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. 2024:2024:10.6084/m9.figshare.26828245.
doi: 10.6084/m9.figshare.26828245. Epub 2024 Aug 27.

Lack of Content Uniformity in Azacitidine Vials

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 , 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 , Kaylee N Meador  2 , Sanda Grahovic  2 , Jessica T Rajcan  2 , Hyungjoo Shon  2 , Anna M Carlson  2 , Taylor M Fuson  2 , Lian Z Haney  2 , Robert A Lodder  4
Affiliations

Lack of Content Uniformity in Azacitidine Vials

James T Isaacs et al. Contact Context. 2024.

Abstract

Azacitidine injections are used to treat specific types of blood cancers. They work by interfering with the growth of cancer cells. Azacitidine for injection is a nucleoside metabolic inhibitor indicated for the treatment of (a) Adult patients with the following FAB myelodysplastic syndrome (MDS) subtypes: Refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMMoL), and (b) Pediatric patients aged 1 month and older with newly diagnosed Juvenile Myelomonocytic Leukemia (JMML). Intra-lot variability was initially detected in one lot of azacitidine for injection in which 17% of the samples scanned in the lot were more than 5 multidimensional SDs from the center of the lot cluster. After the intra-lot variability was detected, inter-lot variability was measured in a spectral library comprising 8 lots of azacitidine for injection.

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Figures

Figure 1.
Figure 1.
Photo of the Azacitidine for Injection drug product from lot 1A389A.
Figure 2.
Figure 2.
Spectra of vials in lot 0J367A. Vial 3 (gold) in the set appears 5.4 SDs from the other vials in the lot. Vial 3 has a stronger peak at about 4625 cm−1 than the other vials from the same lot, and is missing peaks at about 4220 and 4280 cm−1 that the other vials possess.
Figure 3.
Figure 3.
Spectra of vials in lot 0J367A. Vial 3 (gold) in the set appears 5.4 SDs from the other vials in the lot. Vial 3 has stronger peaks at about 5910, 5795, and 5750 cm−1 than the rest of the set of vials from lot 0J367A.
Figure 4.
Figure 4.
Principal component scores of the spectra of the samples from lot 0J367A. Vial 3 from Figure 2 and Figure 3 appears at the far right of the plot. Vial 3 is 5.4 multidimensional SDs from the other vials from the lot.
Figure 5.
Figure 5.
Full spectra of the library of 84 vials from 8 lots of azacitidine.
Figure 6.
Figure 6.
A scatterplot of the spectral data of the library using PCs 1, 2, and 3.
Figure 7.
Figure 7.
A scatterplot of the spectral data of the library on PCs 4, 5, and 6. One vial appears to be a possible outlier, vial number 45. Vial 45 measures 7.3 multidimensional SDs from the center of the spectral library cluster.
Figure 8.
Figure 8.
A scatterplot of the vials in the library on PCs 7, 8, and 9.
Figure 9.
Figure 9.
A plot of the principal component loadings for PC 1 of the azacitidine library. PC 1, as is typical in drugs, shows the effects of baseline variation after multiplicative scatter correction.
Figure 10.
Figure 10.
A plot of the loadings of the spectral library for PC 2.
Figure 11.
Figure 11.
A plot of the loadings of the spectral library for PC 3.
Figure 12.
Figure 12.
A plot of the loadings of the spectral library for PC 4.
Figure 13.
Figure 13.
A plot of the loadings of the spectral library for PC 5
Figure 14.
Figure 14.
A plot of the loadings of the spectral library for PC 6.
Figure 15.
Figure 15.
A plot of the loadings of the spectral library for PC 7
Figure 16.
Figure 16.
A plot of the loadings of the spectral library for PC 8.
Figure 17.
Figure 17.
A plot of the loadings of the spectral library for PC 9.
See this image and copyright information in PMC

References

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