New antimicrobial surfaces

A new antibacterial material that has potential for cutting hospital acquired infections has been developed by scientists. The combination of two simple dyes with nanoscopic particles of gold is deadly to bacteria when activated by light -- even under modest indoor lighting. And in a first for this type of substance, it also shows impressive antibacterial properties in total darkness.

The team, tested several different combinations of the dyes crystal violet (already used to treat staph infections), methylene blue and nanogold, deposited on the surface of silicone. This flexible rubbery substance is widely used as a sealant, a coating and to build medical apparatus such as tubes, catheters and gaskets, and can also be used as protective casings for things like keyboards and telephones.

For further details, see:

Sacha Noimark, Elaine Allan, Ivan P Parkin. Light-Activated Antimicrobial Surfaces With Enhanced Efficacy Induced by a Dark-Activated Mechanism. Chemical Science, 2014; DOI: 10.1039/C3SC53186D

Posted by Tim Sandle

Hepatitis C Virus Infectious for Six Weeks on Surfaces?

According Lance's Science Macrocosm, A group of researchers from the Yale Schools of Medicine and Public Health demonstrated that hepatitis C virus (HCV) can remain infectious for up to six weeks on surfaces at room temperature. Previously, it was thought that HCV could survive for up to four days on surfaces outside the body, this new research extends that number by a month and a half.

The implications of these findings are far reaching, including safety of patients and workers in healthcare settings, as well as reducing viral hepatitis transmission associated with drug use.

The study, which was funded by the National Institute on Drug Abuse (NIDA), and was designed to assess the risk of HCV transmission after infectious material dried on environmental surfaces.

Posted by Tim Sandle

Pharmig news #55

A new edition of the Pharmaceutical Microbiology Interest Group (Pharmig) newsletter has been issued. In the new edition are:

• The nature and environmental impact of control floor level contamination by Gerry Prout
• Latest regulatory and industry news, compiled by Tim Sandle
• Review of preserving cosmetics by Susan Birks

And more…

To obtain a copy, please contact: Pharmig

Posted by Tim Sandle

Pharmacopeial Forum Update 40 (2)

The USP Pharmacopeial Forum has been updated. In the new issue 40 (2), the following changes will be of interest.

Chapter 1083  Good Distribution Practices (Revision proposal target, USP38-NF33 1st Supplement)

A new series of informational chapters describing various aspects of the pharmaceutical supply chain replaces that which appeared as an In-Process Revision in PF 38(2) but since then has been cancelled. USP is proposing this new series of Good Distribution Practices (GDP) general chapters, which were developed based on a review of two existing general chapters, Good Storage and Distribution Practices for Drug Products <1079> and Good Distribution Practices for Bulk Pharmaceutical Excipients <1197>, and the previously proposed general chapter Good Distribution Practices—Supply Chain Integrity <1083>. The new general chapters will cover material flow beginning with initial procurement and continuing throughout the supply chain to delivery to the end user for pharmaceutical components and products, medical devices, and dietary supplements. The chapters will address four main GDP topics—Quality Management System <1083.1>, Environmental Conditions Management <1083.2>, Good Importation and Exportation Practices <1083.3>, and Supply Chain Integrity and Security <1083.4>—highlighting best practices and principles.

Chapter 1083.1 Quality Management System (Revision proposal target, USP38-NF33 1st Supplement)

Chapter 1083.2 Environmental Conditions Management (Revision proposal target, USP38-NF33 1st Supplement)

Chapter 1083.3 Good Importation and Exportation Practices (Revision proposal target, USP38-NF33 1st Supplement)

Chapter 1083.4 Supply Chain Integrity and Security (Revision proposal target, USP38-NF33 1st Supplement)

Chapter 1228 Depyrogenation (Revision proposal target, USP38-NF33 1st Supplement)

As part of the revisions to USP general information chapter Sterilization and Sterility Assurance of Compendial Articles <1211> and the genesis of the <1229> series of chapters, the USP Microbiology Expert Committee decided to separate information on sterilization from depyrogenation. This new chapter provides an overview of depyrogenation and introduces different means of depyrogenation and factors to consider in the selection of an appropriate method, validation of a depyrogenation method, and routine depyrogenation process control.

Chapter 1229.11 Vapour Phase Sterilisation (Revision proposal target, USP38-NF33 1st Supplement)

The USP has proposed separating current general information chapter Sterilization and Sterility Assurance of Compendial Articles <1211> into several individual chapters [see the Stimuli article entitled “An Outline of Planned Changes to USP <1229> Sterilization and Sterility Assurance of Compendial Articles” in PF 38(2)]. Vapour sterilization systems are well suited for surface sterilization of heat sensitive materials. This chapter will provide an overview of vapour phase sterilization and its validation.

Posted by Tim Sandle

Microbe World interviews Tim Sandle about #microbiology

MicrobeWorld explores the world of microbes with vivid images and descriptions. The magazine recently interviewed Tim Sandle about his career, inspirations and the latest developments in microbiology.

Here is an excerpt:

Q) Moving little ahead of your work. You have an experience of pharmaceutical microbiology risk assessment and investigation. Will you please elaborate your work as a risk investigator? How much you feel that risk investigation in the microbiological field is important in this modern world?

Tim Sandle: Risk assessment is of great importance and it is one of the key developments with pharmaceuticals in the past decade. In the past, the focus was on quality control and the idea of simply testing products and environments. This either meant that there was an attempt to 'test into compliance' or that the wrong things were being tested for. The approach also failed to consider how to stop risks from re-occurring.

The new risk management approach is more proactive. It involves looking at processes and considering where microbial contamination is likely to occur. Following this, the severity of the risk is considered, in relation to the environment and to patient harm. Attempts are then made to eliminate or to mitigate the risk. Only after all this has been completed is the monitoring plan decided, and here the objective of the plan is to see how effective the risk mitigation measures have been.

Applying risk assessment involves using tools like HACCP (Hazard Analysis Critical Control Points), which requires the process to be mapped; and FMEA (Failure Modes and Effects Analysis), which is particularly useful for equipment. For example, if you are concerned about the operation of an autoclave and its ability to effectively sterilize an item then FMEA can be a powerful tool.

Aside from machinery and environments, risk assessment is useful for considering the microbial risk to medicines. Where microorganisms are detected, knowing the species, the numbers and the toxins each helps to consider the risk to the patient. There is a body of work around the subject of Quantitative Microbiological Risk Assessment (QMRA), which is very useful. QMRA is the process of estimating the risk from exposure to microorganisms by combining dose response information for the infectious agent with information on the distribution of exposures.

There are four very distinct steps in the risk assessment process. The first step is hazard identification, which involves the collection, organization, and evaluation of all information pertaining to a pathogen or a nutrient. Second is hazard characterization, which determines the relationship between a pathogen and any adverse effects. Third is exposure assessment, which involves determining how much of pathogen might be ingested in a serving of food. The fourth, and last step, is risk characterization, which involves evaluating the risk and related information.

The interview can be accessed here: MicrobeWorld

Posted by Tim Sandle

Revision to EU GMP Annex 15: Qualification and Validation

EU GMP Annex 15, which relates to the important area of qualification and validation, is being revised. Tim Sandle has undertaken an analysis of the chapter and this has been reported to the current edition of Clean Air and Containment Review (CACR).

CACR is an indispensable guide to cleanrooms and clean air technologies, edited by John Neiger. The current issue also features article on gaseous decontamination of clean air devices, a review of diffuser performance in cleanrooms, a history of isolator and containment technology Part 1: Early containment leading to flexible film isolators, and carbon dioxide based solutions for cleanroom garment.

For further details about the current issue, please CACR.

Tim Sandle’s reference is:

Sandle, T. (2014) Revision to EU GMP Annex 15: Qualification and Validation, Clean Air and Containment Review, Issue 18, pp22-23

Posted by Tim Sandle

Antimicrobial resistance

The ability of bacteria to evolve in response to pressure from antibiotics has been recognized since the discovery of penicillin. In less than a century, a complex array of factors has led to the emergence of bacteria that no longer respond to any approved antibiotics. Numerous recent calls to action have highlighted the urgent need to respond to this growing global health threat with improved surveillance and infection control, more judicious use of antibiotics, new prevention measures, and new therapeutic strategies to combat resistant bacteria.

Bacteria can acquire resistance through mutation or through horizontal transfer of genetic information. Resistant members of a population that are exposed to the selective pressure of antibacterial drugs will be amplified, which can ultimately result in treatment failures in the clinic. Resistance genes are ancient (even pre-dating human beings) and ubiquitous, and some of the most worrisome resistance genes have been found in diverse environmental samples, including drinking water. Furthermore, many bacterial species harboring resistance genes can colonize the human gut, skin, and other niches, where they serve as a ready source of infection when host defenses are breached. These bacteria can also serve as a source of AR genes for transfer to other bacteria, facilitating the interspecies spread of resistance.

AR is a complex and multifaceted problem that is driven by many factors, including:

• Bacterial population density in health care facilities, which allows transfer of bacteria within a community and enables resistance to emerge;
• Inadequate adherence to proven hospital hygiene measures;
• An increasing number of high risk populations, including chemotherapy, dialysis, and transplant patients as well as those in long-term care facilities;
• Overuse of antibiotics in agriculture;
• Global travel and trade, which can lead to transfer of resistant infections and resistance genes;
• Poor sanitation in certain areas, which can contaminate water systems and spread resistant bacteria in sewage;
• Inappropriate use of antibiotics in human medicine (e.g., for viral infections);
• Overprescribing of broad-spectrum drugs, which can exert selective pressure on commensal bacteria and predispose to secondary infection; and
• Lack of rapid diagnostics to help guide appropriate use of antibiotics.

Antimicrobial resistance has become a global crisis. In the U.S. alone, drug-resistant infections cause roughly 23,000 deaths a year, and the supply of new antibiotics has dwindled. In a commentary in JAMA this week, NIAID Director Anthony S. Fauci, M.D., along with colleague Hilary D. Marston, M.D., M.P.H., examine the problem and highlight how NIAID has recently adjusted its antimicrobial research efforts to apply innovative approaches to basic, clinical and translational research to address the problem.

To read the JAMA commentary, see JAMA

Posted by Tim Sandle

Microbiome Influences

Researchers find that gender, education level, and breastfeeding can affect humans’ commensal microbial communities.

The human microbiome is essential to health, and its disruption can lead to disease. Now, using data from the Human Microbiome Project (HMP), which has sampled the microbial communities of 300 healthy people at 18 body sites and analyzed additional samples from the same individuals, Patrick Schloss and Tao Ding of the University of Michigan have found that specific life-history events—namely, gender, education, and whether a person was breastfed as an infant—affected the composition of the body’s microbiomes as an adult. They published their results last week (April 16) in Nature.

Interestingly, by tracking microbiome makeup over the course of 18 months, the authors also found that the oral microbial community was the most liable, while those of the vagina and gut stayed relatively stable. Future research should aim to reveal changes over shorter time intervals.
Posted by Tim Sandle

Trimethoprim

In less-developed countries, inexpensive and well-tolerated antibiotics for therapy of streptococcal infections are often not available. Scientists have discovered that trimethoprim may provide an option. Bacteria are not generally resistant to this agent. In a new publication scientists demonstrated three pathways for the development of resistance -- meaning that streptococci can easily become resistant to the antibiotic and pass on this trait quickly.

Trimethoprim inhibits an enzyme of folic acid metabolism called dihydrofolate reductase, which plays an important role in bacterial growth. Trimethoprim thus prevents bacteria from proliferating in the body.

A new study shows that the antibiotic trimethoprim is a therapeutic option for Streptococcus pyogenes infections in some geographical regions of the world.

For further details, see:

R. Bergmann, M. van der Linden, G. S. Chhatwal, D. P. Nitsche-Schmitz. Factors That Cause Trimethoprim Resistance in Streptococcus pyogenes. Antimicrobial Agents and Chemotherapy, 2014; 58 (4): 2281 DOI: 10.1128/AAC.02282-13

 Posted by Tim Sandle

Engineering bacteria to act as sensors

Synthetic biologists programmed Escherichia coli to sense and record environmental stimuli, such as the antibiotic anhydrotetracycline, in the mouse gastrointestinal tract. This way, E. coli can be engineered into living diagnostics capable of non-destructively probing the mammalian gut.

The research has been published in PNAS, in a paper titled "Programmable bacteria detect and record an environmental signal in the mammalian gut".
Posted by Tim Sandle

New USP Pharmacopeial Forum 40 (1)

Some proposed USP changes in the new edition of the USP Pharmacopeial Forum of interest to laboratory staff are:

Chapter 41     Balances (Interim Revision 1 July 2014)

Comments received indicate the potential existence of a problem with the repeatability requirement. When following the procedure as written in the chapter, the use of a large test weight may produce an unintended passing result. In order to correct this problem, the EC proposes to modify the test using the “desired smallest net weight” value as the divisor. The desired smallest net weight can be selected on the basis of the weighing operations performed in that particular balance.

Chapter 852   Atomic Absorption Spectroscopy [NEW] (Revision proposal target, USP38-NF33)

Accuracy and Precision requirements are revised, and other minor corrections are also incorporated.

Chapter 853   Flourescence Spectroscopy [NEW] (Revision proposal target, USP38-NF33)

Additional changes in the section Accuracy in Validation and Verification. The revision clarifies that the acceptance criteria apply to the mean value obtained.

Chapter 854   Mid-Infrared spectroscopy [NEW] (Revision proposal target, USP38-NF33)

Changes are proposed for this new general test chapter. In Wavenumber Accuracy, additional peaks of the polystyrene spectrum are mentioned. In Procedure, the microscope sampling technique is reinstated. In Accuracy in Validation and Verification, the acceptance criteria has been clarified to apply to the mean value obtained. Other minor corrections are also incorporated.

Chapter 857   Ultraviolet-Visible Spectroscopy [NEW] (Revision proposal target, USP38-NF33)

Several changes are proposed in this new general chapter. Under Qualification of UV–Vis Spectrophotometers, the acceptance criteria for Control of Wavelengths are revised. Clarifications are introduced in the Limit of Stray Light test. Accuracy requirements are revised to indicate that the acceptance criteria apply to the mean value obtained. Other minor corrections are also incorporated.

Chapter 1852 Atomic Absorption Spectroscopy – Theory and Practice [NEW] (Revision proposal target, USP38-NF33)

Additional changes are proposed for this new general information chapter.

Chapter 1853 Flourescence Spectroscopy – Theory and practice [NEW] (Revision proposal target, USP37-NF32)

Additional changes are proposed for this new general information chapter.

Chapter 1854 Mid-Infrared Spectroscopy – Theory and Practice [NEW] (Revision proposal target, USP38-NF33)

Additional changes are proposed for this new general information chapter

Posted by Tim Sandle

The Rapid Microbiology Lab: Applying New Technologies to Traditional Methods

“The Rapid Microbiology Lab: Applying New Technologies to Traditional Methods” and includes speakers from our company, Lonza and Charles River.

The event is from 10am to 5pm at the Plum Park Hotel (Watling Street, Towcester, Northants NN12 6LG) and includes lunch.

Agenda

1000 – Arrival, coffee, Tea, Pastries

1015 – Introductions

1030 – The Rapid Microbiology Lab, the role of automation and technology

1100 – Automating the Incubation, Detection, and Enumeration steps without changing sample preparation

1130 – Applying Automation to Sterility Testing

1200 – Lunch

1300 – Applying automation to Environmental Monitoring and Bioburden testing

1345 – The role of technology in Microbial ID

1445 – Creating the paperless lab

1545 – Break

1600 – Validation of automated technologies

1630 – The Importance of Support

1700 – Final Q&A, Departure

For details, see: RapidMicroBio

Posted by Tim Sandle

EU GMP Annex 15 Revisions: Improving Qualification and Validation

Annex 15 of the EU GMP guide is concerned with the ‘Qualification and Validation’ of pharmaceutical facilities, addressing requirements for equipment, utilities and processes that are used for the manufacture of medicinal products. The broad requirement of Annex 15 is that a pharma manufacturer needs to identify what qualification and validation work is required; next, the manufacturer must prove that critical aspects of work are controlled; and finally, the key elements of qualification and validation need to be defined and documented.

Validation and qualification form an important part of the quality system in the pharmaceutical sector and can be defined in different ways. Tim Sandle, Head of Microbiology, BPL, UK discusses some standard definitions from a Good Manufacturing Practice (GMP) perspective.

The article has been published in the current edition of Cleanroom Technology.

The reference is:

Sandle, T. (2014) EU GMP Annex 15 Revisions: Improving Qualification and Validation, Cleanroom Technology, April 2014, pp14-16

If you are interested in reading the article, please contact Tim Sandle

Posted by Tim Sandle

FDA reduces GMP inspection rate

The U.S. Food and Drug Administration (FDA) has announced that it is scaling back the number of routine quality inspections it plans to conduct in the U.S. each year by 40 percent. Instead the FDA will undertake more inspections overseas.

The change has taken place because of FDA concerns with imported medications. The FDA plans to conduct 591 good manufacturing practice (GMP) inspections in fiscal 2014 and 2015 in the U.S. This is down from the 967 performed during 2013-2014. In place, the FDA is aiming to perform 30 percent more foreign GMP inspections, conducting 843 inspections each year. Companies will be chosen for inspection based on the agency’s risk-based inspection model that grants leeway to high-quality companies.

Source: Pharmaceutical Manufacturing

Posted by Tim Sandle

Fungal contamination of pharmaceutical products

The second most common reason for the recall of pharmaceutical products is fungal contamination. To assess current trends and to evaluate risks, Tim Sandle has written an article for the European Pharmaceutical Review.

Most reports relating to the contamination of pharmaceutical products centre on bacterial contamination rather than fungi. The reasons for this may relate to few 'microbiology' laboratories in pharmaceutical organisations having trained mycologists; to an underestimation of the association between fungi and product contamination incidents; and due to a lack of appreciation of the risks that fungi can pose to cleanrooms and controlled environments. This article considers some of these issues and, in doing so, argues that the contamination risk posed by fungi to pharmaceutical products is greater than the level of industrial and academic interest would suggest.

The reference for the article is:

Sandle, T. (2014) Fungal contamination of pharmaceutical products: the growing menace, European Pharmaceutical Review, 19 (1): 68-71

For further details, please contact Tim Sandle

Posted by Tim Sandle