POSINYL membrane filters for depyrogenating solutions

BEA Technologies (BEA) has developed positively charged POSINYL filter elements for depyrogenation of pharmaceutical solutions that cannot withstand  sterilization temperatures.

POSINYL filters consist of enhanced nylon membranes with positively charged sites that adsorb bacterial endotoxins and reduce final pyrogen concentrations to levels lower than those required by current FDA and other pharmaceutical regulations.

Depyrogenation challenges

Removal of bacterial endotoxins from pharmaceutical, blood treatment and other medical products requires is a primary requirement. However, “purified water” can still contain bacterial endotoxins at various concentrations, depending on the origin of the water and the process used to purify it. Increasing attention on guaranteeing absolute sterility of water and absence of pyrogens has not fully addressed elimination of bacterial endotoxins.

Pyrogens are molecules of different chemical nature that exercise biological actions that can cause ‘pyrogenic’ (from Greek “Pyros” meaning fire ) fast and high temperature rises alarming implications for already debilitated patients , to whom are administered injectable solutions.

Pyrogens have different origins and chemical structures that may derive from the cell turnover of microorganisms but also the dead cells of microorganisms inactivated by sterilization processes. The chemical nature of many pyrogens is identified in structures of lipopolysaccharides, macromolecules with a molecular weight of the order of 10,000 / 20,000.In aqueous solutions, these molecules tend to aggregate into complexes with dimensions around 0.1 microns or greater.

Inactivation of pyrogens is made difficult because they are water-soluble and thermostable molecules and therefore resist sterilization using saturated steam. Degrading these molecules beyond potential pyrogenicity could also be achieved by dry heat at >200° C for several hours. However, this procedure is impracticable for the thermolabile solutions used in many pharmaceutical products.

BEA Technologies solution for depyrogenation

In general, it is preferable to generate pyrogen–free solutions, rather than face the problem of depyrogenating solutions already containing endotoxins that could contaminate the finished product.

To do this, it is necessary to prepare a pyrogen-free solvent using pure water that is distilled in conditions such as to guarantee absence of all microbiological and pyrogenic impurities.

In the event, however, that the need to depyrogenate a solution arises, BEA Technologies has designed and builds the “POSINYL” filter elements, consisting of an enhanced Nylon 6.6 membrane with positively charged sites that allow to adsorb the “bacterial endotoxins” and reduce final concentrations to levels lower than those required by current legislation.

POSINYL membrane filter elements are available with sterilizing filtration degree of 0.1 and 0.2 microns both with positive charge. The positive charge is increased by adding functional groups that make explicitan attraction and absorption potential towards cellular fragments and particles marked by a negative charge. These functional groups are additives that comply with the requirements imposed by FDA, EU and other medical and pharmaceutical regulations.

All biocompatibility test data are reported in the Validation Guide that is provided to users before online installation.

Depyrogenation results

Filtration tests already carried out have made it possible to recover whey that was heavily polluted by endotoxins at as level of 227 EU/ml, until the concentration of the same was reduced to a level considered acceptable by the user.

In another case, it was possible to make usable a considerable quantity of polyvinylpirrolidone that had been polluted with 160 Eu / ml of endotoxins.

A first stage of filtration made it possible to reduce the concentration by 10 times, with a second stage of filtration reducing concentration 5-7 EU / ml. Final stage of filtration used 0.1 micron filter elements, allowing concentration to be reduced to just 0.13 EU / ml, making it acceptable for the next stage of use.

For application purposes and to optimize the absorption capacity of “bacterial endotoxins” it was necessary to observe prescribed specific flow rates across the membrane septum, PH between 4 and 8 of solution to be treated , endotoxin concentrations and steam sanitization/sterilization of the filter elements.

When used within the limits and conditions recommended by BEA Technologies, POSINYL filter elements offer high reliability and retention of bacterial endotoxins over long periods of use.

Resources

Click on BEA POSINYL depyrogenation filters for product information.