Dust and other foreign bodies
  • Electrostatic forces
  • Magnetic forces
  • Vibrations (often affected by installation).

Installation and location parameters affecting balance performance cover:

  • The bench, desk or table where the balance is placed should be stable, non-magnetic, vibration-proof and protected against electrostatic charges
  • The location inside an enclosure (usually part of the balance construction) must protect against dust ingress and the influence of air currents
  • The balance must be levelled either with a bubble attachment or an internal levelling device
  • Balances should ideally be left powered on, even if on standby, as they can take many hours or days to acclimatise to the surrounding conditions.

2. Calibration

Calibration is part of the balance qualification to ensure compliance with pre-defined requirements and is usually performed by a competent body such as Northern Balance. Its aim is also to establish traceability of the measurement results to National Standards (held at the National Physical Laboratory in Teddington).

The calibration results are documented in a calibration certificate and must be carried out periodically (as defined by the users’ QMS) and before any maintenance operation is carried out that significantly alters the balance’s measurement performance.

3. Performance tests

Performance tests are carried out to evaluate the random and systematic errors of the balance and consist of a repeatability test (the ‘random’ error or ‘precision’ of the balance) and a sensitivity test (the ‘systematic’ error or ‘accuracy’ of the balance). Again, these are carried out periodically as defined by the users’ QMS.

Repeatability

The repeatability requirement defines a specific test with an acceptance criterion that the balance should meet. A weight no less than 0.1g or more than 5% of the capacity of the balance is added and removed 10 times and the standard deviation (s) is calculated. The minimum weight is defined as equalling 2000 x s. If s is less than 0.41 x d (d is the readability or resolution of the balance) the minimum weight is calculated as 820 x d according to both Ph.Eur. Chapter 2.1.7 and USP Chapter 41.

The ‘minimum weight’ is the smallest net sample mass that can be weighed on the balance while still satisfying this acceptance criterion. This should not be confused with the ‘smallest net weight’, which is the smallest quantity that you need to weigh on the balance on a day-to-day basis. When the smallest net weight is equal to/larger than the calculated minimum weight the Ph.Eur. Chapter 2.1.7 is satisfied.

Sensitivity

The sensitivity test assesses the parameter that most significantly influences the accuracy of the balance. This increases in a linear manner proportionate to the applied load. Random error is dominant at the lower end of the measuring range.  It is assessed with a single test load of between 5% and 100% of the capacity of the balance with an acceptance criterion of 0.05% (USP Chapter 41 = 0.1%) of the load added.

Are the requirements mandatory?

Any weighing performed as part of tests prescribed to establish compliance with a European Pharmacopoeia monograph must be carried out in line with the principles outlined in Ph.Eur. Chapter 2.1.7.  However, Ph.Eur. Chapter 2.1.7 is limited to balances used for analytical purposes and does not cover balances used for manufacturing or other purposes.

What must I do to ensure compliance?

To safeguard compliance against Ph.Eur. Chapter 2.1.7., now is the time to ensure your standard operating procedures (SOPs) encompass the following:

1. Commissioning of periodic calibrations

To safeguard Ph.Eur. Chapter 2.1.7 (and USP Chapter 41) compliance, routine UKAS calibrations should be conducted periodically by a specialist engineer to ensure that readings are accurate when compared to a reference weight.  Although traceable calibrations are also available, Northern Balance only publishes measurement uncertainty on UKAS certificates.

It’s worth noting that in-house test weights and equipment with built-in, calibration features may still require periodic calibrations. This will identify malfunctions or invisible damage from general knocks and movement.

Read our blogs to understand more about calibration types and how to determine calibration frequencies. 

2. Performance of repeatability and sensitivity checks

For convenience and peace of mind, specialist engineers at Northern Balance can perform both repeatability and sensitivity checks immediately after UKAS calibrations to ensure optimal accuracy.

Combining both test results, the new Ph.Eur. Chapter 2.1.7 & USP Chapter 41 Performance Check Certificate has replaced Northern Balance’s Minimum Weights Certificates and satisfies the requirements set out in both Ph.Eur. Chapter 2.1.7 and USP Chapter 41.

With the new requirements now binding, ongoing compliance is critical but need not be a challenge.  For support on adherence with Ph.Eur. Chapter 2.1.7 and/ or USP Chapter 41, please contact our technical weighing experts for complimentary guidance.