Shear Effects on Aluminum Phosphate Adjuvant Particle Properties in Vaccine Drug Products

Kolade, Olatomirin O.; Jin, Wenbin; Tengroth, Charbel; Green, Kenneth D.; Bracewell, Daniel G.

doi:10.1002/jps.24127

Cited by 21 publications

(18 citation statements)

References 22 publications

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“…The propensity of adjuvant particles to self-associate and form agglomerated structures in solution is of particular interest in the study of vaccines and the presence of such entities within stock suspensions has been previously confirmed to some extent using sizing methodologies with a greater upper limit of detection (Burrell et al, 2000b; Lindblad, 2004; Harris et al, 2012). Indeed, the median size obtained herein for Adju-Phos® (7152 ± 308 nm) is in good agreement with that obtained using low angle laser light scattering if typical batch variation is also considered (6.2 μm—Kolade et al, 2015), which adds some legitimacy to both our native stock adjuvant data and approach to sizing despite its noted limitations.…”

Section: Discussionsupporting

confidence: 87%

From Stock Bottle to Vaccine: Elucidating the Particle Size Distributions of Aluminum Adjuvants Using Dynamic Light Scattering

2017

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The physicochemical properties of aluminum salts are key determinants of their resultant adjuvanticity in vivo when administered as part of a vaccine. While there are links between particle size and the efficacy of the immune response, the limited literature directly characterizing the PSD of aluminum adjuvants has stymied the elucidation of such a relationship for these materials. Hence, this comparative study was undertaken to monitor the PSD of aluminum adjuvants throughout the process of vaccine formulation using DLS. A significant proportion of the stock suspensions was highly agglomerated (>9 μm) and Alhydrogel® exhibited the smallest median size (2677 ± 120 nm) in comparison to Adju-Phos® or Imject alum® (7152 ± 308 and 7294 ± 146 nm respectively) despite its large polydispersity index (PDI). Dilution of these materials induced some degree of disaggregation within all samples with Adju-Phos® being the most significantly affected. The presence of BSA caused the median size of Alhydrogel® to increase but these trends were not evident when model vaccines were formulated with either Adju-Phos® or Imject alum®. Nevertheless, Alhydrogel® and Adju-Phos® exhibited comparable median sizes in the presence of this protein (4194 ± 466 and 4850 ± 501 nm respectively) with Imject alum® being considerably smaller (2155 ± 485 nm). These results suggest that the PSD of aluminum adjuvants is greatly influenced by dilution and the degree of protein adsorption experienced within the vaccine itself. The size of the resultant antigen-adjuvant complex may be important for its immunological recognition and subsequent clearance from the injection site.

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Section: Discussionsupporting

confidence: 87%

From Stock Bottle to Vaccine: Elucidating the Particle Size Distributions of Aluminum Adjuvants Using Dynamic Light Scattering

2017

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“…This investigation focused on the integrity of a biopharmaceutical antibody‐fusion protein used in a two‐phased drug delivery system to treat colorectal carcinoma (Bagshawe, ; Michael et al, ). Hence it was imperative that the MFECP1 fusion protein was not degraded or deactivated in anyway which would otherwise result in loss of therapeutic activity (Kolade et al, ). A USD shear device was used to mimic the harsh bioprocessing conditions interacting with the protein during production and purification.…”

Section: Discussionmentioning

confidence: 99%

“…This could allow bioprocessing options to be studied at early stages of the development pathway in parallel to preclinical and clinical trials, thereby reducing the need for expensive pilot scale manufacture. The early prediction of robust and reliable large‐scale bioprocessing will allow speed to market, resulting in exclusivity and high profitability (Kolade et al, ; Rayat, Chatel, Hoare, & Lye, ).…”

Section: Introductionmentioning

confidence: 99%

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The use of a surface active agent in the protection of a fusion protein during bioprocessing

Blas

Tolner

Ward

et al. 2018

Biotech & Bioengineering

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The bioprocessing of a fusion protein is characterised by low yields and at a series of recovery and purification stages that leads to an overall 90% loss. Much of this apparent loss is due to the denaturation of a protein, missing a vital affinity ligand. However, there is evidence of the protection of degradation products which occurs in the presence of shear plus air/liquid interfaces. This study seeks out to characterise the loss and use ultra-scale-down studies to predict its occurrence and hence shows these may be diminished by the use of protective reagents such as Pluronic F68.

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“…During combination vaccine manufacture, the order of addition of components may impact the observed immunogenicity . As the facet of components and their pharmaceutical presentations is huge, the approaches tackling those challenges may differ tremendously depending on the kind of problem …”

Section: General Considerations Requirements and Regulationsmentioning

confidence: 99%

Challenges for the pharmaceutical technical development of protein coformulations

Mueller

Altenburger

Mohl

2017

Journal of Pharmacy and Pharmacology

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Objectives This review discusses challenges to stability, analytics and manufacturing of protein coformulations. Furthermore, general considerations to be taken into account for the pharmaceutical development of coformulated protein drug products are highlighted. Key findings Coformulation of two or more active substances in one single dosage form has recently seen increasing use offering several advantages, such as increased efficacy and/or the overall reduction of adverse event incidents in patients. Most marketed coformulated drug products are composed of small molecules. As proteins are not only comparatively large but also complex molecules, the maintenance of their physicochemical integrity within a formulation throughout pharmaceutical processing, storage, transport, handling and patient administration to ensure proper pharmacokinetics and pharmacodynamics in vivo already represents various challenges for single-entity products. Thus, nowadays, only sparse biologics-based coformulations can be found, as additional complexity during development is given for these products. Summary The complexity of the dosage form and the protein molecules results into additional challenges to formulation, manufacture, storage, transport, handling and patient administration, stability and analytics during the pharmaceutical development of protein coformulations. Various points have to be considered during different stages of development in order to obtain a safe and efficacious product.

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Shear Effects on Aluminum Phosphate Adjuvant Particle Properties in Vaccine Drug Products

Cited by 21 publications

References 22 publications

From Stock Bottle to Vaccine: Elucidating the Particle Size Distributions of Aluminum Adjuvants Using Dynamic Light Scattering

From Stock Bottle to Vaccine: Elucidating the Particle Size Distributions of Aluminum Adjuvants Using Dynamic Light Scattering

The use of a surface active agent in the protection of a fusion protein during bioprocessing

Challenges for the pharmaceutical technical development of protein coformulations

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