Friday, 30 November 2018

The Earth Microbiome Project

The Earth Microbiome Project is a systematic attempt to characterize global microbial taxonomic and functional diversity for the benefit of the planet and humankind.

The Earth Microbiome Project (EMP) is a massively collaborative effort to characterize microbial life on this planet. We use DNA sequencing and mass spectrometry of crowd-sourced samples to understand patterns in microbial ecology across the biomes and habitats of our planet. The EMP is a comprehensive example of open science, leveraging a collaborative network of 500+ investigators, supporting pre-publication data sharing, and crowdsourcing data analysis to enable universal principles to be explored. The standardized collection, curation, and analysis are enabling a robust interpretation of ecological trends.

The Vision: Constructing the Microbial Map for Planet Earth

The EMP was founded in 2010 as a massive crowd-sourced effort to analyze microbial communities across the globe. The general premise was to examine microbial communities from their own perspective. Hence we proposed to characterize the Earth by environmental parameter space into different biomes and then explore these using samples drawn from researchers across the globe. We set out to analyze 200,000 samples from these communities using amplicon sequencing, metagenomics, and metabolomics to produce a global Gene Atlas describing protein space, environmental metabolic models for each biome, approximately 500,000 reconstructed microbial genomes, a global metabolic model, and a data-analysis portal for visualization of processed information.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 29 November 2018

Fungus provides powerful medicine in fighting honey bee viruses

A mushroom extract fed to honey bees greatly reduces virus levels, according to a new paper. In field trials, colonies fed mycelium extract showed a 79-fold reduction in deformed wing virus and a 45,000-fold reduction in Lake Sinai virus compared to control colonies. The hope is that the results of this research will help dwindling honey bee colonies fight viruses that are known to play a role in colony collapse disorder.

In field trials, colonies fed mycelium extract from amadou and reishi fungi showed a 79-fold reduction in deformed wing virus and a 45,000-fold reduction in Lake Sinai virus compared to control colonies.

Though it's in the early stages of development, the researchers see great potential in this research.

Paul E. Stamets, Nicholas L. Naeger, Jay D. Evans, Jennifer O. Han, Brandon K. Hopkins, Dawn Lopez, Henry M. Moershel, Regan Nally, David Sumerlin, Alex W. Taylor, Lori M. Carris, Walter S. Sheppard. Extracts of Polypore Mushroom Mycelia Reduce Viruses in Honey Bees. Scientific Reports, 2018; 8 (1) DOI: 10.1038/s41598-018-32194-8

 Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday, 28 November 2018

Low antibiotic concentration increases antimicrobial resistance

Existing antimicrobial resistance may become increasingly prevalent on its own -- with no interference from antibiotics -- in compact bacterial communities known as biofilms, or when protozoa hunt bacteria for food. Even weak antibiotic concentrations are sufficient to cause a rise in the prevalence of antimicrobial resistance in bacterial populations cultured in laboratory conditions.

Antimicrobial resistance is a trait that can spread within a bacterial species or even across the species barrier. Resistance will expand and become increasingly prevalent when bacteria that survive in an environment containing antibiotics genetically pass on or otherwise distribute this trait to other bacteria.

Recent studies indicate that even weak antibiotic concentrations are sufficient to cause a rise in the prevalence of antimicrobial resistance in bacterial populations cultured in laboratory conditions. Such conditions are brought about when antibiotics used to treat both human and animal infections end up in sewage or elsewhere in the environment.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Tuesday, 27 November 2018

Pharmig Guide to Bacterial Identification

Pharmig’s latest publication is a guide to bacterial identification. The guide discusses why identification is important and what needs to be identified, answering the often-challenging questions of ‘what’, ‘when’ and ‘how often’?

There are several text books on identification. These, however, err towards the clinical. Texts on identification approaches for pharmaceutical microbiology are not common and guidance on understanding the appropriate level of identification is difficult to obtain.

Microbial identification represents an important part of the microbiology function. This includes screening products for objectionable organisms, profiling the environmental microbiota, and investigating out-of-limits events with a view to assigning a probable point of origin. In deciding what and when (and subsequently to what level) to identify, and by the way of which methods, requires an identification strategy. This is a document each microbiology laboratory should develop.

Many parts of pharmaceutical microbiology are outlined in compendia or in guidance documents issued by regulators; included within these are the importance of bioburden assessments of intermediate and finished products, and the need to monitor the environment using standard environmental monitoring methods. What is less clear is expectation with regards to microbial identification. For identification, there are established and emerging methods, based around the microbial phenotype or genotype, yet the choice between systems is not straightforward and the selection depends, in part, on what needs to be identified. Deciding which types of samples to identify; what level of identification is appropriate (morphology, genus, or species); and what can be done with the collected information needs careful thought.

Written by Dr. Anna Lovatt (GSK) and Dr. Tim Sandle (BPL), the guide discusses different methods for phenotypic and genotypic identification, and the latest rapid methods. Troubleshooting sections and case notes are included with each section. The guide comes with a foreword from Andrew Hopkins of the MHRA.

The reference is:

Lovatt, A. and Sandle, T. (2018) Guide to Bacterial Identification, Pharmig, Stanstead Abbotts, UK

For details contact Pharmig

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday, 26 November 2018

FDA calls for new antimicrobials

FDA commissioner Scott Gottlieb recently unveiled a 2019 Strategic Approach for Combatting AMR (antimicrobial resistance) at a meeting organized by Pew.

Pharmaceutical Executive reports how the plan includes policies and programs to encourage development of new drugs, diagnostic tests and vaccines; to promote responsible stewardship of antimicrobials in animals and humans; to improve surveillance of antimicrobial use and resistance; and to advance research for developing new tools, standards and policies in this area.

Gottlieb outlined proposals for devising innovative milestone payments and subscription fees for developers of products targeted at multi-drug resistant organisms. To maintain a robust pipeline for antibiotics, Gottlieb recognized the need to “change the perception that the costs and risks of antibiotic innovation are too high relative to their expected gains.” One proposal is a subscription-based model that charges hospitals a flat rate or licensing fee for access to a certain number of doses each year of a new antimicrobial. By creating a predictable revenue stream, this kind of “pull incentive,” Gottlieb explained, would “create natural markets for drugs targeted to rare but dangerous, multi-drug resistant pathogens that can threaten human health.”

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Sunday, 25 November 2018

Use of Liquids and/or Soft Foods as Vehicles for Drug Administration

FDA has issued new draft guidance: “Use of Liquids and/or Soft Foods as Vehicles for Drug
Administration: General Considerations for Selection and In Vitro Methods for Product Quality Assessments Guidance for Industry.”

The introduction reads: “This guidance applies to orally administered drug products and provides recommendations to sponsors who will use or recommend use of liquids3 18 and/or soft foods as vehicles for drug administration in investigational new drug applications (INDs), new drug applications (NDAs), Biologics License Applications (BLAs), as applicable, and in supplements to these applications. This guidance addresses the approaches recommended for suitability determination of vehicles intended for use with specific drug products by providing the following…Considerations for selection of liquids and/or soft foods as vehicles…Standardized in vitro methodology and data recommendations for drug product quality assessments to qualify vehicle(s) for drug product administration… Recommendations to communicate acceptable (qualified) vehicles in drug product labeling. If certain foods are found unacceptable, they should also be included in the labelling.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Saturday, 24 November 2018

Cost-effective quality management in Europe’s blood sector

The EDQM has issued a set of recommendations for the development of cost-effective and sustainable Quality Management Systems (QMSs) in Blood Establishments (BEs) across Europe. The document follows on from the European Conference on “Sharing best practices: Quality Risk Management, Change Control, Validation and Qualification in Blood Establishments”, held by the EDQM in October 2017 in Strasbourg. These recommendations provide clear guidance for the future technical and regulatory landscape of blood transfusion in Europe from a quality perspective.

With speakers representing the major stakeholders in the sector — competent authorities, inspection bodies, blood establishments and suppliers — the event attracted participants from all over Europe to reflect on current regulatory requirements and discuss QMS best practices, current and future. The 36 speakers presented their know-how and practical experience in the field of qualification, validation, change management and risk management followed by a series of dedicated, practical workshops. With 34 countries present at the event, precedence was given to clarifying these concepts and their interpretation, discussing their practical implementation and shedding light on the roles and responsibilities of the different interested parties. The set of recommendations that ensued from these exchanges constitute a best practices roadmap to assist all stakeholders, from the major influential organisations active in the field (the European Commission, EDQM and European Blood Alliance) to the national authorities, BEs and suppliers of equipment and devices, in their efforts to develop and implement cost-effective and sustainable QMSs.


Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 23 November 2018

Ph. Eur. Supplement 9.7

The 9.7 supplement of European Pharmacopoeia is now available and will be applicable in 38 European countries as from 01 April 2019.

This volume is included in the 2019 subscription (9.6, 9.7 and 9.8) to the 9th Edition of European Pharmacopoeia. This subscription is available for purchase via the EDQM Store in three formats: book, downloadable and online version for PC. 


Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 22 November 2018

Light-engineered bacterial shapes are key to future labs-on-a-chip

Scientists have used light patterns to control the swimming speed of bacteria and direct them to form different shapes, according to a new study in the journal eLife.

Controlling bacteria in this way means it could be possible to use them as microbricks for building the next generation of microscopic devices. For example, they could be made to surround a larger object such as a machine part or a drug carrier, and then used as living propellers to transport it where it is needed.

Escherichia coli (E. coli) bacteria are known to be fantastic swimmers. They can move a distance of ten times their length in a second. They have propellers that are powered by a motor, and they usually recharge this motor by a process that needs oxygen. Recently, scientists found a protein (proteorhodopsin) in ocean-dwelling bacteria that allows them to power their propellers using light. By engineering other types of bacteria to have this protein, it is possible to place a 'solar panel' on every bacterial cell and control its swimming speed remotely with light.

"Much like pedestrians who slow down their walking speed when they encounter a crowd, or cars that are stuck in traffic, swimming bacteria will spend more time in slower regions than in faster ones," explains lead author Giacomo Frangipane, Postdoctoral Scientist at Rome University, Italy. "We wanted to exploit this phenomenon to see if we could shape the concentration of bacteria using light."

To do this, Frangipane and his team sent light from a projector through a microscope lens, shaping the light with high resolution, and explored how E. coli bacteria alter their speed while swimming through regions with varying degrees of illumination.

They projected the light uniformly onto a layer of bacterial cells for five minutes, before exposing them to a more complex light pattern -- a negative image of the Mona Lisa. They found that bacteria started to concentrate in the dark regions of the image while moving out from the more illuminated areas. After four minutes, a recognisable bacterial replica of Leonardo da Vinci's painting could be seen, with brighter areas corresponding to regions of accumulated bacterial cells.

Although the shape formed by the bacteria was recognisable, the team found that the engineered E. coli were slow to respond to variations in light, which led to a blurred formation of the target shape. To remedy this, they used a feedback control loop where the bacterial shape is compared to the target image every 20 seconds, and the light pattern is updated accordingly. This generated an optimal light pattern that shaped cell concentration with much higher accuracy. The result is a 'photokinetic' bacterial cell layer that can be turned into an almost perfect replica of a complex black-and-white target image.

"We have shown how the suspension of swimming bacteria could lead to a new class of light-controllable active materials whose density can be shaped accurately, reversibly and quickly using a low-power light projector," says Roberto Di Leonardo, Associate Professor in the Department of Physics at Rome University. "With further engineering, the bacteria could be used to create solid biomechanical structures or novel microdevices for the transport of small biological cargoes inside miniaturised laboratories."


Giacomo Frangipane, Dario Dell'Arciprete, Serena Petracchini, Claudio Maggi, Filippo Saglimbeni, Silvio Bianchi, Gaszton Vizsnyiczai, Maria Lina Bernardini, Roberto Di Leonardo. Dynamic density shaping of photokinetic E. colieLife, 2018; 7 DOI: 10.7554/eLife.36608

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday, 21 November 2018

Scientists shed new light on hepatitis B virus origins

Researchers have provided new insight on the geographical origins and global spread of two classes of the hepatitis B virus (HBV), according to a study in eLife.

The findings identify the HBV genotypes D and A (HBV-D and HBV-A) as having originated in the Middle East and North Africa. They also reveal considerable differences in the global dissemination patterns of these genotypes, adding to our understanding of both the historic and prehistoric spread of one of the world’s largest viral pandemics.

HBV, the main cause of liver disease, is a global public health concern with an estimated 257 million people living with the infection, according to figures from the World Health Organization*. The virus is classified into nine genotypes (A–I). HBV-A and HBV-D are present around the globe, with A prevailing in Europe and Africa and D in Europe and the Middle East.

“The epidemiological history of HBV-D and HBV-A remains unclear due to a lack of relevant studies,” says lead author Evangelia-Georgia Kostaki, PhD Candidate in Molecular Epidemiology at the National and Kapodistrian University of Athens, Greece. “In order to uncover more of this detail, we wanted to establish how HBV was disseminated across different geographic regions.”

To do this, the team used 916 HBV-D and 493 HBV-A full-genome sequences to reconstruct these genotypes’ global evolutionary development and diversification, known as their phylogeny, and analyse their levels of regional clustering. They revealed that HBV-D’s geographical origin was in North Africa and the Middle East, although they were unable to infer the exact origin accurately from the available data. Their analysis also suggests the origin of HBV-A is close to Africa and Europe, and likely in the Middle East and Central Asia.

“Major dispersal pathways for HBV-D were complex, including different geographic regions,” explains senior author Dimitrios Paraskevis, Assistant Professor of Epidemiology and Preventive Medicine at the National and Kapodistrian University of Athens. “We found low levels of HBV-D transmission occurred locally in North Africa and the Middle East, suggesting a high amount of movement among populations infected with HBV in these areas. This is in line with our previous observations** about the central role of these regions as hubs for human expansion, due to the early development of agriculture and the resulting spread and genetic shuffling of HBV-D.”

Paraskevis adds that after HBV-A’s initial spread in Central Africa, this genotype followed two distinct pathways: one to eastern and southern Africa, and another to sub-Saharan and western Africa. Spillovers later led to major regional transmissions towards Brazil, Haiti and the Indian subcontinent, most likely as a result of the slave trade.

Together, these results highlight considerable differences in the global dissemination patterns of HBV-D and HBV-A, as well as different levels of their regional clustering, which likely reflect the impact of prehistoric and more recent human migrations and other activities on the evolution of these HBV genotypes.



The paper ‘Unravelling the history of hepatitis B virus genotypes A and D infection using a full-genome phylogenetic and phylogeographic approach’ can be freely accessed online at Contents, including text, figures and data, are free to reuse under a CC BY 4.0 license.

Along with Evangelia-Georgia Kostaki and Dimitrios Paraskevis, this research was carried out by Timokratis Karamitros, Garyfallia Stefanou, Konstantinos Angelis and Angelos Hatzakis at the National and Kapodistrian University of Athens, in collaboration with Ioannis Mamais from the European University of Cyprus and Anna Kramvis from the University of the Witwatersrand, Johannesburg, South Africa.


**Dating the origin and dispersal of hepatitis B virus infection in humans and primates

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Tuesday, 20 November 2018

FDA - Elemental impurities in drug products

FDA has issued a new guidance document: “Elemental Impurities in Drug Products Guidance for Industry.”

This guidance provides recommendations regarding the control of elemental impurities of human drug products marketed in the USA consistent with implementation of ICH guidance
for industry Q3D Elemental Impurities This guidance will also assist manufacturers of compendial drug products in responding to the issuance of the USP requirement for the control of elemental impurities.


Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday, 19 November 2018

New Developments with Sterile Disposable Technology and Single-Use Systems for Aseptic Processing

In the past three to five years, there have been a number of advances in single-use sterile, disposable technologies, which have helped to both reduce the risk of contamination and to streamline process operations. The majority of these technological developments are oriented towards the manufacturing of sterile products, particularly aseptically filled products.

In relation to this, Tim Sandle has written a review paper. The introduction is:

The advantages of single-use technology can be summarised as: eliminating the need for cleaning; removing the requirements for the pharmaceutical company to perform in-house sterilization (typically by autoclaving) for all components; reducing the use of cleaning chemicals; assisting with storage requirements; lowering process downtime; and increasing process flexibility and reducing risks of cross contamination. However, single-use technology is still, to an extent, in its infancy and there are a number of validation steps which need to be undertaken before such technology is adopted by a pharmaceutical manufacturer11. These include assessing any leachables or extractables which might arise when the product comes into contact with the single-use technology. The presence of extractables could lead to adulterated product or to the inhibition of any microbial contamination (leading to a false negative result). Other disadvantages are in the availability of the technology (in that not all sizes or types required by pharmaceutical manufacturers are available) and development costs.

This paper examines some of the types of single-use technology available and addresses some of the steps required by pharmaceutical manufacturers to bring the technology online. 

Sandle, T. (2018) New Developments with Sterile Disposable Technology and Single-Use Systems for Aseptic Processing, BioPharma Asia, July / August, pp30-34 - see:

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Sunday, 18 November 2018

Pharmig Annual Conference 2018

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Bacteria in the nose influence cold severity

Colds vary in their severity and for how long they last for. The reason is not solely down to the type of virus or the relative health of individuals. The bacterial population of the nose is also a factor, according to new research.

New research from University of Virginia Health System reveals that the bacteria found in the noses of test subjects fall into six different categories of nasal microbiomes. These varying patterns are associated with differences in cold virussymptom severity. Furthermore, the different microbial compositions link with the viral load level (that is the level of cold virus inside the body).

As an example of the variation, subjects whose noses were abundant with Staphylococcus bacteria tended to have more severe nasal symptoms compared with cold sufferers who carry a lower levels of such bacteria. This occurred even when subjects contracted colds of the same strain of virus.
The findings were based on a study of 152 people. The research did show, however, that there is no reverse effect. That is the microorganisms associated with people who tend to experience less severe colds are not 'beneficial', in that such bacteria could not be transferred to someone who experiences more severe colds in order to reduce the cold virus severity.

Commenting on this, lead scientist Dr. Ronald Turner stated: "The first surprise was that you can kind of identify these different buckets that people kind of fit into, and then the fact that the buckets seem to have some impact on how you respond to the virus and how sick you get was also interesting."

What is certain is that the bacteria around the nose do not cause the cold; what is less clear is how the nasal microbiome contributes to the relatively severity of the cold. Alternatively, it could be that the bacteria play no direct role at all but rather there is a characteristic that makes a person who is more likely to have higher levels of staphylococci in their nose also more likely to catch a cold and suffer 'worse' nasal symptoms. That is, there is a genetic characteristic shared by certain people which leads to the two factors being related. Whether there is an environmental dimension as well, such as an external trigger like pollution that affects both factors cannot yet to be determined.

The research is published in the journal Scientific Reports and it is titled "Nasal microbiota clusters associate with inflammatory response, viral load, and symptom severity in experimental rhinovirus challenge."
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Saturday, 17 November 2018

Superbugs to 'kill millions' by 2050

Millions of people in Europe, North America and Australia will die from superbug infections unless countries prioritise fighting the growing threat posed by bacteria immune to most known drugs, experts predicted Wednesday.

The Organisation for Economic Co-operation and Development (OECD) warned of "disastrous consequences" for public healthcare and spending unless basic hospital hygiene is boosted and unnecessary antibiotic use slashed.

Drug-resistant bacteria killed more than 33,000 people in Europe in 2015, according to new research published separately this week.

In a landmark report, the OECD said 2.4 million people could die from superbugs by 2050 and said the cost of treating such infections would balloon to an average of $3.5 billion (three billion euros) a year in each country included in its analysis.

Michele Cecchini, lead on public health at the OECD, told AFP that countries were already spending an average of 10 percent of their healthcare budgets on treating antimicrobial-resistant (AMR) bugs.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 16 November 2018

EMA launches new corporate website

The European Medicines Agency (EMA) has launched a new version of its corporate website (

The website has a number of new features to improve user experience, including:
an improved search, allowing users to find content easily and to filter their search results. EMA plans to further refine this functionality in the future;
a ‘responsive’ design for cleaner display on mobile devices;
simpler URLs based on the location and title of webpages or documents;
an updated visual design offering users a clearer reading experience and simpler navigation.

“This new version of our website will help us to further improve our communication with our partners and stakeholders, including the European Commission and our networks, and will support us in reaching out to European Union citizens by providing them with evidence-based and accessible information on medicines”, said Guido Rasi, EMA’s Executive Director.

“It is particularly important for me that we were able to achieve this before we move to Amsterdam. As the new corporate website is now hosted in the cloud, independently of EMA’s physical location, it will help us as we enter into our physical relocation process in the months to come.”

The website’s content and structure remain unchanged. Although the site’s URLs are new, URLs from the previous website will continue to work for every page and document, thanks to one-to-one redirects. Although these redirects will be available for an indefinite period, EMA encourages users who have bookmarked any URLs to consider updating them at their convenience now that the new site is live.

The new website has been designed to work optimally on the latest web browsers.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 15 November 2018

Malaria and Malnutrition Causing Unprecedented Mortality Rates in Children

An average of ten children per day died last month in the hospital in Magaria in southern Niger, an alarming mortality rate mostly due to malnutrition and malaria in children under five, said the international medical humanitarian organization Doctors Without Borders/Medecins Sans Frontieres (MSF) on Tuesday. MSF, in collaboration with Niger’s Ministry of Health (MOH), is currently treating 730 children who are admitted to the hospital, including 208 who are critically ill and crowded into the pediatric intensive care unit.

“We have never seen anything like this before, and we fear it’s just the tip of the iceberg,” said Dr. Dorian Job, MSF’s Niger program manager based in Geneva. “Each year, at about this time, we expect a peak in malaria infections, as well as an incidence of malnutrition above emergency thresholds, but we haven’t seen patients overwhelming the hospital in such numbers before.”

Given the number of deaths recorded in mortality surveys conducted during the malaria and malnutrition peaks in previous years, MSF teams believe they are only seeing a sixth of the children who are in need of care. Many of those diagnosed with malaria or malnutrition are also suffering from other diseases.

“While our hospital is already terribly overwhelmed, it’s likely that hundreds of children are seriously ill in the community and not getting the care they need,” Job said. “The children we are seeing are arriving at the hospital extremely late. Sadly, many already have complications so serious that they cannot recover.”

Despite attempts to reduce the number of malaria infections associated with the seasonal peak—including the distribution of malaria prophylaxis to families with children aged between three months and five years—mortality rates remain alarmingly high.

MSF has sent 243 experienced medical staff from across Niger and around the world to ensure patients receive the best possible care inside the hospital and out in the community, where a team is running mobile clinics to care for children closer to home.

“MSF’s hospital in Magaria is the only health facility available in a region for 700,000 to one million people, around 20 percent of whom are under five years old,” Job said. “So while the malaria season is worse this year, it’s not surprising that we are overwhelmed. The health system in the area is chronically underfunded, lacking means, organization, training, and support. This prevents people from accessing care and, in turn, claims lives. We could double our capacity and still not meet the needs of the children aged under five in the community.”

MSF has been working with Niger’s Ministry of Health in the Zinder region of the country since 2005, including in Magaria where MSF runs a 435-bed pediatric unit to improve care for pediatric patients and prevent, detect, and treat childhood diseases. From January 1 to August 31, 11,100 children were admitted to this unit. More than 3,300 children under five were admitted to the unit in August alone. In addition to this facility, MSF also supports 11 health centers, 14 health posts, and six stabilization rooms for children under five in the Magaria area.

Source: MSF

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