ASTM E3230-20

4.1 Conventional stainless-steel process equipment for biopharmaceutical manufacturing require cleaning and sterilization prior to implementation. Single-use systems (SUS), stand-alone equipment typically composed of plastic components and assemblies, are usually assembled in cleanrooms and are usually not cleaned or rinsed prior to implementation (with the exception of filters, which are often rinsed prior to use). SUS cleanliness with respect to particulate matter depends upon the quality of the SUS manufacturing process, and also upon the care and handling of the SUS upon implementation by the end-user.

4.2 In the process of manufacturing single-use components or assemblies, particulate matter may adhere to the interior (fluid contacting) or exterior surfaces of SUS (BPSA). Visual inspection of SUS components and assemblies for particulate matter is often limited by translucent or opaque materials which inhibit visualization, especially of interior fluid-contacting surfaces. Also in some cases, the large size of single-use assemblies significantly reduces the effectiveness of visual inspections. A more complete assessment of particulate matter load requires a method to extract particulate matter from the surfaces of single-use components or assemblies using a test liquid, which makes the particles readily available for analytical characterization using counting, sizing and chemical/physical identification methods.

4.3 Pharmaceutical manufacturers use a wide variety of configurations and sizes of single-use components and assemblies, such as bioreactors, bioprocess containers, tubing, connectors, clamps, valves, sensors and filters. Extraction of particulate matter may be relatively easy from small components with readily accessible surfaces, however, extraction of particulate matter from large and complex assemblies with less readily accessible interior surfaces may require significantly more effort.

4.4 The wide variety of single-use components and assemblies inhibits specification of a narrowly defined extraction procedure with a universally prescribed volume of test liquid and energy input (rinsing/agitation) conditions. The approach described in this practice allows for flexibility and innovative approaches to maximize particle extraction which are specifically tailored to the component or assembly of interest.

4.5 In most cases, relatively small amounts of particulate matter are non-uniformly dispersed over large surface areas, and the particulate matter also is often inhomogeneous in chemical composition and morphology. Standardized single-use components and assemblies with controlled amounts of known standardized particulate matter which simulate real systems are challenging to prepare. Thus in the development of a particle extraction procedure, a practical and expedient methodology is required to assess whether the chosen extraction procedure is effective and extracts as many particles as practically possible

4.6 A well-established standardized methodology for demonstrating effective extraction of particles from the surfaces of automotive components provides guidance (ISO 16232:2018, VDA 19 Part 1). The standard practice described here for the extraction of particulate matter from the surfaces of single-use components and assemblies is closely based upon the principles described in the ISO 16232:2018 standard for automotive components. This “multiple extractions” approach to qualification of an extraction procedure significantly increases the probability that particulate matter adhering to surfaces is removed upon extraction, and that the extraction procedure so qualified is effective. The qualification criterion described in this practice is essentially the same as the “declining criterion” described in ISO 16232:2018. In essence, this criterion requires that during qualification the chosen extraction procedure must achieve an effectiveness of greater than 90% particle removal on a relative basis.

4.7 Note that this practice does not specify the particle measurement method required to count and size the particles. The qualification of the extraction procedure described in this practice will be compatible with particle measurement methods typically used for both so-called “visible” (≥ 100 micron) or “sub-visible” (10 to 100 micron) particle size ranges (USP <788>, USP <1788>, USP <790>), which includes methods such as light obscuration, membrane microscopy or dynamic flow imaging (Guide E3060). In order for this practice to be effective, the chosen particle measurement method shall have been qualified for reliable determination of the particle count (number of particles in the particle size range of interest).

4.8 The overall goal of a chosen extraction procedure for particulate matter on the surfaces of single-use components and assemblies is to maximize the probability that particles are extracted in an effective, practical, consistent and controlled way.