Why the USP 1788 update?

New flow imaging technologies and therapeutic protein solutions widened the scope of USP 1788. Three primary technologies are discussed in each of the sub-parts of the guidance document:

• Light Obscuration (LO) is still the preferred first-pass method for the USP Normative chapters.
• If a solution is unable to be tested using LO, either due to clarity (color, opacity) or viscosity, then the Microscope Method (MM) should be used.
• Flow Imaging (FI) is also useful for overcoming issues with LO and has added benefits of characterizing fibers.

Calibration Considerations

Validate your particle counters and monitoring methods against traceable (NIST or other certification body) size and count standard solutions. Preparation of the calibration/suitability test solutions are important to ensure even mixing and avoid the aggregation of suspended particles. Calibration should take into account the full range of measurements, and demonstrate conformance for sizing.

What about validations?

Details of the validation requirements of a Light Obscuration instrument system are reviewed in, <1788.1>. Some of the factors to consider are:

• Specificity: The ability of a method to determine differentiation between particle types. LO and MM both have low specificity, although captured particles on a filter substrate will allow for secondary analysis.
• Recovery: A challenge to demonstrate the ability of a technique to detect particles of a different refractive index. This information will allow for the description of a method beyond the normative test requirements and add to the characterization library.
• Linearity and Range: Testing to determine the response of the system at known concentrations within the specified operating range and up to the 10% coincidence limit of maximum concentration demonstrates the linearity of the instrumentation chosen. This information is available from vendors.
• Accuracy: There are two variables in accuracy for particle counting: the size of particle and the concentration of particles in suspension. These variables and others, such as flow rate and volume, are challenged as part of the IQ/OQ/PQ.
• Download the full paper for more details on validation considerations.

Verification of Performance

Liquid particle counter systems such as the APSS-2000 from Particle Measuring Systems (PMS) are supplied fully calibrated for the full range of sensitivity (2 µm to > 125 µm), calibration on an annual basis is recommended to verify that there is no shift in primary parameters and that no contamination of the optics has occurred, such that accuracy might be affected. Additional tests to verify the full range of variables are also required and form the validation of an installed system. The following tests are recommended as part of USP 1788.1:

• Sample Volume Accuracy. This verifies the accuracy of the measured sample volume. The test uses particle-free water in a container. The known amount of removed water equals the weight reduction between each extraction.
• Sample Flow Rate. The particle counter is calibrated at a fixed flow rate. The APSS can support several flow rates, but each one has a dedicated calibration curve which must be loaded via supplied software. The verification of flow rate is performed by timing the cycling of the syringe sampler with a known volume of sample. The sample volume divided by time equals the flow rate.
• Diameter Calibration. Calibration is performed using NIST traceable spheres. An internal algorithm aligns the particle size to the signal within the sizing circuits. The APSS 2000 complies with the “Automated Method” for instrument calibration.
• Sensor Size Resolution. The test demonstrates the particle counter’s ability to differentiate between particles of different sizes and that the distribution of signal does not interfere with an adjacent size. A solution of 10 µm particles is used and the ratio of counts between channels is determined. The APSS 2000 complies with the “Automated Method” for instrument resolution.
• Particle Counting Accuracy. A standard solution of known size and concentration is tested for the number of particles per unit volume. The results are verified against the specifications on the supplied, traceable standard.

What’s next?

There are many considerations for Pharma to make with the new USP 1788. Don’t get left behind! Download the full paper and ask our experts for help to ensure you comply with the latest regulations.

Learn more… Read the full paper here.