Biopharma Innovation Updates and Strategies (e-book)

BioPharm International have issued a special e-book. The e-bookexamines strategies to drive innovation in biopharmaceutical development, including extending patent life, new financing options, and working with contract development and manufacturing organization to bridge innovation gaps. Executives at three biopharmaceutical companies at different stages of product development provide insight on driving new drug therapies to market.

For further details see BioPharm International.



Posted by Tim Sandle

Global strategies for the elimination of leprosy

Of the various ‘ancient diseases’, one of the longest lasting (and arguably notorious) is leprosy (leprosy was recognized in the ancient civilizations of China, Egypt and India). Notwithstanding its long history, the disease is one that should be relatively straightforward, with tangible political support, to eliminate as a global health concern. The current strategy is being implemented by the World Health Organization (WHO).

In a new paper, Tim Sandle reviews this strategy and additionally considers some of the current research into leprosy, focused on the areas of diagnosis and treatment.

The reference is:

Sandle, T. (2013). Global Strategies for Elimination of Leprosy: A Review of Current Progress, Journal of Ancient Diseases & Preventive Remedies, 1 (4): e112. doi: 10.4172/2329-8731.1000e112

For a copy of the paper, please contact Tim Sandle

Posted by Tim Sandle

Sterility, Sterilization and Sterility Assurance for Pharmaceuticals (new book)

New book: 'Sterility, Sterilisation and Sterility Assurance for Pharmaceuticals: Technology, Validation And Current Regulations'.

A new book covering a the entire range of different sterilization methods, as well as exploring the related areas of sterility assurance and the concept of sterility, has been published. The book has been written by Tim Sandle.

The key features of the book are:

• The main sterilization methods of physical removal, physical alteration and inactivation
• Discussions of medical devices, aseptically filled products and terminally sterilized products
• An examination of the bacterial, pyrogenic, and endotoxin risks to devices and products.

In terms of the book's importance for pharmaceuticals, medical devices and healthcare:

Failure to adequately control any microbial challenge associated within process or product by robust sterilisation will result in a contaminated marketed product, with potential harm to the patient. Sterilisation is therefore of great importance to healthcare and the manufacturers of medical devices and pharmaceuticals. Sterility, sterilisation and sterility assurance for pharmaceuticals examines different means of rendering a product sterile by providing an overview of sterilisation methods including heat, radiation and filtration. The book outlines and discusses sterilisation technology and the biopharmaceutical manufacturing process, including aseptic filling, as well as aspects of the design of containers and packaging, as well as addressing the cleanroom environments in which products are prepared. Consisting of 18 chapters, the book comprehensively covers sterility, sterilisation and microorganisms; pyrogenicity and bacterial endotoxins; regulatory requirements and good manufacturing practices; and gamma radiation. Later chapters discuss e-beam; dry heat sterilisation; steam sterilisation; sterilisation by gas; vapour sterilisation; and sterile filtration, before final chapters analyse depyrogenation; cleanrooms; aseptic processing; media simulation; biological indicators; sterility testing; auditing; and new sterilisation techniques.

The chapter list is:

• Sterility, sterilization and microorganisms
• Pyrogenicity and bacterial endotoxin
• Regulatory requirements and Good Manufacturing Practices (GMP)
• Gamma radiation
• Electron beam processing
• Dry heat sterilization
• Steam sterilization
• Gaseous sterilization
• Hydrogen peroxide vapor sterilization
• Sterilization by filtration
• Other methods of sterilization
• Depyrogenation and endotoxin
• Cleanrooms, isolators and cleanroom technology
• Aseptic processing and filling
• Media simulation trials
• Cleaning and disinfection of sterile processing facilities
• Biological indicators
• The Sterility Test
• Investigating sterility test failures
• Auditing sterilization processes and facilities.

The book has been published by Woodhead Publishing / Elsevier and is available as a hardback and as an e-book.

Further details of the hardback version and the order page can be found here.

Details of the e-book version and an opportunity to order can be found here.

The book is also available via Amazon and other bookstores.

Harcopy and e-copy

Posted by Tim Sandle

Spaceflight and microbial pathogens: possible drug resistance

At Arizona State University's Biodesign Institute, Cheryl Nickerson and her team have been investigating the intriguing effects of spaceflight on microbial pathogens. Specifically the team reports their recent work examining spaceflight-induced responses in, and infectious disease potential of, the fungal pathogen, Candida albicans.

The new study reports the differential regulation of 452 genes in spaceflight-cultured C. albicans, compared to fungal cells cultured under otherwise identical ground-based conditions. The expression of a wide variety of functionally diverse gene families was altered, including those regulating cell aggregation and budding, biofilm formation and resistance to pathogenesis-related stresses and antifungal drugs.

Therefore, the pathogen in its transformed state poses a significant infectious disease risk.

For further details, refer to the following paper:

Aurélie Crabbé et al. Spaceflight Enhances Cell Aggregation and Random Budding in Candida albicans. PLoS ONE, 2013; 8 (12): e80677 DOI: 10.1371/journal.pone.0080677

Posted by Tim Sandle

The Protein Handbook: A guide to antibody purification and protein analysis

Life Technologies have issued a free protein handbook. According to Life Technologies:

Get exclusive access to the underlying technologies, example protocols, tips and tricks, and references to peer-reviewed product application literature for the entire collection of Novex® gels, tanks and accessories, antibodies, and immunoassays.

And now your free protein handbook is available in a convenient e-book format with links to selection guides, technical support resources, and more.

Sections include: 

• Protein purification
• Protein separation
• Western blotting
• Antibody pairs and ELISAs
• Multiplex assays

Posted by Tim Sandle

The influence of microbiome on autoimmunity

 We live with millions of microorganisms, and this coexistence comes as a mixed blessing. Evolution drove bacteria to not only to survive in humans, but also to protect us by supporting various physiological, metabolic, and immune processes. On the other hand, research implicates bacteria in conditions detrimental to health, like allergies, obesity, multiple sclerosis, and recently rheumatoid arthritis.

Gut bacteria may cause rheumatoid arthritis by attacking the immune system. Using an animal model, scientists found that a bacterium, Prevotella copri, trains the immune system to produce Th17 cells, which in turn release molecules that cause inflammation and bone damage in arthritis. Significantly, Prevotella copri was present in 75% of patients' intestines, as determined by fecal sample testing.

For further details, see Science World

Posted by Tim Sandle

Inner workings of bacterial ‘black box’ – amazing video

Using a pioneering visualization method, researchers from the University of California, Berkeley and the Department of Energy Joint Genome Institute (DOE JGI) made what are, in effect, movies of this complex and vital cellular machinery being assembled inside living cells. They observed that bacteria build these internal compartments in a way never seen in plant, animal and other eukaryotic cells.

For further details see the Genome Institute

Posted by Tim Sandle

Controlling antimicrobial resistance

Antimicrobial resistance is a responsibility of each and every one of us, be it a patient, healthcare professional or policy maker. This is the theme of an interesting article in the journal European Hospital.

The article states:

“In the past four years, in more than a third of EU/EEA countries, there has been a significant increase in the trend towards combined resistance to both Klebsiella pneumoniae and E. Coli; on a more positive note methicillin- resistant Staphylococcus aureus (MRSA) has shown a decrease or stabilisation in most European countries.”

To view the article, go to EH.

Posted by Tim Sandle

Microorganisms in water pipework

The American Society for Microbiology have issued an interesting report titled “Microbes in Pipes: The Microbiology of the Water Distribution System”.

According to ASM: “Most microbes in distribution systems probably do not pose health threats, but when they form biofilms, they can cause physical damage such as corroding pipes and blocking valves. In addition to forming biofilms, some non-pathogenic microorganisms can break down chemicals used to minimize microbial growth and others may release nutrients into the distribution system that support downstream growth of opportunistic pathogens. The extent to which these processes occur in water distribution systems is largely unknown, because these ecosystems have not been characterized.”

To read more, go to the AMS website.

Posted by Tim Sandle

FDA Releases New Q&A on Adhering to QbD Principles

The FDA has released a second question-and-answer document intended to provide guidance to industry on the concept of quality by design.

The document contains nine questions and answers, including:

• 1.      Why would a design space be verified during the product lifecycle? (There are risks inherent in scaling-up or making new model assumptions, and it is necessary to understand these risks.)
• 2.      What is the purpose of design space verification at commercial scale? (to demonstrate control over the product and its quality)
• 3.      How is a design space initially developed and verified at commercial scale? (based on experiments conducted at laboratory or pilot scale, which requires subsequent validation at larger scales)
• 4.      How can a design space be verified at commercial scale? (It is not necessary to repeat at commercial scale the experiments initially conducted to define a design space at lab or pilot scale, but should be guided by the results of risk assessments.)
• 5.      How should design space verification protocol be addressed in the submission? (General and specific requirements for both EMA and FDA are explained.)
• 6.      What if unexpected results/events are obtained during the design space verification studies? (The results should be studied and, if necessary, reported to regulatory authorities.)
• 7.      How can a design space be verified at commercial scale for biological products? (The principles are the same for both chemical and biological products.)
• 8.      What is the difference between process validation and design space verification? (Process validation demonstrates consistency of the process at normal operating ranges, design space verification demonstrates that scale effect and or model assumptions are under control in the new area of design space and do not affect product quality.) 

• 9.      How should design space verification approach be addressed in the pharmaceutical quality system? (Firms should have a written plan for when and how to evaluate the need for design space verification.)

For details see FDA

Posted by Tim Sandle

New weapon against superbugs

 A research team have discovered a protein that kills bacteria. The isolation of this protein, produced by a virus that attacks bacteria, could help protect patients from hospital 'superbugs'.

The protein has been identified by study a bacteriophage called T17. Bacteriophages, often referred to as "phages," are viruses that infect and replicate in bacteria. T7 is a particularly virulent 'phage that infects Escherichia coli bacteria. The researchers have found that one of the proteins, called 0.4, impedes cell division in E. coli, causing the cells of the bacteria to elongate and then die.

Whilst the bacteriophage has a potential use in the fight against hospital superbugs, it remains that no bacteriophage preparation has been approved in Western medicine for treating systemic bacterial infections.

The research was led by Dr. Udi Qimron of Tel Aviv University's Department of Clinical Microbiology and Immunology at the Sackler Faculty of Medicine. The findings have been published in the Proceedings of the National Academy of Sciences. The research paper is titled "Gene product 0.4 increases bacteriophage T7 competitiveness by inhibiting host cell division".

Posted by Tim Sandle

Microfluidic chip sorts 'good' bacteria from 'bad' bacteria

Sometimes the difference between harmless and harmful bacteria is miniscule. For example, with Escherichia coli, the difference between E. coli O157:H7 and less harmful strains are detectable only at the molecular level.

Determining whether or not bacteria are harmful usually requires growing cultures from food or infected patients. This is a time-consuming process that must be carried out in a laboratory. To overcome this, Scientists at Arizona State University's Department of Chemistry and Biochemistry, in the College of Liberal Arts and Sciences, have developed a new device that could significantly speed up the identification process for harmful bacteria and other microorganisms. The team, led by Professor Mark A. Hayes, hopes to create handheld, battery-operated devices that could deliver answers in minutes, instead of days.

Identification takes place within a microscopically small channel in a chip made from glass or silicone polymer. The microchannel features saw-tooth shapes that allow researchers to sort and concentrate microbes based on their unique electrical properties. The phenomenon that makes this work is called dielectrophoresis, which involves an applied voltage that exerts force upon the bacteria. The technique is based on the fact that different bacterial strains possess subtle, but telltale differences in the proteins and other molecules that they express on their surface.

Based on the work so far, the research team plan to create cheap, portable devices that would enable point-of-care or field based analysis.

The new technology has been described in the journal Analytical and Bioanalytical Chemistry, in a paper titled "Differentiation of Escherichia coli serotypes using DC gradient insulator dielectrophoresis".



Posted by Tim Sandle

Microbial diseases of Ancient Egypt: lessons for today

By comparing the ancient forms of diseases from Ancient Egypt with their contemporary equivalents, researchers can attempt learn how particular diseases evolved; what makes them so harmful; and possibly how to stop them. This field of paleopathology is becoming increasingly sophisticated, aided by advances to scientific techniques.

In a new paper, Tim Sandle presents an overview of recent research pertaining to the entwined concerns of paleopathology and Egyptology.

The reference is:

Sandle, T. (2013). Pharaohs and Mummies: Diseases of Ancient Egypt and Modern Approaches, Journal of Ancient Diseases & Preventive Remedies, 1 (4): e110. doi: 10.4172/2329-8731.1000e110

For a copy of the paper, please contact Tim Sandle

Posted by Tim Sandle

Using an antimicrobial skin cleanser before catheterisation

Community nurses’ caseloads may include a large number of catheterised patients and catheter-related infection is a significant problem, with up to 90–100% of those who are catheterised long-term going on to develop a catheter-associated urinary tract infection (CAUTI). For community nurses, ensuring that their
skin and that of the patient has been cleansed before any catheterrelated intervention is paramount.

A new paper published in the Journal of Community Nursing, Tim Sandle  looks at the use of a new antimicrobial cleansing solution (octenilin®; Schülke) and whether its properties reduced the infection risk associated with catheterisation in the community.

The reference is:

Sandle, T. (2013). Using an antimicrobial skin cleanser before catheterisation, Journal of Community Nursing, Vol. 27, No.5, pp30-34

For a copy, please contact Tim Sandle.

10 facts about antibiotics

1. Antibiotics are derived from microorganisms, which presumably synthesize them as defensive compounds.

2. When Alexander Fleming first isolated penicillin from the fungus Penicillium (1928), he called it "mould juice." When mass-produced for WWII, it was nicknamed, "The Wonder Drug" (not to be confused with the "cure all miracle drug," cocaine).

3. There are reports of moldy bread being used to treat wounds to prevent infection. That is not the origin of "Wonder Bread," though.

4. Some antibiotics cause side effects due to their effect on our mitochondria, which are bacteria.

5. 10% of Americans believe antibiotics are addictive. Same % believe antibiotics are ineffective treatment for bacterial infections.

6. Approximately 1/3 of adults in the United States believe that antibiotics can also kill viruses.

7. The biggest consumers of antibiotics are farm animals. Second biggest user is children (who are usually sick with viruses).

8. Prescription of antibiotics to people with viral infections contributes to the evolution of drug-resistant bacteria, which kill tens of thousands each year and cost us billions in health care expenses.

9. The word "antibiotic" (actually "antibiotique") was first used in late 1800s. It meant, "destructive to microorganisms." Most dictionaries, including Google's, retain this original definition.

10. In 1942, Selman Waksman (who stole the discovery of a bacteriaderived antibacterial from his graduate student, Albert Israel Schatz) began using "antibiotics" to refer to compounds that kill only bacteria. The change in definition from #9 likely causes #6, #7, & #8.

Source: AA

Posted by Tim Sandle