Saturday, 31 August 2013

Barrier systems

Barrier systems run the spectrum from simple process demarcation devices to full physical barriers, as is the case with isolators. With global expansion, the need to create well defined and controllable manufacturing environments, quickly and efficiently, has rekindled interest in isolator designs. Restricted access barriers (RABs) represent one of the fastest growing technology solutions for products that cannot be terminally sterilized.

Bikash Chatterjee has provided a brief overview of the technology for Controlled Environments, which can be read on-line.

Posted by Tim Sandle

Friday, 30 August 2013

ATCC webinar for teaching labs

ATCC are running a webinar aimed at setting up microbiological testing area within labs for schools or universities. The details are:

The academic year has begun, but are you ready for it? Let ATCC help you set up your lab! In this presentation, we will discuss some of our products designed with teaching laboratories in mind. We will also provide helpful information and key features about our Culture Guides and the new Introduction to Microbiology Guide. Get your students on the fast track to success!

For details see ATCC

Posted by Tim Sandle

Thursday, 29 August 2013

FDA Guidance Update

According to the Federal Register, the Food and Drug Administration (FDA) has annoucned an initiative in the Center for Drug Evaluation and Research (CDER) involving the review of draft guidance documents issued before 2010 to determine their status, and to decide whether those guidances should be withdrawn, revised, or finalized with only minor changes.

CDER is withdrawing the following guidances:

1. “Manufacturing, Processing, or Holding Active Pharmaceutical Ingredients”—issued April 1998.

2. “Powder Blends and Finished Dosage Units—Stratified In-Process Dosage Unit Sampling and Assessment”—issued November 2003.

3. “Forms for Registration of Producers of Drugs and Listing of Drugs in Commercial Distribution”—issued May 2001.

4. “Disclosing Information Provided to Advisory Committees in Connection With Open Advisory Committee Meetings Related to the Testing or Approval of New Drugs and Convened by CDER, Beginning on January 1, 2000”—issued December 1999.

For information on the four preceding guidances, contact the Office of Compliance in CDER.

5. “Evaluating Clinical Studies of Antimicrobials in the Division of Anti-Infective Drug Products”—issued February 1997.

6. “Empiric Therapy of Febrile Neutropenia—Developing Antimicrobial Drugs for Treatment”—issued July 1998.

7. “Lyme Disease—Developing Antimicrobial Drugs for Treatment”—issued July 1998.

8. “Secondary Bacterial Infections of Acute Bronchitis—Developing Antimicrobial Drugs for Treatment”—issued July 1998.

9. “Streptococcal Pharyngitis and Tonsillitis—Developing Antimicrobial Drugs for Treatment”—issued July 1998.

10. “Uncomplicated Gonorrhea—Developing Antimicrobial Drugs for Treatment”—issued July 1998.

11. “Uncomplicated Urinary Tract Infections—Developing Antimicrobial Drugs for Treatment”—issued July 1998.

12. “Vulvovaginal Candidiasis—Developing Antimicrobial Drugs for Treatment”—issued July 1998.

13. “Bacterial Vaginosis—Developing Antimicrobial Drugs for Treatment”—issued July 1998.

14. “Acute Bacterial Meningitis—Developing Antimicrobial Drugs for Treatment”—issued July 1998.

15. “Acute or Chronic Bacterial Prostatitis—Developing Antimicrobial Drugs for Treatment”—issued July 1998.

16. “Developing Antimicrobial Drugs—General Considerations for Clinical Trials”—issued July 1998.

17. “Catheter-Related Bloodstream Infections—Developing Antimicrobial Drugs for Treatment”—issued October 1999.

For information on the preceding 13 guidances (number 5 through 17), contact the Office of Antimicrobial Products in the Office of New Drugs in CDER.

18. “Labeling Over-the-Counter (OTC) Human Drug Products—Updating Labeling in ANDAs”—issued February 2001.

For information on the preceding guidance (number 18), contact the Office of Drug Evaluation IV in the Office of New Drugs in CDER.

19. “Inhalation Drug Products Packaged in Semipermeable Container Closure Systems”—issued July 2002.

20. “Listed Drugs, 30-Month Stays, and ANDAs and 505(b)(2) Applications Under Hatch-Waxman, as Amended by the Medicare Prescription Drug, Improvement, and Modernization Act of 2003—Questions and Answers”—issued November 2004.

21. “Referencing Discontinued Labeling for Listed Drugs in Abbreviated New Drug Applications”—issued October 2000.

22. “Submission of Patent Information for Certain Old Antibiotics”—issued December 2008.
Show citation box
For information on the preceding four guidances (number 19 through 22), contact the Office of Pharmaceutical Science in CDER.

23. “Qualifying for Pediatric Exclusivity Under Section 505A of the Federal Food, Drug, and Cosmetic Act”—issued September 1999.

Posted by Tim Sandle

Wednesday, 28 August 2013

CDC Releases 2014 Edition of "Yellow Book"

The Centers for Disease Control and Prevention have released the online version of the 2014 edition of CDC Health Information for International Travel, commonly known as the “Yellow Book.” Nicknamed for its yellow cover, this is the ultimate guide for healthy international travel. The most recent version includes special guidance for people who will be living long-term in areas with malaria. The 2014 edition also expanded its chapter on select destinations, providing insiders’ knowledge and specific health risks about popular tourist destinations.

A team of almost 200 experts update this health guide every two years. The Yellow Book provides the latest official CDC recommendations to keep international travelers safe and healthy. It includes a complete catalog of travel-related diseases and up-to-date vaccine and booster recommendations. The information in the book does not just stop with infectious diseases; it also includes advice about preventing and treating common travel-related ailments such as altitude illness, motion sickness, and jet lag. The book offers useful tips on topics such as traveling with pets, packing a travel health kit, avoiding counterfeit medications in foreign countries, and getting travel health and evacuation insurance for emergencies. In addition, the Yellow Book provides advice for people traveling with young children, individuals with disabilities or chronic illnesses, and those traveling for humanitarian aid work or study abroad.

“International travel can be an incredible experience, but it has its risks and the hazards are ever-changing. The Yellow Book clearly and comprehensively gives the most updated health-related precautions and information for traveling internationally,” said Dr. Gary Brunette, chief of CDC’s Travelers’ Health Branch. “By following CDC recommendations, international travelers can stay healthy and safe so they can take full advantage of their traveling experiences.”

For further details see CDC

Posted by Tim Sandle

Tuesday, 27 August 2013

WHO: General guidance for inspectors on “hold-time” studies

The World Health Organisation (WHO) has issued the following document for comment: “General guidance for inspectors on “hold-time” studies revised draft for comment”.

According to the guideline: “Arrangements should exist to ensure that the dispensed starting and packaging materials used, intermediate products, bulk and finished products are stored under appropriate conditions. Storage should not have any negative effect on the processing, stability, safety, efficacy or quality of the materials, intermediate products and bulk products prior to final packing.”

Furthermore: “Good manufacturing practices require that the maximum allowable hold time should be established to ensure that in-process and bulk product can be held, pending the next processing step, without any adverse effect to the quality of the material.”

To access the draft, see WHO

The closing date for comments is 15 September 2013.

Posted by Tim Sandle

Monday, 26 August 2013

Guidance on manufacture of the finished dosage form

The European Medicines Agency (EMA) have issued a paper titled “Concept paper revision of the note for guidance on manufacture of the finished dosage form”.

The paper sets out to underline all aspects of manufacture that are important both for applicant and regulator.

To view the paper, see EMA.

Posted by Tim Sandle

Sunday, 25 August 2013

Molecular assembly of the aerolysin pore

A new research paper of interest, titled "Molecular assembly of the aerolysin pore reveals a swirling membrane-insertion mechanism."

Aerolysin is a cytolytic pore-forming toxin exported by Aeromonas hydrophila, a Gram-negative bacterium associated with diarrhoeal diseases and deep wound infections. The mature toxin binds to eukaryotic cells and aggregates to form holes (approximately 3 nm in diameter) leading to the destruction of the membrane permeability barrier and osmotic lysis.

Published in Nature Chemical Biology, this discovery offers an insight into the fight against pathogens that are increasingly resistant to antibiotics. The abstract reads:

"Aerolysin is the founding member of a superfamily of β-pore–forming toxins whose pore structure is unknown. We have combined X-ray crystallography, cryo-EM, molecular dynamics and computational modeling to determine the structures of aerolysin mutants in their monomeric and heptameric forms, trapped at various stages of the pore formation process. A dynamic modeling approach based on swarm intelligence was applied, whereby the intrinsic flexibility of aerolysin extracted from new X-ray structures was used to fully exploit the cryo-EM spatial restraints. Using this integrated strategy, we obtained a radically new arrangement of the prepore conformation and a near-atomistic structure of the aerolysin pore, which is fully consistent with all of the biochemical data available so far. Upon transition from the prepore to pore, the aerolysin heptamer shows a unique concerted swirling movement, accompanied by a vertical collapse of the complex, ultimately leading to the insertion of a transmembrane β-barrel."

Posted by Tim Sandle

Saturday, 24 August 2013

FDA Circular of Information for the Use of Human Blood and Blood Components

A new FDA guidance document has been issued "Circular of Information for the Use of Human Blood and Blood Components".

The circular provides specific labeling instructions for the administration and use of blood and blood components intended for transfusion. To view the document, see FDA.

Posted by Tim Sandle

Friday, 23 August 2013

The Role of Microbial Testing in Biopharmaceutical Manufacturing

"Critical to biopharmaceutical production is bioburden control and testing...The greatest risks to the product stream are;
  • Bacterial Endotoxins – A pyrogenic product (e.g., lipopolysaccharide) present in the bacterial cell wall. Endotoxin can lead to reactions in patients receiving injections ranging from fever to death.
  • Bacteria, yeast and mold – Microorganisms with the potential for growth in biopharmaceutical products. Gram-negative bacteria have the greatest potential for growth.
  • Mycoplasma – Microorganisms associated with plant and animal-derived materials lacking bacterial cell walls that have the ability to pass through 0.2 μm sterilising filters."
So writes Tony Cundell in an informative article titled "The Role of Microbial Testing in Biopharmaceutical Manufacturing".

To read more about the risks and risk mitigation measures, go to: Biopharm

Posted by Tim Sandle

Thursday, 22 August 2013

Bio-batteries as an alternative source of energy

What is a bacteria powered battery?

The answer is an environmentally friendly 'bio-battery' (or Microbial fuel cell -- MFC). This is a device which directly transforms bacteria into energy. Batteries such as these work in the same way as conventional batteries, but with one difference. The MFC consists of two separate units, the anode and the cathode components, just like the batteries now in current household use. A partly permeable membrane separates the two areas. In contrast to conventional batteries, however, there are bacteria in the anode area of the bio-battery instead of electrolytes.

These break down substrates, in this case glucose, in a metabolic process. This produces electrons that after starting from the anode are finally delivered in an external loop to the cathode. The external circuit is then the one with the battery-powered application, for example, for lights or small motors. In this way, bacteria can produce electric energy. The bio-battery offers an array of advantages.

Due to their simple construction they can be used in regions where there is shortage of electricity, for example, such as in developing countries. An advantage that the bio-battery has over other regenerative energy sources, such as solar and wind power is that they are not dependent on the weather. In the case of bio-batteries, the more nourishment the bacteria receive the more energy they produce. What is more, in theory bacteria are an inexhaustible source of energy as they multiply quickly when supplied with substrates.

Posted by Tim Sandle

Wednesday, 21 August 2013

Antibiotic resistance in probiotic bacteria

Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. The main probiotic bacteria are strains belonging to the genera Lactobacillus and Bifidobacterium, although other representatives, such as Bacillus or Escherichia coli strains, have also been used. Lactobacillus and Bifidobacterium are two common inhabitants of the human intestinal microbiota. Also, some species are used in food fermentation processes as starters, or as adjunct cultures in the food industry. With some exceptions, antibiotic resistance in these beneficial microbes does not constitute a safety concern in itself, when mutations or intrinsic resistance mechanisms are responsible for the resistance phenotype. In fact, some probiotic strains with intrinsic antibiotic resistance could be useful for restoring the gut microbiota after antibiotic treatment. However, specific antibiotic resistance determinants carried on mobile genetic elements, such as tetracycline resistance genes, are often detected in the typical probiotic genera, and constitute a reservoir of resistance for potential food or gut pathogens, thus representing a serious safety issue.

In relation to this important area, a paper titled "Antibiotic resistance in probiotic bacteria" has been written for the journal Frontiers in Antimicrobials (Front. Microbiol., 18 July 2013 | doi: 10.3389/fmicb.2013.00202).

For further details see: Frontiers.

Posted by Tim Sandle

Tuesday, 20 August 2013

Global health review

Kevin M. De Cock , Patricia M. Simone, Veronica Davison, and Laurence Slutsker have written an interesting overview of global health trends and key issues for Emerging Infectious Diseases.

The abstract reads:

“Global health reflects the realities of globalization, including worldwide dissemination of infectious and noninfectious public health risks. Global health architecture is complex and better coordination is needed between multiple organizations. Three overlapping themes determine global health action and prioritization: development, security, and public health. These themes play out against a background of demographic change, socioeconomic development, and urbanization. Infectious diseases remain critical factors, but are no longer the major cause of global illness and death. Traditional indicators of public health, such as maternal and infant mortality rates no longer describe the health status of whole societies; this change highlights the need for investment in vital registration and disease-specific reporting. Noncommunicable diseases, injuries, and mental health will require greater attention from the world in the future. The new global health requires broader engagement by health organizations and all countries for the objectives of health equity, access, and coverage as priorities beyond the Millennium Development Goals are set.”

The article can be accessed on-line here: CDC

Posted by Tim Sandle

USP Chapter 1115 Bioburden Control

After several years of discussion and debate the United States Pharmacopeia (USP) has issued a draft of a proposed new chapter: USP <1115> “Bioburden Control of Nonsterile Drug Substances and Products”. The draft has been released in the Pharmacopeial Forum July/August, 2013.

By appearing in the Pharmacopeial Forum the draft chapter is presented to the industry for comment, with a view to a final chapter being published sometime in 2014. The main basis to the chapter is the setting out of a risk-based approach to monitor and control of the manufacturing facility and process for non-sterile pharmaceutical products. These are important concerns for bioburden has been cited by the U.S. FDA in several warning letters over the past ten years in relation to batch rejection and recall*.

Scott Sutton has more information about the new chapter, including a link to a copy on the Microbiology Network: to view please click here.

*See: Sandle, T. (2012). Review of FDA warning letters for microbial bioburden issues (2001-2011), Pharma Times, Vol. 44, No.12, pp29-30

Posted by Tim Sandle

Monday, 19 August 2013

Could the ‘Black Death’ Become a Re-Emerging Infectious Disease?

Could the ‘Black Death’ Become a Re-Emerging Infectious Disease? This is the subject of an editorial for the Journal of Ancient Diseases & Preventive Remedies, written by Tim Sandle.

Here is an extract:

"Populations are still at risk of plague today. This is due to several reasons including transport and trade, and threats in developing countries where multi-drug resistant pathogens are currently emerging and spreading rapidly. These global problems would require responses at various intersecting levels of public health and political authority: global, national, and local."

The short article can be viewed on-line here.

The reference is:

Sandle T (2013) Could the ‘Black Death’ Become a Re-Emerging Infectious Disease? J Anc Dis Prev Rem 1: e104. doi: 10.4172/2329-8731.1000e104

For a pdf copy, please contact me.

 Posted by Tim Sandle

Sunday, 18 August 2013

Aseptic blow-fill-seal

Blow-Fill-Seal technology refers to the manufacturing technique used to produce small, (0.1mL) and large volume, (500mL +) liquid filled containers. The basic concept of blow fill seal (BFS) is that a container is formed, filled, and sealed in a continuous process without human intervention, in a sterile enclosed area inside a machine. Thus this technology can be used to Aseptically Manufacture sterile pharmaceutical liquid dosage forms.

The process is multi-stepped, firstly pharmaceutical-grade plastic resin is vertically heat extruded through a circular throat, to form a hanging tube called the Parison. This extruded tube is then enclosed within a two-part mould, and the tube is cut above the mould. The mould is transferred to the filling zone, or sterile filling space where filling needles mandrels are lowered and used to inflate the plastic to form the container within the mould. Following the formation of the container, the mandrel is used to fill the container with liquid, following filling the mandrels are retracted and a secondary top mould seals the container. All actions take place inside a sterile shrouded chamber inside the machine. The product is then discharged to a non-sterile area for labelling, packaging and distribution.

In relation to the technology, Chuck Reed has written a white paper on the technology. In the paper some of the environmental advantages of the technology are discussed.

The paper can be accessed here.

Posted by Tim Sandle

Saturday, 17 August 2013

EU considers restricting the use of antibiotics for farming

The European Medicines Agency has recommended that farmers stop using certain antibiotics , citing human health concerns.
Due to growing concerns about the overuse of antibiotics contributing to the global public health threat of drug-resistant bacterial infections in humans, the European Medicines Agency (EMA) has suggested a ban on the blanket use of the antibiotic colistin for farm animals, as reported by the science magazine Nature.
The Digital Journal reported recently about a scientific report that revealed that farm workers who work on farms where high levels of antibiotics are used in farm animals carry a high proportion of antibiotic resistant bacteria compared with farms that are antibiotic-free.
The reason that many farmers have increased their use of antibiotics is for “growth promotion”. Here antibiotics are employed primarily in large, concentrated feedlots for poultry, swine, and cattle, in order to fatten the animals faster, prevent rampant herd disease, and help bring healthy animals to market more quickly.
The argument against this practice is that animals fed low-dose antibiotics not only propagate antibiotic resistant bacteria, but practices also spread these resistant strains to farmers, their families, community residents, and ultimately, hospitalized patients. One of the main concerns is with MRSA (methicillin-resistant Staphylococcus aureus). MRSA was originally a problem within hospitals. However, it has steadily been infecting people outside of health-care settings since at least 1995.
The European agency is now recommending that colistin, which has been used by veterinarians for more than 50 years, should be restricted to infected animals or animals in contact with infections. A statement by the EMA suggests that the: "European Commission should determine the best way to amend the labelling and product literature for colistin containing veterinary medicines to reflect this more restricted pattern of use which is aligned with the principles of responsible use. The advice also recommends strengthening the systems for surveillance for resistance to colistin in order to increase the likelihood of early detection of any rise."
The European Commission will make the final decision about the proposed restriction. Discussing the proposal, Laura Piddock, a microbiologist at the University of Birmingham in the U.K. and director of the campaign body Antibiotic Action, stated: "The EMA recommendation is the precautionary approach, and is laudable. he reality is that we should question the use of any antibacterial agent outside of human medicine and until there is unequivocal evidence showing no effect of animal use upon human health."
The European Commission is developing an Action Plan Against the rising threats from Antimicrobial Resistance, which will be finalized at the end of 2014.
It has also been noted recently that several types of antibiotics, undertaken at Harvard University, can trigger harmful side effects in people.

Posted by Tim Sandle

Friday, 16 August 2013

PDA Technical Report 3: Validation of Dry Heat Processes Used for Depyrogenation

The following PDA technical report has been updated:

PDA Technical Report 3, Revised 2013 (TR 3): Validation of Dry Heat Processes Used for Depyrogenation and Sterilization

PDA has revised TR 3, originally issued in 1981. The revision offers a modern, scientific approach to dry-heat depyrogenation and sterilization processes and includes recommendations for use by industry and regulators. References to appropriate and current scientific publications, international regulatory documents, journal articles, technical papers and books are used where more detail and supportive data can be found.

For details see: PDA

Posted by Tim Sandle

Thursday, 15 August 2013

NEW BRP: Human Hepatitis B immunoglobulin BRP (Y0001414)

The European Pharmacopoeia (Ph. Eur.) Commission has adopted a new Biological Reference Preparation (BRP) for the assay of Hepatitis B immunoglobulin products according to the Ph. Eur. monographs 0722 (Human Hepatitis B immunoglobulin) and 1016 (Human Hepatitis B immunoglobulin for intravenous administration). The new Human Hepatitis B immunoglobulin BRP batch 1 is available on the EDQM website under catalogue reference Y0001414.

The Reference Standards Catalogue lists all the reference standards officially valid for the uses prescribed in the European Pharmacopoeia monographs. It gives a list of newly adopted standards, a Batch Validity Statement (BVS) for reference standards, 2687 Safety Data Sheets, and 1386 leaflets are available to download.

Posted by Tim Sandle

Wednesday, 14 August 2013

Joe Ridge

It is with sadness that I learnt today of the passing of Joe Ridge. Joe was the publisher of the company Euromed.

Joe had been ill will pancreatic cancer. He was a kind and helpful man, and a publisher of an interesting range of books and journals.

Euromed produce a number of periodicals, including The GMP Review, Clean Air and Containment Review (which of great value to the cleanroom community), Industrial Pharmacy Journal and the vital European Journal of Parenteral & Pharmaceutical Sciences, which as covered a lot of pharmaceutical microbiology.

I worked with Joe in putting together a recent book, along with Madhu Rahu Saghee, about cleanooms called "Cleanroom Management in Pharmaceuticals and Healthcare". Joe was a great help in putting this large volume together (which runs to 26 chapters across 600 pages).

Joe's vision in relation to pharmaceutical and healthcare publications will be greatly missed.

Posted by Tim Sandle

Rapid Microbial Method: poster

To effectively apply a Rapid Microbial Method (RMM) technique and leverage its value, the end user must match his or her application and requirements to the beneŽfits and performance of the RMM.

Understanding the general approach to validation as well as the inter-relationships between personnel and their qualiŽfications,guidance and regulations, statistics employed, test equipment, test protocols, and data analysis techniques enhances this evaluation. Through this holistic understanding, more robust dialogue can be fostered, and ultimately, a more successful adoption of an RMM technology may be realized.

Goals of Validation Architecture include:

• Delivers meaningful and relevant content to end user
• Can e ectively determine “that the performance characteristics of the RMM meet the requirements for the intended application, in comparison to the traditional method” (USP<1223>)
• Harmonizes statistical approach and methods that satisfy related guidelines (e.g. EP, ISO, TR33, JIS...)
• Methods and results withstand the rigor, scope, and neutrality expected by Regulators

To view an interesting poster on this subject (from BioVigilant Systems, Inc.), click here.

Posted by Tim Sandle

BioVigilant’s IMD-A 300 and IMD-A 350 systems

The IMD-A series of systems is designed to continuously monitor air and instantaneously detect the presence of both single and agglomerated microbes in real time. Testing was performed to demonstrate that the IMD-A systems are equivalent to, if not better than, the compendial microbiological method as per USP <1223> and EP 5.1.6 guidelines. Comparison of the IMD-A systems to the compendial method was gauged through the side-by-side testing of four IMD-A systems, two of each model, and three air samplers common to the pharmaceutical manufacturing environment: the SAS Super 100, MAS 100NT, and SMA. In order to stringently assess all systems, a highly homogenous, state-of-the-art aerosol test chamber was employed in order to ensure that these systems were sampling the same aerosol environment concurrently throughout the extensive test trials.

BioVigilant has maintained close communications with the FDA regarding the test plan, statistics utilized, and the subsequent results obtained, now summarized in a fact sheet (click here for more details).

Posted by Tim Sandle

Tuesday, 13 August 2013

William Hewitt

It is with  sadness that I've learnt of the recent passing of William (Bill) Hewitt, a biologist of some distinction. He was also part of the original team that set up the Pharmaceutical Microbiology Masters degree run from the University of Manchester, and he was a support of Pharmig.

William Hewitt authored three important books on biological assays during the 1970s and 1980s:
  • 'Microbiological Assay for Pharmaceutical Analysis: A Rational Approach'
  • 'Theory and Application of Microbiological Assay'
  • 'Microbiological Assay: An Introduction to Quantitative Principles and Evaluation'

The introduction to one of the books captures the aims of Bill's work:

"Microbiological Assay for Pharmaceutical Analysis: A Rational Approach provides a lucid explanation of the sources of error in microbiological assay and helps analysts choose efficient assay designs that will minimize those sources of error. Beginning with a review of the theoretical basis for the quantitative aspects, the author discusses microbiological assay as a branch of pharmaceutical analysis and distinguishes it from biological assay in general. He draws attention to the microbiological aspects that may not be so obvious to the chemical analyst and to the analytical aspects that may not be so obvious to the microbiologist."

As a supreme innovator and educator in the field, he will be missed.

Posted by Tim Sandle

Exposure to Subclinical Lipopolysaccharide

An interesting paper has been written by Wilbur Lew and colleagues relating to endotoxin exposure. The paper has been published in PLoS One and it is titled “Recurrent Exposure to Subclinical Lipopolysaccharide Increases Mortality and Induces Cardiac Fibrosis in Mice.”

The abstract reads:

“Circulating subclinical lipopolysaccharide (LPS) occurs in health and disease. Ingesting high fatty meals increases LPS that cause metabolic endotoxemia. Subclinical LPS in periodontal disease may impair endothelial function. The heart may be targeted as cardiac cells express TLR4, the LPS receptor. It was hypothesized that recurrent exposure to subclinical LPS increases mortality and causes cardiac fibrosis… Recurrent exposure to subclinical LPS increases mortality and induces cardiac fibrosis.”

For further details, see PLoS One.

Posted by Tim Sandle

Monday, 12 August 2013

Stimuli Article on Lifecycle Management of Analytical Procedures

The members of the USP Validation and Verification Expert Panel, working under the direction of the General Chapters—Physical Analysis Expert Committee, are posting a Stimuli article to present their current thinking on lifecycle management of analytical procedures.

The Expert panel suggests that the traditional approaches to validation, transfer, and verification should be integrated into the analytical procedure lifecycle process rather than be viewed as separate entities. This applies the modern concept of a lifecycle model to analytical procedures. This stimuli article should be considered as a roadmap for new validation standards that will be developed and presented over the course of the next couple of years.

To view the article, go to: USP

Posted by Tim Sandle

Sunday, 11 August 2013

Risk assessing cleanrooms

Current thinking, and regulatory expectations, requires that risk assessment tools and techniques are adopted for cleanroom management. To explore this subject further, from a contamination control perspective, Tim Sandle has written an introductory article for the publication Hospital Pharmacy Europe.

In the article, Dr Sandle considers how a risk based approach can be applied to the construction and review of an environmental monitoring programme, as part of an overall contamination control perspective.

For further details see HPE.

Sandle, T. (2013): Risk assessment and monitoring of cleanrooms, Hospital Pharmacy Europe, May / June 2013, pp54-56

Posted by Tim Sandle

Saturday, 10 August 2013

New rapid test for the 'Black Death'

Diagnosing the presence of Yersinia pestis, the cause of plague has been advanced through a rapid method.

Scientists working with Peter Seeberger, Director at the Max Planck Institute of Colloids and Interfaces (MPIKG) in Potsdam and Professor at the Freie Universität Berlin, have come up with a simple, inexpensive and reliable method of detecting the bacterium. The research team, specialising in glycochemistry and glycobiology, first identified and synthesised an oligosaccharide structure on bacterial surface before combining it with a protein to heighten the immunological effect. The presence of antibodies against this surface glycan in the blood of infected patients can be a biomarker of diagnostic value in Yersinia pestis infections. The Potsdam-based scientists also used the antigen to create antibodies which can directly detect the plague pathogen in infected samples.

In order to specifically detect the plague pathogen, the scientists first had to identify an oligosaccharide in a lipopolysaccharide on the surface of Yersinia pestis. This oligosaccharide would serve as a specific antigen. They then synthesised the complex compound in a multi-step process. Subsequently, the chemists bound the sugar molecule to a protein which is used in many vaccines to heighten the immune reaction. The resulting glycoprotein produced by the sugar-protein compound was used to trigger an immune reaction in mice. The scientists used this circumstance to create antibodies to the plague pathogen using murine immune cells.

For further details, refer to the following paper:

Chakkumkal Anish, Xiaoqiang Guo, Annette Wahlbrink, Peter H. Seeberger. Plague Detection by Anti-carbohydrate Antibodies. Angewandte Chemie International Edition, 2013; DOI: 10.1002/anie.201301633

Posted by Tim Sandle

Friday, 9 August 2013

Washed-up microbe can kill anthrax

San Diego scientists say they have found a compound in the ocean off Santa Barbara, Calif., that can kill anthrax and other infectious diseases.
A science team have identified a new chemical compound from the sea that may become an effective treatment against the potentially the disease anthrax, according to LA Jolla Light.
Anthrax is an acute disease caused by the bacterium Bacillus anthracis. Most forms of the disease are lethal, and it affects both humans and animals. Respiratory infection in humans initially presents with cold or flu-like symptoms for several days, followed by severe (and often fatal) respiratory collapse.
The newly discovered compound comes from a microorganism known as Streptomyces. This was isolated in 2012 and it has taken the course of a year to extract and test out the compound against the anthrax bacterium. The compound has been named anthracimycin. According to X-Ray Mag, initial testing has shown the compound to be potent in killing both anthrax (Bacillus anthracis) and MRSA (methicillin-resistant Staphylococcus aureus).
The discovery was made by a team led by William Fenical from the Scripps Institution of Oceanography at UC San Diego. Discussing the research, Fenical told Medical News Today:
“The last chemically-novel antibiotic was introduced in 1993. The vast majority of our antibiotics are derivatives of well-known chemical structures, many of which were discovered over 40 years ago. To overcome the medical emergency we face with drug-resistant infectious diseases such as MRSA, we need to discover entirely new antibiotics. By new, I mean compounds with chemical formulations never seen before.”
Fenical went onto add: “Anthracimycin is just such a discovery. It is composed of a chemical structure never seen or envisioned in the past. Its potency against anthrax and MRSA suggests that this new structure type should be carefully explored by those industries that are developing antibiotics."
The research has been published in the journal Angewandte Chemie.

Posted by Tim Sandle

Thursday, 8 August 2013

Flagellum failure lets bacteria turn

When headed the wrong way, some bacteria turn by letting their propellers flop, according to Cristy Gelling at Science News.

The newly discovered turning mechanism explains how a marine bacterium can control its direction using only a single flagellum, a stiff, rotating appendage that propels the cell forward. Turning depends on a mechanical characteristic that engineers might consider a failure if the flagellum were human-made: the tendency of flexible materials to buckle under pressure.

To read more, refer to the following research paper:

K. Son, J. Guasto, and R. Stocker. Bacteria can exploit a flagellar buckling instability to change direction. Nature Physics. Published online July 7, 2013. doi:10.1038/NPHYS2676

Posted by Tim Sandle

Wednesday, 7 August 2013

Amazing new fungus video

An interesting new video of fungal cells has been made.

The video shows millions of nuclei flowing through the tube-like filaments, or hyphae, of a single fungus cell (of the species Neurospora crassa). 

To see the video, click here.

The video was produced as part of a study by UCLA mathematician Marcus Roper's research group that was the first to measure and explain this dynamic movement of nuclei in the cells of a fungus.
More details about the fungus are provided in the following paper:

M. Roper, A. Simonin, P. C. Hickey, A. Leeder, N. L. Glass. Nuclear dynamics in a fungal chimera. Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1220842110

Posted by Tim Sandle

Tuesday, 6 August 2013

Probiotics can help fight Salmonella infections

New research has revealed how a probiotic bacterium used to treat irritable bowel syndrome can soothe gut bacterial infections caused by Salmonella.
Probiotics are types of 'good' or 'benefical' bacteria. As well as aiding the immune system and digestion, scientists thunk that mixtures of pro biotic bacteria can help to reduce the growth of certain types of bacteria. Due to this, scientists are looking at the right types of probiotic bacteria.
Specifically, microbiologists have been studying a probiotic strain of Escherichia coli (not all strains of E. coli are harmful). A research group have found that a type of E. coli (called Nissle 1917 or Mutaflor) reduces Salmonella colonization by competing with the pathogen for iron, an essential nutrient that salmonella acquires in the gut in order to replicate at high levels.
Types of Salmonella bacteria can potentially cause illnesses such as typhoid fever, paratyphoid fever, and other food borne illness. Most persons infected with Salmonella develop diarrhea, fever, and abdominal cramps 12 to 72 hours after infection.
For many decades E. coli Nissle 1917 strain has been administered to patients with a variety of bowel disorders (such as ulcerative colitis and Crohn’s disease). It now appears that this beneficvial bacterium could be used to treat other types of disease.
The study was conducted by UC Irvine microbiologists and the findings have been published in the journal Cell Host & Microbe, in a paper titled "Probiotic Bacteria Reduce Salmonella Typhimurium Intestinal Colonization by Competing for Iron."

Posted by Tim Sandle

Monday, 5 August 2013

FDA issues fecal transplant guidance

The U.S. Food and Drug Administration (FDA) has issued a guidance note about fecal transplants. A fecal transplant involves transferring the stool of a healthy person into the gut of someone with an antibiotic resistant microbe infection.
Fecal transplants (or 'fecal bacteriotherapy') appear to have a high success rate. The technique aims to restore the balance between good bacteria and bad bacteria in the colon.
The success rate was studied recently in the New England Journal of Medicine, where the process was concluded to be successful in curing 15 out of 16 patients suffering from a recurrent diarrheal infection of the problem microbe Clostridium difficile. This bacterium is one of the so-called problem bacteria, noted for being resistant to many antibiotics.
To work, the technique requires fecal matter to be transferred to the patient being transplanted through a series of enemas. With the New England study, the transplants were compared with administrations of the he antibiotic vancomycin, and the transplants worked more effectively.
In light of the success rate, the Digital Journal reported that the the American Gastroenterological Association regards fecal transplants as "a promising treatment.".
Given that fecal transplants are being tried more often, the U.S. FDA has decided that the transplants require review and regulation. The FDA has declared that fecal transplants meet the definition of a biologic therapy. This means that researchers who want to perform the procedure will now have to submit an investigational new drug (IND) application, via the FDA. To aid medics, the FDA this week released a guidance note.
One stipulation that the FDA requires is that the treating physician obtains adequate informed consent from the patient or his or her legally authorized representative before therapy begins.

Posted by Tim Sandle