You might evaluate the biosafety/analytical tests that you perform on the
final product itself. I assume these methods would identify and quantitate
any residual host and/or construct proteins, and any shedding enzyme. Would
any of these also indicate the presence of TSE-related biomolelcules? Are
you planning to validate your filtration method as a TSE particle-clearing
step? There is a large body of analytical and regulatory literature on
biosafety testing for adventitious materials and models for viral clearance
studies. In developing your product, these would be areas of major concern,
I suspect.
I also assume that you are obtaining the bovine enzyme from approved sources
that perform adequate tests to demonstrate the biosafety and quality of each
lot of the purified native enzyme. Given the current restrictions on
bovine-sourced materials, if the purified native form of a bovine protein
that is used in the preparation of a drug is significantly cheaper than a
recombinant form, are you "getting what you are paying for"?
Nadine Ritter
BioReliance
nritter@bioreliance.com
> -----Original Message-----
> From: Paul Tressel [SMTP:pault@allelix.com]
> Sent: Friday, November 06, 1998 11:24 AM
> To: Recipients of ABRF List
> Subject: GLP/GMP
>
> Would FDA approve the following process?
>
> An immobilized native bovine enzyme is used to release a drug from its
> recombinant construct. The drug is then passed through a 5,000 MW
> cellulose triacetate membrane (the drug could be mixed with a 10,000
> dalton fluorophore as a QC/QA test of the membrane integrity, prions
> having >23kD molecular weight). Would this solve the problem of
> requiring the immobilized native bovine enzyme to be absolutely free of
> TSEs(multiple ultrafiltration membranes could be used for added
> insurance)? The reason for even asking this question is that "native
> bovine enzyme" is not only much less expensive than the recombinant
> form, but is also enzymatically superior.