Heat-stable measles vaccine produced by spray drying

Ohtake, Satoshi; Martin, Russell; Yee, Luisa; Chen, Dexiang; Kristensen, Debra; Lechuga‐Ballesteros, David; Truong‐Le, Vu

doi:10.1016/j.vaccine.2009.11.024

Cited by 113 publications

(87 citation statements)

References 41 publications

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“…Temperature (Black, 1959;Boriskin et al, 1988;Musser et al, 1960;Rapp et al, 1965), pH (Black, 1959;Musser et al, 1960) and salt concentrations (Boriskin et al, 1988;Rapp et al, 1965) were the most important factors analyzed, then. Recently, some work has focused on stability studies for MV vaccines after production and purification (Burger et al, 2008;Ohtake et al, 2010). While these virus particles are stabilized with different agents or are even lyophilized, this stability studies are not representative for measles virus particles under production conditions.…”

Section: Ajbbmentioning

confidence: 99%

Influence of Process Conditions on Measles Virus Stability

Weiss

Salzig

Röder

et al. 2013

American Journal of Biochemistry and Biotechnology

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Recombinant measles viruses are currently tested in clinical trials as oncolytic agent to be applied in cancer therapy. Contrary to their use as vaccine where 10 3 infectious virus particles per dose are needed, for cancer therapy 10 9 virus particles should be provided per dose. This leads to other challenges for the production process when compared to vaccine production. This study presents measles virus stability with regard to conditions during production and storage of the virus. Relevant process parameters such as temperature (4-37°C), pH (pH 4-11), conductivity (1.5 to 137.5 mS cm ) and oxygen partial pressure were analyzed. The infectivity of measles virus particles decreased highly at 37 and 32°C, while at 22 and 4°C it remained stable for several hours or even days, respectively. The thermal inactivation reactions followed first order kinetics and the thermodynamic parameters enthalpy and entropy were estimated. Towards changes in pH measles virus particles were very sensitive, while no inactivation could be observed with varying conductivity. Measles virus incubation at an oxygen partial pressure of 100% did not lead to any loss of infectivity. The results show which parameters should be considered and controlled strongly in the production process to further raise measles virus yields for the high amount needed in cancer therapy approaches.

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Section: Ajbbmentioning

confidence: 99%

Influence of Process Conditions on Measles Virus Stability

Weiss

Salzig

Röder

et al. 2013

American Journal of Biochemistry and Biotechnology

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“…The main factors that influence the stability and activity of biopharmaceuticals during spray-drying are inlet temperature, oxygen environment, and inclusion of stabilizing excipients. Vaccines and proteins can be successfully spray-dried with little physical or chemical damage [37,41,42] and will be discussed further in section "Challenges Specific to Spray-Dried Biopharmaceuticals." Excipients such as amino acids, sugars, and polymers may be incorporated in the formulation to stabilize biopharmaceuticals during the spray-drying process and for long-term storage following spray-drying [43,44].…”

Section: Spray-drying Process Optimization For Biopharmaceuticalsmentioning

confidence: 99%

Spray-Drying of Biopharmaceuticals

Ledet

Graves

Bostanian

et al. 2015

Lyophilized Biologics and Vaccines

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“…Certain amino acids and their salts are potent stabilizers in the freeze-drying of proteins, frozen storage of liposomes, and spray drying of vaccines. [5][6][7][8][9][10][11] Application of the amino acid excipients that protect proteins through particular mechanisms not achievable by saccharides (e.g., aggregation-reducing effect of L-arginine (L-Arg) in aqueous solution) would increase formulation strategies in lyophilization of marginally stable proteins. 5,8,[12][13][14][15] Physical states (e.g., crystallinity, crystal polymorph) of the components are important factors that determine chemical and conformational stability of proteins during the freeze-drying process and subsequent storage.…”

mentioning

confidence: 99%

Amorphous–Amorphous Phase Separation of Freeze-Concentrated Protein and Amino Acid Excipients for Lyophilized Formulations

Izutsu¹,

Yoshida²,

Shibata³

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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The objective of this study was to elucidate the mixing state of proteins and amino acid excipients concentrated in the amorphous non-ice region of frozen solutions. Thermal analysis of frozen aqueous solutions was performed in heating scans before and after a heat treatment. Frozen aqueous solutions containing a protein (e.g., recombinant human albumin, gelatin) or a polysaccharide (dextran) and an amino acid excipient (e.g., L-arginine, L-arginine hydrochloride, L-arginine monophosphate, sodium L-glutamate) at varied mass ratios showed single or double T g ′ (glass transition temperature of maximally freeze-concentrated solutes). Some mixture frozen solutions rich in the polymers maintained the single T g ′ of the freeze-concentrated amorphous solute-mixture phase. In contrast, amino acid-rich mixture frozen solutions revealed two T g ′s that suggested transition of concentrated non-crystalline solute-mixture phase and excipient-dominant phase. Post-freeze heat treatment induced splitting of the T g ′ in some intermediate mass ratio mixture solutions. The mixing state of proteins and amino acids varied depending on their structure, salt types, mass ratio, composition of co-solutes (e.g., NaCl) and thermal history. Information on the varied mixing states should be valuable for the rational use of amino acid excipients in lyophilized protein pharmaceuticals.Key words amorphous; freeze drying; thermal analysis; protein formulation; stabilization; mixing Freeze-drying is a popular method to formulate therapeutic proteins that are insufficiently stable in aqueous solutions during storage.1) Several freeze-dried therapeutic protein formulations contain multiple excipients, including stabilizers, bulking agents, pH buffer agents, and tonicity modifiers besides active pharmaceutical ingredient (API).2-4) Sucrose and trehalose are popular stabilizers that protect proteins from dehydration-induced irreversible structural changes during the process and from chemical degradation during storage. Certain amino acids and their salts are potent stabilizers in the freeze-drying of proteins, frozen storage of liposomes, and spray drying of vaccines.5-11) Application of the amino acid excipients that protect proteins through particular mechanisms not achievable by saccharides (e.g., aggregation-reducing effect of L-arginine (L-Arg) in aqueous solution) would increase formulation strategies in lyophilization of marginally stable proteins. 5,8,[12][13][14][15] Physical states (e.g., crystallinity, crystal polymorph) of the components are important factors that determine chemical and conformational stability of proteins during the freeze-drying process and subsequent storage. [16][17][18] The stabilizing effects of disaccharides are attributed to protection of protein conformation by the substitution of surrounding water molecules and by holding protein molecules in lower molecular mobility glassstate amorphous solids. Crystallization of some sugar alcohols (e.g., mannitol) during the freezing segment of lyophilization deprives the...

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Heat-stable measles vaccine produced by spray drying

Cited by 113 publications

References 41 publications

Influence of Process Conditions on Measles Virus Stability

Influence of Process Conditions on Measles Virus Stability

Spray-Drying of Biopharmaceuticals

Amorphous–Amorphous Phase Separation of Freeze-Concentrated Protein and Amino Acid Excipients for Lyophilized Formulations

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