Skip to main content

Main menu

  • Home
  • Content
    • Current Issue
    • Past Issues
    • Accepted Articles
    • Email Alerts
    • RSS
    • Terms of Use
  • About PDA JPST
    • JPST Editors and Editorial Board
    • About/Vision/Mission
    • Paper of the Year
  • Author & Reviewer Resources
    • Author Resources / Submit
    • Reviewer Resources
  • JPST Access and Subscriptions
    • PDA Members
    • Institutional Subscriptions
    • Nonmember Access
  • Support
    • Join PDA
    • Contact
    • Feedback
    • Advertising
    • CiteTrack
  • .
    • Visit PDA
    • PDA Letter
    • Technical Reports
    • news uPDATe
    • Bookstore

User menu

  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
PDA Journal of Pharmaceutical Science and Technology
  • .
    • Visit PDA
    • PDA Letter
    • Technical Reports
    • news uPDATe
    • Bookstore
  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart
PDA Journal of Pharmaceutical Science and Technology

Advanced Search

  • Home
  • Content
    • Current Issue
    • Past Issues
    • Accepted Articles
    • Email Alerts
    • RSS
    • Terms of Use
  • About PDA JPST
    • JPST Editors and Editorial Board
    • About/Vision/Mission
    • Paper of the Year
  • Author & Reviewer Resources
    • Author Resources / Submit
    • Reviewer Resources
  • JPST Access and Subscriptions
    • PDA Members
    • Institutional Subscriptions
    • Nonmember Access
  • Support
    • Join PDA
    • Contact
    • Feedback
    • Advertising
    • CiteTrack
  • Follow pda on Twitter
  • Visit PDA on LinkedIn
  • Visit pda on Facebook
Research ArticleResearch

Filling of High-Concentration Monoclonal Antibody Formulations into Pre-Filled Syringes: Filling Parameter Investigation and Optimization

Wendy Shieu, Sarah A. Torhan, Edwin Chan, Aaron Hubbard, Benson Gikanga, Oliver B. Stauch and Yuh-Fun Maa
PDA Journal of Pharmaceutical Science and Technology March 2014, 68 (2) 153-163; DOI: https://doi.org/10.5731/pdajpst.2014.00973
Wendy Shieu
Pharmaceutical Processing and Technology Development, Genentech, a member of the Roche Group, South San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sarah A. Torhan
Pharmaceutical Processing and Technology Development, Genentech, a member of the Roche Group, South San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Edwin Chan
Pharmaceutical Processing and Technology Development, Genentech, a member of the Roche Group, South San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Aaron Hubbard
Pharmaceutical Processing and Technology Development, Genentech, a member of the Roche Group, South San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Benson Gikanga
Pharmaceutical Processing and Technology Development, Genentech, a member of the Roche Group, South San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Oliver B. Stauch
Pharmaceutical Processing and Technology Development, Genentech, a member of the Roche Group, South San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yuh-Fun Maa
Pharmaceutical Processing and Technology Development, Genentech, a member of the Roche Group, South San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: maay@gene.com
  • Article
  • Figures & Data
  • References
  • Info & Metrics
  • PDF
Loading

Abstract

Syringe filling, especially the filling of high-concentration/viscosity monoclonal antibody formulations, is a complex process that has not been widely published in literature. This study sought to increase the body of knowledge for syringe filling by analyzing and optimizing the filling process from the perspective of a fluid's physical properties (e.g., viscosity, concentration, surface tension). A bench-top filling unit, comprising a peristaltic pump unit and a filling nozzle integrated with a linear actuator, was utilized; glass nozzles were employed to visualize liquid flow inside the nozzle with a high-speed camera. The desired outcome of process optimization was to establish a clean filling cycle (e.g., absence of splashes, bubbles, and foaming during filling and absence of dripping from the fill nozzle post-fill) and minimize the risk of nozzle clogging during nozzle idle time due to formulation drying at or near the nozzle tip. The key process variables were determined to be nozzle size, airflow around the nozzle tip, pump suck-back (SB)/reversing, fluid viscosity, and protein concentration, while pump velocity, acceleration, and fluid/nozzle interphase properties were determined to be relatively weak parameters. The SB parameter played an especially critical role in nozzle clogging. This study shows that an appropriate combination of optimal SB setting, nozzle size, and airflow conditions could effectively extend nozzle idle time in a large-scale filling facility and environment.

LAY ABSTRACT: Syringe filling can be considered a well-established manufacturing process and has been implemented by numerous contract manufacturing organizations and biopharmaceutical companies. However, its technical details and associated critical process parameters are rarely published. The information on high-concentration/viscosity formulation filling is particularly lacking. The purpose of this study is three-fold: (1) to reveal design details of a bench-top syringe filling unit; (2) to identify and optimize critical process parameters; (3) to apply the learning to practical filling operation. The outcomes of this study will benefit scientists and engineers who develop pre-filled syringe products by providing a better understanding of HC formulation filling principles and challenges.

  • Prefilled syringe
  • High-concentration monoclonal antibody
  • Peristaltic pump
  • Suck-back
  • Formulation drying
  • © PDA, Inc. 2014
View Full Text

PDA members receive access to all articles published in the current year and previous volume year. Institutional subscribers received access to all content. Log in below to receive access to this article if you are either of these.  

If you are neither or you are a PDA member trying to access an article outside of your membership license, then you must purchase access to this article (below). If you do not have a username or password for JPST, you will be required to create an account prior to purchasing. 

Full issue PDFs are for PDA members only.

Note to pda.org users

The PDA and PDA bookstore websites (www.pda.org and www.pda.org/bookstore) are separate websites from the PDA JPST website. When you first join PDA, your initial UserID and Password are sent to HighWirePress to create your PDA JPST account. Subsequent UserrID and Password changes required at the PDA websites will not pass on to PDA JPST and vice versa. If you forget your PDA JPST UserID and/or Password, you can request help to retrieve UserID and reset Password below.

Log in using your username and password

Forgot your user name or password?

Log in through your institution

You may be able to gain access using your login credentials for your institution. Contact your library if you do not have a username and password.
If your organization uses OpenAthens, you can log in using your OpenAthens username and password. To check if your institution is supported, please see this list. Contact your library for more details.

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.

patientACCESS

patientACCESS - Patients desiring access to articles

Full issue PDFs are for PDA members only. You can join PDA at www.pda.org. 

PreviousNext
Back to top

In This Issue

PDA Journal of Pharmaceutical Science and Technology: 68 (2)
PDA Journal of Pharmaceutical Science and Technology
Vol. 68, Issue 2
March/April 2014
  • Table of Contents
  • Index by Author
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on PDA Journal of Pharmaceutical Science and Technology.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Filling of High-Concentration Monoclonal Antibody Formulations into Pre-Filled Syringes: Filling Parameter Investigation and Optimization
(Your Name) has sent you a message from PDA Journal of Pharmaceutical Science and Technology
(Your Name) thought you would like to see the PDA Journal of Pharmaceutical Science and Technology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
5 + 11 =
Solve this simple math problem and enter the result. E.g. for 1+3, enter 4.
Citation Tools
Filling of High-Concentration Monoclonal Antibody Formulations into Pre-Filled Syringes: Filling Parameter Investigation and Optimization
Wendy Shieu, Sarah A. Torhan, Edwin Chan, Aaron Hubbard, Benson Gikanga, Oliver B. Stauch, Yuh-Fun Maa
PDA Journal of Pharmaceutical Science and Technology Mar 2014, 68 (2) 153-163; DOI: 10.5731/pdajpst.2014.00973

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Filling of High-Concentration Monoclonal Antibody Formulations into Pre-Filled Syringes: Filling Parameter Investigation and Optimization
Wendy Shieu, Sarah A. Torhan, Edwin Chan, Aaron Hubbard, Benson Gikanga, Oliver B. Stauch, Yuh-Fun Maa
PDA Journal of Pharmaceutical Science and Technology Mar 2014, 68 (2) 153-163; DOI: 10.5731/pdajpst.2014.00973
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results and Discussion
    • Conclusions
    • Conflict of Interest Declaration
    • Acknowledgments
    • References
  • Figures & Data
  • Info & Metrics
  • References
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • Low-Volume Aseptic Filling Using a Linear Peristaltic Pump
  • Filling of High-Concentration Monoclonal Antibody Formulations: Investigating Underlying Mechanisms That Affect Precision of Low-Volume Fill by Peristaltic Pump
  • Filling of High-Concentration Monoclonal Antibody Formulations into Pre-filled Syringes: Investigating Formulation-Nozzle Interactions To Minimize Nozzle Clogging
  • Google Scholar

More in this TOC Section

  • Container Closure Integrity of Vial Primary Packaging Systems under Frozen Storage Conditions: A Case Study
  • Advances in Large Volume Subcutaneous Injections: A Pilot Tolerability Study of an Innovative Needle-Free Injection Platform
  • Quantification and Stability Impact Assessment of Drop Stresses in Biologic Drug Products
Show more Research

Similar Articles

Keywords

  • Prefilled syringe
  • High-concentration monoclonal antibody
  • Peristaltic pump
  • Suck-back
  • Formulation drying

Readers

  • About
  • Table of Content Alerts/Other Alerts
  • Subscriptions
  • Terms of Use
  • Contact Editors

Author/Reviewer Information

  • Author Resources
  • Submit Manuscript
  • Reviewers
  • Contact Editors

Parenteral Drug Association, Inc.

  • About
  • Advertising/Sponsorships
  • Events
  • PDA Bookstore
  • Press Releases

© 2023 PDA Journal of Pharmaceutical Science and Technology ISSN: 1079-7440

Powered by HighWire