Suppression of the Test for Abnormal Toxicity from the European Pharmacopoeia

During its 159th plenary session, the European Pharmacopoeia Commission endorsed the complete suppression of the test for abnormal toxicity from the European Pharmacopoeia (Ph. Eur.).

As part of this exercise, 49 monographs revised to remove the test for abnormal toxicity were adopted by the Commission; notably, these included 36 monographs on vaccines for human use. In addition, as the general chapter Abnormal Toxicity (2.6.9) will no longer be referenced in any monograph, it will subsequently be rendered obsolete and will also be deleted from the Ph. Eur.

The Ph. Eur. Commission remains fully committed to the reduction of animal use wherever possible in pharmacopoeial testing, in accordance with the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes. The decision to suppress the test for abnormal toxicity at the 159th session of the Ph. Eur. Commission is a strong illustration of this commitment.

See: abnormal toxicity

Posted by Dr. Tim Sandle

Decoy molecules target E. coli to treat UTI in mice

Researchers have designed sugar molecules that block E. coli bacteria from binding to urinary tissues, allowing the bacteria to be washed out of the urinary tract. The compounds represent a step toward treating UTIs without antibiotics.

The bacteria E. coli cause 80 percent of UTIs, leading to painful, burning urination. The bacteria then sometimes travel to the kidneys, causing back pain and fever. In rare cases, they spread to the blood, a potentially lethal complication.

Often, UTIs can be cleared up with antibiotics, but 10 to 20 percent of cases do not respond to current first-line drugs. Hultgren and his colleagues are working on an alternative that would prevent bacteria from causing disease, which may help reduce dependency on antibiotics.

E. coli's first step in causing UTIs is to latch onto sugars on the surface of the bladder with long, hairlike structures called pili. Hultgren and co-senior author James W. Janetka, PhD, an associate professor of biochemistry and molecular biophysics, previously created mannosides, modified forms of a sugar called mannose, that the bacteria favor over typical sugars on the bladder wall. When mice with UTIs were given the mannosides, the E. coli in their bladders grabbed hold of those molecules and were swept away.

Researchers have shown that E. coli also can latch onto galactose, another sugar molecule found on urinary tissues. A drug that undermines the bacteria's ability to stay in the body is less likely to drive resistance because, unlike antibiotics, it would not force bacteria to die or evolve resistance in order to survive, the researchers said.

The researchers also demonstrated that the galactoside prevented the bacteria's adhesive protein from sticking to human kidney tissue.

See:

Vasilios Kalas, Michael E. Hibbing, Amarendar Reddy Maddirala, Ryan Chugani, Jerome S. Pinkner, Laurel K. Mydock-McGrane, Matt S. Conover, James W. Janetka, Scott J. Hultgren. Structure-based discovery of glycomimetic FmlH ligands as inhibitors of bacterial adhesion during urinary tract infection. Proceedings of the National Academy of Sciences, 2018; 201720140 DOI: 10.1073/pnas.1720140115



Posted by Dr. Tim Sandle

Testing water for coliforms using a rapid method

Microbial control of pharmaceutical water systems is not only about numbers of microorganisms estimated to be present, as recovered through bioburden testing of a given volume of sampled water; microbiologists additionally need to know the types of organisms present within water.

With this a new article of interest has been published:

Marflitt, A. and Sandle, T. (2018): Evaluation of Readycult® Coliforms 100 Presence/Absence Test for the screening of coliforms and Escherichia coli in pharmaceutical water samples, European Journal of Parenteral and Pharmaceutical Science, 22 (4): 118-125

The abstract is:

The microbiological monitoring of water systems in pharmaceutical facilities requires an assessment of total microbial count, with an action level applicable to the water grade. It is also considered good practice in many facilities to assess water for the presence/absence of identified objectionable microorganisms. Included among these ‘objectionables’ are coliforms, as indicators of substandard water. The traditional approach for assessing for coliforms in water is using a specialised agar. This approach requires an incubation time within the region of 3 to 5 days. This paper assesses an alternative method, which provides a result within 18 to 24 hours. The method evaluated was the Readycult® Coliforms 100, which contains both a chromogenic substrate (to show the presence of coliforms) and a fluorogenic substrate (to show the presence of Escherichia coli). Through a series of experimental tests involving different grades of pharmaceutical water and different microorganisms, the Readycult® Coliforms 100 was shown to be suitable as a rapid microbiological method for screening water, with reactions produced comparable to conventional methods.

For further details, contact Tim Sandle

Posted by Dr. Tim Sandle

BSI Brexit Position Paper

British Standards Instiutte (BSI) has consulted its members and stakeholders about the possible implications of Brexit for standards. The BSI Brexit Position Statement sets out the eight key principles on which BSI’s post-Brexit position is based.

Since the UK voted to leave the EU in June 2016, BSI, in its capacity as the UK’s National Standards Body, has consulted its members and stakeholders about the possible implications of Brexit for standards.

As a result, BSI’s post-Brexit position is to continue to provide UK experts with the standards development framework to support trade in the UK, across Europe and globally. To enable this, our stakeholders are clear that BSI should remain a full member of the European Standards Organizations.

The Brexit Position Paper sets out the eight key principles on which our position is based. These principles are supported by statements from a range of BSI’s stakeholders, including industry associations and individual companies, consumer groups, users of standards and professional institutions.

Use this link to download aPDF of the paper now.

Social stress leads to changes in gut bacteria

Exposure to psychological stress in the form of social conflict alters gut bacteria in Syrian hamsters, according to a new study by Georgia State University.

It has long been said that humans have "gut feelings" about things, but how the gut might communicate those "feelings" to the brain was not known. It has been shown that gut microbiota, the complex community of microorganisms that live in the digestive tracts of humans and other animals, can send signals to the brain and vice versa.

In addition, recent data have indicated that stress can alter the gut microbiota. The most common stress experienced by humans and other animals is social stress, and this stress can trigger or worsen mental illness in humans. Researchers at Georgia State have examined whether mild social stress alters the gut microbiota in Syrian hamsters, and if so, whether this response is different in animals that "win" compared to those that "lose" in conflict situations.

Hamsters are ideal to study social stress because they rapidly form dominance hierarchies when paired with other animals. In this study, pairs of adult males were placed together and they quickly began to compete, resulting in dominant (winner) and subordinate (loser) animals that maintained this status throughout the experiment. Their gut microbes were sampled before and after the first encounter as well as after nine interactions. Sampling was also done in a control group of hamsters that were never paired and thus had no social stress.

Posted by Dr. Tim Sandle

U.S. E. coli outbreak

The CDC, the FDA, several states, and U.S. Department of Agriculture’s Food Safety and Inspection Service are investigating a multistate outbreak of Shiga toxin-producing E. coli O157:H7 infections.

The investigation started by the New Jersey Department of Health, working together with the CDC and FDA. In New Jersey, ill people included in the outbreak had test results showing the presence of E. coli bacteria. Laboratory testing is ongoing to link their illnesses to the outbreak using DNA fingerprinting.

See: Bio Exoert for further details

Posted by Dr. Tim Sandle

Feasibility of eliminating rabies in Africa

The Swiss Tropical and Public Health Institute, together with European and African collaborators (including the Institut Pasteur in Paris), carried out a mass dog vaccination in Chad and determined its effect on human rabies exposure. The study employed a bio-mathematical method for estimating the transmission dynamics of rabies. The researchers conclude that with political will and the necessary funding, elimination of rabies is possible in Africa.

Rabies is a viral disease that kills tens of thousands of people every year, predominantly in Africa and Asia. The disease is transmitted through the bites of infected dogs and foxes (read the disease fact sheet concerning rabies). In West- and Central Europe, rabies was eliminated some 20 years ago. Switzerland was declared free of rabies in 1999 after implementing a strategy targeting foxes.

The study is one of the first research projects to apply a rigorous phylodynamic method to dog rabies, and hence, it expands upon the normative phylogenetics (i.e. assessing the genetic relatedness of virus strains) with the dynamics of transmission over time. This made it possible to calculate the reproductive number of rabies among the dogs after the first mass dog vaccination in 2012.

See:

Jakob Zinsstag, Monique Lechenne, Mirjam Laager, Rolande Mindekem, Service Naïssengar, Assandi Oussiguéré, Kebkiba Bidjeh, Germain Rives, Julie Tessier, Seraphin Madjaninan, Mahamat Ouagal, Daugla D. Moto, Idriss O. Alfaroukh, Yvonne Muthiani, Abdallah Traoré, Jan Hattendorf, Anthony Lepelletier, Lauriane Kergoat, Hervé Bourhy, Laurent Dacheux, Tanja Stadler, Nakul Chitnis. Vaccination of dogs in an African city interrupts rabies transmission and reduces human exposure. Science Translational Medicine, 2017; 9 (421): eaaf6984 DOI: 10.1126/scitranslmed.aaf6984

Posted by Dr. Tim Sandle

What is NAD+ and Why Is It a Hot Topic in Longevity Science?

You may have repeatedly been hearing about NAD+ in health and nutrition circles and, honestly, wondering to yourself what is NAD+?

We’re here to help you understand the importance of NAD+, its functions, its relationship with aging, and why the longevity science community can't stop talking about it.

A guest post by Frank L. Jaksch Jr..

What is NAD+?

Nicotinamide adenine dinucleotide, or NAD+, is a coenzyme that can be found in every cell in your body. In a healthy body, all the necessary NAD+ is created by utilizing vitamin B3 (also known as niacin, or nicotinamide).
Why is NAD+ important?

To put it simply, NAD+ is important because it is required for the necessary biological processes that allow life to happen.

By assisting in the transfer of energy from fatty acids and glucose to the mitochondria (the "powerhouses of the cell") which, in turn, convert them to cellular energy, NAD+ plays a pivotal role in your cellular metabolism. Additionally, NAD+ plays a significant role in regulating how quickly your cells age.

Here are some of the other roles that NAD+ plays in the body:


● Unfolded Protein Response - a protein's shape dictates its function and NAD+ makes sure the form is correct

● Liver Health - your liver breaks down fats for energy and keeps your blood sugar balanced (among other things) and requires NAD+

● Sirtuins - a family of proteins that governs longevity in organisms and needs NAD+

● DNA Health - the systems that fix errors in our DNA require NAD+

● Circadian Rhythm - your sleeping cycle (and everything to do with it) requires NAD+

● Calcium Signaling - communication in the cell requires NAD+

● Stem Cell Maintenance - to have healthy stem cells you need NAD+

● Gene Expression - in response to changing conditions (such as nutrition and stress), your genes are always getting turned on and off, which (surprise!) require NAD+
What causes a decline in NAD+?

The levels of NAD+ decline as a result of the aging process, as well as due to a sedentary lifestyle and overeating. When NAD+ levels decline, the number and density of the mitochondria are also reduced which results in less efficiency or potential dysfunction.

The result of declining NAD+ levels can lead to adverse health consequences, including a slower metabolism. In other words, weaker mitochondria suggest the beginning of the end for your body.
What does NAD+ have to do with aging?

Good question! So, in addition to all the other jobs it has, NAD+ activates enzymes called “sirtuins” (SIRT1 and SIRT3), which help control your genes in ways that promote healthy aging.

The higher your NAD+ levels, the better activated your SIRT1 and SIRT3 enzymes are. This means you get to have healthier mitochondria essential to good health for your body. Makes sense?

As your levels of NAD+ decline with aging, this also results in less engaged sirtuins, less healthy mitochondria, and an “older” body (think: less energy, achy joints, poor memory).
Why is it a hot topic in longevity science?

Despite first being discovered over 110 years ago, everyone is currently talking about NAD+ because many significant discoveries have emerged over the past couple of decades.

Recently, NAD+ has become a hot topic in longevity science thanks to an influential study published by David Sinclair, professor of genetics at Harvard Medical School. In the study, Sinclair and his colleagues bred mice with a defect in SIRT1. As a result of this defect, these mice aged rapidly and showed significant problems with their mitochondria.

However, once the mice turned 22 months old, they were given increased levels of NAD+, and the results were incredible. The mice had less insulin resistance, less inflammation, and less muscle wasting.

As a result of the increase of NAD+ levels, the mice began to appear as though they were merely six months old (for humans, that would be the equivalent of a 60-year-old’s cells shifting to being more like those that belong to a 20-year-old).

This study (and others like it) has led to the idea that increasing NAD+ levels could be a possible way to maintain long-term health in humans.
How do you increase NAD+ levels?

There is still a long path ahead for NAD+ research, but there are some ways you can increase your levels.

1. Exercise

When you work out, your body needs more NAD+ to produce more energy which puts your mitochondria into overdrive. The good news is that your body doesn't halt producing additional NAD+ when you finish exercising. So, by consistently working out, you will be able to increase your mitochondrial pumping protein.

2. Consume fermented foods and beverages

Fermented foods and drinks such as kimchi, kombucha (anything that undergoes the chemical process of fermentation by exposure to lactobacilli) receive, as a byproduct, a small amount of NAD+ which you then consume. Another reason to add kombucha to your morning routine!


3. Take an NAD+ booster

You can also take an NAD+ booster such as nicotinamide riboside (NR) which is a potent form of vitamin B3 that extends various health benefits, including endurance, performance, weight management, cardiovascular health, anti-aging, cognitive function and neuroprotection. If you opt to take an NR supplement (with your doctor's guidance), then take 100 to 250 mg each morning.

That being said, too much vitamin B can damage your liver and lead to other harmful effects.

There is still no conclusive evidence that NAD+ can reverse the aging process; however, by eating healthy, exercising regularly, wearing sunscreen, cutting down on alcoholic beverages, and taking vitamin D supplements, you are well on your way to staying young forever.

AUTHOR BIO

Frank L. Jaksch Jr. is the Chief Executive Officer and a co-founder of ChromaDex. He oversees research, strategy and operations for the Company with a focus on scientific and novel products for pharmaceutical and nutraceutical markets. Mr. Jaksch earned a B.S. in Chemistry and Biology from Valparaiso University.

The Problem of Biofilms and Pharmaceutical Water Systems

Biofilms are problematic to pharmaceutical water systems. If a biofilm develops then an out-of-control situation is likely to emerge. Such a situation can often only be detected from point-of-use samples and since several excursions are required to alert of the probability of a biofilm, the biofilm will most likely have become significantly established at this point in time. This article assesses biofilms and pharmaceutical water systems, considering prevention and control measures; looking at what can be meaningfully gleaned from monitoring; and measures required to address biofilms.

Tim Sandle has written an article for American Pharmaceutical Review. The reference is:

Sandle, T. (2017) The Problem of Biofilms and Pharmaceutical Water Systems, American Pharmaceutical Review, 20 (7): http://www.americanpharmaceuticalreview.com/Featured-Articles/345440-The-Problem-of-Biofilms-and-Pharmaceutical-Water-Systems/

The article can be accessed here: APR

Posted by Dr. Tim Sandle

US Food and Drug Administration Good ANDA submission practices

This draft guidance intended to assist applicants preparing to submit to FDA abbreviated new drug applications (ANDAs).

This guidance highlights common, recurring deficiencies that may lead to a delay in the approval of an ANDA. It also makes recommendations to applicants on how to avoid these deficiencies with the goal of minimizing the number of review cycles necessary for approval.

FDA is also issuing a Good ANDA Assessment Practices Manual of Policies and Procedures which establishes good ANDA assessment practices for the Office of Generic Drugs and the Office of Pharmaceutical Quality to increase their operational efficiency and effectiveness.

See: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM591134.pdf


Posted by Dr. Tim Sandle

First Ph. Eur. monograph on a monoclonal antibody

The European Pharmacopoeia Commission has achieved an important milestone in the field of biotherapeutic products with the adoption of the monograph for Infliximab concentrated solution (2928).

The Ph. Eur. Commission embarked upon the setting of public standards for therapeutic monoclonal antibodies (mAbs) in 2014 with a pilot phase and following extensive consultation with its stakeholders.

See: https://www.edqm.eu/en/node/16070

Posted by Dr. Tim Sandle

Benefits of Laboratory Glove Boxes with Gas Purging Option

At the time of experimenting in the laboratory, you may never know what would happen next. However, the fact is with the help of Laboratory Glove Boxes with Gas Purging Option, you can actually control the atmosphere glove boxes. It is known by many names. Some knows it by the name of inert atmosphere glove box, dry box, nitrogen box, and even the anaerobic box to name a few. For such type of box to function in the most convenient manner, there is an internal atmosphere which is first removed. It is then well replaced with the purified inert gas which is more commonly either argon or nitrogen.

A guest post by Naveen Kumar 

Understanding the operation of the Box:

The prime role of the Laboratory Glove Boxes with Gas Purging Option is to make sure you actually safeguard yourself from the harmful atmosphere that is likely to happen in the changing environment at the time of experimenting. This type of gas is based on the refill operation and gas removal process. The moisture level and oxygen level gets reduced to around 1% and is done either with the solution or through the displacement. If it is not used with the automatic purge control system then there is a requirement of the inert gas which is needed for better safety. With such box, the atmospheric pressure systematic position and the regulation of the same get introduced to the chamber through the internal ambient and inlet atmosphere.

Know the benefits of Inert Atmosphere Glove Boxes

The best part about Laboratory Glove Boxes with Gas Purging Option is the use of argon and nitrogen that would lessen down the concentration of the oxygen within the equipment that would reduce the effects of the oxidation. Such type of gas is mostly used because of the huge abundance and relatively less cost. It is most probably used for preventing the unwanted chemicals reaction such as hydrolysis and oxidation. This way the degrading process becomes a lot simpler. Besides, the reason such gloves is used is because of the inert gasses which gets naturally dried out and does not hold any kind of mistier.

Things you must not ignore:

Such type of Desiccator Box is usually kept under the high pressure which is then well with the surrounding air. This way the blocking of the ambient room is done along with the contamination blockage. Other alternative options do exist such as PVC, Acrylic and even the polycarbonate which is quite in demand. The air that usually passes through the membrane is then allows to absorb the moisture from the chamber’s outside and then pass it inside.

Laboratory Glove Boxes with Gas Purging Option is something that makes sure there is a regular pressure of course in a positive manner to make sure the contamination blockage is done while the moisture inflow is initiated. Besides, it also activates the high flow purge in response to the pressure that gets dropped to make sure it becomes effective and fast while the air lock gets opened up. It also works as the guard again the protection damage.

Posted by Dr. Tim Sandle

Different Type Of Laboratory Fume Hoods and Laboratory Glove Boxes

A laboratory fume hood can also be called an exhaust hood, it is a ventilation system which is designed to limit the exposure of hazardous and toxic fumes, vapours and dust. This is the primary function of a laboratory fume hood to act as a ventilation unit. The secondary function involves safeguarding or protecting against chemical spill over and unwanted runaway reactions. It also acts as aphysical barrier and helps in preventing fires.

A guest post by Naveen Kumar

There are basically two types of Laboratory Fume Hoods one is Ductless Exhaust Fume Hoods and the other one is Ducted fume hoods

Ductless Exhaust Fume Hoods ventilate and remover of hazardous chemical fumes or vapours through activated charcoal filters. Thus, allowing thesafe indoor release of exhaust. The HEPA / ULPA filters provide the clean and particle-free environment.

Ducted fume hoods, on the other hand, ventilate to theouter side and provide the more protection against chemically dangerous fumes. Now let’s look at the different variations in Ductless Exhaust Fume Hoods and Ducted Hume Hoods.

Ducted Fume Hoods - High Clearance

High clearance construction laboratory fume hoods also referred as ducted exhaust hoods or chemical fume hoods are available in different sizes from 18″ to 72″ width, they include spill chemical tray/ polypropylene worksurface. These are ideal for applications which require exterior ducting for exhaust and require full visibility of the fume hood interior. These fume hoods have two optional fan modules with adjustable air speed. Ducted fume hoods are ideal for soldering or chemical processing that requires the removal of potentially hazardous fumes from low-level corrosive vapours. These can be made of Polycarbonate, non-dissipative PVC and ESD PVC construction materials.

Ductless Fume Hoods- Portable
Carbon & HEPA filtered enclosures are also known as filtered fume hoods. These are ductless laboratory enclosures that remove hazardous fumes, vapours and particles from the laboratory. These ductless containment hoods are available in sizes of 24″, 32″ width and can be used for removing chemical fumes, dust particles, pharmaceutical powder and solvent or acid vapour.

Ducted Fume Hoods - Polypropylene

Polypropylene laboratory fume hoods are very durable and chemical resistant are turnkey ventilation system designed for applications that require exterior ducting for exhaustion. These chemical fume hoods are bottomless that can be placed over the standard size worktables. These laboratory exhaust hoods can be equipped with fan module. These are agreat choice in cases in which chemical processing requires the removal of potentially hazardous fumes.

Ducted Fume Hoods- Stainless Steel

Stainless steel fume hoods have good resistance power to a wide range of chemicals and act as excellent moisture and heat resistants. They can be decontaminated and cleaned easily and they are ESD safe, that makes them suitable for electrostatic-sensitive applications. The sash is static dissipative PVC and worksurface is optional and removable. They come with or without exhaust blower unit depending on your need. Their Primary function is to provide personal protection against toxic fumes, vapours and dust but is not compatible with some acids.

Containment Ventilated Enclosures (CVE)

Containment ventilated enclosures are also known as HEPA filtered exhaust hood or powder containment hood. These are good for powder handling, such as non-sterile hazardous drug compounding in pharmacies. They can be used to protect theuser from particles at the same time while weighing, mixing, preparing, compounding, dispensing, administering HDs or low to moderately hazardous powders.

Ductless Down flow Workstations

The down flow hoods are constructed from polypropylene and have a removable stainless-steel work surface that can be easily removed and cleaned. They collect powders or vapours through perforations on the work surface. These are available in 24”, 32”, 36” width. They are perfect for handling pharmacy drugs & medicines, chemical latent print development, solvent and chemical preparations.

Check out the air lock features of Closed Laboratory Glove Boxes

It is a known fact that most of the laboratories in both commercial and domestic sectors used quality closed loop filtration globe options in an effective way. It is widely recommended for people to check for quality glow boxes because it plays a crucial role for people to improve the results on a regular basis. Most of the Laboratories have made it mandatory for people to use Laboratory Glove Boxes while examining a biological sample from time to time.

Why used Closed Loop Filtration Glove Boxes

Closed loop filtration boxes have been used widely in large-scale Laboratories because it helps them to perform necessary tests in order to find accurate results on a regular basis. Some of the quality closed-loop filtration boxes provide an easy option for people to work in a quick span of time. Closed loop filtration glow boxes are widely used because it provides a convenient option for people to adjust the temperature and features based on the requirement in an effective way.

Features of Closed Loop Filtration Glove Boxes

Effective air lock features - Air lock features plays a crucial role for every user because it helps them to adjust the glove box to find accurate results in a quick span of time. It is highly recommended for people to check for equality Laboratory Glove Boxes because it helps them to use the airlock features for a long span of time without compromising on the performance effectively.

Constant temperature adjustment - It is necessary for people don't look for a constant temperature adjustment while working on a Laboratory Glove Boxes because it helps them to find accurate results in a quick span of time. Most of the people would prefer to use a quality glove box because it helps them to adjust the temperature without causing any contamination of the sample in an effective way

Healthy option - It is evident that using quality Laboratory Glove Boxes plays a vital role while working in the laboratory because minor contamination could cause infection to the people from time to time. It is necessary for people to stay healthy and away from infections because of biological samples, as it could decrease the productivity and cause a lot of health problems in an effective way.

Low-contamination - It is necessary for people to check for the contamination levels while working in both commercial and domestic Laboratories on a regular basis. A Laboratory Glove Boxes provides efficient protection to biological samples without contaminating in an effective way.

Posted by Dr. Tim Sandle

Bacteria Produce Gold by Digesting Toxic Metals

Bacterium C. metallidurans has found a way to extract valuable trace elements from a compound of heavy metals without poisoning itself.

The rod-shaped bacterium C. metallidurans primarily lives in soils that are enriched with numerous heavy metals. Over time some minerals break down in the soil and release toxic heavy metals and hydrogen into their environment. There is one interesting side-effect: the formation of tiny gold nuggets.

In nature, C. metallidurans plays a key role in the formation of so-called secondary gold, which emerges following the breakdown of primary, geologically created, ancient gold ores. It transforms the toxic gold particles formed by the weathering process into harmless gold particles, thereby producing gold nuggets.

To learn about this remarkable bacterium, see Laboratory Manager magazine.

Posted by Dr. Tim Sandle