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Immediately after the availability of highly permeable membranes in 1979, membrane plasma separation was introduced as a mode of extracorporeal blood purification by the nephrology group at Klinikum Grosshadern of the Ludwig Maximilians University of Munich (F.R.G.). The new therapy was applied primarily in the management of immunologically mediated renal and extrarenal disorders as well as in paraproteinemias. We also have witnessed a widespread application of this extracorporeal treatment as a last resort in otherwise refractory clinical conditions. Over the years, the group at Grosshadern has contributed to the development, as well as to the laboratory and clinical testing, of new plasma separation membranes, simplified plasmapheresis formats (e.g., spontaneous membrane plasma separation), and several plasma fractionation procedures (e.g., cascade filtration, adsorption). Whenever indicated and possible, plasma fractionation procedures, rather than unselective plasma exchange, are performed in an appropriate clinical situation.

Derived mathematical models are employed to compare cascade filtration plasmapheresis in the dead-end and single-pass formats. The high filtration fraction and low sieving coefficients associated with single-pass cascade filtration are shown to require treatment of the retentate concentration profile in an integrated rather than a length-averaged fashion. The models are best applied to specific simulations, but in general predict that (a) for a given membrane, the dead-end format will yield a higher albumin recovery but a lower macroglobulin rejection than single pass; (b) the single-pass format is more suited to loose membranes and the dead-end to tight membranes; and (c) in the single-pass but not the dead-end format, solute recovery is conveniently independent of the quantity filtered. Agreement between predicted and measured performance is good, although a larger data base would be required for complete validation of the models.

This is a revision of the IDE Application Form, “How to Comply with the Food and Drug Administration's New ‘Investigational Device Exemption (IDE)’ Regulations, Including an Application Form“ originally published in Artificial Organs, Volume 4, Number 4, November 1980. This publication updates the IDE application form to facilitate compliance with the amended investigational device exemption regulations now in effect.