Saturday 30 November 2013

Falsified Medicines Directive (FMD)

The UK MHRA has published on its website an overview of the medicines regulation and guidance in relation to the FMD as it applies to the UK.

European Directive 2011/62/EU of the European Parliament and of the Council (the Falsified Medicines Directive) amends Directive 2001/83/EC on the Community code relating to medicinal products for human use.

The Falsified Medicines Directive is transposed through The Human Medicines (Amendment) Regulations 2013 [SI 2013/1855] which came into force on 20 August 2013.

For further details, see FMD

Posted by Tim Sandle

Friday 29 November 2013

Best Practices in Managing Microbial Excursions

The European Pharmaceutical Review is hosting a webinar titled ‘Best Practices in Managing Microbial Excursions’ on Tuesday December 3rd.

The brief for the webinar is:

“Learn from industry experts some practices to help better manage the investigation process and how to design processes to minimize unnecessary excursions.

Microbial excursions as a result of an out of specification result from a quality control test can be time consuming and costly. The investigation of the root cause, analysis of the risk to the product, and determination of corrective/preventative actions take hours of manpower and resources and often are caused by issues around personnel practices, keying errors, and incubation errors.”

The webinar is presented by Guenther Gapp, Tim Sandle and David Jones.

For further details see: EPR

Posted by Tim Sandle

How Staph toxin disarms the immune system

Researchers at NYU Langone Medical Center have discovered a new mechanism by which the deadly Staphylococcus aureus bacteria attack and kill off immune cells. Their findings, published today in the journal Cell Host & Microbe, explain a critical survival tactic of a pathogen that causes more skin and heart infections than any other microbe.

Scientists have long known that Staph releases an arsenal of toxins to puncture immune cells and clear the way for infection. But only recently have they begun to understand exactly how these toxins work.

Earlier this year, researchers explained how one of those toxins, a protein called LukED, fatally lyses T-cells, macrophages and dendritic cells, all types of white blood cells that help fight off infection. The LukED toxin, they showed, binds to a surface receptor called CCR5 (the same one exploited by HIV).  But their discovery failed to explain how the bacterial toxin kills other types of white blood cells, such as neutrophils, that lack the CCR5 receptor.

Now some recent work solves this puzzle, showing for the first time how receptors on neutrophils (a common type of white blood cell) also enable binding of the LukED toxin. The researchers found that LukED latches onto surface receptors called CXCR1 and CXCR2, creating the same deadly pores that it does when it latches onto CCR5 receptors.

For further details, refer to the following paper:

Tamara Reyes-Robles, Francis Alonzo, Lina Kozhaya, D. Borden Lacy, Derya Unutmaz, Victor J. Torres. Staphylococcus aureus Leukotoxin ED Targets the Chemokine Receptors CXCR1 and CXCR2 to Kill Leukocytes and Promote Infection. Cell Host & Microbe, 2013; 14 (4): 453 DOI: 10.1016/j.chom.2013.09.005

Posted by Tim Sandle

Thursday 28 November 2013

FDA Releases Report on Personalized Medicine

The report describes the concept and various definitions of personalized medicine and notes that it typically involves both a diagnostic device (e.g., assays to measure genetic factors and imaging equipment) and a therapeutic product. FDA’s role and responsibilities in this field include considering benefits and risks when evaluating medical products, providing guidance to encourage development, being informed about advances and ensuring that information is used appropriately throughout the industry, and working with stakeholders to evaluate and validate new diagnostics and therapeutics. FDA is responsible for “identifying opportunities for streamlining regulatory processes and advancing the science and tools that will help drive innovation,” notes the report. 

For further details, see FDA

Posted by Tim Sandle

Wednesday 27 November 2013

EMA and FDA Release QbD Guidance

FDA and the European Medicines Agency (EMA) have published a second joint question-and-answer document that provides guidance on the quality-by-design (QbD) concept. The guidance focuses on design space verification and reflects the conclusions reached by European Union and US regulators.

In March 2011, FDA and EMA launched a three-year pilot program for the parallel assessment of certain quality or chemistry manufacturing and control (CMC) sections of applications that are relevant to QbD. The objective of the program is to share knowledge and harmonize implementation of the QbD concept. Experts from the Japanese Pharmaceuticals and Medical Devices Agency participate as observers in the program.

According to EMA, the pilot program is open to selected procedures, including applications for initial marketing authorizations, type-II variations, and scientific advice. Participation in the pilot program is voluntary. Interested applicants and sponsors should notify both agencies three months prior to submission of an application.

To access the document, see FDA/EMA.

Posted by Tim Sandle

Tuesday 26 November 2013

USP updates on sterilization

Tim Sandle has written an overview of the updates to the Unites States Pharmacopeia in relation to sterilization and sterilization technologies. The reference for the article is:

Sandle, T. (2013). USP updates: cleanrooms and sterilization, Clean Air and Containment Review, Issue 16, pp24-25

If you are interested in reading the article, please contact Tim Sandle

Posted by Tim Sandle

Evolving E. coli

Scientists show that Escherichia coli cells continue to become more fit, even over tens of thousands of generations.

Since 1988, Michigan State University’s Richard Lenski has led the Escherichia coli Long-term Experimental Evolution Project (LTEE)—12 flasks of bacteria that have been evolving in the lab for more than 58,000 generations. In the latest report from the project, Lenski and colleagues have shown that peak fitness—the point in an organism’s evolution when it is maximally adapted to its environment—does not seem to have an upper limit.

Lenski’s team thawed E. coli taken from the LTEE at 41 different time points during the past 25 years and cultured the samples from different generations together in varied combinations with the most current generations. They evaluated fitness based on how fast the bacteria grew and found that even between 40,000 and 50,000 generations, there was a 3 percent increase in mean fitness. The scientists generated a model, which predicted that even if the experiment continued for 2.5 billion years, there would not be an upper bound to fitness.

Their findings have been published in the journal Science. The paper is titled "Long-Term Dynamics of Adaptation in Asexual Populations".

Posted by Tim Sandle

Get Smart About Antibiotics Week 2013

Infections caused by resistant bacteria have become more common, and many bacteria have become resistant to multiple antibiotics. CDC released a report in September 2013 documenting that each year more than two million people in the United States get infections that are resistant to antibiotics and at least 23,000 people die as a result. This trend demands urgent action by patients, healthcare providers, facility administrators and health care insurers to preserve the last lines of defense against many of these germs. In conjunction with Get Smart About Antibiotics Week (November 18-24), the American Academy of Pediatrics, in collaboration with CDC, released new guidance for treating common pediatric upper respiratory infections.

The abstract from the journal reads:

“Most upper respiratory tract infections are caused by viruses and require no antibiotics. This clinical report focuses on antibiotic prescribing strategies for bacterial upper respiratory tract infections, including acute otitis media, acute bacterial sinusitis, and streptococcal pharyngitis. The principles for judicious antibiotic prescribing that are outlined focus on applying stringent diagnostic criteria, weighing the benefits and harms of antibiotic therapy, and understanding situations when antibiotics may not be indicated. The principles can be used to amplify messages from recent clinical guidelines for local guideline development and for patient communication; they are broadly applicable to antibiotic prescribing in general. Pediatrics 2013;132:1146–1154”

Posted by Tim Sandle

Monday 25 November 2013

8th Edition of the European Pharmacopoeia

The 8th Edition of the European Pharmacopoeia has an implementation date of 1 January 2014. It contains more than 2220 monographs and 340 general chapters and 2500 descriptions of reagents. It is comprised of two initial volumes, and as for other recent editions, non-cumulative supplements will be issued three times a year following the decisions taken at each session of the European Pharmacopoeia Commission.

The texts of the European Pharmacopoeia (Ph. Eur.) concern the qualitative and quantitative composition of medicines, the tests to be carried out on medicines, on the raw materials used in the production of medicines and on the intermediates of synthesis. It contains texts covering substances, excipients and preparations for pharmaceutical use of chemical, animal, human or herbal origin, homoeopathic preparations and homoeopathic stocks, antibiotics, as well as dosage forms and containers. The texts also cover biologicals, blood and plasma derivatives, vaccines and radiopharmaceutical preparations. They are legally binding.
Posted by Tim Sandle

Sunday 24 November 2013

Listeria and disinfectant resistance

Research suggests that listeria is developing resistance to the most frequently used compounds. As part of studies into mechanisms of resistance, Stephan Schmitz-Esser at the University of Veterinary Medicine, Vienna (Vetmeduni Vienna) has uncovered the mechanism for resistance to benzalkonium chloride.

The research centres on listeria acquiring new genetic material from other bacteria.

For more on this research, refer to:

Anneliese Müller, Kathrin Rychli, Meryem Muhterem-Uyar, Andreas Zaiser, Beatrix Stessl, Caitriona M. Guinane, Paul D. Cotter, Martin Wagner, Stephan Schmitz-Esser. Tn6188 - A Novel Transposon in Listeria monocytogenes Responsible for Tolerance to Benzalkonium Chloride. PLoS ONE, 2013; 8 (10): e76835 DOI: 10.1371/journal.pone.0076835

Posted by Tim Sandle

Saturday 23 November 2013

15 Years in Pharmaceutical Microbiology

How has the pharmaceutical microbiology arena progressed over the last 15 years? In a review of some major hurdles and milestones, the American Pharmaceutical Review has interviewed some leading microbiologists including Donald Singer (Global Lead Quality Manager, Microbiology, GlaxoSmithKline) and Luis Jimenez, Ph.D. (Biology and Horticulture Department, Bergen Community College).

For example, Donald Singer notes:

"In Microbiology, some milestones I can note:
  • Regulatory scrutiny of sterile products manufacturing has continued to increase and has led to guidance requirements for risk rationale; for example, the rewrite of 21CFR612 for sterility testing, the FDA Guideline for Container Closure Integrity in lieu of Sterility Testing, the MHRA ‘GMP’ Annex 1 pre-fi ltration bioburden action ‘limit’, and the USP <1116> contamination recovery rate recommendation
  • Alignment of regulatory guidance with ICH Quality standards Q7, Q8 and Q9 which impact microbiological risk
  • Increased published articles and books about pharmaceutical microbiological control
  • Forums and media for communicating microbiological issues and solutions have increased Some hurdles I have seen are:
  • Diffi culty in the implementation of new alternative methodologies and concern regarding ‘equivalency’ to pharmaceutical standard methods
  • Economics leading to Microbiology labs to lean staffi ng, less capabilities, less time to innovate, and concern for improvement of supervision of analytical teams that lack experience or suffi cient knowledge in the fi eld
  • Increase in instrument-based technology jumped ahead of adequate education for users to make good scientifi c decisions
  • Continuation in pockets of the industry where management lacking scientific knowledge oversee microbiology operations."
To read more of what they have to say, see APR.

Posted by Tim Sandle

Friday 22 November 2013

New insight into irritable bowel syndrome and gut bacteria

New findings from the Institute of Food Research are providing insights into the interaction between bacteria and mucins, and how the specificity of these interactions affects health. The IFR researchers looked at Ruminococcus gnavus. This is a common species of gut bacteria found in over 90% of people, including infants just a few days old. It has also been implicated in gut-related health conditions. A number of studies have shown that patients suffering from Inflammatory Bowel Diseases have a disproportionate representation of R. gnavus.

This study looked at two different R. gnavus strains. Although both R. gnavus strains can use mucins, only one had the ability to survive when mucins were the sole source of food.

Comparing the genomes of the R. gnavus strains identified gene clusters used to breakdown mucins. Differences in these genes explain the different abilities of the strains to use mucins. The mucin sugar structures change in different parts of the gut and over time, suggesting the strains may be adapted for different environments or to colonise us at different times. For example, the R. gnavus strain adapted to survive solely on mucins may give it the ability to colonise the guts of newborn babies, when mucins represent the only sources of sugars for bacteria. In adults, the strains of bacteria that degrade mucins are the ones most likely to contact the cells underneath the mucus and so these strains are the ones most likely to influence health.

For further details, see the following paper:

Emmanuelle H. Crost, Louise E. Tailford, Gwenaelle Le Gall, Michel Fons, Bernard Henrissat, Nathalie Juge. Utilisation of Mucin Glycans by the Human Gut Symbiont Ruminococcus gnavus Is Strain-Dependent. PLoS ONE, 2013; 8 (10): e76341 DOI: 10.1371/journal.pone.0076341

Posted by Tim Sandle

Thursday 21 November 2013

Bats and disease

Emerging infectious diseases pose a significant threat to human and animal welfare. A high proportion of emerging and reemerging infectious diseases are zoonoses derived from wildlife. Bats harbour more zoonotic viruses per species than rodents and are now recognised as a significant source of zoonotic agents. Henipaviruses, coronaviruses, filoviruses, and the rabies-causing lyssaviruses have all been shown to be transmissible from bats to humans - often through an intermediate host—with fatal consequences. Despite the obvious risk bat viruses pose to human health, it must be acknowledged that most outbreaks of bat-borne zoonotic diseases are a consequence of human activities. From an ecological perspective, bats are a remarkable and ecologically important group with many unique biological features.

There is more on this topic at PLOS Pathogens.
Posted by Tim Sandle

Wednesday 20 November 2013

Virus testing of raw materials

The European Medicines Agency have issued some reports examining the necessity of screening certain in-coming raw materials for viruses.

These are:

Use of bovine serum in the manufacture of human biological medicinal products. Reference: CPMP/BWP/1793/02. Issued in June 2013.

With this document, the guidance notes: “Different risks are associated with the use of such raw materials. Indeed, the nature and quality of the bovine serum used in the manufacturing process can profoundly influence the quality of the finished product. In particular, the potential presence of extraneous agents in bovine serum represents a risk to the safety of the biological medicinal product.”

Use of porcine trypsin used in the manufacture of human biological medicinal products. Reference: EMA/CHMP/BWP/814397/2011. Issued in March 2013.

Posted by Tim Sandle

Tuesday 19 November 2013

From antimicrobial to anticancer peptides

Antimicrobial peptides (AMPs) are part of the innate immune defense mechanism of many organisms. Although AMPs have been essentially studied and developed as potential alternatives for fighting infectious diseases, their use as anticancer peptides (ACPs) in cancer therapy either alone or in combination with other conventional drugs has been regarded as a therapeutic strategy to explore.

This is the basis of an interesting article by Diana Gaspar, and colleagues at the Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal. The article has been published by Frontiers in Microbiology.

The reference is:

Gaspar D, Veiga AS and Castanho MARB (2013) From antimicrobial to anticancer peptides. A review. Front. Microbiol. 4:294. doi: 10.3389/fmicb.2013.00294

Posted by Tim Sandle

Monday 18 November 2013

Where did syphilis come from?

Did Columbus bring the disease syphilis back with him from the New World, or was it in Europe all along? Katherine Wright, winner of the Wellcome Trust science writing prize 2013, has investigated this issue in a fascinating article.

Here is an excerpt, all about the spread of Treponema pallidum:

"As its many names attest, contemporaries of the first spread of syphilis did not know where this disease had come from. Was it indeed the fault of the French? Was it God's punishment on earthly sinners?
Another school of thought, less xenophobic and less religious, soon gained traction. Columbus's historic voyage to the New World was in 1492. The Italian soldiers were noticing angry chancres on their genitals by 1494. What if Columbus had brought the disease back to Europe with him as an unwelcome stowaway aboard the Pinta or the Niña?"

To read the full article, see The Guardian.

Posted by Tim Sandle

New book: Sterility, Sterilisation and Sterility Assurance

A new book of interest has been published. The book is titled ‘Sterility, sterilisation and sterility assurance for pharmaceuticals: Technology, validation and current regulations’ and it has been written by Tim Sandle. The book has been published by Woodhead Biomedicine, an imprint of Elsevier.

The book addresses the following concerns:
  • The main sterilisation methods of physical removal, physical alteration and inactivation.
  •  Discussions relating to medical devices, aseptically filled products and terminally sterilised products.
  • Bacterial, pyrogenic, and endotoxin risks to devices and products.
  • The latest technology in the field.
  • Current thinking behind risk assessment and good manufacturing practices. 
Throughout 18 chapters, the book outlines and discusses sterilization technology and the biopharmaceutical manufacturing process, including aseptic filling, as well as aspects of the design of containers and packaging and addresses the cleanroom environments in which products are prepared.

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 book is available directly from the publisher or via Amazon and other good booksellers (such as Waterstones and Powells).

The Amazon links are:

Amazon U.S.

Amazon U.K.

Amazon Canada

Amazon China

Amazon France

Amazon Germany

Amazon Austria

Amazon Italy

Amazon Spain

Amazon India

Amazon Japan

An e-book version is available from the publisher.

Tim Sandle is Head of Microbiology at the Bio Products Laboratory, Elstree, UK and a visiting tutor with the School of Pharmacy and Pharmaceutical Sciences, Manchester University, UK


Sandle, T. (2013). Sterility, sterilisation and sterility assurance for pharmaceuticals: Technology, validation and current regulations, Woodhead Publishing, Oxford

Sunday 17 November 2013

Microbes can help solve murder mysteries

Studies on decomposing mice suggest that the microbial content of a corpse can offer clues as to how old a body is and the approximate time that death occurred.
From studies on dead and decaying mice, where the microorganisms were examined, researchers have been able to narrow down the times of death of mice to three-day windows. This is by identifying the microbes present in and on their bodies using DNA sequencing. This came from studies on 40 decomposing mice over 48 days.
Commenting on the study, Jessica Metcalf, a postdoc at the University of Colorado Boulder and an author of the study, told NPR’s All Things Considered that: "What we’re looking for is whether the microbial community changes in a clock-like manner." The answer was 'yes it does'.

To show this, researchers collected samples of archaea, microbial eukaryotes, and bacteria from their skin, from within their abdominal cavities, and from soils associated with each corpse. They found that the bacteria, particularly those from the order Rhizobiales, were especially useful for estimating time of death.
The team is now working to estimate time of death in humans using a similar approach. Currently researchers estimate time of death by looking at the development of blow fly larvae in corpses. The new research suggests that the microorganisms could present an equivalent method or even something more accurate.
The findings have been published in the journal eLife. The free-to-read paper is titled "A microbial clock provides an accurate estimate of the postmortem interval in a mouse model system."

Posted by Tim Sandle

Saturday 16 November 2013

Innovations in biosimilar product development

Total BioPharma have issued a new e-book of interest on biosimilars.

The potential benefits that biosimilars offer are well celebrated through providing improved patient access to affordable, effective and complex treatments. The demand for affordable treatments in the face of escalating healthcare costs is high but a number of hurdles present themselves when bringing a biosimilar from bench to market.

For further details, see Total BioPharma.

Posted by Tim Sandle

Friday 15 November 2013

Screening for hospital pathogens

A new microfluidic device (for handling small volumes of fluids) has been developed by researchers to screen for hospital pathogens like Pseudomonas aeruginosa.
Pseudomonas aeruginosa is a bacterium common in soil and water; it has also been associated with hospital acquired infections. People with weakened immune systems are at a particular risk, especially from the disease cystic fibrosis (the forming thick layers of mucus in the lungs).
To help the diagnosis of the pathogen, MIT researchers have developed a new microfluidic device that could speed the monitoring of bacterial infections associated with cystic fibrosis and other diseases. The advantage with the device is that it can screen patient samples faster and with greater accuracy.
The microfluidic chip is etched with tiny channels, each resembling an elongated hourglass with a pinched midsection. Researchers injected bacteria through one end of each channel, and observed how bacterial cells travel from one end to the other. The cells were propelled by electrical forces. Depending on the type of bacterial cell, they either passed through the channel's narrow section or were trapped at the opening. By using this method, the researchers could screen which bacteria are pathogens and which are harmless.
To demonstrate the method, the researchers examined ordinary strains of P. aeruginosa, along with mutant strains that were missing certain genes required to make the dangerous pathogens. From their experiments, the researchers found that their device is able to distinguish benign bacterial cells from those that are more likely to be pathogenic.
The study was a collaboration between scientists at Ghent University, Belgium, and the University of Queensland, in Australia. The findings have been published in the journal PLOS One. The paper is called “Dielectrophoresis-Based Discrimination of Bacteria at the Strain Level Based on Their Surface Properties.”

Posted by Tim Sandle

Thursday 14 November 2013

New edition of the Pharmacopeial Forum

A new edition of the Pharmacopeial Forum has been issued. This is Volume 39, Number 6 (Nov– Dec 2013).

Items of interest include:
Chapter 7 - Labelling

(Revision proposal target, USP38-NF33)

The previous proposal in PF 38(1) was cancelled and a new proposal was published in PF 38(6). This new proposed general chapter provides definitions and standards for labelling of official articles. On the basis of comments received, this general chapter is being revised to include new provisions and edits to previously proposed revisions.

Chapter 1787 - Measurement of Sub visible Particulate Matter in Therapeutic Protein Injections [New proposed chapter]

(Revision proposal target, USP38-NF33)

Posted by Tim Sandle

Wednesday 13 November 2013

Updates to United States Pharmacopeia

The 1st Supplement to USP36-NF31 has recently been issued. Updates of interest are:

Biological Tests and Assays

Chapter 87 - Biological Reactivity Tests. In Vitro

Changes to the following sections: Introduction, Cell Culture Preparation, Agar Diffusion Test, Direct Contact Test, and Elution Test

Chapter 88 - Biological Reactivity Tests, In Vivo

Changes to the following sections: Introduction, Classification of Plastics, Extracting Media, Systemic Injection Test, Intracutaneous Test, Implantation Test, and Safety Test—Biologicals.

Physical Tests and Determinations

Chapter 643 - Total Organic Carbon

Changes to: Introduction, Bulk Water and addition of Sterile Water section.

Chapter 645 - Water Conductivity

Changes to sample collection procedure for Sterile Water.

General Information

 Chapter 1031 - The Biocompatibility of Materials Used in Drug Containers, Medical Devices and Implants

Introduction; In Vitro Testing, In Vivo Testing, and Class Designation for Plastics and Other Polymers; Biocompatibility of Medical Devices and Implants; and Guidance in Selecting the Plastic or Other Polymer Class Designation for a Medical Device
Chapter 1118 - Monitoring Devices – Time, Temperature and Humidity

The general information chapter has been re-written and the devices described in this chapter are those most commonly used to monitor the controlled storage and established distribution of drug products following Good Distribution Practices (GDP).

In addition, some further sterilization chapters have been produced:

Chapter 1229 - Sterilisation of Compendial Articles [NEW]
Chapter 1229.1 - Steam Sterilisation by Direct Contact [NEW]
Chapter 1229.2 - Moist Heat Sterilisation of Aqueous Liquids [NEW]

There has also been an update to the chapter relating to water:

Chapter 1231 - Water for Pharmaceutical Purposes

Types of water, Chemical Considerations

The 2nd Supplement to USP36-NF31 is shortly to be issued. Items of interest here include:

Apparatus for Tests and Assays

Chapter 16 - Automated Methods of Analysis. This chapter has been deleted.

General Information

 Chapter 1030 - Biological Assay Chapters – Overview and Glossary [NEW]

Chapter 1034 - Analysis of Biological Assays - Appendix–Glossary, Glossary, and Glossary References added.

The USP–NF is a single–volume combination of two official compendia, the United States Pharmacopeia (USP) and the National Formulary (NF). Monographs for drug substances and preparations are featured in the USP. Excipient monographs are in the NF.

Posted by Tim Sandle

Tuesday 12 November 2013

Pathogen Safety: Would you like a free pass?

Dear Group Member,

In the run-up to the Pathogen Safety Summit taking place next week, this group has been offered the opportunity to participate in a competition to receive a free pass to the summit!

Please see their message below:

We understand that the constant evolution of pathogens threatening to overcome your biosafety strategies is a real challenge. How would you like a complimentary guest pass* to attend our upcoming PathogenSafety Summit in Munich on 18th - 20th November, to hear practical strategies to this from the experts?

Our partners have contributed towards 2 free passes to the summit, to enable you to join Heads of QA/QC, Process Development, Microbiologists and Viral Specialists from organisations including the FDA, Genzyme, CSL Behring, Merck-Millipore, ISIA and Rentschler Biotechnologie! They will be hearing unpublished research and in-depth case studies about how to:
   * KEEP CALM AND CARRY ON when your manufacturing facility reports contamination – interactive sessions with Synthon
   * Ensure quality when sourcing raw materials and replacing animal-derived media components – strategies from Genzyme and Cobra Biologics
   * Accelerate detection of Mycoplasma using rapid microbial methods and statistical tools – case study from MSD
   * Perform cell line viral risk assessments in harmony with EU Annex 2 and ICH Q5A – key insights from Novartis
   * Troubleshoot and discuss your challenges utilising new technologies with the FDA

And we don't want you to miss out! Entering our prize draw is simple - just email with your details below:

Job Title:
Phone No.:

If you are unable to make it yourself, please do feel free to forward this opportunity to a colleague who may be interested!  For more information take a look at the agenda online.

I look forward to hearing from you very shortly.

Kind regards,

Jon Shah
Pathogen Safety Summit
T: +44 (0)20 7036 1305 | E: | W:

*Complimentary passes offered by IQPC are non-transferrable between organisations and only transferrable between individuals within the same organisation where written permission is obtained from IQPC in advance. Complimentary passes are available to Pathogen Safety Summit end-user companies only. The offer does not extend to any company whose main or partial business is the provision of products or services of any kind to the aforementioned company types. IQPC reserves the right to revoke or refuse issue of complimentary tickets at any time.

Posted by Jon Shah

Evaluation, Validation and Implementation of Alternative and Rapid Microbiological Methods

PDA Technical Report 33, Revision 2013 (TR 33): Evaluation, Validation and Implementation of Alternative and Rapid Microbiological Methods has now been issued.

Technical Report No. 33, Revision 2013 (TR 33):Evaluation, Validation and Implementation of Alternative and Rapid Microbiological Methods is intended to provide guidance for the successful evaluation, validation, and implementation of alternative and rapid microbiological methods needed by the pharmaceutical, biotechnology and medical device industries to assure product quality.

For further details, see PDA

Posted by Tim Sandle

Monday 11 November 2013

CRE: The new superbug?

Carbapenem-resistant Enterobacteriaceae (CRE) is a group of gram-negative bacteria, including Klebsiella species and Escherichia coli, that have high levels of resistance to carbapenem antibiotics.

On 7 March 2013, CNN reported:

“Hospitals need to take action against the spread of a deadly, antibiotic-resistant strain of bacteria, says the Centers for Disease Control and Prevention. The bacteria kill up to half of patients who are infected.

“The bacteria, called carbapenem-resistant Enterobacteriaceae or CRE, have increased over the past decade and grown resistant to even the most powerful antibiotics, according to the CDC. In the first half of 2012, 200 health care facilities treated patients infected with CRE.”

According to the CDC:

“Healthy people usually do not get CRE infections. In healthcare settings, CRE infections most commonly occur among patients who are receiving treatment for other conditions. Patients whose care requires devices like ventilators (breathing machines), urinary (bladder) catheters, or intravenous (vein) catheters, and patients who are taking long courses of certain antibiotics are most at risk for CRE infections.

“Some CRE bacteria have become resistant to most available antibiotics. Infections with these germs are very difficult to treat, and can be deadly—one report cites they can contribute to death in up to 50% of patients who become infected.”

Elsevier has some interesting references to CRE, which can be found here.
Posted by Tim Sandle

Consideration for infection control

Infection control is one of the most important aspects of healthcare and is based on the objectives of preventing transmission of infection between patients, and on the prevention of patients from contracting nosocomial infections (hospital acquired infections).

To explore the main routes of contamination and to explore some of the preventative measures that can be adopted, Tim Sandle and Jennifer Sandle have written a review article for Arab Medical Hygiene.

The article considers surfaces, equipment, clothing, flooring, staff screening, staff training, vaccination, good building design, infection surveillance, hand sanitisation, and cleaning and disinfection.

The reference is:

Sandle, T. and Sandle, J. (2013). An Important Aspect of Healthcare: Outlining the many considerations of infection control, Arab Medical Hygiene, October 2013, pp34-39

For a copy, please contact Tim Sandle

Posted by Tim Sandle

Sunday 10 November 2013

Clean Air and Containment Review

A new edition of Clean Air and Containment Review is available (issue 16). This excellent publication covers cleanrooms, controlled environments, clean air devices, and contamination.

The latest issue features the following articles:
  • Control of floor level contamination by Gerry Prout
  • Cleanroom lighting and LEDs by Graham Gould
  • Biological indicators for hydrogen peroxide vapour technology by Lynne Murdoch
  • Trends in healthcare cleanroom practice: single-use sterile disposable technology by Tim Sandle
  • Conference report: GERPAC 2013 by Tim Coles
For details about subscribing, see CACR.

Posted by Tim Sandle

Bicontamination: New PHSS Technical Monograph

The PHSS (Pharmaceutical and Healthcare Sciences Society) have issued a monograph on biocontamination control: PHSS Technical Monograph No 20 (2013).

The monograph was put together by a team of healthcare and pharmaceutical professionals (Pharmaceutical Microbiology’s Tim Sandle was part of the team). The monograph has been reviewed by the U.K. regulatory inspection agency, the MHRA.

The contents are:
  • Section 1. Introduction and scope includes a review of the challenges and requirements for Bio-contamination control and cross contamination control with a holistic approach to monitoring and proactive investigations in response to increased risk from changes in biocontamination profiles.
  • Section 2. Bio-contamination characterisation and risk profiling. Methodologies and strategies that profile bio-contamination through establishing control, in operations and holistic monitoring.
  • Section 3. Bio-contamination control principles and best practice guidance considering Quality by Design, different processes, control attributes, background environments and Barrier technologies.
  • Section 4. Bio-contamination monitoring including classical and Rapid Micro Methods (RMM).
  • Section 5. Bio-contamination Deviation management including considerations and guidance in completing investigations and undertaking corrective and preventative actions (CAPA).

For further details, see the PHSS

Posted by Tim Sandle

Saturday 9 November 2013

Key concerns for infection control

Clostridium difficile and norovirus appear to be the main causes of concern for infection control professionals as we enter the winter months according to the latest survey. Conducted at Infection Prevention 2013, the survey revealed that 48% of the respondents highlighted C difficile as the primary cause of concern and 36% highlighted norovirus.

Carried out by Bioquell, a provider of no-touch infection control solutions to the healthcare industry, the survey of 170 infection control nurses and senior practitioners were asked to rank various pathogens in order of priority and also indicate any others that they were concerned about. The findings revealed that CPE (carbapenemase-producing Enterobacteriaceae) was becoming a major concern (19%). Additionally, Acinetobacter (2%), MRSA (4%) and VRE (4%) were further potential issues being faced by infection control teams.

For more details, see Hospital Pharmacy Europe.

Posted by Tim Sandle

Pharmig: 21st Annual Microbiology Conference

Pharmig (Pharmaceutical Microbiology Interest Group), is hosting its 21st Annual Microbiology Conference. The event - the leading microbiology event for UK and Ireland - is taking place on 20th & 21st November, 2013.

The venue is the Oxford Belfry Hotel - Oxford.

The key speakers are:
  • Di Morris, Pharmaceutical Solutions Ltd (ex MHRA)
  • Andrew Matthews, Quantum Pharmaceuticals
  • Barbara Gerten, Merck Millipore
  • Michael Miller, Microbiology Consultants, LLC & Owner
  • Edel Fitzmaurice, Fitzmaurice Scientifi c Ltd
  • Julie Roberts, J. Roberts Associates Ltd
  • Dr Anthony Hilton, Aston University
  • John Hutcheson, Hutch20 Ltd
  • Dr Simon Richards, MEDDEV QA Ltd
  • Rachel Blount, Nitritex
  • David Keen, GlaxoSmithKline
  • Dr Tim Sandle, Bio Products Laboratory
  • Tony Mayhall, Custom Pharmaceuticals
  • Stephen McGrath, TEVA Pharmaceuticals Ireland
  • Paul Newby, GlaxoSmithKline
For further details, see Pharmig.

Posted by Tim Sandle

Friday 8 November 2013

New Microbe Found in Spacecraft Cleanrooms

A rare, recently discovered microbe that survives on very little to eat has been found in two places on Earth: spacecraft cleanrooms in Florida and South America.

Tersicoccus phoenicis is an aerobic, non-motile, Gram-reaction-positive cocci and is associated with two strains: 1P05MAT and KO_PS43. The bacteria is berry-shaped and found in spacecraft assembly clean room facilities: Tersi is from the Latin for clean, Coccus is from the Greek for berry and Phoenicis is derived from NASA's Phoenix Mars Lander, the spacecraft being prepared in 2007 when the bacterium was first discovered in the Florida clean room.

Microbiologists often do thorough surveys of bacteria and other microbes in spacecraft cleanrooms. Fewer microbes live there than in almost any other environment on Earth, but the surveys are important for knowing what might hitch a ride into space. If extraterrestrial life is ever found, it would be readily checked against the census of a few hundred types of microbes detected in spacecraft cleanrooms.

The work to keep cleanrooms extremely clean knocks total microbe numbers way down. It also can select for microbes that withstand stresses such as drying, chemical cleaning, ultraviolet treatments, and lack of nutrients. Perversely, microbes that withstand these stressors often also show elevated resistance to spacecraft sterilization methodologies such as heating and peroxide treatment.

"We want to have a better understanding of these bugs, because the capabilities that adapt them for surviving in cleanrooms might also let them survive on a spacecraft," says microbiologist Parag Vaishampayan of NASA's Jet Propulsion Laboratory, Pasadena, Calif., lead author of the 2013 paper about the microbe. "This particular bug survives with almost no nutrients."

This population of berry-shaped bacteria is so different from any other known bacteria, it has been classified as not only a new species, but also a new genus, the next level of classifying the diversity of life. Its discoverers named it Tersicoccus phoenicis. Tersi is from Latin for clean, like the room. Coccus, from Greek for berry, describes the bacterium's shape. The phoenicis part is for NASA's Phoenix Mars Lander, the spacecraft being prepared for launch in 2007 when the bacterium was first collected by test-swabbing the floor in the Florida cleanroom.

Some other microbes have been discovered in a spacecraft cleanroom and found nowhere else, but none previously had been found in two different cleanrooms and nowhere else. Home grounds of the new one are about 2,500 miles apart, in a NASA facility at Kennedy Space Center and a European Space Agency facility in Kourou, French Guiana.

A bacterial DNA database shared by microbiologists worldwide led Vaishampayan to find the match. The South American detection had been listed on the database by a former JPL colleague, Christine Moissl-Eichinger, now with the University of Regensburg in Germany. She is first co-author of the paper published this year in the International Journal of Systematic and Evolutionary Microbiology identifying the new genus.

The same global database showed no other location where this strain of bacteria has been detected. That did not surprise Vaishampayan. He says, "We find a lot of bugs in cleanrooms because we are looking so hard to find them there. The same bug might be in the soil outside the cleanroom but we wouldn't necessarily identify it there because it would be hidden by the overwhelming numbers of other bugs."

A teaspoon of typical soil would have thousands more types of microbes and billions more total microbes than an entire cleanroom. More than 99% of bacterial strains, as identified from DNA sequences, have never been cultivated in laboratories, a necessary step for the various types of characterization required to identify a strain as a new species.

Microbes that are tolerant of harsh conditions become more evident in cleanroom environments that remove the rest of the crowd.

"Tersicoccus phoenicis might be found in some natural environment with extremely low nutrient levels, such as a cave or desert," Vaishampayan speculates. This is the case for another species of bacterium (Paenibacillus phoenicis) identified by JPL researchers and currently found in only two places on Earth: a spacecraft cleanroom in Florida and a bore hole more than 1.3 miles deep at a Colorado molybdenum mine.
Ongoing research with Tersicoccus phoenicis is aimed at understanding possible ways to control it in spacecraft cleanrooms and fully sequencing its DNA. Students from California State University, Los Angeles, have participated in the research to characterize the newly discovered species.

Posted by NASA

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