Reuse of column resins raises inspector eyebrows.

SAN FRANCISCO - Not only is FDA concerned about the proper cleaning and validation of purification columns, but also the reuse of resins.

BioReliance's Gail Sofer told IIR that some indications that a resin may be deteriorating are changes in specs such as flow rate, elution profile, HETP or A(sub)s values, regeneration/re-equilibration profile, or decreasing product yields.

Sofer quoted directly from a few validation recommendations pertaining to regenerated columns, as presented by FDA to Amgen during a May 1997 audit. She said FDA wrote:

Amgen also was instructed to set limits for carried-over protein for the regenerated resin, and to give data on endotoxin and contaminant protein levels for product lots made using regenerated resin, Sofer added.

Companies also must assure that any potentially retained virus would be destroyed or removed before reuse, for instance through the cleaning and regeneration process, according to Howard Levine, president of BioProcess Technology Consultants, Concord, MA.

"You have to do this inactivation study on your own, with your own reagents, etc." and not rely on manufacturer's data or past experience, he said.

Levine also suggested using old resin instead of new when validating a column for licensing because the used resin will be closer to actual production conditions.

Another 483 that Sofer mentioned, from 1996, pointed out the necessity of documenting any obvious changes in the column behavior after reuse. The 483 described "a brownish material (concentrated at the top of a column that is not repacked). That nature of this material has not been identified and it [is] not removed during regeneration."

Sofer then presented a method for validating the reuse of discolored column resin, taken from actual data provided by Amgen.

While unpacking the resin, a gray discoloration was found in the top 10% of an ion exchanger. Five alkaline, salt and acid wash solutions did not remove the gray color, nor any UV-absorbing material, but they did remove a bit of protein.

Bleach also did not remove the stain. And since the beads retained their shape, flow capacity, and performance, the researchers concluded that they could continue using the resin.