Thursday, 19 October 2017

Cilia: 'The bouncer' of bacteria


A new paper, from University of Southern California, elucidates the active role of cilia in regulating flow for bacteria filtering and enhancing chemical communication.

The paper, published in the Proceedings of the National Academy of Sciences, describes a framework for the role of fluid mechanics in letting symbiotic bacteria in an organism and enhancing chemical communication between the symbiont and the host organism. The results are contrary to previous research which assumes that cilia solely play a "clearance function." They could shed light on the role cilia -- which are the size of one hundredth of a single human hair -- play in human respiratory system and even in the reproductive systems and the brain. Their findings could also provide insights on how cilia dysfunction within organs affect for example, pulmonary conditions or infertility (how cilia help sperm reach eggs).

To learn about how cilia might work in the human body, Kanso, in collaboration with symbiosis expert McFall-Ngai and biofluid expert Janna Nawroth studied bobtail squid. The researchers examined how these squids in their nascent stage allow symbiotic bacteria Vibrio Fischeri to enter into their ciliated light organs, which play a crucial role in camouflaging the ink sacks of the otherwise translucent organism while they hunt for food at night. The scholars sought to know: why does this bacterium gain access and why do all bacteria fail to accumulate within the squid's light organ? In addition, they sought to explain what, if any, is the role of cilia in allowing access?

Researchers discovered that a vortical or "donut-like" flow generated by the cilia was kicking away most particles. The role of the fluid motion in filtering particles by size was verified using a physics-based mathematical model. One of the core findings was that there were two distinct flows taking place by two different types of cilia. Longer cilia move in a "wave-like" fashion which creates a vortical flow field that filters particles and then shorter cilia which beat randomly keep the particles in place and gently mix the local flow. This random motion by the cilia and fluid mixing enhance the chemical screening of bacteria. To further prove the important role played by cilia, the researchers also found that if cilia are "killed," particles will accumulate everywhere in the organism.

See:

Janna C. Nawroth, Hanliang Guo, Eric Koch, Elizabeth A. C. Heath-Heckman, John C. Hermanson, Edward G. Ruby, John O. Dabiri, Eva Kanso, Margaret McFall-Ngai. Motile cilia create fluid-mechanical microhabitats for the active recruitment of the host microbiomeProceedings of the National Academy of Sciences, 2017; 114 (36): 9510 DOI: 10.1073/pnas.1706926114

Posted by Dr. Tim Sandle

Wednesday, 18 October 2017

Microbiologist Wins International Prize for Biology


Rita Colwell, a Distinguished University Professor in the University of Maryland Institute for Advanced Computer Studies, has been named the 2017 laureate of the International Prize for Biology for her outstanding contributions to marine microbiology, bioinformatics, microbiomes and the understanding and prevention of cholera.

Colwell is the thirty-third recipient of the International Prize for Biology, generally recognized as one of the most prestigious honors a natural scientist can receive. Past laureates include such other renowned b
iologists as John B. Gurdon, Motoo Kimura, Edward O. Wilson, Ernst Mayr, and Thomas Cavalier-Smith.
In awarding the prize, Japan’s Society for the Promotion of Science honored Colwell as a pioneer in the use of computational tools and DNA sequencing to identify and classify marine bacteria and other microorganisms, work that helped lay the foundation for the bioinformatics revolution.

The prize also recognizes Colwell’s life-saving contributions to the understanding and prevention of cholera, an acute diarrheal disease, caused by ingestion of water or food contaminated with Vibrio cholera, which according to the World Health Organization is responsible for approximately 1 to 4 million illnesses and 20,000 to 140,000 deaths each year.

Colwell, whose career bridges the disciplines of microbiology, ecology, infectious disease, public health, and computer and satellite technology, continues to be a leader in bioinformatics, notably in understanding microbiomes and the application of this knowledge to human health and the diagnosis and treatment of disease. This includes her current work as founder and chairman of CosmosID, Inc., a microbial genomics company focused on molecular diagnostics of human pathogens and antimicrobial resistance.

“It is an extraordinary honor to be named recipient of the International Prize for Biology, a very special honor for a biologist,” said Colwell. “I am deeply grateful to the Japan Society for the Promotion of Science for this award. I have many friends and colleagues in Japan and look forward to continuing my many collaborations with them.”

The selection committee also cited Colwell's transformational work in these areas:

  • Establishing the taxonomy of vibrio bacteria, which includes Vibrio cholerae.
  • Identifying a previously unknown survival strategy of dormant vibrio cells, which the committee said "has had a profound influence on microbiology and medicine.”
  • Showing how climate change has expanded the habitat range of vibrios, and the occurrence of cholera.
  • Helping prevent the spread of cholera in developing countries by discovering and demonstrating an effective way to use the sari, the traditional dress of women on the Indian subcontinent, as a filter to remove vibrio-carrying plankton from drinking water drawn from ponds, rivers and other surface waters.

There is no Nobel Prize for biology, but Japan’s International Prize for Biology is one of three prizes often considered to be biology’s equivalent. The other two honors often placed in this category are the Balzan Prize and Crafoord Prize.

"We are extremely proud of Dr. Colwell's indelible impact on the field of biology and, more importantly, on human lives," said UMD Interim Vice President for Research Amitabh Varshney. "We applaud her fearless pursuit of translational research and life-saving solutions to global health challenges."

The International Prize for Biology was instituted in April 1985 by the Committee on the International Prize for Biology. The prize, consisting of a certificate, a medal and an award of 10-million yen (more than $90,000) is given to the recipient, along with an imperial gift, a silver vase bearing the imperial crest. The award presentation ceremony and a subsequent reception in honor of Colwell will held in late 2017 at the Japanese Academy in Japan.

Colwell joined the University of Maryland faculty in 1972 and has been a Distinguished University Professor at the University of Maryland and the Johns Hopkins University, Bloomberg School of Public Health since 2004. She is chairman emeritus at Canon US Life Sciences, Inc. She holds a dozen U.S. patents, most involving computational biology.

Colwell’s passion for science was obvious at an early age. As a sixth-grader, her school principal said to her, “You received the highest science test score ever.  You have a responsibility to meet your potential and you must go to college.” But this was in the 1940s, and discrimination against women, especially in the sciences, was an obstacle.  Hurdles she faced included a high school science teacher who told her not to bother with chemistry in college, as it was not a career suitable for women, and a department chair who denied her a master’s degree fellowship because they were “wasted on women.” Colwell’s steely determination to succeed was apparent, then and now.

Her decision to pursue a career in genetics introduced her to the emerging field of molecular biology and the very earliest use of computers in the pursuit of understanding complex biological systems. In the 1960s, Colwell was the first researcher in the U.S to develop a computer program to analyze bacteriological data. She continued and expanded this work at the University of Maryland beginning in 1972. Today, bioinformatics is used at the very forefront of biological scientific research due to her efforts, along with colleagues, to promote the use of computing tools to facilitate the study of biology.


Colwell’s lifelong passion for studying environmental microbiology, especially in marine environments was fostered by her childhood fascination with the ocean. This passion led to her discovery, in the 1970s, of the presence of Vibrio cholerae, the causative agent of cholera, in the waters of Chesapeake Bay. At the time, conventional wisdom held that cholera was spread from person to person, or from consuming tainted food or drinking water and that its presence in the environment could only be due to the release of sewage into rivers, lakes, streams, and other waters. She proved that the bacteria were native to the aquatic environment, attached to zooplankton, and that that certain bacteria, such as Vibrio species, are capable of entering a dormant state.

Colwell has received a great many awards and recognitions, including the 2017 Vannevar Bush Award given by the U.S. National Science Board; the 2010 Stockholm Water Prize awarded by the King of Sweden; the 2006 National Medal of Science awarded by the president of the United States; and the Order of the Rising Sun, Gold and Silver Star bestowed by the Emperor of Japan. She is the recipient of 61 honorary degrees from institutions of higher education and has a geological site in Antarctica, Colwell Massif, named in recognition of her work in the polar regions.

Colwell was the 11th director of the National Science Foundation and the first woman to head the agency. She also co-chaired the Committee on Science, National Science and Technology Council.  She has held numerous advisory positions in the U.S. government, nonprofit science policy organizations, and private foundations and has authored or co-authored 19 books and more than 800 scientific publications.

 Colwell also has served as chairman of the Board of Governors of the American Academy of Microbiology, president of the American Association for the Advancement of Science, Washington Academy of Sciences, American Society for Microbiology, Sigma Xi National Science Honorary Society, International Union of Microbiological Societies, and American Institute of Biological Sciences.  She is a member of the National Academy of Sciences, Royal Swedish Academy of Sciences, Royal Society of Canada, Royal Irish Academy, Bangladesh Academy of Science, Indian Academy of Science, American Academy of Arts and Sciences, American Philosophical Society and the National Academy of Inventors. 

Posted by Dr. Tim Sandle

Tuesday, 17 October 2017

How Listeria monocytogenes can survive in extreme environmental conditions


It is difficult to eliminate L. monocytogenes from post processing contamination of food production lines since this pathogen is common in various environments outside processing plants, and can endure in food processing environments. Listeria monocytogenes has better survival ability than most other food pathogens, resulting in the colonization of Listeria in food processing environment. In the recent past, researchers have identified several hypervariable (easily changeable regions) regions of the bacterial genome called Genetic Insert Stress Survival Islet 1 (SSI-1). The SSI-1 is a five-gene islet that contributes to the growth of L. monocytogenes in suboptimal conditions ..… Read More at BioExpert Corner.
Posted by Dr. Tim Sandle

Monday, 16 October 2017

New standards for cleanroom construction


Tim Sandle has written a new article for Cleanroom Technology around the subject of cleanroom construction. A new part of ISO 14644 – part 14 – came out last year which covers cleanroom equipment specification. Tim Sandle looks at why it was introduced and its relevance for those specifiying equipment for use inside cleanrooms.

Cleanrooms are designed to minimize the ingress of airborne particles (achieved through HEPA or ULPA filters) and to control what happens to particles generated within the cleanroom. Good air flow design — such as turbulent flow — helps to prevent particles from being deposited onto surfaces (particles settle by two primary mechanisms: gravitational sedimentation and turbulent deposition). The removal of these particles is achieved through the extraction of room air with the addition of clean air into the room (air exchange rates). The flow of particles in air from a less clean area can also be blocked from entering an area of a higher cleanliness level through positive pressure differentials.

The reference is:

Sandle, T. (2017) Applying design and construction standards to cleanroom builds, Cleanroom Technology, 25 (8): 16-18

For further details, please contact Tim Sandle

Posted by Dr. Tim Sandle

Sunday, 15 October 2017

Solutions for the automated infeed and loading of medical products


Wolfertschwenden– Presentations from MULTIVAC at this year's Compamed will include solutions for the automated infeed and loading of medical products within the packaging procedure. In addition to a syringe infeed system for loading pre-filled glass or plastic syringes with process reliability and control, these will also include handling modules and carrier systems. They ensure that optimum product protection is achieved, as well as raising the efficiency of the entire packaging line and increasing process reliability.

A packaging line for the GMP-compliant thermoforming packaging of medical products will give an example of how intelligently used automation components can make the packaging procedure more secure, hygienic and reliable. The line is equipped with an automatic syringe infeed system. The infeed system consists of a product infeed conveyor, a separating wheel, a trapezoidal belt, a 3-axis robot and a H 242 handling module. It enables up to 300 pre-filled glass or plastic syringes per minute to be loaded into the pack cavities with process reliability and control. All the modules are synchronised with the thermoforming packaging machine and can be operated via its control terminal in a very convenient way.

But there are also many other automation components available for orientating, separating and infeeding a wide range of medical products. MULTIVAC's wide product range comprises a large number of belt and carrier systems as well as specific infeed systems, which can be designed individually to the product-related requirements depending on the products being packed and the particular upstream processes. As an example, needles and syringe plungers , which are supplied to the line as bulk products, can be separated by means of vibrating units and centrifuges, before being transferred in single or even several rows to the packaging machine. Syringes, bags, ampoules and vials can be presented to the machine by means of separating units and transport conveyors, which are specifically matched to the product. The examples mentioned above show, how the individual products are prepared by the infeed system in such a way, that they can be precisely positioned for picking up by a robot and loading into the pack cavities.

In addition to this, MULTIVAC will also be exhibiting at the trade fair a wide range of handling modules, which can be equipped individually with a variety of kinematics and easy-change gripper systems for loading the pack cavities accurately and hygienically. These handling modules can also be used for unloading the finished packs from the machine and transferring them to downstream equipment. The grippers are matched exactly to the particular product, which is frequently very light or sensitive. This minimises the fault rate and ensures that a high level of pack quality is achieved.

Thanks to their design and particular features, all the system components are characterised by their high level of GMP compliance. They can easily be integrated into the control unit of the particular packaging machine.

Posted by Dr. Tim Sandle

Saturday, 14 October 2017

Klebsiella species share drug resistance genes


Three different species of Klebsiella bacteria can cause life-threatening infections in hospital patients and that all three share genes that confer resistance to the most commonly used antibiotics, new research shows. The study improves physicians' understanding of Klebsiella infections and could point toward better ways to fight multi-drug resistant strains of these bacteria.

The researchers sequenced the entire genome of 1,777 Klebsiella from clinical specimens across the greater Houston area. Until now, Klebsiella pneumoniae was thought to be the culprit in most serious Klebsiella infections. However, the research team noticed a group of 28 samples that looked genetically different.

Depending on the collection, between 2-12 percent of the samples had been misidentified as Klebsiella pneumoniae, and were in fact two related species, Klebsiella variicola or Klebsiella quasipneumoniae. K. variicola and K. quasipneumoniae had previously been characterized as commensal, nonpathogenic bacteria of the GI tract or agricultural pests, which rarely caused human infections. Long's team found they were capable of causing invasive and severe infections in patients, with the same rate of mortality as K. pneumoniae.

See:

S. Wesley Long, Randall J. Olsen, Todd N. Eagar, Stephen B. Beres, Picheng Zhao, James J. Davis, Thomas Brettin, Fangfang Xia, James M. Musser. Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing Klebsiella pneumoniae Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 307mBio, 2017; 8 (3): e00489-17 DOI: 10.1128/mBio.00489-17

Posted by Dr. Tim Sandle

Friday, 13 October 2017

WHO Specifications for Pharmaceutical Preparations


The World Health Organization (WHO) Expert Committee on Specifications for Pharmaceutical Preparations meets now annually and their reports (Technical Report Series) include all adopted guidelines in the form of Annexes. The 51st report has now been published.

See: WHO

Special book offer for readers:



Posted by Dr. Tim Sandle

Thursday, 12 October 2017

Microbial Identification strategy for pharmaceutical microbiology


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 which 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 with 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; which level of identification is appropriate (morphology, genus, or species); and what can be done with the collected information needs careful thought. A further decision point is whether the testing laboratory carries out the testing ‘in house’ or contracts out the function. This article addresses these points and provides a basis of the microbiologist in each pharmaceutical or healthcare organization to develop a microbial identification strategy.

This is the introduction to an article by Tim Sandle for the Journal of GxP Compliance (a special edition devoted to Microbiology).

The reference is:

Sandle, T. (2017) Microbial Identification strategy for pharmaceutical microbiology, Journal of GxP Compliance, 21 (4): 11-20: http://www.ivtnetwork.com/article/microbial-identification-strategy-pharmaceutical-microbiology

For further details, please contact Tim Sandle.

 Posted by Dr. Tim Sandle

Wednesday, 11 October 2017

A new estimate of biodiversity on Earth


To date, about 1.5 million species have been formally described in the scientific literature, most of them insects. Proportionally, bacteria comprise less than 1% of all described species.

Scientists generally agree that many more species exist than are formally described, but they disagree about how many there really are. Some studies have estimated 2 million or fewer, whereas others suggest as many as 12 million (one recent study even suggested the planet could be home to a trillion species).

In a new paper published in The Quarterly Review of Biology (September 2017), researchers from the University of Arizona have estimated that there are roughly 2 billion living species on Earth, over a thousand times more than the current number of described species.

In coming up with their estimate, the researchers took advantage of the fact that many estimates now agree on the projected number of insect species, around 6.8 million. They incorporated new estimates of species boundaries revealed by DNA sequences, which suggest there might be six times as many insect species, increasing the total to 40 million for insect species alone.

They then reviewed all groups of organisms associated with insects as parasites or symbionts. They found that each insect species most likely hosts a unique species of mite, roundworm (nematode), a one-celled fungus called a microsporidian, and a one-celled organism called an apicomplexan protist (which cause malaria in humans).


Most importantly, the researchers estimated that each insect species is likely to host at least 10 bacterial species found nowhere else. Based on these estimates, they deduce that there should be around 2 billion species on Earth.

The authors also suggest that the diagram of which taxonomic groups contain the most species, or the "Pie of Life," is very different from traditional estimates. Rather than being dominated by insects, as traditionally shown, their estimates show a pie dominated by bacteria (70 to 90% of all species), with insects (and animals in general) having a much smaller slice.

See:

Brendan B. Larsen, Elizabeth C. Miller, Matthew K. Rhodes, John J. Wiens. Inordinate Fondness Multiplied and Redistributed: the Number of Species on Earth and the New Pie of LifeThe Quarterly Review of Biology, 2017; 92 (3): 229 DOI: 10.1086/693564



Posted by Dr. Tim Sandle

Tuesday, 10 October 2017

A Guide to Applying the Four Pillars of ICH Q10


A white paper of interest from Pharmaceutical Manufacturing:

This White Paper will detail not only the applications of the four pillars and their corresponding QMS applications, but also additional QMS functions that help to ensure ICH Q10 compliance. These include:

A Guide to Applying the Four Pillars of ICH Q10 flexibility, allowing the end user to better adapt to the system; integration, which enables processes to collaborate with others across the enterprise; and traceability, which essentially provides user with “breadcrumbs” allowing them to look back throughout all the steps that were taken in a process.

For details see: Pharmaceutical Online

Posted by Dr. Tim Sandle

Monday, 9 October 2017

Sterilization: Practical Approaches


A new e-book has been published: Sterilization: Practical Approaches offers practical approaches to sterility testing, Gamma Irradiation for single use disposables, sterilization using EtO and dry heat, ophthalmic preparations and contamination control.

The content is:
  • Compliance Aspects of Sterility Testing
  • Ensuring Sterility: Autoclaves, Wet Loads and Sterility Failures
  • Preparing for Regulatory Inspections of Sterile Facilities: The Focal Points
  • Biological Indicators for Steam Sterilization: Failure Investigations
  • Containment System Sterility
  • Sterility Test Failure Investigations
  • Variations in the Resistance of Biological Indicators used to Assess Sterilization

The reference is:

Sandle, T. (2017) Sterilization: Practical Approaches, PDA/DHI, River Grove, Il, USA.

For further details see: PDA

Posted by Dr. Tim Sandle

Sunday, 8 October 2017

Digital colony counters making microbiology easier


For microbiologists the process of counting bacterial colonies can be tedious and mistakes can happen. Laboratory managers are turning attention to automated, digital devices to streamline processes.

Technology review by Tim Sandle

The ‘lean’ laboratory is one of the buzz phrases in terms of the management of quality control functions inside many healthcare and pharmaceutical facilities. The “lean labs” approach “focuses on cost control, improving sample throughput, and reviewing whether each sample tested adds value or produces meaningful information.” One example of how this might be realized is through the application of digital, automated colony counters.
Many pharmaceutical companies have successfully implemented automatic colony counters, such as Evans Vanodine, which ran a successful study with technology company Symbiosis. A second successful example of implementation was at the Murdoch Childrens Research Institute. With the latter case, the laboratory commented digitalization had addressed “errors introduced during the manual counting process and recording of information” as well as leading to a “significant reduction in time taken to analyze colony counting data.”
Colony counting is the mainstay of many microbiology laboratories. Microbial culture media in the form of semi-solid agar is used to grow up microbial colonies of enumeration. Many microbiological techniques rely on accurate determination of colony forming units (CFUs). For many large laboratories hundreds to thousands of plates require counting each day, after incubation. This is not only repetitious (and arguably a waste of time for employed graduate scientists) it can lead to errors and thus problems of data integrity. In low count assays minor counting errors will have significant effects. A second type of error is when numbers of CFUs on a plate can lead to false results due to overcrowding of bacteria.
Salmonella growing on XLD agar. Xylose lysine deoxycholate agar (XLD agar) is a selective growth med...
Salmonella growing on XLD agar. Xylose lysine deoxycholate agar (XLD agar) is a selective growth medium used in the isolation of Salmonella and Shigella species from clinical samples and from food.
Graham Beards
The colony counting process can, however, be automated with digital capture and counting of colonies and there are several big players in this emerging market. Examples include bioMerieux’s EasyCount 2 - EC2 and the ProtoCOL automated counter series. In addition, there is the Whitley aCOLyte (Synbiosis, Cambridge, UK) and the AID BacSpot (AID, Strassberg, Germany).
In terms of functionality, automated colony counters offer:
Standardized and accurate results. Accuracy is important since colony counting can be affected by numerous parameters related to the physical properties of the colony: size, shape, contrast, and overlapping colonies. To achieve this requires automatic colony separation (for when colonies are positioned close to each other).
Ability to count colonies within appropriate parameters (such down to 50 microns and measure zones accurately to 0.5 millimeters, within detection limits of 0.1 millimeters).
Ability to visualize white light and fluorescent colonies.
The ability to count the entire plate or sectors of the plate.
Results obtained within one second per plate.
The display of real-time full-color on-screen images.
Zoom function for looking at smaller colonies.
Software to allow for data collection and analysis. Data should ideally be transferrable to a Laboratory Information Management System (LIMS).
A technician viewing agar plates on a colony counter  Tim Sandle s laboratory.
A technician viewing agar plates on a colony counter, Tim Sandle's laboratory.
The essential elements of automated, digital colony counters include a circular dark field illuminator and a camera with a resolution of 3.3 megapixels or higher (many systems have cameras of higher quality); software with appropriate algorithms; an automated plate holder (with a toolbox to enable communication between the software and the image analyzer). With the software algorithm many work on the basis of A Bayes classifier. This is a simple probabilistic classifier used to study the geometric properties such as ratio between major and minor axis of the group are used to verify the number of colonies contained in the group.

This inoculated MacConkey agar culture plate cultivated colonial growth of Gram-negative  small rod-...
This inoculated MacConkey agar culture plate cultivated colonial growth of Gram-negative, small rod-shaped and facultatively anaerobic Klebsiella pneumoniae bacteria.
CDC
Validation of automated colony counters is important. To ensure the validity of their data, microbiologists need to establish that their automated colony counting method is as accurate as a precise manual count before they implement any new process into their workflow
Weaknesses can occur where there are mixed colonies or, due to inhomogeneity of the agar thickness, discrimination is not possible for all areas of the plate. A further weakness is where confluent growth occurs. The light also needs to be right. These issues can be overcomes as a paper by Brugger and colleagues demonstrates. The researchers found that white light dark field illumination works well but a blue dark field illumination gave the best discrimination of all (“Automated Counting of Bacterial Colony Forming Units on Agar Plates”, published in PLoS One).
Digital, automated microbial colony counting fits well with the lean laboratory concept and current industry concerns with data integrity. It also makes the life of the laboratory technician easier.


Saturday, 7 October 2017

Understanding Biosafety Levels


The handling of any biological agent requires an understanding of the agent and the risk of exposure to personnel, the facility, and the environment. The U.S. CDC and the NIH have used risk assessment to develop four ascending biosafety levels of containment required for use with biological agents, as follows:

  • BSL 1 – work or processing involving well-characterized agents not known to cause disease in healthy adult humans, and of minimal potential hazard to personnel and the environment
  • BSL 2 – working with or processing agents of moderate potential hazard to personnel and the environment
  • BSL 3 -- processing or handling of indigenous or exotic agents that may cause serious or potential lethal disease as a result of exposure by the inhalation route
  • BSL 4 –working with or processing a dangerous and exotic agent that poses a high individual risk of aerosol-transmitted laboratory infection and life-threatening disease.


In April 2002, the NIH published guidelines specifically directed at the industry that took a similar approach, but with more detail, called NIH Guidelines on Recombinant DNA:

  • Risk Group 1 (RG1) – the agents used are not associated with disease in healthy adult humans
  • Risk Group 2 (RG2) – the agents are associated with human disease that is rarely serious and for which preventive or therapeutic interventions are often available
  • Risk Group 3 (RG3) – the agents are associated with serious or lethal human disease for which preventive or therapeutic interventions may be available
  • Risk Group 4 (RG4) – the agents are likely to cause serious or lethal human disease for which preventive or therapeutic interventions are not usually available


This is an extract from an interesting article by Herman F. Bozenhardt and Erich H. Bozenhardt. The full text is available on Pharmaceutical Online.

Posted by Dr. Tim Sandle

Friday, 6 October 2017

Europe and U.S. Regulators Increase Cooperation on Inspections


The European Commission, the FDA, and the European Medicines Agency (EMA) have signed a new confidentiality agreement that allows regulators on both sides of the Atlantic to share non-public and commercially confidential information, including trade secrets about inspections.


The new agreement formally recognizes that FDA's EU counterparts have the authority and demonstrated ability to protect the relevant information, according to the EMA statement.

“This step now allows the sharing of full inspection reports, allowing regulators to make decisions based on findings in each other’s inspection reports and to make better use of their inspection resources to focus on manufacturing sites of higher risk.”

Posted by Dr. Tim Sandle

Thursday, 5 October 2017

Epigenetic drugs show promise as antivirals


Some epigenetic pharmaceuticals have the potential to be used as broad spectrum antivirals, according to a new study. The study demonstrated that histone methyltransferases EZH2/1 inhibitors, which are being used in cancer clinical trials, have activity against a variety of viruses, including herpes simplex virus (HSV).

Many DNA viruses, including HSV, are subject to epigenetic regulation where productive infection, persistence, and latency are determined, in part, by the modulation of chromatin associated with viral genomes. For a number of years, research laboratories including that of Thomas Kristie, PhD, a principal investigator in the Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, have focused on studying the epigenetic regulation of HSV. The virus impacts a significant proportion of the world's population, and primary infection and subsequent recurrent reactivation can result in disease ranging from mild lesions to severe ocular or neurological damage.

EZH2/1 are histone-lysine N-methyltransferase enzymes that are epigenetic repressors that suppress gene transcription via propagation of repressive H3K27me3 enriched chromatin domains. Currently, multiple EZH2/1 inhibitors are being developed and evaluated in cancer clinical trials. "Some specific cancers are based on "gain of function" mutations in EZH2. Additionally, it has been proposed that in some cancers, these enzymes repress anti-oncogenes and treatment with EZH2/1 inhibitors might result in re-expression of these anti-oncogenes." said Dr. Kristie.

In the new study, researchers evaluated the impact of a series of these EZH2/1 inhibitors on HSV. Given that EZH2/EZH1 has been implicated in repression of herpesvirus gene expression, the researchers expected to see induction of viral gene expression. However, they found instead that the inhibitors resulted in reduced HSV gene expression and lytic infection in vitro and in vivo.

See:

Jesse H. Arbuckle, Paul J. Gardina, David N. Gordon, Heather D. Hickman, Jonathan W. Yewdell, Theodore C. Pierson, Timothy G. Myers, and Thomas M. Kristie. Inhibitors of the Histone Methyltransferases EZH2/1 Induce a Potent Antiviral State and Suppress Infection by Diverse Viral PathogensmBio, July/August 2017 DOI: 10.1128/mBio.01141-17

Posted by Dr. Tim Sandle