Tuesday, 30 August 2016

Contamination Control in Healthcare Product Manufacturing, Volume 4


A new edition of Contamination Control in Healthcare Product Manufacturing has been published. This is volume 4.

Contamination Control in Healthcare Product Manufacturing, Volume 4, edited by Russell E. Madsen and Jeanne Moldenhauer, is primarily focused on microbiological contamination and the methods used to monitor and control it, a secondary focus looks at chemical contamination that may result from the use of cleaning and disinfecting agents. There is something for almost everyone who has responsibility for developing or using microbiological contamination control programs and systems.


Edited by experts and written by global subject matter professionals, this vital addition to the Contamination Control series offers new chapters covering current, relevant information including:

Regulatory changes relative to ISO 14644, Parts 1 and 2
Updates to ISO 11737-1
Risks of spores including preventive measures and disinfection
Utilities, surfaces and practices that impact cleanrooms
Cleanroom gowning and behavior
Regulatory guidance and how-to relative to handwashing
Contamination in water systems
Contamination in gaskets, drains, cooling systems and many other problem areas
And more including chapters covering Monitoring relative to USP <1116>, control limits, excursions, risk-based big data in aseptic processing and methods for effective use of Maldi-Tof

Tim Sandle has contributed two chapter to volume 4:

Sandle, T. (2016) ISO 14644 Parts 1 and 2 - The revised cleanroom standard and contamination control. In Madsen, R. E. and Moldenhaurer, J. (Eds.) Contamination Control in Healthcare Product Manufacturing, Volume 4, DHI, River Grove, USA, pp3-32

Sandle, T. (2016) Risk of microbial spores, prevention measures and disinfection strategies. In Madsen, R. E. and Moldenhaurer, J. (Eds.) Contamination Control in Healthcare Product Manufacturing, Volume 4, DHI, River Grove, USA, pp59-95

For details see: PDA

Posted by Dr. Tim Sandle

Monday, 29 August 2016

Health infographic



Posted by Dr. Tim Sandle

Influenza alters the gut microflora

New study on respiratory viral infections and the gut

Influenza is one of the most contagious viral infections of the nose, throat and lungs. Symptoms include fever, extreme tiredness, sore throat, stuffy nose and muscle aches. Some infected people will also develop gastrointestinal symptoms such as nausea, vomiting and diarrhea; however, the molecular mechanisms involved are unclear. A new study in mice shows that influenza virus infection in the lungs alters the gut microbiota and immune responses via type I interferons.

Posted by Dr. Tim Sandle

All U.S. Blood Donations Should Be Screened For Zika


The Food and Drug Administration is recommending that blood banks screen all blood donations in the U.S. for the Zika virus. The expansion of testing won't happen all at once. The FDA is advising blood establishments in 11 states to begin testing within the next four weeks. Those states include Alabama, Arizona, California, Georgia, Hawaii, Louisiana, Mississippi, New Mexico, New York, South Carolina and Texas.

Currently, Zika is being spread by mosquitoes in South Florida, Puerto Rico and the U.S. Virgin Islands, as well as most countries in the Caribbean and Central and South America. There are a total of 2,517 cases of Zika in the U.S. states and D.C., according to the Centers for Disease Control and Prevention, with 9,011 more in U.S. territories.

Posted by Dr. Tim Sandle

Sunday, 28 August 2016

Temperature mapping


An initial temperature mapping exercise should be carried out on the storage area before use, under representative conditions.

The U.K. MHRA have an interesting blog post on GDP and temperature mapping. Here is an excerpt:

"Temperature monitoring equipment should be located according to the results of the mapping exercise, ensuring that monitoring devices are positioned in the areas that experience the extremes of fluctuations.

The mapping exercise should be repeated according to the results of a risk assessment exercise or whenever significant modifications are made to the facility or the temperature controlling equipment."

For more details see MHRA Blog.



Posted by Dr. Tim Sandle

Saturday, 27 August 2016

Candida auris


Candida auris is an emerging fungal pathogen, associated with bloodstream infections, wound infections and otitis, first identified as the cause of a hospital outbreak in England in 2015.

C. auris has been associated with bloodstream infections, wound infections and otitis. It has also been cultured from urine and the respiratory tract, although it is not known if positive cultures from these sites represent infections or colonisations.

To find out more, see: Public Health England.

Posted by Dr. Tim Sandle

An Overview Of IVC Filters: What Does Research Say?


By Michael Monheit

A 2013 editorial in the journal of the American Association questioned the existence of IVC filters that have been on the market for a very long time without proof of efficacy. The medical journal pointed out that IVC filters should work given that they work on the logic that you can prevent a traveling blood clot from reaching the lungs by catching it through placing a small wire net in the largest body vein.

America's largest manufacturers of IVC filters are Cook Medical and C.R. Bard who are credited for making seven different models, which include several that have been withdrawn from the market due to safety concerns. There has been a widespread use of these devices since their inception and have made their way to thousands of bodies.

Were The Devices Tested?

No member of the vast medical community could determine how effective the device was until 30 years after their invention when a French study was conducted between 1997 and 2005 besides a 1973 study. During this time, the manufacturers would come up with new features and ease the process of implantation for healthcare professionals.

The new designs were spurred by many studies that showed little benefits and serious long-term consequences associated with IVC filters that were designed for permanent implantation. Since the very first device to the present, the benefits of IVC filters remain completely untested which means they may be useless. BloodThinnerHelp.com states that the only clinical trial to assess the effectiveness of IVC filters done in 1973, revealed that they had no effect on ultimate mortality rates, but they would reduce the rate of pulmonary embolism

According to the US Food and Drug Administration (FDA) in 1979, approximately 2,000 IVC filters were implanted mainly to patients likely to suffer from a pulmonary embolism. 28 years later after numerous product redesigns, an estimated 167,000 patients had received IVC filters with an increased demand for the product.

Why Is There Legal Action Being Taken Now?

Despite IVC filters being widely accepted for many years, there has never been empirical evidence that shows that they perform the function they are being sold for. The previously mentioned French study was conducted on 400 patients with deep vein thrombosis, a lower limbs blood clot that can pass up to block veins in the lungs. This risk is usually referred to as pulmonary embolism and is what IVC filters are designed to prevent. Out of the 400, 200 were treated with only "standard anticoagulant treatments" such as warfarin while the other half were outfitted with IVC filters. Subsequently, for eight years the researchers recorded health outcomes and tracked the progress of patients.

The results revealed that IVC filters indeed lower the risk of pulmonary embolism (thus preventing blood clots from reaching the lungs). Twenty-four patients from the group without filters suffered from "symptomatic" PE, while only nine from the group with the filters did. Unfortunately, the devastating result was that patients with IVC filters were at an increased risk to develop deep vein thrombosis. It was apparent that filters would cause one of the conditions they were designed to treat.

FDA On IVC filters

Apart from facing several civil lawsuits, Cook Medical and C.R. Bard have been hit with several formal warnings from FDA. Bard has received a warning letter citing eight violations of FDA requirements, the worst violation being manufacturing and marketing IVC models not cleared for sale by FDA and failure to report serious complications to the FDA.

The FDA released an update of its 2010 safety communication in 2014 that retrievable IVC filters shouldn't be left for too long in patients and should be removed by doctors between 29 and 54 days after being implanted. Now there have been over 200 personal injury lawsuits that have been filed against Cook Medical, by patients who have suffered from the lack of medical research of the devices. Lawsuits have alleged that Cook marketed a defective medical device and falsely represented its efficacy and did not adequately warn the public of the potential dangers associated with it.

Author Bio:

Michael Monheit, the managing attorney at Monheit Law, has been working to assist individuals and families who have been harmed by defective drugs and products. In fact, Mr. Monheit served on the Plaintiff’s Steering and Executive Committee for MDL 1148. He understands how stressful it can be to stand up to a major corporation and is committed to making sure that plaintiffs know they have someone on their side.


Friday, 26 August 2016

Identification of Listeria species, and other non sporing Gram positive rods


A systematic approach is needed to differentiate clinically encountered, morphologically similar, aerobic and facultatively anaerobic, non-sporing Gram positive rods.

A publication covering the identification of Listeria species, and other non sporing Gram positive rods, except Corynebacterium, has been issued by UK Standards for Microbiology Investigations (document SMI ID 3).

There are currently ten validly named species in the genus Listeria: L. monocytogenes, L. ivanovii, L. seeligeri, L. innocua, L. welshimeri, L. grayi, L. fleischmannii, L. marthii, L. rocourtiae and L. weihenstephanensis. Of these ten species, the first six can potentially cause infections in humans, albeit rarely in some cases.

Listeria species are short Gram positive rods, 0.4-0.5 x 0.5-2.0μm, with rounded ends, occurring singly or in short chains and occasionally appearing filamentous. Members of the genus are facultative anaerobes, non-sporing, non-acid fast and do not possess a capsule. Listeria species are motile by peritrichous flagella when grown at 20°C - 25°C and display a characteristic “tumbling” motility. The optimum growth temperature (but not for motility) is 30-37°C.

Colonies on blood agar are non-pigmented and may resemble those of β-haemolytic streptococci.

To access the publication see Public Health England.

Posted by Dr. Tim Sandle

Thursday, 25 August 2016

Microbes affect the world’s atmosphere


Microbiologists have discovered how a tiny yet abundant ocean organism helps regulate Earth's climate. They showed that these tiny, hugely abundant bacteria could make the environmentally important gas, dimethyl sulfide.

Research published in Nature Microbiology has revealed how a bacterial group called 'Pelagibacterales' plays an important function in keeping Earth's atmosphere stable.

The project was led by Prof Steve Giovannoni and Dr Jing Sun at Oregon State University, in collaboration with researchers from UEA among others. The researchers showed that these tiny, hugely abundant bacteria could make the environmentally important gas, dimethyl sulfide. Researchers at UEA identified and characterised the gene that is responsible for this property.

Dr Jonathan Todd from UEA's School of Biological Sciences said: "These types of ocean bacteria are among the most abundant organisms on Earth -- comprising up to half a million microbial cells found in every teaspoon of seawater.

"We studied it at a molecular genetic level to discover exactly how it generates a gas called dimethylsulfide (DMS), which is known for stimulating cloud formation.

"Our research shows how a compound called dimethylsulfoniopropionate that is made in large amounts by marine plankton is then broken down into DMS by these tiny ocean organisms called Pelagibacterales.

"The resultant DMS gas may then have a role in regulating the climate by increasing cloud droplets that in turn reduce the amount of sunlight hitting the ocean's surface."

For further details, see:

Jing Sun, Jonathan D. Todd, J. Cameron Thrash, et al. The abundant marine bacterium Pelagibacter simultaneously catabolizes dimethylsulfoniopropionate to the gases dimethyl sulfide and methanethiol. Nature Microbiology, 2016; 16065 DOI: 10.1038/nmicrobiol.2016.65

Posted by Dr. Tim Sandle

Wednesday, 24 August 2016

ISO 50001 on energy management under revision



Improving energy performance and reducing energy costs is one of the most important tasks that organizations throughout the world have to achieve. ISO 50001 on energy management can help organizations with this exercise.
Since its publication five years ago, ISO 50001 has gained much importance. In fact, nearly 7 000 organizations were already certified to the standard at the end of 2014.

ISO 50001, Energy management systems – Requirements with guidance for use, specifies requirements for establishing, implementing, maintaining and improving an energy management system. The aim is to enable an organization to follow a systematic approach in achieving continual improvement of energy performance, including energy efficiency, use and consumption.

After five years of existence, time has come to revise ISO 50001 to ensure it remains a useful tool for all types of businesses and organizations around the world.

For further details see ISO

Posted by Dr. Tim Sandle

Tuesday, 23 August 2016

Standard to validate microorganism testing methods (food)


ISO 16140:2003 for the validation of alternative (proprietary) microbiological methods has just been revised. The new multipart standard provides a specific protocol and guidelines for the validation of methods both proprietary (commercial) or not. Proprietary methods are generally cheaper to use, produce results faster than traditional culturing methods and are simpler to perform as they require fewer technical skills. What’s more, most are partly or completely automated, so easier to use in less experienced laboratories, such as factory and commercial laboratories and with less technical human resources.


Two parts of ISO 16140 series now published

ISO 16140-1:2016, Microbiology of the food chain – Method validation – Part 1: Vocabulary, describes the terminology used in microbial testing, while ISO 16140-2:2016, Microbiology of the food chain – Method validation – Part 2: Protocol for the validation of alternative (proprietary) methods against a reference method, is dedicated to the validation of proprietary microbiological methods. They are designed to help food and feed testing laboratories, test kit manufacturers, competent authorities, and food and feed business operators to implement microbiological methods. ISO 16140-2 includes two phases, the method comparison study and the interlaboratory study, with separate protocols for the validation of qualitative and quantitative microbiological methods.

Over a hundred alternative methods have been validated based on the previous version of ISO 16140, and the standard was updated to provide new insights on the validation of microbiological methods and experience gained from conducting validation studies across the world. Today, many alternative (mostly proprietary) methods exist that are used to assess the microbiological quality of raw materials and finished food products and monitor the microbiological status of manufacturing processes. The developers, end-users and authorities need a reliable common protocol for the validation of such alternative methods. With this new protocol, the data generated will also provide potential end-users with performance data for a given method, thus enabling them to make an informed choice on the adoption of a particular (alternative) method. This data can also serve as a basis for the certification of a method by an independent organization.

 “The validation according to ISO 16140-2 will lead to a higher reliability of the alternative method test result and the users will benefit from having microbiological test results available sooner. Most likely, this will contribute to greater food safety,” explained Paul in ‘t Veld, the Convenor of Working Group 3 on method validation (ISO/TC 34/SC 9/WG 3 whose secretariat is held by NEN, ISO member for the Netherlands) that is responsible for the development of the ISO 16140 series.

Posted by Dr. Tim Sandle

Monday, 22 August 2016

Revised monocyte activation test chapter



During its 155th Session, held in Strasbourg on 21-22 June 2016, the European Pharmacopoeia Commission adopted a revision of the general chapter Monocyte-activation test (2.6.30) in order to make it more widely useable by stakeholders and thus facilitate a reduction in testing on live animals.

The MAT is suitable, after product-specific validation, as a replacement for the rabbit pyrogen test (RPT). The MAT offers significant advantages over animal testing: based on the human fever response, it provides a more relevant prediction of pyrogenic activity than the RPT, it can detect endotoxin and non-endotoxin pyrogens and is applicable to a greater variety of products than the RPT; moreover, it is more accurate as well as more cost- and time effective than the RPT.

For further details see: EDQM

Posted by Dr. Tim Sandle

Sunday, 21 August 2016

Strategy for disrupting bacterial biofilms


Biofilms are communities of bacteria that adhere to a surface and are nearly impossible to eradicate when they are pathogenic, or disease-causing. Fortunately, a discovery from the laboratories of Lauren Bakaletz, PhD, and Steven Goodman, PhD, in The Research Institute at Nationwide Children's Hospital, provides strong evidence that an innovative therapeutic approach may be effective in the resolution of bacterial biofilm diseases.

"Most, if not all, chronic and recurrent bacterial infections include a biofilm in the disease course," says Dr. Bakaletz, director of the Center for Microbial Pathogenesis in The Research Institute at Nationwide Children's and senior author of the recent study, published in the journal EBioMedicine. "Biofilms are sophisticated, towering communities of bacteria that are very resistant to clearance by either our own immune system or the action of antibiotics."

These chronic and recurrent bacterial infections include urinary tract infections, which result in nearly half a million emergency room visits annually, middle ear infections, sinusitis, and chronic wound infections, to name a few.

"Given how common and troublesome biofilm diseases are, we endeavored to develop a novel approach to disrupt these biofilms," continues Dr. Goodman, principal investigator in the Center for Microbial Pathogenesis at The Research Institute and co-author of the study. "This way, traditional antibiotics and/or the body's own natural immune system could now kill the bacteria released from the biofilm that had caused the infections, thus hopefully providing a cure."

This novel approach involved targeting extracellular DNA (eDNA) and associated DNABII proteins in biofilms, which are common components of biofilms and help maintain the structure of biofilms. Researchers built on their previous work, which demonstrated that an antibody directed against DNABII proteins resulted in the catastrophic collapse of bacterial biofilms.

"One method that we and many of our colleagues who also study biofilms rely upon is to allow the bacteria we are specifically interested in to form a biofilm in a special culture vessel in the lab," says Dr. Bakaletz. "Once that biofilm is mature, we then attempt to disrupt it by targeting specific bacterial proteins within the biofilm."

Using a form of microscopy called confocal scanning light microscopy and COMSTAT analysis software, a program that analyzes image stacks of biofilms, they were able to take a series of images of the biofilm both before and after treatment, according to researchers. This allowed them to determine how effectively they had disrupted the biofilm and released the bacteria that created it.

Of the results, Dr. Bakaletz explains, "We showed that our biofilm disruption technology was highly effective against many different bacteria that cause a variety of human diseases; that it worked synergistically with a traditional antibiotic -- tobramyacin, which alone was completely ineffective against the biofilm; and further, that it also worked very well in two unique models of human respiratory tract disease."

The monoclonal antibodies used in these studies -- a type of protein made in the laboratory that can bind specifically to its DNABII protein target -- are presently being adapted for delivery to human patients in clinical trials, says Dr. Bakaletz.

"We are very excited to develop this technology further, with the hope of making a difference in both human and animal health," adds Dr. Goodman. "We are currently both raising funds and identifying partners that can help us achieve these goals."

For further details see:

Laura A. Novotny, Joseph A. Jurcisek, Steven D. Goodman, Lauren O. Bakaletz. Monoclonal antibodies against DNA-binding tips of DNABII proteins disrupt biofilms in vitro and induce bacterial clearance in vivo. EBioMedicine, 2016; DOI: 10.1016/j.ebiom.2016.06.022

Posted by Dr. Tim Sandle

Saturday, 20 August 2016

Pharmeuropa reviews


Pharmeuropa 28.1 contains two draft monographs of interest:

2.2.2    Degree of coloration of liquids

This draft corresponds to Stage 4 within the Pharmacopoeial harmonisation process (Ph. Eur., JP, and USP). The coordinating pharmacopoeia is the USP.


0333                Heparin Sodium

Related substances: the proposal is to introduce a disregard limit to the related substances test, in line with the principles of general chapter 2.2.46 Chromatographic separation techniques. The current text does not specify a quantitative limit for ‘any other impurity’ and compliance with the acceptance criterion depends on the sensitivity of the method.

Pharmeuropa 28.2 contains two further draft monographs of interest:

1473    Soya-bean oil, refined

Identification: reference to the test for composition of fatty acids has been added since it is more specific than that for identification of fatty oils by TLC; the latter has been maintained as second identification.
Composition of fatty acids: the term ‘and isomer’ has been included in the limit for oleic acid since baseline separation of oleic acid and its more abundant positional isomer, cis-vaccenic acid, is not achieved with the current method

2034                Substances for Pharmaceutical Use

In line with the implementation strategy of the ICH Q3D guideline, a new paragraph on elemental impurities has been added to this general monograph. Its aim is to clarify requirements for substances for pharmaceutical use used for the production of medicinal products that are outside of the scope of general chapter 5.20 (which will be aligned with the ICH Q3D guideline). For medicinal products within the scope of general chapter 5.20, the limits for elemental impurities apply to the medicinal product.

In addition, a sentence has been added to the production section to highlight the need during risk assessment, to take any necessary account of potential elemental impurities derived from intentionally added catalysts and reagents.

Pharmeuropa is an online EDQM publication. Draft monographs are published in Pharmeuropa for public enquiry, which lasts for three months. Comments received are processed by EDQM, at this stage the draft can be amended and republished. If no further revision is required the draft monograph is proposed to the European Pharmacopoeia Commission if adopted an implementation date is given and this is about one year after the adoption of the monograph.

Posted by Dr. Tim Sandle

Friday, 19 August 2016

New drug target for Zika

Scientists potentially have found a way to disrupt Zika and similar viruses from spreading in the body.


A team at Washington University School of Medicine in St. Louis has identified a single gene pathway that is vital for Zika and other flaviviruses to spread infection between cells. Further, they showed that shutting down a single gene in this pathway—in both human and insect cells—does not negatively affect the cells themselves and renders flaviviruses unable to leave the infected cell, curbing the spread of infection.

The study, published in Nature, points to a potential drug target for Zika and other flaviviruses such as dengue and West Nile that have major impacts on public health.

To identify genes that flaviviruses rely on, Diamond and his colleagues utilized a gene editing technology called CRISPR that is capable of selectively shutting down individual genes. Viruses must hijack host cells to replicate and spread, making them dependent upon the genetic material of the organisms they infect. If a cell lacks a gene that the virus requires for infection, the virus will be stopped in its tracks, and the cell will survive. Such evidence indicates that the missing gene is vital to viral spread and should be studied further.

Of the nine key genes Diamond and his colleagues identified, one called SPCS1, when disabled, not only reduces viral infection but appears to have no adverse effects on the cells the scientists studied. The researchers performed the first experiments on West Nile virus and then showed that the same results held true for other Flaviviridae family members, including Zika, dengue, yellow fever, Japanese encephalitis and hepatitis C viruses.

While the absence of this gene shut down the spread of flaviviruses, the researchers found that eliminating the gene had no detrimental effect on other types of viruses, including alphaviruses, bunyaviruses and rhabdoviruses.

For further details, see: Nature.

Posted by Dr. Tim Sandle