What are the process challenges involved in API filtration and purification?
The increased need to fast track APIs to market and to minimise validation activities, although challenging, has presented
significant opportunities for new product developments in purification. The requirement to remove any residual metal catalyst
from API synthetic process streams co-exists with the drive to establish modular platforms for flexibility and scale-up; thus,
once an effective metal adsorbent is identified, the process scale-up requirements must be considered. The use of adsorbents
in bulk powder form has inherent disadvantages, particularly when scaling up for production operation (i.e., dust handling,
personal protection and equipment cleaning). In some instances, the metal adsorbent selected for pilot scale operations is
found to be unsuitable at a larger production scale because of cost considerations or fundamental changes in process step
conditions, for example. The adsorption of metal species is influenced by temperature, pH and solvent composition; therefore
it is often necessary to re-consider the choice of adsorbent if any or all of these conditions change for scale up following
process optimisation. The use of chemically aggressive solvents, such as acetone, tetrahydrofuran and dimethylformamide,
in API manufacture, although not preferred, may also be required for catalytic synthetic steps. Consequently, these can present
compatibility challenges to the material components of the systems.
The move to having flexible scalable systems for process filtration has also influenced the development of filter products
to provide modular solutions. The use of filter media impregnated by adsorbent powder, such as activated carbon modules, to
avoid the use of bulk powder handling has been widened to consider how other adsorbent materials or speciality metal scavengers
can be similarly immobilised. This approach can only be successful when the adsorptive properties are not impaired by the
immobilisation procedure. Laboratory and pilot laboratory testing can confirm efficacy and also accurately size area requirements
for process scale up. The cost of implementation can be offset by the removal of what will become redundant existing filtration
steps, previously used for the bulk powder removal.
In API bioprocessing, host cell impurity removal at clarification and in downstream processing is an area of focus and the
use of charged membranes as encapsulated capsules could decrease expensive chromatography column usage. The adoption of single-use
systems in bioprocessing process steps is generally not restricted through chemical compatibility issues, as seen with synthetic
API processes. However, alkali-resistant capsules are required in bioprocessing manufacturing if caustic solutions are used
for validated depyrogenation procedures.