Molecular Filtration and Purification in the Biopharmaceutical Industry

Molecular Filtration (MFI) is defined as the process of separation of two or more substances. This is achieved by a variety of interactions between the substance or objects to be removed and the molecular filter.

In addition the substance that is to pass through the molecular filter must be a fluid, that is, a liquid or gas. The simplest method of molecular filtration is to pass a solution of a solid and fluid through a porous interface so that the solid is trapped or retained, while the fluid passes through.

This principle relies upon the organophobicity of the ceramic membrae and the organics making up the fluid, and the particles making up the solid. Molecular filtration is widely used within the biopharmaceutical industry to remove these contaminants.

Microorganism removal is either required to achieve a sterile filtrate to reduce the bioburden and therefore avoid elevated levels of endotoxins which is an indirect indicator of the presence of cell-debris from Gram negative organisms

REGULATORY RECOMMENDATIONS

As regards the EU and FDA, both the guideline CPMP, April 1996, and EC Annex 1, as well as the FDA’s Aseptic Guide (2002) recommend the use of redundant 0.2/0.22-mm-rated membranes.

FDA’s new aseptic guideline states, “use of redundant filtration should be considered in many cases.” The placement of the filters is to be “as close as possible” (or practical) to the filling needles. The usual location is indeed just before the filling needles or before the reservoir that feeds them.

In practice the “recommendations” are enforced as if they were law. In Europe, this usage is becoming the common practice, whereby the difference between redundant and serial filtration has to be regarded.

Redundant is defined as two filter of the same pore being connected. Whereas, serial filtration means, commonly, a piece of equipment, usually a tank, is connected by two filters of the same pore size.

The recommendation is not based on any known survey or experimental data, nor have the regulatory authorities explained their reasoning. Those responsible for the public safety are often obliged to make decisions when adequate supporting data are not yet available.

Over-design is a normal response to uncertainties. By way of automated integrity testing machines, that avoid invasions of the filtration train downstream of the final filter, the integrity testing of a filter can be performed without endangering the asepsis of the system. When repetitive filters are used, each in its own housing each can be integrity tested separately. When in the same holder, neither filter can be tested without invading the space separating them unless some very unusual arrangements are devised. This is one disadvantage of relying on repetitive filters.