Compounding Sterile Preparations

The ASHP Discussion Guide for Compounding Sterile Preparations has been written by Eric S. Kastango. It provides an important overview of the complexities and regulatory requirements for sterile compounding. The guide focuses on USP Chapter 797, Pharmaceutical Compounding: Sterile Preparations.

Here is the executive summary:

“Over the past three decades, several pharmacy practice documents have been published in hopes of establishing a standard of practice for compounding sterile preparations that could be universally adopted. None of these documents was successful in achieving this goal. However, on January 1, 2004, USP Chapter 797, Pharmaceutical Compounding: Sterile Preparations, which is published in USP 27/NF 22, came into effect. USP Chapter 797 details the procedures and requirements for compounding sterile preparations and sets standards that are applicable to all practice settings in which sterile preparations are compounded. These standards may be adopted and enforced by state boards of pharmacy and surveyable by accreditation organizations. This discussion guide will provide important information about Chapter <797> and its procedures and requirements. As pharmacists, we have been given the right to compound, but as professionals, we have the obligation to compound right.”

To access, see ASHP.

Posted by Tim Sandle

Environmental Disinfection Systems

The ECR institute have a useful on-line review of different environmental disinfection systems, including UV and hydrogen peroxide technologies:

“In this article, we focus on products that use one of two methods to reduce room bioburden (i.e., the number of microorganisms within the room): UV light and hydrogen peroxide.”

“UV light and hydrogen peroxide share the following characteristics: (1) they cannot be used in an occupied space, (2) they are used after room cleaning to ensure maximum effectiveness, (3) they add to room turnover time, (4) they leave no harmful residue, and (5) they have no residual antimicrobial effect (i.e., they do not continue to kill microorganisms after a new patient is brought into the room).”

To view the article, go to ECR.

Posted by Tim Sandle

A Guide to Biosafety & Biological Safety Cabinets

ESCO have produced an interesting on-line guide to Biosafety and Biological Safety Cabinets.

The guide looks at different biosafety levels and the design requirements for safety cabinets, in a non-commercial way.

To view the guide, go to Biosafety.

Posted by Tim Sandle

Hydrogen peroxide vaporizers

The journal Clinical Infectious Diseases has an article about hydrogen peroxide vaporizers. In the study the devices were placed in single hospital rooms after routine cleaning to disperse a thin film of the bleaching hydrogen peroxide across all exposed hospital equipment surfaces, as well as on room floors and walls.

The study examines the impact on surfaces in relation to bacteria. The reference is:

C. L. Passaretti, J. A. Otter, N. G. Reich, J. Myers, J. Shepard, T. Ross, K. C. Carroll, P. Lipsett, T. M. Perl. An Evaluation of Environmental Decontamination With Hydrogen Peroxide Vapor for Reducing the Risk of Patient Acquisition of Multidrug-Resistant Organisms. Clinical Infectious Diseases, 2012; 56 (1)

Posted by Tim Sandle

Environmental monitoring: psychrophilic and psychrotolerant microorganisms

The purpose of microbiological environmental monitoring is to assess the microbial quality of the cleanroom. Most environmental monitoring is traditionally focused upon the examination of mesophilic micro-organisms. There has been a regulatory shift towards requesting monitoring data concerning micro-organisms with optimal growth rates that fall outside of mesophilic conditions (what might be called extremophiles: micro-organism requiring severe conditions for growth as defined by extremes of temperature, pH, chemical oxidizing agents, hypersalinity or certain types of ultraviolet light).

In particular, regulatory agencies have enquired about the possibility of micro-organisms that can tolerate cold conditions (psychrotolerant) or that will only grow in cold conditions (psychrophilic) being present within cold room environments.

To assess this, Tim Sandle and Kerry Skinner have undertaken research to examine the likelihood and recovery of psychrophilic and psychrotolerant micro-organisms within pharmaceutical manufacturing environments.

The research has been published in the Journal of Applied Microbiology.  The abstract reads:

“Psychrophilic micro-organisms were not detected and those considered to be psychrotolerant were only found in low numbers. Pyschrotolerant organisms were recovered under both low temperature incubation conditions and under standard conditions (between 20 and 35°C). Further evaluation may be required, using alternative agar, and microbiologists should regularly review the species recovered to note differences between different environments.”

The reference is:

Sandle, T. and Skinner, K. (2013). Study of psychrophilic and psychrotolerant microorganisms isolated in cold rooms used for pharmaceutical processing, Journal of Applied Microbiology, doi:10.1111/jam.12101

For further details see PubMed or BioNity

Posted by Tim Sandle

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 EMS

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.

Amazon US

AmazonUK

It is also available via other Amazon stores worldwide.

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

Posted by Tim Sandle

New armour against a post-antibiotic era

The recent warning issued by the World Health Organisation that gonorrhoea is becoming resistant to the last drugs in our armoury heightens awareness of the need for new antibiotics, as do the many reports of new hospital ‘superbugs’. There is some excellent primary research on antibiotic discovery – including exciting developments in metagenomics on the Norwich Research Park – but the issue is how to translate this research into marketable treatments.

In relation to this important area of research, David Livermore (Professor of Medical Microbiology at Norwich Medical School) has written an interesting overview for Laboratory News.

Here is an extract:

“One concern for the future is the re-emergence of classical diseases that we had thought banished to history, for example tuberculosis. The other worry is that without effective antibiotics, we won’t any longer be able to conduct the many types of modern medicine that lead to immunosuppression. These include therapies for autoimmune disorders and cancer treatments. Many routine surgeries may also become too dangerous to perform owing to the risk of untreatable infection. The concept of a ‘post-antibiotic era’, where common infections can no longer be successfully treated, has been around since the early ‘90s. At that time, resistance amongst Gram-positive bacteria was rising rapidly. Penicillin-resistant pneumococci were widespread internationally1 and vancomycin-resistant enterococci were also circulating in hospital specialist units2, most extensively in the US. Methicillin-resistant Staphylococcus aureus (MRSA) were relatively uncommon in serious infections at the start of the 1990s, but proliferated to the point, from 2000-3, where they accounted for 40% of all Staphylococcus aureus infections and 10% of all UK bloodstream infections. Similar rises were seen in most of Europe (except the Netherlands and Scandinavia), and in the USA.”

To read more, see Laboratory News.

Amazon book discounts
Posted by Tim Sandle

Which cleanroom standards are being revised?

The various cleanroom standards can sometimes be confusing and the revision process is at times hard to follow. Listed below are those cleanroom standards that are currently undergoing revision:

ISO/DIS 14644-1 Cleanrooms and associated controlled environments -- Part 1: Classification of air cleanliness by particle concentration (DIS resolution – – Enquire Stage 40.92)

ISO/DIS 14644-2 Cleanrooms and associated controlled environments -- Part 2: Specifications for monitoring to provide evidence of cleanroom performance by ACP (DIS resolution – Enquire Stage 40.92)

ISO/CD 14644-3 Cleanrooms and associated controlled environments -- Part 3: Test methods (Preliminary Stage – 00)

ISO/FDIS 14644-10 Cleanrooms and associated controlled environments -- Part 10: Classification of surface cleanliness by chemical concentration (out for FDIS vote – Approval Stage 50.20)

Posted by Tim Sandle

Applying a risk matrix to media fills

Media trials are a regulatory requirement for aseptic processing manufacturers. Given that not every product combination can be assessed on multi-product filling lines, some assessment criteria is required to select the ‘worst-case’ filling run parameters.

To examine this, a peer reviewed paper written by Tim Sandle and colleagues discusses the main criteria suitable for such an exercise and illustrates the application using a case study. In doing so, the paper examines the adoption of a risk-based matrix approach for the selection of product simulations used when conducting media filling trials.

Here is an extract:

“What is less clear is where there are filling lines used for multi-product filling. A media fill can measure clearly not every combination of vial and container closure at each required interval; with large facilities, a rotational program could take many years to complete (which would additionally mean that either a problematic fill or the combination deemed to present the greatest potential contamination risks to product would not be assessed very often). To address this issue, many manufacturers adopt a matrix approach in order to assess the product types deemed to be of the greatest challenge to the process or that are at a greater risk of microbial contamination.”

The reference for the paper is:

Sandle, T., Leavy, C. and Needham, G. (2012). A Risk Matrix Approach for Media Simulation Trials, Journal of Validation Technology, Vol. 18, No.4, pp70-78

If you wish to read the article, please contact Tim Sandle.

Posted by Tim Sandle

FDA Guidance on Clinical Site Data

FDA has issued draft guidance: Specifications for Preparing and Submitting Summary Level Clinical Site Data for CDER’s Inspection Planning, which provides current FDA specifications for preparing and submitting a summary-level clinical-site dataset in electronic form for NDAs, BLAs, and NDA or BLA supplemental applications submitted to FDA’s CDER.

For details, see FDA



Posted by Tim Sandle

Microbes expel swarms of vesicles

Scientists have presented the first evidence that marine cyanobacteria release billions and billions of vesicles.

A research team have published the first evidence of vesicle production by marine cyanobacteria in Science .

“The finding that vesicles are so abundant in the oceans really expands the context in which we need to understand these structures,” MIT postdoc Steven Biller, the lead author on the paper, said in a press release.

So far, what Biller and his colleagues do know is that cultured Prochlorococcus—the most numerous photosynthetic organism on earth—continually produce vesicles, which contain proteins, DNA, and RNA; seawater samples are also abundant in vesicles. Vesicles collected from the wild contained DNA from a variety of organisms, suggesting that other microbes also shed them.

Further, the researchers found that nonphotosynthetic bacteria grown in the lab could be sustained with vesicles as their only source of carbon. “That’s kind of neat,” Marvin Whiteley, a microbiologist at the University of Texas, Austin, who was not involved in the study, told Wired. “It really changes how we think about marine ecosystems and how they’re set up and how nutrients are provided.”

Biller’s colleague Sallie Chisholm, a professor of biology at MIT, told LiveScience that it’s not clear why the microbes are making vesicles. “If you have an organism eking out a living in a really dilute environment, where nutrients are extremely low, why would it cast things off into the environment that would limit its own growth?” Chisholm asked. “We figure these vesicles have to have some important function. ”
Posted by Tim Sandle

FDA Guidance on Electronic Submissions

FDA has issued a draft guidance relating to electronic submissions. Guidance for Industry: Providing Submissions in Electronic Format—Summary Level Clinical Site Data for CDER’s Inspection Planning is one in a series of guidance documents intended to assist sponsors and applicants making certain regulatory submissions to FDA in electronic format.

The draft guidance describes FDA’s recommendation that applicants submit summary-level clinical-site datasets in a standardized electronic format. This guidance generally applies to submissions of summary-level clinical-site datasets for new drug applications (NDAs), biologics licensing applications (BLAs), and NDA and BLA supplemental applications containing new clinical-study reports that are submitted to FDA’s Center for Drug Evaluation and Research (CDER). The purpose of the guidance is to assist applicants in the submission of a clinical dataset that describes and summarizes the characteristics and outcomes of clinical investigations at the level of the individual study site (summary-level clinical-site data). The summary-level clinical-site dataset is intended to facilitate the use of a risk-based approach for the timely identification of clinical investigator sites for on-site inspection by CDER during the review of marketing applications. The guidance refers to a number of technical specification documents and other resources. These technical specification documents and resources are available online to make them more accessible to applicants.

For details, see FDA.

Posted by Tim Sandle

Genetically identical bacteria can behave in different ways

Although a population of bacteria may be genetically identical, individual bacteria within that population can act in radically different ways, according to a new study.

The authors suggest that this phenomenon is important in the bacteria's struggle for survival. The more diversity a population of bacteria has, the more likely it will contain individuals able to take advantage of a new opportunity or overcome a new threat, including the threat posed by an antibiotic.

The study was carried out by University of Washington researchers, who showed that when a bacterial cell divides into two daughter cells there can be an uneven distribution of cellular organelles. The resulting cells can behave differently from each other, depending on which parts they received in the split.

For further details see:

M. Christen, H. D. Kulasekara, B. Christen, B. R. Kulasekara, L. R. Hoffman, S. I. Miller. Asymmetrical Distribution of the Second Messenger c-di-GMP upon Bacterial Cell Division. Science, 2010; 328 (5983): 1295 DOI: 10.1126/science.1188658

Posted by Tim Sandle

Staphylococcus aureus lingers deep in our noses

Humans' noses may have hidden crevices where the bacteria that cause staph infections can be found in high numbers. Scientists have known for decades that the nose was a primary reservoir of Staphylococcus aureus. However, a deeper look within the nasal cavity revealed previously unidentified spots that harbored the potentially dangerous bacteria. The discovery could explain why some people only get rid of Staphylococci bacteria for a short amount of time when treated, researchers report in Cell Host & Microbe ("Nasal Microenvironments and Interspecific Interactions Influence Nasal Microbiota Complexity and S. aureus Carriage").

The team also found that when more of the bacteria Corynebacterium pseudodiphtheriticum was present in the nose, there were fewer S. aureus microbes. C. pseudodiphtheriticum may make a molecule that blocks the growth of S. aureus and, if identified, could lead to the development of a new drug to treat or prevent staph infections.

The points of the research are:

• Phylogenetic composition of nasal communities differed by site epithelium type
• Bacterial diversity was greater at the mucosal sites than at naris
• Abundance of two Corynebacterium species correlated with S. aureus carriage status
• These Corynebacterium species and S. aureus interact at mucosal habitats and in vitro

Posted by Tim Sandle

Microbiome

Scientists have amassed substantial evidence that people and other animals form a unit with their resident bacteria, archaea, fungi and viruses — the collection of microbes known as the microbiome. In fact, only about 10 percent of a person’s cells are human; microbes make up the other 90 percent.

Treating a host, such as the human body, and its resident bacteria as a unit — or at least as an ecosystem with intimately interconnected parts — offers various benefits. The superorganism approach may help researchers better understand how diet, chemicals and other environmental factors affect health, for instance.

Everyone carries a slightly different microbial mix. Strong evidence indicates that some differences stem from diet or habitat. But even mice raised under uniform lab conditions still have individualized microbiomes. In October, two groups presented research suggesting that host genes play a role in selecting which microbes are allowed to settle in and on the body (SN: 11/30/13, p. 11). Immune system genes may be especially important in screening suitable microbial companions.

People with immune system problems have more types of bacteria and fungi on their skin. New research shows that some of those microbes may contribute to eczema-like rashes. That finding supports the idea that the immune system grants visas to friendly microbes while keeping out dangerous interlopers.

Newborns rein in their own immune systems to allow bacteria to take hold, one study found (SN: 12/14/13, p. 10). Previously, researchers thought that babies’ immune systems were just too immature to control microbes. But the new work shows that in mice and human umbilical cords, blood cells carry an immune-suppressing protein that prevents defenders from fighting off beneficial bacteria.

In mice, pups of stressed moms picked up a different mix of bacteria during birth than those born tonon-stressed moms, researchers reported at the Society for Neuroscience meeting in November. Those bacteria may affect early brain development and possibly contribute to disorders such as autism and schizophrenia (SN: 12/14/13, p. 13).

A study reported in December may strengthen the link between autism and gut microbes (SN Online: 12/5/13). Caltech researchers found that mice with autism-like symptoms have a different mix of gut microbes than normal mice do. Those microbes make chemicals that leak from the intestines into the bloodstream (and perhaps the brain), producing behavioral changes. Treating the mice with the beneficial bacterium Bacteroides fragilis improved some symptoms, suggesting that altering the microbial mix might help some children with autism.

Once established, friendly bacteria shield their hosts from harmful invaders and may keep the immune system from overreacting. Harvard researchers discovered that some intestinal microbes make immune-calming molecules that can help reduce the kind of inflammation that afflicts the bowels in diseases like colitis (SN: 8/10/13, p. 14).

Even friendly bacteria put their own needs first, though. Another Harvard group found that some strains of a common gut microbe called Eggerthella lenta can rob heart patients of a drug called digoxin if the bacteria don’t get enough protein from their hosts (SN Online: 7/19/13). Some microbes change chemicals in meat into artery-cloggers (SN: 5/18/13, p. 14) or cause pain all on their own (SN: 10/5/13, p. 16).

Microbiomes not only alter the biochemical milieu in individuals, but can also influence relationships between entire species. Or even the course of evolution. A study of jewel wasps, for instance, suggests that their microbiomes can prevent two species from successfully breeding with one another (SN: 8/10/13, p. 13).
Hybrid male offspring of the two species die as larvae, an effect long explained as incompatibility between the species’ genes. But when Seth Bordenstein of Vanderbilt University and his colleague Robert Brucker removed microbes from the hybrid larvae, the wasps survived. That finding indicates that microbes in the wasps’ guts and not just the wasp genes contribute to keeping the two species from interbreeding.

The microbial momentum continues to build...

Posted by The Scientist

Fungal Contamination in Pharmaceutical Products and Cleanroom Risk (webinar)

Dr Tim Sandle (Pharmig Committee Member) will present a one hour lecture on Fungal Contamination in Pharmaceutical Products and Cleanroom Risks (including a Q&A section) on Wednesday 19th February at 2pm (GMT).

The session will cover:

• Review of fungal contamination recalls 
• Types of fungi isolated 
• Cleanroom and operator contamination sources 
• Implications: environmental monitoring, disinfectant testing and media QC 

FEES: Pharmig Member £70 sterling / Non Member £100 sterling

Payment can be made by credit card via www.pharmig.org. uk and clicking on meetings and Fungal Webinar.

Or, you can email the Pharmig office who will contact you for card details info@pharmig.org.uk

Or, by raising a purchase order (this needs to be sent to the Pharmig office before the start of the webinar)

If you have any questions please call Pharmig on +44 (0) 1920 871 999 / email: info@pharmig.org.uk

After registering, you will receive a confirmation email containing information about joining the webinar.

View System Requirements
Posted by Tim Sandle

TB vaccine 'could help prevent MS'

An anti-tuberculosis vaccine could prevent multiple sclerosis, early research suggests. A small-scale study by researchers at the Sapienza University of Rome has raised hopes that the disease can be warded off when early symptoms appear.

More research is needed before the BCG vaccine can be trialled on MS patients.MS is a disease affecting nerves in the brain and spinal cord, causing problems with muscle movement, balance and vision. Early signs include numbness, vision difficulties or problems with balance.

In the study, published in the journal Neurology, Italian researchers gave 33 people who had early signs of MS an injection of BCG vaccine.The other 40 individuals in the study were given a placebo. After five years, 30% of those who received the placebo had not developed MS, compared with 58% of those vaccinated.

Continue reading the main story

Your body is mostly microbes

 In 2013, scientists amassed substantial evidence that people and other animals form a unit with their resident bacteria, archaea, fungi and viruses — the collection of microbes known as the microbiome. In fact, only about 10 percent of a person’s cells are human; microbes make up the other 90 percent.

Many researchers point out that ultimately, every species is out for itself. Nevertheless several new studies argue in favor of considering animals as superorganisms composed of host and microbes. Some scientists even advocate lumping a host organism’s genes with those of its microbes into one “hologenome.”

Treating a host, such as the human body, and its resident bacteria as a unit — or at least as an ecosystem with intimately interconnected parts — offers various benefits, scientists say. The superorganism approach may help researchers better understand how diet, chemicals and other environmental factors affect health, for instance.

Everyone, including identical twins, carries a slightly different microbial mix. Strong evidence indicates that some differences stem from diet or habitat. But even mice raised under uniform lab conditions still have individualized microbiomes. In October, two groups presented research suggesting that host genes play a role in selecting which microbes are allowed to settle in and on the body (SN: 11/30/13, p. 11). Immune system genes may be especially important in screening suitable microbial companions.

People with immune system problems have more types of bacteria and fungi on their skin. New research shows that some of those microbes may contribute to eczema-like rashes. That finding supports the idea that the immune system grants visas to friendly microbes while keeping out dangerous interlopers.

Newborns rein in their own immune systems to allow bacteria to take hold, one study found (SN: 12/14/13, p. 10). Previously, researchers thought that babies’ immune systems were just too immature to control microbes. But the new work shows that in mice and human umbilical cords, blood cells carry an immune-suppressing protein that prevents defenders from fighting off beneficial bacteria.

In mice, pups of stressed moms picked up a different mix of bacteria during birth than those born tonon-stressed moms, researchers reported at the Society for Neuroscience meeting in November. Those bacteria may affect early brain development and possibly contribute to disorders such as autism and schizophrenia (SN: 12/14/13, p. 13).

A study reported in December may strengthen the link between autism and gut microbes (SN Online: 12/5/13). Caltech researchers found that mice with autism-like symptoms have a different mix of gut microbes than normal mice do. Those microbes make chemicals that leak from the intestines into the bloodstream (and perhaps the brain), producing behavioral changes. Treating the mice with the beneficial bacterium Bacteroides fragilis improved some symptoms, suggesting that altering the microbial mix might help some children with autism.

Once established, friendly bacteria shield their hosts from harmful invaders and may keep the immune system from overreacting. Harvard researchers discovered that some intestinal microbes make immune-calming molecules that can help reduce the kind of inflammation that afflicts the bowels in diseases like colitis (SN: 8/10/13, p. 14).

Even friendly bacteria put their own needs first, though. Another Harvard group found that some strains of a common gut microbe called Eggerthella lenta can rob heart patients of a drug called digoxin if the bacteria don’t get enough protein from their hosts (SN Online: 7/19/13). Some microbes change chemicals in meat into artery-cloggers (SN: 5/18/13, p. 14) or cause pain all on their own (SN: 10/5/13, p. 16).
Microbiomes not only alter the biochemical milieu in individuals, but can also influence relationships between entire species. Or even the course of evolution. A study of jewel wasps, for instance, suggests that their microbiomes can prevent two species from successfully breeding with one another (SN: 8/10/13, p. 13).

Posted by Tim Sandle

European Journal of Parenteral & Pharmaceutical Sciences

The European Journal of Parenteral & Pharmaceutical Sciences is a peer reviewed journal, published by Euromed Communications on behalf of the Pharmaceutical and healthcare Sciences Society (PHSS). The journal covers a number of subject relating to pharmaceutical microbiology.

The website for the journal has recently been updated and the 18 current volumes have each been indexed. The journal is also searchable on Scopus.

To view the index, go to Euromed

Posted by Tim Sandle

European Pharmacopoeia 8th Edition

The 8^th edition of the European Pharmacopeia had an implementation date 1st Jan 2014. The monographs and general chapters that are new, or that have been revised, corrected or deleted for the 8th Edition are:

2.2.40  Near-infrared spectroscopy                                                                

General revision to introduce process analytical technology (PAT) concepts such as in- and on-line measurements. Furthermore, duplication with EMA text “Guideline on the use of Near Infrared Spectroscopy (NIRS) by the pharmaceutical industry and the data requirements for new submissions and variations” (under revision) has been avoided.

3.2.9.   Rubber closures for containers for aqueous parenteral preparations, for powders and freeze-dried powders                                                 

• Identification A: requirement for elasticity deleted since test cannot be performed on all types of rubber closures; identifications B and C renamed A and B respectively.
• Identification B: possibility of recording FTIR-ATR spectra directly on surface of sample introduced.
• Identification C: limit adapted and now depends on total ash content of type sample.
• Solution S: water for injections R replaced with water R; use of another container for preparation of solution S added.
• Volatile sulfides: description of preparation of standard solution revised.

Human plasma for fractionation (0853)                                             

Individual plasma units: questions have arisen amongst some users of the monograph over the reference to freezing plasma intended for the production of non-labile proteins ‘as soon as possible’ after collection. This is because time limits of 24 h (plasma obtained from plasmapheresis) and 72 h (plasma obtained from whole blood) are also given for freezing. For clarification, the reference to ‘as soon as possible’ has been deleted and the monograph now states the maximum acceptable time limits for freezing of plasma following collection. Additionally, in the context of using suitable methods to conserve labile proteins as much as possible, the reference to good manufacturing practice (GMP) has been deleted because there are steps taken that do not necessarily fall under the scope of GMP which contribute to the quality of plasma and the conservation of labile proteins.

2.4.13  Sulfates

Insertion of text: ‘the prescribed’ solution.

Human Albumin solution (0255)

Correction:  ‘preparation’ to ‘test solution’.

Posted by Tim Sandle

Biopharma Innovation Updates and Strategies (e-book)

BioPharm International have issued a special e-book. The e-bookexamines strategies to drive innovation in biopharmaceutical development, including extending patent life, new financing options, and working with contract development and manufacturing organization to bridge innovation gaps. Executives at three biopharmaceutical companies at different stages of product development provide insight on driving new drug therapies to market.

For further details see BioPharm International.



Posted by Tim Sandle

Global strategies for the elimination of leprosy

Of the various ‘ancient diseases’, one of the longest lasting (and arguably notorious) is leprosy (leprosy was recognized in the ancient civilizations of China, Egypt and India). Notwithstanding its long history, the disease is one that should be relatively straightforward, with tangible political support, to eliminate as a global health concern. The current strategy is being implemented by the World Health Organization (WHO).

In a new paper, Tim Sandle reviews this strategy and additionally considers some of the current research into leprosy, focused on the areas of diagnosis and treatment.

The reference is:

Sandle, T. (2013). Global Strategies for Elimination of Leprosy: A Review of Current Progress, Journal of Ancient Diseases & Preventive Remedies, 1 (4): e112. doi: 10.4172/2329-8731.1000e112

For a copy of the paper, please contact Tim Sandle

Posted by Tim Sandle

Sterility, Sterilization and Sterility Assurance for Pharmaceuticals (new book)

New book: 'Sterility, Sterilisation and Sterility Assurance for Pharmaceuticals: Technology, Validation And Current Regulations'.

A new book covering a the entire range of different sterilization methods, as well as exploring the related areas of sterility assurance and the concept of sterility, has been published. The book has been written by Tim Sandle.

The key features of the book are:

• The main sterilization methods of physical removal, physical alteration and inactivation
• Discussions of medical devices, aseptically filled products and terminally sterilized products
• An examination of the bacterial, pyrogenic, and endotoxin risks to devices and products.

In terms of the book's importance for pharmaceuticals, medical devices and healthcare:

Failure to adequately control any microbial challenge associated within process or product by robust sterilisation will result in a contaminated marketed product, with potential harm to the patient. Sterilisation is therefore of great importance to healthcare and the manufacturers of medical devices and pharmaceuticals. Sterility, sterilisation and sterility assurance for pharmaceuticals examines different means of rendering a product sterile by providing an overview of sterilisation methods including heat, radiation and filtration. The book outlines and discusses sterilisation technology and the biopharmaceutical manufacturing process, including aseptic filling, as well as aspects of the design of containers and packaging, as well as addressing the cleanroom environments in which products are prepared. Consisting of 18 chapters, the book comprehensively covers sterility, sterilisation and microorganisms; pyrogenicity and bacterial endotoxins; regulatory requirements and good manufacturing practices; and gamma radiation. Later chapters discuss e-beam; dry heat sterilisation; steam sterilisation; sterilisation by gas; vapour sterilisation; and sterile filtration, before final chapters analyse depyrogenation; cleanrooms; aseptic processing; media simulation; biological indicators; sterility testing; auditing; and new sterilisation techniques.

The chapter list is:

• Sterility, sterilization and microorganisms
• Pyrogenicity and bacterial endotoxin
• Regulatory requirements and Good Manufacturing Practices (GMP)
• Gamma radiation
• Electron beam processing
• Dry heat sterilization
• Steam sterilization
• Gaseous sterilization
• Hydrogen peroxide vapor sterilization
• Sterilization by filtration
• Other methods of sterilization
• Depyrogenation and endotoxin
• Cleanrooms, isolators and cleanroom technology
• Aseptic processing and filling
• Media simulation trials
• Cleaning and disinfection of sterile processing facilities
• Biological indicators
• The Sterility Test
• Investigating sterility test failures
• Auditing sterilization processes and facilities.

The book has been published by Woodhead Publishing / Elsevier and is available as a hardback and as an e-book.

Further details of the hardback version and the order page can be found here.

Details of the e-book version and an opportunity to order can be found here.

The book is also available via Amazon and other bookstores.

Harcopy and e-copy

Posted by Tim Sandle

Spaceflight and microbial pathogens: possible drug resistance

At Arizona State University's Biodesign Institute, Cheryl Nickerson and her team have been investigating the intriguing effects of spaceflight on microbial pathogens. Specifically the team reports their recent work examining spaceflight-induced responses in, and infectious disease potential of, the fungal pathogen, Candida albicans.

The new study reports the differential regulation of 452 genes in spaceflight-cultured C. albicans, compared to fungal cells cultured under otherwise identical ground-based conditions. The expression of a wide variety of functionally diverse gene families was altered, including those regulating cell aggregation and budding, biofilm formation and resistance to pathogenesis-related stresses and antifungal drugs.

Therefore, the pathogen in its transformed state poses a significant infectious disease risk.

For further details, refer to the following paper:

Aurélie Crabbé et al. Spaceflight Enhances Cell Aggregation and Random Budding in Candida albicans. PLoS ONE, 2013; 8 (12): e80677 DOI: 10.1371/journal.pone.0080677

Posted by Tim Sandle

The Protein Handbook: A guide to antibody purification and protein analysis

Life Technologies have issued a free protein handbook. According to Life Technologies:

Get exclusive access to the underlying technologies, example protocols, tips and tricks, and references to peer-reviewed product application literature for the entire collection of Novex® gels, tanks and accessories, antibodies, and immunoassays.

And now your free protein handbook is available in a convenient e-book format with links to selection guides, technical support resources, and more.

Sections include: 

• Protein purification
• Protein separation
• Western blotting
• Antibody pairs and ELISAs
• Multiplex assays

Posted by Tim Sandle

The influence of microbiome on autoimmunity

 We live with millions of microorganisms, and this coexistence comes as a mixed blessing. Evolution drove bacteria to not only to survive in humans, but also to protect us by supporting various physiological, metabolic, and immune processes. On the other hand, research implicates bacteria in conditions detrimental to health, like allergies, obesity, multiple sclerosis, and recently rheumatoid arthritis.

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.

For further details, see Science World

Posted by Tim Sandle

Inner workings of bacterial ‘black box’ – amazing video

Using a pioneering visualization method, researchers from the University of California, Berkeley and the Department of Energy Joint Genome Institute (DOE JGI) made what are, in effect, movies of this complex and vital cellular machinery being assembled inside living cells. They observed that bacteria build these internal compartments in a way never seen in plant, animal and other eukaryotic cells.

For further details see the Genome Institute

Posted by Tim Sandle

Controlling antimicrobial resistance

Antimicrobial resistance is a responsibility of each and every one of us, be it a patient, healthcare professional or policy maker. This is the theme of an interesting article in the journal European Hospital.

The article states:

“In the past four years, in more than a third of EU/EEA countries, there has been a significant increase in the trend towards combined resistance to both Klebsiella pneumoniae and E. Coli; on a more positive note methicillin- resistant Staphylococcus aureus (MRSA) has shown a decrease or stabilisation in most European countries.”

To view the article, go to EH.

Posted by Tim Sandle

Microorganisms in water pipework

The American Society for Microbiology have issued an interesting report titled “Microbes in Pipes: The Microbiology of the Water Distribution System”.

According to ASM: “Most microbes in distribution systems probably do not pose health threats, but when they form biofilms, they can cause physical damage such as corroding pipes and blocking valves. In addition to forming biofilms, some non-pathogenic microorganisms can break down chemicals used to minimize microbial growth and others may release nutrients into the distribution system that support downstream growth of opportunistic pathogens. The extent to which these processes occur in water distribution systems is largely unknown, because these ecosystems have not been characterized.”

To read more, go to the AMS website.

Posted by Tim Sandle

FDA Releases New Q&A on Adhering to QbD Principles

The FDA has released a second question-and-answer document intended to provide guidance to industry on the concept of quality by design.

The document contains nine questions and answers, including:

• 1.      Why would a design space be verified during the product lifecycle? (There are risks inherent in scaling-up or making new model assumptions, and it is necessary to understand these risks.)
• 2.      What is the purpose of design space verification at commercial scale? (to demonstrate control over the product and its quality)
• 3.      How is a design space initially developed and verified at commercial scale? (based on experiments conducted at laboratory or pilot scale, which requires subsequent validation at larger scales)
• 4.      How can a design space be verified at commercial scale? (It is not necessary to repeat at commercial scale the experiments initially conducted to define a design space at lab or pilot scale, but should be guided by the results of risk assessments.)
• 5.      How should design space verification protocol be addressed in the submission? (General and specific requirements for both EMA and FDA are explained.)
• 6.      What if unexpected results/events are obtained during the design space verification studies? (The results should be studied and, if necessary, reported to regulatory authorities.)
• 7.      How can a design space be verified at commercial scale for biological products? (The principles are the same for both chemical and biological products.)
• 8.      What is the difference between process validation and design space verification? (Process validation demonstrates consistency of the process at normal operating ranges, design space verification demonstrates that scale effect and or model assumptions are under control in the new area of design space and do not affect product quality.) 

• 9.      How should design space verification approach be addressed in the pharmaceutical quality system? (Firms should have a written plan for when and how to evaluate the need for design space verification.)

For details see FDA

Posted by Tim Sandle