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Before an Active Pharmaceutical Ingredient (API) can be applied to a drug for commercialization, it must go through proper filtration to ensure that it is isolated from any impurities.  Ensuring that your Contract Manufacturing Organization (CMO) implements the most state-of-the-art filtration technologies is critical to the delivery of safe and effective drugs.

Before you can understand the process your CMO must go through in filtering APIs, consider the reasons behind it.

Removing Unwanted Particle in API Production

There are many reasons to remove larger particles in the chemicals used in API production. Because manufacturing of most APIs is done using chemical processing, removing unwanted particles will improve process efficiency and protect the quality of the products created by the processes. Effective harvesting and purification processes play an essential role in ensuring that biopharmaceutical manufacturing processes provide biologic drug substances with uniform and consistent properties.

Each chemical component or raw material used in API production has its own unique characteristics. Filters are used to ensure that the ingredients are free of harmful particulates and they must be chosen based on those characteristics.

Importance of Consistency

When formulating biopharmaceutical drug products, biologic APIs must have consistent product properties. Variation in the concentration of product- and/or process-related impurities is extremely important since it can affect the safety and/or efficacy of the product, yet certain process-related impurities can be challenging to reduce to acceptable levels.

Yet advances in technology are helping biologic API manufacturers improve the consistency of APIs with advanced filters. It is essential that your CMO has an analytical department that is compliant with CFR Part II, and in all process testing, method development, method qualification and method validation.

The Anatomy of a Typical API

APIs are frequently seen as free-flowing solids that are orally administered as drugs.  The solid API is formed from precipitation or recrystallization in solvents. The solvent which is typically organic, must be removed from the slurry in order to isolate the final API.  That is where a pressure filter comes in – a key tool for API filtration at PCI Synthesis.

The Role of Pressure Filters

A pressure filter is a giant vessel with a plate dividing the top and bottom.  The plate holds a filter cloth, which is woven to form micropores, which can be anywhere from 1-150 microns in diameter. At PCI Synthesis, we use micropores that are typically 8-10 microns in diameter, which is sufficient to hold most crystal-sized API that are produced. The filter also includes an agitator which is used to mix the resulting wetcake.

In this type of filtration, the product slurry is charged to the filter.  The liquid and soluble substances, known as the filtrate, flow through the micropores, and the solid wetcake remains behind in the pressure filter.

The filtration is usually followed by washing to remove additional impurities left behind during the filtration.  The final step in the filtration is the drawdown, in which a vacuum is applied to the bottom of the filter to remove as much solvent as possible.

Pressure filters have the added benefit of being isolated from the outside environment.  Nitrogen is used to inert the filter to prevent oxidation.  Inertion also prevents the flammable solvent from igniting. The filter is connected to the slurry input and filtrate receiver by a hard pipe or flexible hose to maintain an inerted position, which helps to maintain the integrity of the product.

Pressure filters also have drying capabilities, via an electrical coil or heat transfer fluid, which allow for drying under heat and vacuum in the inerted environment.   Once dried the solid API is removed from the pressure filter through a slide discharge door for milling and final packaging.

There are many steps in the production of an API.  The filtration process is where an API truly becomes a drug for oral administration.  Implementing proper filtration is key to ensuring safe and effective drug delivery.