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. 2024:2024:34.

Potential Process Control Issues With Abatacept

James T Isaacs  1 , Philip J Almeter  1   2 , Aaron N Hunter  1 , Thomas A Lyman  1 , Stephanie P Zapata  1 , Bradley S Henderson  1 , Seth A Larkin  1   2 , Lindsey M Long  1   2 , Megan N Bossle  1   2 , Smaran A Bhaktawara  1   2 , Matthew F Warren  1   2 , Austin M Lozier  1   2 , Joshua D Melson  1   2 , Savannah R Fraley  1   2 , Eunice Hazzel L Relucio  1   2 , Margaret A Felix  1 , Jeffrey W Reynolds  3 , Ryan W Naseman  1   2 , Thomas L Platt  1   2 , Robert A Lodder  4
Affiliations

Potential Process Control Issues With Abatacept

James T Isaacs et al. Contact Context. 2024.

Abstract

Abatacept is a medication administered through intravenous infusion. It is supplied as a sterile, white, preservative-free, freeze-dried powder. Each vial of drug contains 250 mg abatacept, maltose, monobasic sodium phosphate, and sodium chloride for administration. Abatacept is a fusion protein consisting of the extracellular domain of CTLA-4 linked to the modified Fc portion of human immunoglobulin G1. It is produced using recombinant DNA technology. Abatacept is indicated for moderately to severely active rheumatoid arthritis in adults and polyarticular juvenile idiopathic arthritis in pediatric patients 6 years of age and older. It can be used as monotherapy or in combination with other disease-modifying antirheumatic drugs or methotrexate. Inter-lot variability was detected in a library of 132 vials spread across 34 lots of abatacept-maltose for injection by the University of Kentucky Drug Quality Task Force. A subcluster detection test was run on 13 vials that were shown to be an outlier group (rtn=0.9940, rtest=0.9551, rlim=0.9865, p=0.02). Five of these vials individually appeared 4 or more standard deviations from the library cluster.

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Figures

Figure 1.
Figure 1.
Vials of abatacept from lot ACC6785. The drug is a sterile, white, preservative-free, lyophilized powder for intravenous administration.
Figure 2.
Figure 2.
One hundred thirty-two smoothed spectra of 34 lots of abatacept-maltose vials. The areas with differentiating spectral features are marked at 4257, 4532, 4763, and 5150 cm−1.
Figure 3.
Figure 3.
Scatterplot of the scores of the first 3 principal components of the spectral library shown in Figure 2.
Figure 4.
Figure 4.
The mean spectrum of the 34 lots in the library is shown in blue, while the spectrum of vial 57 is shown in red. Vial 57 is 5.6 SDs from the center of the cluster. The difference between vial 57 and the rest of the library is probably not due to moisture content, given the similarity of the peak at 5150 cm−1.
Figure 5.
Figure 5.
Another rotated view of the scatterplot of the scores of the first 3 principal components of the spectral library shown in Figure 3. Vial 18 is displaced in the direction of moisture.
Figure 6.
Figure 6.
The mean spectrum of the 34 lots in the library is shown in blue, while the spectrum of vial 18 is shown in red. Vial 18 is 4.0 SDs from the center of the cluster. The difference between vial 18 and the rest of the library is probably due to moisture content (note the peak at 5150 cm−1).
Figure 7.
Figure 7.
The mean spectrum of the 34 lots in the library is shown in blue, while the spectrum of vial 114 is shown in red. Vial 114 is 3.8 SDs from the center of the cluster. The difference between vial 114 and the rest of the library is probably not due to moisture content, given the similarity of the peak at 5150 cm−1.
Figure 8.
Figure 8.
Another view of the scatterplot of the scores of the first 3 principal components of the spectral library shown in Figure 5.
Figure 9.
Figure 9.
Scatterplot of the scores of principal components 4 through 6 of the spectral library shown in Figure 2. The apparent outliers are vials 10, 18, 55, 69, 95, 10, 86
Figure 10.
Figure 10.
QQ plot from the subcluster detection test for the spectral library vs. the apparent outliers. PCs 1-3, mean=0.9940, SD=0.0037, 98% limit is 0.9865. r=0.9551 so the 2 groups do not match. If the two groups matched, the QQ plot would show a straight line with a slope of one and an intercept of zero.
Figure 11.
Figure 11.
Principal component loadings for PC1 of the abatacept-maltose library.
Figure 12.
Figure 12.
Principal component loadings for PC2 of the abatacept-maltose library.
Figure 13.
Figure 13.
Principal component loadings for PC3 of the abatacept-maltose library.
Figure 14.
Figure 14.
Principal component loadings for PC4 of the abatacept-maltose library.
Figure 15.
Figure 15.
Principal component loadings for PC5 of the abatacept-maltose library.
Figure 16.
Figure 16.
Principal component loadings for PC6 of the abatacept-maltose library.
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References

    1. BMS, 2021. Orencia “Highlights Of Prescribing Information,” https://packageinserts.bms.com/pi/pi_orencia.pdf, retrieved Aug. 28, 2023.
    1. Dempsey RJ, Davis DG, Buice RG Jr, & Lodder RA (1996). Biological and medical applications of near-infrared spectrometry. Applied Spectroscopy, 50(2), 18A–34A.
    1. Drug Shortages Canada (2021). https://www.drugshortagescanada.ca/shortage/146256. Retrieved Aug. 20, 2023
    1. FDA, 2013. Orencia “Highlights Of Prescribing Information” https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125118s171lbl.pdf, Retrieved Aug. 20, 2023
    1. Isaacs JT, Almeter PJ, Henderson BS, Hunter AN, Platt TL, & Lodder RA (2023a). Variability in Content of Hydrocortisone Sodium Succinate. Contact in context. DOI: 10.6084/m9.figshare.23573532 - DOI - PMC - PubMed

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