Tuesday, 31 December 2019

STOP TB Partnership Launches: Updated Global Plan to End TB

The Stop TB Partnership today launched the Global Plan to End TB 2018-2022, which calls for 2.6 billion USD per year for vital research and development of new tuberculosis (TB) diagnostic tools, new drug regimens and a new vaccine, and 13 billion USD per year for TB care and prevention. With the new Global Plan, the Stop TB Partnership is also launching the largest ever call for proposals, 2.5 million USD, to fund grassroot organizations as part of the TB response as well as new, child-friendly drug-resistant TB treatments.

In September 2018, Heads of State and Government assembled at the United Nations committed to a series of bold targets in the fight against TB. Unlike previous five-yearly plans, the updated Global Plan for 2018-2022 is deliberately aligned to the time frame of the UN High-Level Meeting (UNHLM) on TB targets and provides an estimate of the resources needed to achieve these targets.

If the Global Plan is fully funded and implemented, countries will reach UNHLM on TB treatment targets set for 2022, including putting 40 million people on treatment for TB, including 3.5 million children and 1.5 million people with drug-resistant TB. This will lead to 1.5 million fewer deaths due to TB, and the return on investment will be 44 USD for 1 USD spent. On the other hand, a five-year delay in increasing funding for TB research and development would lead to approximately 2 million more people dying and an additional 13.9 million people developing TB.

Funding levels do not match political commitments
Funding is critical. To achieve these goals, 13 billion USD every year is needed globally for TB care and prevention—approximately twice the current level invested. And 2.6 billion USD is needed every year for research and development of new diagnostics, new drugs and a new vaccine—approximately three times the current level invested.

Many countries will have difficulties reaching these funding levels. While high-income countries, BRICS (Brazil, Russia, India, China, and South Africa) and upper-middle-income countries can tap domestic budgets to reach the necessary funding levels, low-income and lower-middle-income countries will need increased external funding. The Global Fund to Fight AIDS, Tuberculosis and Malaria provides nearly 80% of external funding for TB programs but the envelope provided is very small versus the actual needs, with a total of 840 million USD/year.

The announcement was made in Indonesia, one of the top three highest TB burden countries in the world, with nearly one million people developing the disease each year. In its 2016 National Strategic Plan, the Indonesian Ministry of Health pledged to end TB in the country by 2030.

Pediatric- DR TB

At the event, Stop TB’s Global Drug Facility (GDF) officially launched the Pediatric Drug-Resistant TB (DR-TB) Initiative. Of the estimated 1.1 million children under the age of 15 who became sick with TB around the world in 2018, an estimated 32,000 had DR-TB. Of those, fewer than 5% are diagnosed and receive treatment. Even fewer of those under the age of five received treatment.

Until recently, only 500 young children globally with DR-TB received treatment, and those who were treated were put on medicines intended for use in adults. Yet, children require different formulations for treatment than adults—ones that are more aligned with the smaller size of children and that can be taken more easily, for example dispersed in water rather than crushed and mixed. With so few children with DR-TB being diagnosed and treated globally, getting these new formulations developed, produced and distributed is difficult.

The Pediatric Drug-Resistant TB Initiative aims to ensure access to the best possible treatments for children suffering from one of the deadliest diseases in the world. GDF together with the Sentinel Project on Pediatric DR-Tuberculosis worked to identify early adopter countries that could implement the new pediatric formulations quickly and pooled their demand, leading to the introduction of these life-saving medicines in countries in less than 12 months.

Already procured by 56 countries and introduced in Haiti and Nigeria, among others, the oral medicines come in a dissolvable, flavored form—replacing the adult doses in tablet form that had to be crushed or split so that the proper therapeutic levels could be met and removing the injectables with their terrible and permanent side effects. GDF was also able to negotiate substantial price reductions, ranging from 30% to 85%, depending on the medicines used.

In 2019 alone, Stop TB’s GDF provided over 1,100 treatments for children with drug-resistant TB around the world, ​more than double the number of children under five years of age historically treated each year for DR-TB.

However, the world is far away from the 2018 UNHLM on TB and Global Plan to end TB target of treating 115,000 children with DR-TB by the year 2022, including 47,000 young children in need of these new, child-friendly formulations.

Critical grassroots outreach receives funding infusion
The Stop TB Partnership also launched the largest-ever call for proposals for TB-affected community and civil society grassroots organizations.

An estimated 30% of the 10 million people who developed TB disease in 2018 did not access or receive proper care. This call for proposals recognizes the fact that we cannot reach these key and vulnerable populations unless we work with TB-affected communities and the organizations that support them. Only through collaboration with these organizations can we end TB.

Supported by USAID and the Global Fund to Fight AIDS, Tuberculosis, and Malaria, each grant will be between 25,000 and 150,000 USD to cover 12 months of activities.

The Challenge Facility for Civil Society grant mechanism will fund proposals that address barriers in screening and treatment services; promote community outreach, education and advocacy; organize legal responses to systemic discrimination; and facilitate monitoring of the TB response, holding governments accountable to the commitments made in the United Nations declaration on TB.

The call for proposals covers 14 high TB-burden countries: Bangladesh, Cambodia, DR Congo, India, Indonesia, Kenya, Mozambique, Myanmar, Nigeria, Pakistan, Philippines, South Africa, Tanzania, and Ukraine. It also covers the following regions: Anglophone Africa, Francophone Africa, Asia, Latin America and the Caribbean and Europe.

In 2018, ten million people fell ill from TB and 1.5 million people died from the disease, taking a huge toll on human and economic health in countries worldwide. Roughly 30% of the new infections went undetected and unmonitored, however, and the TB epidemic will never be fully controlled until all infections are tracked and treated.

"It is not just about launching the Global Plan, it is also about launching concrete tools and funding to implement it. We have the largest ever call for proposal from grassroot organizations as we must ensure that civil society and communities remain our full partners in ending TB. And we share with the world the pediatric formulations for children with drug resistant TB. I feel we are finally starting to get what we need to end TB. There is a long way to go, but we see light at the end of the tunnel."

Dr. Lucica Ditiu, the Executive Director of the Stop TB Partnership

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Monday, 30 December 2019

How New Technologies are Revolutionizing Physical Therapy

The healthcare industry is experiencing rapid change as a result of new technologies. With physical therapy being one field that is seeing some of the most significant changes, patient care is getting more efficient and more effective.

A guest post by Alexandra Warner

We now see robotics becoming more common in a physical therapy setting, and patients can now use a range of tools that can be accessed from a smartphone or tablet. The technological tools are enabling direct access to physical therapy in New Jersey and other states across the nation. These advancements will provide patients with improved outcomes and physical therapy professionals will be able to achieve better results in less time.

With the latest tech on the horizon, patients and physical therapists can expect a much brighter future for rehabilitation services. The following are four of the trends that are helping to shape the future of patient care in physical therapy.
Apps for Physical Therapy

Smartphones and tablets have changed the modern world in a number of ways. We are now seeing smartphones moving into healthcare and that includes physical therapy. You have apps that can help patients with their physical therapy exercises. Beyond that, there are diagnostic tools that can be used on a phone and apps that help patients connect with physical therapy professionals.

One example is the Sway Medical app. This FDA-cleared app uses the sensors on a smartphone to perform tests for balance and reaction time. This can provide medical professionals with an easy way to test and get information on patients who have suffered some type of head injury.


Different robotic systems are now showing great promise in physical therapy. One example is treadmills that use robotic legs to assist with gait training. With these systems, a harness holds the patient and a pair of robotic legs will help them walk.

As an extension of robotics, you also have exoskeletons that are helping patients relearn how to walk. Consider the ReWalk exoskeleton as an example. This lightweight exoskeleton can help the patient stand, sit, walk and turn. Some models can even climb stairs.

PT on a Gaming Console

Some physical therapists have been using video games for PT for some time. Much of this started with the Nintendo Wii, but it has gotten even better as video game technology has improved. With a device like the Microsoft Kinect, the motion-capture sensors allow the patient to move in a way that fits better with real-world movement. Games are even being designed specifically for the purposes of creating a better and more effective physical therapy experience.
PT in VR

Virtual reality is almost an extension of video games in physical therapy. When using VR for physical therapy, programs can be created to put the patient in a more pleasant environment. Developers can even make games that will encourage the patient to do various physical therapy exercises. With the right VR gear, the system can also collect data and track the patient’s progress.

These technologies are doing a lot of good in the physical therapy industry. Patients are seeing better outcomes than could have been expected in the past and PT professionals are able to help more patients with their time. These are significant benefits that are only going to increase as these technologies develop and become more accessible.

Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Sunday, 29 December 2019

Is Pharma Ready For Serialization? The Answer Lies In Digital Technology

New legislation requiring pharmaceutical companies to implement 'serialization' is now coming into force. This means that no counterfeit product should enter the supply chain and no legitimate product is diverted from its intended destination. To work effectively, serialization requires a comprehensive system to track and trace the passage of prescription drugs through the entire supply chain. The application of track and trace principles can help to avoid counterfeit medicines from entering the supply chain. To be effective, digital technologies such as blockchain and RFID-enabled tag and trace systems need to be embraced.

In relation to this important topic, Tim Sandle has written a new article:
Sandle, T. (2019) Is Pharma Ready For Serialization? The Answer Lies In Digital Technology, BioPharma Trend, November 2019 at: https://www.biopharmatrend.com/post/122-is-pharma-ready-for-serialization-the-answer-lines-in-digital-technology/ (accessed 20th November 2019)

Here is an extract:

For pharmaceutical manufacturers to meet the requirements of serialization, this involves careful planning and considerable cost. To achieve serialization, every drug product pack needs to be uniquely identified with digital information - a machine-readable code, and for the product to be registered in an external database to permit each individual item to be traceable. Two technologies are helping pharmaceutical companies with serialization requirements: tag technology and blockchain.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Saturday, 28 December 2019

Mycoplasma Conference Summary

For further details see: Roche

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Lifestyle is a threat to gut bacteria

The evolution of dietary and hygienic habits in Western countries is associated with a decrease in the bacteria that help in digestion. These very bacteria were also found in the Iceman, who lived 5300 years ago, and are still present in non-Westernized populations in various parts of the world. The depletion of the microbiome may be associated with the increased prevalence, in Western countries, of complex conditions like allergies, autoimmune and gastrointestinal diseases, obesity.

The industrialization process in Western countries had a huge impact on its content. This was confirmed by a study on the bacteria found in the intestine of Ötzi, the Iceman who, in 1991, emerged from the ice of the Ötztal Alps, where Italy borders with Austria. Scientists of Eurac Research examined samples of the mummy's bacteria, confirming the findings of the researchers of the University of Trento who had analyzed the genome of intestinal microorganisms of over 6500 individuals from all continents.

Previous studies by the University of Trento had demonstrated that there is a connection between the microbiome's bacterial content and the increase, in Western countries, of obesity, autoimmune and gastrointestinal diseases, allergies and other complex conditions. In the study that appeared today in Cell Host & Microbe, researchers from Cibio of the University of Trento and Eurac in Bolzano/Bozen demonstrated that the differences between Western and non-Western or prehistoric microbiome lie in the decrease of some types of bacteria that process complex and vegetal fibers in the intestine.

That may have been caused by the Westernization process. Changes in diet, which is now higher in fat and low in fibers, a sedentary lifestyle in an urban setting, the development of new hygiene habits and the widespread use of antibiotics and other medical products have, with no doubt, made our life safer, but impacted the delicate balance of our microbiome.

The study focused, in particular, on Prevotella copri, a microbe that, when is found in our intestine, is usually the most represented. P. copri is present in 30% of Western individuals.


Adrian Tett, Kun D. Huang, Francesco Asnicar, et al. The Prevotella copri Complex Comprises Four Distinct Clades Underrepresented in Westernized Populations. Cell Host & Microbe, 2019; DOI: 10.1016/j.chom.2019.08.018

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 27 December 2019

EMA advises companies on steps to take to avoid nitrosamines in human medicines

EMA’s human medicines committee (CHMP) is requesting as a matter of precaution that marketing authorisation holders for human medicines containing chemically synthesised active substances review their medicines for the possible presence of nitrosamines and test all products at risk. If nitrosamines are detected in any of their medicines, marketing authorisation holders must inform authorities promptly so that appropriate regulatory actions can be taken.

A notice  to this effect is being sent out to marketing authorisation holders with information on the actions they should take. A questions-and-answers document is also available on EMA’s website.
Marketing authorisation holders are responsible for ensuring that every batch of their finished product is of satisfactory quality, including the active substances and other ingredients used to make them. They should take into account the published guidance along with knowledge of the manufacturing processes for their products and all other relevant scientific evidence.

Steps companies should take:

  • Evaluate possibility of nitrosamines being present in every concerned medicine within 6 months
  • Prioritise evaluations, starting with medicines more likely to be at risk of containing nitrosamines
  • Take into account findings from CHMP’s review of sartans
  • Notify authorities of outcome of risk evaluations
  • Test products at risk of containing any nitrosamines
  • Immediately report detection of nitrosamines to authorities
  • Apply for necessary changes to marketing authorisations to address nitrosamine risk
  • Complete all steps within 3 years, prioritising high risk products

See: https://www.ema.europa.eu/en/news/ema-advises-companies-steps-take-avoid-nitrosamines-human-medicines

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 26 December 2019

Bacterial resistance to two critical antibiotics widespread in Southeast Asia

Resistance to two critical antibiotic types, one a "drug of last resort" when all others fail against some "superbugs," are widely distributed in Southeast Asia, raising the risk of untreatable infections, say a team of investigators led by Georgetown University Medical Center.

The study is a comprehensive analysis of resistance to two critical classes of drugs, carbapenems and polymyxins, in eleven nations of Southeast Asia.

The World Health Organization (WHO) has urgently called for global surveillance of antibiotic resistance, and, along with U.S. Centers for Disease Control and Prevention (CDC), identified resistance to these drugs as critical threats. To help better understand the risk in Southeast Asia, the researchers searched widely, extracting and analyzing available international scientific and clinical data. They evaluated resistance to these drugs among E. coli and Klebsiella, two common bacteria that can cause severe infections in humans, particularly in health care settings.

The picture the data paints is of a serious emerging public health threat. The investigators' findings included that resistance to carbapenems, often at significant levels, and resistance to polymyxins, were each widespread and geographically overlapped in 8 countries. Both bacteria also carry and can spread "mobile genetic elements" which can contain genes responsible for conferring resistance that may be transmitted to other bacteria, facilitating the rapid spread of resistance.

Carbapenems have, until recently, been the "go to" treatment for E. coli and Klesiella resistant to more commonly used drugs. However, carbapenem resistant strains have spread around the world.


Marissa D. Malchione, Laura M. Torres, David M. Hartley, Michala Koch, Jesse Goodman. Carbapenem and Colistin Resistance in Enterobacteriaceae in Southeast Asia: Review and Mapping of Emerging and Overlapping Challenges. International Journal of Antimicrobial Agents, 2019; DOI: 10.1016/j.ijantimicag.2019.07.019

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday, 25 December 2019

New insight into the infectivity of E coli discovered

Medical microbiologists have established how the bacterium Escherichia coli knows how to cause the worst possible infection. The new insight should assist with preventing the foodborne illnesses.

Researchers at the University of Virginia School of Medicine have shown how the common foodborne pathogen Escherichia coli (E. coli) assesses where and when to begin colonizing the human colon. This is through signalling, which signals to the organism that it is in a low-oxygen environment (as with the large intestine). This switches the virulence factor and provides the bacterium with a more effective means for establishing a stronger infection. In essence, E. coli has the capacity to wait until it has reached the-low oxygen large intestine before striking as specific genes are activated.

E. coli is commonly found in the lower intestine of humans and most other warm-blooded  animals. Many are harmless; however, some serotypes can cause serious food poisoning in their hosts. Some types of E. coli can cause gastrointestinal infections, as an example (especially as the result of food poisoning). The biggest risk serotypes E. coli produce toxins (Shiga toxins) that can cause severe illness.

Commenting on the new assessment, principal scientists Dr. Melissa Kendall said: “Bacterial pathogens typically colonize a specific tissue in the host. Therefore, as part of their infection strategies, bacterial pathogens precisely time deployment of proteins and toxins to these specific colonization niches in the human host.”

The researcher adds that this mechanism enables the bacteria to conserve energy and hide from being detected by the body’s immune systems. This is known as a virulence factor, which is when a substance released by a microorganism allows it to evade host defences or cause serious injury to the host.

The new research delivers the prospect that through understanding how bacterial pathogens sense where they are in the body, microbiologists may be able to prevent E. coli from sensing where they are inside a human host. This should lead to the organisms passing through the body without causing an infection.

The new research has been published in the journal Proceedings of the National Academy of Sciences. The research paper is titled “The sRNA DicF integrates oxygen sensing to enhance enterohemorrhagic Escherichia coli virulence via distinctive RNA control mechanisms.”

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Tuesday, 24 December 2019

Happy Holidays!

I'd like to wish all readers of Pharmaceutical Microbiology all the best wishes for the Holiday season!

Thank you for supporting this website and our LinkedIn and Facebook groups.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Monday, 23 December 2019

New standard for maintaining business continuity

ISO 22301, Security and resilience – Business continuity management systems – Requirements, is the world’s first International Standard for implementing and maintaining an effective business continuity plan. It enables an organization to have a more effective response and a quicker recovery, thereby reducing any impact on people, products and the organization’s bottom line.

Key improvements to the latest version include clearer structure and terminology to foster a better understanding of what is required and updates to remain in line with all other ISO management system standards.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Sunday, 22 December 2019

Reports of Dengue Infections Plummet in Areas Where Wolbachia Has Been Established in Mosquitoes

Amid a global surge of infections with dengue and fears climate change will make it worse, an international alliance of researchers presented new evidence today showing reports that the disease fell dramatically in communities in Indonesia, Vietnam, Brazil and Australia. The reduction in dengue cases occurred in communities where they had released lab-grown mosquitoes carrying Wolbachia, a naturally occurring bacteria that prevents mosquitoes from transmitting infections when they bite humans.

Presenting today at the Annual Meeting of the American Society of Tropical Medicine and Hygiene (ASTMH), researchers at the World Mosquito Program (WMP) reported a key finding: a 76% reduction in dengue transmission in a community in Indonesia that endures frequent dengue outbreaks and a similar reduction in cases of dengue and chikungunya in an urban area near Rio de Janeiro, Brazil.

“We are very encouraged by the public health impact we are seeing – it highlights the potential of this approach to fight dengue and related mosquito-borne diseases at a global scale,” said Professor Cameron Simmons, Director of Impact Assessment and an expert in the epidemiology of dengue at WMP. “Evidence is rapidly accumulating that areas where Wolbachia-infected mosquitoes have been deployed have fewer reports of dengue than untreated areas.”

Often called break-bone fever for the searing joint pain it produces, dengue also can lead to fatal complications. There are no drugs to treat the disease. The only licensed dengue vaccine has been saddled with safety issues. The ASTMH Annual Meeting will feature a highly-anticipated update from a late-stage trial with a new dengue vaccine, but experts stress that many tools are needed to control the disease.

The WMP Wolbachia trials are ongoing and, given the promising results thus far, are being rapidly expanded to Colombia, Sri Lanka, India and Western Pacific island nations. These trials are driven by a large body of evidence indicating that establishing Wolbachia in local mosquito populations could offer a safe way to reduce dengue infections. Wolbachia-infected mosquitoes can be created in the laboratory by injecting it into their eggs. Wolbachia also has been shown to inhibit chikungunya and Zika.

While presenting at the ASTMH conference today, Katie Anders, PhD, an expert in the epidemiology of dengue at WMP, and her colleagues noted that the work in Indonesia involved an experimental release in 2016 of Wolbachia-infected mosquitoes in an area of about 65,000 people adjacent to Yogyakarta City, Indonesia. The city on the island of Java is home to about 400,000 people who routinely face risks of dengue infections. The 76% reduction represented notifications of dengue among the targeted population recorded by local health authorities, compared with an untreated control area nearby.

Anders reported results from a smaller field study near Nha Trang, Vietnam where very few cases of dengue were reported during the year following the 2018 release of Wolbachia-infected mosquitoes. This low case incidence in the intervention area was documented at a time in which Nha Trang itself was experiencing one of its largest dengue outbreaks ever.

Anders also presented results published earlier this year showing local dengue transmission ceased in Far North Queensland, Australia. Beginning eight years ago, releases of Wolbachia-infected mosquitoes in local communities in this region led to a 96% reduction in cases of dengue-transmission.

The researchers stressed that all of the mosquito releases have been preceded by intensive community outreach and education efforts to inform local communities about the safety of Wolbachia bacteria and the potential impact of the releases on the surrounding ecosystem. Advocates of this approach to fighting dengue noted that it has several advantages over other methods. Wolbachia has none of the toxicity of conventional insecticides and it does not require genetically modifying the mosquitoes. It is also self-sustaining, which should make it highly cost effective.

Wolbachia is naturally present in the majority of insects. But it’s not found in the Aedes aegypti mosquitoes that are the main carriers, or vectors, of dengue, chikungunya and Zika—all of which belong to a class of viruses called arboviruses.

“This is exciting work, carried out in the midst of an explosion in dengue infections that health authorities are finding very difficult to control,” said ASTMH President Chandy C. John, MD, MS, FASTMH. “The combination of advanced science and committed community engagement is impressive—and essential to its success.”

Using Wolbachia to Target Both Chikungunya and Dengue in Brazil

Luciano Moreira, PhD, WMP’s Program Lead in Brazil, reported preliminary results showing cases of dengue and chikungunya fell by more than 70% in 2018 – 2019 among 100,000 people in two different areas Niterói, a city near Rio, following the release of Wolbachia-infected mosquitoes in their neighborhoods.

Moreira and his team at Fundação Oswaldo Cruz (Oswaldo Cruz Foundation) also noted, however, that because dengue incidence was generally low throughout Rio and Niteroi during the field trials, it was more difficult to show a comparative reduction in Wolbachia-treated areas. There was, though, a clear difference compared to untreated areas.

“There has been an epidemic of chikungunya in these areas,” Moreira said. “And disease surveillance by the Ministry of Health is showing there was 75% less chikungunya in Niteró where we released the mosquitoes compared with areas where we are not working.”
Chikungunya is a disease that can lead to chronic, debilitating joint pain and, while native to sub-Saharan Africa, it is becoming a growing problem across Latin America and the Caribbean.

Meanwhile, dengue is once again surging in Brazil, with infections in 2019 up almost 600% and deaths rising by 220%. It’s part of a trend in which, last year, dengue infections globally reached near record highs, with especially large outbreaks in Asia and Latin America. Dengue is common in Puerto Rico, the U.S. Virgin Islands and American Samoa, and local transmission has occurred in Florida, Texas and Hawaii.

Moreira said Brazil’s Ministry of Health is keen to expand efforts to test the capacity of Wolbachia-infected mosquitoes as a tool for controlling outbreaks of dengue and chikungunya. There is also interest in using Wolbachia to help protect people from Zika as well. While the intense Zika outbreak of 2016 is over, there are concerns it could return in Brazil and elsewhere.

Moreira said plans are now underway to target 1.5 million people with releases of Wolbachia-infected mosquitoes in Brazil. Meanwhile, Anders said work is also underway in Yogyakarta City to conduct a gold-standard trial that involves a population of about 350,000.

Existing evidence of reductions in dengue linked to the Wolbachia mosquitoes is entirely consistent with earlier modelling predictions of the likely impact. There have been no safety concerns in any of the communities where Wolbachia has been deployed. “We are very excited that this self-sustaining and cost-effective method has been embraced by communities and is delivering the public health benefits we expected it would,” said the WMP’s Simmons. “Our challenge now is to work with partners and governments to bring the method to 100 million people by 2023.”
With insecticide resistance eroding the life-saving power of bed nets—a major malaria-fighting tool—researchers reported today that in a clinical trial that involved distributing millions of treated nets to households across Uganda, far fewer children showed evidence of malaria parasites after sleeping under nets newly formulated to disarm a mosquito’s key resistance mechanisms.

The results presented today at the Annual Meeting of American Society of Tropical Medicine and Hygiene (ASTMH) emerged from the largest trial ever undertaken to assess the malaria-fighting power of long-lasting insecticidal nets (LLINs), which are credited with playing the dominant role in cutting malaria deaths in half over the last 15 years. But there is concern that rising resistance in mosquitoes to pyrethroids, the key insecticide incorporated into the fabric of the nets, is contributing to a recent stall in the decline of malaria infections and deaths—and to a rise of both in some parts of Africa.

“The results from Uganda show that by using an insecticide formulation that interferes with the mechanisms mosquitoes use to defeat pyrethroids, we are seeing a significant restoration of pyrethroid efficacy—not back to pre-resistance levels, but enough to buy us critically needed time while we develop new insecticides and interventions,” said Martin Donnelly, MSc, PhD, an expert in the genetics of insecticide resistance at the Liverpool School of Tropical Medicine and a co-leader of the LLIN Evaluation in Uganda Project, or LLINEUP.

At the ASTMH session, the LLINEUP study team presented data from blood tests of over 23,000 children 2 to 10 years old. The data show that for the children who slept under nets augmented with piperonyl butoxide (PBO)—a chemical that blocks enzymes mosquitoes employ to “detoxify” pyrethroids—the number testing positive for malaria parasites 12 months after the nets were distributed was 27% lower than for children sleeping under nets that were treated solely with pyrethroid insecticides. Moreover, households supplied with the PBO-treated nets had 80% fewer malaria-carrying mosquitoes compared to households using conventional LLINs.

“We think nets with this new formulation would do a better job of preventing malaria than standard nets, particularly in areas of high-level insecticide resistance, and could reduce the burden of malaria,” said Sarah Staedke, MD, PhD, DTM&H, a Uganda-based malaria epidemiologist with the London School of Hygiene and Tropical Medicine and the Infectious Disease Research Collaboration, a co-leader of the project.

The trial was conducted in close partnership with a bed net campaign led by Uganda’s Ministry of Health and supported by The Against Malaria Foundation that, in the last few years, has distributed millions of bed nets free of charge across a large swath of the country. Both the PBO and non-PBO nets had been treated with pyrethroids, which are safe for humans and were, until recently, lethal to mosquitoes. But their ability to stop the insects is steadily declining.

Donnelly cautioned that while the increased efficacy offered by PBO-treated nets is great news, it’s likely just a matter of time before mosquitoes evolve to evade the compound. He noted that PBO does not shut down all the enzymes mosquitoes employ to overcome pyrethroids. He said that he and other scientists studying the genetic mechanisms of resistance believe mosquitoes will eventually emerge that are increasingly impervious to the effects of PBOs.

But he thinks that the PBO nets could be a very good stopgap for several years. In the meantime, the World Health Organization (WHO) will review the evidence from the Uganda study to determine whether to recommend their adoption while testing continues for a long-term solution. For example, there are newer nets being developed that use two active ingredients or a novel insecticide that employ a different mode of action than pyrethroids to kill mosquitoes. Donnelly said there are efforts underway to conduct trials in Uganda to test this new generation of nets against the PBO nets.

The other good news from the Uganda trial is that despite rising levels of resistance, the study showed nets without PBOs can reduce the prevalence of malaria parasites, even if they are not as effective as when net campaigns were first launched more than a decade ago. Children sleeping under the non-PBO nets had a lower prevalence of malaria parasites than they did before the nets were distributed—though the reduction was not as large as for the children sleeping under the PBO-treated nets. LLINs are now used in half or more of all households in sub-Saharan Africa, which shoulders most of the world’s malaria burden, compared to only about 2% in 2000.

Moses Kamya, M.Med, MPH, PhD, the Executive Director of the Uganda Infectious Disease Research Collaboration (IDRC), a study co-leader, said that “there is still an advantage to using any type of LLIN because when you sleep under either type of net, you’re less likely to contract malaria. But the greater reduction in malaria from the PBO-treated nets is significant and switching to this type of net in national malaria control campaigns should be considered.”

“Keeping up with resistance is a constant battle, and ASTMH researchers from around the world are working hard to stay ahead of it. With mosquitoes continually evolving resistance to insecticides, this research provides valuable data that will help to guide the difficult decisions about how best to deploy LLINs to combat malaria in sub-Saharan Africa,” said ASTMH President Chandy C. John, MD, MS, FASTMH.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Saturday, 21 December 2019

EMA releases guidance to companies on avoiding nitrosamines in drugs

The European Medicines Agency (EMA) has asked the human medicines committee (CHMP) to provide guidance on avoiding the presence of certain carcinogenic ingredients in drugs, after nitrosamines were found to be present in a prevalent form of blood pressure medication.

The regulatory body is drafting directions on nitrosamine impurities in medications containing chemically synthesised active substances.

The CHMP will produce guidance on reducing nitrosamine impurities to marketing authorisation holders.

“We will continue to work with our partners to address the presence of nitrosamines and reassure patients about the quality of their medicines,” says the Executive Director Professor Guido Rasi.

Nitrosamines are classified as probable human carcinogens, following animal studies.

Following the identification of the carcinogenic ingredient in sartans, the EMA is seeking a “proactive approach” for other classes of medicines. The ingredient has been detected in batches of pioglitazone and in batches of ranitidine.

See: https://www.ema.europa.eu/en/news/ema-advises-companies-steps-take-avoid-nitrosamines-human-medicines

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 20 December 2019

FDA approves first live, non-replicating vaccine to prevent smallpox

The FDA has announced the approval of Jynneos Smallpox and Monkeypox Vaccine, Live, NonReplicating, for the prevention of smallpox and monkeypox disease in adults 18 years of age and older determined to be at high risk for smallpox or monkeypox infection. This is the only currently FDA-approved vaccine for the prevention of monkeypox disease. Although naturally occurring smallpox disease is no longer a global threat, the intentional release of this highly contagious virus could have a devastating effect.

This approval reflects the U.S. government’s commitment to preparedness through support for the development of safe and effective vaccines, therapeutics, and other medical countermeasures. Jynneos will be available for those determined to be at high risk of either smallpox or monkeypox infection.

This vaccine is also part of the Strategic National Stockpile (SNS), the nation’s largest supply of potentially life-saving pharmaceuticals and medical supplies for use in a public health emergency that is severe enough to cause local supplies to be depleted. The availability of this vaccine in the SNS will help ensure that the vaccine is accessible in the U.S. if needed.

See: https://www.fda.gov/news-events/press-announcements/fda-approves-first-live-non-replicating-vaccine-prevent-smallpox-and-monkeypox

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Thursday, 19 December 2019

Drug Supply Chain Security Act (DSCS)

In 2019 the FDA announced it had received comments and feedback from wholesale distributors expressing concern with industrywide readiness for implementation of the verification of saleable returned product requirement for wholesale distributors. Specifically, stakeholders have described challenges with implementation of verification of the product identifier on saleable returned drug product packages or sealed homogenous cases due to a number of factors, including:

1.      The very large volume of saleable returned product requiring verification.
2.      The need to refine and test verification systems during actual production using real-time volumes of saleable returned product rather than simply in pilots.
3.      The complexities of building an interoperable, electronic system with the capabilities to timely and efficiently verify the large volume of saleable returned products amid immature technologies.

While this was noted, the FDA will continue with the agreed implementation date of November 27, 2020 (FDA, 2019).

FDA (2019) Wholesale Distributor Verification Requirement for Saleable Returned Drug Product—Compliance Policy Guidance for Industry, U.S. Department of Health and Human Services Food and Drug Administration, September 2019 at: https://www.fda.gov/media/131005/download (accessed 6th November 2019)

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Wednesday, 18 December 2019

10 Tips for Choosing Pharmaceutical Equipment

The pharmaceutical industry has an enormous amount of influence and enjoys spectacular profits year after year. When it comes to maintaining a successful pharmaceutical lab, however, all this success is hard-won. It’s important to choose the right equipment the first time to uphold the quality and effectiveness your patients and partners are counting on. Here’s what to look for.

A guest post by Megan R. Nichols

1. Choose Equipment That’s Easy to Clean

You likely don’t need reminding of the high purity levels required in the pharmaceutical sector. With this in mind, it’s vital to choose lab equipment that’s easy to clean.

As an example, curved tube exchangers can be more difficult to sterilize than straight ones. When even a tiny amount of residue could compromise the next batch, it’s imperative to take every design detail, no matter how small, seriously. 

2. Know Which Equipment Minimizes Leaks

Leaks are undesirable in any manufacturing or distribution process. In pharmaceuticals, they can be especially impactful and unsafe. While choosing lab equipment, consider these options for reducing leaks and cross-contamination:
  • Fully welded tubesheets are designed to minimize the chances of sustaining a leak while processing pharmaceuticals
  • Double tube sets for heat exchangers can be designed with channels that drain away any leaks safely. 
3. Match With Your Heat Transfer Fluids

The growth of the pharmaceutical industry is part of why the heat transfer fluid (HFT) market is likely to surpass $4.2 billion in value by 2024.

Lots of pharmaceutical processes rely on heat transfer fluids, but not all equipment is designed for compatibility with the most effective HTFs. Silicone-based HTFs are pumpable at low temperatures but are still ideal for high-temperature processes, according to Dow Chemical. Lab equipment must be compatible with all liquids in play, but especially with heat transfer fluids. 

4. Get a Custom Design

There may be times when a pharmaceutical company has a problem without an obvious solution or needs a unique piece of equipment but doesn’t know how to fabricate it. For times like these, it might be worth pursuing a custom-engineered solution to achieve repeatable processes and high-quality product output every time.

For example, a pharma company needed and successfully sourced an electropolished basket with extremely fine tolerances for treating contact lenses. A good fabrication specialist knows which materials, like surgical-grade stainless steel, are appropriate for the pharmaceutical industry. Certain techniques finishing techniques give the smoothness and purity required for exceptionally delicate operations. 

5. Check Warranty and Customer Service Details

Nobody who relies on complex and valuable equipment for their daily workflows wants to think about downtime. It’s an expensive hassle — and not every OEM takes problems seriously if they do arise.

You need extremely dependable equipment. That means you need to find designers and manufacturers with lots of satisfied clients and a spotless track record for safety and quality. It’s important to ask questions about customer service responses, too, like how quickly a company will get you a replacement if something goes wrong. 

6. Make Sure the Environment Is Ready

As you’re working to procure lab equipment, it’s essential to make sure you’re welcoming your new assets into a suitable work environment. For quality control (QC) laboratories, especially, it’s important to create an environment that minimizes the chance for errors and malfunctions. This includes the following:
  • Proper ventilation and an air circulation system that reduces particulates
  • Enough space that each equipment station can be used comfortably and safely
  • Ample but not overly harsh lighting to ensure good visibility
  • Separate, controlled areas for specimen storage, servers, gas cylinders, and other sensitive or volatile materials 
7. Employ a Tracking System

Many of the latest pieces of equipment have GPS, Bluetooth, RFID, NFC (near-field communication) and other Internet of Things protocols built in. They help administrators and quartermasters tag, track and locate their company’s important tools and equipment.

The same systems provide a wealth of data on ambient and environmental conditions. Pharmaceutical companies — especially those involved in the transportation of temperature-sensitive products — benefit from the real-time operational visibility these technologies provide. 

8. Insist on Good User Experience

The manufacturers of your potential new lab equipment should be able to demonstrate how it works, how to operate it and why it could make a difference in your daily operations.

It’s fair to expect a moderate learning curve any time you adopt a new tool or technology. Nevertheless, if you find a provider with equipment that feels natural to use, you’ll probably see productivity and financial benefits for years to come. 

9. Find Experienced and Compliant Manufacturers

The consequences of poor quality in the pharmaceutical industry are high, which is why there are several standards groups with compliance requirements. When procuring lab and pharmaceutical equipment, look for manufacturers bearing endorsements from:
  • ASTM
  • FDA
  • ISO
  • GMP
  • cGMP 
10. Ask About Local Technical Support

One of the most frustrating things experienced in this line of work is having a piece of equipment fail and not having local technical support to fall back on.

The companies whose equipment you rely on should have agents, distributors and other partners close enough to your region that you’ll never get stuck with downtime while you wait for help to arrive.

There’s a lot that goes into procuring pharmaceutical equipment. With these 10 fundamentals in mind, however, you’ll be better prepared to outfit your lab or company and start finding clients.
Pharmaceutical Microbiology Resources: http://www.pharmamicroresources.com

Tuesday, 17 December 2019

New change control guidance

A new document of interest has been issued relating to change controls:

“Draft PIC/S Recommendation on How to Evaluate / Demonstrate the Effectiveness of a Pharmaceutical Quality System in relation to Risk-based Change Management”

The purpose of this draft document is to provide guidance on evaluating and demonstrating the effectiveness of a PQS in relation to risk-based change management. This is in recognition of the fact that the PIC/S GMP Guide requires companies to demonstrate the effectiveness of their PQS and to apply quality risk management (QRM) principles to change control activities.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

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