Tuesday, 24 January 2017

Assuring Data Integrity for Life Sciences (book)

A useful book has been published - 'Assuring Data Integrity for Life Sciences' - edited by Siegfried Schmitt.

This new book provides a truly global perspective on data integrity and the solutions available to address this serious issue. It includes two main sections: the regulatory and historic background of data integrity, and practical advice on how to prevent or rectify data integrity breaches.

Each chapter is written by renowned, highly experience subject matter experts in the fields of compliance and data integrity, and includes a "how to" section with practical, implementable advice. Content is up to date with the latest regulations and guidances, making this the most relevant reference source of its kind. Useful checklists and aide memoirs can be customized by the discerning reader. This book should be equally useful for the quality unit professional, operations manager, validation experts and regulators.

The modular structure allows readers to pick chapters of special interest without having to reach the chapters in order. However, given the usefulness and universal application the "nuggets of wisdom" and advice provided, it is anticipated that readers will want to read the publication in its entirety.

The book is available from the PDA store, or by using the flyer below.

Posted by Dr. Tim Sandle

Monday, 23 January 2017

Development of cleanrooms: historical review

Tim Sandle has traced the history ofcleanrooms in two part feature. Part 1 covers the early concept of clean spaces, as required for surgery, and traces these to developments immediately post-war. Part 2 will address the coming of modern cleanroom designs for pharmaceuticals and healthcare.

The abstract reads:

“This article discusses the development and progress of cleanrooms and describes the significant historical milestones, taking the eighteenth century concept of a ‘clean space’ to the twenty-first century cleanroom. The history of cleanrooms is intimately entwined with two strands of technological development: medicine and military. The medical origins can be traced back to the attempts to create a clean environment, first for field surgery and later for operating theatres; whilst the military applications stem from attempts to assemble precision engineered mechanisms in environments where dust particles posed a risk to the device mechanics. Further on, developments with the atomic power, spacecraft and electronics spurred technological advances in cleanrooms, followed by the later application of cleanrooms in the pharmaceutical industry, led to the modern cleanroom technology of the twenty-first century.

This article is in two parts. Part one looks at the concept of clean air and the development of cleanrooms up until the 1960s. Part 2 addresses the developments since the 1970s and the driver for a unified, international cleanroom standard.”

The reference is:

Sandle, T. (2016) The development of cleanrooms: an historical review. Part 1: From civil war to safe surgical practice, The Journal – Institute of Science & Technology, Autumn 2016, pp41-47 (ISSN 2040-1868)

For further details, please contact Tim Sandle

Posted by Dr. Tim Sandle

Sunday, 22 January 2017

Microbiology: An oral history

A BBC radio program about the history of microbiology is available for download as an mp3:

Melvyn Bragg and guests discuss the history of microbiology. We have more microbes in our bodies than we have human cells. We fear them as the cause of disease, yet are reliant on them for processes as diverse as water purification, pharmaceuticals, bread-making and brewing. In the future, we may look to them to save the planet from environmental hazards as scientists exploit their ability to clean up pollution. For microbes are the great recyclers on the earth, processing everything – plants, animals and us. Without microbes life would grind to a halt. How did we first discover these invisible masters of the universe? The development of microscopes in the 17th Century played a key part, but for a while science seemed stuck in this purely observational role. It is only when Louis Pasteur and Robert Koch began to manipulate microbes in the lab two hundred years later that stunning advances were made. These breakthroughs led to an understanding of how microbes transform matter, spread disease and also prevent it with the development of antibiotics and vaccines.With John Dupré, Professor of Philosophy of Science at Exeter University; Anne Glover, Professor of Molecular and Cell Biology at Aberdeen University; and Andrew Mendelsohn, Senior Lecturer in the History of Science and Medicine at Imperial College, University of London.

To listen, go to: BBC radio

Posted by Dr. Tim Sandle

Saturday, 21 January 2017

Scientists examine bacterium found 1,000 feet underground

Researchers find a bacterium 1,000 feet underground (called Paenibacillus) that is resistant to 18 different antibiotics and uses identical methods of defense as similar species found in soils. The scientists identified five novel pathways that were of potential clinical concern.

The results show the bacterium is resistant to 18 different antibiotics and uses identical methods of defense as similar species found in soils. This suggests that the evolutionary pressure to conserve these resistance genes has existed for millions of years -- not just since antibiotics were first used to treat disease.

Among the different ways that the bacteria could be resistant to antibiotics, the scientists identified five novel pathways that were of potential clinical concern. Finding these new pathways is particularly valuable, as it gives researchers time to develop new drugs to combat this type of resistance, potentially decades before it will become a problem for doctors and their patients.

For further details see:

Andrew C. Pawlowski, Wenliang Wang, Kalinka Koteva, Hazel A. Barton, Andrew G. McArthur, Gerard D. Wright. A diverse intrinsic antibiotic resistome from a cave bacterium.Nature Communications, 2016; 7: 13803 DOI:10.1038/ncomms13803

Posted by Dr. Tim Sandle

Friday, 20 January 2017

Contamination Control Under Foot

Control of airborne and surface microorganisms and airborne particles in a cleanroom is achieved through the physical operation of the heating, ventilation, and air conditioning system and cleaning and disinfection techniques.

Even with these factors taken into account, contamination can still occur. One area of concern is the entry of personnel2 and the movement of equipment into and out of cleanrooms.3 Traditional ways to control these activities have centered on gowning techniques and the cleaning of equipment. To accomplish this, cleanroom mats are frequently used to remove particles from footwear and from trolley wheels.

Research undertaken at an independent laboratory evaluates the performance of temporary adhesive mats and semi-permanent polymeric flooring in retaining contamination from footwear, and particle generation from removing layers of the adhesive mats.

To view the research and the article, see: Controlled Environments magazine.

Posted by Dr. Tim Sandle

Thursday, 19 January 2017

Good Manufacturing Practice and Marketing Authorisation Holders

The European Medicines Agency has released a “Concept paper on Good Manufacturing Practice and Marketing Authorisation Holders.”

The current EU Guide to GMP refers in several places to Marketing Authorisation Holder (MAH) companies and their responsibilities in relation to GMP ensuring that the manufacturing authorisation holder can comply with GMP. These range from a responsibility to perform a task (e.g. review of periodic quality review), to acting at the interface with manufacture and control of the medicinal product (e.g. provision of current dossier information to facilitate the manufacturer’s compliance with the marketing authorisation). These responsibilities for MAHs are spread over various chapters and annexes of the Guide, and are quite numerous. There appears, however, to be a lack of clarity and understanding as to what these responsibilities actually are in their totality, and what they mean for MAHs at a practical level.

The concept paper can be viewed here.

Posted by Dr. Tim Sandle

Wednesday, 18 January 2017

Smartphones Battle Antimicrobial Resistance

A team of UCLA researchers has developed an automated diagnostic test reader for antimicrobial resistance using a smartphone. The technology could lead to routine testing for antimicrobial susceptibility in areas with limited resources.

Antimicrobial-resistant bacteria are posing a severe threat to global public health. In particular, they are becoming more common in bacterial pathogens responsible for high-mortality diseases such as pneumonia, diarrhea, and sepsis.

Part of the challenge in combatting the spread of these organisms has been the limited ability to conduct antimicrobial susceptibility testing in regions that do not have access to labs, testing equipment and trained diagnostic technicians to read such tests.

The UCLA device connects to a smartphone and has a plate that can hold up to 96 wells for testing. An array of LEDs illuminates the sample and then the phone’s camera is used to sense small changes in light transmission of each well containing a different dose selected from a panel of antibiotics. Images are sent to a server to automatically perform antimicrobial susceptibility testing and the results are returned to the smartphone in about one minute.

The researchers then tested the device in clinical settings at UCLA. They used special plates prepared with 17 different antibiotics targeting Klebsiella pneumoniae, a bacteria containing highly resistant antimicrobial profiles. During the clinical tests, they used 78 samples from patients. Their results showed that the mobile-phone-based reader meets the FDA-defined criteria for laboratory testing, with a detection accuracy of 98.2 percent.

The lowest concentration of antibiotic that prevented the growth of bacteria is used to track drug resistance. A criterion — that is susceptible to antibiotics or resistant to them — is assigned to each bacteria/drug combination in order to guide the physician in treatment decisions. A susceptible result indicates that the organisms that have infected the patient should respond to therapy, while a resistant organism will not be inhibited by the concentrations of antibiotic achieved with normal dosages used for that drug.

For further details see UCLA.

Posted by Dr. Tim Sandle

Tuesday, 17 January 2017

Contamination Control in Healthcare Manufacturing (book)

The latest in the series from Masden and Moldenhauer is available, covering such key topics as
  • 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
For details please see the PDA store or use the flyer below
Posted by Dr. Tim Sandle

Monday, 16 January 2017

The battle against Flu: How can technology help?

According to Public Health England’s Annual Flu Report, there have been more than three million deaths in the UK since 2006 from flu. Nick Hawkins, Managing Director atEverbridge EMEA, discusses how mass notification solutions can be used by health care providers to stop the death toll rising.

Recent figures released by the Office for NationalStatistics (ONS) show that last year an ineffective vaccine combined with low immunisation rates across the UK resulted in the largest percentage increase in flu deaths since 1968.

Who is most at risk?

Whilst anyone can catch flu, its symptoms have a devastating effect on certain groups including the over 65’s, pregnant women, young children, and diabetes sufferers. The latest report from Public Health England shows vaccination rates within these groups have decreased in the last twelve months.

So what can be done to improve the communication between NHS organisations and citizens about the flu virus? What tools can medical professionals use to manage flu vaccination programmes and any severe outbreaks of the virus?

The power of critical communications technology

Critical communications platforms are already in use by several organisations within the NHS. Hospitals use the technology to co-ordinate with staff and deploy resources in the event of an emergency, and ambulance services use it to communicate more effectively with first responders and residents during major incidents. So how can local NHS Trusts and GP practices use the technology in the fight against flu?

Communication platforms can be used to send targeted notifications directly to individuals. These critical messages can be sent quickly and reliably via several different communication channels—including SMS, email, text-to-speech alerts, social media and push notifications. In fact, the most effective platforms have the capability to send out notifications via more than 100 communication paths and devices, enabling organisations to communicate with residents much more effectively than before.

This would allow health care providers to communicate directly with vulnerable people during the winter months. During flu season GP practices could send out messages to diabetes sufferers and the elderly to remind them to book a flu vaccination.

By moving away from the current blanket-approach to a more targeted methodology, the technology enables health care providers to directly reach out to patients— even when they are outside of a medical facility—and provide them with useful health information tailored to their individual circumstances. Targeted messaging means patients are aware that their local healthcare provider has prioritised their health and are therefore more inclined to take action following a critical notification from their doctor.

Central to the success of critical communications platforms are two key functions.  The first is the capability to deliver messages using a variety of different methods – known as multi-modal communications. The second is effective two-way communication, which is the ability for recipients to respond to notifications quickly and easily, acknowledge receipt and confirm actions or declare status.

Importance of multi-modality

No communications channel is 100% reliable 100% of the time, so multi-modality transforms the speed at which people receive the message.  Multi-modality facilitates communication via more than 100 different communication devices and contact paths as diverse as smartphones, tannoy systems and digital signage.  Multi-modality enables multiple methods of delivering vital preventative information during breakouts of flu.

Two-way or no-way

Just as multi-modality ensures it is easier to receive a message, two way communications makes it simpler to confirm a response. Organisations can use communications platforms to create and deliver bespoke templates that require simple one-button press responses. In doing so, the number of responses increases significantly.

For instance, GP surgeries could send out a critical notification asking local residents if they are feeling unwell and whether they need an appointment. Residents can reply instantly, providing health care professionals with an overview of the scale of the issue and how best to deploy resources.
Combined, these two functions enable organisations to respond smarter and faster. In situations where multi-modal communications and response templates are deployed together, response rates to messages increase from around 20% to more than 90%. This increase means residents are better informed of the dangers of flu, more aware of what measures to take and able to inform medical professionals when they need assistance.

Emergency communications during an outbreak

Whilst most common strains of flu are treatable with modern medicine, the virus continues to evolve. In 2009, the UK found itself amid a ‘swine flu’ pandemic—the antibiotic resistant H1N1 influenza virus.  In recent weeks, scientists have also discovered a new severe strain of H5N8 avian flu which is spreading across Eastern and Central Europe.

Critical communications platforms could be used by hospitals and first response teams to communicate with on-call staff and deploy medical resources to treat patients and quarantine the virus. Users could also harness the platform’s geo-location data to assess the most affected areas and prioritise those patients with the most critical needs.

As a result, pressure on the NHS and local GP’s would be reduced, and vulnerable patients in need of urgent assistance would receive more efficient treatment.

Flu remains a killer yet often blunt tools such as national newspaper and radio advertising are used to advise the public of the need to be vaccinated.  The digital age facilitates new and more engaging ways to communicate.  Emergency communications platforms deliver a more personalised form of two-way communication to drive higher response rates and consequently improve public wellbeing, likely at a small proportion of the cost of traditional communications methods. 

Data Integrity Considerations for the Pharmaceutical Microbiology Laboratory

Data integrity refers to maintaining and assuring the accuracy and consistency of data over its entire life-cycle, and is a critical aspect to the design, implementation and usage of any system which stores, processes, or retrieves data. Data integrity is a key regulatory concern and guidance documents have been produced by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Moreover, data integrity in relation to the microbiology laboratory features in several FDA warning letters, especially in relation to sample handling and reading.

This is the subject of a new paper from Tim Sandle. The reference is:

Sandle, T. (2016) Data Integrity Considerations for the Pharmaceutical Microbiology Laboratory, Journal of GXP Compliance, 20 (6): 1-12

The paper can be found on the IVT website here.

For further details, please contact Tim Sandle

Posted by Dr. Tim Sandle

Sunday, 15 January 2017

Breast milk contains over 700 different bacteria

To understand and to characterize the range of different bacteria the scientists used DNA sequencing to identify the set of bacteria contained within breast milk, according to a research brief. The totality of microorganisms within an environment is called the microbiome.

The researchers noticed some difference between mothers, Eureka! notes. The difference was that the milk of overweight mothers or those who put on more weight than recommended during pregnancy contains a lesser diversity of species. If the premise that a wide variety of species is important for a developing child's immune system, then the finding has implications. A related finding was that the hormonal state of the mother at the time of labor also plays a role in the diversity of milk bacteria.
The study was led by María Carmen Collado, researcher at the Institute of Agrochemistry and Food Technology (IATA-CSIC) and Alex Mira, researcher at the Higher Public Health Research Centre (CSISP-GVA).

The research is of importance, Live Science reveals, because the breast milk received from the mother is one of the factors determining how the bacterial flora will develop in the newborn baby. The bacteria contained within the human gut have been shown to affect the health of a person, including a likelihood of obesity.

The next strand of research is likely to lead to a comparison between breast milk and infant formula to see if the range of bacteria in breast milk helps to prevent the baby from developing allergies, asthma and autoimmune diseases.

The results have been published in the American Journal of Clinical Nutrition.

Posted by Dr. Tim Sandle

Saturday, 14 January 2017

The impact of particles on pharmaceuticals

Sometimes it's the smallest details that have the biggest impact on pharmaceutical performance. That's certainly true when it comes down to the properties of particles and their impact on pharmaceutical performance. Subtle changes in particle size, shape and distribution can have a major impact on pharmaceutical solubility, stability and efficacy.

This is the baiss of an article by Chris Aiken, RSSL Physical Sciences Laboratory Manager for Outsouring Pharma.com. Here is an exract:

It's no surprise therefore that particle analysis often forms part of the basic characterisation of the physical, structural and behavioural attributes of Active Pharmaceutical Ingredients (APIs), excipients, and final drug products. Such analysis is often performed for QC release, pharmacopoeial testing, process development and troubleshooting. However, it is often worthwhile to further interrogate the physico-chemical properties of materials even if they are not reported as part of a manufacturer’s Certificate of Analysis (CoA). This is because this type of extended characterisation can help to identify the (potential) cause of variations in the behaviour of particles and finished product attributes during drug development and formulation. It's also useful in spotting potential problems when evaluating new suppliers, changing or adding manufacturing sites, or scaling up production.

Of course, the value and utility of data gleaned from such analyses will depend on the specific tests that are carried out. However, the bottom line is that spending some time on properly characterising materials before making potentially critical R&D, formulation or manufacturing decisions will more often than not save more time and money further down the line. For example, thorough particle characterisation can help to prevent API and final product wastage. It can even potentially prevent failure during clinical trials, preempt processing or manufacturing issues, and avoid repeated batch failure (OOS results) during production.

The article can be read here.

Posted by Dr. Tim Sandle

Friday, 13 January 2017

Remembering Scott V.W. Sutton

IVT Network remembers Scott Sutton, a premier microbiologist, author, IVT Network Advisory Board Member, friend and mentor to many, By Jeanne Moldenhauer

Dr. Sutton worked at Bausch and Lomb and Alcon Laboratories in the research and development laboratories. He was responsible for the development of many microbiological methods. Later in his career at Alcon Laboratories, he did much of the early development work that led to Alcon Laboratories to be the first drug company to obtain approval of a rapid microbiological sterility test for their products.

After leaving Alcon, Scott became a Pharma Consultant at Vectech Pharmaceutical Consultants. When he left Vectech, he consulted through his own company, The Microbiology Network, Inc. Scott promoted pharmaceutical microbiology in many ways. He taught many courses, operated the Pharmaceutical Microbiology Forum, which presented conferences for the pharmaceutical industry as well as issuing the PMF newsletter for microbiologists. Scott also moderated the PMF List, an international discussion group for microbiologists and served in various capacities on the USP Panel of Experts. His experience in pharmaceutical microbiology was a level higher than most microbiologists. He always had a new thought or concept to challenge the current beliefs in microbiology, even if the beliefs came from regulatory authorities.

During much of his career, Scott also taught at local universities where students were able to learn from his great experience.

Scott was very involved with trade organizations also. One of these organizations was the Parenteral Drug Association (PDA). Over the years, he sat on several task forces, wrote books and book chapters for the Technical Books committee, published numerous articles, and was a frequent lecturer and instructor for the organization.

Scott also always tried to help if you went to him to ask a question or help in finding a literature reference. He had an extensive literature database including the specific literature and a system to easily find the article. If it was written about pharmaceutical microbiology, you could be almost certain he read the article.

He taught several courses for IVT as well and served on the editorial board of this group. One time, he gave a talk on how we one can use social media for microbiology. It was amazing how much research he put into the topic, including the full day a week he spent researching new topics on microbiology.

While at a PDA meeting on Monday October 19, 2015 Scott was at a vendor party and suddenly passed away. He was predeceased by his father, George L. and survived by his wife of 35 years, Mary Ellen. Their children include: Jessica (Shane) Logan, David and Steven Sutton; grandchildren, Jacob and Hannah; Scott’s mother, Grace Guidry; brother, Mark H. (Wendi); and several nieces and nephews.

The pharmaceutical industry as a whole recognizes the value of Scott’s work over the years. He will be truly missed!

Below is a sample of Scott Sutton's vast work for the IVT Network:

Successful Use of a Contract Microbiology Laboratory

Qualification of a Contract Microbiology Laboratory

Hand Washing - A Critical Aspect of Personal Hygiene in Pharma

If desired, contributions can be made to the Scott Sutton Memorial Fund, 150 Parkway Drive, North Chili, NY 14514

Thursday, 12 January 2017

Reducing Human Error In Pharmaceutical Manufacturing

Human error is the cause of most pharmaceutical manufacturing failures, according to Martin Boisvert. The traditional approach has been to pass as much of the operation as possible on to machines and computers, which tend to be more reliable. New advances in workflow software, however, now make human actions more reliable by guiding them in implementing standard procedures. This combines machine-like efficiency and accuracy with the flexibility of human operation.

This is the basis of an article published on Pharmaceutical Online. Here is an extract: “Workflow software ensures that, in response to a designated event, operators have at hand all information necessary to perform time-critical interventions that might be necessary to carry out stored maintenance sequences, error correction protocols or other standardized procedures. For any given problem, workflow assures that the right people, have the right information, at the right time.”

The article can be accessed here: Pharma Online

Posted by Dr. Tim Sandle

Wednesday, 11 January 2017

Antibodies in breast milk could help to combat HIV

Scientists have found important antibodies in the breast milk of an HIV infected mother which can protect the mother’s baby from HIV. This could lead to the development of a new vaccine.

According to a research brief, the HIV (human immunodeficiency virus) can be transmitted from mother to child via breastfeeding. However, the chance of infection is much lower when compared with other body fluids. Scientists have calculated that the chance of a baby contracting HIV is 1 in 10, where the mother is HIV-infected.

The reason for this has emerged from some recent research. Scientists based at Duke University has determined that antibodies from special cells (called B-cells) in mother’s milk are able neutralize HIV.

Fierce Biotech states that this research involved isolating cells from the breast milk of an HIV-infected woman in Malawi, three days after the birth of her child. The research was specific to the HIV-1 strain of the virus.

The implications of the research are that it could lead to an HIV vaccine. The findings may also help researchers with new investigations into adult-to-adult transmission, in addition to mother-to-child transmission

The scientific team was led by Sallie Permar, an assistant professor of pediatrics and infectious diseases. The research findings were presented in a paper titled “Isolation of HIV-1-Neutralizing Mucosal Monoclonal Antibodies from Human Colostrum”. The paper was published in the journal Public Library of Science (PLoS) One

Posted by Dr. Tim Sandle