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Journal of Blood Medicine Volume 12, 2021 - Issue
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Original Research

Recombinant FVIII Products (Turoctocog Alfa and Turoctocog Alfa Pegol) Stable Up to 40°C

Mariasanta Napolitano1 Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo Reference Regional Center for Thrombosis and Hemostasis, Hematology Unit, Palermo, ItalyORCID Iconhttps://orcid.org/0000-0001-8934-2936View further author information
ORCID Icon,
Arne Agerlin Olsen2 Novo Nordisk A/S, Biopharm Manufacturing Development, Gentofte, DenmarkView further author information
,
Anne Mette Nøhr2 Novo Nordisk A/S, Biopharm Manufacturing Development, Gentofte, DenmarkCorrespondence[email protected]
ORCID Iconhttps://orcid.org/0000-0002-8577-4798View further author information
ORCID Icon &
Hermann Eichler3 Saarland University and Saarland University Hospital, Institute of Clinical Haemostaseology and Transfusion Medicine, Homburg (Saar), GermanyView further author information
Pages 9-20 | Published online: 25 Jan 2021

Figures & data

Figure 1 ICH quality guidelines for pharmaceutical stability storage. (https://q1scientific.com/ich-quality-guidelines/)

Notes: Long-term testing conditions for: Zone I, 21°C/45% RH (temperate); Zone II, 25°C/60% RH (subtropical and Mediterranean); Zone III, 30°C/35% RH (hot/dry); Zone IV, 30°C/75% RH (hot/very humid). Data from WHO.Citation19
Abbreviations: ICH, International Council on Harmonisation; RH, relative humidity; WHO, World Health Organization.
Figure 1 ICH quality guidelines for pharmaceutical stability storage. (https://q1scientific.com/ich-quality-guidelines/)

Figure 2 Study design.

Notes: The stability of turoctocog alfa dry powder product was assessed after storage at 5°C for 27 months followed by 40°C for 3 months (reference samples maintained at 5°C for 3 months) and after storage at 30°C for 9 months following storage at 5°C for 21 months. The stability of turoctocog alfa pegol dry powder product was also assessed after storage at 5°C for 27 months, followed by 40°C for 3 months and after storage at 30°C for 12 months following storage at 5°C for 18 months.
Abbreviations: AH, ambient humidity; IU, international units; RH, relative humidity.
Figure 2 Study design.

Figure 3 Oxidized forms of turoctocog alfa dry powder samples as the rate of oxidation (Arrhenius correlation) (A), when stored at 5°C for 21 months followed by storage at 30°C for 9 months (B), 5°C for 27 months followed by storage at 40°C for 3 months (C), and when stored at 5°C for 30 months (D), 30°C for 12 months (E), and 40°C for 6 months (F). Oxidized forms of turoctocog alfa pegol dry powder samples when stored at 5°C for 18 months followed by storage at 30°C for 12 months (G), 5°C for 27 months followed by storage at 40°C for 3 months (H), and when stored at 5°C for 30 months (I), 30°C for 12 months (J), and 40°C for 6 months (K). Shelf-life limits for both products are shown by the horizontal dotted lines.

Abbreviations: IU, international units; T, temperature (in degrees Kelvin).
Figure 3 Oxidized forms of turoctocog alfa dry powder samples as the rate of oxidation (Arrhenius correlation) (A), when stored at 5°C for 21 months followed by storage at 30°C for 9 months (B), 5°C for 27 months followed by storage at 40°C for 3 months (C), and when stored at 5°C for 30 months (D), 30°C for 12 months (E), and 40°C for 6 months (F). Oxidized forms of turoctocog alfa pegol dry powder samples when stored at 5°C for 18 months followed by storage at 30°C for 12 months (G), 5°C for 27 months followed by storage at 40°C for 3 months (H), and when stored at 5°C for 30 months (I), 30°C for 12 months (J), and 40°C for 6 months (K). Shelf-life limits for both products are shown by the horizontal dotted lines.

Figure 4 Potency of turoctocog alfa dry powder samples when stored at 5°C for 21 months followed by storage at 30°C for 9 months (A), 5°C for 27 months followed by storage at 40°C for 3 months (B), 5°C for 30 months (C), 30°C for 12 months (D), and 40°C for 6 months (E). Potency of turoctocog alfa pegol dry powder samples when stored at 5°C for 18 months followed by storage at 30°C for 12 months (F), 5°C for 27 months followed by storage at 40°C for 3 months (G), 5°C for 30 months (H), 30°C for 12 months (I), and 40°C for 6 months (J). Upper and lower shelf-life limits for both products are shown by the horizontal dotted lines.

Abbreviation: IU, international units.
Figure 4 Potency of turoctocog alfa dry powder samples when stored at 5°C for 21 months followed by storage at 30°C for 9 months (A), 5°C for 27 months followed by storage at 40°C for 3 months (B), 5°C for 30 months (C), 30°C for 12 months (D), and 40°C for 6 months (E). Potency of turoctocog alfa pegol dry powder samples when stored at 5°C for 18 months followed by storage at 30°C for 12 months (F), 5°C for 27 months followed by storage at 40°C for 3 months (G), 5°C for 30 months (H), 30°C for 12 months (I), and 40°C for 6 months (J). Upper and lower shelf-life limits for both products are shown by the horizontal dotted lines.

Figure 5 Water content of turoctocog alfa dry powder samples when stored at 5°C for 21 months followed by storage at 30°C for 9 months (A), 5°C for 27 months followed by storage at 40°C for 3 months (B), 5°C for 30 months (C), 30°C for 12 months (D), and 40°C for 6 months (E). Water content of turoctocog alfa pegol dry powder samples when stored at 5°C for 18 months followed by storage at 30°C for 12 months (F), 5°C for 27 months followed by storage at 40°C for 3 months (G), 5°C for 30 months (H), 30°C for 12 months (I), and 40°C for 6 months (J). Shelf-life limits for both products are shown by the horizontal dotted lines.

Abbreviation: IU, international units.
Figure 5 Water content of turoctocog alfa dry powder samples when stored at 5°C for 21 months followed by storage at 30°C for 9 months (A), 5°C for 27 months followed by storage at 40°C for 3 months (B), 5°C for 30 months (C), 30°C for 12 months (D), and 40°C for 6 months (E). Water content of turoctocog alfa pegol dry powder samples when stored at 5°C for 18 months followed by storage at 30°C for 12 months (F), 5°C for 27 months followed by storage at 40°C for 3 months (G), 5°C for 30 months (H), 30°C for 12 months (I), and 40°C for 6 months (J). Shelf-life limits for both products are shown by the horizontal dotted lines.

Figure 6 HMWP of turoctocog alfa dry powder samples when stored at 5°C for 21 months followed by storage at 30°C for 9 months (A), 5°C for 27 months followed by storage at 40°C for 3 months (B), 5°C for 30 months (C), 30°C for 12 months (D), and 40°C for 6 months (E). HMWP of turoctocog alfa pegol dry powder samples when stored at 5°C for 18 months followed by storage at 30°C for 12 months (F), 5°C for 27 months followed by storage at 40°C for 3 months (G), 5°C for 30 months (H), 30°C for 12 months (I), and 40°C for 6 months (J). Shelf-life limits for both products are shown by the horizontal dotted lines.

Abbreviations: HMWP, high molecular weight protein; IU, international units.
Figure 6 HMWP of turoctocog alfa dry powder samples when stored at 5°C for 21 months followed by storage at 30°C for 9 months (A), 5°C for 27 months followed by storage at 40°C for 3 months (B), 5°C for 30 months (C), 30°C for 12 months (D), and 40°C for 6 months (E). HMWP of turoctocog alfa pegol dry powder samples when stored at 5°C for 18 months followed by storage at 30°C for 12 months (F), 5°C for 27 months followed by storage at 40°C for 3 months (G), 5°C for 30 months (H), 30°C for 12 months (I), and 40°C for 6 months (J). Shelf-life limits for both products are shown by the horizontal dotted lines.

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