Plant Equipment Spotlight: PCI’s Pressure Filter for Developmental APIs

As an integrated API manufacturer, PCI is fortunate to have three pressure filters in it's manufacturing facility.

Posted: January 1, 2008

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API Manufacturing and Pharmaceutical Manufacturing

As an integrated API manufacturer, PCI is fortunate to have three pressure filters in it’s manufacturing facility. Our pilot/developmental unit is called PFN3 and was manufactured by Guedu. It is a jacketed, agitated, pressure filter that we use to filter, wash, re-slurry, and finally dry compounds during developmental production. PFN3 is used exclusively with our 7 vessel pilot system consisting of our 50-200gal reactors. All of the internal contact surfaces are constructed of Hastelloy C-276 and the jacket and peripherals are constructed of 316-stainless steel. It has a nominal liquid volume of 200 gallons, a mixing volume of 50 gallons and depending on the bulk density of the material it can process anywhere from 10-200kg of product.

The bottom of the filter is a perforated 0.75 square meter bottom plate over which a Hastelloy-C screen and filter cloth are attached. The bottom plate is removable from the filter to allow for filter cloth changes, cleaning, product changeover, and maintenance of the internals when required.

Since the unit so versatile and capable of 4 different unit operations, materials processed in it never see any human contact or are ever exposed to the environment as it is equipped with a direct packaging system.

Capabilities and Accessories

The unit is equipped with a variable speed hydraulic motor driven agitator that has two low profile blades designed for solids agitation. When rotated backwards, the agitator compresses the product onto the bottom plate and the filtrate is forced out of the cake.

Nitrogen gas can also be applied to the top of the filter as a means to inert the vessel, to pressurize the liquid to speed up the filtration, and to purge the product during drying. Vacuum can be applied to either the top of the filter, through the vacuum system waste receiver, or to the bottom through a filtrate recovery vessel.

The filter is jacketed to allow for heating and cooling of the product in the filter. For cooling, the jacket is connected directly to our cooling water system. Heat for drying is provided by a steam injector on a tempered water loop. This feature can be used for controlling temperatures during either filtration or drying of products. There are also three zones for temperature control on the unit which include the side jacket; the dust filter housing jacket; and the agitator shaft jacket. For some products the heated agitator shaft has been shown to cut down drying times in half.

In addition there are four different sprayer nozzles: the ring sprayer, the two shower sprayers, and the agitator shaft sprayer. The ring sprayer is exclusively to rinse isolated product. The two showers are located opposite of each other and they are used to spray the vessel walls during a clean-out. The agitator shaft sprayer is used to clean the agitator shaft. There is also a side sampling port where one can remove wet or dried material to do analytical testing. The unit also has a built in dust collection unit which is designed to prevent product loss to the vacuum system.

The unit can also be fitted with a “DoverPac” bagging attachment to the discharge nozzle. The DoverPac is a continuous packaging liner system designed to handle compounds that are hydroscopic, high toxicity, or whenever there is a requirement that the material not be expose to the atmosphere during final isolation. The system is fully automated and contained as material is discharged from the unit directly into the DoverPac Liner through a sealed chamber. The top and bottom ends are then heat sealed and then the sealed bag is placed into a lined drum for shipment.

Quality Documents and Cleaning Methods

PCI has numerous general SOP’s for operating our PFN3. More specific instructions are included in all the batch records. There are additional SOP’s for maintenance as well. Our maintenance protocol includes routine, monthly, and yearly PM items. Routine maintenance includes product changeover and filter cloth removal. Cleaning the unit for all product changeovers is always specific to the previous product. The cleaning protocol includes taking and analyzing swab samples from various points inside the unit. In addition the IO/OQ for the unit has been fully validated and meets all the requirements for cGMP manufacturing.

Cleaning the unit for product changeover will be specific to the previous product. The cleaning agent is charged through all four sprayers on the unit and is circulated from the bottom of filter to the main slurry charge port and through the side slurry port. This is done to remove any gross amount of residual material. The unit is then flushed with water and scrubbed by hand from the man-way and from the side discharge valve. The base of the unit is lowered and the old cloth is removed while the walls and base are cleaned. New cloths are installed to the base and to the dust collection unit. Cleaning with fresh cleaning agent is repeated again to remove any final traces of previous product. Finally the unit is rinsed with the appropriate rinse agent and the rinse samples are removed for final analysis.

Unit Operations and Manufacturing

The unit is typically fed slurries of various chemical compounds to the top of the vessel where the solids are retained by the filter cloth and the filtrate is drained through the bottom plate to a receiver. The solids in the slurries can be either the product or an impurity in the product. The filter is used to remove these solids from the solvent. After that, the filter can be used to

  • Re-slurry and wash the solids with a solvent
  • Stir the solids to expose the material to the filter cloth
  • Re-slurry the material for transfer back to a reactor
  • Packing of the solids to help squeeze solvent out of the solids
  • Stirring of the solids to enhance drying.

Filtration through the bottom filter cloth can be accomplished by either applying vacuum through the bottom of the filter or purging with inert gas above the solid layer. Use of both pressure and vacuum allows for faster filtration of slurries as compared to Buchner filters, which relies on vacuum alone.

Products can be dried on the unit through the application of heat to the jacket, purging with nitrogen through the product, and/or the application of vacuum on the filter. Each product has its own requirements as to the correct combination of utilities based on maximum temperatures allowed for drying and the products tendency for lumping during drying. Almost all products that can be isolated on either the centrifuge or on an open top Buchner filter can be isolated on a pressure filter but it has the added feature of being an agitated pressure vessel. As an agitated pressure vessel, the filtered product can be transferred as a slurry to another reactor, dried within the vessel, or packaged directly from the vessel. As stated earlier this is advantageous because it reduces handling of the product and thus reduces exposure to potential sources of contamination since all these operations are contained in a single vessel.

If you have a project that produces a highly toxic, hydroscopic, or air sensitive compound please call our Business Development Team to see how our PFN3 could meet your needs.

Related posts:

Quality APIs for Competitive Advantage
Key Questions To Ask Your CMO About Their Analytical Capabilities
Ensuring Industry Compliance in Identifying Genotoxic Impurities in APIs
Is Your CMO Qualified to Handle Your API Project?
API Quality Risk Management

About the Author

Ed Price CEO of PCI Synthesis
Ed is the President and CEO of PCI Synthesis (PCI), he serves as a co-chair of the New England CRO/CMO Council and sits on the Industrial Advisory Board for the Department of Chemical Engineering at UMass, Amherst. Ed is also a long standing member of the American Chemical Society and advises the Bulk Pharmaceutical Task Force of the Society of Chemical Manufacturer’s and Affiliates (SOCMA).

Do you have questions? Talk to Ed.