Thursday, 6 August 2020

Antimicrobial Activity of Silver-Treated Bacteria


Silver is a potent antimicrobial agent against a variety of microorganisms and once the element has entered the bacterial cell, it accumulates as silver nanoparticles with large surface area causing cell death. At the same time, the bacterial cell becomes a reservoir for silver. 

This leads onto a new study of interest.

This study aims to test the microcidal effect of silver-killed E. coli O104: H4 and its supernatant against fresh viable cells of the same bacterium and some other species, including E. coli O157: H7,

Multidrug Resistant (MDR) Pseudomonas aeruginosa and Methicillin Resistant Staphylococcus aureus (MRSA). Silver-killed bacteria were examined by Transmission Electron Microscopy (TEM). Agar well diffusion assay was used to test the antimicrobial efficacy and durability of both pellet suspension and supernatant of silver-killed E. coli O104:H4 against other bacteria. 

Both silver-killed bacteria and supernatant showed prolonged antimicrobial activity against the tested strains that extended to 40 days. The presence of adsorbed silver nanoparticles on the bacterial cell and inside the cells was verified by TEM. Silver-killed bacteria serve as an efficient sustained release reservoir for exporting the lethal silver cations. This promotes its use as a powerful disinfectant for polluted water and as an effective antibacterial which can be included in wound and burn dressings to overcome the problem of wound contamination. 

Reference:



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

Wednesday, 5 August 2020

Guideline on the quality of water for pharmaceutical use


The European Medicines Agency has produced the final version of its guideline ‘Guideline on the quality of water for pharmaceutical use’.

The guidance has been issued to provide a regulatory perspective on the production of Water for Injection (WFI) using methods other than distillation, as per the earlier revision in the European Pharmacopeia.



The issuing of the new guidance, in July 2020, follows an earlier draft (with the same title) which was published in 2018. The draft remained out for public comment until mi- May 2019. 

The purpose of the guidance is to set out the water quality requirements for specific pharmaceutical production process (human and veterinary medicinal products, and Advanced Therapy Medicinal Products).This relates to three different pharmaceutical water qualities: WFI, purified water and water for the production of extracts. The quality of mains (supply) water is outlines, although this is not considered to be water of pharmaceutical quality.

See: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-quality-water-pharmaceutical-use_en.pdf

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

Tuesday, 4 August 2020

The latest revision of EU GMP Annex 1 signals a new regulatory paradigm


A new edition of GMP Review has been published (edited by Tim Sandle). In the new edition is a paper by Dr. Sandle, looking at the essential elements of the latest revision of Annex 1 of EU GMP.
The aim of Annex 1 is to set out the minimum standards for the manufacture of sterile products (both aseptically filled and terminally sterilised), which takes place within cleanrooms and barrier devices. There is a major focus within the Annex on the need for a contamination control strategy, purposefully designed for each facility; and for each manufacturer to be using the principles of quality risk management.

While there are several essential points to consider for the contamination control strategy, those that appear to be given the greatest weighting (from this author’s reading of the text) are:
  • ·         Maintaining the critical processing zone.
  • ·         The aseptic assembly of filling equipment.
  • ·         Aseptic connections (these should be sterilized by steam-in-place whenever feasible).
  • ·         Special focus on aseptic compounding and mixing.
  • ·         The risks abound the replenishment of sterile product, containers and closures.
  • ·         Concerns around the removal and cooling of items from heat sterilizers.
  • ·         Staging and conveying of sterile primary packaging components.
  • ·         Aseptic filling, sealing, transfer of open or partially stoppered vials, including interventions.
  • ·         Loading and unloading of a lyophilizer.
It is unsurprising that each of these relate to aseptic processing, the highest-risk area of pharmaceutical manufacturing. 

The reference is:

Sandle, T. (2020) The latest revision of EU GMP Annex 1 signals a new regulatory paradigm, GMP Review, 19 (1): 4-6

For details, contact Tim Sandle.

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

Monday, 3 August 2020

Cancer biomarkers in HIV-infection patients with and without drug addiction


Pathogenesis of the connection of HIV-infection and cancer is a problem for medical professionals and presents an interesting area for research. The aim of the study was to investigate the level of cancer biomarkers in HIV-infected patients with a background of narcotic drugs use, via parenteral administration, and in HIV-infected patients without a similar background.


Akhmaltdinova, L.L., Azizov, I. S., Tyukhtina, Z. P., Serdyuk, L. I., Kozachenko, N.V., Sandle, T., Moraru, D. and Chesca, A. (2020) Cancer biomarkers in HIV-infection patients with and without drug addiction, Acta Medica Mediterranea, 36: 1129-1132


Researchers analyzed the serum from 30 HIV-positive injecting drug users and30 HIV-positive patients without drug addiction. A control group consisted of 30 healthy people (negative in screening for HIV-infection) and a comparison group of 23 patients with drug dependence but no HIV-infection. The researchers used the xMap method on Bioplex 3D with a set cancer biomarkers panel: sHER-2, sEGFR, sIL-6Rα, FGF, sVEGFR-2, PECAM1, PDGF AB/BB, G-SCF, sTIE2, SCF, sVEGFR-1, osteopantin.

The research revealed the increased levels of sHER-2, sEGRf, sIL-6RA, sVEGfr2, PECAM1, sTIE2 in all HIV-infected patients. SCF and FGF markers were increased only in injecting drug users (HIV+/HIV-). The drug addicts with HIV had the increased level of inflammatory markers sIL-6RA, PECAM 1, osteopantin and the level of HER-2.

This study of carcinogenesis biomarkers showed its own peculiarities in HIV-positive patients, including complications for those with drug addiction.

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

Sunday, 2 August 2020

COVID-19: consider cytokine storm syndromes and immunosuppression


As of March 12, 2020, coronavirus disease 2019 (COVID-19) has been confirmed in 125 048 people worldwide, carrying a mortality of approximately 3·7%, compared with a mortality rate of less than 1% from influenza. There is an urgent need for effective treatment. Current focus has been on the development of novel therapeutics, including antivirals and vaccines. Accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome. We recommend identification and treatment of hyperinflammation using existing, approved therapies with proven safety profiles to address the immediate need to reduce the rising mortality.

An interesting article has been published in The Lancet.

As during previous pandemics (severe acute respiratory syndrome and Middle East respiratory syndrome), corticosteroids are not routinely recommended and might exacerbate COVID-19-associated lung injury. However, in hyperinflammation, immunosuppression is likely to be beneficial. Re-analysis of data from a phase 3 randomised controlled trial of IL-1 blockade (anakinra) in sepsis, showed significant survival benefit in patients with hyperinflammation, without increased adverse events.

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

Saturday, 1 August 2020

COVID-19 immunotherapy program


Fab’entech, a Lyon-based biopharmaceutical laboratory specializing in emergency immunotherapy, announces today the launch of a program to develop an immunotherapy treatment against COVID-19. This treatment will be used for severely ill patients requiring respiratory assistance. Human clinical trials should start in early 2021.

In order to meet new public health challenges, Fab’entech has created a development and production platform based on a polyclonal immunotherapy technology which enables targeted recognition of a virus or toxin and its specific neutralization. Fab’entech has already demonstrated the effectiveness and safety of this approach while developing its own products. This new COVID-19 program stems from the R&D and industrial platform developed by Fab’entech over the last decade, which draws on technology proven in the treatment of infectious diseases.

In January 2020 Fab’entech raised €8.5 million ($9.6M) from the Definvest fund of the Ministry of the Armed Forces, managed by Bpifrance, also from Institut Mérieux and from its historic shareholders. These funds helped Fab’entech move forward with a new industrial site that meets the requirements of both the EMA (European Medicines Agency) and the FDA (Food and Drug Administration). Located near Lyon, this new unit will ensure the production of immunotherapy treatments against COVID-19 in France and will quickly ramp up to increase its production capacities and provide treatments to cover other markets.

“Fab’entech will play an important role in the fight against and control of the COVID-19 pandemic,” said Dr. Bertrand Lépine, founder of Fab’entech. “We are convinced that this treatment will contribute toward reducing the use of critical care units and will mean many patients can be successfully treated, whilst also freeing up the healthcare system.”

Unlike monoclonal antibodies, polyclonal antibodies make it possible to target different parts of the antigen of interest. Polyclonal antibodies are therefore more suited to the modifications that the antigens may undergo, such as those resulting from virus mutations. Using an antigen derived from SARS-CoV-2, the company was able to launch a program to develop F(ab’)2 polyclonal antibodies, which will be administered to patients by injection with the aim of establishing passive immunity.

The polyclonal antibodies neutralize the virus and therefore slow down its progression in the organism, giving the patient’s immune system time to produce its own antibodies. Furthermore, these have a synergistic effect with other existing therapies, which Fab’entech was able to demonstrate in animals with H5N1 influenza by co-administering its anti-H5N1 product with oseltamivir. The study also showed a reduction in the nasal viral load, which is directly related to the level of contagiousness of the virus.

The process used by Fab’entech makes it possible to keep only the active part of the F(ab’)2 fragments and removes the Fc fragments from the antibodies. This prevents an excessive immune response by the patient, which could lead to a ‘cytokine storm’. Based on a strategy similar to convalescent plasma therapy, this approach is a standardized, safer, more reproducible and easily scalable solution.


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

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