Wednesday, 31 December 2014

Ciliopathies and human diseases


Cilia, microscopic, tentacle-like extensions from biological cells, have risen from relative obscurity and are now considered important to the understanding of many human afflictions. Ciliopathies often make themselves known as syndromes with widely varying effects on a number of tissue types. This is the subject of a new study.

There are number of human diseases in which cilia may play a role; for example, some cancers and neurological diseases may be related to ciliopathies. Because of the limitations placed on research involving humans, the authors propose the use of model species ranging from the green alga Chlamydomonas to the house mouse to further study the role of cilia. The study authors write, "We can anticipate that new and improved techniques will open new avenues for gaining further insight into these immensely important and ever more fascinating cell organelles."

For details see:

Jason M. Brown and George B. Witman. Cilia and Diseases. BioScience, December 2014 DOI: 10.1093/biosci/biu174


Posted by Tim Sandle

Tuesday, 30 December 2014

Gut microbes and the blood-brain barrier

Gut microbes appear to influence the development of the blood-brain barrier in mice, before and soon after they’re born, according to a study published in Science Translational Medicine.

“It’s absolutely fascinating to think that gut bacteria can control permeability of the blood-brain barrier,” Caltech microbiologist Sarkis Mazmanian, who was not involved in the study, told The Scientist.

The blood-brain barrier (BBB), which shields the organ from blood-borne infections, toxins, and more, is created by steadfast connections called tight junctions between the endothelial cells that line its blood vessels. So effective is the barrier that most proteins and molecules cannot pass through; those that do generally require selective transport via specific receptors.

A similar barrier—made up of epithelial cells and tight junctions—lines the intestine and stops the trillions of microbes present in the gut from escaping into the body. It’s known that the gut bacteria themselves control integrity of this intestinal barrier, said Sven Pettersson of the Karolinska Institute in Sweden who led the new study.

The team compared development of the BBB between germ-free fetal mice and those with normal microbiomes. As expected, the mice with normal microbiomes exhibited normal closure of the BBB toward the late stages of fetal development—a traceable antibody that could be detected readily entering the brain in the early fetus became restricted to blood vessels later on. In the fetuses whose mothers were germ-free, however, the antibody continued to enter brain tissue even late in pregnancy.

This increased barrier permeability was associated with low expression and disorganization of tight junction proteins and was shown by additional methods to persist into adult life. That is, pups that were born to germ-free mothers and that remained germ-free throughout life had leakier BBBs as adults.

Reference:

V. Braniste et al., “The gut microbiota influences blood-brain barrier permeability in mice,”Science Translational Medicine, 6:263ra158, 2014.


Posted by Tim Sandle

Monday, 29 December 2014

Understanding bacterial toxins target human cells will help develop new drugs

New drugs  and treatment strategies will be developed from research that provides a new understanding of how bacterial toxins target human cells.

Cholesterol-dependent cytolysins (CDCs) are toxins produced by major bacterial pathogens, most notably Streptococcus pneumoniae and group A streptococci, which collectively kill millions of people each year.
The toxins were thought to work by interacting with cholesterol in target cell membranes, forming pores that bring about cell death.

Bacteria invest energy into creating these toxins because they act as virulence factors. By targeting immune cells such as macrophages the bacteria will be protected against phagocytosis and destruction by respiratory burst. The presence of cholesterol in the membrane of the target cell is required for CDC pore formation. The arrangement of cholesterol molecules in the bilayer is important for successful binding

Published in the journal Proceedings of the National Academy of Sciences, the research is an international collaboration between Professor James Paton from the University of Adelaide in South Australia and Professor Michael Jennings from Griffith University, and collaborators at the University of Queensland and Department of Microbiology, New York University School of Medicine.

To access, go to PNAS

Posted by Tim Sandle

Sunday, 28 December 2014

GMPs for food products: disinfection


A new paper of interest by Sofija Petkovska1 and Biljana Gjorgjeska, in relation to food hygiene control, published in Journal of Hygienic Engineering and Design.

The abstract reads:

The usage of different disinfectants in the food and pharmaceutical industry provides a possibility for application of certain level of assurance related to microbiological cleanness by using different types of disinfectants which have different spectrum of operation. Used disinfectants residues which stay on the critical points of the equipment after cleaning become potential contaminants of the products and they can be unsafe for the users’ health. Because of this reasons, the Good Manufacture Practice standards recommend validation of the production equipment cleaning procedures including the aspects of microbiological cleanness
and determination of residues of disinfectants.

According to the Republic of Macedonia regulation acts, an application of HACCP system is recommended which will provide safe food with good quality. The methods and control points described in the general principles of this standard are internationally recognized and are from essential meaning. We would recommend in the control of the residues of disinfectants the general principles of HACCP to be used together with the principles of Good Manufacture Practice (GMP) which is well known standard recommended for pharmaceutical production. The validation plan should include determination of the residue quantity of the disinfectant after cleaning with the disinfectant used. The control method for determination of the residue quantity depends on the chemical characteristics of the disinfectant used. In general, specific methods that are sensitive and give possibility for the detection and quantification of selected disinfectant should be used.

Foe details, see food micro.

Posted by Tim Sandle

Saturday, 27 December 2014

Single use systems



BioPharm have issued a free e-book on single-use technology.

In the guide, the authors discuss trends in single-use bioreactors, disposable chromatography, and best practices for reducing particulates in single-use systems. In addition, budgeting and sourcing single-use components from multiple suppliers is explored. The latest technologies introduced for single-use applications are also explored.

Issue topics include:
  • Best Practices for Reducing Particulates in Single-Use Systems
  • Trends in Single-Use Bioreactors
  • Advances in Disposable Chromatography
  • Budgets for Single-Use Systems
  • Sourcing Single-Use Components
  • New Single-Use Technologies Roundup

For details see BioPharm

Posted by Tim Sandle

Friday, 26 December 2014

New E-Book: Analytical and Bioanalytical Testing


The editors of Pharmaceutical Technology review best practices and methods for analytical and bioanalytical testing. Topics include method transfer during scale up, viral contamination detection, analytical quality by design, screening methods for compliance with USP <232>, and validation of a bead-based multiplexed kit for quantification of nine different cytokines. A roundup of analytical instruments, systems, and software introduced in 2014 will be included.

Issue topics include:
  • Rapid Screening of Pharmaceutical Materials for Compliance with USP<232> using ICP-MS
  • Validation of a Multiplex Bead-Based Assay for the Quantification of a Panel of Nine Cytokines to be used for Clinical Sample Analysis
  • Method transfer during scale up
  • Viral contamination detection
  • Analytical Quality by Design
  • New Analytical Technologies Roundup
For details, see: Pharm Tech

Posted by Tim Sandle

Thursday, 25 December 2014

Precise measurements of microbial ecosystems

Biologists have described the complex relationships within an ecosystem through a new model. The model ecosystem was a “biological wastewater treatment plant”. In it live numerous species of bacteria which are involved in the wastewater purification process.

For the analyses of the treatment plant ecosystem, the researchers employed Systems Biology methods. Wastewater destined for treatment comprises energy-rich substrates including fats, proteins, carbohydrates and many other substances that serve as nutrients for the resident bacteria. Every wastewater treatment plant is therefore a complex ecosystem.

The basis for this are the so-called "omics" -- genomics, transcriptomics, proteomics and metabolomics -- combined with new bioinformatic methods for integrated data analysis.

There is one species of bacteria that stands out and has grabbed the researchers' attention: Microthrix parvicella, whose genome sequence the LCSB group first decrypted two years ago. This bacterium can absorb and store an especially large amount of lipids. In winter, up to 50 percent of all bacteria on the surface of treatment tanks belong to this species.

The implication is that the lipids from wastewater stored in the bacteria are a renewable energy source since they can be easily converted into biodiesel.

For further details see:

Emilie E. L. Muller, Nicolás Pinel, Cédric C. Laczny, Michael R. Hoopmann, Shaman Narayanasamy, Laura A. Lebrun, Hugo Roume, Jake Lin, Patrick May, Nathan D. Hicks, Anna Heintz-Buschart, Linda Wampach, Cindy M. Liu, Lance B. Price, John D. Gillece, Cédric Guignard, James M. Schupp, Nikos Vlassis, Nitin S. Baliga, Robert L. Moritz, Paul S. Keim, Paul Wilmes. Community-integrated omics links dominance of a microbial generalist to fine-tuned resource usage. Nature Communications, 2014; 5: 5603 DOI: 10.1038/ncomms6603

Posted by Tim Sandle

Wednesday, 24 December 2014

Risk based environmental monitoring webinar


Stay current with industry best practices for Environmental  Monitoring. Join us for an educational webinar on how  to implement a Risk-Based approach with your current Environmental Program.  

Topics covered include:
  • Proven risk assessment techniques designed to develop or simply fine-tune your EM program.
  • How the use of environmental monitoring software improves your program through continuous monitoring ensuring a state of control.
  • Actual case studies that illustrate examples of key concepts.
  • How to achieve Lean Manufacturing through the use of such techniques.
Speakers:
Dr. Tim Sandle, Experienced Microbiologist, Quality Professional, Auditor & Technical Writer
Ilona Endisch , Associate Director of Product Innovation at Novatek International

Registrations will open in January 2015, however please  reserve your place today. We look forward to having you join us at this event!

Event organized by Novatek International:

To register, go to Novatek.


Posted by Tim Sandle

Merry Christmas


Thank you for supporting Pharmaceutical Microbiology this year.

I'd like to wish all readers the best for the holiday season.



Tim Sandle

Tuesday, 23 December 2014

One kiss holds 80 million bacteria

A healthy dose of microbes are swapped between kissing couples, according to a study published in Microbe.

Researchers in Amsterdam swabbed the mouths and collected saliva from 21 couples visiting a zoo in the city both before and after they shared 10-second kiss. They found that the couples tended to have similar microbes inhabiting their mouths, likely because they share kisses, food, and space on a regular basis.

Apparently, being with somebody for an extended amount of time and having a relationship leads to a similar collection of bacteria on the tongue (reference: Time.)

When the researchers had one partner sip a probiotic yogurt drink, which contains bacteria not normally present in the mouth, prior to kissing their mate again, they found that an average of 80 million bacteria were swapped between kissers.

Posted by Tim Sandle

Monday, 22 December 2014

Antibiotic action: India and U.K.

UK Science & Innovation Network, India and the Royal Society of Chemistry have put together a report of interest. The report is titled: “Report on the UK-India Workshop and Roundtable on Mitigating Anti-microbial Resistance (AMR) and Controlling Infectious Diseases.”

The report is based on a meeting between the two bodies.

The key finding is:

“R&D in Central Nervous System (CNS) and antimicrobials has decreased significantly over the last 20 years globally. There is declining interest among Indian and global pharma companies to undertake research in AMR drug discovery due to the long gestation period, low returns and lack of expertise. For example, most drug discovery chemists do not understand the biology of the disease. There are fewer number of infectious diseases biologists in India.”

The report can be accessed here: Antibiotics

Posted by Tim Sandle

Sunday, 21 December 2014

The gliding mechanism of Mycoplasma gallisepticum

The ability to move enables many mycoplasmas and bacteria to reach a specific niche or to leave hostile environments. The organism Mycoplasma gallisepticum is a poultry pathogen that is capable of gliding over solid surfaces. Scientists have now identified the proteins responsible for this gliding mechanism.
Mycoplasma gallisepticum is related to the human pathogen Mycoplasma pneumoniae, the causative agent of human bronchitis and pneumonia. Researchers have found that its abilityto glide requires the proteins GapA, CrmA and Mgc2.

For further details see:

Ivana Indikova, Martin Vronka, Michael P Szostak. First identification of proteins involved in motility of Mycoplasma gallisepticum. Veterinary Research, 2014; 45 (1): 99 DOI: 10.1186/s13567-014-0099-2

Posted by Tim Sandle

Saturday, 20 December 2014

Understanding how Pseudomonas aeruginosa infects

One of the world's most prolific bacteria, Pseudomonas aeruginosa, manages to afflict humans, animals and even plants by way of a mechanism not before seen in any infectious microorganism -- a sense of touch. Pseudomonas is the first pathogen found to initiate infection after merely attaching to the surface of a host.

The researchers found, however, that the bacteria could not infect another organism when a protein on their surface known as PilY1 was disabled.

To demonstrate the bacteria's wide-ranging lethality, Siryaporn infected ivy cells with the bacteria then introduced amoebas to the same sample; Pseudomonas immediately detected and quickly overwhelmed the single-celled animals.

For further details, see:

Siryaporn, S. L. Kuchma, G. A. O'Toole, Z. Gitai. Surface attachment induces Pseudomonas aeruginosa virulence. Proceedings of the National Academy of Sciences, 2014; DOI: 10.1073/pnas.1415712111

Posted by Tim Sandle

Friday, 19 December 2014

Last-line drug resistance poses 'alarming' European health threat

More and more infections in Europe are proving able to evade even the most powerful antibiotics, posing an alarming threat to patient safety in the region, health officials said  recently.

Releasing annual data on antibiotic resistant superbugs, the European Centre for Disease Prevention and Control (ECDC) said bacterial infections resistant to carbapenems - a major last-line class of antibiotics used to treat hospital-acquired superbugs - are ever more common in the European Union.

"With a smaller number of effective antibiotics, we are gradually returning to the 'pre-antibiotic era' when bacterial diseases could not be treated and most patients would die from their infection," said Marc Sprenger, the ECDC's director.

The Stockholm-based ECDC also said it had for the first time collected data on resistance among infections caused by a bacteria called Klebsiella pneumoniae to a powerful but older antibiotic known as colistin - and had found alarming signs.

"According to our data, resistance to colistin was observed in 5% of Klebsiella pneumoniae isolates for the EU overall," Sprenger said.

Klebsiella pneumoniae is a common cause of pneumonia, urinary tract and bloodstream infections in hospital patients. If antibiotics are unable to treat them effectively, patients can face long, costly stays in hospital, and risk dying.

Colistin is a last-resort antibiotic developed several decades ago that has serious side effects and limitations to its use, but has become essential for treating carbapenem-resistant Klebsiella pneumoniae infections.

Drug resistance is driven by the misuse and overuse of antibiotics, which encourages bacteria to evolve to survive and develop new ways of beating the drugs.

It has been a feature of medicine since Alexander Fleming's discovery of penicillin in 1928, but has become a major global health threat as new drug development has failed to keep pace with the bugs' ability to develop resistance to them.

The ECDC data showed an increase of carbapenem resistance in Klebsiella pneumoniae to a population-weighted EU average percentage of 8.3% in 2013 from 4.6% in 2010.

Vytenis Andriukaitis, Europe's commissioner for health and food safety, said the near doubling of resistance in some bacteria in three years was "truly alarming" and illustrated the need to tackle the issue from all directions.

"Antimicrobial resistance is one the most pressing public health issues of our time," he said in a statement as the data were published.

For further details see: European Commission

Posted by Tim Sandle

Thursday, 18 December 2014

Timeline report for superbug research


A new report which sets out the foundation for future research into anti-microbial resistance (AMR) has been published by the Medical Research Council (MRC). The report tells the story of key research achievements over the past thirty years, showcasing some of the best advances and providing the groundwork for a cross-Council collaboration on AMR research.

Antimicrobial resistance is a huge and complex problem for healthcare and agriculture. Antibiotics have been used to treat bacterial infections in humans and animals for 70 years, but these medicines are becoming less and less effective. No new classes of antibiotics have been discovered for 25 years and some strains of bacteria are now unharmed by the drugs designed to kill them.

In the UK alone £275 million has been spent on research in this area since 2007, yet, to date, no effective solutions have been found. It has been estimated that current antibiotics may be useless within the next two decades.

The UK Research Councils have joined together in an historic initiative to tackle this global problem. Coordinating a network of medical researchers, biologists, engineers, vets, economists, mathematicians and designers, the MRC will help to drive through new discoveries and advancements.

The AMR initiative, which has been heralded as a war cabinet for AMR research, pulls together all seven research councils and looks to deliver exciting new research projects on four fronts:
  • Understanding resistant bacteria in the context of the host.
  • Accelerating therapeutic and diagnostics development.
  • Understanding the real world interactions.
  • Behaviour within and beyond the health care setting.
  • The report published today offers a timeline and case studies in each area supported by the Biotechnology and Biological Sciences Research Council (BBSRC), Engineering and Physical Sciences Research Council (EPSRC) and the Medical Research Council (MRC). From how American Bullfrogs might help to treat wounds infected with MRSA, to how a smartphone app helps healthcare professionals choose the best course of treatment to ensure antimicrobials are prescribed appropriately, the report provides a shop window on AMR research.
Dr Des Walsh, Head of Infections & Immunity at the Medical Research Council (MRC) said: “Years of research mean that we are now in a better position than ever to get to the bottom of how and why some bugs are resistant to antibiotics. But we need to understand AMR at every level and in every environment – from labs to livestock, from finding new diagnostic tools to educating professionals and the public, which is why the MRC is leading the Funders’ Forum and working with all of the research councils providing millions in support to the best research projects designed to beat this problem.”

For further details, see MRC

Posted by Tim Sandle

Wednesday, 17 December 2014

Are alcohol wipes effective in the presence of protein?

Research suggests that alcohol wipes are capable of destroying the widest range of microbial contamination
(including Mycobacteria, the genus of bacteria that includes the infectious cause of tuberculosis). Alcohol wipes are virucidal against ‘enveloped’ viruses, such as HIV and hepatitis B and against the ‘non-enveloped’ viruses, such as poliovirus, rhinoviruses and hepatitis A. However, in addition to microbial contamination, surfaces may also be contaminated with protein residues such as blood and pus. It has been suggested that alcohol may bind protein to stainless surfaces and the presence of protein may compromise the efficacy of alcohol based wipes.

This issue is the basis of an article by Tim Sandle. The reference is:

Sandle, T. (2014) Are alcohol wipes effective in the presence of protein?, The Dentist, October 2014, pp92-94

A similar article,. outlining good cleaning practices has also been published:

Sandle, T. (2014) Keeping surfaces microbe free, Dental Nursing (Infection Control), October 2014, p1

For a copies, please contact Tim Sandle


Posted by Tim Sandle

Tuesday, 16 December 2014

European Pharmacopeia - Preparation of Sterile Products

Chapter 5.1.1 of the European Pharmacopeia is undergoing review and a draft has been published in Pharm Europa, titled “Methods of Preparation of Sterile Products.”

In relation to the changes:
  • In the introduction, the reference to GMP has been removed;
  • In the section Sterility assurance level, the reference to exponential inactivation has been removed as membrane filtration is not a first order process;
  • The sections on the different sterilisation processes, where appropriate, now have the same format: principle, equipment, sterilisation cycle, cycle effectiveness and routine control; where required, relevant information has been added;
  • Modern concepts for validation of steam sterilisation have been added;
  • A wider description of the equipment suitable for dry heat sterilisation has been provided;
  • In the section Ionising radiation sterilisation, the reference to European Notes for Guidance
  • has been removed;
  • In the section Gas sterilisation, two different types of agents are defined: alkylating agents and oxidising agents. The establishment of the cycle effectiveness has been described in more detail;
  • In the section Membrane filtration, the description of the microbial challenge test has been removed as it is proposed for inclusion in the revised chapter on biological indicators;
  • In the section Aseptic preparation, freeze-drying under aseptic conditions is added.

The draft can be found in Pharmeuropa edition 26.4

Posted by Tim Sandle

Monday, 15 December 2014

Spectrophotometric particle counters

Spectrophotometric particle counters are the main item of cleanroom monitoring technology to have emerged in recent years. The counters can differentiate inert particles from ‘biologic’ particles (where biologic may indicate a microorganism). This article outlines a summary of a study that examined the application of spectrophotometric particle counters for the risk assessment of a cleanroom that underwent deactivation and reinstatement cleaning. The study demonstrates how establishing a particle and biologic particle baseline can provide useful information to compare the environmental condition of a cleanroom pre- and post-maintenance shutdown.


This is the basis of a new article by Tim Sandle for Clean Air and Containment Review. The reference is:

Sandle, T. (2014) Applying spectrophotometric monitoring to risk assessments in biopharmaceutical cleanrooms, Clean Air and Containment Review, Issue 20, pp22-25

The current issue also features a discussion on the application of ventilation equations to cleanrooms, by Bill Whyte and colleagues; a discussion on the chemical influence on ISO 14644 standards by Dick Gibbons; the history of isolator technology by Doug Thorogood; and the history of ultra clean operating theatres by Amanda Parkin…and more.

For details see CACR


For details about Tim Sandle’s study, please contact him directly.

Posted by Tim Sandle

Sunday, 14 December 2014

Order of incubation for culture media used for environmental monitoring


A research paper of interest:

Examination of the order of incubation for the recovery of bacteria and fungi from pharmaceutical-grade cleanrooms.

By Sandle T.

Abstract

A study was undertaken to compare microbial recoveries from pharmaceutical-grade cleanrooms using two different incubation regimes and a general-purpose agar (Tryptone Soy Agar). One temperature regime (A) incubated plates first at 30 degrees C to 35 degrees C, followed by 20 degrees C to 25 degrees C; the second temperature regime (B) began the incubation with plates at 20 degrees C to 25 degrees C, followed by 30 degrees C to 35 degrees C. The experimental outcomes demonstrated that there was no significant difference with the total microbial count when measured using a t-test (0.05 significance level; 95% confidence interval). However, with the recovery of fungi, the second incubation regime (B), which began with the lower 20 degrees C to 25 degrees C temperature, produced higher incidents and numbers of fungi. While this finding might provide the basis for adopting one incubation regime over another, a review of the types of cleanrooms recovering fungi suggests that fungal incidents are low, and they are more often confined to specific areas. Thus, as an alternative, incubation regimes could be varied to suit different cleanroom environments or a selective mycological agar adopted for specific areas.

Published in:  2014 May-Jun;18(3):242-7.

For further details or to request a copy, please contact: Tim Sandle

Mutated flu concerns

About half of the H3N2 influenza samples tested in the United States encode altered antigens from the strain used to produce this year’s vaccine.

While widespread vaccination is still the best defense against the influenza virus, the US Centers for Disease Control and Prevention (CDC) warned recently that many of this year’s circulating strains are different from the ones used to formulate the annual flu vaccine.

So far this season, more than 90 percent of the reported flu cases in the US are of the H3N2 subtype, and 52 percent of the samples tested have mutations in antigen-encoding genes compared to the sample used to produce the annual vaccine.

For further details, see The Scientist.

Posted by Tim Sandle

Saturday, 13 December 2014

Keeping healthcare facilities clean

Keeping healthcare facilities clean is an issue of great importance. In an interesting review for Controlled Environments, outlines some of the key issues for the avoidance of microbial contamination. These are:

1.      Housekeeping – “Bacteria and germs can hide in surprising places: one national study found that soap dispensers – more specifically, the nozzle users press to obtain soap – harbored more bacteria and germs than toilet seats.”
2.      Plant maintenance – “In 2001 the largest historic outbreak of Legionnaire’s disease is estimated to have sickened more than 800 in Murcia, Spain. Subsequent investigation linked the outbreak to a hospital cooling tower.”
3.      Codes or a higher standard of care – “In designing new or renovated healthcare spaces, serious consideration should be given to the level of desired design, based upon the function of the space, its clinical program, and the risk of HAIs.”
4.      Humidity control – “Humidity levels play a major role in maintaining health and avoiding impacts from bacteria, viruses, fungi, mites, molds, and chemical interactions.”
5.      Air – “The pinnacle of superior air quality depends upon the volume of new air circulating in a space, dilution, carefully calibrated filtration and, where appropriate, either positive or negative pressurization.”

The article can be read in full here.

Posted by Tim Sandle

Friday, 12 December 2014

The coming crisis in antibiotics - TED talk

Antibiotic drugs save lives. But we simply use them too much — and often for non-lifesaving purposes, like treating the flu and even raising cheaper chickens. The result, says researcher Ramanan Laxminarayan, is that the drugs will stop working for everyone, as the bacteria they target grow more and more resistant. He calls on all of us (patients and doctors alike) to think of antibiotics — and their ongoing effectiveness — as a finite resource, and to think twice before we tap into it. It’s a sobering look at how global medical trends can strike home.

To view the video and for details see: TED

Posted by Tim Sandle

Thursday, 11 December 2014

TGA - Consultation: Interim guideline on antimicrobial resistance risk data

Australian health officials (Therapeutic Goods Administration) are seeking comments on the following document: “Interim guideline on microbial resistance risk data for antibacterial medicinal products.”

With guidance:

·         The data that should be included with applications to register a new antibacterial medicinal product or to extend use of products already registered, as set out in the draft document is:

·         Microbial resistance safety data, including data on the propensity for promoting resistance and cross-resistance, as a basic requirement for the assessment of all new antibacterial agents.

Human antibiotic-resistance prevalence data in the Product Information.

Bacterial resistance

The hazard with regard to details of bacterial resistance patterns in relevant microorganisms in vitro may be characterised by providing: – Minimum inhibitory concentration (MIC) data of the antibacterial agent against bacterial species likely to be affected. MIC distribution data should be presented for targeted bacterial species and for relevant non-targeted bacterial species. Estimated rates of development of the expression of resistance, such as indicated from in vitro studies of passaged microorganisms in the presence of the antibacterial agent, may be included. – Details of microbial resistance patterns in relevant human isolates which have emerged with the use of the antibacterial agent, or related substances, overseas and/or in Australia should be provided when available. This would include changes identified in MICs of the antibacterial agent against isolates of bacterial species likely to be affected collected from clinical trials or from wider clinical use. The risk assessment should state whether Australian data are included and Australian data should be provided where available and recent. Interim guideline on antibacterial resistance risk data

  • Data on mechanisms of resistance pathways in relevant microorganisms.
  • Data on in vitro cross-resistance with other antibacterial agents in the same class in targeted and non-targeted bacterial species.


Data on co-selection of resistance by unrelated antibacterial agents

Genetics of resistance

The genetics of resistance may be characterised by providing:
  • Data on resistance genes.
  • Location of resistance genes (chromosomal, transferable elements).
  • Data on transfer of resistance genes between bacterial species.

To access the document, see TGA

Posted by Tim Sandle

Wednesday, 10 December 2014

Advancing new tools to fill in the microbial tree of life

In a perspective piece published in the journal Science, Eddy Rubin, Director of the U.S. Department of Energy Joint Genome Institute (DOE JGI), a DOE Office of Science User Facility, along with Microbial Program Head Tanja Woyke, discusses why the time is right to apply genomic technologies to discover new life on Earth. In this perspective they propose the division of microbial life on Earth into three categories: explored, unexplored, and undiscovered. The first can be grown in the laboratory. The second encompasses the uncultivated organisms from environmental samples known only by their molecular signatures. The third, the focus of the perspective, is the yet-undiscovered life that up until now has eluded detection.

For details see:

T. Woyke, E. M. Rubin. Searching for new branches on the tree of life. Science, 2014; 346 (6210): 698 DOI: 10.1126/science.1258871

Posted by Tim Sandle

Tuesday, 9 December 2014

WHO revises non-sterile process validation

The World Health Organization (WHO) is revising its guidance on non-sterile processing validation. The guidance is titled “Revision of the Supplementary Guidelines on Good manufacturing Practice: Non-sterile process validation.”

The process of updating began in 2013. In August 2014 a new draft was circulated for comments. The final version is expected early in 2015.

Process validation data should be generated for all products to demonstrate the adequacy of the manufacturing process. The validation should be carried out in accordance with GMP and data should be held at the manufacturing location whenever possible and be available for inspection.

Central to the guidance is risk assessment, as the guidance states: “risk-based approach in validation is recommended. The use of in-line, online and/or at-line controls and monitoring are recommended to ensure that a process is in a state of control during manufacture.”

The current draft can be viewed here: WHO

Posted by Tim Sandle

Monday, 8 December 2014

Microbiological Monitoring Roundtable

For someone concerned with return on investment (RoI) in pharmaceutical manufacturing, how does microbiological monitoring relate to product quality?

Recently American Pharmaceutical Review conveyed a panel of experts to discuss this important issue. The expert panel were:


The thoughts and opinions of these microbiologists can be read here




Posted by Tim Sandle

1 million visits

This blog - Pharmaceutical Microbiology - was formed 5 years ago this week. The blog has, for the most part, delivered a daily posting of relevance to pharmaceuticals, healthcare or to microbiology.

Coinciding with this anniversary I'm also please to announce that the site has received over 1 million page views.

Thank you for supporting this website. It exists as a service for pharmaceutical microbiologists and it relies upon your support and interest.

Thanks again.



Tim Sandle


Sunday, 7 December 2014

How cells defend themselves against antibiotics

ABC Transporters are proteins that are embedded in the cell membrane and facilitate the transport across cellular barriers not only of an almost unlimited variety of toxic substances, but also of substances that are essential for life. They also play a role in the development of antibiotic resistance. A research group has now succeeded in elucidating the detailed structure of this transporter.

For details see:

JungMin Kim, Shenping Wu, Thomas M. Tomasiak, Claudia Mergel, Michael B. Winter, Sebastian B. Stiller, Yaneth Robles-Colmanares, Robert M. Stroud, Robert Tampé, Charles S. Craik, Yifan Cheng. Subnanometre-resolution electron cryomicroscopy structure of a heterodimeric ABC exporter. Nature, 2014; DOI: 10.1038/nature13872

Posted by Tim Sandle