Friday, 28 February 2014

How bacteria evade antibiotics

A step forward has been made in understanding how a subset of bacterial cells escape being killed by many antibiotics. It appears that cells become "persisters" by entering a state in which they stop replicating and are able to tolerate antibiotics. Unlike antibiotic resistance, which arises because of genetic mutations and is passed on to later generations, this tolerant phase is only temporary, but it may contribute to the later development of resistance.

For further details, refer to the following research paper:

S. Helaine, A. M. Cheverton, K. G. Watson, L. M. Faure, S. A. Matthews, D. W. Holden. Internalization of Salmonella by Macrophages Induces Formation of Nonreplicating Persisters. Science, 2014; 343 (6167): 204 DOI: 10.1126/science.1244705

Posted by Tim Sandle

Rare Disease Day



Today, Feb 28, is the seventh Rare Disease Day. Rare Disease Day is an annual, awareness-raising event co-ordinated by EURORDIS at the international level and by National Alliances and Patient Organisations at the national level.

The main objective of Rare Disease Day is to raise awareness amongst the general public and decision-makers about rare diseases and their impact on patients’ lives.

A disease or disorder is defined as rare in Europe when it affects fewer than 1 in 2000. A disease or disorder is defined as rare in the USA when it affects fewer than 200,000 Americans at any given time.

One rare disease may affect only a handful of patients in the EU (European Union), and another touch as many as 245,000. In the EU, as many as 30 million people alone may be affected by one of over 6000 rare diseases existing.
  • 80% of rare diseases have identified genetic origins whilst others are the result of infections (bacterial or viral), allergies and environmental causes, or are degenerative and proliferative. 
  • 50% of rare diseases touch children. 
  • Characteristics of rare diseases
Over 6000 rare diseases are characterized by a broad diversity of disorders and symptoms that vary not only from disease to disease but also from patient to patient suffering from the same disease.

Relatively common symptoms can hide underlying rare diseases leading to misdiagnosis and delaying treatment. Quintessentially disabling, the patients quality of life is affected by the lack or loss of autonomy due to the chronic, progressive, degenerative, and frequently life-threatening aspects of the disease.

For further details see: Rare Disease Day






The fact that there are often no existing effective cures adds to the high level of pain and suffering endured by patients and their families.
Posted by Tim Sandle

Thursday, 27 February 2014

Reviewing liquid sporicides


Since their introduction, liquid sporicides have become one of the products of choice for many biological research and production facilities wherever high-level microbial control is critical. Although they are marketed as low-toxicity products, appropriate care during use is essential to prevent potentially dangerous conditions, exposures, and injuries.

An interesting overview of sporicidal disinfectants has been written for Lab Manager magazine. The article can be accessed on-line. The focus of the article is with health and safety and matters such as residues.

A fuller overview of sporidical disinfectant types and their validation requirements can be found in the ‘Cleaning and Disinfectant Handbook’. To find out more about this book, see this page.

Posted by Tim Sandle

Wednesday, 26 February 2014

Regulating the E.coli genetic clock



Rice biochemist Matthew Bennett and his team developed a robust synthetic genetic clock that allows Escherichia coli bacteria to accurately keep time in a wide temperature range. The clock, which regulates the production of proteins, does not speed up or slow down with changing temperatures, and offers one possible solution to a problem that has hindered the advance of synthetic biology.

Escherichia coli is a Gram-negative, facultatively anaerobic, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms (endotherms). Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in their hosts, and are occasionally responsible for product recalls due to food contamination. The harmless strains are part of the normal flora of the gut, and can benefit their hosts by producing vitamin K2, and preventing colonization of the intestine with pathogenic bacteria

The results were published recently in the Proceedings of the National Academy of Sciences.

The revelation will be of interest to biologists who study regulatory systems, particularly circadian rhythms, but it may be most valuable to synthetic biologists who wish to reprogram cellular regulatory mechanisms for biotechnology.

For further details see:

F. Hussain, C. Gupta, A. J. Hirning, W. Ott, K. S. Matthews, K. Josic, M. R. Bennett. Engineered temperature compensation in a synthetic genetic clock. Proceedings of the National Academy of Sciences, 2014; DOI: 10.1073/pnas.1316298111#sthash.cSNkoieN.dpuf

Posted by Tim Sandle

Tuesday, 25 February 2014

Ensuring Contamination Control


Disinfectants used in hospitals and biopharmaceutical facilities should be selected with care, not least to show that they are compatible with the detergents used to clean, with the surfaces intended to be disinfected and with each other. In this exclusive extract from ‘The CDC Handbook: A Guide to Cleaning & Disinfecting Cleanrooms’, Dr Tim Sandle outlines the essential requirements for the validation of disinfectants, focusing upon European standards.

To view the article on-line, go to EMH

To read the full chapter and to read about types of disinfectants for surface, hand and air hygiene in the pharmaceutical and hospital setting please purchase Tim Sandle’s new book: The CDC Handbook: A Guide to Cleaning and Disinfecting Cleanrooms’, edited by Dr. Tim Sandle.

The Amazon US link is: U.S. Cleanroom

For Amazon UK click here

It is also available via other Amazon stores worldwide.

To see a list of the chapters, see Sandle Disinfection Book.

Posted by Tim Sandle

Pharmig Cleanroom Clothing Survey - 2014

Pharmig (Pharmaceutical Microbiology Interest Group) are seeking your help in completing this questionnaire to help Pharmig assess cleanroom clothing practices in the healthcare and pharmaceutical sector. The aim of this being three-fold:

1) To publish the findings as an article on ‘Best practice on control and use of cleanroom garments’ in the Pharmig newsletter and on the Pharmig website

2) To gauge if there is sufficient topical information to produce a training day on Cleanroom Clothing

3) To review if there is sufficient information to produce a Pharmig Guide on Best Practice…

Please note:

1. Please can you complete the attached survey in capital letters or by typing your replies

2. You do not have to complete all the attached sections – just those that you have experience and knowledge in

3. Please complete (where applicable) by FRIDAY MARCH 21st. All questionnaires received back by that date will be entered into a draw to receive an electronic Amazon voucher to the value of £40

4. Surveys can be emailed back to info@pharmig.org.uk or posted to:

Pharmig,

T5 The Maltings,

Roydon Road,

Stanstead Abbotts,

Hertfordshire, EN10 7LN





Thank you Tim Sandle & Rachel Blount on behalf of the Pharmig Committee






To complete the survey: click here

Monday, 24 February 2014

Recent changes to bacterial taxonomy


There have been a series of significant changes to bacterial taxonomy following advances in gene sequencing. This had led to many hundreds of changes to bacterial nomenclature (the two part Latinized name). Whilst it can be debated as to the practical significance of many of these changes the pharmaceutical microbiologist needs be aware of the more significant alterations so that he or she can ensure that laboratory procedure reflect contemporary scientific developments (and that when we engage in dialogue with each other we can ensure that we are each talking about the same micro-organisms).

This is the basis of a review article by Tim Sandle looking at changes to bacterial taxonomy. The article has been written for the magazine Micrographia Today. The reference is:

Sandle, T. (2014) Recent changes to bacterial taxonomy, Micrographia Today, 1 (1): 31-36

The current issue can be viewed here: We The Microbiologist

Posted by Tim Sandle

Sunday, 23 February 2014

British Pharmacopoeia @150

Recently the British Pharmacopoeia celebrated 150 years of publication.

The British Pharmacopoeia (BP) is an annual published collection of quality standards for UK medicinal substances. It is used by individuals and organizations involved in pharmaceutical research, development, manufacture and testing. The current structure of the pharmacopoeia is:

Volumes I and II

Medicinal Substances

Volume III

Formulated Preparations
Blood related Preparations
Immunological Products
Radiopharmaceutical Preparations
Surgical Materials
Homeopathic Preparations

Volume IV

Appendices
Infrared Reference Spectra
Index

Volume V

British Pharmacopoeia (Veterinary)

Volume VI

British Pharmacopoeia
British Pharmacopoeia (Veterinary)
British Approved Names

To celebrate this landmark anniversary the Medicines Healthcare Products Regulatory Agency (MHRA) is hosting a special event “The Quality of Medicines – Future Evolution” on 9 April 2014 which brings together international regulators, pharmacopoeial authorities and the pharmaceutical industry, providing a unique opportunity to collaborate.

Topics on the agenda include:
  • data integrity considerations in Good Manufacturing Practice Quality Control (GMP QC) laboratories.
  • harmonisation and the latest technological developments in biological, biosimilar medicines and innovations such as quality by design.

Posted by Tim Sandle

The influence of the gut microbiota on neurology

We live with millions of microorganisms and these bacteria influence many aspects of our physiology. There is tantalizing evidence that our gut microbiota can influence our state of mind — affecting mood and behavior.

In the current issue of Cell, scientists reported evidences that link gut microbes to autism spectrum disorders (ASD) in a mouse model. They show that compositional and structural shifts of microbes and associated metabolites can trigger ASD symptoms, indicating gut microbiota can modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders (Cell 155, 1451–1463, December 19, 2013). 

Posted by Tim Sandle

Saturday, 22 February 2014

Achieving Quality and Compliance Excellence in Pharmaceuticals



'Achieving Quality and  Compliance Excellence in Pharmaceuticals' is a book covering a range of topics relating to GMP, edited by Madhu Raju Saghee.

Here are the topic covered and a list of the expert authors:

1 Fundamentals of Global GMP Requirements by Atul Shirgaonkar

2 Effective CAPA Management for Optimal Compliance by Michael Hopper

3 Laboratory Compliance and Handling Out-of-Specification (OOS) Results in the  Laboratory  by John Lanese and A.V. Prabhu

4 Effectively Incorporating Quality Risk Management into Quality Systems by Tim Sandle and Sanjit Singh Lamba

5 Monitoring and Controlling Process Drift for Enhancing Quality by Nandkumar Chodankar

6 Qualification and Validation by Tim Sandle

7 Process Validation by Mark F. Witcher

8 Documents, Records, and Part 11 Compliance by Janet Gough

9 Change Control and Management by R. Raghunandanan

10 Deviation Management by Alicia Tébar Pérez

11 Internal Quality Assessments/Self-Audits by R. Raghunandanan

12 Designing an Effective GMP Training Program by David Markovitz

13 Behavioural GMPS (bGxP®): A New Paradigm in Compliance Management by Brian Szukala

14 Supplier Quality Management by Ajit Basrur and David Stephon

15 Understanding the United States Pharmacopeia (USP) by Robert D. Seltzer

16 Spotting Overall Weak GMP Compliance Systems by Robert D. Seltzer

17 Meaningful Performance Metrics for Compliance by Roger Janczak

18 Implementing ICH Q 10: A Pragmatic Approach by Alok Ghosh and Nilanjana Basu

19 Compliance Aspects of APIs Manufacturing by Richard Einig

20 Compliance Aspects of Sterile Manufacturing by Tim Sandle and Madhu Raju Saghee

21 Domestic and International U.S. Food and Drug Administration (FDA) Inspections by Robert D. Seltzer

22 Avoiding FDA Enforcement Actions: An Optimal and Sustainable Compliance
Program by Areta Kupchyk

23 Developing a Master QMS Plan by John E. Lincoln

24 Trends in cGMP Compliance by Mitch Manning

For a free chapter extract and further details about the book go to: GMP

To purchase a copy of the book, see Achieving Quality and Compliance Excellence in Pharmaceuticals

Posted by Tim Sandle

Friday, 21 February 2014

Importance of Hand Sanitisation

Importance of Hand Sanitisation By Tim Sandle

Hands, whether gloved or ungloved, are one of the main ways of spreading infection or for transferring microbial contamination. The use of hand disinfectants is part of the process of good contamination control for personnel working in hospital environments, or those involved in aseptic processing and within cleanrooms. Although there are many different types of hand sanitizers available there are differences with their effectiveness and several do not meet the European standard for hand sanitization.

Personnel working in hospitals and cleanrooms carry many types of microorganisms on their hands and such microorganisms can be readily transferred from person to person or from person to equipment or critical surfaces. Such microorganisms are either present on the skin not multiplying (transient flora, which can include a range of environmental microorganisms like Staphylococcus and Pseudomonas) or are multiplying microorganisms released from the skin (residential flora including the genera of Staphylococcus, Micrococcus and Propionibacterium). Of the two groups, residential flora are more difficult to remove. For critical operations, some protection is afforded by wearing gloves. However gloves are not suitable for all activities and gloves, if not regularly sanitized or if they are of an unsuitable design, will pick up and transfer contamination.

Therefore, the sanitization of hands (either gloved or ungloved) is an important part of contamination control either in hospitals, to avoid staff-to-patient cross contamination or prior to undertaking clinical or surgical procedures; and for aseptic preparations like the dispensing of medicines. Moreover, not only is the use of a hand sanitizer needed prior to undertaking such applications, it is also important that the sanitizer is effective at eliminating a high population of bacteria. Studies have shown that if a low number of microorganisms persist after the application of a sanitizer then the subpopulation can develop which is resistant to future applications.

There are many commercially available hand sanitisers with the most commonly used types being alcohol-based liquids or gels. As with other types of disinfectants, hand sanitizers are effective against different microorganisms depending upon their mode of activity. With the most common alcohol based hand sanitizers, the mode of action leads to bacterial cell death through cytoplasm leakage, denaturation of protein and eventual cell lysis (alcohols are one of the so-called 'membrane disrupters'). The advantages of employing alcohols as hand sanitizers include a relatively low cost, little odour and a quick evaporation (limited residual activity results in shorter contact times). Furthermore alcohols have a proven cleansing action.

In selecting a hand sanitiser the pharmaceutical organisation or hospital will need to consider if the application is to be made to human skin or to gloved hands, or to both, and if it is required to be sporicidal. Hand sanitisers fall into two groups: alcohol based, which are more common, and non-alcohol based. Such considerations impact both upon cost and the health and safety of the staff using the hand sanitiser since many commonly available alcohol based sanitisers can cause excessive drying of the skin; and some non-alcohol based sanitisers can be irritating to the skin. Alcohol hand sanitizers are designed to avoid irritation through possessing hypoallergenic properties (colour and fragrance free) and ingredients which afford skin protection and care through re-fatting agents.

Alcohols have a long history of use as disinfectants due to inherent antiseptic properties against bacteria and some viruses. To be effective some water is required to be mixed with alcohol to exert effect against microorganisms, with the most effective range falling between 60 and 95% (most commercial hand sanitizers are around 70%). The most commonly used alcohol based hand sanitisers are Isopropyl alcohol or some form of denatured ethanol (such as Industrial Methylated Spirits). The more common non-alcohol based sanitisers contain either chlorhexidine or hexachlorophene. Additives can also be included in hand sanitizers in order to increase the antimicrobial properties.

Before entering a hospital ward or clean area hands should be washed using soap and water for around twenty seconds. Handwashing removes around 99% of transient microorgansisms (although it does not kill them) (4). From then on, whether gloves are worn or not, regular hygienic hand disinfection should take place to eliminate any subsequent transient flora and to reduce the risk of the contamination arising from resident skin flora.

The technique of hand sanitisation is of great importance as the effectiveness is not only with the alcohol but also relates to the 'rub-in' technique. For example:

-Dispense a small amount of hand gel onto the palm of one hand by
-pressing down on the pump dispenser
-Put hands together and proceed to rub the hand gel into both hands. Pay particular attention to the following areas:
-Fingernails
-Back of hands
-Wrists
-Between webs of fingers
-Thumb
-Allow hands to dry, this should take no more than 60 seconds

Regular applications of the hand sanitizer are required and also prior to carrying out critical activities. This is because alcohols are relatively volatile and do not provide a continual antimicrobial action. Although microorgansisms are removed from material like latex more readily than from skin, a regular frequency of hand sanitization should still be applied to gloves.

There are very few safety concerns with hand sanitizers and the occupational exposure is relatively low, although this can build up in enclosed spaces. Care should be taken when using sanitizers near naked flames (which can occur where gas burners are used in laboratories).

In conclusion, hand sanitisation is an important procedure for staff to follow in healthcare and pharmaceutical settings. Hand sanitization is one of the main methods for preventing the spread of infection in hospitals and contamination within pharmaceutical operations. This required level of control requires the use of an effective hand sanitizer.

Posted by Tim Sandle

Thursday, 20 February 2014

New edition of the ‘Green guide’ (GDP)


A new edition of the ‘Green Guide’ is now available:  Rules and Guidance for Pharmaceutical Distributors, MHRA (Medicines and Healthcare products Regulatory Agency), 2014.

This new edition of Rules and Guidance for Pharmaceutical Distributors (the Green Guide), provides you with a single source of guidance to, and legislation for, the distribution of medicines in Europe and UK.

The Green Guide reproduces all the elements of the new Rules and Guidance for Pharmaceutical Manufacturers and Distributors 2014 (the Orange Guide) that are relevant to distributors. So if you’re involved in the wholesale supply, distribution and brokering of medicines for human use and the distribution of active substances, this is the one-stop guide you need.

Since the last edition in 2007, there have been significant changes and additions to the detailed European Community guidelines on Good Distribution Practice (GDP). The Community code relating to medicinal products for human use has also been substantially amended.

This new edition of Rules and Guidance for Pharmaceutical Distributors brings together information that you need to know about these important changes, and includes:
  • A revised EU Guide for good distribution practice
  • Revisions to the EU Directive on medicines for human use
  • New chapters for brokers of finished medicines and manufacturers, importers and distributors of active substances as a result of the Falsified Medicines Directive 2011/62/EU
  • Updated chapters on the work of the MHRA
  • Extracts from the UK's consolidated human medicines legislation
  • A new appendix of names and addresses of other EU medicines regulators.

With its restructured contents and index and a fresh design, it’s easier than ever to find the answers you need.

For details see: Green Guide

Posted by Tim Sandle

Wednesday, 19 February 2014

Performance Characteristics Of Automated LAL Tests

Performance Characteristics Of Automated LAL Tests 

Tim Sandle
By Tim Sandle, Ph.D, M.A., BSc (Hons), CBiol, MSBiol., MIScT
Introduction
The use of automated Limulus amebocyte lysate (LAL) methods to perform Bacterial Endotoxin Testing (BET) is now commonplace in most pharmaceutical laboratories. By automated I am referring to the use of software driven heated tube and plate readers for turbidimetric or chromogenic LAL testing for laboratories testing against Ph. Eur. 2.6.14 or USP <85>.
These ‘semi' - automated methods have a number of advantages over the gel-clot method in both testing terms, such as easier demonstration of inhibition / enhancement testing, and in aiding cGMP through the various reports that can be obtained. The Gel-clot test is still widely used and, by virtue of its relative simplicity, remains a robust method. However, laboratories facing ever more regulation are more often employing quantitative methods.
Testing using the automated methods requires validation, which any reputable laboratory demonstrates, in simple terms, by testing three different lots / batches at a sample within the maximum valid dilution and demonstrate freedom from interfering substances. The automated instruments themselves will have been calibrated by the supplier for factors like uniformity of temperature.
Not all laboratories, however, have examined these instruments for their performance characteristics in the way that a biochemist would look at the equipment used for conducting more classical assays. Yes – for some microbiologists it's news that the LAL test is an assay. Due to the fractions of endotoxin (in terms of weight of lipopolysaccharide) that the test detects it cannot fall within the tight scope that the biochemist would apply to an assay, for aspects like accuracy or precision or other parameter pulled out of the ICH guidelines.
This doesn't mean that microbiologists can ignore the performance of their instruments. This article sets out some of the performance characteristics which could be considered for automated LAL instruments. I am not suggesting that these all need to be looked at or that already busy microbiology lab have to grapple with yet another validation task. However, the microbiologist responsible for such systems should at least understand their strengths and limitations. Types of automated LAL instruments Automated LAL instruments fall into two broad categories depending upon the nature of the test: turbidimetric (where the rate of turbidity (or the ‘gelation') of the lysate is proportional to the amount of endotoxin present) and chromogenic (where a synthetic ‘yellow' chromogenic substrate is used in the clotting cascade and the intensity of this yellow is related to the amount of endotoxin). Turbidimetric tests are read using photometric instruments (such as spectrophotometers) and chromogenic tests are more often read using ELISA plate readers. This article doesn't attempted to weigh up the pros or cons of competing instrumentation (or step into the cut throat world of competing LAL reagent suppliers) except to acknowledge that different types of software affect the test and different manufacturer's lysates differ considerably, not least in the sensitivity to LAL Reactive Materials, such as, glucans.
Applying performance characteristics

I am probably taking it as read that some performance characteristics should be applied to automated LAL tests. Understanding the abilities of the instrumentation is important in examining and interpreting test results and in defending those test results against misunderstanding from Production and QA departments. Some characteristics will be included in annual or six-monthly calibrations of the instrument, such as, temperature distribution, and others are shown through demonstration of the suitability of the instrument over time, such as the results from the negative control samples (the ‘blanks' to assayist).
What assay characteristics can be applied to automated LAL testing so that the performance of the instruments and test can be judged? In this article the following will be examined:

Limit of Detection
Limit of Quantitation
Reproducibility
Repeatability
Precision
Accuracy
Robustness

I would suggest that these factors need to be performed, examined and filed as part of the instrument's equipment validation.
Tim Sandle, Ph.D, M.A., BSc (Hons), CBiol, MSBiol., MIScT – Dr. Sandle is the Head of Microbiology at the UK Bio Products Laboratory. Dr. Sandle is a chartered biologist and holds a first class honors degree in Applied Biology; a Masters degree in education; and obtained his doctorate from Keele University. His role involves overseeing a range of microbiological tests, batch review, microbiological investigation and policy development. In addition, he is an honorary consultant with the School of Pharmacy and Pharmaceutical Sciences, University of Manchester and is a tutor for the university's pharmaceutical microbiology M.Sc course. Dr. Sandle serves on several national and international committees relating to pharmaceutical microbiology and cleanroom contamination control (including the ISO cleanroom standards). He is currently chairman of the PharMIG LAL action group and serves on the NBS cleaning and disinfection committee. He has written over eighty book chapters, peer reviewed papers and technical articles relating to microbiology. He is currently the editor of the Pharmaceutical Microbiology Interest Group Journal and runs an on-line microbiology forum (www.pharmig.blogspot.com). Dr. Sandle is an experienced auditor and frequently acts as a consultant to the pharmaceutical and healthcare sectors.

Posted by Tim Sandle

Tuesday, 18 February 2014

WHO update endotoxin guidance


The World health Organization has updated its guidance document on the Bacterial Endotoxin Test. the document is available as a draft for public comment. The document is titled:

“IMPLEMENTATION OF THE 1 REVISED GENERAL MONOGRAPH ON PARENTERAL PREPARATIONS IN THE INTERNATIONAL PHARMACOPOEIA: LIMITS FOR THE TEST FOR BACTERIAL ENDOTOXINS (3.4)”.

With the document, individual monographs on injectable dosage forms in the
International Pharmacopoeia (Ph.Int.) were investigated with a view to add a limit for bacterial endotoxins to each monograph that currently does not include such a requirement. The result of the review is that a number of endotoxin limits have been proposed.

Furthermore, in the new general monograph on Parenteral preparations the following statement is made:

“For powders and concentrates for injections and intravenous infusions, the amount of the preparation to be tested and the nature and volume of the liquid in which it is to be dissolved, suspended or diluted is specified in the individual monograph.”

The new guidance proposes to delete this sentence since the preparation of the sample solution is described in Chapter 3.4 Test for bacterial endotoxins. The text requires that samples should be dissolved or diluted in aqueous solutions so that the final solutions do not exceed the maximum valid dilution (MVD).

The aim is for the document to be implemented in October 2014. The draft can be viewed via the WHO website.

Posted by Tim Sandle

Monday, 17 February 2014

Biologics and biosimilars: the regulatory environment

Biologics and biosimilars: the regulatory environment is a challenging area. To examine this, Tim Sandle has written a review of the current status for the journal Clean Air and Containment Review.

"The manufacture of biosimilars is complex and the processes raise quality and regulatory concerns. Of interest to readers of this journal, most biologics are prepared within cleanrooms and, due to their heat-sensitive nature, most types are aseptically filled within ISO 14644 class 5 environments", writes Dr. Sandle. "Furthermore, due to the risks associated with genetically modified microorganisms, many require special containment systems. This article considers some of the recent international regulatory issues."

To read more, see the 17th edition of Clean Air and Containment Review. Details can be found here.

Sandle, T. (2014). Biologics and biosimilars: the regulatory environment, Clean Air and Containment Review, Issue 17, pp20-21.

Posted by Tim Sandle

Sunday, 16 February 2014

Learn about the Human Microbiome


The American Society for Microbiology have produced an information guide to the human microbiome and the therapeutic possibilities that the current research into the human microbiota presents.

In summary:

“The human microbiome, the collection of trillions of microbes living in and on the human body, is not random, and scientists believe that it plays a role in many basic life processes. As science continues to explore and better understand the role of the human microbiome. A new report from the American Academy of Microbiology addresses questions about this growing area of research.”

For further details and to download the report, see ASM

Posted by Tim Sandle

Saturday, 15 February 2014

Environment affects organism complexity

Scientists have demonstrated that organisms with greater complexity are more likely to evolve in complex environments, according to research published this week in PLOS Computational Biology.

The conclusion of the paper is that each virtual organism was made using a particular form of genetic encoding to create three-dimensional models and then simulated in a physically-realistic virtual world. Creatures that evolved in flat landscapes had a simple shape, but could not adequately navigate more complex environments. Later environments were designed with elevated "ice blocks." These obstacles were constructed so that each organism had to reach inside the gaps between the blocks to move forwards.

For further details see:

Joshua E. Auerbach, Josh C. Bongard. Environmental Influence on the Evolution of Morphological Complexity in Machines. PLoS Computational Biology, 2014; 10 (1): e1003399 DOI: 10.1371/journal.pcbi.1003399

Posted by Tim Sandle

Friday, 14 February 2014

Keeping tuberculosis in check

Mycobacterium tuberculosis is a major cause of death worldwide, and a formidable foe. Most healthy people can defend themselves against tuberculosis, but they need all parts of their immune system to work together. A study published in PLOS Pathogens reveals how a special class of immune cells called "invariant natural killer T cells" make their contribution to this concerted effort.

Specifically, when invariant natural killer T (iNKT) cells encounter infected macrophages--the human target cells of Mycobacterium tuberculosis, or Mtb--the iNKT cells somehow prevented Mtb from growing and multiplying inside the macrophages.

For further details, refer to:

Alissa C. Rothchild, Pushpa Jayaraman, Cláudio Nunes-Alves, Samuel M. Behar. iNKT Cell Production of GM-CSF Controls Mycobacterium tuberculosis. PLoS Pathogens, 2014; 10 (1): e1003805 DOI: 10.1371/journal.ppat.1003805

Posted by Tim Sandle

Thursday, 13 February 2014

Eighth edition of the ‘Orange guide’ (GMP)


The eighth edition of EU GMP guidance is now available:

‘Rules and Guidance for Pharmaceutical Manufacturers and Distributors’ (The Orange Guide), MHRA (Medicines and Healthcare products Regulatory Agency), 2014

This is the eighth edition of Rules and Guidance for Pharmaceutical Manufacturers and Distributors, compiled by the MHRA. Commonly known as The Orange Guide, it remains an essential reference for all manufacturers and distributors of medicines in Europe. It provides a single authoritative source of European and UK guidance, information and legislation relating to the manufacture and distribution of human medicines.

Since the 2007 edition there have been significant changes and additions to the detailed European Community guidelines on Good Manufacturing Practice (GMP), as well as substantial amendments to the Community code relating to medicinal products for human use.

This new edition covers these important changes as well as featuring
  • Changes to the EU Guide on GMP, including the addition of Part III
  • Revised EU Guide for good distribution practice
  • Revisions to the EU Directive on medicines for human use
  • New chapters for brokers of finished medicines and manufacturers, importers and distributors of active substances as a result of Falsified Medicines Directive 2011/62/EU
  • Updated chapters on the work of the MHRA
  • Extracts from the UK's consolidated human medicines legislation
  • New appendix of names and addresses of other EU medicines regulators.
With restructured contents and index and a fresh design, the new edition of The Orange Guide offers easy navigation of these important changes.

For details: Orange Guide

Posted by Tim Sandle

Wednesday, 12 February 2014

Risk Management of Contamination Prevention or cure?

Alan Fisher has written an interesting article called 'Risk Management of Contamination Prevention or cure?' for Pharma Focus Asia. Here is an extract:

"Contamination remains one of the major dangers to the integrity of pharmaceutical products. The risks associated with contamination are greatly increased through the current trends of reducing costs whilst increasing output. Additional complications from outsourcing, nanotechnology and test methods are resulting in change, uncertainty and increased risks which need to be managed."

To read the article, go to PharmaFocus.
Posted by Tim Sandle

Adopting Single-Use Systems

The adoption of single-use systems in biopharmaceutical production originated with the desire to minimize cleaning and associated validation. Before long, bioprocessors recognized the value of flexibility, reduced capital costs, and faster campaign turnaround times attainable through disposable bioprocess equipment. Single-use technologies have evolved from a supporting role for upstream operations (e.g., media storage and cell harvest) to near-complete platform processes that include all downstream processing steps except chromatography.

John Schmitz has written an informative overview of the technology for BioPharm International. The article can be viewed on-line here.

Posted by Tim Sandle

FDA Guidance - Pharmacy Compounding of Human Drug Products


Draft Guidance - Pharmacy Compounding of Human Drug Products Under Section 2 503A of the Federal Food, Drug, and Cosmetic Act
This guidance announces FDAs intention with regard to enforcement of section 503A of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 353a) to regulate entities that compound drugs, now that section 503A has been amended by Congress to remove the advertising and solicitation provisions that were struck down as unconstitutional by the U.S. Supreme Court in 2002. Several parts of section 503A require rulemaking and consultation with a Pharmacy Compounding Advisory Committee to implement. This guidance explains how those provisions will be applied pending those consultations and rulemaking. It also describes some of the possible enforcement actions FDA may bring against individuals or firms that compound drugs in violation of the FD&C Act. This guidance does not apply to registered outsourcing facilities under section 503B of the 26 FD&C Act. Guidance for outsourcing facilities has been issued separately. See Guidance 503A and guidance 503B.

For details see: Guidance 503A and Guidance 503B

Posted by Tim Sandle

Tuesday, 11 February 2014

Innovations in Cleanroom Technology


Cleanrooms provide critical support for the production of life saving products and components (pharmaceutical preparations and medical devices), lifesaving operations (surgical units) are part of the fabric of modern industrial production (electronics manufacture). Given this central role, the modern conception of the 'cleanroom', with specially filtered air, set pressure differentials, appropriate airflows, gowned staff and with the application of disinfectants, is a development of the 1950s (although aspects of 'clean air' date back much further as the second chapter of this book explains). From the 1960s conception cleanrooms have evolved in terms of improvements to the control of the physical environment, to minimising contamination risks from operators through the use of barrier technology, and more recent use of single-use systems (biodisposable technologies).

In relation to this, Tim Sandle has undertaken a review of innovations in cleanroom technology for the magazine Pharma Times. The reference is:

Sandle, T. (2013). Innovations in Cleanroom Technology, Pharma Times, 45 (12): 14-15

To request a copy, please contact Tim Sandle.

Posted by Tim Sandle

Monday, 10 February 2014

Good practices for Pharmaceutical Microbiology Laboratories



Tim Sandle’s review of ‘Good practices for Pharmaceutical Microbiology Laboratories’ was one of the top 5 most read articles on the GMP Logfile website.

As an introduction to his analysis, Dr. Sandle wrote:

“The Good Practices document has some similarities with the USP chapter <1117> “Microbiological Best Laboratory Practices” and together the two chapters are of importance given that there only other significant regulatory document is the FDA inspection guide “Microbiological Pharmaceutical Quality Control Labs”, which is now a little out of date and was last revised by the FDA in 1993. With regard to European GMPs and compendia there is no equivalent guidance or pharmacopoeial chapter.”

To view this article, go to GMP Logfile.

Note: the article was originally published in GMP REVIEW, VOL.11 NO.3 OCTOBER 2012.

Posted by Tim Sandle

Sunday, 9 February 2014

Mass spectrometry imaging used for tissue analysis

Scientists from Imperial College London (ICL) have developed a method that uses mass spectrometry imaging (MSI) to analyse biological samples based on their chemical makeup.

The MSI technique uses technologies that reveal how hundreds or thousands of chemical components are distributed in a tissue sample.

Until now there has not been a formula to apply this technology to identify tissue types, but the ICL researchers have this week outlined a method for processing MSI data and building a database of tissue types.

For further details see Laboratory Talk

Posted by Tim Sandle

Saturday, 8 February 2014

The Benefits Of Isolator And Aseptic Processing


Gary Partington has written an article on isolators and aseptic processing for Pharmaceutical Online.

Here is an extract:

“Isolators have been around the Pharmaceutical Industry since the early 1980s and in the Nuclear Industry (glovebox technology) since the 1950s. The intent of isolators is to create an airtight barrier or enclosure around a piece of equipment or process which provides absolute separation between the operator and product. The operator can perform tasks through half-suits or glove ports. Isolators provide a specific environment inside the isolator using HEPA filters. The environment can be positive pressure or negative, can have humidity control, oxygen control, use unidirectional airflow, and can either protect the product from the operator as with aseptic processes, or protect the operator from the product as with potent product handling. The earliest uses of aseptic isolators were for sterility testing. Sterility test isolators make up most of the aseptic isolators in use and are available in many different sizes and configurations. Sterility test isolators do not need to be installed in a classified area. No formal requirement exists for a Grade D environment, but the area should be controlled to allow only trained personnel. The room should also have temperature and humidity control.

Autoclaves (steam sterilizers) used to prepare media for sterility testing were interfaced with isolators to keep the entire sterility test process under isolator conditions. Additional uses for aseptic isolators include component transfers, charging of sterile powders, and interface isolators for filling machines, depyrogenation ovens, and lyophilizers.”

For more information and to access the complete article, see Pharma Online.

Posted by Tim Sandle

Friday, 7 February 2014

The influence of the microbiome on immune response

Bite sized though or the day:

Gut bacteria may cause rheumatoid arthritis by attacking the immune system. Using an animal model, scientists found that a bacterium, Prevotella copri, trains the immune system to produce Th17 cells, which in turn release molecules that cause inflammation and bone damage in arthritis. Significantly, Prevotella copri was present in 75% of patients' intestines, as determined by fecal sample testing (Science News, 4 November 2013). 



Posted by Tim Sandle

Thursday, 6 February 2014

Real time monitoring for food safety



A review of the Global Food Safety Partnership (GFSP)’s approach to real time technologies to ensure food safety has been written for the Laboratory Network.

Here is an extract:

“According to the GFSP, there is an ongoing world food safety problem that threatens every economy and food company, challenging governmental regulatory authorities, sickening millions of people each year, introducing barriers to trade, and hurting corporate bottom lines. According to the US Food and Drug Administration (FDA), “We live in a world where confidence is a key pillar of the global food system – and consumer expectations for food safety are high.” Hence it is keen to see a global supply chain operate to ensure that food products are safe for consumption.”

To view the article, see Laboratory Network

Posted by Tim Sandle

Wednesday, 5 February 2014

Advantages Of Gamma Irradiation For Effective Sterilization Methods



Betty Howard has written an article on Gamma Irradiation for Laboratory Network. The abstract reads:

“This article reviews the considerations for using gamma irradiation in pharmaceutical manufacturing. Specifically, the author examines what gamma irradiation is, how it works, and what manufacturers need to consider when evaluating the method for terminal sterilization of a product or component. The article, while not exhaustive, is intended to provoke consideration of this effective sterilization method.”

The article covers some important considerations in relation to this sterilization method.

To view the article, see Laboratory Network

Posted by Tim Sandle

Tuesday, 4 February 2014

Applications of Molecular Microbiological Methods | Book



A new book of interest:

Applications of Molecular Microbiological Methods

Publisher: Caister Academic Press

Editor: Torben L. Skovhus, Sean M. Caffrey and Casey R.J. Hubert Det Norske Veritas (DNV), Bergen, Norway; Genome Alberta, Calgary, Canada; Newcastle University, Newcastle, UK; respectively

The details are:

Innovative, constructive and continually evolving technologies are propelling microbiology into an exciting new era. This new era will witness the harnessing and control of complex microbial communities in a huge variety of applications in the industrial, medical and environmental spheres. State-of-the-art tools are being developed and utilized to analyse the molecules that microorganisms possess and generate, including DNA, RNA, proteins, lipids and cellular metabolites.

This book, written by international experts in the field, presents emerging molecular methods that allow the diversity of a microbial community to be surveyed and its functions to be investigated. The first part of the book provides examples of the application of molecular microbiological methods in various industrial applications. Part two deals with the identification of microorganisms in medical settings while the third part presents case studies that use molecular methods to assess the structure and function of microbial communities in natural environments. The fourth part of the book describes in greater detail the methods and technologies featured in the preceding case studies including metagenomics, stable isotope probing, fluorescence in situ hybridization, quantitative PCR, reverse transcription PCR and single cell methods. These detailed descriptions enable readers to evaluate the applicability of various tools for approaching questions and case studies of their own.

This practical, authoritative and up-to-date volume is a valuable resource for anyone applying or developing molecular methods in any area of microbiology and is a recommended acquisition for all microbiology laboratories.

For further details see Horizon Press

Posted by Tim Sandle