On Penicillin

Melvyn Bragg and guests discuss penicillin, discovered by Alexander Fleming in 1928. It is said he noticed some blue-green penicillium mould on an uncovered petri dish at his hospital laboratory, and that this mould had inhibited bacterial growth around it. After further work, Fleming filtered a broth of the mould and called that penicillin, hoping it would be useful as a disinfectant. Howard Florey and Ernst Chain later shared a Nobel Prize in Medicine with Fleming, for their role in developing a way of mass-producing the life-saving drug. Evolutionary theory predicted the risk of resistance from the start and, almost from the beginning of this 'golden age' of antibacterials, scientists have been looking for ways to extend the lifespan of antibiotics.

For further details, see BBC Science.

Posted by Dr. Tim Sandle

New survey on microbiological control of tissues

The European Pharmacopoeia (Ph. Eur.) Commission has decided to elaborate a new general chapter on microbiological control of tissue. The aim of the survey is to gather information from relevant stakeholders to enable the Ph. Eur. experts in charge of the elaboration of this chapter to have a clear vision on the current situation regarding the characteristics of tissue preparations used in Europe and how they are monitored with regard to microbiological control.

To access the survey, see EDQM.

This survey will end on 2nd September 2016.

Posted by Dr. Tim Sandle

Ebola map may help prepare for future outbreaks

A team from the Center of International Forestry Research, Manchester Metropolitan University, and the Universidad de Málaga have applied analytical techniques that indicate where the Ebola virus is likely to be found in more favorable conditions. These models take into account a number of non-human mammalian species as well as environmental variables for predicting the presence of the virus.

By assuming that more mammalian species than simply fruit bats may be involved in its presence and spread, the map suggests that the Ebola virus may be even more widespread than formerly suspected. The map indicates that more favorable areas for the virus extend throughout the coastal areas of West and Central Africa, stretching from Cameroon to Guinea and into the East into the East African Lakes region.

For further details see:

Jesús Olivero, John E. Fa, Raimundo Real, Miguel Ángel Farfán, Ana Luz Márquez, J. Mario Vargas, J. Paul Gonzalez, Andrew A. Cunningham, Robert Nasi. Mammalian biogeography and the Ebola virus in Africa. Mammal Review, 2016; DOI: 10.1111/mam.12074

Posted by Dr. Tim Sandle

Bioprocessing & Sterile Manufacturing

Pharmaceutical Technology's new eBook addresses a range of pressing bioprocessing and sterile manufacturing topics.

Features include a report on accelerated scale-up for vaccine production, a review of the new ISO 1464 Parts 1 and 2 standards for air cleanliness classification, aseptic filling advances, a flexible approach to cleanroom design, a science-driven approach for microbial control, removing genotoxic impurities, regulatory enforcement and drug shortages, and qualification and validation of single-use shipping systems.

For details, see: Pharmtech

Posted by Dr. Tim Sandle

Why Is Prescription Drug Abuse on the Rise?

The number of opioid prescriptions written in the United States now equals the number of adults in the country, and things only seem to be getting worse. Legally-prescribed pain killers led to 1.9 million cases of addiction and 18,893 overdose deaths in 2014 alone. This corresponds to an increasing prevalence in pain in the United States.

Pain leaves its sufferers disabled and socially isolated. There is no doubt that it requires treatment. However, treatment usually means the use of opioid drugs, and while they are the most effective drug to treat it, they are also terribly addictive.

A guest post by Megan Ray Nichols

Some Prescription Drugs Are Chemically Similar to Narcotics

Opioids are a synthetic drug that inhibits the brain and body’s ability to feel pain. Chemically, they are remarkably similar to the predecessor of which it is a derived from, namely, the opium poppy, which is also used to produce heroin and morphine — some of the most addictive substances on Earth.

Other drugs, like Adderall, which is used to treat ADHD and is frequently abused by students and lots of other young adults trying to get a boost in concentration for their work and studies, is almost identical to methamphetamine. There is the perception that because some drugs, like OxyContin or Adderall, are FDA-approved and prescribed by a doctor, they are safe to use.

Both chemists and physicians know better, though. There just aren’t many alternatives in terms of drug therapy for sufferers yet.

Addiction Isn’t Always Obvious

And the images portrayed by many public health campaigns and anti-drug ads are misleading, further damaging efforts to really help those struggling with drug abuse. People who are addicted to drugs do not always look like the face-picking, emaciated “meth-head” that is so often depicted in the media — they can be highly functioning and successful people like bankers, pop stars, or your neighbors.

The inaccurate portrayal of addiction can lead people into a false sense of security in believing that they are in control of their habits, but like some of those famous aforementioned examples, denial of their drug addiction led to death. This is why if you or someone that you know is suffering from addiction, it’s important to seek help as soon as possible. Almost six percent of young adults report abusing prescription drugs — they are an especially important demographic because of the life-altering implications of substance abuse starting from an early age. The sooner you end the cycle of drug abuse, the easier recovery will be.

More Prescriptions Correlates to More Addiction

There are no easy solutions to this problem, but we can at least explore why prescription drug abuse has increased so much in recent years in the United States. Without understanding the origins of the problem, it’s unlikely we’ll find a proper fix. To be as simple as possible, the prescription drug crisis has its roots in the common availability of pain medication that was once far more strictly regulated. Opioids such as heroin have long been used in to relieve pain. But they were mostly used for the most extreme situations.

However, as recounted in the National Review, all of this changed in the 1980s, when the medical industry began using them to relieve long-term pain. OxyContin, released in 1996, represented the culmination of this trend. The drug is a controlled release of oxycodone, a potent opioid cultivated from the Persian poppy. It was also around this time that more powerful drugs like Adderall started being prescribed to “cure” hyperactivity.

Many quickly became addicted. Patients wouldn’t believe that something from a doctor could be harmful. This went on for an extended period of time for several reasons.

First, drugs like OxyContin were immensely profitable. It is estimated to have made Purdue Pharma, its producer, some $31 billion since its inception. Second, addiction risks were severely underestimated. In 2007, Purdue lost a lawsuit, claiming it misled patients about addiction risks. That was far too late. Today, an estimated 15 million people use prescription drugs recreationally in the U.S.

Authorities have, of course, cracked down in some ways on the over-prescription of legal prescription drugs. However, instead of taming that problem, it has created a huge and lucrative black market for prescription drugs as well as related drugs like heroin — and regulating Mexican drug cartels or smugglers tends to be more difficult than US-based pharmaceutical companies.

Solutions to the Crisis Require Both Drug Research and Behavioral Change

Fortunately, there are some solutions on the horizon. For one, we should develop pain and ADHD therapies that do not require addictive drugs. This could mean the development of new medicines, or it could mean increased research into alternative therapies. We also need fair and accurate drug education campaigns. Depicting all drug addicts as people having erratic behavior and terrible appearances misleads people into thinking that they do not have any problems with substance abuse because they do not look like the stereotype.

Finally, the U.S. needs to de-stigmatize addiction therapy. It shouldn’t surprise anyone to see elderly or successful people undergoing rehabilitation for addiction treatment, nor should they be penalized in their work or social lives.

Prescription drug abuse is on the rise, and both medical practitioners and policy makers need to take steps to address this issue before more lives are affected.

Post by Megan Ray Nichols

FDA - Product Design to Minimize Medication Errors

The U.S. Food and Drug Administration has produced a new guidance for industry of interest. It is titled “Safety Considerations for Product Design to Minimize Medication Errors.”

The introduction reads:

The recommendations in this guidance apply broadly to the development of drug and biologic products. Accordingly, this guidance is intended for sponsors of investigational new drug applications (INDs); applicants of new drug applications (NDAs), biologics licensing applications (BLAs), abbreviated new drug applications (ANDAs); and manufacturers of prescription drugs marketed without an approved application or over-the-counter (OTC) monograph drugs. This guidance provides a set of principles for using a systems approach to minimize medication errors relating to product design and container closure design and thus enhance patient safety.

The recommendations in this guidance document are intended to provide best practices on how to improve the drug product and container closure design for all prescription and non-prescription drugs and biologic products regulated by the Center for Drug Evaluation and Research (CDER), which are referred to collectively in this guidance as products. The guidance also provides examples of product designs that have resulted in postmarketing medication errors…”

The document can be accessed here: FDA

Posted by Dr. Tim Sandle

Water Activity for Risk Assessing Pharmaceutical Products

Water activity is an established concept for food science, especially with the assessment of food preservation and understanding which microorganisms might present a risk to the manufacturing process in relation to particular ingredients. Where there has been less research and discussion is with effect of water activity and appreciating the risks in relation to pharmaceutical products.

To highlight the importance of this, Tim Sandle has written a short review article for the Journal of Pharmaceutical Microbiology.

The reference is:

Sandle T. The Importance of Water Activity for Risk Assessing Pharmaceutical Products, J Pharm Microbiol. 2016, 2 (1): 1-2

For further details, please contact Tim Sandle

Posted by Dr. Tim Sandle

THEORY AND PRACTICE FOR MEDICAL DIAGNOSIS

Details about a new book about medical pathology.

The IP Erasmus Project Classic and Modern Methods for Molecular Diagnostics in Human Pathology, coordinated by Transilvania University of Braşov between 2011-2013 had a follow up in the publication of a new volume. The book chapters were written or coordinated by the Project partners, as well as by other collaborators, interested both in the Project and in disseminating the results of their research.

Transilvania University of Bra ov

This book release contributes towards increasing the visibility of our university, strengthening its reputation in and outside Romania.

Posted by Dr. Tim Sandle

Proper Cleaning And Maintenance Of A Laboratory Balance

Keeping a balance cleaned and maintained can dramatically increase the life of your balance and the quality of your weighing results.

This is the subject of an article by Michelle Sheridan, Weighing Specialist, Sartorius Corporation, for Laboratory Network.

“Quality-relevant work steps, such as the measuring process itself, but also cleaning, calibration and maintenance, should be described in your Standard Operating Procedures (SOPs). Following your SOPs can mean that you will have consistent and precise weighing results at all times. Sartorius balances can meet your requirements for laboratory and production areas, and allow for easy and simple cleaning. Care of the balance’s cleanliness reduces disturbances during the weighing process.”

The article can be accessed here.

Posted by Dr. Tim Sandle

Alcohol Alters Gut Microbiome

Direct liver cell damage by alcohol has been well established as one of the primary causes of liver disease. Recent work by scientists at UC San Diego demonstrates that, in addition, alcohol can lead to liver disease by causing an imbalance in the gut microflora. Humans produce two natural broad-spectrum antimicrobial proteins called REG3B and REG3G that surveil gut mucosal bacteria and prevent overgrowth. Alcohol causes a down-regulation in the genes encoding for REG3B and REG3G leading to bacterial overgrowth, an increase in microbial translocation, immune activation and further cell damage, including the liver. Mice with REG3B/REG3G knockouts have more severe liver disease while mice with REG3G over-expression avoid liver damage. This work adds to the increasing importance of gut health on a wide range of disease.

For further details, see BDTI

Posted by Dr. Tim Sandle

MHRA data integrity guidance: 18 months on

Eighteen months have passed since the MHRA published its GMP data integrity guidance. Since then we have seen pharmaceutical industry make significant effort to implement the guidance globally. It has been encouraging to see industry stakeholders and regulatory partners adopting a common approach in their own publications and the messages and themes being echoed in online discussions, workshops and conference presentations.

David Churchwood has written an interesting post on the latest data integrity developments.

Here is an extract:

"During this busy period we have also been working on the next phase of MHRA guidance, which has a GxP focus (good laboratory practice, good clinical practice, good manufacturing practice, good distribution practice and good pharmacovigilence practice). Data integrity is important throughout the pharmaceutical lifecycle, and GxP regulatory requirements have a common focus of requiring confidence in the quality and the integrity of the data used for decision-making."

Here is a link to the new MHRA consultative document: MHRA data.



Posted by Dr. Tim Sandle

Managing Regulatory Inspections

When it comes to being prepared for an inspection from a regulatory authority, the combination of practice and preparation will often make the difference between success and failure.

Pharmaceutical Manufacturing are hosting a useful article by Joachim del Boca on regulatory inspections.

Here is an extract:

“Regulatory agencies are increasing their vigilance on the (bio-)pharmaceutical industry with greater scrutiny placed upon aseptic manufacturing facilities. Perhaps one of the most significant changes in this attentiveness has been in the area of data integrity. A recent increase in the number of incidents where a company’s data was falsified or poorly documented has led to new regulations.”

The article can be accessed here.

Posted by Dr. Tim Sandle

Crash Testing Bacteria (video)

Smashing into a solid wall at 670 miles per hour doesn’t even leave a mark. Brigham Young University Chemistry professor Daniel Austin and his graduate students are learning just how hard it can be to kill bacteria.

The research group, funded by NASA, is studying high velocity impact of bacterial spores. More specifically, the group is trying to find the speed limit above which bacteria won’t survive when they crash into a hard surface.

“There should be a velocity at which they’ll splat and die, but we haven’t reached it,” Austin says. “We can get pretty close to the speed of sound, and we’re planning to go to higher velocities in the near future, but it’s not easy to do.”

To test velocity, bacteria are loaded into a vacuum chamber and then launched by a blast of air at speeds nearing 300 meters per second.

The group’s recently published study in Planetary and Space Science is the first of its kind to test the impact survivability rate of bare bacteria.

Although the main focus of the research is answering the question of how much force the bacteria can withstand, NASA has funded the research because of the planetary protection implications of the study: if bacteria can survive the ejection from one planet and the impact of landing on another planet, there are potential concerns about cross contamination of bacteria between those planets. However, Austin is quick to acknowledge that there are other factors, like UV light, that may kill the bacteria in transition.

Even though the initial publication’s lead authors Brandon Barney and Sara Pratt have graduated, Austin continues to mentor current students as they develop the research. The group is now collaborating with Microbiology professor Richard Robison as they continue the quest for higher impact speeds. They anticipate that blasting bacteria at one kilometer per second (more than 2,200 miles per hour) should be more than enough to kill the bacteria, but the group hasn’t yet been able to create those speeds in the lab.

“We seem so frequently surprised at what bacteria can survive, and this just adds to the list,” Austin says. “Our understanding of the limits of life have expanded a lot since the 1970s as we find bacteria surviving and even thriving under extreme conditions.”

In testing the limits of bacteria, Austin’s team has additionally observed an unusual elasticity of the bacterial spores, which may have potential applications in nanotechnology.



Posted by Dr. Tim Sandle

CDC expanding disease identification tool

MicrobeNet allows better and quicker germ identification and health response, in some news from the U.S. Centers for Disease Control (CDC).

Everyone has heard of common germs like E.coli or influenza, but what about Streptobacillus moniliformis or Capnocytophaga? If not treated quickly, both can kill people within days. But they are so rare that doctors and labs probably have never seen them and may mistake them for more common diseases like meningitis. Enter MicrobeNet, an innovative online tool designed by the Centers for Disease Control and Prevention (CDC) that, since 2013, has helped laboratorians and doctors get the information they need to accurately diagnose causes of disease faster and save lives.

MicrobeNet provides laboratorians with unprecedented access to CDC's virtual microbe library of more than 2,400 rare and emerging infectious bacteria and fungi at no cost. The recent multi-state outbreak of Elizabethkingia in Wisconsin, Illinois and Michigan underscores the need for a tool like MicrobeNet in diagnostic laboratories. Hospitals and health departments using MicrobeNet can identify rare bacteria like Elizabethkingia quicker, and know they’re comparing their results to the most comprehensive and accurate disease database available.

In partnership with Bruker Corp., CDC has recently added a new module to MicrobeNet that allows labs to search the protein signatures of the bacteria and compare them to the rare pathogens in CDC's MicrobeNet library by using Bruker's MALDI Biotyper systems. Using MALDI to test is extremely fast and cheaper to run than many other types of testing, making the technology increasingly popular among labs. The new MicrobeNet module will be immediately available to laboratorians and clinicians using the Bruker system in labs nationwide. Until the addition of the MALDI library, MicrobeNet offered two ways to search pathogens: by DNA sequence or biochemical tests (chemical reactions caused by the bacteria).

MicrobeNet can dramatically improve the health of people in the United States and around the world by cutting the time for testing from about a week to a few hours.

"MicrobeNet has the potential to revolutionize public health," said John R. McQuiston, PhD, team lead for CDC's Special Bacteriology Reference Laboratory and CDC's lead for MicrobeNet. "This system helps public health labs and hospitals quickly identify some of the most difficult pathogens to grow and detect. In turn, MicrobeNet will help treat patients faster and allow health departments to respond to public health emergencies more effectively."

For further details, see: CDC.

Posted by Dr. Tim Sandle

First female-to-male sexual transmission of Zika virus infection

The New York City report of female-to-male sexual transmission of Zika virus infection is the first documented case of sexual transmission of Zika from a woman to her sex partner and adds to the growing body of knowledge about the sexual transmission of Zika. All previously reported cases of sexually transmitted Zika virus infection have been spread from men to their sex partners.

News from the U.S. Centers for Disease Control and Prevention (CDC):

CDC recommends that all pregnant women who have a sex partner who has traveled to or resides in an area with Zika use barrier methods every time they have sex or they should not have sex during the pregnancy. Although no cases of woman-to-woman Zika transmission have been reported, these recommendations now also apply to female sex partners of pregnant women.

CDC is currently updating recommendations for sexually active people in which the couple is not pregnant or concerned about pregnancy and for people who want to reduce personal risk of Zika infection through sex.

For more on this, see: CDC

Posted by Dr. Tim Sandle

Criteria for the Selection of Rapid Microbiological Methods

Rapid microbiological method technologies aim to provide more sensitive, accurate, precise, and reproducible test results when compared with conventional, growth-based methods. Rapid methods normally involve some form of automation and the methods often capture data electronically. With several different technologies available on the marketplace, the microbiologist has a difficult, and sometimes expensive, choice to make in selecting the optimal method. This article outlines some of the considerations that need to be considered for their selection.

The reference for the article, by Tim Sandle, is:

Sandle, T. (2016) Key Criteria for the Selection of Rapid and Alternative Microbiological Methods, American Pharmaceutical Review, 19 (3): 46-48

For further details, please contact Tim Sandle

Posted by Dr. Tim Sandle

Bacteria 'see' like tiny eyeballs

Biologists say they have solved the riddle of how a tiny bacterium senses light and moves towards it: the entire organism acts like an eyeball.

In a single-celled pond slime, they observed how incoming rays are bent by the bug's spherical surface and focused in a spot on the far side of the cell.

By shuffling along in the opposite direction to that bright spot, the microbe then moves towards the light.

Other scientists were surprised and impressed by this "elegant" discovery.

Despite being just three micrometres (0.003mm) in diameter, the bacteria in the study use the same physical principles as the eye of a camera or a human.

This makes them "probably the world's smallest and oldest example" of such a lens, the researchers write in the journal eLife.



Posted by Dr. Tim Sandle