Standard Practice for Qualification of Procedures for the Extraction of Particulate Matter from the Surfaces of Single-Use Bioprocessing Equipment

Importancia y uso:

4.1 In the process of manufacturing single-use bioprocessing equipment (single-use systems, SUS), particulate matter may adhere to the interior (fluid contacting) or exterior surfaces of SUS (BPSA). Visual inspection of SUS 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 SUS significantly reduces the effectiveness of visual inspections. A more complete assessment of the count and sizes of particulate matter requires a particle quantification test method whereby a SUS is extracted with a test liquid (extraction procedure), the resulting extraction liquid converted into a test sample (test sample preparation procedure), and the test sample analyzed (particle measurement procedure) to determine the particle count and sizes in the test sample. Guide E3466 and Practice E3468 describe in detail the overall development and validation of particle quantification test methods for SUS. This practice focuses on the specific requirements for qualifying the extraction procedure, the first procedure in a particle quantification test method.

4.2 Pharmaceutical manufacturers use a wide variety of configurations and sizes of SUS, such as bioreactors, mixers, and bioprocess containers. Extraction of particulate matter may be relatively easy from small SUS with readily accessible surfaces, however, extraction of particulate matter from large and complex SUS with less readily accessible interior surfaces may require significantly more effort.

4.3 The wide range of SUS size and complexity 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 SUS of interest.

4.4 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 SUS with controlled amounts of standardized reference 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.

4.5 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 SUS 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.

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

Subcomité:

E55.07

Referida por:

E3468-25, E3466-25, E3411-24, E3425-24

Volúmen:

14.01

Número ICS:

11.120.99 (Other standards related to pharmaceutics)

Palabras clave:

biopharmaceutical manufacturing; extraction; particle; particulate matter; single-use system;