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 ARTICLE

A Novel Approach to the Statistical Evaluation of Media Fill Tests by the Difference from No Contamination Data

Kunio Kawamura and Hiroshi Abe
PDA Journal of Pharmaceutical Science and Technology November 2004, 58 (6) 309-320;
Kunio Kawamura
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiroshi Abe
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • References
  • Info & Metrics
  • PDF
Loading

Abstract

It is obvious that, in the media fill test and process simulation test, positive numbers in total fills should not have any significant difference from zero or asepsis. There are many reports concerning the definition of “sterility” or “asepsis.” However, any scientific and practical methods to demonstrate “no significant difference from zero” have not been reported up to now. The existing criteria, such as “less than 0.1%,” “less than 0.05%,” and “less than two positives” are not appropriate to assure the integrity of processes, and sometimes lead to erroneous results. The purpose of this report is to demonstrate novel, reasonable and practical methods and criteria based on scientific and statistical consideration.

According to the ISO 13408-1 Aseptic Processing of Health Care Products, Part 1 (1998), General Requirement for Aseptic Processing, the action level for the number of positive units in media fill tests is specified as 0.1%, and the alert level is 0.05%. In this paper it is shown that the existing ISO standard and other official methods are inappropriate in that zero contaminated units (sterile product) is outside the confidence range of probable distribution of contaminated units, even though the contaminated units are less than 0.1% in larger numbers of fills, and even less than 0.05%. This indicates that the limit of 0.1% or 0.05% is inappropriate in cases of larger numbers of fills. For sterile products, the number of contaminated units other than “zero” at the statistical confidence range must be judged to be contaminated units in process and as non-sterile. In order to harmonize this criteria—“no significant difference from zero”—with the existing criteria, the new criteria may be combined with only the existing criteria of 0.05% in smaller number of fills.

  • Process Simulation Test
  • Media Fill Test
  • Sterility Assurance
  • Acceptance Probability
  • Aseptic Processing
  • Action Level
  • Alert Level

Footnotes

  • Copyright © Parenteral Drug Association. All rights reserved.

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
Vol. 58, Issue 6
November/December 2004
  • Table of Contents
  • Index by Author
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.
A Novel Approach to the Statistical Evaluation of Media Fill Tests by the Difference from No Contamination Data
(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.
4 + 1 =
Solve this simple math problem and enter the result. E.g. for 1+3, enter 4.
Citation Tools
A Novel Approach to the Statistical Evaluation of Media Fill Tests by the Difference from No Contamination Data
Kunio Kawamura, Hiroshi Abe
PDA Journal of Pharmaceutical Science and Technology Nov 2004, 58 (6) 309-320;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
A Novel Approach to the Statistical Evaluation of Media Fill Tests by the Difference from No Contamination Data
Kunio Kawamura, Hiroshi Abe
PDA Journal of Pharmaceutical Science and Technology Nov 2004, 58 (6) 309-320;
Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • References
  • Info & Metrics
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • Tailored Media-Fill Test Protocols Inspired by 68Ga Kit-Based Radiopharmaceuticals
  • Challenging our aseptic skills using more-rigorous media-fill tests
  • Google Scholar

More in this TOC Section

  • Monitoring of Mannitol Phase Behavior during Freeze-Drying Using Non-Invasive Raman Spectroscopy
  • Long-Term Stabilization of a New Freeze-Dried and Albumin-Free Formulation of Recombinant Human Interferon Alpha 2b
  • Pharmaceutical Development of an Intravenous Dosage Form of Diacetylmorphine Hydrochloride
Show more RESEARCH ARTICLE

Similar Articles

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

© 2025 PDA Journal of Pharmaceutical Science and Technology Print ISSN: 1079-7440  Digital ISSN: 1948-2124

Powered by HighWire