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1-Protease Inhibitor for Treatment of -Antitrypsin Deficiency
Director, Global Medical Affairs Professional Services, Baxter Healthcare Corporation, One Baxter Way, Westlake Village, California 91362-3811, fax 805/372-3312. jim_gemberling{at}baxter.com
Manager, Global Medical Affairs Professional Services, Baxter Healthcare Corporation
Published Online, March 14, 2006. www.theannals.com, DOI 10.1345/aph.1E061d
1-antitrypsin deficiency, a genetic disease. These
therapies have been welcomed in the "alpha-1 community" as new
options for a growing population of newly diagnosed patients. However, we
would like to provide some clarification regarding specific activity, purity,
and functional activity.
Specific activity, as labeled in the product insert, refers to the release
specification for the product of each
manufacturer.2-%4
Each lot must meet that minimum specification. In the case of Aralast, the
package insert lists the specific activity as not less than
0.55.2 In
August 2005, an analysis was completed by Baxter Healthcare to examine the
manufacturing process for Aralast with regard to overall protein
concentration, 1-protease inhibitor concentration,
and specific activity. The analysis included Aralast manufacturing data from
October 2002 through October 2004, which consisted of 148 manufacturing lots.
The mean ± SD total protein content was 21.6 ± 2.4 mg/mL, with a
mean 1-protease inhibitor concentration of 21.3
± 1.7 mg/mL. Mean specific activity is derived from total protein
content and 1-protease inhibitor concentration.
Analysis of the 148 lots of Aralast demonstrated a mean specific activity of
1.0 ± 0.12 with a coefficient of variation (CV) of 12% ratio of the
standard deviation to the mean.
Statistical process control charts were constructed for each of these
measures, and it was concluded that this analysis revealed that the mean
specific activity of 1.0 represents a stable and consistent process average.
Examination of the CV (8% and 11% for a mean
1-protease inhibitor concentration and mean total
protein, respectively) for each measure revealed that each was within
expectations for reasonable assay variation. Finally, the statistical process
control charting revealed that the process is remarkably stable, consistent,
and in a state of control.
Purity of these products refers to the amount of 1
antitrypsin protein in the product. All 3 products have trace or small amounts
of other naturally occurring serum proteins normally found in all
plasma-derived products. Unfortunately, Louie et al. characterized the
products as not pure and impure without a complete explanation of this
terminology, which can be easily misunderstood as meaning contaminated or
otherwise inferior. All 3 products have been approved by the Food and Drug
Administration and have been deemed safe and well tolerated.
Functional activity is the most relevant specification of the
1-protease inhibitor products. Functional activity
delineates the capacity of the 1 antitrypsin in
neutralizing the neutrophil elastase, which is responsible for damage to the
lung. All 3 1-protease inhibitor products are labeled
and dosed according to the amount of functionally active
1-protease inhibitor expressed in mg per vial. Each
lot will be slightly different and is labeled and dosed accordingly.
References
1-protease inhibitor for treatment of
-antitrypsin deficiency. Ann Pharmacother 2005;39: 1861-9.
Epub 11 October 2005. DOI 10.1345/aph.1E0611-proteinase inhibitor human). Los Angeles:
Alpha Therapeutic, December 2002.1-proteinase inhibitor human). Elkhart, IN:
Bayer Corporation, March 2003.1-proteinase inhibitor human). Kankakee, IL:
ZLB Behring LLC, Augst 2004.
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