Expanding Bedside Filtration—A Powerful Tool to Protect Patients From Protein Aggregates

Werner, Benjamin Patrick; Winter, Gerhard

doi:10.1016/j.xphs.2018.07.022

Cited by 12 publications

(11 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, we tested an in-line filter as a mitigation strategy, which might be used clinically for minimizing delivery of protein particles to patients during IV administration. Earlier studies have documented that such filters are extremely effective at removing microparticles from IV solutions of protein drugs 93,114 .…”

Section: Effects Of Pts Transportation Of IV Bags On Particle Formation In Iv Solutions With Mabmentioning

confidence: 99%

Effects of Transportation of IV Bags Containing Protein Formulations Via Hospital Pneumatic Tube System: Particle Characterization by Multiple Methods

Linkuvienė

Ross

Crawford

et al. 2022

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

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.

show abstract

Section: Effects Of Pts Transportation Of IV Bags On Particle Formation In Iv Solutions With Mabmentioning

confidence: 99%

Effects of Transportation of IV Bags Containing Protein Formulations Via Hospital Pneumatic Tube System: Particle Characterization by Multiple Methods

Linkuvienė

Ross

Crawford

et al. 2022

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

show abstract

“…5 Change to a soft rubber stopper, 12 use steam sterilized rather than gamma-sterilized stoppers, 13 and/or use an effective in-line filter during administration. 14,16 Systemic and local toxic effects in patients due to leachables. 17 Residual metal elements and/or organic compounds from the CSTD contact materials may potentially leach into the drug solution.…”

Section: Proposed Approach For Demonstrating Compatibility With Cstdsmentioning

confidence: 99%

“…Use an in-line filter to remove protein particles. 14,16 Avoid CSTDs containing high levels of silicone oil or lubricants that may pose a risk to product stability. Patient may be underdosed due to adsorption of the protein to CSTD contact surfaces.…”

Section: Proposed Approach For Demonstrating Compatibility With Cstdsmentioning

confidence: 99%

An Industry Perspective on Compatibility Assessment of Closed System Drug-Transfer Devices for Biologics

Besheer

Burton

Galas

et al. 2021

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

The Formulation Workstream of the BioPhorum Development Group (BPDG), an industry-wide consortium, has identified the increased use of closed system drug-transfer devices (CSTDs) with biologics, without an associated compatibility assessment, to be of significant concern. The use of CSTDs has increased significantly in recent years due to the recommendations by NIOSH and USP that they be used during preparation and administration of hazardous drugs. While CSTDs are valuable in the healthcare setting to reduce occupational exposure to hazardous compounds, these devices may present particular risks that must be adequately assessed prior to use to ensure their compatibility with specific types of drug products, such as biologic drugs, which may be sensitive. The responsibility of ensuring quality of biologic products through preparation and administration to the patient lies with the drug product sponsor. Due to the significant number of marketed CSTD systems, and the large variety of components offered for each system, a strategic, risk-based approach to assessing compatibility is recommended herein. In addition to traditional material compatibility, assessment of CSTD compatibility with biologics should consider additional parameters to address specific CSTD-related risks. The BPDG Formulation Workstream has proposed a systematic risk-based evaluation approach as well as a mitigation strategy for establishing suitability of CSTDs for use.

show abstract

“…Furthermore, micron aggregates were detected in ejected solutions from prefillable syringes due to increased antibody adsorption to the syringe surface (40). Interestingly, it was shown that bedside filtration could significantly reduce the quantity of submicron-and micron-sized aggregates before BP injection (41). Finally, it is suggested that subcutaneous administration of antibody solutions could also favor aggregation due to the forced interaction between monomers in highly concentrated solutions (42,43).…”

Section: Aggregation Processmentioning

confidence: 99%

“…On the other hand, in vivo studies are currently focusing on the oligomeric antibodies and their immunogenicity (68,69). Indeed, nanometric-sized aggregates could be found in preparations and are hardly ever detected and eliminated before the administration of the therapeutic antibody (38,41). Contrary to subvisible aggregates, oligomers would probably be uptaken by endocytosis, which is yet to be confirmed (67).…”

Section: The Role Of Antibody Aggregates In the Initiation Of A Specimentioning

confidence: 99%

Immunogenicity of Bioproducts: Cellular Models to Evaluate the Impact of Therapeutic Antibody Aggregates

2020

View full text Add to dashboard Cite

Patients treated with bioproducts (BPs) frequently develop anti-drug antibodies (ADAs) with potential neutralizing capacities leading to loss of clinical response or potential hypersensitivity reactions. Many factors can influence BP immunogenicity and could be related to the patient, the treatment, as well as to the product itself. Among these latter factors, it is now well accepted that BP aggregation is associated with an increased potential for immunogenicity, as aggregates seem to be correlated with ADA development. Moreover, the presence of high-affinity ADAs suggests a CD4 T-cell dependent adaptive immune response and therefore a pivotal role for antigenpresenting cells (APCs), such as dendritic cells (DCs). In this review, we address the in vitro methods developed to evaluate how monoclonal antibodies could trigger the immunization process by focusing on the role of aggregated antibodies in the establishment of this response. In particular, we will present the different cell-based assays that have been used to assess the potential of antibodies and their aggregates to modulate cellular mechanisms leading to activation and the biological parameters (cellular activation markers, proliferation and secreted molecules) that can be measured to evaluate the different cell activation stages and their consequences in the propagation of the immune response. Indeed, the use of such strategies could help evaluate the risk of BP immunogenicity and their role in mitigating this risk.

show abstract

Expanding Bedside Filtration—A Powerful Tool to Protect Patients From Protein Aggregates

Cited by 12 publications

References 51 publications

Effects of Transportation of IV Bags Containing Protein Formulations Via Hospital Pneumatic Tube System: Particle Characterization by Multiple Methods

Effects of Transportation of IV Bags Containing Protein Formulations Via Hospital Pneumatic Tube System: Particle Characterization by Multiple Methods

An Industry Perspective on Compatibility Assessment of Closed System Drug-Transfer Devices for Biologics

Immunogenicity of Bioproducts: Cellular Models to Evaluate the Impact of Therapeutic Antibody Aggregates

Contact Info

Product

Resources

About