Wednesday, 31 January 2018

Antimicrobial Resistance



Antimicrobial Resistance (AMR) is the ability of microorganisms to resist antimicrobial treatments, especially antibiotics. AMR is a natural phenomenon but an accumulation of factors, including excessive and inappropriate use of antimicrobial medicines on humans and animals and poor hygiene or infection control practices, transformed AMR into a serious threat to public health worldwide.

News from the European Commission:

AMR not only has a direct impact on human and animal health - due to the failure in the treatment of infectious diseases - but also carries a heavy economic cost.

AMR is already responsible for an estimated 25,000 deaths per year in the EU. Current worldwide mortality from AMR is estimated at 700,000 deaths per year. Inaction is projected to cause yearly millions of deaths globally and by 2050 AMR has the potential to become a more common cause of death than cancer.

It also has wide impacts on the economy, with higher costs of treatments and economic losses due to reduced productivity caused by sickness. In the EU alone it is estimated that AMR annually costs EUR 1.5 billion in healthcare costs and productivity losses. The World Bank warns that, by 2050, drug-resistant infections could cause global economic damage on a par with the 2008 financial crisis.

AMR spreads through global tourism, transfer of patients between healthcare facilities within and from outside the EU, and through trade in food and animals.

It is an important global economic and a societal challenge that can't be tackled by countries or public administrations alone. Therefore, the problem needs a comprehensive "One Health" approach to it. That means that a holistic, multi-sectorial approach, involving many different sectors (public health, food safety, bio-safety, environment, research and innovation, international cooperation, animal health and welfare as well as non-therapeutic use of antimicrobial substances) is needed to tackle this complex problem.

Tuesday, 30 January 2018

GMP guidelines specific to Advanced Therapy Medicinal Products (ATMPs)


New from the European Medicines Agency – “These Guidelines develop the GMP requirements that should be applied in the manufacturing of ATMPs that have been granted a marketing authorisation and of ATMPs used in a clinical trial setting.”

These Guidelines are specific to ATMPs. Other documents developing GMP requirements for medicinal products which are contained in Volume 4 are not applicable to ATMPs, unless specific reference thereto is made in these Guidelines.

See: EMA

Posted by Dr. Tim Sandle

Monday, 29 January 2018

Microbiological Test Data - Assuring Data Integrity


Ed Tidswell and Tim Sandle have written a paper on data integrity and microbiology:

Marketed drugs and devices possess specifications including critical microbiological quality attributes purposed to assure efficacy and patient safety. These attributes are legislated requirements intended to protect the recipient patient. Sampling, microbiological testing, interpretation of data for final products, raw materials and intermediates all contribute to a cohesive assessment in the assurance of finished product quality. Traditional culture-based microbiological methods possess inherent and unavoidable variability, recognized by the compendia and which might lead to erroneous conclusion pertaining to product quality. Such variability has been associated and intrinsically linked with data integrity issues; manufacturers have subsequently been encouraged by regulatory authorities to introduce multiple microbiologists or checks to prevent such issues. Understanding microbiological variability is essential such that genuine data integrity issues are identified. Furthermore, a range of meaningful preventative strategies are feasible beyond increasing the capacity of the quality control microbiological laboratory. This short review describes the legislative requirements, inherent microbiological variability and realistic actions and activities that genuinely assure patient safety.

The paper has been published by the PDA.

The reference is:

Tidswell, E. C. and Sandle, T. (2017) Microbiological Test Data - Assuring Data Integrity, PDA J Pharm Sci Technol; doi:10.5731/pdajpst.2017.008151

Sunday, 28 January 2018

Pharmaceutical Microbiology Playing a Vital Role in Human's Life


Microbiology refers to the study of micro-organisms which can either be unicellular or cell cluster based microscopic organisms. Prime examples of these are eukaryotes like fungi, prokaryotes and protists. Premature ejaculation causes and symptoms are studied as well. In the intellect of an inferior in human’s life, microbiology refers to the study of life and organisms that are too diminutive for studying with a naked eye. It also includes immunology which is the study of immune system.

Guest post by Dr Amol Bamane

Microbiology means the study of microorganisms like bacteria, fungi, algae, virus, etc. Literally, 'micro' means small, 'bio' means life and 'loge' means study. It helps us to understand these small organisms and the benefits that can be cultivated from them.

Pharmaceuticals mean in simple terms products that are obtained from pharmaceutical companies. Pharmaceutical companies manufacture drugs that are used to treat various diseases in humans. These are basically classified as drugs that are given with prescription of a medical practitioner and over-the-counter drugs.

Premature ejaculation cure and medicine help in improving health of people by treating their particular diseases. An extensive research process is followed before these drugs are let out into the market. Clinical testing is conducted before these drugs are used for humans. They are first tried on animals to test their safety and affectivity. Later these drugs reach patients through the prescriptions of physicians.

Microbiological culture is the technique of reproducing and cultivating microbial organisms by letting them breed in a prearranged culture media under disciplined laboratory condition. It is also known as microbial culture. Microbial cultures helped in determining the type of organism or determining the presence and abundance of the microorganism in the sample which is tested.

In a medical sense, the pharmaceutical formulation is a process in which drugs or remedial medications are produced with the combinations of different chemicals and active drugs. Formulation involves the complete process right from developing a drug to its final acceptance by the patient. Pharmaceutical Formulations include the study of some important factors like pH, particle size, solubility and polymorphism.

The orally taken drugs are available in the form of capsule or tablet, while the other types of medications forms are cream, gel, ointment, powder and paste etc. Thus we can classify these finished pharmaceutical formulations as below:

  • Tablets 
  • Capsules 
  • Injections 
  • Ointments 
  • Syrups 
  • Birth Control Device 
  • Vaccines 
Top 10 Pharma Companies in India:

Indian Pharma Industry is growing with a faster pace day by day at global level. As per records Indian Pharmaceutical Industry is the second fastest growing industry. So know about the top 10 pharmaceutical companies in India as per their latest sales revenue:

1. Ranbaxy Laboratories Limited

2. Cipla

3. Ipca Labs

4. Dr. Reddy's Laboratories

5. Lupin

6. Sun Pharma

7. Cadila Health

8. Wockhardt

9. Aurobindo Pharma Ltd

10. Jubilant Life

Types of Culture Media

It can be classified in different ways. Some of the examples of its classifications are; based on the consistency it can be divided as solid, liquid and semi-solid medium. On the other hand, based on the constituents or ingredients, it can be categorized as simple, complex, synthetic and special medium.

Dehydrated culture media contains those media with ingredients like vegetable extracts, peptones, sodium salts, agar content, and sources of carbohydrate, etc. for the media preparation and growth of micro-organisms. These can be briefly divided into Agar, Broth and Semisolid Media. These are wildly used in microbiology, research, pharmaceutical, food and dairy, waste water, veterinary, etc. they provide the environment favorable for the growth of organisms. They must be stored in a specific temperature and up to specific period of time. The expiry date and the storage conditions are mentioned on the labels.

FDA or Food and Drug Administration are the authority that decides whether the drug is fit for administering to humans or not. Pharmaceuticals are continuously under the scrutiny of the FDA. Any complaints after or during the use of the drugs are reported to the FDA and they have the authority to revoke license to sale of those drugs. They analyze the whole process of testing and packaging before issuing license for sale.

Rasyog Ayurveda has become a significant part of health care due to their humongous contribution towards betterment of sexual life. It has helped to increase life span by treating diseases that had been otherwise incurable.

Now days it is our need to have small knowledge about various medicines and medications. So let's know more about Pharmaceutical Drugs to make ourselves more aware about our health.

In India, there are many highly reputed companies that produced Microbiological Culture Media Products including antibiotics powder. These companies have been successfully supplying media products to various vital industries like food and beverage, research, agriculture and other industries. Titan Media is one of the leading companies that deal with these products which help in supporting the very survival of mankind.

New Guidance for Sterile Products Manufacture is Coming: Review of EU GMP Annex 1


The importance of the new Annex 1 draft is that it not only signals changes in approach from European regulators around the safeguards needed for sterile products manufacture, it further signals a new global direction given that the FDA took part in the document review through the PIC/S convention.

Tim Sandle has written an article examining the main changes and to discuss the implications for those involved with sterile products manufacture.

There are four broad areas of change to the draft, in terms of tone and emphasis. These are reflected at various intervals in the document (often through repeated occurrences). These areas are:

  1. The global acceptance and implementation of ICH Q9 (Quality Risk Management) and Q10 (Pharmaceutical Quality System), is not reflected in the current Annex. The new draft contains many references to Quality Risk Management (QRM) in particular, emphasizing that QRM should be used as a proactive tool. There are now 92 instances of the word “risk” in the new draft, an increase from 20 in the previous version.
  2. There have been advances in sterile manufacturing technology, especially with RABS and isolators. There have also been advances with rapid microbiological methods, which the draft Annex acknowledges.
  3. There was some ambiguity with the current version and these needed correction or clarification
  4. Annex 1 is often beyond sterile manufacturing, including aspects of non-sterile manufacturing. The scope of the new draft has been modified and broadened to reflect this.
The purpose of this article is to review the primary changes, in relation to these broad themes, and to better understand the new paradigm for sterile drug products manufacture. This will be helpful for those wishing to comment on the draft and to those seeking to prepare for the using of the final document (anticipated to be later in 2018), since many of the key concepts are unlikely to change.

The reference is:

Sandle, T. (2018) New Guidance for Sterile Products Manufacture is Coming: Review of EU GMP Annex 1, Journal of GxP Compliance, 22 (1): 1-10 (http://www.ivtnetwork.com/article/new-guidance-sterile-products-manufacture-coming-review-eu-gmp-annex-1)

Posted by Dr. Tim Sandle

Pancreatic cancer connected to mouth bacteria


The oral microbiome (that bacteria found in the mouth) can, if imbalanced, enhance the risk of a person developing pancreatic cancer. The finding adds to growing reports about the association between human microbes and disease.


Pancreatic cancer is an aggressive form of cancer. This is because the cancer progresses without any evident symptoms resulting in diagnosis only being possible once the cancer has already spread. The mortality rate is also very high. This makes research into the disease an important medical priority. Pancreatic cancer is caused by the abnormal and uncontrolled growth of cells in the pancreas – a large gland that's part of the digestive system.
One area of inquiry is with the human microbiome. These communities of microorganisms, in different environments, shape health processes, ranging from digestion (and thus influencing obesity) and immune responses. Ill-health effects can arise when populations of beneficial bacteria decline and less desirable bacteria increase in numbers.
Looking at the microbial population in the mouth, scientists from New York University Langone’s Laura and Isaac Perlmutter Cancer Center have established a relationship between pancreatic cancer and oral health.
The research involved examining the bacterial contents in mouthwash samples taken from 732 people over the course of 10 years. Over this period, 361 people were diagnosed with the pancreatic cancer. The data analysis found a correlation between pancreatic cancer and the higher numbers of two types of bacteria:Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Both of these bacteria are associated with cause gum disease and periodontitis. With those that did not develop cancer, the microbes were either not detected or found in relatively low numbers.
Lead researcher Jiyoung Ahn explains to Laboratory Roots: “Our study offers the first direct evidence that specific changes in the microbial mix in the mouth - the oral microbiome - represent a likely risk factor for pancreatic cancer along with older age, male gender, smoking, African-American race, and a family history of the disease.”
The researchers hope their finding can become the basis for a routine screening procedure. The results are preliminary and have yet to be published in a peer reviewed journal.

Posted by Dr. Tim Sandle

Saturday, 27 January 2018

Therapy alternative to farm animal antibiotics


Despite longstanding scientific concerns, antibiotics continue to be given to farm animals as a means of producing leaner meat. This helps to spread antibiotic resistance. A new type of therapy offers an alternative.

One concern with parts of the farming industry is the indiscriminate use of antibiotics for farm animals, with the intention of producing better quality meat from animals like cows and pigs (there is a secondary reason, which relates to treating animal infections). Microbiologists have expressed concerns over this practice since it represents a significant contributor to the spread of antimicrobial resistance in human society. For example, farm workers who work on farms where high levels of antibiotics are used in farm animals carry a high proportion of antibiotic resistant bacteria compared with farms that are antibiotic-free.

There are several alternative to the use of antibiotics for animals. These include probiotics, prebiotics, oligosaccharides, antimicrobial peptides and essential oils. However, things called phages are beginning to to receive increased attention.
To come up with an alternative to the practice, scientists based at Leicester University have demonstrated that it should be possible to develop an alternative therapy to tackle diseases in pigs. This is based on bacteriophages.

Bacteriophages are viruses that infect (through injection of the viral genome into the bacterial cell cytoplasm) and can kill bacteria. One reason form looking closely at bacteriophages is because of their special characteristics, including widespread distribution, self-replication and a lack of effects on the normal microflora of any treated animals.

The lead researcher, Professor Martha Clokie has recently presented results to a pig industry meeting in Solihull. Speaking with the BBC, the researcher states that based on the early results phage therapy could, one day, be extended from pigs to humans and this would be "completely transformative for human health".
The academic adds: "There are many infections that we just can't treat with antibiotics because they have become resistant to them. So using the phage therapy for specific diseases could change the way we treat infection. It could give us a whole new armoury." This follows Professor Clokie and her team identifying a range of disease-killing phages. The research was funded by the U.K. based Agriculture & Horticulture Development Board.
In related, although more troubling antimicrobial news, Nature reports how eighteen months ago a gene that confers resistance to colistin (which is known as an ‘antibiotic of last resort') merged in bacteria isolated from pigs in China. Since this first case was reported, the resistance gene, termed mcr-1, has been found around the world at an rapidly accelerating rate.

Posted by Dr. Tim Sandle

The new concept of automatic gloved hand sanitization


Traceability, management and data integrity: The new concept of automatic gloved hand sanitization. Please see below a new innovation from AB Scientific.

Posted by Dr. Tim Sandle

Friday, 26 January 2018

Space agencies are looking at space microbes


Wherever you find people you find microorganisms and life onboard the International Space Station is no exception. Do these organism behave differently and do any differences pose a threat to astronauts?

These are some of the questions that scientists have been grappling with as part of the studies into extended stays in space and in preparation for deep space missions, such as the planned trip to Mars.

In terms of major pathogen threats the risks are generally lower on the International Space Station than on Earth, which reflects the overall cleaner environment and the manufacture of space craft and equipment on Earth inside controlled environments called cleanrooms. In such environments the level of airborne particulates, and hence microorganisms, is controlled together with an enhanced cleaning and disinfection regime.

In addition to these practices, it is standard procedure for astronauts assigned to the space station to spend 10 days in pre-flight quarantine. This is to assess, for instance, whether an astronauts has the flu. An influenza outbreak in space would be disastrous since it could incapacitate the throe crew.

Another reason for trying to minimize pathogens in space is because microgravity appears to weaken the immune system, so NASA need to be careful to reduce the chances of spaceflyers catching nasty bugs before they lift off. This happens because a protein called osteopontin, which is a stress hormone connected with bone loss in space, appears to be linked with a condition that leads to the wasting of the spleen and thymus organs. These organs create white bloods cells that battle infections, and the condition leads to a general weakening of the immune system.

This also means that microbiological monitoring needs to be take place onboard the space station. This is to help assess astronaut health; it is also experimental, to see whether common-Earth bound microorganisms undergo significant alternations in space.
According to Dr. Mark Ott, who is a microbiologist at Johnson Space Center. Roscosmos (the Russian space agency): "Once every three months, we sample from two locations in each module of the U.S. segment of the station."
Ott explains that samples are collected from surfaces and from the air. These are cultured using classic microbiological culture-based growth techniques where plates containing a growth medium with agar are used. It is common to use one medium to target bacteria and a different medium for fungi. There's a flaw here in that only those organisms that are culturable on the agars selected and under the incubation parameters used will be recoverable.

The plates are preserved and then returned to the ground with astronaut exchanges. Back on Earth the plates are assessed and, where microbial growth occurs, microbiologists perform identification.
With the types of microbes recovered these are not dissimilar from the types recovered on Earth. The results of environmental monitoring show very few isolates are of the type that would make people sick. If any of medical importance are recovered, a special cleaning protocol is imitated. Sometimes the issue is segregation, as Ott explains: "It may be something typically found in a bathroom, for example, but that you wouldn't want in an office space," the researcher contextualizes.
A further microbiological issue on the space station is with the treatment and control of drinking water. On the space station, as it would be on Earth, drinking water is chemically treated to ensure that it is safe to drink. Water also needs to be controlled so that bacterial proliferation is prevented once water has been treated, while it is stored.

With any of the monitoring if something atypical is recovered then instead of standard cultural techniques and conventional identifications (which look at the microbial phenotype), the organisms are sent for genotypic testing. Here microbial DNA is used for the identification. This allows closely related species to be differentiated. The types of organisms more often subjected to this analysis are spore forming organisms of the genera Bacillus.

In terms of on-going analysis what the scientists are keen to establish are the most common types of organisms likely to survive on-board the space station and whether these would pose any problems for extended stays or for future deep space missions. Of particular interest is the impact of space upon an astronaut's own microbiome and how this affects the human immune system.
This forms part of a wider international study called the "Study of the Impact of Long-Term Space Travel on the Astronauts' Microbiome." Work to support this initiative, which has been on-going since 2013, includes, taking regular samples from different parts of the astronauts' bodies. As part of this study, the likelihood and consequences of alterations in the microbiome due to extreme environments, and the related human health risk, will be assessed.

In April 2017, five post-doctoral fellowships were awarded by NASA to help review and characterize the microbes recovered from the space station and from the bodies of astronauts. Such research will be of continuing importance since it is unavoidable that every time humans venture into space, so microorganisms come with us.

Posted by Dr. Tim Sandle

Thursday, 25 January 2018

Cases of superbug Clostridium difficile increase


The most troubling cases of C. difficile infection, termed multiple recurring C. difficile infections (mrCDI), are becoming more common, according to a new university research study.

The study comes from the University of Pennsylvania School of Medicine and it highlights a concern within the U.S. healthcare network (made up of 40 million patient records). The data was drawn from a large, nationwide health insurance database. The big data analysis not only informs about the general Clostridium difficile rate (which affects over half a million U.S. citizens each year), it shows the extent of recurrent infections.

Clostridium difficile infection refers to a symptomatic infection due to the spore-forming bacterium. By being spore forming the organism is hard to kill. Symptoms of infection can include watery diarrhea, fever, nausea, and abdominal pain. Further complications can include pseudomembranous colitis, toxic megacolon, perforation of the colon, and sepsis.

Multiple recurring C. difficile infections raise concerns because recurrent infections increase the risk of death for already vulnerable patients. Reoccurrence also signals that attempts at eradication of this infection are failing. Furthermore recurrent cases also tend to involve more virulent strains of the bacterium. These risks have been described in an article for the journal Anaerobe headed “A case of multiple recurrence of Clostridium difficile infection with severe hematochezia in an immunocompromised host.”

The propensity of recurrence occurs in 15 to 35 percent of patients who initially respond to antimicrobial therapy. Due to the need to switch to different antibiotics, and the added complication of antibiotic resistance, the recurrent cases are especially difficult to treat and they contribute to significant morbidity and mortality and increased health care expenditures. Antibiotics called metronidazole, vancomycin, and fidoxamicin are often used to treat infections, but resistance can arise.

According to the new analysis, the reason for the sharp rise in mrCDI's incidence is uncertain; what is clear is that the cases are growing (rising by 43 percent over a recent ten year period). What the report does highlight is need for new approaches to treatment. An example of this is with fecal microbiota transplantation, where beneficial intestinal bacteria from one patient are infused into another to help out-compete the infective C. difficile.


This needs more study, however, according to Professor James D. Lewis from the University of Pennsylvania: “While we know that fecal microbiota transplantation is generally safe and effective in the short term, we need to establish the long term safety of this procedure."
Posted by Dr. Tim Sandle

Wednesday, 24 January 2018

Big investments for human microbiome research


The human microbiome relates to the human microbiota, which is the aggregate of microorganisms that resides on or within any of a number of human tissues and biofluids. This includes the skin, mammary glands, placenta, seminal fluid, salivaconjunctiva, gastrointestinal tracts and so on. The organisms include bacteria, archaea, protists, fungi and viruses. The human microbiome is a definition beyond the ‘microbiota’, referring to the collective genomes of resident microorganisms.

The Human Microbiome Project (HMP) was a U.S. National Institutes of Health (NIH) initiative that set the goal of identifying and characterizing the microorganisms which are found in association with both healthy and diseased humans, based on a budget of $115 million. The aim was to inform about human health or disease.

Drawing on the wealth of data provided by the HMP, many companies are investing in microbiome based research. As a report in Forbes notes: “Capitalizing on new understanding of how imbalances in this ecosystem contribute to disease, a handful of startups aim to give physicians better weapons to fight conditions such as cancer, autoimmune disorders and infection.”

Examples include Vedanta Biosciences Inc., a start-up that has teamed up with New York University Langone Medical Center to study how bacteria can be used in the battle against tumors. Drug delivery is a related area with start-up Blue Turtle Bio utilizing bacteria from the gut microbiome as a drug delivery platform for supplemental enzymes intended to treat enzyme-deficient disease states.

In a separate area, Human Longevity Inc., is putting $220 million into the sequencing of microbiome DNA to uncover disease-associated imbalances in microbial populations. This latter case is aimed at the development of personalized medicines for patients with different conditions. Similarly, Johnson & Johnson is collaborating with a start-up called Second Genome to look for targets for drugs that work by modifying what bacteria live in the intestine with the goal of coming up with new treatments for ulcerative colitis.

Research is also governmental: the White House recognized the microbiome's importance (albeit just prior to President Trump assuming office) with an announcement of the National Microbiome Initiative. This is a $221 million investment plan which includes a $100 million investment by the Bill & Melinda Gates Foundation.

Some examples of this wave of research and investment includes the digitization of the microbiome information (some scientists have termed this “iHMP”). To decode the details of the microbial ecology requires high resolution genome sequencing feeding into Big Data supercomputers. The video below gives an overview of such projects:

One example is with a research team that has taken the important step in modeling the complexity of the human gut’s bacterial communities on the computer, as Pharmaceutical Microbiology Resources reports. The research team hails from the Luxembourg Centre for Systems Biomedicine of the University of Luxembourg.

For the project, the researchers gathered all known data on the metabolism of 773 bacterial strains and using these data developed a computer model for each bacterial strain. This collection can now be used with a computer program to simulate metabolic processes with the goal of investigating how the different organisms affect the metabolism of other microbes as well as that of the human host. This generates a series of predictive metabolic models so that diseases can be better understood and disease treatments theoretically tested ahead of drug development.

The Luxembourg approach was detailed in the journal Nature Biotechnology, with the research paper titled “Generation of genome-scale metabolic reconstructions for 773 members of the human gut microbiota.”

Posted by Dr. Tim Sandle

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