Saturday 30 June 2018

Pharmig publications

Factsheets cleanroom isolates

Standard microbiology text books are biased to medical bacteria. These factsheets provide pharmaceutical microbiologists with details on the most common isolates from pharmaceutical cleanrooms.

The factsheets provide descriptive information and characteristics of the main organisms, to help microbiologists tasked with investigations, together with full colour colony and growth characteristics, and typical Gram-stain profiles, to assist those who carry out identifications.

These laminated sheets are ideal for use on the laboratory bench, to assist microbiologists as they carry out their work, and as handy training aids.

Factsheets on fungi

Regulators have stated that knowledge of fungal identification is weak in microbiology laboratories, and many inspectors expect fungi to be identified as part of microbial contamination tracking. The problem is, few text books focus on the most common cleanroom isolates.

Pharmig has addressed a gap by profiling the most common fungi found in cleanrooms (based on FDA recalls) and presenting full colour guides to the cultivation and identification of these fungi.  Included with the macroscopic and microscopic images is detailed advice on where these fungi are found and what the implications for their recovery means.

These laminated sheets are ideal for use on the laboratory bench, to assist microbiologists as they carry out their work, and as handy training aids.

Rapid and alternative methods

Most microbiologists are seeking to invest in and develop rapid or alternative microbiological methods, in order to produce more accurate and faster results. There are also advantages in terms of automation and data integrity.

Finding out about the different technologies and then selecting between methods can be challenging. This publication provides an overview of different types of technologies and profiles many of the current methods available.

The guide also provides microbiologists (and their management chain) with guidance on selecting and qualifying methods (running the IQ, OQ and PQ spectrum). Also included is detail on how to build a case for justifying a method, considering factors like return on investment.

Factsheets on objectionable organisms

Objectionable organisms is a buzz phrase in the pharmaceutical sector, prompted by a push from regulators to consider those microorganisms beyond those described in the pharmacopeia as specified organisms that might pose a risk to products.

This series of factsheets describes the criteria for determining whether an organism is objectional or not (looking at things like product risk profiles and the patient population), and presents profiles of many common objectionales. These organisms have been selected based on their commonality to the environment and appearance in recall observations from inspectors.

The fact sheets use colour photographs illustrating growth on agar and by Gram-stain. These are supported by facts relating to the organism’s profile and methods for identification.

The sheets are presented in a pack and together provide a unique, informative and colourful guide to an important area of quality control microbiology.

Factsheets on Microbial Limits Test organisms

The Microbial Limits Test is the mainstay of many pharmaceutical microbiology laboratories. While the test is common there are challenges, such as identifying and characterising the specific microorganisms described in the pharmacopeia.

These factsheets are designed to act as a training aid for new staff, and an aide memoire for more experienced staff. The sheets use colour photographs to illustrate growth on agar and by Gram-stain. Each organism is additionally profiled, with information relating to the organism’s profile and risks to the patient.

The sheets are laminated and presented in a pack and together provide a unique, informative and colourful guide to an important area of quality control microbiology.

Best Practices in Microbiological Documentation – Electronic Pack One

Microbiology laboratories contain many computerised systems, SOPs, protocols and forms. When setting up a microbiology laboratory, generating the required documentation is a huge task. This Pharmig pack provides all of the necessary templates you’ll need in a downloadable and editable format.

The pack includes:

·         Training in setting up electronic systems.
·         Advice on electronic systems.
·         Templates for laboratory SOPs and protocols.
·         Examples of test forms for a range of common QC microbiology tests.
·         The full range of validation documentation for laboratory equipment, from URS to IQ, OQ, and PQ files.

The various files will also be of interest to the established laboratory manager, serving as a useful best practice benchmark.

Setting up and Managing an Effective Training Programme in the Micro Laboratory – Electronic Pack Two

In every regulatory inspection training features and the training folder of the microbiologist is certain to be inspected. Are you using the most appropriate format for your training? This pack provides an array of templates for the full range of QC microbiology tests.

Just as important as training is assessment. But how to assess? What should be practically demonstrated? Which questions to ask of the trainee? This pack provides a range of downloadable and fully editable assessments for everything from microbial identifications to environmental monitoring.

Also included are templates to allow laboratory managers to track, trace and trend training. By purchasing this pack, the managers and the microbiology team will be audit ready.

LAL factsheets

Endotoxin testing is an important area for many microbiology laboratories. Training in the LAL test is often best broken down into bite-sized chunks, and these factsheets provide single-point lessons on the key aspects of the test.

Areas covered include:

·         What is LAL/BET?
·         Calculation of endotoxin limits
·         Medical devices
·         Gel clot methods
·         Photometric methods
·         Product validation quantitative methods

These areas are explained in clear and concise language, together with practical examples and with illustration.

The sheets are presented in a pack and they are laminated, making them an ideal bench-side training aid.

Best practices for the Bacterial Endotoxin Test: A Guide to the LAL Assay

The core parts of the LAL test for endotoxin is described in the main pharmacopeia, but there are many things left out and others that are less clear, especially when training new staff.

This comprehensive guide describes how to:

·         How to undertake method development.
·         How to validate new samples.
·         Explains concepts like maximum Valid Dilution and Endotoxin Limits.
·         Outlines how to run a depyrogenation study.
·         Looks at medical device testing.
·         Contains a detailed trouble shooting guide.

This book provides a useful reference document for LAL users.

Current perspectives on Environmental Monitoring

All microbiologists need to carry out environmental monitoring, whether this is of a major plant or within the laboratory safety cabinet. Many aspects of monitoring are not well described and this Pharmig book addresses this.

The book contains chapters written by industry experts, covering:

·         How to set up an environmental monitoring programme.
·         Cleanroom microbiology.
·         How to evaluate environmental monitoring methods.
·         How to clean and disinfect effectively.
·         Tips for achieving particulate control.
·         How to run a risk assessment following an adverse trend.

Whether a beginner or an advanced practitioner, this guide has something for pharmaceutical microbiologists and their management teams.

Microbiological Control for Non-Sterile Pharmaceuticals

There is far more guidance for sterile manufacturers than those involved with non-steriles in relation to microbial contamination risks and control measures. To address this gap, Pharmig has produced this guide for microbiologists working in this field.

The guide covers:

·         Best facility design requirements.
·         Microbial risks in non-sterile manufacturing.

·         Best practice tips for achieving microbial control.
·         How to clean and disinfect effectively.
·         Advice on undertaking risk assessments.
·         Microbiological testing.
·         Environmental monitoring.

The guide helps steer the microbiologists through the regulatory expectations, offering many practical examples.

Guide to Cleanroom Operation and Contamination Control

Cleanrooms are the fabric within which most pharmaceutical processing takes place, yet not all pharmaceutical microbiologist are familiar with how they work and the contribution they make to minimising contamination.

In addition there are several different cleanroom standards and making sense of these and drawing comparisons can be changing. 

This Pharmig guide:

·         Describes the contamination control features of cleanrooms.
·         Explain the different cleanroom standards and how they compare.
·         Provides detail of the recently updated ISO 14644 standard (Parts 1 and 2).
·         Descries the different test methods for cleanrooms, like particle classification; pressure monitoring; air change rates and so on.

The guide is useful for microbiologists and cleanroom managers – helping to link engineering principles for microbiologists.


Posted by Dr. Tim Sandle

Friday 29 June 2018

Beyond Killing Tuberculosis

Historically, our view of host defense against infection was that we must eliminate pathogens to eradicate disease. However, this perspective has recently been challenged as scientists have taken a lesson from plant biologists about an ancient strategy involving the ability to “tolerate” rather than “resist” infection to maintain health. This concept, referred to as “disease tolerance”, provides an opportunity to develop new strategies that mitigate the consequences of infection.

Since the discovery of Mycobacterium tuberculosis, or Mtb, (the bacteria causing TB) over a century ago, great progress has been made in defining strategies that facilitate elimination of the bacteria. For instance, the discovery of antibiotics was a major breakthrough in the treatment of active TB. However, greater than 90 per cent of TB-infected individuals tolerate the bacteria without any treatment.

Dr. Maziar Divangahi, a pulmonary immunologist and associate director of the Translational Research in Respiratory Diseases Program at the Research Institute of the McGill University Health Centre (RI-MUHC), and a member of the McGill International TB Centre in Montreal, has been trying to explain why the vast majority of people infected with Mtb can tolerate the infection without developing disease. Clinicians refer to this condition as “latent tuberculosis”, and it affects a quarter of the global population. “TB is a perfect example of disease tolerance,” says Dr. Divangahi.

Dr. Divangahi’s team found that rather than fighting to resist the pathogen, the body’s tolerance to Mtb is the key mechanism for preventing the spread of the infection. More surprisingly, they found that having excessive levels of T cells, which are known as soldiers of our immune system, could cause more harm than good.

“We always thought that having more T cells would provide better protection against TB. Instead, we found that it could imbalance disease tolerance causing extensive tissue damage and ultimately killing the host,” says Dr. Divangahi, lead author of the study published today inScience Immunology, who is the also the associate director of the Meakins-Christie Laboratories.

Disease tolerance versus host resistance

Our body’s defense system is divided into two arms: one is resistance, which aims to eliminate the pathogen, while the other is tolerance, which is designed to control the tissue damage caused by the infection.

“While disease tolerance is an established field of research in simple organisms such as plants, our understanding of this host defense strategy in humans is very limited,” says Dr. Divangahi.

Although, immunologists and vaccinologists have made progress in the study of host resistance to infectious diseases, little is known about the mechanisms of disease tolerance in humans.

A key protein in disease tolerance

Dr. Divangahi’s team determined that a protein in the mitochondria called cyclophilin D (CypD) acts as a key checkpoint for T cell activation. Through collaboration with Dr. Russell Jones from McGill University, who is an international expert in T cell biology, they identified that CypD is required for controlling T cell metabolism. “T cells are traditionally considered to be important in eliminating Mtb,” says Dr. Divangahi. “However, we found that increasing T cell activation in mice by eliminating a metabolic checkpoint unexpectedly compromised host survival without any impact on the growth of Mtb.”

“In contrast to conventional thinking, we show that T cells are essential for regulating the body’s tolerance to Mtb infection,” explains one of the study’s first authors, Dr. Nargis Khan, who is currently a postdoctoral fellow in Dr. Divangahi’s lab at the RI-MUHC.

Giving the widespread drug resistance to various Mtb strains the limited pipeline of effective antibiotics and the lack of an efficient vaccine, alternative approaches to treat TB are urgent. “If we could understand the mechanisms of ‘natural immunity’ that controls TB in 90-95 per cent of infected individuals,” says Dr. Divangahi,“we will able to design a novel therapy or vaccine to substantially reduce the worldwide burden of this ancient disease.”
Posted by Dr. Tim Sandle

Thursday 28 June 2018

Pharmig News #71

The latest edition of Pharmig News has been issued (edition #71). In this issue:

  • Update on Pharmig events
  • Report from PHSS conference on Annex 1
  • Pharmig’s response to the draft Annex 1
  • Review of new electronic training module
  • Regulatory update
  • And more..
Copies have been sent to Pharmig members. If you are interested in reading a copy, contact:

There are two pieces by Tim Sandle in the newsletter:

The EU GMP Annex 1 draft was subject to a consultation period during which interested partiels submitted responses. Pharmig was one of the member organisations that submitted a response. Pharmig welcomed the draft and see it as a long overdue reclarification of the requirements of sterile products manufacturing. The stronger link to Quality Risk Management and references to new technologies were particularly welcomed.

Sandle, T. (2018) Pharmig’s response to EU GMP Annex 1 draft concept paper, Pharmig News, 71, pp4-7

Pharmig has established an interactive on-line training platform. The first module covers cleaning and disinfection, aimed at GMP cleanrooms. To understand how e-learning can be delivered effectively, Tim Sandle interviewed one of the co-developers, Laura Guardi.

Sandle, T. (2018) Insight into Pharmig’s new e-learning module, Pharmig News, 71, pp7-9

Posted by Dr. Tim Sandle

Monday 25 June 2018

ISO sanitation workshop

According to the World Health Organization (WHO), it is estimated that 2.3 billion people around the world have no access to safe, clean toilets, and where there are sanitation facilities, the waste is often not safely managed. The cost of lives is enormous, contributing to an estimated 280 000 deaths every year, not to mention the detrimental impact on people’s well-being and the environment.

News from ISO…

New technologies such as community-scaled faecal sludge treatment units, which essentially treat the waste at a community level even where there are no suitable wastewater treatment systems in place, are emerging to address this, providing a lifeline for many. Yet in order for this new technology to take off, internationally agreed guidelines are required.
As a first step, a new ISO International Workshop Agreement (IWA) has just been published, developed in partnership with the Bill & Melinda Gates Foundation and led by ANSI, ISO’s member for the USA.

IWA 28Faecal sludge treatment units – Energy independent, prefabricated, community-scale resource-recovery units – Safety and performance, will help to facilitate the commercialization and expansion of such treatment units into the market, making them safer and more accessible to those who need them.

At the same time, a new ISO project committee – ISO/PC 318Community scale resource oriented sanitation treatment systems – has just been formed. Bringing together international experts, it will build on the information and expertise gathered to develop IWA 28, a major step to help realize the potential of such technologies and, ultimately, save lives.
Raymond Lee, Chair of the workshop that created IWA 28, said the committee would draw on the more than 130 experts from 27 countries involved in its development to turn the IWA into a much needed International Standard.

Posted by Dr. Tim Sandle

Sunday 24 June 2018

Report on the International API inspection programme published

As part of the Certification of Suitability procedure, the EDQM runs an inspection programme for API manufacturers and is committed to optimise the inspection resources as much as possible. Therefore it has been an active member of the International API Inspection Programme since its creation back in 2008, together with the EMA, several European Union national authorities and international partners.

The report can be accessed here: EDQM

Posted by Dr. Tim Sandle

Friday 22 June 2018

MHRA on Brexit

MHRA update to pharmaceutical companies on exit preparations. MHRA is aware that companies who market pharmaceuticals in the EU and UK will need to plan and make decisions in advance of the UK’s departure from the EU in March 2019.

The UK’s intention remains to secure an implementation period based on the existing structure of EU rules and regulations as quickly as possible, and to agree a deep and special future partnership. MHRA will continue to advise businesses on the basis of the UK position and will continue to work with the EMA in planning for the UK’s withdrawal from the EU and future relationship.

Companies have been asking for detail about UK legislative requirements in different scenarios. MHRA has been working closely with industry associations and other stakeholders and further details on all these issues and more – both Day One and longerterm proposals – will be published when appropriate.

The UK intends to agree a time-limited implementation period with the EU, and both parties have recognised its importance. Should however there be no implementation period,
MHRA’s approach would be in line with the following principles:

The European Union (Withdrawal) Bill will convert the existing EU legislative framework into UK law at the moment of exit, so there would be no sudden changes to the UK regulatory framework.

MHRA would be pragmatic in establishing UK regulatory requirements. We would give adequate notice and ensure that companies had sufficient time to implement any changed requirements.

Where possible, MHRA would be making use of the information it already has to complete administrative tasks for continuity of work and licences.

MHRA would ensure the minimum disruption and burden on companies as the UK exits the EU, while building on the existing relationship between MHRA and firms.


Posted by Dr. Tim Sandle

Tuesday 19 June 2018

Guidance for pharmaceutical companies to prepare for UK’s withdrawal from EU

The European Medicines Agency (EMA) and the European Commission have updated their guidance to help pharmaceutical companies prepare for the United Kingdom’s (UK) withdrawal from the European Union (EU).

Updates to the questions-and-answers document are marked ‘NEW’ and include information on how the UK’s withdrawal will affect the status of inspection outcomes by the UK national competent authority and batch release processes for medicines that are subject to Official Control Authority Batch Release (OCABR) and Official Batch Protocol Review (OBPR). The document also clarifies how scientific opinions of the Committee for Medicinal Products for Human Use (CHMP) for ancillary medicinal substances in medical devices requested by UK notified bodies will be affected. In addition, it includes new information on back-up arrangements for Qualified Persons for Pharmacovigilance (QPPVs) and on marketing multi-country packs of medicines, where one of the countries in which the packs will be sold includes the UK.

The Agency has also published an updated version of its practical guidance for industry which outlines the steps that companies should follow to make sure that necessary changes to their marketing authorisation are made by the end of March 2019, to allow for the continued marketing of their medicine in the Union after Brexit. The document should be read in conjunction with the updated questions-and-answers document. All updates are marked ‘NEW’.

Companies are reminded to plan for the UK’s withdrawal from the EU on 29 March 2019 in order to avoid any impact on the continuous supply of medicines for human and veterinary use within the EU and are advised to regularly check EMA’s dedicated webpage on the consequences of the UK’s withdrawal from the EU.

Posted by Dr. Tim Sandle

Monday 18 June 2018

Automated, Digital Colony Counting: Qualification and Data Integrity

Many laboratory managers have given attention to automated, digital devices to streamline the plate counting processes. Such devices have been commonplace to the clinical laboratory for some time; although adoption within pharmaceutical laboratories has been slower. Recent regulatory interest in data integrity and the economic pressures driving the ‘lean’ laboratory, with a focus on cost control, improving sample throughput, and reviewing whether each sample tested adds value or produces meaningful information, may account for the growing interest.

This paper considers the selection and adoption of automated, digital capture colony counters within the pharmaceutical microbiology laboratory. The focus is on how such devices can be qualified (or validated) and how data integrity concerns can be addressed, provided that the former has been appropriately planned and executed.

To understand how these devices work, and how accurate they are, plus how data integrity considerations must be handled, Tim Sandle has written a paper for the Journal of GxP Compliance.

The reference is:

For details, contact Tim Sandle

Posted by Dr. Tim Sandle

Wednesday 13 June 2018

Next Steps After Finding an Environmental Isolate

You’ve identified an organism in your environment. Now what? If you work in a non-sterile pharmaceutical manufacturing laboratory, chances are you’ve encountered this question.

The Microbiologics blog has an interesting guide to examining environmental isolates. Here is an extract:
“You know environmental monitoring doesn’t stop at detection, but what are the correct next steps to keep your products safe and laboratory in compliance? Instances of U.S. Food and Drug Administration (FDA) warning letters and observations associated with inadequate environmental isolate testing are on the rise. As a result, laboratories are seeking guidance to determine what to do with their environmental isolates. These laboratories may consider including the isolates in disinfectant efficacy, growth promotion or antimicrobial effectiveness challenge tests.”

For details see: Microbiologics

Posted by Dr. Tim Sandle

Thursday 7 June 2018

High risk of malaria transmission after blood transfusions in sub-Saharan Africa

A new study suggests that in certain areas of sub-Saharan Africa, nearly one in four blood bank supplies contain the parasites that cause malaria. Another study, focusing on the blood supply of Equatorial Guinea’s capital, Malabo, found much higher levels of latent malaria infection, most of it—more than 89 percent—at a level that commonly-used diagnostic technology cannot detect. Both studies were presented at the 7th Multilateral Initiative on Malaria (MIM) Pan African Malaria Conference in Dakar, Senegal.

Sub-Saharan Africa carries the highest burden of malaria in the world. According to the World Health Organization (WHO), 90 percent of all malaria cases are located in the region. In the quest for elimination of malaria, all sources of disease transmission, including the region’s blood banks, need to be addressed.

The first study, “A systematic review and meta-analysis of the risk of transfusion-transmitted malaria from blood donors in sub-Saharan Africa,” conducted by Dr Selali Fiamanya and colleagues from the Worldwide Antimalarial Resistance Network (WWARN),gathered results from 24 studies to assess malaria prevalence among 22,508 blood donors. Pooled prevalence of malaria parasitemia was 23.46 percent (95%CI: 19.7% – 27.2%), ranging from 6.5 percent to 74.1 percent, including more than 10 studies from Nigeria, Africa’s most populous country.

Half of all children receiving blood transfusions need the procedure to address malaria-induced anemia, the failure to keep these blood banks safe puts children and their parents at risk. Dr. Fiamanya’s study shows that without better vigilance, children receiving transfusions to address malaria’s impacts risk exposure to more malaria-causing parasites.

“Malaria is one of the primary infections that can be transmitted through a blood transfusion in sub-Saharan Africa,” said Dr. Fiamanya at WWARN. “Our research is only the first line of inquiry needed to address this risk. Pregnant women and children receive the majority of transfusions in this region. The technical challenges of diagnosing and removing the Plasmodium parasites from the blood banks requires further analysis, but we know already that these findings threatens the next generation—our future.”

The second study, “Prevalence of Malaria Parasites at the Malabo Blood Bank on Bioko Island, Equatorial Guinea,” conducted by Dr. Claudia Daubenberger, colleagues at the Swiss Tropical and Public Health Institute, and Dr. Tamy Robaina at the Malabo Blood Bank, with support from Marathon Oil Corporation and the Equatoguinean Ministry of Health and Social Welfare, used a more sensitive diagnostic test—quantitative polymerase chain reaction (qPCR) assays—to examine 200 blood samples collected in the country’s capital, Malabo.

Typically, rapid diagnostic tests (RDTs) and thick blood smear microscopy are used to diagnose malaria as these tests are much easier to deploy and use in the field. Neither diagnostic test can detect latent malaria infection, however, and low-level or asymptomatic infections can hide reservoirs of parasites that fuel future malaria outbreaks.

Using the qPCR assays, which are currently too expensive and unsuitable for most field conditions, Dr. Daubenberger and colleagues found that 29.5 percent of the blood samples were contaminated. All of the samples thought to be free of the malaria parasite held very low concentrations of the parasites—under 100 parasites per microliter of blood.

“With better screening technology and practices in place, blood banks in sub-Saharan Africa can be well placed to serve as a surveillance system, helping to monitor malaria and other transfusion-transmitted infectious diseases,” said Dr. Daubenberger. “Our findings clearly reinforce World Health Organization recommendations that all transfusion recipients receive preventive malarial treatments. This disease is a treatable and preventable burden that few patients needing blood transfusions can afford.”

The Pan African Malaria Conference is organized every three-to-four years by the MIM secretariat in collaboration with a group of African institutions. This year’s meeting falls four months after the release of the WHO’s 2017 World Malaria Report, which found there is a dire need for new malaria interventions, particularly in sub-Saharan Africa. The report found that despite recent advances, overall progress against global malaria control has stalled. In 2016, there were an estimated 216 million cases of malaria, about 5 million cases more than in 2015. Ninety percent of these cases occurred in sub-Saharan Africa.

This year’s malaria conference in Dakar is running parallel to The Malaria Summit, Ready to beat malaria, which is taking place alongside the Commonwealth Heads of Government Meeting (CHOGM) in London on 18th April 2018. This will bring together business leaders, philanthropists, scientists, Heads of States and civil society to announce significant new commitments to mobilize domestic resources, increase investment and develop new innovation and approaches towards beating malaria. The commitments sit alongside a call to action urging the Commonwealth as a whole—who represent citizens making up six out of ten malaria cases globally—to commit to accelerating progress against malaria, the world’s oldest and deadliest disease.

Posted by Dr. Tim Sandle

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