Wednesday, 24 April 2019

Results of Trial to Stem Hospital-Acquired Bacterial Infections Published

New findings from a large, randomized clinical trial that compared two infection control techniques are already being incorporated into practice within the network of U.S. community hospitals where the trial took place.

The trial evaluated whether daily bathing with the antiseptic soap chlorhexidine (CHG)—and in those patients with methicillin-resistant Staphylococcus aureus (MRSA), adding the nasal antibiotic mupirocin—more effectively reduced hospital-acquired bacterial infections than bathing with ordinary soap and water. While no statistically significant difference between the two intervention groups was seen within the population overall, the researchers did find that one subset of patients—those with medical devices—experienced a substantial benefit if they received the CHG/mupirocin intervention.

The ABATE (Active Bathing to Eliminate) Infection trial was initiated through the National Institutes of Health’s Common Fund program and was managed by the National Institute of Allergy and Infectious Diseases (NIAID), an NIH component. Results of the study, which involved about 330,000 adult patients in non-intensive care units in the HCA Healthcare system, appear today in The Lancet. Susan S. Huang, M.D., M.P.H., of the University of California Irvine School of Medicine, led the research team.

Previous clinical trials in intensive care units (ICUs) had shown that hospital-acquired infections could be dramatically reduced through such practices as CHG bathing, noted Dr. Huang. “Because there was a clear benefit with bacterial decolonization in the ICU setting, we pursued this trial to determine if similar interventions would reduce hospital-acquired infections in non-ICU settings, where the majority of such infections occur,” she said. Decolonization refers to the removal of skin-surface bacteria that are normally harmless, but that may enter the bloodstream following surgery or other procedures and cause infection, including life-threatening sepsis.

During a five-month recruitment period, 53 community hospitals (comprising 194 non-ICU units) throughout the HCA Healthcare system were randomized to either the routine bathing arm or the CHG bathing plus mupirocin arm of the study. Five hospitals withdrew, leaving 24 hospitals in each arm of the 21-month-long intervention. During that period, the 330,000 patients enrolled in the trial had 1.3 million days of hospital care.

The study was implemented as a quality improvement effort using staff and caregivers already working in the units. “We provided resources including coaching calls, training binders, and instructional handouts for patients and caregivers, as well as a training video with actors that demonstrated how caregivers might answer patient concerns about CHG bathing,” said Dr. Huang. Computer-based training was provided to 14,000 staff members in the participating hospitals. On request, trial team members visited sites to demonstrate CHG bathing techniques, but investigators were not on-site throughout the trial.

Within the overall study population, the research team found no statistically significant difference between the study arms. However, patients with medical devices, such as central venous catheters or lumbar drains, benefitted from the CHG/mupirocin intervention. Among that subset of patients, investigators recorded a 30 percent decrease in bloodstream infections and a nearly 40 percent decrease in antibiotic-resistant bacteria, including MRSA and vancomycin-resistant enterococcus, compared to rates seen in similar patients in the standard bathing arm of the trial. The benefit of CHG bathing for patients with devices is notable, said Dr. Huang. Although they represented only 12 percent of the total non-ICU patient population, patients with devices had a disproportionately high risk for bacterial infection: they accounted for 37 percent of MRSA and VRE clinical cultures and more than half of all bloodstream infections.

“The ABATE Infection trial is a good example of what a large-scale, pragmatic clinical trial can achieve within a relatively short period of time,” said NIAID Director Anthony S. Fauci, M.D. “This trial also highlights the value of partnerships between academic investigators and healthcare delivery organizations,” he said.

Classic clinical trials typically recruit and enroll patients one by one, and are often costly, labor-intensive and time-consuming. According to Dr. Huang, pragmatic trials complement the strengths of classic clinical trials, but because they are performed under ‘real world’ conditions—for example, by weaving quality improvement strategies into existing care routines—they are usually less expensive.

“The results of the ABATE Infection trial are already being incorporated into infection prevention efforts,” said Jonathan Perlin, M.D., Ph.D., chief medical officer of HCA Healthcare and a co-author of the new study. “The HCA system is using this decolonization strategy as a best practice for patients with medical devices across our 179 affiliated hospitals,” he said.

In addition to Dr. Huang and collaborators at the University of California Irvine, the study team included investigators from HCA Healthcare, Harvard Medical School and Harvard Pilgrim Health Care Institute, Rush Medical College and the Centers for Disease Control and Prevention. It was conducted as part of the NIH Collaboratory for pragmatic clinical trialsto address questions of major public health importance. The antiseptic product was contributed by Sage Products and MoInlycke. The companies providing product to the trial had no role in the design, conduct, analysis or publication of the ABATE Infection trial.

Reference: SS Huang et al. Chlorhexidine versus routine bathing to prevent multidrug-resistant organisms and all-cause bloodstream infection in general medical and surgical units (ABATE Infection trial): a cluster-randomised trial. The Lancet DOI: 10.1016/S0140-6736(18)32593-5 (2019).

Source: NIH

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Tuesday, 23 April 2019

Short Regimen for Preventing TB Found Safe When Co-administered with New First-line HIV Drug

In an important moment for tuberculosis (TB) control, a new study finds that a shorter regimen to prevent TB can be safely co-administered with dolutegravir (DTG)—the first-line drug to treat HIV in many high-burden TB countries. Presented today at the Conference on Retroviruses and Opportunistic Infections (CROI), the study found that weekly administration of rifapentine and isoniazid (3HP) for three months in adults with HIV taking DTG was well-tolerated, with no need for dose-adjustment. The findings put to rest fears of potential drug interactions with DTG and pave the way for scale-up of the 3HP regimen in 12 high-burden TB countries across three continents.

“We’ve known for some time that preventive therapy for TB is a critical component of any effort to control the TB epidemic,” said Prof. Gavin Churchyard, group CEO of the Aurum Institute and co-principal investigator on the study. “But current treatment options are too long and potentially more toxic. These findings will allow us to move forward with co-administration of 3HP and DTG, offering the best treatment options to those who need it the most.”

The study, funded by Unitaid and carried out in South Africa by the Aurum Institute and the Johns Hopkins University Center for TB Research, looked at the safety and pharmacokinetics of giving 3HP with DTG. Researchers enrolled 60 adults with HIV, who received DTG for eight weeks, then began 3HP; after completion of 3HP, all participants were followed for four more weeks. Overall, co-administration of DTG and 3HP was well-tolerated.

Read more:

Monday, 22 April 2019

Bacterial Endotoxin Risks to Pharmaceutical Water Systems: Three Case Studies

Well-maintained and operated water systems should not see endotoxin detected regularly. Where endotoxin detection occurs, this is due to a special cause event, signifying that something untoward has occurred. To illustrate what can sometimes occur, a short article by Tim Sandle presents three cases studies.

The reference and link is:

Sandle, T. (2019) Bacterial Endotoxin Risks to Pharmaceutical Water Systems: Three Case Studies, Rapid Microbiology. Online article at: 

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Sunday, 21 April 2019

`SuperTowel’ Shows Potential to Limit Spread of Disease in Humanitarian Crises

A new hand-washing product dubbed the SuperTowelTM could become a useful complementary tool for fighting disease outbreaks in humanitarian crises where limited access to soap and clean water aggravates the spread of conditions like diarrhea and cholera, according to a new study published today in the American Journal of Tropical Medicine and Hygiene.

A team led by researchers from the London School of Hygiene and Tropical Medicine found that various prototypes of the hand-towel-size SuperTowel, made from high-tech microfiber that can neutralize many disease-causing microbes, were more effective than hand-washing with soap at removing bacteria. The product was developed for situations like crowded refugee camps, war-torn cities, and natural disasters where diseases spread by hands that have come into contact with fecal matter are a major humanitarian challenge.

The SuperTowel has to be dipped in a small amount of water to work, but the researchers found it required much less water than normal handwashing. The current study tested the towel in volunteers whose hands had been deliberately exposed to a relatively harmless strain of Escherichia coli (E. Coli)bacteria that, in other forms, can cause severe diarrhea. The researchers said additional studies are needed in more challenging conditions.


Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Saturday, 20 April 2019

‘Sentinel Chickens’ Shed Light on US Resurgence of Deadly Mosquito-Borne Virus

Analysis of “sentinel chickens”—flocks deployed specifically to detect the presence of mosquito-borne diseases—reveals the Florida Panhandle as the likely epicenter of a rare but deadly virus that has re-emerged in recent years to spread as far north as Canada, according to a new study published recently in the American Journal of Tropical Medicine and Hygiene.

Researchers at Vanderbilt University Medical Center, in collaboration with the Florida Department of Health and the University of South Florida, investigated transmission patterns for Eastern equine encephalitis virus, or EEEV, the deadliest mosquito-borne disease in North America. After decades of sporadic activity, the virus re-emerged about 14 years ago with a spate of cases from Florida to New England and into Nova Scotia, Canada. Infections, which can sicken humans and horses, can progress to a dangerous brain infection. And while that’s rare in humans—only about 70 cases have been reported since 2008—the fact that 30 (43 percent) of victims died has prompted intensive surveillance.

In the current study, researchers analyzed blood samples from thousands of chickens used by state health officials across Florida from 2005 to 2016 to alert them to the presence of EEEV. Chickens can get infected but don’t get sick or transmit the disease. Evidence from the chickens revealed that EEEV is present year-round in the Florida Panhandle and that the region could be “seeding” the virus for the rest of Florida and for Northeastern states as well (EEEV is not found west of the Mississippi River). They believe their findings could lead to disease control efforts in the Panhandle that could reduce risks elsewhere in the United States.


Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 19 April 2019

Newly isolated human gut bacterium reveals possible connection to depression

Researchers have established a correlation between depression and a group of neurotransmitter-producing bacteria found in the human gut.
The research team from the U.S. Department of Energy’s (DOE) Argonne National Laboratory, Northeastern University and elsewhere made the connection by first isolating the KLE1738, a bacterium that has a surprising dependency upon a brain chemical called gamma-aminobutyric acid (GABA).
The association of microbial GABAmetabolism with mental health is highly compelling,”
said Jack Gilbert, group leader for microbial ecology at Argonne who also holds new faculty appointments at the University of California, San Diego, in the Department of Pediatrics and at Scripps Institution of Oceanography.
The general ability of the microbiome to produce and/or consume GABA has not been as broadly described before, and a bacterium dependent on GABAhas never been reported.”
Gilbert and 18 co-authors published their findings on December 102018, in Nature Microbiology.
Because of its unique growth requirements, nobody else has reported growing KLE1738,”
said Philip Strandwitz, the article’s lead author and a postdoctoral research associate at Northeastern University’s Antimicrobial Discovery Center. Strandwitz and his colleagues have proposed the name Evtepia gabavorous for KLE1738. They will more fully describe the bacterium in a future publication.

KLE1738 had previously appeared on the ?most wanted list” of the National Institutes of Health, meaning that it had yet to be cultured, despite its relative prevalence in the human gut. The bacterium has been detected in nearly 20 percent of the human gut microbiomes available in the Integrated Microbial Next Generation Sequencing Database.
Gut microbiota, the entire collection of microorganisms found in that habitat, affect many important functions, including the immune response and the nervous system. Nevertheless, many microorganisims residing in the human gut remain uncultured, which the research team called ?an obstacle for understanding their biological roles” in the Nature Microbiologyarticle.
More such microorganisms probably remain uncultured because they require key growth factors that are provided by neighboring bacteria in their natural environments, but not under artificial laboratory conditions. During an extensive screening process, the team found that KLE1738 required the presence of Bacteroides fragilis, a common human gut bacterium, to grow.
Further biological testing and purification led to the isolation of GABA as the growth factor produced by Bacteroides fragilisGABA was, in fact, the only nutrient tested during the experiments that supported the growth of KLE1738.
In the next research phase, the team explored the possible connection between Bacteroides and depression. Stool samples and functional magnetic resonance imaging measurements of brain activity were collected from 23 subjects suffering from clinically diagnosed depression.
The researchers found an inverse relationship between the relative abundance of fecal Bacteroidesand functional connectivity in a part of the brain associated with elevated activity during depression. This means that low abundance of Bacteroides was associated with high activity in that part of the brain, and vice versa.
A good first step is to repeat our findings in additional human cohorts, which we are actively exploring,”
said Strandwitz of further research.
When it comes to depression, animal models are often difficult to translate, which is why we are so excited about human studies. “

Recent work published in the journals Science and Cell have identified the presence of sensory neurons in the gut that are hard-wired to the brain. ?
It would be great to explore whether microbial GABA can act as a signal via that pathway,”
said Anukriti Sharma, a co-author of the Nature Microbiology article and a postdoctoral scholar at Argonne.
Strandwitz and co-author Kim Lewis, a distinguished university professor at Northeastern, have founded a biotechnology company, Holobiome, to develop microbiome-based therapeutics that target diseases of the nervous system. Gilbert is a member of the company’s scientific advisory board. Additional research will be needed, however, before it may become possible to develop a treatment for people suffering from depression.
Significant work must be done to first, validate the link between microbial GABA producers and depression. And second, if validated, identify the right approach to develop bacterial — or some sort of intervention — as therapeutics.”

Strandwitz said.
Source: Microbiome Times

Thursday, 18 April 2019

New disease surveillance tool

A new computational method called 'CATCH' designs molecular 'baits' for any virus known to infect humans and all their known strains, including those that are present in low abundance in clinical samples, such as Zika. The approach can help small sequencing centers around the globe conduct disease surveillance, which is crucial for controlling outbreaks.

Scientists have been able to detect some low-abundance viruses by analyzing all the genetic material in a clinical sample, a technique known as "metagenomic" sequencing, but the approach often misses viral material that gets lost in the abundance of other microbes and the patient's own DNA.
Another approach is to "enrich" clinical samples for a particular virus. To do this, researchers use a kind of genetic "bait" to immobilize the target virus's genetic material, so that other genetic material can be washed away. Scientists in the Sabeti lab had successfully used baits, which are molecular probes made of short strands of RNA or DNA that pair with bits of viral DNA in the sample, to analyze the Ebola and Lassa virus genomes. However, the probes were always directed at a single microbe, meaning they had to know exactly what they were looking for, and they were not designed in a rigorous, efficient way.

What they needed was a computational method for designing probes that could provide a comprehensive view of the diverse microbial content in clinical samples, while enriching for low-abundance microbes like Zika.

Short for "Compact Aggregation of Targets for Comprehensive Hybridization," CATCH allows users to design custom sets of probes to capture genetic material of any combination of microbial species, including viruses or even all forms of all viruses known to infect humans.

To run CATCH truly comprehensively, users can easily input genomes from all forms of all human viruses that have been uploaded to the National Center for Biotechnology Information's GenBank sequence database. The program determines the best set of probes based on what the user wants to recover, whether that's all viruses or only a subset. The list of probe sequences can be sent to one of a few companies that synthesize probes for research. Scientists and clinical researchers looking to detect and study the microbes can then use the probes like fishing hooks to catch desired microbial DNA for sequencing, thereby enriching the samples for the microbe of interest.

Tests of probe sets designed with CATCH showed that after enrichment, viral content made up 18 times more of the sequencing data than before enrichment, allowing the team to assemble genomes that could not be generated from un-enriched samples. They validated the method by examining 30 samples with known content spanning eight viruses. The researchers also showed that samples of Lassa virus from the 2018 Lassa outbreak in Nigeria that proved difficult to sequence without enrichment could be "rescued" by using a set of CATCH-designed probes against all human viruses. In addition, the team was able to improve viral detection in samples with unknown content from patients and mosquitos.

See: Hayden C. Metsky, Katherine J. Siddle, Adrianne Gladden-Young et al. Capturing sequence diversity in metagenomes with comprehensive and scalable probe design. Nature Biotechnology, 2019; 37 (2): 160 DOI: 10.1038/s41587-018-0006-x

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday, 17 April 2019

New strategy to tackle “don’t eat me” signal on cancer cells

Myeloid immune cells kill cancer cells by eating them but cancer cells prevent this from happening by giving out a 'do not eat me' signal. Led by immunologists Ton Schumacher (Netherlands Cancer Institute and Oncode) and Ferenc Scheeren (Leiden University Medical Center), researchers from various research institutes have discovered a new method to inhibit the 'don’t eat me' signal, and have therefore found a new target for immunotherapy.

On 4 March 2019, the researchers published an article on this topic in the scientific journal Nature Medicine.

The “don’t eat me” signal

Different types of immune cells have different strategies to fight cancer cells. For example, some immune cells—myeloid cells—kill cancer cells by eating them. Cancer cells can prevent this by expressing proteins on their surfaces which give out inhibiting signals to the immune cells. One example is the 'don’t eat me' signal, officially called CD47, which ensures that the cancer cell stays alive.

Researchers around the world are now looking for medicines to block this “don’t eat me” signal. One method for doing so is to intervene on the surface of the cell, by covering the CD47 molecules on cancer cells with a specific antibody.

This method of blocking the CD47 signal from cancer cells is currently being clinically developed and is promising, but there are side effects, such as a decrease in red blood cells. On top of that, patients require a weekly IV to block the CD47 molecules on cancer cells adequately.

Are there any other ways to counteract the “don’t eat me” signal CD47? To investigate this, PhD student Meike Logtenberg, lead author of the article, set up a collaboration with experimental geneticist Thijn Brummelkamp, who uses a unique method to map the genetic regulation of any desired protein in a cell. "With this screening method you can potentially find new targets," says Meike Logtenberg.

Screening the CD47 molecule

Together with the immunologists, Brummelkamp screened CD47, which also plays a role in healthy cells as an immune system check, and found that the QPCTL enzyme is a crucial protein in forming the “don’t eat me” signal. QPCTL changes the structure of the CD47 protein and without any QPCTL activity, the CD47 molecules are no longer able to give off an inhibiting signal to myeloid cells.

Research leader Ton Schumacher: "In collaboration with the groups of Jeanette Leusen (UMC Utrecht) and Timo van den Berg (Sanquin Research), we then showed that as soon as we inhibited the activity of this enzyme, we instantly blocked the “don’t eat me” signal on tumor cells. Identifying this new target is especially relevant because the substances we can use to inhibit the QPCTL enzyme are likely to have some advantages over the strategies currently being clinically developed to inhibit the CD47 signal route."

Blocking the signal

With a QPCTL inhibitor, for example, it becomes easier to control how long you want to block the signal, and so-called small molecule inhibitors are easier to administer than antibodies. Moreover, the substance does not inhibit the CD47 molecules on the healthy red blood cells that a patient receives during a blood transfusion to fight anaemia.

Clinical studies

The researchers expect that QPCTL inhibitors will be available for testing in clinical studies in the coming years. First clinical trials are expected to take place in patients with blood cancer.


Logtenberg et al., ‘Glutaminyl cyclase is an enzymatic modifier of the CD47- SIRP axisand target for cancer immunotherapy’, Nature Medicine 4 March 2017 doi: 10.1038/s41591-019-0356-z

Corresponding author: Ton Schumacher
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Tuesday, 16 April 2019

EDQM and EU Commission discuss improving plasma supply management

The EDQM and the European Commission (EC) brought together stakeholders involved in the field of plasma to discuss ways forward for improving plasma supply management and donor protection, during a symposium organised in Strasbourg on 29 and 30 January 2019. As emphasised by those present at the meeting, this was the first time that all stakeholders in the sector had met to exchange their views on how to increase the supply of plasma for fractionation in Europe, while ensuring adequate protection of both donors and patients.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday, 15 April 2019

Cleanroom facility of the future

Tim Sandle was featured in the American Pharmaceutical Review video ‘Clean facility of the future’.

Biopharmaceuticals have traditionally been produced in sterile environments as a means to ensure product quality and to reduce failed batches. In addition, as more scrutiny is put on the manufacture of all types of products, oral solid dosage manufacturers are investing in equipment, technologies and expertise to move their processes towards a cleaner manufacturing environment.

How do both sides of the industry ensure their products are produced in clean modern facilities? What are the latest tools, techniques, services and best practices to manufacture the highest quality products while minimizing or eliminating the possibility of batch failures or regulatory intervention?

The Clean Facility of the Future documentary will explore these issues and more by talking to many thought leaders on this topic including: regulatory, end-users, consultants, equipment/service providers.

People interviewed:
  • Poonam Bhende
  • Tony Cundell, Ph.D.
  • Lori Daane, Ph.D.
  • Sandra Gay, Ph.D.
  • Lisa Graham, Ph.D.
  • Patricia Hughes
  • Ian Jennings, SVP
  • David Jones, Ph.D.
  • Michael Lindsay
  • Michael Miller, Ph.D.
  • Paula Peacos
  • Tim Sandle, Ph.D.
  • Allison Scott, Ph.D.
  • Donald C. Singer
  • Krista Spreng, Ph.D.
  • Jeff Weber

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Sunday, 14 April 2019

Custom-made proteins may help create antibodies to fight HIV

A new way to create proteins that can sneak through HIV's protective coating may be a step toward understanding the key components needed for developing a vaccine for the virus, according to researchers.

Using computational modeling, a team of researchers led by Penn State designed and created proteins that mimicked different surface features of HIV. After being immunized with the proteins, rabbits developed antibodies that were able to bind with the virus.

"We were able to show that by using our designed proteins, the blood was able to spontaneously generate antibodies that can inhibit the infection of HIV in cellular models," said Cheng Zhu, a postdoctoral fellow at Penn State College of Medicine. "When we incubated the HIV virus, its infectivity was dramatically reduced by the rabbits' blood."
Zhu added that the study provides a novel way to design proteins for vaccines.

"The proteins -- or immunogens -- we developed aren't a finished product, but we were able to show evidence that it's possible to do," Zhu said. "Moreover, it's also very exciting that we were able to create a new method to tailor make proteins, which could open the door for developing vaccines for other infections, as well."

"Even if we develop an antibody for a particular strain of the virus, that antibody may not even notice the next strain of the virus," Dokholyan said. "In order to develop broadly neutralizing antibodies -- antibodies that neutralize multiple strains of a virus -- we need to find something that remains constant on the virus for those antibodies to latch onto."
According to Dokholyan, HIV uses a coating of carbohydrates to protect a protein on its surface called Env. While this protein could be a potential target for vaccines, the carbohydrate coating makes it difficult or impossible for antibodies to access and neutralize it.

But sometimes, holes naturally appear in this coating, exposing the Env protein to potential antibodies. Zhu said he and the other researchers wanted to find a way to target these holes.
"The idea would be to do molecular surgery to copy sections of the virus's surface and paste them onto different, benign proteins, so they would look but not act like the Env protein," Zhu said. "Hopefully, this would allow the immune system to recognize the virus and create antibodies to neutralize it in the future."

The researchers used computational models to design proteins that would mimic the conserved protein surface of different strains of HIV to be used in the vaccine. Dokholyan said that while usually proteins are engineered by changing one amino acid at a time, they wanted to try a different approach.

"Instead of changing one amino acid at a time, it's a large surface of the HIV strain that is cut and then plugged onto a different protein," Dokholyan said. "It's an important milestone be able to do these major molecular surgeries, and it's very exciting that the strategy worked with a very high accuracy."

After creating immunogens that used the new, HIV-mimicking proteins, the researchers immunized the rabbits and drew blood samples once a month. After analyzing the samples, the researchers found that the blood contained antibodies that were able to bind onto HIV.
The researchers said that while the findings are promising, there is still more work to be done.
"It's important that we were able to generate an immune response to HIV and show that it's possible as a proof of concept," Dokholyan said. "But, we still need to improve the antibodies' neutralization abilities and other aspects before it can become a viable vaccine."
Dokholyan said that in the future, the protein design method could potentially help create and personalize vaccines for different diseases in various areas in the world.

"Diseases can vary by location, for example, there are different strains of HIV in various countries or regions," Dokholyan said. "If we can easily customize proteins for vaccines, that's a good example of where personalized medicine is going to play a role."
The National Institutes of Health helped support this research.


Cheng Zhu, Elena Dukhovlinova, Olivia Council, Lihua Ping, Edgar M. Faison, Shamit S. Prabhu, E. Lake Potter, Stephen L. Upton, Guowei Yin, James M. Fay, Laura P. Kincer, Ean Spielvogel, Sharon L. Campbell, S. Rahima Benhabbour, Hengming Ke, Ronald Sw

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Saturday, 13 April 2019

Elemental impurities reference standards

The EDQM has updated the leaflets of its reference standards for elemental impurities (lead solution CRS, cadmium solution CRS, mercury solution CRS and arsenic solution CRS) with further information to facilitate their use and make traceability transparent. The mass fractions of the assigned element are traceable to the SI units (mole and kilogram) through an uninterrupted chain, similar to certified reference materials established by a national metrological institute.

More detailed information on the assigned value and the associated expanded uncertainty is now included in the leaflets accompanying the reference standards. In addition, the solvent composition is explicitly stated, as well as the density of the solution. The specific primary materials used to achieve the link to the SI units are also indicated.

Elemental impurities naturally occurring in the environment are amongst the greatest potential sources of contamination. Public health standards, such as the ICH Q3D Guideline for Elemental Impurities, require careful risk assessments of sources for elemental impurities. The changes are part of the EDQM’s efforts to provide efficient support to users of its pharmaceutical reference standards. These reference standards also underpin the European Pharmacopoeia (Ph. Eur.) chapter describing the determination of elemental impurities (2.4.20.).

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 12 April 2019

How fungi influence global plant colonization

The symbiosis of plants and fungi has a great influence on the worldwide spread of plant species. In some cases, it even acts like a filter. This has been discovered by an international team of researchers with participation from the University of Göttingen. The results appeared in the journal Nature Ecology & Evolution.

In the colonisation of islands by plant species, it isn't just factors like island size, isolation and geological development that play an important role, but also the interactions between species. The scientists found that the symbiosis of plant and fungus -- the mycorrhiza -- is of particular importance. The two organisms exchange nutrients via the plant's fine root system: the fungus receives carbohydrates from the plant; the plant receives nutrients that the fungus has absorbed from the soil.

"For the first time, new data on the worldwide distribution of plant species in 1,100 island and mainland regions allows us to investigate the influence of this interaction on a global scale," says Dr Patrick Weigelt from the University of Göttingen's Department of Biodiversity, Macroecology and Biogeography, who worked on the study. The results: mycorrhiza-plant interactions, which are naturally less frequent on islands because the two organisms rely on each other, mean that the colonisation of remote islands is hindered. The lack of this symbiotic relationship may act like a brake on the spread of the plants. This is not the case for plant species introduced by humans, as fungi and plants are often introduced together. Head of Department, Professor Holger Kreft, adds, "The proportion of plant species with mycorrhiza interactions also increases from the poles to the equator." One of the most prominent biogeographic patterns, the increase in the number of species from the poles to the tropics, is closely related to this symbiosis.

Dr Camille Delavaux, lead author from the University of Kansas (US), explains, "We show that the plant symbiotic association with mycorrhizal fungi is an overlooked driver of global plant biogeographic patterns. This has important consequences for our understanding of contemporary island biogeography and human-mediated plant invasions." The results show that complex relationships between different organisms are crucial for understanding global diversity patterns and preserving biological diversity. "The absence of an interaction partner can disrupt ecosystems and make them more susceptible to biological invasions," Weigelt stresses.


Camille S. Delavaux, Patrick Weigelt, Wayne Dawson, Jessica Duchicela, Franz Essl, Mark van Kleunen, Christian König, Jan Pergl, Petr Pyšek, Anke Stein, Marten Winter, Peggy Schultz, Holger Kreft, James D. Bever. Mycorrhizal fungi influence global plant biogeography. Nature Ecology & Evolution, 2019; 3 (3): 424 DOI: 10.1038/s41559-019-0823-4

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 11 April 2019

Call for experts to join the Ph. Eur. Network

The EDQM is renewing its call for expressions of interest to join the European Pharmacopoeia (Ph. Eur.) as an independent scientific expert. Professionals from national authorities (e.g. pharmacopoeial authorities, official medicines control laboratories, licensing authorities and inspectorates), the private sector (pharmaceutical or chemical industries), academia, research organisations and other experts are encouraged to apply. This is an ideal opportunity to take part in the work of the Ph. Eur., to network with professionals with various backgrounds and from all over Europe and beyond, and to help shape Ph. Eur. texts, internationally-recognised quality standards for medicines.

Experts provide a vital and invaluable contribution to the elaboration and maintenance of Ph. Eur. texts. In return, they are given a unique opportunity to expand their knowledge of the Ph. Eur. and the European regulatory system, share information and experience, better understand the difficulties linked to the elaboration and revision of pharmacopoeial texts and network with their peers.

The terms of reference of the Ph. Eur. Groups of Experts and Working Parties for which candidates from non-Ph. Eur. member states may apply are provided in the Terms of reference and profile for members of Groups of Experts and Working Parties.
Applications will be examined by the Ph. Eur. Commission at its 165th session (26-27 November 2019) when all Ph. Eur. Groups of Experts and Working Parties will be (re)appointed. Potential candidates from Ph. Eur. Member States are invited to contact their National Pharmacopoeia Authorities.

For further details, see:

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Special offers