Saturday, 10 October 2015

New links between gut microbes and mental health in children

Interesting microbiome news from Genscript:

As we learn more about the human microbiome, evidence keeps mounting that the 'Gut-Brain Axis' enables our intestinal bacteria to influence our mood and mental health:
A recent study in Brain, Behavior, and Immunity finds that differences in gut microbiome composition are associated with differences in temperament in healthy toddlers.
A new study in Pediatric Research finds an association between early probiotic intervention and the risk of neuropsychiatric disorders (ADHD and Asperger syndrome) later in childhood.
A new review discusses new evidence from epidemiology an animal studies on bidirectionality of gut-brain communication across development and efforts to prevent or treat psychological disorders by modifying intestinal flora.

Posted by Victor Grayson

Friday, 9 October 2015

Revised Annex 17 on the Real Time Release Testing

Consultation has begun on EU GMP Guidelines, revised Annex 17 on the Real Time Release Testing.

In terms of the scope of the document:

“This document is intended to outline the requirements for application of a Real Time Release Testing (RTRT) approach in manufacturing, where the control of critical parameters and relevant material attributes may be used as an alternative to routine finished product testing of medicinal products. The main aim of the changes to this guideline is to incorporate the application of RTRT to any stage in the manufacturing process and to any type of finished products, including active substances and intermediates.”

The consultation runs until December 11, 2015.

For more details see the European Commission

Posted by Tim Sandle

Thursday, 8 October 2015

European Pharmacopoeia 8.6

Review of Supplement 8.6: Implementation date 1st Jan 2016. Items of interest are copied below.

Revised texts

2.2.20  Potentiometric titration                                                          

General method updated to introduce modern autotitrator instruments; reference to mercury- containing electrodes deleted following the entry into force of EU Regulation 847/2012 restricting the use of mercury in measuring devices


Anticoagulant and preservative solutions for human blood (0209): Identification A: name of CRS modified to indicate degree of hydration; system suitability performed using reagents instead of CRSs (valid for ACD and CPD).

Lysine hydrochloride (0930): Ammonium: presented as a separate limit test from the test for ninhydrin-positive substances

Polysorbate 80 (0428): 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

Sodium hydroxide (0677): Chlorides, Sulphates: limits increased.

Sucrose (0204): Identification B: system suitability performed using reagents instead of CRSs.

Posted by Tim Sandle

Wednesday, 7 October 2015

Unlocking the human microbiome

Katherine Pollard, senior investigator at the Gladstone Institutes, developed a suite of new statistical software to rapidly and accurately estimate the presence and function of microbes in a metagenome. Their programs--called MicrobeCensus, ShotMAP and PhyloCNV--made significant methodological improvements that allowed the scientists to accurately quantify the specific strains in the human microbiome using sequencing reads as short as 50 base pairs.

Using the new tools, Pollard's lab investigated a reported finding that obese people have a lower ratio of bacteria from the phylum Bacteroidetes to bacteria from the phylum Firmicutes compared with lean individuals. Although the scientific literature and the general media had heralded this association as noteworthy, several reports questioned its existence.

To test the validity of the association, Pollard's group conducted an extensive assessment of the relationship between body mass index (BMI) and the taxonomic composition of the gut microbiome. Their meta-analysis of data from multiple studies did not find a significant association between BMI and the relative abundance of any bacterial species.

For further details see the American Statistical Association.

Posted by Tim Sandle

Dengue fever breakthrough

An international research team led by the University of Pittsburgh Graduate School of Public Healthhas shown that epidemics of dengue, which is caused by a mosquito-borne virus, across southeast Asia appear to be linked to the abnormally high temperatures brought by the El Niño weather phenomenon.

Now, as the most intense El Niño in nearly two decades is emerging in the Pacific, the finding – reported in today’s issue of the Proceedings of the National Academy of Sciences (PNAS) – may be a harbinger of a spike in cases of the dangerous hemorrhagic fever throughout southeast Asian countries early next year.

“Large dengue epidemics occur unexpectedly, which can overburden the health care systems,” said lead author Willem G. van Panhuis, M.D., Ph.D., assistant professor of epidemiology at Pitt Public Health.

“Our analysis shows that elevated temperatures can create the ideal circumstance for large-scale dengue epidemics to spread across a wide region. The ability to predict and prepare for these epidemics should lead to more effective disease surveillance and control efforts.”

Dengue virus is transmitted by mosquitoes in the tropics and subtropics. It causes an estimated 390 million infections each year. Though there is no specific pharmaceutical treatment, supportive therapy can greatly improve outcomes.

In many countries, reported cases of dengue wax and wane during the rainy season following a repeating annual cycle. So far, it has been difficult to predict when these epidemics will become unusually large, spreading beyond country borders.

“This study will contribute toward a better understanding of the cyclical nature of dengue,” said co-author Lam Sai Kit, Ph.D., professor at the University of Malaya in Malaysia. “Based on the extensive data analyzed and the conclusions reached, it will help to improve early warning systems for impending large outbreaks in the region. Now that the new El Niño has started, these findings will help us prepare for a worst-case scenario, and immediate measures can be taken to counter its effect in the next few months.”

The research team collected and analyzed 18 years of monthly dengue surveillance reports on a total of 3.5 million reported cases in 273 provinces in eight countries in southeast Asia. By bringing the data together from several countries, the scientists were able to see patterns – or synchronicity – in dengue transmission across the entire region.

“This is another example of extracting valuable information from routinely collected public health data that was just sitting around in basements and computer archives across these countries,” said Dr. van Panhuis.

In 1997 and 1998, dengue transmission was very high, matching up perfectly with high temperatures that allowed mosquitoes to reproduce faster and spread dengue virus more efficiently. These high temperatures were caused by an exceptionally strong El Niño season, which occurs when rising sea water temperatures in the eastern Pacific move westward. This phenomenon occurs about every five years, with one of the largest episodes expected in the coming months.

This study also found that urban areas act as dengue epidemic “pacemakers” because of their constant supply of new people who are susceptible to dengue. In addition, traveling waves of large epidemics were found to emerge from west Thailand, central Laos and the southern Philippines.

“Given the increased cross-border mobility of people, strong evidence of global warming and the potential for rapid global proliferation of infectious diseases, a better understanding of how contagious diseases spread over long distances is essential for global health security,” said Dr. van Panhuis. “During this study, we’ve created a foundation for improved multi-country collaboration to improve infectious disease surveillance, analysis and control. We should systematically combine disease data from multiple countries to continuously monitor the risk of epidemics at regional scales.”

 Posted by Tim Sandle

Tuesday, 6 October 2015

Identification of Yersinia species

Public health England has issued “UK Standards for Microbiology Investigations ID 21: identification of Yersinia species.”

Members of the genus Yersinia are Gram-negative, catalase-positive and oxidase-negative, facultatively anaerobic straight rods to coccobacilli. Cells are 0.5 - 0.8μm by 1-3μm in size and show bipolar staining (“closed safety-pin appearance”). They have both respiratory and fermentative type of metabolism.

The document provides guidance about the identification of these organisms. To access the document, see Public Health England.

Posted by Tim Sandle

Monday, 5 October 2015

Autoclaves, wet loads and the issue of sterility

Steam sterilization is a critical process in the pharmaceutical and related industries. Modern autoclaves are computer-controlled and reliably provide a defined sterilization cycle. This paper considers some of the potential causes for wet loads and addresses some of the measures that can be taken to address occurrences.

In relation to this, Tim Sandle has written a paper on some of the causes and corrective actions for autoclave wet load issues.

The reference is:

Sandle, T. (2015) Ensuring Sterility: Autoclaves, Wet Loads, and Sterility Failures, Journal of GXP Compliance, 19 (2): 1-10

For a copy, please contact Tim Sandle

Posted by Tim Sandle

Sunday, 4 October 2015

ISO 14001: 2015 - published

ISO 14001:2015, which sets out the requirements for an environmental management standard, is one of the world’s most widely used standards and a key business tool for many organizations. With more than 300 000 certificates currently issued around the world, it ranks high on the agenda of many organizations worldwide who place importance on their environmental impact.

A newly revised version has just been published, to ensure it remains relevant to the marketplace. ISO 14001:2015 responds to the latest trends, such as an increasing recognition by companies of the need to factor in both external and internal elements that influence their impact, including climate volatility.

Other key improvements in the new version include: 
  • A greater commitment from leadership
  • An increased alignment with strategic direction
  • Greater protection for the environment, with a focus on proactive initiatives
  • More effective communication, driven through a communications strategy
  • Life-cycle thinking, considering each stage of a product or service, from development to end-of-life
For further details see: ISO

Posted by Tim Sandle

Saturday, 3 October 2015

ISO 9001:2015 – published

The latest edition of ISO 9001, ISO's flagship quality management systems standard, has just been published. This concludes over three years of revision work by experts from nearly 95 participating and observing countries to bring the standard up to date with modern needs.

ISO 9001:2015 replaces previous editions and certification bodies will have up to three years to migrate certificates to the new version.

ISO 9000, which lays down the concepts and language used throughout the ISO 9000 family of standards, has also been revised and a new edition is available.

For further details see: ISO

Posted by Tim Sandle

Friday, 2 October 2015

Compliance and Risk Management

Pharmaceutical Manufacturing has issued an e-book on “State of Pharmaceutical Quality: Compliance and Risk Management”.

EtQ and Pharmaceutical Manufacturing partnered recently to survey pharmaceutical and biotech industry professionals in manufacturing, quality, compliance and regulatory. The objective was to have a better understanding of the pharmaceutical pain points. This presentation will discuss the survey results, and what they mean for the future of the industry.

For details see: Pharma Manufact.

Posted by Tim Sandle

Thursday, 1 October 2015

SGM becomes Microbiology Society

The Society for General Microbiology has been renamed as the Microbiology Society. It is the largest learned microbiological society in Europe with a worldwide membership based in universities, industry, hospitals, research institutes and schools.

For details, see the Microbiology Society.

Posted by Tim Sandle

Wednesday, 30 September 2015

EU GMP Annex 15

In February 2014 the draft for the revision of Annex 15 “Qualification and Validation” was published. Now the draft has been published as final document and will be valid as of 1 October 2015.

The introduction reads:

“This Annex describes the principles of qualification and validation which are applicable
to the facilities, equipment, utilities and processes used for the manufacture of medicinal
products and may also be used as supplementary optional guidance for active substances
without introduction of additional requirements to EudraLex, Volume 4, Part II. It is a
GMP requirement that manufacturers control the critical aspects of their particular
operations through qualification and validation over the life cycle of the product and
process. Any planned changes to the facilities, equipment, utilities and processes, which
may affect the quality of the product, should be formally documented and the impact on
the validated status or control strategy assessed. Computerised systems used for the
manufacture of medicinal products should also be validated according to the
requirements of Annex 11. The relevant concepts and guidance presented in ICH Q8, Q9,
Q10 and Q11 should also be taken into account.”

For details see: EU GMP

Posted by Tim Sandle

Tuesday, 29 September 2015

Innovations in cleanrooms and environmental monitoring

Pharmaceutical manufacturers of both sterile and non-sterile products, and medical devices, are required to demonstrate that manufacturing processes and procedures minimise any potential contamination to the product from the manufacturing environment. Contamination can arise from a number of sources: water, air, surfaces and personnel, each of which poses a potential risk to product.

These risks of contamination are avoided by putting environmental controls in place (through correct grade of air-supply, satisfactory cleaning and disinfection practices and so on). Where controls cannot off-set every contamination risk, and also as a means to demonstrate the level of control, environmental monitoring programmes are devised and put into action.

In addressing this, Tim Sandle surveys the latest innovations in cleanrooms and environmental monitoring for Express Pharma.

The reference is:

Sandle, T. (2015) Innovations in cleanrooms and environmental monitoring, Cleanrooms: Express Pharma Special Supplement, July 2015, pp12-14

The article can be accessed here.

Posted by Tim Sandle

Monday, 28 September 2015

US Compounding, Inc: Recall - Lack of Sterility Assurance

US Compounding, Inc. is voluntarily recalling all lots of sterile products aseptically compounded and packaged by USC and that remain within expiry due to FDA concern over a lack of sterility assurance. The sterile products were distributed nationwide to patients, providers, hospitals, or clinics between March 14, 2015 and September 9, 2015. If the sterility of a compounded preparation intended to be sterile is compromised, patients may be at risk. USC is asking all patients and providers that received sterile compounded products from USC between March 14, 2015 and September 9, 2015, and that remain within expiry.

For further details, see FDA Medwatch

Posted by Tim Sandle

Sunday, 27 September 2015

Ethylene glycol: health effects

Public Health England has issued a report on ethylene glycol (also known as 1,2-ethanediol, ethane-1,2-diol, or mono ethyl glycol) for use in responding to chemical incidents.

Ethylene Glycol is clear, colourless liquid with a syrup-like consistency. Ethylene glycol can be made by reacting water with a chemical called ethylene oxide. Other names for ethylene glycol include mono ethyl glycol or MEG.

Drinking ethylene glycol is dangerous and can cause damage to the kidneys which may lead to serious illness or death if large quantities are swallowed.

The report is headed “Ethylene glycol: health effects, incident management and toxicology.”

Posted by Tim Sandle