Rare Disease Day

Rare Disease Day is an observance held on the last day of February to raise awareness for rare diseases and improve access to treatment and medical representation for individuals with rare diseases and their families.

Every year, thousands of events are organised around the world during the month of February to mark the occasion of Rare Disease Day. Patient organisations, healthcare professionals, researchers, policymakers and other members of the rare disease community organise Rare Disease Day events.

Building awareness of rare diseases is so important because 1 in 20 people will live with a rare disease at some point in their life. Despite this, there is no cure for the majority of rare diseases and many go undiagnosed. Rare Disease Day improves knowledge amongst the general public of rare diseases while encouraging researchers and decision makers to address the needs of those living with rare diseases.


Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Using ‘living antibiotics’ to battle AMR

Antimicrobial resistance (AMR) means normally treatable infections are becoming difficult to cure with antibiotics. However, researchers at Okinawa Institute of Science and Technology Graduate University (OIST), Japan, may have a solution using bacteria that preys on other bacteria. Bdellovibrio bacteriovorus is a bacterium that feeds on Gram-negative bacteria, which include well-known, disease-causing bacteria like E. coli and Salmonella. In lab tests, the OIST team have successfully been able to manipulate B. bacteriovorus’ genes to attack its prey faster in the presence of a drug called theophylline. Manipulating the bacterium’s natural behaviour in this way could lead to potential new treatments for a variety of different infections.

Source: Phys.Org 

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Using bacteria to reduce dairy waste

The process of making dairy products generates a lot of waste in the form of acid whey, but a team of scientists from Cornell University, USA, and University of Tübingen, Germany, have discovered a way to turn this waste into useful compounds using bacteria. Acid whey is mostly made up of sugars and acid, but is too acidic to be fed back to livestock as is. Using reactor tanks filled with bacteria found in gut microbial communities, the research team noticed that acid whey could be converted into more useful substances like caproic and caprylic acid, which are natural antimicrobials and can be used in livestock feed. Alternatively, more processing could turn the production waste into compounds that can be further refined into biofuels. In reusing waste products, both options would offer more sustainable and cost-effective alternatives than are currently used.

From: Science Direct

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

The microbiology behind wine going bad

With many wines, laying them down for a long period improves them and this is a factor in good wines becoming great wines. However, sometimes wines go off and develop a bad smell. New research reveals why.

Sometimes a wine has been in storage, with the expectation that the bottle of vino, when opened, will produce something special to the palate and to the nose. To create the delightful bouquet, within wine there are volatile and non-volatile compounds that contribute to the makeup of a wine's aroma.

Occasionally a bottle is removed from the cellar and, when opened, there is a highly unpleasant smell. The main cause of this off-odor is hydrogen sulphide, which delivers to the affected wine an aroma of sewage or rotten eggs.

Hydrogen sulfide

Hydrogen sulfide is the chemical compound and presented as a colorless chalcogen hydride gas. At certain levels it is very poisonous, corrosive, and flammable. Hydrogen sulfide is typically generated as a result of the microbial breakdown of organic matter in the absence of oxygen (as would be found in a sewer). With microorganisms, this is a form of anaerobic digestion undertaken by sulfate-reducing microorganisms.

Sulfate-reducing microorganisms can be traced back to 3.5 billion years ago and are considered to be among the oldest forms of microbes, having contributed to the sulfur cycle soon after life emerged on Earth.

Why wine goes off?

Although the chemical that causes off-wine has been established, the specific causes have always been uncertain. Now, with hydrogen sulphide, scientists have identified some potential sources of this stinky compound.

According to Laboratory Manager magazine, hydrogen sulphide is produced naturally during fermentation. However, the bulk of the gas disappears or is removed in subsequent winemaking steps. Why it sometimes re-emerges after bottling has been a puzzle.

One theory, with a touch of irony, is that it might derive from polysulfanes and other sulfur byproducts created during the actual act of hydrogen sulphide removal.

Research process

For the study, the scientists developed a model wine that was composed of a mixture of polysulfanes. Taking this wine, the researchers treated it with antioxidants like sulfur dioxide and ascorbic acid. These additives are introduced to many wines as preservatives during bottling.

Once this was prepared, the researchers identified and calculated the concentration of a several sulfur compounds in the wine after six months of storage. It was discovered that polysulfanes containing four or more linked sulfur atoms per molecule were most likely to decompose during wine storage. This reaction correlated with elevated levels of hydrogen sulphide.

It was further found that the polysulfane decomposition and hydrogen sulphide release occurred more frequently in the wine treated with sulfur dioxide compared with untreated wine or wine only treated with ascorbic acid.

The inference from this discovery is that wines with polysulfane additives are most likely to experience re-emergent hydrogen sulphide. This finding is set to be tested out on a bigger scale.

The study was funded by Wine Australia and the Australian government.

Research paper

The new research has been published in the Journal of Agricultural and Food Chemistry. The research paper is titled: “Liberation of Hydrogen Sulfide from Dicysteinyl Polysulfanes in Model Wine.”

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Medical device QMS harmonisation

The US FDA has made a formal announcement of its intention to replace certain aspects of the existing Quality System Regulation (QSR) with specifications of the international consensus standard ISO 13485:2016. This change is currently at the proposed rule stage.

ISO 13485:2016 specifies requirements for a quality management system where an organization needs to demonstrate its ability to provide medical devices and related services that consistently meet customer and applicable regulatory requirements. Such organizations can be involved in one or more stages of the life-cycle, including design and development, production, storage and distribution, installation, or servicing of a medical device and design and development or provision of associated activities (e.g. technical support). ISO 13485:2016 can also be used by suppliers or external parties that provide product, including quality management system-related services to such organizations.

In relation to this, Tim Sandle has written an article:

Sandle, T. (2018) Medical device QMS harmonisation: FDA to align with ISO 13485, GMP Review, 17 (3): 4-8

For details, please contact Tim Sandle

 Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Zaire ebolavirus found in a bat in West Africa

The government of Liberia, in partnership with the Center for Infection and Immunity (CII) at the Columbia University Mailman School of Public Health and EcoHealth Alliance, announced the discovery of Ebola virus in a bat in Liberia. This is the first finding of Zaire ebolavirus in a bat in West Africa, adding to other evidence suggesting bats serve as a natural wildlife reservoir for Ebola and other related viruses. Scientists found both genetic material from the virus and ebolavirus antibodies in a Greater Long-fingered bat (Mineopterus inflatus) in Liberia's northeastern Nimba District. CII has been working to identify and characterize novel viruses at the intersection of humans and animals, on a global scale, for more than three decades. This work is a part of the USAID PREDICT project, which aims to better understand the animal reservoirs, seasonality, and transmission of viruses that can cause epidemic diseases.

Ebola virus belongs to the Filoviridae family which also includes the Marburg and Cueva viruses. Like other zoonotic diseases (SARS, influenza, and rabies), Ebola virus is harbored by a natural animal reservoir, in Ebola's case believed to include one or more species of bat, based on previous scientific studies. Prior Ebola outbreaks in Central Africa have been associated with deforestation and bushmeat hunting, where human cases were linked to contact with and consumption of chimpanzees, gorillas, and duikers that were infected. These animals were also victims of Ebola virus and it's still a mystery as to exactly how they were infected. However, there is substantial evidence that filoviruses, such as Ebola and Marburg virus, are carried by bats. Marburg virus was recently discovered for the first time in Sierra Leone in its known bat reservoir, but it has historically been difficult to identify bats infected with Ebola virus.

Bats play a critical role in ecosystems around the world, by removing pest insect species and pollinating fruiting trees, for example. The finding of Ebola virus in a bat should not be taken as a reason to exterminate, remove or harass bats in their natural environment. In fact, previous work shows that efforts to remove wildlife populations can lead to enhanced disease spread.

This is the first identification of Ebola virus in a bat in West Africa. There are six species of Ebola virus and Zaire ebolavirus is the one responsible for causing the West African Ebola epidemic which infected nearly 30,000 people between 2013 and 2016. Researchers at CII are working to determine whether the strain found in the bat is exactly the same one associated with the 2013-2016 outbreak. The evidence so far from about 20 percent of the virus' genome suggests that it is closely related. Zaire ebolavirus is also responsible for the ongoing outbreak in the Democratic Republic of Congo, which is now the second deadliest Ebola outbreak in history.

No human cases of Ebola are linked to this discovery and Liberia has remained free of any new human cases since the 2013-2016 outbreak. However, this finding brings us closer to understanding where human Ebola cases come from.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Airborne survival of bacteria in aerosol droplets from coughs and sneezes

The airborne transmission of diseases including the common cold, influenza and tuberculosis is something that affects everyone with an average sneeze or cough sending around 100,000 contagious germs into the air at speeds of up to 100 miles per hour.

New research led by scientists from the University of Bristol and published today in the Journal of the Royal Society Interface, outlines a new technique that, for the first time, examines directly the environmental factors that control the transmission of disease to the level of a single aerosol particle and a single bacterium.

Aerosol droplets are a typical route for the transport of pathogens, such as bacteria and viruses, and the airborne transmission of disease.

The impact of environmental factors (such as relative humidity, temperature, atmospheric oxidants and the presence of light) on the viability and infectivity of pathogens in aerosol droplets remains poorly understood.

For example, although the seasonal variation in influenza cases is known, the environmental factors determining the differences in airborne transmission of the virus is not well understood.

To help understand this process better, scientists have established a novel approach for forming aerosol droplets containing a specific number of bacteria, trapping a cloud of these droplets of exact known population and simulating their environmental exposure over a time from five seconds to several days.

The aerosol droplets are then gently sampled onto a surface to determine how many bacteria have survived their time in the aerosol phase.

The study reports on the benchmarking of this new approach, demonstrating the many advantages over conventional techniques, which include introducing large populations of droplets to large rotating drums or capturing droplets on spiders' webs.

Not only can measurements be made down to the single bacterium/single droplet level requiring very little quantity of aerosol (picolitres), but high time resolution (one second) measurements of viability can be made, allowing the first quantitative studies of the influence of dynamic factors transforming the aerosol (for example evaporation, condensation) on viability.

For example, the study shows that during evaporation of droplets, the concentration of typical salts can rise way beyond their solubility limit, placing considerable osmotic stress on the bacteria and reducing viability.

See: Mara Otero Fernandez, et al. Assessing the airborne survival of bacteria in populations of aerosol droplets with a novel technology. Journal of The Royal Society Interface, 2019; 16 (150): 20180779 DOI: 10.1098/rsif.2018.0779

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

New take on the CRISPR system may help fight antibiotic resistance

Researchers from the University of Wisconsin-Madison (WI, USA) have developed a new way to use CRISPR, this time as a potential method for reducing antibiotic resistance. By targeting the genes most effected by existing antibiotics, it is possible to determine how best to improve the drugs or how to develop new ones.

“What we need to do is to figure out new weaknesses in these bacteria,” commented system developer Jason Peters to Biotechnqiues.

Traditionally, the CRISPR system is used for gene editing, cutting DNA at the target gene and making edits while the cell repairs the damage. In comparison, this new method, known as Mobile-CRISPRi, works by binding to DNA and blocking other proteins from gaining access and activating transcription, thereby reducing gene expression and protein synthesis.

CRISPRi is a defanged form of CRISPR that has been engineered to be unable to cut DNA due to a catalytically inactive Cas9 protein. To make it mobile, the team utilized the process of conjugation, a kind of bacterial sex where bacteria link up and exchange DNA. This allowed the CRSIPRi to be transferred from an E. coli model into the disease-causing species being studied. These included Pseudomonas, Salmonella, Staphylococcus and Listeria, among others.

“You basically mix the bacteria together and it happens,” Peters commented about conjugation; “It doesn’t get much easier than that.”

The results, recently published in Nature Microbiology, showed that when the amount of protein that is targeted by the antibiotic is reduced, the bacteria becomes much more sensitive to the drug at a lower concentration.

When discussing the meaning of his technique, Peters stated: “What that means is that you can now do studies on how antibiotics work directly in these pathogens. That could give us a better clue about how these drugs work in the different organisms and potentially what we can do to make them better.”

Manipulating genes in established cultures of lab bacteria such as E. coli is relatively simple, the problem comes when dealing with bacteria recently isolated from their previous environment. The Mobile-CRISPRi system could be easily transferred and open doors for understanding how bacteria colonize.

Peters is offering the use of the new system to other labs, allowing other researchers to study the germs of their choice.

“So now it’s going to be completely available to the community,” said Peters. “Now this gives people a path forward.”

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Pharmacovigilance Inspection Metrics April 2017 to March 2018

The MHRA GPvP inspectorate published their latest inspection metrics for the period from April 2017 to March 2018.

Pharmacovigilance (PV) is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem. WHO established its Programme for International Drug Monitoring in response to the thalidomide disaster detected in 1961. Together with the WHO Collaborating Centre for International Drug Monitoring, Uppsala, WHO promotes PV at the country level. At the end of 2010, 134 countries were part of the WHO PV Programme. The aims of PV are to enhance patient care and patient safety in relation to the use of medicines; and to support public health programmes by providing reliable, balanced information for the effective assessment of the risk-benefit profile of medicines.

See: https://mhrainspectorate.blog.gov.uk/2018/12/04/pharmacovigilance-inspection-metrics-april-2017-to-march-2018/

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

EMA Regulatory Science to 2025

EMA (European Medicines Agency) has published this proposed plan for advancing the Agency’s engagement with regulatory science over the next five to ten years, covering both human and veterinary medicines.

The strategy includes developments and challenges in medicines development that EMA together with the Commission and NCAs experts have identified in a thorough process of

mapping and selection. Now EMA wants to hear from stakeholders.

See: https://www.ema.europa.eu/documents/regulatory-procedural-guideline/ema-regulatory-science-2025-strategic-reflection_en.pdf

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Alternations in gut microbiota in pregnancy

Recent studies have shown that maternal gut microbiota in humans primes the offspring's immune and metabolic development during pregnancy and lactation. Due to environmental factors that are impractical to control in human studies, however, much remains unknown around changes in maternal gut microbiota during these stages. A new study published in The FASEB Journal utilized a pig model to enable exploration of maternal gut microbiota change due to pregnancy and lactation.

To rule out the confounding factors in human studies of diet and host genetics, a group of researchers examined fresh fecal samples from two breeds of sows. Based on these samples, they conducted comparative analyses of gut microbiota (including Coriobacteriaceae and Escherichia) and short-chain fatty acids (SCFAs) across different stages of gestation, lactation, and non-pregnancy.

Coriobacteriaceae and Escherichia were found to gradually increase over gestational time irrespective of breed, indicating that they are likely associated with the progression of pregnancy. Relative to the gestation and non-pregnancy periods, lactation was associated with an increase in SCFA production in both breeds, suggesting that this phase has a distinct gut microbial structure and higher metabolic activity than the other phases.

See:

Hongbin Liu, Chengli Hou, Ning Li, Xiaoya Zhang, Guolong Zhang, Feiyun Yang, Xiangfang Zeng, Zuohua Liu, Shiyan Qiao. Microbial and metabolic alterations in gut microbiota of sows during pregnancy and lactation. The FASEB Journal, 2019; fj.201801221RR DOI: 10.1096/fj.201801221RR

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

E-learning module from Pharmig supports Annex 1 disinfection requirements

In December 2017, the European Medicines Agency issued a new draft of EU GMP Annex 1 for sterile medicinal products manufacture. 1 While the draft has yet to be converted into a finalised document, much of what is contained within the document is being used by European inspectors to assess facilities (this is unsurprising given that the revisions are intended to codify current best practices). Central to the update is the requirement for each facility to develop a contamination control strategy, and central to such a strategy is the cleaning and disinfection of cleanrooms. The application of detergents and disinfectants to well-designed and operated cleanrooms is essential for contamination control.

Tim Sandle has written a new article on e-learning solutions for cleaning and disinfection practices:

Pharmig, the not-for-profit professional organisation representing pharmaceutical microbiologists, has recognised these trends and the associated need to address cleaning and disinfection training and competency standards. Part of Pharmig’s remit is to develop training and education in relation to microbiology. Weighing up different options for delivering training, Pharmig selected an e-learning route and subsequently developed an interactive training package. This article considers the benefits of e-learning, the new on-line module from Pharmig, as well as the key requirements from the revised Annex 1 in relation to disinfection contamination control.

Reference:

Sandle, T. (2018) E-learning module from Pharmig supports Annex 1 disinfection requirements, Clean Air and Containment Review, Issue 36: 20-23

For details contact Tim Sandle


Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

The Problem of Bacterial Spores and Sporicidal Disinfection (webinar)

There have been a number of pharmaceutical and healthcare product recalls associated with bacterial contamination, and a number of these are associated with spore forming organisms. In addition, there have been some reported cases of patient illness, especially in relation to aseptically produced medicines. Investigations have shown that poor contamination control has led to spores being prevalent in the production environment. Improved contamination control strategies are required to prevent such incidents from occurring.

Incidents of bacterial spore contamination of medicinal products are increasing. Regulators are concerned about the link between product recalls and the process environment. Pharmaceutical and healthcare facilities need to have a robust bio-contamination control program in place. This webinar outlines the origins and risks of spores, strategies to reduce incidents, and the selection and incorporation of sporicidal agents into the contamination control program.

Date: Thursday, 21 February 2019 | Time: 10:00 AM PST, 01:00 PM EST | Duration: 60 Minutes

See: https://onlinecompliancepanel.com/webinar/The-Problem-of-Bacterial-Spores-and-Sporicidal-Disinfection-505059

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

How to save time in autoclaving cycles

The normal packaging activity inside a cleanroom solicits some fundamental reflections on the times, effectiveness and safety of the operation itself:

● packaging is a time-consuming operation
● the use of medical paper involves risks related to the nature of the intrinsically weak material, which is corruptible after autoclaving, subject to breakage if wet, and with a medium-quality microbiological barrier
● the safety of the entire operation, as regards the possible release of particles and the uniformity of sterilization, is compromised

Pharmaclean® line of covers and bags for packaging, protection and sterilization solves time, efficacy and safety problems at the same time.

In this case a filling needle: the application is simple and fast, as well as the closure (without adhesive tape). In a short time, we are ready for autoclaving.




After applying the cover to the part of the tube terminal, insert the filling needle into the dedicated bag. We are ready for the sterilization phase.

The use of Pharmaclean® covers and bags makes the packaging operation and subsequent sterilization, fast, effective and safe.

● tear and puncture resistance
● easy to remove
● closure with laces, no adhesive tape
● possibility of customization
● no limit of shape or size
● low particle release
● excellent microbiological barrier
● uniform steam penetration over the entire surface
● ease in preparing the instruments
● protects against microbiological and particulate contamination during the various stages of the production process

Pharmaclean® produces standard and customized covers and bags according to the specific needs of the individual customer.




The use of Tyvek®, compared to medical paper, is a guarantee of absolute protection given the intrinsic characteristics of the material.

Manufactured with a flash spinning process, Tyvek® fabric is made of continuous and strong high-density polyethylene fibers, with intrinsic barrier properties, without requiring thin layers or additional coatings. This exceptional combination of barrier protection and breathability makes Tyvek® the ideal fabric for packaging and protection. Compared to medical papers, Tyvek® offers an optimal balance between resistance to microbial penetration, tear resistance, puncture resistance and cleanliness. And unlike paper and film for medical use, Tyvek® is compatible with all commonly used sterilization methods, including VHP.

Pharmaclean® by AM Instruments

www.aminstruments.com

www.pharmaclean.com

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology