Silicone Oil-Free Polymer Syringes for the Storage of Therapeutic Proteins

Werner, Benjamin Patrick; Schöneich, Christian; Winter, Gerhard

doi:10.1016/j.xphs.2018.10.049

Cited by 25 publications

(6 citation statements)

References 34 publications

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“…The advantages of the glass syringe are experienced usage, low cost, and low oxygen permeability. However, silicone oil, which is inevitably coated into the glass barrels as a lubricant, has been recognized to induce protein aggregation or particle formation in the products [24,54,55]. For example, insulin, abatacept, and other biopharmaceuticals have been reported to be highly sensitive to silicone oil [56,57].…”

Section: Pfss and Auto-injectorsmentioning

confidence: 99%

“…In the case of antibody drugs, the oxidation, especially that of methionine residue is a crucial concern [55,62]. The oxidation of methionine residues in monoclonal antibodies (mAbs) may affect not only their biological efficacy but also serum half-lives [63][64][65].…”

Section: Pfss and Auto-injectorsmentioning

confidence: 99%

“…Amano, et al showed that methionine oxidation was suppressed when a therapeutic antibody was filled in a COP syringe and stored in a blister pack with an oxygen absorber [62]. An alternative approach to reduce the oxidation of proteins is the storage of biopharmaceuticals in nitrogen-filled aluminum pouches [55].…”

Section: Pfss and Auto-injectorsmentioning

confidence: 99%

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Development of syringes and vials for delivery of biologics: current challenges and innovative solutions

Yoneda

Torisu

Uchiyama

2021

Expert Opinion on Drug Delivery

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Introduction: Several new biopharmaceutical dosage forms have developed over time, such as lyophilized vial, liquid vial, and liquid prefilled syringe formulations. This review summarizes major pharmaceutical dosage forms and their advantages, disadvantages, and countermeasures against the shortcomings of each formulation. The appropriate combination of active pharmaceutical ingredients, excipients, and containers should be selected for the safe and less burdensome administration to the patients. Finally, we note certain opinions on the future development of not only therapeutic proteins but also gene therapeutics.Areas covered: This review is to discuss the challenges of the development of dosage forms to improve pharmaceutical stability and how they can be overcome. Expert opinion: Silicone oil-free syringes are highly preferable for minimizing subvisible particles in the drug. It can be proposed that materials with less protein adsorption property are preferable for the suppression of protein aggregation. It is required to minimize adverse effects of biopharmaceuticals through proper quality control of the drug in a container, based on the understating of physicochemical stability of the protein in solution, the physicochemical properties of the container, and their combinations.

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Section: Pfss and Auto-injectorsmentioning

confidence: 99%

Section: Pfss and Auto-injectorsmentioning

confidence: 99%

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Development of syringes and vials for delivery of biologics: current challenges and innovative solutions

Yoneda

Torisu

Uchiyama

2021

Expert Opinion on Drug Delivery

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“…32,33 EtO adducts, similar to other types of chemical modifications to proteins, may also promote immunogenicity in patients treated with protein therapeutics. [34][35][36] More recently, EtO and steam-sterilized polymer syringes were compared to determine the effect of residual EtO on HSA degradation (48). Although the amount of residual EtO in the EtO-sterilized syringes was below the International Organization for Standardization limit, EtO adducts to cysteine and methionine residues in HSA could be readily detected by liquid chromatography and mass spectrometry.…”

Section: Ethylene Oxide Sterilization (Eto)mentioning

confidence: 99%

Stress Factors in Primary Packaging, Transportation and Handling of Protein Drug Products and Their Impact on Product Quality

Narhi

Chou

Christian

et al. 2022

Journal of Pharmaceutical Sciences

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…Previous studies showed for liquid formulations that protein oxidation in COP syringes can be successfully suppressed when the syringes were stored in a blister pack containing an oxygen absorber [ 25 , 26 ]. Similarly, another approach investigated by Werner et al prevented oxidation of therapeutic proteins by storage of COP syringes in nitrogen-filled aluminum pouches [ 27 ]. So far, lyophilizates in COP vials have not really been thought of as a relevant configuration, and the use of absorbers as enabling tools has not been considered in this context.…”

Section: Introductionmentioning

confidence: 99%

Minimizing Oxidation of Freeze-Dried Monoclonal Antibodies in Polymeric Vials Using a Smart Packaging Approach

Härdter

Menzen²,

Winter

2021

Pharmaceutics

Self Cite

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Primary containers made of cyclic olefin polymer (COP) have recently gained attention since they may overcome several risks and shortcomings of glass containers as they exhibit a high break resistance, biocompatibility, and homogeneous heat transfer during lyophilization. On the downside, COP is more permeable for gases, which can lead to an ingress of oxygen into the container over time. Since oxidation is an important degradation pathway for monoclonal antibodies (mAbs), the continuous migration of oxygen into drug product containers should be avoided overall. To date, no long-term stability studies regarding lyophilizates in polymer vials have been published, potentially because of the unbearable gas permeability. In this study, we demonstrate that after lyophilization in COP vials and storage of these vials in aluminum pouches together with combined oxygen and moisture absorbers (“smart packaging”), oxidation of two lyophilized therapeutic antibodies was as low as in glass vials due to the deoxygenated environment in the pouch. Nevertheless, active removal of oxygen from the primary container below the initial level over time during storage in such “smart” secondary packaging was not achieved. Furthermore, residual moisture was controlled. Overall, the smart packaging reveals a promising approach for long-term stability of biopharmaceuticals; in addition to COP’s known benefits, stable, low oxygen and moisture levels as well as the protection from light and cushioning against mechanical shock by the secondary packaging preserve the sensitive products very well.

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Silicone Oil-Free Polymer Syringes for the Storage of Therapeutic Proteins

Cited by 25 publications

References 34 publications

Development of syringes and vials for delivery of biologics: current challenges and innovative solutions

Development of syringes and vials for delivery of biologics: current challenges and innovative solutions

Stress Factors in Primary Packaging, Transportation and Handling of Protein Drug Products and Their Impact on Product Quality

Minimizing Oxidation of Freeze-Dried Monoclonal Antibodies in Polymeric Vials Using a Smart Packaging Approach

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