Sub-Visible Particle Measurement by Light Obscuration
Sub-Visible Particle Measurement to the Ph Eur 2.9.19 and USP<788> by Light Obscuration set the standards for solutions for injection or infusion which are required to be clear and practically free from particles when examined under suitable conditions of visibility.
The USP & Ph Eur set limits for the acceptable quantity of particulate matter in solutions for injection or infusion depending on the size of the container as follows in the table below:
Limits for Solutions for Infusion or Injection (Ref Ph Eur)
< 25 particles per ml > 10 µm & < 3 particles per ml > 25 µm
< 6000 particles per container > 10 µm & < 600 particles per container > 25 µm
The above limits are set for patient safety with adverse reactions concerns, e.g. mechanical obstruction with lung as target, injection site reactions, phlebitis and granuloma.
Sub-Visible Particle Measurement
Parenteral drugs are generally administered to patients by means of injections and must be essentially free of visible particles. The system requirements for a light obscuration instrument utilized to comply with Ph Eur 2.9.19 and USP<788> include a light obscuration sensor with appropriate sample feeding device, a sensor and a sampler.
The sensor must be calibrated for size at a number of points, tested for resolution, and validated for count efficiency. The concentration range should be greater than the concentration of the particles to be counted. The dynamic range must contain the smallest size particle to be quantified.
The accuracy of the sample volume must be within 5% of the appropriate sample volume for the test. For reporting, particle concentration must be greater than 10 and 25µm.
Sources of Particles
Particulate contamination can come from the solution itself and its ingredients, the production process and its variables (the environment, equipment & personnel), the products packaging and the preparation of the product for administration. These can be divided into two sources:
- Extrinsic from environmental contamination, manufacturing equipment, primary packaging e.g. stainless steel, hair, fibres, glass, rubber etc.
- Intrinsic from the formulation, excipients, API, Proteins etc.
For the Biopharmaceutical industry protein products may contain proteinaceous particles at release, or protein particles may form during storage. Industry experience has demonstrated that therapeutic proteins such as monoclonal antibodies can exhibit a propensity for self-association, leading to the formation of aggregates that range in size from nanometres (oligomers) to microns (subvisible and visible particles). As a result, the requirement for drug product appearance for monoclonal antibodies was changed from “without visible particles” to “without visible particles unless otherwise authorised or justified”.
For all your Sub-Visible Particle Measurement requirements - Source Bioscience’s analytical division is a leading independent, MHRA approved (cGMP) contract research organisation that specialises in the provision of chemical and microbiological laboratory services for all phases of drug development. We support the pharmaceutical research and development process from preclinical enabling studies for investigational medical products (IMPs), through the clinical research phases to batch release testing into the market place.
As part of our provision of the service we conform to current Good Manufacturing Practices (cGMP). We have a proven track record of working in partnership with Pharmaceutical companies providing support services that are not core to their business, releasing people and management time to add value to the pharmaceutical drug development process.
For further information and prices please contact us or call +44(0)1159739012