Wednesday, 30 July 2014

European Hand Sanitizer Standards are updated


Two European Hand Disinfectant Standards have recently been updated.  They are BS EN 1499 2013 Edition, “Chemical disinfectants and antiseptics. Hygienic handwash. Test method and requirements (phase 2/step 2),” and BS EN 1500 2013 Edition, “Chemical disinfectants and antiseptics. Hygienic handrub. Test method and requirements (phase 2/step 2).”  Both are available now from Document Centre Inc., an authorized Standards Distributor.

The two standards apply to products for hygienic hand cleansing for disinfection in medical situations like hospitals, clinics and nursing homes, as well as for general use in the workplace and home.  The tests allow for the evaluation of the reduction of “transient microbial flora” (bacterial organisms) on hands when used by volunteers.

BS EN 1499:2013 covers cleansing by use of a hand wash product.  It replaces the previous BS EN 1499:1997 Edition.  However, results from tests using the previous edition are still valid.

Changes to BS EN 1499 are neutralization (in Section 5.5.1.2), the procedure in Annex A, and a complete revision of all Annexes.  The committee has worked to adapt the standard to the most recent state of the science, correcting errors and ambiguities.  The standard was also edited for better comprehension and readability.

BS EN 1500:2013 provides tests for the effectiveness of hand rubs.  Again, while the new document replaces the now obsolete BS EN 1499:1997, tests done to the old standard are still valid.

Changes to the BS EN 1500 again cover neutralization (Section 5.5.1.2) and updating of the Annexes.  The number of volunteers in Section 5.5.1.4 and the statistical evaluation from Section 5.8 have also been changed.  The same need to update the content to meet current “best practices” and to make for easier reading again apply.

While these standards have been developed by CEN for European adoption, they are used in many other jurisdictions (Canada, for example).  With the on-going concern regarding the spread of medically resistance infections in hospital and other medical settings, these requirements are essential in protecting the public.

BS EN Standards (the official English Language Editions of EN documents) are available from Document Center’s web store, www.document-center.com.  Or contact us by phone (650-591-7600), fax (650-591-7617) or email (info@document-center.com).  For more standards on this topic, see Document Center’s List of Standards on Disinfectants and Antiseptics.

Source: Standards Forum

Posted by Tim Sandle

Tuesday, 29 July 2014

European Antibiotic Awareness Day Evaluation Report

Public Health England have made available a report examining the activities surround the most recent European Antibiotic Awareness Day.

European Antibiotic Awareness Day (EAAD) is a Europe-wide initiative led by the European Centre for Disease Prevention and Control (ECDC). It takes place on 18th November every year to encourage responsible use of antibiotics by healthcare staff and the public to preserve their effectiveness for future generations.

The recommendations for 2014 initiatives are:
  • 1.      Develop a strategy for monitoring implementation and a measurable outcome evaluation of public behavioural changes around antibiotic usage.
  • 2.      Develop a clear and succinct set of messages that can be shared and used for unified online activity by all participating bodies across human and veterinary medicine. For social media messages use easily identifiable hashtags that highlight EAAD in 2014, England or UK.
  • 3.      Use eye catching press releases aimed at the public to further national media interest in EAAD.
  • 4.      New resources could include: “anti-prescriptions” and an infographic that illustrates the resistance data over time with a comparison of UK to Europe or global data trends.
  • 5.      Investigate centralised printing capabilities for trusts so they can order materials to be printed professionally using higher quality paper and ink.
  • 6.      Liaise with NHS Choices editorial teams and gov.uk web teams to publish resources and links between the two platforms as appropriate.

To view the report, go to EAAD

Posted by Tim Sandle

Monday, 28 July 2014

Selecting cleanroom disinfectants

One of the more difficult tasks facing pharmaceutical organisations is with the selection of disinfectants, particularly in ensuring that the disinfectants selected are appropriate and that the effectiveness of the disinfectants are periodically assessed. The need for a scientific rationale for the selection of disinfectants is outlined in the USP Chapter <1072> ‘Selection of a Disinfectant for Use in a Pharmaceutical Manufacturing Environment’. The selection of a disinfectant involves the careful consideration of a number of factors and this article outlines the most important factors which need to be taken into account. This article provides an overview of disinfectants and can be used as a guideline for those who manage cleanrooms and for those tasked with auditing and assessing cleanrooms. This represents an important area for discussion between the contract pharmaceutical organisation and the user.


In relation to this, Tim Sandle has written an article for the A3P publication i. The reference is:

Sandle, T. (2014) Selecting cleanroom disinfectants, La Vague, Issue 42, pp28-31

If you are interested in reading a copy, please contact TimSandle.

Posted by Tim Sandle

USP37-NF32 – items of interest

The USP–NF is a single–volume combination of two official compendia, the United States Pharmacopeia (USP) and the National Formulary (NF). Monographs for drug substances and preparations are featured in the USP. Excipient monographs are in the NF.

Here are some items of interest from the new edition:

General Chapters

645:     Water Conductivity

Revision to the following sections: Introduction, Instrument Specifications and Operating Parameters, and Bulk Water

1197:   Good Distribution Practices for Bulk Pharmaceutical Excipients

Section 1: Introduction and Scope; Section 2: Quality, Organization, and Documentation; Section 4: Returned Goods, Dispatch, Transport, Importation, Adulteration, and Traceability; Section 5: Excipients Used in Pharmacy Compounding; and Appendix: Definitions and Acronyms


1191    Rheometry [a new chapter]

Monographs

Heparin Sodium, changes to the monograph are:

IDENTIFICATION
1H NMR spectrum, Test A; Chromatographic Identity, Test B; Anti-Factor Xa to Anti-Factor IIa Ratio, Test C; Molecular Weight Determinations, Test D (added); and Identification Tests—General, Sodium, Test E

ASSAY
Anti-Factor IIa Potency

IMPURITIES
Limit of Galactosamine in Total Hexosamine, Nucleotidic Impurities, and Protein Impurities

ADDITIONAL REQUIREMENTS
USP Reference Standards

Posted by Tim Sandle

World Hepatitis Awareness Day



Viral hepatitis – a group of infectious diseases known as hepatitis A, B, C, D, and E – affects millions of people worldwide, causing acute and chronic liver disease and killing close to 1.4 million people every year. Hepatitis remains largely ignored or unknown. In April this year, World Health Organization (WHO) issued new recommendations on treatment of hepatitis C. In May, World Health Assembly delegates from 194 Member States adopted a resolution to improve prevention, diagnosis, and treatment of viral hepatitis.

The date of July 28th was chosen for World Hepatitis Day in honor of the birthday of Nobel Laureate Professor Baruch Samuel Blumberg, who discovered the hepatitis B virus.

On World Hepatitis Day, 28 July 2014, WHO and partners urge policy-makers, health workers and the public to "think again" about this silent killer.

World Hepatitis Day provides an opportunity to focus on specific actions, such as:
  • strengthening prevention, screening and control of viral hepatitis and its related diseases;
  • increasing hepatitis B vaccine coverage and integration of the vaccine into national immunization programmes;
  • coordinating a global response to viral hepatitis.

Posted by Tim Sandle

Sunday, 27 July 2014

Anti-microbial coatings with a long-term effect for surfaces

Researchers have now produced antimicrobial abrasion-resistant coatings with both silver and copper colloids with a long-term effect that kill germs reliably and at the same time prevent germs becoming established.

The researchers were able to prove the double microbicidal and biofilm-inhibiting action using the standardized ASTM E2 180 test process. The new material can be applied to a variety of substrates such as plastic, ceramic or metal using conventional techniques such as spraying or dipping, and cures thermally or photochemically. Selective variation of the individual components allows the developers to react to the particular and different needs of potential users. As part of the EU-sponsored CuVito project, the developers are now looking at increasingly using copper colloids and copper ions as well as silver which they hope will open up other fields of application.

For further details, see: INM - Leibniz-Institut für Neue Materialien gGmbH.

Posted by Tim Sandle

Saturday, 26 July 2014

Rapid Microbial Methods: A Q&A with Dr. Tim Sandle

Rapid microbial methods (RMM) have become a prevalent topic in microbiology quality control (QC)—particularly among QC labs with lean or paperless initiatives. However, RMM is not necessarily a one-size-fits-all proposition for every facility or process. Furthermore, in highly regulated industries such as pharmaceutical manufacturing, it can be difficult to sway the industry away from the tried and true traditional method.

Rapid Micro Biosystems recently had the opportunity to speak with Dr. Tim Sandle, head of microbiology at Bio Products Laboratory, regarding his perspective on RMM and the pharmaceutical manufacturing industry in general.

Q: What is your take on RMM and what advantages do you think it has for QC labs?

Dr. Sandle: I think rapid methods are the future. I think the rate of implementation has been slower than, perhaps people saw five or 10 years ago. But I think it’s a conservative industry. However, rapid methods offer the advantage of time to result, which is increasingly important with modern manufacturing. Also with automation, rapid methods take out a degree of subjectivity in interpreting results, and also help avoid error in preparing samples.

Q: Why do you think the adoption of RMM is slower than people saw a few years back?

Dr. Sandle: I think one of the problems is some pharmaceutical peers list standard methods, which require validation because they are standard methods. Now, in recent years, both the European and the United States pharmaceutical peer chapters have said rapid methods can be used in lieu of the standard methods; however, they need to be validated. Then you have a group of people who say, "Well, timed results are only mildly important to us, so it's easier for us not to change methods.” That's one reason.

Then sometimes there are confused messages from regulatory authorities. Some support rapid methods, some don't. But that is changing and we are seeing greater support. Then, there is a naturally conservative industry where a rapid method will be shown to one company and their first question will be, "Who else is using this?" If a big pharmaceutical company is using it, then others might use it. But if no one else is using it, some may not want to be the first to adopt the technology.

Then there are the long lead times in terms of method validation. There are a lot of parameters and variables to cover.

Q: What do you think are some of the industry’s hot topics right now?

Dr. Sandle: The biggest thing at the moment is risk assessment—the move to building in quality by design. The need to build in as much real-time testing as possible is increasingly important. Tracking the quality through the process and taking readings and things whilst products are being manufactured, rather than waiting for the final result is important—particularly with something like a sterility test, which I think is the rapid method everyone wants to champion. Many want to be the first to get it into the market. With the compendial method, it takes 14 days to get sterility test results. With an RMM, the time to result is much quicker.

So if something goes wrong with the test, not only do you have to go through the process again, but it might take a week or so to fill it then run the sterility test. At this point, with the traditional method, three to four weeks may have gone by before anyone realizes there's a contamination. That's why there's a thrust to building quality into the process itself.

Q: You frequently publisher in your industry. Aside from the subjects you research, are there topics you find interesting as a thought leader in your industry?

Dr. Sandle: Aside from rapid methods, I think the trend at the moment is about non-sterile products and which microorganisms may or may not cause patient harm. There's a big debate around things that come under the label of objectionable microorganisms, and what is and what isn't objectionable.

There's also a lot of interest in fungal contamination, which has been neglected in relation to bacteria. However, it might be causing more patient risk than has previously been thought.

Posted by Tim Sandle

Linking gut microbiota to obesity

The human gut microbiome is influenced by many factors, such as antibiotic usage, disease status, seasonal changes, and aging. In recent years, diet has emerged as one of the most important factors believed to affect the composition and activity of the gut microbiome. A recent article published in Nature reported that diet "rapidly and reproducibly alters the human gut microbiome." (2014, Nature 505, 559.) 

The abstract to this interesting paper reads:

“Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals2, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.”

Posted by Tim Sandle

Friday, 25 July 2014

Immunology in the skin (video)

The skin is the body's primary barrier against physical insults and microbial pathogens. It represents a unique environment in which cells of the immune system interact with skin cells to maintain tissue homeostasis and induce immune responses. Diverse and functionally specialized subsets of cells of the immune system sense and respond to infection or various barrier breaches to activate an immune response and eventually return to homeostasis. However, deregulated immune responses can also cause skin disorders such as psoriasis. This animated video introduces the environment and key participants in skin immunity in the steady state and disease.



Posted by Tim Sandle

Thursday, 24 July 2014

Lung Microbiome Research


The the lung microbiome play a key role in respiratory health.

If the human digestive tract were a river from the mouth extending through the stomach and intestines, ending at the anus, the lungs would be pools alongside that river that are often swept by eddying currents, according to Gary Huffnagle from the University of Michigan, who began studying the bacterial communities that inhabit these pool-like organs nearly a decade ago. “There’s a constant flow into [the] lungs of aspirated bacteria from the mouth,” he said. But through the action of cilia and the cough reflex, among other things, there’s also an outward flow of microbes, making the lung microbiome a dynamic community.

The surface area of the healthy lung is a dynamic environment. The respiratory organ is constantly bombarded by debris and microbes that make their way from the mouth and nose through the trachea. Ciliated cells on branching bronchioles within the lungs beat rhythmically to move debris and invading microbes, while alveolar macrophages constantly patrol for and destroy unwelcome bugs.

The lung microbiome is about 1,000 times less dense than the oral microbiome and about 1 million to 1 billion times sparser than the microbial community of the gut, said Huffnagle. That is in part because the lung lacks the microbe-friendly mucosal lining found in the mouth and gastrointestinal tract, instead harboring a thin layer of much-less-inviting surfactant to keep the respiratory organs from drying out. In a review article published in The Lancet Respiratory Medicine this March, Huffnagle and his colleagues argued that the lungs are like the South Pacific, with small islands of clustered bacteria and wide stretches of unpopulated regions between them. It appears that the lung microbiome is populated from the oral microbiome, and among this population exists a small subset of bacteria that can survive the unique environment of the lung. The most common bacteria found in healthy lungs are Streptococcus, Prevotella, and Veillonella species.

Source: The Scientist


Wednesday, 23 July 2014

Growth Direct™ System for Environmental Monitoring and Bioburden Applications

Rapid Micro Biosystems announces the commercial availability of
The Growth Direct™ System for Environmental Monitoring and Bioburden Applications
New instrument and applications improve the efficiency of microbial quality control processes while significantly reducing the time-to-result

Bedford, MA (June 9, 2014) – Rapid Micro Biosystems, the provider of automated, rapid, non-destructive detection and enumeration technologies in microbiology, today announced the launch of the next generation of Growth Direct™ System and accompanying applications. The Growth Direct™ System is designed to automate the incubation, detection, enumeration and reporting steps for environmental monitoring and bioburden applications in pharmaceutical quality control laboratories.  The technology is based on the detection of the natural auto-fluorescence of microorganisms; requiring no additional reagents to detect growing colonies. The Growth Direct™ System can handle both the environmental monitoring and bioburden (in-process and water) applications.

The environmental monitoring application for the Growth Direct™ System automates the high volume testing typically found in the combination of air, surface and personnel monitoring. 

·         Delivers efficiency: Automated reading and data transfer to laboratory information management systems (LIMS) frees personnel from tedious handling and counting of hundreds of plates a day allowing resources to focus on higher value activities.
·         Audit trail: The system provides a complete, error-free record of all activities and results.
·         System can be located near production: On a large site, the Growth Direct™ System can be located near manufacturing, increasing efficiency and reducing the travel risk with critical samples.

The Bioburden Testing application for the Growth Direct™ System advances the already validated technology in the area of in-process bioburden and water testing.

·         Automated: Tedious, manual steps associated with the assay are eliminated.  Users simply prepare the sample and load it into the system. The system automatically handles serial incubations and processes samples 24/7.
·         Rapid results: Positive results starting within hours and final results in about half the time of the compendial method.
·         Simplified Validation: Because the test is considered “automated compendial”, the validation requirements are lessened, speeding time to value.

“These applications build upon the existing Growth Direct™ technology currently used in FDA and EMEA regulated manufacturing facilities,” said Sarath Krishnaswamy, VP R&D for Rapid Micro Biosystems. “The system combines robust automation, state of the art camera technology and powerful image analysis software to automatically analyze and enumerate any growing colonies.”

“We developed the Growth Direct™ System and the applications from in-depth customer input while meeting the rigorous requirements of the industry,” states Julie Sperry, Chief Commercial Officer. “Demand for the product has been very strong; customers immediately recognize the value the system will deliver their organizations.”
    
“Our team has been working diligently to deliver a solution that revolutionizes the operations of Pharmaceutical Quality Control,” said Steve Delity, President and CEO of Rapid Micro Biosystems. “The entire company is poised to launch these new products and facilitate successful customer implementation while continuing the development of two additional systems; the Growth Direct™ System for Sterility testing and a Combination Growth Direct™ System that provides the ultimate in flexibility by concurrently testing any of the applications.”


About Rapid Micro Biosystems:
Rapid Micro Biosystems delivers the Growth Direct™ System, an automated, non-destructive rapid detection and enumeration technology based on the compendial method for microbial quality control in pharmaceutical manufacturing.  The system automates and accelerates detection and enumeration in the areas of sterility testing, environmental monitoring, and bioburden testing, eliminating manual steps and analysis.  The detection technology, first developed and patented by Dr. Don Straus, Ph.D., uses the natural auto-fluorescence of microbes and requires no reagents. For more information about Rapid Micro Biosystems visit www.rapidmicrobio.com

Contact:
Mark Severns
Rapid Micro Biosystems
mseverns@rapidmicrobio.com

Posted by Tim Sandle

Tuesday, 22 July 2014

New high-tech pathogen-identification method

Using a new method for identifying bacteria and fungi in patient specimens led to a 92 percent cost reduction in the reagents needed to run clinical microbiology tests. From April 1, 2013 to March 31, 2014, scientists at UNC Hospitals, in the U.S. led a cost-analysis study. The lab used the MALDI-TOF MS to identify specific microorganisms from 21,930 samples from patients at UNC Hospitals. Specimens consisted of enteric pathogens, enterococci, gram negative non-glucose fermenters, staphylococci, streptococci, and yeast.

MALDI-TOF MS stands for Matrix-Assisted Laser Desorption Ionization-Time of Flight mass spectrometry. It analyzes proteins from incubated specimens and identifies the specimens by comparing them to known microorganisms in a database. Two companies -- Bruker Corporation and bioMérieux, Inc. -- have developed slightly different versions of the technology.

The new test results were presented at the 2014 General Meeting of the American Society for Microbiology in Boston on May 18.

Source: University of North Carolina School of Medicine

Posted by Tim Sandle

European Pharmacopeia update: 8.3

European Pharmacopoeia 8th Edition - Review of Supplement 8.3

Below is a list of monographs and general chapters that are new, or that have been revised, corrected or deleted for the 8th Edition (supplement 8.3) of the European Pharmacopeia.

General Chapters

2.2.29  Liquid Chromatography                                                                 


The chapter has been revised to include a reference to LC systems using short columns and reduced particle-size stationary phases, such as sub-2 µm particles, and mobile phases at high pressure but avoiding reference to trading names such as e.g. UPLC, RRLC, etc.

2.4.22  Composition of fatty acids by gas chromatography                     

Content of oleic acid: sentence added to clarify that content of oleic acid is sum of oleic acid (18:1 n-9) and cis-vaccinic acid (18:1 n-7)


2.7.5    Assay of Heparin                                                                  

The clotting assay in sheep plasma has been replaced by a more specific chromogenic assay for anti-factor IIa activity following an international collaborative study (Gray E., Hogwood J., Rigsby P. et al. An international collaborative study to value assign the 6th international standard for unfractionated heparin and the US pharmacopeial heparin reference standard for assay lot F. Ref: WHO/BS/09.2124. WHO Expert Committee on Biological Standardization; 2009).

The revised chapter also comprises an assay for anti-factor Xa activity, which is used to establish the ratio of anti-factor Xa to anti-factor IIa activity, used as an identification criterion in the unfractionated heparin monographs (heparin sodium (0333), heparin calcium (0332)). As part of this revision, heparin sodium BRP was recalibrated for use with these new methods.

3.2.1    Glass containers for pharmaceutical use                                       

Production: section introduced to address the risk related to potential delamination of glass containers, by raising awareness of the glass manufacturers and users of the glass containers in the pharmaceutical industry to the factors contributing to the phenomenon

Harmonisation with ISO 4802-1 and 4802-2: adjustments made to avoid ambiguities with ISO, including an additional volume specification for containers of 2-3 mL in Table 3.2.1.-3 and Table 3.2.1.-7

Hydrolytic resistance of glass grains: alternative grinding device introduced to include state-of-the-art equipment that increases reproducibility of sample preparation.



Monographs

Acetic acid, glacial (0590)                                                                
           
Reducing substances: test revised to replace potassium dichromate (proscribed under REACH regulation).

Ethanol (96 per cent) (1317)                                                

Volatile impurities: formula for calculation of the content of acetaldehyde and acetal has been corrected.

Heparin sodium (0333)                                                        

Definition. The scope has been restricted to heparin material of porcine origin since some of the latest requirements do not apply to materials of other origins and that heparin medicinal products currently on the European market are all of porcine origin. Further to the replacement of the clotting assay by 2 chromogenic assays for anti-factor IIa activity and anti-factor Xa activity in general chapter 2.7.5. Assay of heparin, potency is now measured by the assay of anti-factor IIa activity.

Production. A statement was introduced during the last revision, which requires testing for identity of the source species and the absence of material from other likely cross-contaminant species. Further indications have been added that reflect current widely spread practices.

Identification: a requirement for the ratio of anti-factor Xa activity to anti-factor IIa activity has been introduced; a ratio of 1 is typical of unfractionated heparin.

Sodium: range modified in line with current batch data

Sucrose (0204)                                                                      

This monograph has been revised to indicate its status within the context of International Harmonisation, a collaboration between the Japanese Pharmacopoeia, the United States Pharmacopeia and the European Pharmacopoeia. A footnote has been included in the text to refer to chapter 5.8. Pharmacopoeial harmonisation.


 Posted by Tim Sandle

Monday, 21 July 2014

Order of incubation for recovery of bacteria and fungi


One of the dilemmas for the environmental monitoring of controlled environments, when a single culture medium is used, is with the order and length of incubation. The two most common regimes adopted are either 20-25oC followed by 30-35oC and 30-35oC followed by 20-25oC. There have been very few published studies to help the microbiologist with the selection of the optimal incubation regime.

Tim Sandle has written a peer-reviewed research article for the International Journal of Pharmaceutical Compounding. In the article, Dr. Sandle presents experimental data which examines the optimal order of incubation and compares recovery rates for bacteria and fungi.

The conclusion of the study is that the incubation regime has an impact on the numbers of microorganisms recovered and the incidence of recovery. Specifically, where the recovery of fungi is important, the research indicates that the 20-25oC followed by 30-35oC is superior.



Sandle, T. (2014) Examination of the Order of Incubation for the Recovery of Bacteria and Fungi from Pharmaceutical Cleanrooms, International Journal of Pharmaceutical Compounding, 18 (3): 242 – 247
 Posted by Tim Sandle

Posted by Tim Sandle

Special offer: Sterility Testing of Pharmaceutical Products (book)


Sterility Testing of Pharmaceutical Products

by: Tim Sandle (published by PDA/DHI)

The central argument of the book is that control of the process and environmental control are considerably more important guarantors of sterility than the questionable comfort gained from a 'pass' result at the end of the incubation of a sterility test.

This book balances theoretical, and sometimes philosophical, discourses about the nature of sterility and the conceptual problems of microbial viability with sound practical guidance on how to validate the sterility test, problematic products as well as solutions on how to control the environment and review manufacturing process parameters, while navigating the regulatory minefield.

The aim of the book is to present the sterility test as a final product release test as seen in the past, the present and with a view towards the future and is aimed at quality assurance personnel, production staff, microbiologists, students and those with an interest in medicinal products.

By Tim Sandle
Member Price: $240 $204 | Nonmember Price: $299 $254.15 | Government Price: $210 $178.50

Enter Campaign Code summer2014 during checkout. See PDA books.


Posted by Tim Sandle