Excipients labelling

The European Medicines Agency (EMA) has updated this guidance relating to excipients labelling. Here Marketing Authorisation (MA) holders and applicants will need to identify the excipients included in any human medicine authorised in the EU in its product information.


The notification states that guidance is available from the European Commission and European EMA on what needs including in the labelling and package leaflet.

 

See: https://www.ema.europa.eu/en/human-regulatory/marketing-authorisation/product-information/reference-guidelines/excipients-labelling

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

Recall trends and the primary causes for product recalls

Pharmaceutical product recalls relate to a type of flaw, ranging from mislabelling to contaminated ingredients. Generally, pharmaceutical companies conduct voluntary recalls in collaboration with a regulatory agency. This article looks at recent data for pharmaceutical recalls pertaining to the US and Europe, both as overall trends and in relation to specific occurrences. The assessment suggests that the rate of recalls is increasing.

Tim Sandle has written a new article:

Recall trends and the primary causes for product recalls, GMP Review, 19 (2): 4-9

The types of pharmaceutical products that undergo a recall are as varied as the available products on the market. They include over-the-counter, prescription and compounded drugs, ranging from tablets and capsules, injectable drugs, liquids, lotions and creams, and many more. Similarly, the reason for recalls are equally varied although there is more commonality in terms of the general types of problems that trigger recalls to occur.

The leading causes of pharmaceutical recalls are sterility, the presence of particulate/foreign matter, and failed specification testing, according to figures from the US Office of Pharmaceutical Quality. Every recall is different, so the financial impact varies greatly. It is based on a number of factors, including the number of units affected and the global reach of the recall. There are also indirect costs that need to be factored in. For example, if pharmaceutical companies don’t work with partners to execute the recall, their internal staff must step in at the expense of their usual duties.

This article presents the main types of recalls occurring within the US, Europe and other territories, noticing some differences in trends and approaches to recalls.
 

For details, please contact Tim Sandle

Or go to Euromed Communications to see how you can subscribe to GMP Review

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

Poor gut health connected to severe COVID-19

The connection between COVID-19 symptoms and other underlying health conditions continues to be researched. A new finding draws a connection between symptom severity and intestinal health, in relation to the gut microbiome.

As an example of one of the connections between COVID-19 symptom severity and an underlying health condition, it as been established that diabetes can make the disease worse. This is possibly because the coronavirus triggers inflammation in the body and high blood (glucose) sugar levels also cause inflammation inside our body, hence the action of the virus exacerbates the diabetic condition. 

With the new strand of research, scientists have examined emerging evidence suggesting that poor gut health adversely affects COVID-19 prognosis. Central to this the microbiome and the variations between the microbial communities in the gut between individuals. 

 The human microbiome refers to the totality of microorganisms and their genetic interactions within a given niche. The human body is an intricate system that hosts trillions of microbial cells across the epithelial surface, and within the mouth and gut. These microorganisms play a role in human physiology and organ function, including digestion and immunity. 

The research finds that intestinal dysfunction appears to exacerbate the severity of coronavirus infection. This is through enabling the virus to access the surface of the digestive tract and the internal organs. These organs are, in particular, vulnerable to infection because the cells have ACE2 on their surfaces, which is the protein target of the coronavirus. 

In terms of the cause, the researchers consider diet to be an important determinant. Of concern is the so termed "western diet", which is characterized by a diet low in fiber. A fiber-deficient diet is one of the main causes of altered gut microbiomes. 

The research has been published in the journal mBio, and it is titled "Do an Altered Gut Microbiota and an Associated Leaky Gut Affect COVID-19 Severity?"

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

Bacteria that survive on deadly copper surfaces

The descendants of regular wild-type bacteria can evolve to survive for a long time on metallic copper surfaces that would usually kill them within a few minutes. An international research team led by Martin Luther University Halle-Wittenberg (MLU) and the Bundeswehr Institute of Microbiology was able to produce these tiny survivalists in the lab and has been able to study them more closely. 

 

Bacterial infections are usually treated with antibiotics. However, in recent decades many pathogenic bacteria have developed an increasing tolerance to common drugs. So-called multidrug-resistant bacteria are of particular concern as they can no longer be combated with most antibiotics. Copper surfaces -- for example on door handles -- are a good weapon to fight these germs. 

Most bacteria die within minutes after landing on a copper surface.On the copper surfaces, however, the bacteria are literally flooded to death with copper ions because that they can no longer stave them off using their normal defence strategies.

Two typical species of bacteria, Escherichia coli and Staphylococcus aureus, are theoretically able to adapt to survive on copper surfaces. Researchers placed the bacteria on the surfaces for only a few minutes before returning them to a normal culture medium where they were allowed to recover. This process was repeated several times, with the survivors gradually being exposed to the deadly surface for longer and longer periods of time. Within three weeks, the researchers had produced bacteria that could survive for more than one hour on a copper surface. 

The inference is that if copper surfaces are not cleaned regularly, insulating layers of grease can begin to form on them, which could produce a similar development over time.

Using comprehensive genetic analyses, the researchers sought to understand why the bacteria no longer died on the surfaces. 

What happened was not genetic, but physiological: The bacteria's metabolism slowed down to a bare minimum and they fell into a kind of hibernation. Because most antibiotics aim to disrupt the metabolism of growing bacteria, they are almost completely ineffective against these special bacteria, which are also known as "persisters." 

There are always a handful of persisters in every generation. These are not considered antibiotic-resistant bacteria, because their offspring are once again susceptible to the drugs.

Normally only a tiny proportion of bacteria become persisters. However, in the case of the isolated bacteria, it was the entire population. Although they were able to grow just as fast as their predecessors, they were also able to rescue themselves by switching rapidly into an early state of persistence under adverse conditions. 

The bacteria also inherited this capability over 250 generations, even though the offspring had not come into contact with a copper surface.

It is recommended that copper surfaces be cleaned regularly and thoroughly with special agents so that no persister bacteria can develop in the first place. 

---

Journal Reference:


Pauline Bleichert, Lucy Bütof, Christian Rückert, Martin Herzberg, Romeu Francisco, Paula V. Morais, Gregor Grass, Jörn Kalinowski, Dietrich H. Nies. Mutant Strains of Escherichia coli and Methicillin-Resistant Staphylococcus aureus Obtained by Laboratory Selection To Survive on Metallic Copper Surfaces. Applied and Environmental Microbiology, 2020; 87 (1) DOI: 10.1128/AEM.01788-20

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

Salmonella swimming behavior provides clues to infection

Salmonella enterica serovar Typhimurium bacteria (S. Typhimurium) commonly cause human gastroenteritis, inflammation of the lining of the intestines. The bacteria live inside the gut and can infect the epithelial cells that line its surface. Many studies have shown that Salmonella use a 'run-and-tumble' method of short swimming periods (runs) punctuated by tumbles when they randomly change direction, but how they move within the gut is not well understood.

S. Typhimurium use flagella -- long whip-like projections -- to move through fluids. When the flagella rotate counterclockwise, they form a rotating bundle behind the bacteria and propel them forward. However, the flagella frequently switch rotation from counterclockwise to clockwise, disrupting the bundle and causing the bacteria to tumble and change direction. Using special microscopes and cameras to observe live S. Typhimurium, the scientists found that bacteria grown under conditions that activate their invasive behavior swam in longer straight runs because the flagella did not switch rotation from counterclockwise to clockwise. 

Bacteria lacking McpC still demonstrated the "run-and-tumble" method of swimming under these conditions and had an invasion defect in a calf intestine model, indicating that straight swimming is important for efficient invasion of intestinal epithelial cells.

 

USA National Institutes of Health scientists believe they have identified a S. Typhimurium protein, McpC (Methyl-accepting chemotaxis protein C), that allows the bacteria to swim straight when they are ready to infect cells. This new study, published in Nature Communications, describes S. Typhimurium movement and shows that McpC is required for the bacteria to invade surface epithelial cells in the gut.

The study authors suggest that McpC is a potential target for developing new antibacterial treatments to hinder the ability of S. Typhimurium to infect intestinal epithelial cells and colonize the gut.

See:

Kendal G. Cooper, Audrey Chong, Laszlo Kari, Brendan Jeffrey, Tregei Starr, Craig Martens, Molly McClurg, Victoria R. Posada, Richard C. Laughlin, Canaan Whitfield-Cargile, L. Garry Adams, Laura K. Bryan, Sara V. Little, Mary Krath, Sara D. Lawhon, Olivia Steele-Mortimer. Regulatory protein HilD stimulates Salmonella Typhimurium invasiveness by promoting smooth swimming via the methyl-accepting chemotaxis protein McpC. Nature Communications, 2021; 12 (1) DOI: 10.1038/s41467-020-20558-6

 

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

Physical virology shows the dynamics of virus reproduction

 

The reproductive cycle of viruses requires self-assembly, maturation of virus particles and, after infection, the release of genetic material into a host cell. New physics-based technologies allow scientists to study the dynamics of this cycle and may eventually lead to new treatments. 

The laws of physics govern important events in their reproductive cycle. Recent advances in physics-based techniques have made it possible to study self-assembly and other steps in the reproductive cycle of single virus particles and at sub-second time resolution. 

Viruses hijack cells and force them to make the protein building blocks for new virus particles and to copy their genetic material (either RNA or DNA). This results in a cellular soup full of virus parts, which self-assemble to produce particles of encapsulated RNA or DNA.

No external energy is required for this process. And even in vitro, most viruses will self-assemble quickly. This process was traditionally studied in bulk material, averaging out the behaviour of large numbers of virus particles. 

Over the last few years, technologies have been developed to study these individual particles in real-time. One of those is fast Atomic Force Microscopy (AFM). An atomic force microscope scans surfaces with an atom-sized tip and is therefore able to map their topology. 

Single-molecule fluorescence is also used to study viruses, for example, the attachment of viral proteins to DNA. 

Using optical tweezers, researchers can hold two tiny beads on either end of a DNA molecule. When viral proteins bind to the DNA, this will coil up and bring the two beads closer together. This is visualized by fluorescent markers attached to the beads.

Alternatively, proteins with fluorescent markers can be observed while they attach to viral DNA or to other proteins. A third technology is to use an optical microscope to measure interference of light that is scattered by virus particles. These patterns reveal the structure of the particles during assembly. 

Other steps in the virus cycle can also be studied. New technology is now revealing the physical dynamics of viruses. It allows scientists to study how genetic material is incorporated and which physical principles guide this process. Most antiviral drugs disrupt the first steps in infection, such as the binding of virus particles to their host cells. Using this new dynamic information, we could develop drugs that block self-assembly or other important steps in the reproductive cycle of the virus. 

Insight into the physics of virus particles is also important for their use in research, for example as building blocks in nanotechnology or as carriers for antigens in vaccines. Several of the leading COVID-19 vaccines use adenoviruses to deliver the gene for the SARS-CoV-2 spike protein to cells, which then express this gene and consequently generate an immune response.

See:

Robijn F. Bruinsma, Gijs J. L. Wuite, Wouter H. Roos. Physics of viral dynamics. Nature Reviews Physics, 2021; DOI: 10.1038/s42254-020-00267-1

Greenland melting likely increased by bacteria in sediment

Bacteria are likely triggering greater melting on the Greenland ice sheet, possibly increasing the island's contribution to sea-level rise, according to scientists. That's because the microbes cause sunlight-absorbing sediment to clump together and accumulate in the meltwater streams, according to new study. The findings can be incorporated in climate models, leading to more accurate predictions of melting.

The Greenland ice sheet covers about 656,000 square miles -- most of the island and three times the size of Texas, according to the National Snow & Ice Data Center. The global sea level would rise an estimated 20 feet if the thick ice sheet melted.

With climate change, sea-level rise and coastal storms threaten low-lying islands, cities and lands around the world.

Most scientists ignore sediment in glacial streams that form on top of the Greenland ice sheet as meltwater flows to the ocean, but the Rutgers-led team wanted to find out why they accumulated so much sediment. In 2017, scientists flew drones over an approximately 425-foot-long stream in southwest Greenland, took measurements and collected sediment samples. They found that sediment covers up to a quarter of the stream bottom, far more than the estimated 1.2 percent that would exist if organic matter and cyanobacteria did not cause sediment granules to clump together. They also showed that streams have more sediment than predicted by hydrological models.

See:

Sasha Z. Leidman, Åsa K. Rennermalm, Rohi Muthyala, Qizhong Guo, Irina Overeem. The Presence and Widespread Distribution of Dark Sediment in Greenland Ice Sheet Supraglacial Streams Implies Substantial Impact of Microbial Communities on Sediment Deposition and Albedo. Geophysical Research Letters, 2020; DOI: 10.1029/2020GL088444

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

EDQM webinars

EDQM (European Directorate for the Quality of Medicines and Healthcare) is all set for the two webinars in order to enhance the knowledge of the audience. They have always given quality driven and essential information. 

A guest post by Aparna Rane

1) Nitrosamines

Its all about Nitrosamines. This webinar will provide users and stakeholders with an update on the different activities related to nitrosamine impurities, including a detailed overview of the new general chapter. It will also include a recap of the Ph. Eur. approach to keeping the monographs aligned with the latest regulatory decisions.

The webinar will take place on 21 January 2021, from 1 p.m. to 2:30 p.m. (Paris, France)

N-Nitrosamine impurities: Latest update on the Ph. Eur. Approach

See: https://www.edqm.eu/en/events/new-webinar-n-nitrosamine-impurities-latest-update-ph-eur-approach

 

 

2) Data protection in Blood sector

Its all about the needed data protection for the Blood establishments. The webinar will focus on data protection in the blood sector, the impact and challenges faced by European blood establishments.

The webinar will take place on 17 February 2021, from 2 p.m. to 5 p.m. (Paris, France).

Data Protection in the Blood Sector: Impact and Challenges for Blood Establishments’

See: https://www.edqm.eu/en/events/new-webinar-data-protection-blood-sector-impact-and-challenges-blood-establishments 

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