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. 2023:2023:10.6084/m9.figshare.23524530.
doi: 10.6084/m9.figshare.23524530. Epub 2023 Jun 20.

Quality Variations in Thyrotropin Alfa

James T Isaacs  1 , Philip J Almeter  1   2 , Bradley S Henderson  1 , Aaron N Hunter  1 , Thomas L Platt  1 , Cristian Samano-Garcia  3 , Robert A Lodder  4
Affiliations

Quality Variations in Thyrotropin Alfa

James T Isaacs et al. Contact Context. 2023.

Abstract

Thyrotropin alfa is a heterodimeric glycoprotein containing human thyroid stimulating hormone (TSH). It is used as an adjunctive diagnostic tool for serum thyroglobulin (Tg) testing with or without radioiodine imaging in the follow-up of patients with well-differentiated thyroid cancer who have previously undergone thyroidectomy. Inter-lot variability in the Fourier transform near-infrared spectra of 30 samples obtained from four separate lots of Thyrogen® was detected in the Drug Quality Study (DQS). The vials fell into two distinct groups (rtst = 0.90, rlim= 0.98, p=0.02). In addition, one vial of the 30 (3%) appeared 4.7 multidimensional SDs from all of the other vials, suggesting that it also represents a different material.

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Figures

Figure 1.
Figure 1.
Vials of thyrotropin alfa for injection from lot BY0484. The drug appears as a white freeze-dried powder.
Figure 2.
Figure 2.
Spectra of 30 vials from lots OY0272, BY0349, BY0351, and BY0484 from 4100–4900 cm−1.
Figure 3.
Figure 3.
Spectra of 30 vials from lots 0Y0272, BY0349, BY0351, and BY0484 from 5750–6750 cm−1.
Figure 4.
Figure 4.
Spectra of 30 vials from lots 0Y0272, BY0349, BY0351, and BY0484 cluster into 2 groups. The groups are significantly different according to the subcluster detection test (rtst = 0.90, rlim= 0.98, p=0.02).
Figure 5.
Figure 5.
The blue line connects the vials and lots in Figure 4 in order. The blue line crosses between the two groups 13 times because both groups contain vials from all of the lots.
Figure 6.
Figure 6.
On the next 4 PCs (4, 5 and 6) for the 4 lots, only one vial appears unusual. Vial 2 is displaced 4.6 standard deviations from the other 29 vials.
Figure 7.
Figure 7.
PC loadings of the thyrotropin alfa library composed of spectra of the four lots (0Y0272, BY0349, BY0351, and BY0484).
Figure 8.
Figure 8.
Loadings of the second PC of the spectral library. Major peaks appear at 4087, 4440, 4676, 6546, 7010, and 7918 cm−1.
Figure 9.
Figure 9.
Loadings of the third PC of the spectral library. Major peaks are noted on the graph.
Figure 10.
Figure 10.
Loadings of the fourth PC of the spectral library. Major peaks are noted on the spectrum.
Figure 11.
Figure 11.
Loadings of the fifth PC of the spectral library. Major peaks are noted on the graph.
Figure 12.
Figure 12.
Loadings of the sixth PC of the spectral library. Major peaks are noted on the graph.
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References

    1. Drug Shortages Canada, 2022. Drug Shortage Report for THYROGEN, Report ID 152688. https://www.drugshortagescanada.ca/shortage/152688. Last accessed Jun. 9, 2023.
    1. FDA. 2020. HIGHLIGHTS OF PRESCRIBING INFORMATION for Thyrogen. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020898s063s065..., retrieved Jun. 8, 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. Isaacs JT, Almeter PJ, Henderson BS, Hunter AN, Platt TL, & Lodder RA (2023b).Spectrometric Analysis of Dantrolene Sodium. Contact in context, 2023. - PMC - PubMed
    1. Isaacs JT, Almeter PJ, Henderson BS, Hunter AN, Platt TL, & Lodder RA (2023b).Spectral Intra-Lot and Inter-Lot Variability in Carfilzomib. Contact in context, 2023. - PMC - PubMed

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