Happy New Year!

I'd like to wish all readers a Happy New Year and all the best for 2020!



Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Mycoplasma Conference Summary

For further details see: Roche

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Happy Holidays!

I'd like to wish all readers of Pharmaceutical Microbiology all the best wishes for the Holiday season!

Thank you for supporting this website and our LinkedIn and Facebook groups.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Microbiology Roundtable

American Pharmaceutical Review has run another in its Microbiology Roundtable features. Here is an extract from Tim Sandle:

Q. In general, what are some of the current critical issues/trends facing pharmaceutical manufacturers in regards to microbiology testing and remediation?

Sandle:  One of the biggest issues is with time-to-result, which is affected by the (largely) continued dependency upon culture-based methods and which is symptomatic by the slow take-up of rapid microbiological methods. Being able to obtain data faster, enables better responses.

While rapid methods will undoubtedly help, it remains that contamination control and good design are the most important considerations. There is little value testing if a given process has not been correctly designed to minimize the ingress of contamination, Of the different routes in, the main one remains people and the way they behave. Be it sterile or non-sterile manufacturing, designing systems and putting in place barriers to reduce the opportunity for personnel to get close to the product are paramount.

The reference is:

Microbiology Roundtable (2019) Michael Reynier, Jordi Iglesias, Tony Cundell, Suzanne Williams, Frank Panofen, Paula Peacos, Tim Sandle, Quinton Inglet, Jonathan Swenson, American Pharmaceutical Review, pp86-91

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Digital transformation of pharmaceuticals - what's new?

Here is my article on digital transformation of pharmaceuticals - "Becoming Pharma 4.0: How Digital Transformation Is Reshaping Pharmaceuticals".

The digital transformation of biopharmaceutical manufacturing is continuing at a rapid pace as companies attempt to mine the sources of data available. Innovations include predictive analytics, big data analytics, and creating the digital plant. Digital transformation offers a mechanism to revise its business model, to improve production processes, to design new drugs faster by using artificial intelligence to screen compounds and to increase responsiveness to customers. Furthermore, the volume of data processed by pharmaceutical firms shows no sign of slowing down. This means pharmaceutical companies must act quickly in terms of building core internal digital capabilities and moving beyond their traditional IT functions to all areas of the business.

See : https://www.biopharmatrend.com/post/109-becoming-pharma-40-how-digital-transformation-is-reshaping-pharmaceuticals/

Good Distribution Practice: A Handbook for Healthcare Manufacturers and Suppliers

An excellent new two-volume book has been published, vital for those working in pharmaceuticals and healthcare:

Good Distribution Practice: A Handbook for Healthcare Manufacturers and Suppliers - Edited by Siegfried Schmitt.

A two-volume reference publication, discussing in detail global regulations and practices. Over 30 professionals and experts share their knowledge, interpret the regulations and provide a plethora of best-practice examples.

Volume 1
Following an introduction into the subject of Good Distribution Practice (GDP), the key topics covered in this volume relate to:

• The applicable GDP regulations globally, including serialization
• Qualified Person (QP) and Responsible Person (RP) in GDP
• GDP as part of the Quality Management System (QMS)
• Good Distribution Practice - the industry perspective
• GDP Checklist

Volume 2

Following an introduction into the subject of Good Distribution Practice (GDP), the key topics covered in this volume relate to:

• De-risking the supply chain
• Serialisation and Packaging in Practice
• Other chapters provide details about packaging materials. 

The authors not only introduce the readers to the options available, but more importantly help assure that the selection of packaging materials is linked to shipping routes, pharmaceutical material properties and lastly costs. 

The book is available from the PDA Bookstore:

PDA - Volume 1

PDA Volume 2

Or from Amazon :

Volume 1

Volume 2

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Robust Quality Audits Are The Solution To Avoiding Expensive Recalls

Compliance is an affirmative indication or judgement that the supplier of a product or service has met the requirements of the relevant specifications, contract or regulation; also the state of meeting the requirements. Compliance is something that meets both the text and the spirit of a requirement. This is the central message of the book Audit and Control for Healthcare Manufacturers” by Tim and Jennifer Sandle (published by DHI, http://www. dhibooks.com/books/17351.html)

Robust Quality Audits Are T... 

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Biocontamination Control for Pharmaceuticals and Healthcare

A new book has been published – “Biocontamination Control for Pharmaceuticals and Healthcare” by written Tim Sandle. The book outlines a biocontamination strategy that tracks bio-burden control and reduction at each transition in classified areas of a facility. This key part of controlling risk escalation can lead to the contamination of medicinal products, hence necessary tracking precautions are essential. Regulatory authorities have challenged pharmaceutical companies, healthcare providers, and those in manufacturing practice to adopt a holistic approach to contamination control. New technologies are needed to introduce barriers between personnel and the environment, and to provide a rapid and more accurate assessment of risk. This book offers guidance on building a complete biocontamination strategy.

Biocontamination Control fo... by Tim Sandle on Scribd

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

ISO 14644-16:2019 – Part 16: Energy efficiency in cleanrooms and separative devices

A new standard has been issued:

“This document gives guidance and recommendations for optimizing energy usage and maintaining energy efficiency in new and existing cleanrooms, clean zones and separative devices. It provides guidance for the design, construction, commissioning

and operation of cleanrooms.

This document covers all cleanroom-specific features and can be used in different areas to optimize energy use in electronic, aerospace, nuclear, pharmaceutical, hospital,

medical device, food industries and other clean air applications.

It also introduces the concept of benchmarking for the performance assessment and comparison of cleanroom energy efficiencies, while maintaining performance levels to ISO 14644 requirements.

See: https://www.iso.org/standard/66331.html

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Robust Quality Audits Are The Solution To Avoiding Expensive Recalls

Audit and Control for Healthcare Manufacturers” by Tim and Jennifer Sandle (published by DHI, http://www.dhibooks.com/books/17351.html)

Robust Quality Audits Are T... by Tim Sandle on Scribd

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

The Use of Microbiological Culture Media Article

Free-to-read article on microbial culture media best practices.

The Use of Microbiological ... by Tim Sandle on Scribd

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

NOW IS THE TIME for Animal Welfare in Pharma

Symposium - Animal Welfare in Pharma Join us at a symposium to celebrate the 60th anniversary of the 3Rs guiding principles (Reduction, Refinement and Replacement) for ethical use of animals in lab testing. Experts from the pharma industry will present ongoing initiatives to apply the 3Rs principles throughout the pharma process: from the drug development to production and batch release; there are many ways to avoid the use of animals.

NOW IS THE TIME for Animal ... 

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Microbial community with small diversity cleans up algal blooms

Algae blooms regularly make for pretty, swirly satellite photos of lakes and oceans. They also make the news occasionally for poisoning fish, people and other animals. What's less frequently discussed is the outsize role they play in global carbon cycling. A recent study now reveals surprising facts about carbon flow in phytoplankton blooms. Unexpectedly few bacterial clades with a restricted set of genes are responsible for a major part of the degradation of algal sugars.

Algae take up carbon dioxide (CO2) from the atmosphere and turn the carbon into biomass while releasing the oxygen back to the atmosphere. Fast algal growth during phytoplankton blooms leads to a massive transfer of carbon dioxide into algal biomass. But what happens to the carbon next?

"Once the algae die, the carbon is remineralized by microorganisms consuming their biomass. It is thus returned to the atmosphere as carbon dioxide. Alternatively, if the dead algae sink to the seafloor, the organic matter is buried in the sediment, potentially for a very long time," explains first author Karen Krüger from the Max Planck Institute for Marine Microbiology in Bremen. "The processes behind the remineralization of algal carbon are still not fully understood."

Thus, Krüger and her colleagues investigated microorganisms during spring algal blooms in the southern North Sea, at the island of Heligoland. They specifically looked at the bacterial use of polysaccharides -- sugars that make up a substantial fraction of the algal biomass. Together with colleagues from the Max Planck Institute, the University of Greifswald and the DOE Joint Genome Institute in California, Krüger carried out a targeted metagenomic analysis of the Bacteroidetes phylum of bacteria, since these are known to consume lots of polysaccharides. In detail, the scientists looked at gene clusters called polysaccharide utilisation loci (PULs), which have been found to be specific to a particular polysaccharide substrate. If a bacterium contains a specific PUL, that indicates it feeds on the corresponding algal sugar.

"Contrary to what we expected, the diversity of important PULs was relatively low," says Krüger. Only five major polysaccharide classes were being regularly targeted by multiple species of bacteria, namely beta-glucans (such as laminarin, the main diatom storage compound), alpha-glucans (such as starch and glycogen, also algal and bacterial storage compounds), mannans and xylans (typically algal cell wall components), and alginates (mostly known as slimy stuff produced by brown macroalgae). Of these five substrates, only two (alpha- and beta-glucans) make up the majority of substrates available to the bacteria during a phytoplankton bloom. This implies that the most important polysaccharide substrates released by dying algae are made up of a fairly small set of basic components.

"Given what we know of algal and bacterial species diversity, and the enormous potential complexity of polysaccharides, it came as no small surprise to see such a limited spectrum of PULs, and in only a relatively small number bacterial clades," co-author Ben Francis from the Max Planck Institute for Marine Microbiology sums up in an accompanying comment. "This was especially unexpected because previous studies suggested something different. An analysis of more than 50 bacterial isolates -- i.e. bacteria that can be cultured in the lab -- that our working group carried out in the same sampling region revealed a much broader diversity of PULs," he adds.

During the course of the algal bloom, the scientists observed a distinct pattern: In early bloom stages, fewer and simpler polysaccharides dominated, while more complex polysaccharides became available as the bloom progressed. This might be caused by two factors, Francis explains: "First, bacteria will in general prefer easily degradable substrates such as simple storage glycans over biochemically more demanding ones. Second, more complex polysaccharides become increasingly available over a blooms' course, when more and more algae die."

This study provides unprecedented insights into the dynamics of a phytoplankton bloom and its protagonists. A fundamental understanding of the bulk of glycan-mediated carbon flow during phytoplankton bloom events is now within reach. "Next, we want to dig deeper into processes underlying the observed dynamics," says Krüger. "Moreover, it will be interesting to investigate polysaccharide degradation in habitats with other carbon sources, such as the Arctic Seas or the sediment."

See:

Karen Krüger, Meghan Chafee, T. Ben Francis, Tijana Glavina del Rio, Dörte Becher, Thomas Schweder, Rudolf I. Amann, Hanno Teeling. In marine Bacteroidetes the bulk of glycan degradation during algae blooms is mediated by few clades using a restricted set of genes. The ISME Journal, 2019; DOI: 10.1038/s41396-019-0476-y



Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Is anxiety linked to our gut microbiome?

Microbiome research has advanced considerably since the first results from the U.S. National Institutes of Health led Human Microbiome Project were released. One area of interest is the connection between our microorganisms and anxiety symptoms. At first glance, the connection between the array of different microorganisms that are found within the human gut and feelings such as anxiety is not an obvious one. However, there is a growing level of evidence that variations within microbial communities are influential upon metabolic processes.

Human microbiome

The human microbiome refers to the totality of microorganisms and their genetic interactions within a given niche. Our understanding of the microbiome has advanced following a study of 300 men and women, who volunteered to take part in an international study. The advancement in understanding relating to developments with the methods used to characterize the microorganisms (including metagenomics) and the in-depth nature of the study, relating to the sampling of many body parts over a prolonged period of time, and drawing upon of the subjects from different geographical locales.

FDA microbiologist prepares DNA samples for gel electrophoresis analysis

FDA / File

With the specific effects in relation to the human gut, then the understanding by scientists of the gut-brain axis has increased during the past ten years, suggesting a bidirectional nature between the gut and brain microbiome interactions. This includes a connection relating to the pathophysiology and pathogenesis of irritable bowel syndrome (IBS), as an example.

In another research field, there is growing evidence of psychiatric and neurologic disorders like autism spectrum disorders, affective disorders, Parkinson's disease, and multiple sclerosis, being connected to the human gut microbiome.

The reason for this is that, with most people, the gut microbiota assist with the healthy functioning of the immune system. Furthermore, organisms assist with the metabolism by contributing inflammatory mediators, vitamins, and nutrients. Moreover, microbiologists have demonstrated that the intestinal microbiota can modulate communication between the intestinal tract and human brain via the nervous, immune, and endocrine systems.

It may be possible to treat superbugs with a predatory bacteria.

University of Nottingham

However, when the intestinal microbial balance is altered, then changes occur and these can be manifest in terms of physical, and potentially mental, symptoms. One area being investigated in relation to a mental system is anxiety.

Anxiety

Anxiety is an emotion characterized by an inner turmoil. It is often accompanied by nervous behaviour, somatic complaints, and rumination. The condition includes subjectively unpleasant feelings of dread over anticipated events. When experienced regularly the individual may suffer from an anxiety disorder. The global incidence of anxiety disorder is estimated to be between 3-25 percent. Typical treatment for anxiety is usually psychopharmacological therapies and psychotherapy.

New research

With the new research, scientists have attempted to see if anxiety symptoms can be improved by regulation of intestinal microorganisms. By assessing some 3,334 published articles the researchers focus on 21 major studies. Across these studies,1,503 participants included "patients with IBS (10 studies), healthy controls (six studies) and other patients with chronic diseases such as chronic fatigue syndrome (CFS), rheumatoid arthritis (RA), obesity, fibromyalgia, and type 2 diabetes mellitus."

Of the 21 studies, 14 had chosen probiotics as interventions to regulate intestinal microbiota (IRIFs), and seven chose non-probiotic ways, such as adjusting daily diets. Those studies that utilized "interventions regulating intestinal flora" consisting of probiotics with Lactobacillus alone or a mixture of Lactobacillus, Streptococcus, and Bifidobacterium, showed some positive results. Overall, 11 of the 21 studies suggested a positive effect on anxiety symptoms by regulating intestinal microbiota, meaning that more than half (52 percent) of the studies showed this approach to be effective.

Some of the bacteria found by scientists in 3.5-billion-year-old fossils are now extinct, while others are similar to contemporary microbes

MARTIN BERNETTI, AFP/File

To draw these conclusions the review was subjected to meta-analysis, considering the research design, subjects, interventions, and anxiety assessment scales. This drew out the connected between anxiety and disturbances to the gut microbiome and indicated that it may be possible to regulate the intestinal microbiota through the use of probiotics, although further research will be required.

The researchers conclude: "We find that more than half of the studies included showed it was positive to treat anxiety symptoms by regulation of intestinal microbiota.

"There are two kinds of interventions (probiotic and non-probiotic interventions) to regulate intestinal microbiota, and it should be highlighted that the non-probiotic interventions were more effective than the probiotic interventions. More studies are needed to clarify this conclusion since we still cannot run meta-analysis so far."

Research paper

The new research has been published in the British Medical Journal, with the research paper titled “Effects of regulating intestinal microbiota on anxiety symptoms: A systematic review.”

Written by Dr. Tim Sandle, Pharmaceutical Microbiology

Microbes can grow on nitric oxide

Nitric oxide (NO) is a central molecule of the global nitrogen cycle. A study reveals that microorganisms can grow on NO. Their results change our view of the earth's nitrogen cycle and how microorganisms regulate the release of greenhouse gases from natural and human-made environments.

Intriguingly, long before there was oxygen on Earth, nitric oxide was available as a high-energy oxidant, and might have played a fundamental role in the emergence and evolution of life on Earth. A study by Max-Planck-scientist Boran Kartal and colleagues now published in Nature Communications sheds a new light on microbial transformations of this molecule. Yes they can -- with implications for our climate.

One major question about nitric oxide remained unanswered up to now: Can organisms use it to grow? "One would think so," Kartal explains, "as nitric oxide has been around since the emergence of life on earth." However, no microbe growing on NO has been found -- until now. Kartal and his colleagues from Radboud University in the Netherlands have now discovered that the anaerobic ammonium-oxidizing (anammox*) bacteria directly use NO to grow. In detail, these microorganisms couple ammonium oxidation to NO reduction, producing nothing but dinitrogen gas (N2) in the process.

The latter -- the sole production of N2 -- is particularly intriguing: Some microbes convert NO to nitrous oxide (N2O), which is a potent greenhouse gas. N2, in contrast, is harmless. Thus, each molecule of NO that is transformed into N2 instead of N2O is one less molecule adding to climate change. "In this way, anammox bacteria reduce the amount of NO available for N2O production, and reduce the amount of released greenhouse gas," Kartal explains. "Our work is interesting in understanding how anammox bacteria can regulate N2O and NO emissions from natural and human-made ecosystems, such as wastewater treatment plants, where these microorganisms contribute significantly to N2-release to the atmosphere."

Nitric oxide is a central molecule in the global cycling of nitrogen. "These findings change our understanding of the earth's nitrogen cycle. Nitric oxide has been primarily thought of as a toxin, but now we show that anammox bacteria can make a living from converting NO to N2," says Kartal. The present study raises new questions. "Anammox, a globally important microbial process of the nitrogen cycle relevant for the earth's climate, does not work the way we assumed it did." Moreover, other microbes than the ones investigated here could be using NO directly as well. Anammox bacteria are found all over the planet. "In this sense, the anammox microbes growing on nitric oxide could also be basically everywhere," Kartal continues.

Now, Kartal and his group at Max Planck Institute in Bremen are exploring different ecosystems from all around the world, hunting for specialized nitric oxide converting microorganisms. They want to understand better how microbes use NO in environments both with and without oxygen. This will probably pave the way to the discovery of new enzymes involved in nitric oxide transformation. "Basically, we want to understand how organisms can make a living on NO."

See: Ziye Hu, Hans JCT Wessels, Theo van Alen, Mike SM Jetten and Boran Kartal. Nitric oxide-dependent anaerobic ammonium oxidation. Nature Communications, 2019 DOI: 10.1038/s41467-019-09268-w

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology