Thursday 25 April 2019

From The Floor Up: The Battle to Control HAIs

Floors, often overlooked in the past as a major factor of environmental contamination leading to increased HAI rates, are, in fact, a contributor to this very expensive and life-impacting problem. Studies have shown that floors harbor HAI pathogen organisms. These pathogens may not be neutralized by using mops that bind disinfectants or may be transported through unexpected means, including socks or laundered mops damaged by the laundering process and reducing their ability to effectively clean or disinfect the floor.

Download this whitepaper, which discusses:
  • Human and financial implications of HAIs.
  • Microfiber laundered mops retain residual pathogens.
  • Impact of laundry processes on microfiber’s structure and efficacy.
  • Moving to single-use mops.
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday 8 April 2019

Cleaning and Cleanrooms e-book

Pharmaceutical Manufacturing: Understanding Your Process Series  - Cleaning and Cleanrooms (e-book)

In the past 15 years, PDA/DHI has published more than 1,000 practical scientific and regulatory chapters, written by global subject matter experts, which have been designed to help pharmaceutical and biotech manufacturers stay abreast, streamline processes and comply with regulators.

We have now collected bestsellers and added materials that have not published before in electronic book form covering three vital topics:
  • Cleaning and Cleanrooms
  • Sterilization
  • Environmental Monitoring
These easily accessible, reasonably priced, informative collections offer background and hands-on applications that will help with a myriad of activities for manufacturers.

The Cleaning and Cleanrooms collection features a two-part history of cleaning and cleanrooms, classifications, supplies, sanitization and several other important topics. The book is edited by Tim Sandle and Jeanne Moldenhauer.

  • The Development of Cleanrooms: An Historical Review Part 1: From Civil War to Safe Surgical Practice by Tim Sandle(New)
  • The Development of Cleanrooms: An Historical Review Part 2: The Path Towards International Harmonization by Tim Sandle (New)
  • Understanding Cleanroom Classifications by Jeanne Moldenhauer. (Chapter excerpted from Contamination Control in Healthcare Product Manufacturing, Volume 3, Chapter 12 published 2014.)
  • Cleanroom Supplies by Jeanne Moldenhauer. (Chapter excerpted from Environmental Monitoring: A Comprehensive Handbook, Volume 1, Chapter 11 published 2005.)
  • Practical Aspects of Cleaning, Sanitizing and Disinfecting Rooms and Surfaces by Jeanne Moldenhauer. (Chapter excerpted from Environmental Monitoring: A Comprehensive Handbook, Volume 1, Chapter 12 published 2005.)
  • Cleaning Validation: Process Life Cycle Approach by Paul Lopolito and Elizabeth Rivera. (Chapter excerpted from Contamination Control in Healthcare Product Manufacturing, Volume 3, Chapter 10 published 2014.)

Available to download. Prior to purchase please view the download instructions and Terms of Usage.
Format: PDF (1 file 1.72 MB)

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday 4 April 2019

Monocyte activation test - live webinar

Monocyte activation test: a powerful tool to assess pyrogenic risk in the pharmaceutical process
Microbial risk in the pharmaceutical manufacturing process cannot be limited to viable microorganisms. Even if drug substances are manufactured in clean conditions and final drug products are sterilized, some subcellular microbial components may remain at the end of the manufacturing process.

To minimize the risk of subcellular microbial components remaining in the final drug product, a risk assessment approach of the whole manufacturing process can be applied, as described by Friedrich von Wintzingerode1.

These subcellular contaminants often include Pathogen Associated Molecular Pattern (the so-called PAMPs) that can trigger the human immune system leading to inflammatory response and constitute a pyrogenic risk for patients. That’s why ensuring the absence of such components in the final drug product before batch release is key for product quality and patient safety.

In any case, testing for endotoxins in the final drug product before batch release is currently a minimum requirement from regulations. To reinforce the risk management approach, a new recommendation was added to the European Pharmacopeia chapter 5.1.10 « Guidelines for using the test for bacterial endotoxins » requiring users to carefully evaluate the risk for pyrogens (i.e. endotoxins and non-endotoxin pyrogens) before implementing the Bacterial Endotoxin Test (BET) as the sole pyrogenicity test. This is because the BET is designed to detect endotoxins only, leaving room for missing non-endotoxin pyrogens that could be responsible for fever reaction in patients.

The EP chapter 5.1.10 also indicates that “To rule out the presence of non-endotoxin pyrogens in substances or products, the use of the monocyte-activation test (2.6.30) is recommended at release or during development of the production process”. Indeed, the Monocyte Activation Test (MAT), mimics the human immune reaction to pyrogens by detecting all kinds of pyrogens that trigger the monocytes through the toll-like receptor (TLR) pathway, making it a powerful tool to assess pyrogenic risk in pharmaceutical process.

The PyroMAT™ System, our ready-to-use MAT kit using a monocytic cell line, has demonstrated the ability to detect a wide range of pyrogens. Each batch of PyroMAT™ cells is qualified for the expression of all the surface TLRs to ensure the detection of both endotoxins and non-endotoxin pyrogens. With our PyroMAT™ System, we provide a new solution for sensitive, robust, and easy-to-perform pyrogen testing.

New tools to assess the risk of microbial impurities in the pharmaceutical manufacturing process

Join the live webinar on April 9th, 2019, 10:00 am CEST

For more information about the PyroMAT™ System, click here

1 von Wintzingerode F. Biologics Production: Impact of Bioburden Contaminations of Non-Sterile Process Intermediates on Patient Safety and Product Quality.  Am Pharm Rev. 2017 Apr;20(3)

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday 3 April 2019

Suicide system in tuberculosis bacteria might hold key to treatment

Tuberculosis (TB) is one of the top ten causes of death worldwide. In 2017, 10 million people around the world fell ill with TB and 1.3 million died. The genome of the bacterium that causes TB holds a special toxin-antitoxin system with spectacular action: once the toxin is activated, all bacterial cells die, stopping the disease. An international research team co-led by the Wilmanns group at EMBL in Hamburg investigated this promising feature for therapeutic targets. They now share the first high-resolution details of the system in Molecular Cell.

Mycobacterium tuberculosis is the bacterium that causes TB in humans. Its genome holds 80 so-called toxin-antitoxin (TA) systems: sets of closely linked genes that encode both a toxic protein and an antitoxin: a toxin-neutralising antidote.

When the bacteria are growing normally, toxin activity is blocked by the antitoxin’s presence. But under stress conditions such as lack of nutrients, dedicated enzymes rapidly degrade the antitoxin molecules. This activates the toxin proteins in the cell and slows down the growth of the bacteria, allowing them to survive the stressful environment.

Novel NAD+-degrading toxin triggers cell death of tuberculosis-causing bacteria. The illustration shows sections of Mycobacterium tuberculosis bacteria. The Pac-Man symbolizes the toxin, which in the absence of its antitoxin counterpart, ‘eats up’ the NAD+, causing the cell to die. In the bacterium in the back, the Pac-Man’s mouth is blocked by the antitoxin, preventing the degradation of NAD+ and allowing the cell to grow normally. Illustration by Beata Edyta Mierzwa.

One particular TA system has a more drastic effect: in the absence of the antitoxin, the toxin kills the bacteria. As this system holds potential for therapeutic targets, researchers from EMBL Hamburg, the IPBS at the CNRS/Université de Toulouse, and the Crick Institute in London joined forces to study this TA system in more detail.

“Our goal was to see the TA system’s structure, so we could try to understand and even manipulate it. It was as if we were working blindly before”, says Annabel Parret, EMBL staff scientist in the Wilmanns group, who led the project.

The high-resolution structure of the toxin-antitoxin system. CREDIT: EMBL Hamburg

The high-resolution structure – solved within eight months by first author Diana Freire – revealed a large and compact system with a double-doughnut shape. “It looks like a diamond, and it is very stable,” says EMBL group leader Matthias Wilmanns. The structure resembles the toxins of cholera and diphtheria: diseases that caused epidemics with hundreds of thousands of people dying even within the past 100 years.

Knowledge of the structure gave important guidance for further studying the system’s biochemistry – a challenging part of the project. By using an interdisciplinary approach, the team were able to discover the details of the TA system’s mode of action. When the toxin dissociates from its antidote, it becomes activated and starts to degrade essential cellular metabolites called NAD+ molecules. This “suicide” activity ultimately leads to the death of all bacterial cells. Why the bacteria have such a suicide system is puzzling, but there is no doubt it has the potential to be exploited as a drug target.

“Our collaborators in Toulouse were already able to extend the lifetime of mice infected with TB by activating the toxin in a controlled way,” says Parret. “If we find molecules that can disrupt the TA system – and thus trigger cell death – in TB patients, that would be the perfect drug.”

The team will now screen thousands of small molecules to see if they have this capability. However, the structure of the TA system is so stable that it will be a big challenge to find an entry point where they can go in to break it. Wilmanns: “But if we succeed, this could be a new approach for treating TB and other infectious diseases.”

This project was a collaboration between researchers from the Wilmanns group at EMBL Hamburg and the Neyrolles group at the IPBS, CNRS/Universit√© de Toulouse, and involved the Carvalho group at the Francis Crick Institute in London. The research team has started a partnership to work towards a potential TB drug, through EMBL’s technology transfer arm EMBLEM.

Source article:

Freire, D.M., Gutierrez, C., et al. An NAD+ phosphorylase toxin triggers Mycobacterium tuberculosis cell death. Molecular Cell, published online 18 February 2019.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday 1 April 2019

New edition - Industrial Pharmaceutical Microbiology: Standards & Controls

A new edition of “Industrial Pharmaceutical Microbiology: Standards & Controls”. The 5th edition  - fully revised and expanded - is edited by Dr. Tim Sandle. This publication covers the entire spectrum of industrial and pharmaceutical microbiology, as applicable to those working in pharmaceuticals, medical devices, biotech, and healthcare, as well as academia.

The book is available from the publisher - please see the Euromed website 

The reference is:

Sandle, T. (2019) Industrial Pharmaceutical Microbiology: Standards & Controls, 5th edition, Euromed Communications, Passfield, UK 

What readers are saying:

"This book is not simply about the science of microbiology for it takes the science into to the industrial setting and offers invaluable advice on how to apply it to the manufacture of pharmaceutical and healthcare products, and for keeping such products within microbial control. A further strength with the book is its topicality, in having the most recent regulations and standards featured. The book features 25 chapters covering environmental monitoring, water systems, vaccines, safety, biological indicators and microbiology laboratory management. Picking the stand-out chapters is difficult, because there are so many good ones. … In summary this book is essential for every pharmaceutical laboratory: scientific, topical and practical."

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

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