Microbioz India, September 2021 Lab 2021

Microbioz India, September 2021 Edition | 1

Microbioz India, September 2021 Edition | 2

Microbioz India, September 2021 Edition | 3

Microbioz India, September 2021 Edition | 4

Contact: Email : [email protected] Tel: +91-9082974025 Microbioz India, September 2021 Edition | 5

Microbioz India, September 2021 Edition | 6

Microbioz India, September 2021 Edition | 7

33 51 22 12 24 Cover Story 12 Pharmaceutical Mycelia: A story of statins Featured Article 18 28 Conducting Research on Highly Pathogenic Viruses Using Virus Pseudotypes: The Influence of Ultrapure Water on Data Quality Business News IBM Research and Arctoris accelerate closed loop drug discovery with AI and Cloud Product Launches 4238 All You Need to Know About the Zebrafish Model in Biomedical and Applied Research Microbioz India, September 2021 Edition | 8

Microbioz India, September 2021 Edition | 9

ycelial cultures were obtained from fragments of F. officinalis fruiting bodies. The taxonomic position of the mushroom mycelium was confirmed using the PCR method. The presence of organic compounds was determined by HPLC–DAD analysis. The cover story of this month titled: “Pharmaceutical Mycelia: A story of statins” contributed by LGC Mikromol. As the story suggests Cholesterol: we all know the word, and its negative associations. So is all cholesterol bad? It’s not that simple – the fatty substance known as cholesterol is not only ingested through food, but also created by the liver, and has crucial functions without which we wouldn’t be alive. These functions include contributing to cell wall structure, forming digestive bile acids in the intestine, and enabling the production of vitamin D and certain hormones. Cholesterol is carried round the body in two types of lipoproteins, low-density lipoprotein (LDL) and high-density lipoprotein (HDL). The edition has a featured article entitled “Conducting Research on Highly Pathogenic Viruses Using Virus Pseudotypes: The Influence of Ultrapure Water on Data Quality” contributed by Sartorius. From 2013 to 2016, more than 11,000 people died of Ebola virus infections in West Africa. This most recent epidemic shows how dangerous so-called emerging viruses can be. Virus pseudotypes can be used to easily investigate the entry pathways of such viruses. Novel viruses, termed emerging viruses, pose a threat to human health of a magnitude that should not be underestimated. Dear subscribers, we could not imagine anything better than to have your essential criticism and proposals since they help us to concoct much better material each time. For any suggestion and feedback please feel free to write: [email protected] Disclaimer: Microbioz India, September 2021 Edition | 10 Neither the Microbioz India nor its publishers nor anyone else involved in creating, producing or delivering the Microbioz India (in printed, web or CD format) or the materials contained therein, assumes any liability or responsibility for the accuracy, completeness, or usefulness of any information provided in the Microbioz India Magazine (in printed, web or CD format), nor shall they be liable for any direct, indirect, incidental, special, consequential or punitive damages arising out of the use of the Microbioz India magazine.

Microbioz India, September 2021 Edition | 11

Cover Story Pharmaceutical Mycelia: A story of statins Cholesterol: we all know the word, and its negative associations. So is all cholesterol bad? It’s not that simple – the fatty substance known as cholesterol is not only ingested through food, but also created by the liver, and has crucial functions without which we wouldn’t be alive T hese functions include contributing to cell HDL absorbs cholesterol and carries it back wall structure, forming digestive bile acids to the liver, which can regulate cholesterol levels in the intestine, and enabling the and clear some from the body if necessary. LDL production of vitamin D and certain hormones. carries the majority of your body’s cholesterol and Cholesterol is carried round the body in two types can cause build-up in blood vessels when there is of lipoproteins, low-density lipoprotein (LDL) and too much of it in your blood – potentially leading high-density lipoprotein (HDL). to heart attack or stroke. Microbioz India, September 2021 Edition | 12

Cover Story By 2012 atorvastatin/Lipitor had become the top- selling pharmaceutical of all time, and One of the most even in the latest list of most prescribed drugs in commonly prescribed the US (2021 list – using 2018 prescription data), it medications in the world, still sits at the no 1 spot, at 112 million statins are a group of prescriptions. agents used to both lower the level of LDL Magic mushrooms cholesterol in the blood and for Statins are secondary metabolites – low-weight their antithrombotic molecular compounds produced by and anti- microorganisms and plants – produced from inflammatory filamentous fungi. effects. These actions help to prevent blood Microbioz India, September 2021 Edition | 13 clotting and build-up on blood vessel walls, thus reducing the risk of heart attacks and strokes. Common statins today include atorvastatin, fluvastatin, simvastatin and rosuvastatin. History While many statins are now produced synthetically, their natural precursors were predominantly produced from Aspergillus and Penicillium fungus species. In the 1970s Japanese scientist Akira Endo began investigating HMG CoA in microorganisms and discovered mevastatin from the fungus Penicillium citrinum. Mevastatin is considered the first statin to be isolated and developed, although it never reached the market. The first statin to market, lovastatin, was isolated from the fermentation broth of Aspergillus terreus in the 1970s by Alfred Alberts, who worked for Merck, and made available to the public in 1987 as Mevacor. But it was atorvastatin, first patented by Warner-Lambert in 1986, that was to take statins stratospheric. A five-year study published in 1994 researching the effects of Merck’s synthetic lovastatin alternative, simvastatin, on patients with high cholesterol and heart disease found a 35% reduction in their cholesterol and 42% lower chance of dying of heart attack in the period. Early results comparing atorvastatin to simvastatin indicated that Warner-Lambert’s drug was both more potent and had fewer side effects, so in 1996 atorvastatin reached market under the name Lipitor, in a joint agreement with Pfizer, who later acquired Warner- Lambert. Lipitor soon became a popular prescription, its arrival coinciding with an increase in average weight and cholesterol levels seen across many developed societies, and by 2003 was the best-selling medication in the US.

Cover Story As many secondary metabolites serve as defence These two compounds can then be modified to give semi-synthetic statins – pravastatin, which molecules against other microbes, despite being is derived from mevastatin, and simvastatin, which is derived from lovastatin. derived from fungi they often have antimicrobial or The third class of statins are fully synthetic, including fluvastatin, rosuvastatin and ator antifungal activity. vastatin, among others. Fluvastatin was the first fully synthetic drug to be developed. Atorvastatin is Fungi are an incredibly diverse group of eukaryotic commonly sold as a calcium complex, featuring two atorvastatin ions and a calcium ion. Rosuvastatin is organisms once considered like plants, though marketed in the same way. molecular evidence has shown that they are Structurally, the natural and semi-synthetic compounds are similar, sharing a chiral β-hydroxy- actually more closely related to animals δ-lactone (or in the case of pravastatin an open chain analogue) and a hexahydronaphthalene than to plants, with a shared common ancestor system. Pravastatin has an additional hydroxyl group on its hexahydronaphthalene group, and this who split from plant life. There are clues to their is obtained by microbial hydroxylation of mevastatin. The addition of this hydroxyl group distance from plants in their cell walls made of means pravastatin has a much higher solubility in water. The fully synthetic statins possess the same chitin – not found in the plant world but common 3,5-cis-dihydroxy acid motif seen in pravastatin, but a heterocyclic ring replaces the in insects – rather than cellulose, their lack of hexahydronaphthalene structure. Simvastatin possesses an additional methyl group chlorophyll, production of spores and in the on the butyrate ester, lending the drug a much higher bioavailability than lovastatin. To obtain mycelium, the branching filamentous structure of simvastatin, lovastatin is reduced using lithium hydroxide, resulting in a compound hyphae. with two hydroxy groups that are susceptible to reaction (Figure 2). Since the hydroxy on the Fungi absorb nutrients through this mycelium and lactone functional group is necessary for enzyme binding, it is protected by organosilicon compound many exist in a symbiotic relationship with trees, TBDMS in the presence of imidazole, leaving the other hydroxy free to react with 2,2- grasses and crops, known as a mycorrhiza. This dimethylbutyryl chloride. complex association is essential to plant life and the mycelia of fungi can span entire forests – the largest know organism is Armillaria ostoyae, which covers 3.4 square miles (8.8 km2) in the Malheur National Forest. It is aged between 1900 and 9600 years old. Some species of fungi are even carnivorous, with mycelia that can digest living organisms such as nematodes: species in the saprotrophic Pleurotus mushroom genus are good examples. While lovastatin was found in A. terreus, it is also produced in some higher fungi, most of which are in the Pleurotus genus. It is most known in P. ostreatus, the oyster mushroom, which contains up to 2.8% lovastatin on a dry weight basis, but can also be found in P. djamor, Imleria badia, and Cantharellus cibarus, among others. Edible mushrooms, meanwhile, have been collected for food for thousands of years, with archaeological evidence that they may have been used as far back as 6800 years ago in Neolithic China. Many mushrooms are psychoactive, which led to roles in medicinal and ceremonial activities in indigenous tribes. Even the common red-and-white spotted mushroom Amanita muscaria or fly agaric, which features in children’s picture books, garden ornaments and video games, is actually hallucinogenic. Chemistry of statins Statins can be divided into three groups based on how they are obtained. As mentioned, mevastatin and lovastatin are naturally occurring statins obtained via fermentation methods. Microbioz India, September 2021 Edition | 14

Cover Story In this case, the lactone group is hydrolysed in the liver to form a hydroxy acid form (Figure 3) which If the hydroxy group isn’t properly protected the bears a considerable similarity to the structure of compound can undergo esterification to give Imp HMG CoA. This similarity in structure allows the B, or be completely removed to give Imp C. statins to fit into the active site of HMG-CoA Simvastatin can also dimerise (Imp D). reductase and competitively inhibit cholesterol synthesis. Mechanism of action Outlook: Mushroom for growth? Statins work by binding competitively to an While statins are already hugely popular drugs, enzyme known as HMG-CoA reductase. This is a there is evidence that these fungi-derived rate-controlling enzyme in the mevalonate compounds may have even more medical uses than pathway, the metabolic process responsible for currently confirmed. cholesterol production. The enzyme catalyses the Even within their current medical functions, they conversion of metabolic intermediate HMG-CoA may have more expansive potential uses: few to mevalonic acid. controlled trials of statins have included patients over 70 years old, because the assumption has been A clear difference between most of the that their effects would be of limited use in people natural statin compounds and the synthetic with a shorter life expectancy, and might even be ones is the presence and absence of a damaging. However, a 2020 observational lactone group. This is because mevastatin, study of 320,000 patients aged 75 years and lovastatin and simvastatin are older, free of heart disease and taking statins for the administered in their prodrug first time, found a 25% lower risk for death and a form. Prodrugs are an important 20% lower risk for cardiovascular death over seven class of drug delivery systems, years than those not prescribed statins. A further which provide a means to improve two studies have also indicated that statin use bioavailability, improve how a drug benefits elderly patients as much, if not more than, interacts with cells, and prevent unwanted younger ones. side effects. Prodrugs themselves are Data has also indicated that statin use could help chemically inactive, but after administration protect against cardiotoxic chemotherapy, with are metabolised into the pharmacologically statins associated with a 55% reduced likelihood of active drug. hospitalisation for heart failure in breast cancer chemotherapy patients over five years in one analysis. Outside cardiovascular use, statins have also been suggested to have therapeutic potential in a wide range of other areas, from dementia to lung cancer. Stroke risk seems to be reduced through statin use, with meta-analysis of 19 studies finding that the prevention of ischemic stroke was striking enough to outweigh any associated risk. Compelling studies also suggest that statins offer ‘endothelial protection…as well as antioxidant, anti-inflammatory and anti- platelet effects’, which could have potential for treatment not only of stroke but also in neurological disorders such as Alzheimer’s, Parkinson’s and MS. Microbioz India, September 2021 Edition | 15

Cover Story This is where Mikromol can help – we support your pharmaceutical quality testing for a wide range of statin APIs and related impurities, with certified reference standards created by our expert chemists. If even some of these many potential additional uses for statins prove to be fruitful, it will further cement their place in the pharmaceutical hall of fame. But one thing’s for sure: these versatile compounds have already changed the world for the better. About the author Lungs are also impacted: statins have also been Dulcie Phipps is an Assistant demonstrated to have potential to lower the Global Product Manager at mortality rate in patients with chronic LGC. obstructive pulmonary disease (COPD), and in A chemist with a passion for population studies long-term statin use has been nature, she grew up in associated with improved overall lung the glens of Perthshire, cancer survival times. Scotland. Phipps’ academic There has also been exploration of prescription of background includes a Marine statins for immune and inflammatory disorders, to Science HNC, an MSc in Chemistry from the University of treat parasitic diseases, and for their antibacterial Glasgow, and a European work placement focusing on properties. Whatever the clinical use, they all have lanthanide chemistry at Uppsala University, Sweden. After one aspect in common: they need high quality, safe completing her degree, she moved to Luckenwalde, and reliable pharmaceuticals to provide patients Germany, to work for LGC. with efficacy and peace of mind. Microbioz India, September 2021 Edition | 16

Microbioz India, September 2021 Edition | 17

Featured Article Conducting Research on Highly Pathogenic Viruses Using Virus Pseudotypes: The Influence of Ultrapure Water on Data Quality This application note was first published by Sartorius- click here for the full application note and references F rom 2013 to 2016, more than 11,000 Furthermore, the surrounding circumstances of a people died of Ebola virus infections in globalised society involving increased travel also West Africa. This most recent epidemic enable dissemination of pathogenic viruses around shows how dangerous so-called emerging viruses the world, even before the onset of clinical can be. Virus pseudotypes can be used to easily symptoms. Within the last 100 years, multiple investigate the entry pathways of such viruses. introductions of emerging viruses into the human population have occurred, which have led to local Novel viruses, termed emerging viruses, pose a epidemics or worldwide outbreaks (pandemics; see threat to human health of a magnitude that should Table 1). not be underestimated. These viruses have acquired the ability to infect In particular, the Ebola virus most recently raised humans either as a consequence of interspecies concerns across the globe, as the West African transmission or of naturally occurring changes in Ebola virus epidemic, which claimed more than the viral genome. Infections caused by emerging 11,000 lives, devastatingly demonstrated the danger viruses often result in serious diseases or even death posed by emerging viruses. Research involving as the human immune system may not be capable emerging viruses is often limited to high- of combatting an unfamiliar virus, especially of containment laboratories of biosafety levels (BSL) zoonotic origin. Various factors promote the 3 and 4 (see Table 1). Working in BSL-4 occurrence and spread of emerging viruses. These laboratories is highly laborious, expensive and include ecological factors, such as deforestation to permitted only at a few locations so that rapid gain new land for development, and also our scientific progress in characterizing viral pathogens lifestyle involving global mobility, as well as and developing antiviral drugs is difficult to achieve international commerce. Thus, the loss of habitat increases the probability that people, pets and farm Given this situation, virus pseudotypes offer an animals will come in contact with wildlife species attractive option for studying the entry of highly originally inhabiting isolated areas and therefore pathogenic viruses into cells safely and efficiently. not previously encountered as natural hosts of emerging viruses. Microbioz India, September 2021 Edition | 18

Featured Article This is possible as not the entire pathogen is The purity level of the laboratory water used analysed, but rather only its components that influences the quality of VSV pseudotypes mediate host cell entry, the envelope proteins. These represent the key to virus entry into cells. After it could be shown in the previous trials that VSV pseudotypes are suitable models for studying In the case of virus pseudotypes, envelope proteins the host cell entry of highly pathogenic viruses, the of highly pathogenic viruses are incorporated into next issue to be clarified was the particular a carrier virus (pseudotyping), which cannot influence that the purity level of the laboratory replicate autonomously, i.e., are replication water used has on the quality of VSV pseudotypes. deficient. Commonly used systems for During production of VSV pseudotypes, various pseudotyping are based on rhabdoviruses (e.g., buffers and solutions are employed that are all vesicular stomatitis virus, VSV; Fig. 1) and prepared with water. However, it must be noted retroviruses. The objective of this study was to that not just any type of water suffices for verify whether the envelope protein-mediated entry preparation of these reagents. Rather, the right of virus pseudotypes reflects host cell entry of choice of purity level must be made for laboratory intact viruses. In addition, this investigation was use. To investigate whether the use of ultrapure designed to determine which influence the level of water yields higher quality VSV pseudotypes, two purity of the reagents used, in this case laboratory batches of VSV pseudotypes were generated in a water, has on the production of virus pseudotypes parallel experiment: One batch was prepared using demineralised water from a central lab water supply It is known that the Middle East respiratory source (conductivity of 3.7 – 4.1 μS/cm at 19°C) as syndrome coronavirus (MERS-CoV, formerly the basic solvent for all solutions and buffers, while called human coronavirus, EMC = hCoV-EMC), a further batch utilising solutions and buffers based binds to the cell surface through the interaction on Arium® Pro VF ultrapure water (conductivity between the viral spike glycoprotein (S) and the 0.055 μS/cm compensated to 25°C) was generated. cellular membrane protein dipeptidyl peptidase 4 (DPP4), thus enabling cell entry [7]. To confirm Microbioz India, September 2021 Edition | 19 whether this also applies in the context of VSV pseudotypes, target cells were transfected with an expression vector for DPP4 or an empty expression plasmid (no receptor). As expected, the directed expression of DPP4 led to a significant increase in the host cell entry of VSV pseudotypes if the pseudotypes had MERS-CoV S embedded in their envelope (see Fig. 2A). Influenza A viruses, the causative agents of influenza disease, require terminal sugar structures, so-called sialic acids occurring as natural modifications on cellular membrane glycoproteins and glycolipids, as receptors to mediate entry into target cells (see literature for further reading [8]). To study whether the incorporation of influenza A viral envelope proteins in VSV pseudotypes also results in sialic acid-dependent cell entry, VSV pseudotypes with H1N1 (1918) HA/NA were employed, and the sialic acids were enzymatically removed from the surfaces of target cells. As expected, removal of sialic acids resulted in a dramatic decrease in the host cell entry of VSV pseudotypes that had H1N1 (1918) HA/NA embedded in their envelope (see Fig. 2B). This finding confirms that virus pseudotypes reflect the entry mechanism of authentic influenza A viruses into cells.

Featured Article The use of pseudotypes also reduces the considerable labour intensity involved in high- EBOV GP and MERS-CoV S as envelope proteins containment laboratories requiring whole-body were examined. Following parallel production of protection suits, as well as the considerable costs VSV pseudotypes by maintaining identical and the limitations entailed by such lab work (e.g., incubation conditions, the target cells were no access to equipment that is not directly located inoculated and the envelope protein-mediated inside the high-containment laboratory). entry of VSV pseudotypes was quantified. This Furthermore, compared with authentic, highly experimental setup demonstrated that host entry pathogenic viruses, virus pseudotypes minimise the (as a parameter for the degree of quality) of the risk of infection of lab personnel following VSV pseudotypes produced using Arium® Pro VF unintentional exposure, thus representing a ultrapure water as the basic solvent for all buffers significant safety aspect. Optimisation of the and solutions was significantly higher compared production process, for example, through the use with that of pseudotypes for which demineralised of highly pure reagents, particularly those based on water was employed in their production. water, can additionally contribute to improving the sensitivity of subsequent test procedures, Conclusion increasing production quantities and thus further lowering production costs In conclusion, it can be stated that virus pseudotypes are important tools for investigating This application note was first published by host cell entry of highly pathogenic viruses. As Sartorius- click here for the full application note these virus pseudotypes do not restrict research on and references. Find out more on the importance such highly pathogenic viruses to BLS-3 or BLS-4 of the quality of ultrapure water, among other laboratories, this enables a larger number of factors, for the production of such virus scientific facilities to conduct such research. As a pseudotypes. result, the cell entry of emerging viruses can be characterised and suitable detection procedures and Other Covid 19 related resources- Sartorius Covid antiviral strategies (medications, vaccines) can be 19 Resource page developed faster. Microbioz India, September 2021 Edition | 20

Microbioz India, September 2021 Edition | 21

Featured Article Sartorius Unveils LIVECell, a Deep-Learning Dataset for Label-Free, Quantitative Cell Segmentation in Nature Methods Source: Sartorius Newsroom  Open-source, manually annotated, expert-validated dataset includes more than 5000 label-free phase- contrast microscopy images acquired by the Incucyte® Live-Cell Analysis System, consisting of more than 1.6 million cells of eight cell types with distinct morphologies  Diversity of the dataset enables its use for more effective training of neural networks for creation of customized machine learning algorithms, leading to more accurate segmentation of additional cell types The Life Science Group Sartorius today While neural networks can learn and adapt to announced publication of an article identify and segment a variety of cells, they first in Nature Methods describing the require training with high quality datasets company’s LIVECell (Label-free In Vitro image representative of the breadth of the cell Examples of Cells) deep-learning dataset for label- morphologies to be encountered. free, quantitative segmentation of live cell images. The open- source dataset includes 5000 label-free phase contrast microscopy images consisting of more than 1.6 million cells of eight cell types with distinct morphologies that have been manually annotated. The set of images includes cells grown from initial seeding densities to fully confluent monolayers, resulting in a large variation in cell size and shape. IncuCyte-S3-SX5-mAb-Monoclonal- “The ability to derive Antibodies-Sartorius physiologically relevant data Achieving accurate segmentation in microscopy from label-free microscopy images is a cornerstone images is essential for quantitative downstream of pharmaceutical research and datasets containing analysis but is a challenging task. Traditional image images of millions of cells facilitate exploration of analysis methods often require tedious algorithm biological phenomena with great statistical power,” customization and rigorous tuning of parameters said Rickard Sjögren, PhD, Senior Scientist, specific to the cell morphology of interest.“The Sartorius Corporate Research. diversity of cell types and confluence conditions “To compensate for a lack of image resolution, captured and annotated in the LIVECell dataset however, sophisticated imaging processing pipelines are necessary to generate the accurate cell- overcomes these challenges by facilitating the by-cell, pixel-by-pixel segmentations necessary to capture subtle changes in cell size, shape and training of deep learning-based segmentation texture, particularly if the goal is to investigate events at the level of cellular subpopulations or models,” said Tim Jackson, PhD, Senior Image individual cells.” Processing Engineer, Sartorius BioAnalytics Product Development. “Researchers now have an unprecedented, high-quality label-free segmentation resource and starting point for training neural networks. Microbioz India, September 2021 Edition | 22

Featured Article The high-throughput Incucyte® system was Due to the nature of neural network-based essential for building the image dataset as it allowed algorithms being orders of magnitude more capture of a very high volume of high-quality complex than traditional image analysis, this data images. Use of a high-throughput label-free culture set will allow for more robust segmentation of system eliminated the risk of biological artifacts, various cell morphologies, and ultimately minimize while leads to increased confidence in the output of user-introduced biases.” algorithms based on the dataset. Prior to launch of the LIVECell dataset, the largest Source: Sartorius Newsroom dataset of label-free images available to researchers For further information on the LIVECell data consisted of 4,600 images derived from 26,000 set, please visit: https://sartorius- cells. research.github.io/LIVECell/ For more information on the Incucyte® Sartorius collaborated with the German Research system, please visit: www.sartorius.com/incucyte Center for Artificial Intelligence (DFKI) to demonstrate the utility of this dataset and plans to continue work with the Center to further advancements in deep learning for the life sciences community. Images of the eight different cell lines (human breast cancer (3), human glioblastoma, human hepatocyte carcinoma, human neuroblastoma, human ovarian cancer, mouse microglia) were captured every four hours, over the course of three to five days using an Incucyte® Live-Cell Analysis system. Microbioz India, September 2021 Edition | 23

Featured Article Detection of Mastitis Pathogens in Raw Milk of Symptomatic Cows Mycoplasma and especially Mycoplasma bovis This application note describes a method for the as well Staphylococcus aureus and Streptococcus detection of differentpathogens with the Mastit 4C agalastiae are harmful pathogens for cows Kit by DNA Diagnostic on the qTOWER³ and and calves, which can cause proves its specificity. inflammation and the Mastitis disease. Mastitis leads Materials and Methods to a reduction in the quantity of milk, which, in The Mastit4C Kitfrom DNADiagnostic wasused to addition to animal health and welfare, is also an isolate bacterial DNA from milk. The number of important economic factor for farmers. In veterinary samples of the protocol was adapted. All steps were diagnostics it is important to isolate the harmful performed in a 1.5 ml reaction tube. After the bacteria from the milk and to detect them precisely. transfer of the Pre-lysis buffer from the 96 Since Deep Well Plate to the 1.5 ml reaction tube, 500 µl of raw milk were added. One sample was contaminated Mycoplasma bovis has no cell wall and is therefore with different pathogens to test the performance of naturally resistant to antibiotic therapy, therapy is the extraction and detection. particularly difficult. Only isolation of the symptomatic cows can prevent it fromspreading. qTOWER³ Series The extraction of bacterial DNA from milk is a To detect Mycoplasma, Staphylococcus and challenge due to the diversity of ingredients, such as Streptococcus in the samples, the detection part of fat, sugarandproteins.That’swhyaspecialextraction the Mastit 4C kit of DNA Diagnostic in combination kit or procedure is recommended, for instance the with the qTOWER³ by Analytik Jena were used. The Mastit 4C Kit by DNA Diagnostic which is perfectly qPCR protocol was adapted to the qTOWER³. optimized for the extraction of bacterial DNA from milk. The extracted nucleic acid can then be detected using the qTOWER³ for quantitative real-time PCR and the Mastit 4C Kit from DNA Diagnostic. The detection kit Mastit 4C Kit detects up to four targets in parallel like Staphylococcus aureus, Streptococcus agalastiae and Mycoplasma bovis and Mycoplasma species and provides an amplification control in addition. Microbioz India, September 2021 Edition | 24

Featured Article Samples and Reagents Sample 5 shows Ct-values for HEX (Staphylococcus  Mastit 4C Kit (DNADiagnostic) aureus), ROX (Streptococcus agalactiae) as well for Cy5  Raw Milk (Dairy farm) (Mycoplasma species). Instrumentation Conclusion  qTOWER³ (Analytik Jena) The resultsof the IAC show, that the amplification of  qTOWER³ Software: qPCR soft3.4 the Mastit 4C Kit in Analytik Jena’s qTOWER³ is working perfectly together. First of all, we resume, Results and Discussion that the whole experimentis valid due to the resultsof Before the values were checked for the different the NTC (No template control)and Positive control. pathogens, the internal amplification control was Furthermore, the Internal Amplification Control is applied to verify the results. The criteria for valid present in all samples so that results of the different results is an Internal Amplification Control (IAC) raw milk samples from cows with symptoms of lower thana Ct-value of 32. Mastitis are positive or negative for the several All samples show Ct-values between 23 and 31 so pathogens. To summarize this experiment the the result of the other targets are acceptable. combination of qTOWER³ (Analytik Jena) and Mastit 4C kit (DNA Diagnostic) could be a solution Samples number 2 and 3 show positive IAC, but are for customers, which want to detect pathogens in negative for all the other channels, resulting in a milk. negative diagnosis. Samples number 1 and 4 show a For more information: positive signal for the ROX channel, resulting in [email protected] contamination with Streptococcus agalactiae, whereas www.analytik-jena.com the signal for sample number 4 is very low. Microbioz India, September 2021 Edition | 25

Featured Article Environment Research & Heavy Metals: A Toxic Relationship What are heavy metals? This potential exposure can then be put into a Heavy metals are naturally occurring elements & toxicological perspective by comparison with the are a group of metals and metalloids that have so-called provisional tolerable weekly intake relatively high density and are toxic even at ppb (PTWI) values for toxic metals, which have been levels. Examples include Pb, As, Hg, Cd, Zn, Ag, established by the Food and Agriculture Cu, Fe, Cr, Ni, Pd, and Pt. Organization of the World Health Organization (FAO-WHO) (De Smet, 1999; WHO, 1981, 1979). Many pharmacopoeias contain heavy metal detection methods that are usually based on color reactions with special reagents such as thioacetamide or diethyldithiocarbamate, and the amount present is estimated by comparison with a standard (WHO, 1988a). Multiple industrial, domestic, agricultural, medical Why carry out heavy metals testing and and technological applications have led to their analysis? wide distribution in the environment; raising Interestingly, small background levels of these concerns over their potential effects on human elements are common in the environment but large health and the environment. amounts of any of them may cause acute or chronic Their toxicity depends on several factors including toxicity (poisoning). This is why regular heavy the dose, route of exposure, and chemical species, metals testing and analysis especially within as well as the age, gender, genetics, and nutritional industry is so important. status of exposed individuals. These metallic elements are considered systemic toxicants that are known to induce multiple organ damage, even at lower levels of exposure. They are also classified as human carcinogens (known or probable) according to the U.S. Environmental Protection Agency, and the International Agency for Research on Cancer. This review provides an analysis of their environmental occurrence, production and use, potential for human exposure, and molecular mechanisms of toxicity, genotoxicity, and carcinogenicity. The potential intake of the toxic metal can be Heavy metal toxicity can result in damaged or estimated on the basis of the level of its presence in reduced mental and central nervous function, lower the product and the recommended or estimated energy levels, and damage to blood composition, dosage of the product. lungs, kidneys, liver, and other vital organs. Microbioz India, September 2021 Edition | 26

Featured Article Hence Abdos has come up with the idea Long-term exposure may result in slowly of Maxi RCF Trace metal-free centrifuge progressing physical, muscular, and neurological degenerative processes that tubes that are free of 18 different Trace mimic Alzheimer’s disease, Parkinson’s disease, muscular dystrophy, and multiple metals. sclerosis. Allergies are not uncommon and repeated long-term contact with  Abdos maxiRCFTM Trace Metal some metals or their compounds may even cause cancer. Free centrifuge tubes are Environmentally Relevant Most manufactured using high purity Hazardous HMs and Metalloids virgin USP Class VI Medical grade Heavy metals are among the most investigated environmental pollutants. polypropylene, conforming to US Almost any heavy metal and metalloid may be potentially toxic to biota FDA 21 CFR, free from natural depending upon the dose and duration of exposure. Many elements are classified rubber & heavy metal. into the category of heavy metals, but some are relevant in the environmental  Abdos maxiRCFTM Trace Metal context. Free Centrifuge Tubes withstand List of the environmentally relevant most toxic heavy metals and metalloids contains Cr, Ni, Cu, 20,000xg RCF. Zn, Cd, Pb, Hg, and As. Heavy metal pollutants most common in the  Pure, Additive Free, Natural environment are Cr, Mn, Ni, Cu, Zn, Cd, and Pb. In 2009, Many reports has suggested four metals, Color Cap for easy labelling and i.e., Cr, Cd, Pb, Hg, and the metalloid As, as the highest priority pollutants for control. Some other Trace Metal free. heavy metals are also hazardous to living organisms depending upon dose and duration of exposure.  Abdos maxiRCFTM Trace Metal For example, Mansouri et al. have found Ag as more toxic than Hg to a freshwater fish. Free Centrifuge Tubes work How Important Is Trace Metals Analysis in excellently in high density gradient Your Specimen Samples? separation of samples We at Abdos realized the fact that collection and transport of your samples have to be organized in  Abdos MaxiRCFTM Trace Metal Trace metal-free collection lab ware. And if a specimen is received in a non-metal-free container, Free centrifuge tubes are abnormal results or false positives will be reported. specifically manufactured to ensure that common trace metals and elements that can interfere with experiments are below an ICP-MS detection level of one part per billion (< 1ppb). Metals included in testing are: Zinc, Iron, Copper, Manganese, Aluminum, Silicon, Nickel, Vanadium, Phosphorous, Cobalt, Chromium, Lithium, Selenium, Cadmium, Mercury, Arsenic and Lead. Scan for more details Author Name: Vinod Joshi Product Manager - International Div., Abdos Labtech Pvt ltd Microbioz India, September 2021 Edition | 27

Business News Thomas A. Fleming, Arctoris Co-Founder & COO, explained “The future of drug discovery is IBM Research and Arctoris computational, with AI and robotics paving the accelerate closed loop way for better treatments to reach patients sooner. drug discovery with AI and We are excited about partnering with IBM Cloud Research on a world-first closed loop drug discovery project bringing together two leaders in Source: IBM Research the field of AI and robotics-powered drug discovery. This collaboration will showcase how I BM Research and Arctoris announced they the combination of our unique technology are investigating the application of AI and platforms will lead to accelerated research based on automation to accelerate closed loop better data enabling better decisions.” molecule discovery. IBM Research has “This collaboration is a great example of the developed RXN for Chemistry, an online platform enablement that AI, Cloud and Automation can have in the space of material design. The leveraging state-of-the-art Natural Language integration between the two complementary technologies reveals how it is more and more Processing (NLP) architectures to automate important in R&D to turn great research into great viable products.” said Dr Teodoro Laino, synthetic chemistry. Representing chemical Distinguished Scientist at IBM Research Europe – Zurich. reactions via SMILES (Simplified Molecular Input Dr Matteo Manica, Research Scientist at IBM Line Entry System), the system is able Research Europe – Zurich, coordinating the project, stated that: “This is a unique opportunity to perform highly accurate reaction to quantify the impact of AI and automation technologies in accelerating scientific discovery. In predictions using its powerful AI. our collaboration, we demonstrate a pipeline to perform iterative design cycles where generative Optimised synthetic routes are then models suggest candidates that are synthesized with RoboRXN and screened with Ulysses. The data used as input for RoboRXN, an produced by Ulysses will then be used to establish a feedback loop to retrain the generative AI and automated platform for molecule improve the proposed leads in a completely data- driven fashion.” synthesis. The collaboration is currently on-going; financial terms were not disclosed. Arctoris has developed Ulysses, an end-to-end automated platform for drug discovery research. The platform ensures accuracy, precision, and reproducibility by leveraging robotic experiment execution and digital data capture technologies across cell and molecular biology and biochemistry/biophysics. Experiments conducted with Ulysses generate more than 100 times more datapoints per assay compared to industry standard, leading to deeper insights and accelerated progress compared to manual methods. The two platforms are now being combined for the first time in a research collaboration that will see new small molecule inhibitors for undisclosed targets being designed, made, tested, and analysed (DMTA) in an autonomous, closed loop approach. Concretely, IBM Research will design and synthesize novel chemical matter (Design, Make), to be profiled and evaluated by Arctoris (Test, Analyze), with the resulting data informing the subsequent iteration of the DMTA cycle. Microbioz India, September 2021 Edition | 28

Microbioz India, September 2021 Edition | 29

Business News Existing approaches to predict developability and identify sequence liabilities that are based on ENPICOM introduces a simple sequence analysis scale well in terms of powerful liability prediction the required computational resources, but do not solution to de-risk antibody provide sufficient accuracy, as they fail to development consider the 3D structure of the antibody. Structural modeling, on the other hand, provides Source: ENPICOM detailed insight into the surface exposure of unwanted motifs, leading to highly reliable E NPICOM, an innovative liability predictions. Performing these bioinformatics software company, predictions in a high-throughput manner is announced today at the Biologics UK incredibly challenging and time-consuming, as it conference new IGX Platform capabilities to requires significant computational resources and accurately annotate exposed liabilities, perform specialized software infrastructure. ENPICOM structural modeling of antibodies at scale, and solves these challenges by integrating SAbPred determine developability profiles using directly into the IGX Platform. SAbPred is customizable penalties. This major development developed by the Oxford Protein Informatics allows researchers to improve their candidate Group and is a validated, peer-reviewed, and selection by making accurate developability globally recognized toolbox for accurate and predictions for thousands of sequences at the efficient structural analysis of antibodies. same time, in a secure, intuitive environment. “The three main challenges in the analysis of “The spectacular progress in the field of antibody liabilities we aim to address are accuracy, discovery calls for more powerful tools to throughput, and ease of use.” commented Dr effectively leverage all generated data. Nicola Bonzanni, co-founder and Chief Product ENPICOM has tackled the challenge of Officer at ENPICOM. “The IGX Platform candidate pool expansion with the launch of the enables researchers to fully utilize the added Antibody Discovery Module earlier this year. The value of NGS data. You can accurately predict new liability analysis capabilities we are adding exposed liabilities for thousands of sequences at today will enable scientists to easily select better once, easily assess the developability of antibodies with even greater confidence”, said candidates, and proceed with your selection with Jos Lunenberg, co-founder and Chief Executive confidence.” Officer at ENPICOM. Feature highlights From thousands of sequences to that needle-in- The new IGX-Annotate App enables scientists a-haystack antibody. to accurately predict exposed liabilities, configure custom liability penalties, and integrate developability information throughout their entire workflow. In addition, researchers can now better gauge antibody developability by comparing characteristics of newly discovered antibody candidates to those already brought to the market. The new Select page provides a flexible environment to compare and rank the most promising antibody candidates based on user- defined characteristics. It brings antibody sequences, experimental metadata, and in silico predictions together into one comprehensive overview, making it easy to select the best candidates to express in the lab or move further down the development pipeline. Microbioz India, September 2021 Edition | 30

Business News Scientists using the IGX Platform can now: • Use a validated tool to independently perform structural modeling analysis and accurately annotate liabilities. • Increase candidate success by flagging exposed liabilities early in the discovery phase and identify antibodies with the best developability properties. • Annotate structural liabilities for thousands of sequences and integrate the developability information throughout their entire workflow. The first issue of PRONEWS focuses on the purpose and passion that drives the team at • Configure their own liability penalties through APCC. The first story in this issue of PRONEWS is about personalized medicine alias an intuitive UI to compute scores that align with precision medicine – which is a treatment of cancer at its molecular profile. Precision their de-risking strategy. Oncology is all set to revolutionize the way Cancer is diagnosed, monitored and treated. • Benchmark candidate developability profiles The other stories describe the medical efficiencies of the medical physics team and the against a database of clinically validated pediatric cancer combined management team. The issue also has three patient case studies antibodies. addressing various types of cancers such as Cytoreductive Surgery and HIPEC gynecologic • Overlay developability characteristics on cancer, proton therapy for breast cancer and the evolving landscape of systemic management of information-rich visualizations like phylogenetic lung cancer. Commenting on the occasion of the launch, Dr trees to prioritize and select the best candidates. Prathap C Reddy, Chairman of Apollo Hospitals, said, “Technology has percolated every industry, The IGX Platform and the Antibody Discovery and one must keep up with the trends to offer best patient care. From the latest technologies Module provide an end-to-end cloud solution and cancer treatments, we’re now revolutionizing the way we update our patients, clinicians, that enables researchers to easily perform partners and followers about new initiatives and the latest developments in cancer care and at complicated tasks such as clustering, phylogeny, APCC, on a regular basis. It gives me great pleasure in launching the India’s first video and prediction of exposed liabilities in a secure newsletter- PRONEWS by Apollo Proton Cancer Centre.” and scalable environment. With the addition of Sharing her thoughts, Dr Sapna Nangia, Editor in Chief of PRONEWS Apollo Proton Cancer these new tools, researchers can now expand Centre, said, “At Apollo Proton Cancer Centre, we tread new ground as the first center in this their candidate pool and improve their antibody part of the world to offer proton therapy. selection. To learn more about performing accurate liability predictions and de-risking antibody development with the IGX Platform, join the free webinar on September 28, 2021. Apollo Proton Cancer Centre Launches India’s First Video Newsletter Source: AP Cancer Centre (APCC), the first Proton Therapy Centre in South Asia & the Middle East, launched India’s first video newsletter – PRONEWS. Aimed at reaching readers with the latest in Cancer care and treatment, PRONEWS will be a quarterly compilation that will educate, empower and elevate the knowledge of its readers. Microbioz India, September 2021 Edition | 31

Business News It’s such an honor to contribute to various life We continue our leadership with site science fields from cardiovascular research to specialized robotic surgery and personalized medicine. We also offer immunology and even groups working with comprehensive cancer care comprising cancer surgery, chemotherapy and image organoids.” – said Kjell Steps, Account Manager guided intensity modulated radiotherapy, administered with compassion and at CytoSMART Technologies diligence. The new format of our newsletter, then, naturally, reflects this The CytoSMART Research Grant in a nutshell: pioneering spirit. It is my pleasure, as the editor-in-chief, to be present at the 1.The applicant can apply for a Lux2, Lux3 FL, launch of the first video PRONEWS, a capsule depicting our passion for and or Omni live-cell imaging microscope. expertise in cancer management.” 2.The applicant will be provided with the After a successful winter initiative, CytoSMART necessary training needed for operating the Research Grant project resumes again device. Source: CytoSMART Technologies 3.The digital microscope can be used for 4-18 CytoSMART Technologies today opened months. the application of CytoSMART Research Grant for 2021 Autumn. The 4.The applicant must be currently registered at an CytoSMART Research Grant is an initiative to help motivated students and researchers improve educational institution or employee of a research their project’s quality. The grant offers one of the CytoSMART live-cell imaging devices that can be group or research institution. used for research purposes for a specified period. The CytoSMART automated incubator-friendly 5.The applicant must perform research that will microscopes are suitable for monitoring cell cultures in any research topic that could benefit highly benefit from using real-time imaging from live-cell imaging. The application period starts on September 6 and will last until October devices. A minimum qualification of an 15, 2021. “We started this initiative at the beginning of undergraduate degree. 2021, and we never thought it could be as successful as I turned out to be. The number of To learn more about the CytoSMART Research applicants and the innovativeness of their research proposals were outstanding. Also, the Grant and application process, visit the official fact that live-cell imaging devices can play such a valuable role in these projects, is an indescribable CytoSMART website. reward for all the efforts we have put into these systems. About CytoSMART CytoSMART Technologies is a specialist in the development and manufacturing of smart microscope systems for life science laboratories. The company was founded in 2012 by a team of biologists and engineers who were convinced that a new generation of miniaturized microscopes, powered by artificial intelligence for image analysis, would allow biologists to make discoveries more efficiently and at scale. In 2018 CytoSMART was selected by Microsoft for its prestigious Scale Up program. CytoSMART’s microscopy solutions are used in research laboratories worldwide. Microbioz India, September 2021 Edition | 32

Business News Viedoc Technologies achieves certification to ISO/IEC 27001:2013 Source: Viedoc Technologies He continues, the ISO certification will benefit our clients by speeding up the auditing process and Viedoc Technologies was recently assuring them of the highest standards in information presented with its ISO/IEC 27001:2013 security, critical in clinical studies. certificate affirming that the company’s Requiring accreditation of vendors is an increasing operation globally, adheres to the trend today. And Viedoc is one of only a few in the internationally recognized standard for industry to fully meet this requirement. The ISO/IEC information security management. The certification certification assures new clients of the highest quality ensures clients worldwide that Viedoc has and level of data security when using Viedoc. implemented processes and procedures for This certificatin is a huge competitive advantage and implementing, maintaining, and continually takes us closer to our ambition of being one of the improving its information security management leading eClinical Suite players in the market, adds system. Mats. We have always been committed to following a high- About Videoc quality and consistent security management system to guarantee all data we process is well protected. But to Viedoc Technologies is an ISO 27001 certified developer of ensure we are doing our best and make it easier for modern cloud-based eClinical systems, founded in Uppsala, our clients to easily verify this, we set out to achieve Sweden. Since its inception in 2003, Viedoc is challenging the the ISO 27001 certification, says Jens Pettersson, standard for conducting clinical trials by creating user-friendly, Chief Information Security Officer. scalable software that complies with the demands of every phase The certification process has enabled us to adopt and of a clinical study – making what matters more accessible. Our implement the applicable requirements for an commitment to working for a healthier world by accelerating all information security management system (ISMS) at aspects of a clinical trial brings therapies to the market faster. As a Viedoc. It includes people, processes, and IT systems result, Viedoc is trusted by 9 of the top 10 pharmaceutical by applying a risk management process, adds Jens. companies, as well as leading research institutions and businesses Obtaining this certification is a recognition and within Biotech, CRO, Medical Device and Consumer health, all promise to our clients that our processes are world- over the world. Visit www.viedoc.com to learn how your Clinical class, says Mats Klaar, CEO. Study can benefit from Viedoc’s eClinical Suite. About the certificate ISO/IEC 27001 is an international standard on information security management. It is known worldwide for providing requirements for an information security management system (ISMS) Microbioz India, September 2021 Edition | 33

Business News IB1001 has a very compelling safety profile, easy oral administration [sachet mixed with water], affirming its very IntraBio Reports favourable risk/benefit profile as a treatment for this devastating disease.” Statistically Significant and Professor Antony Galione, FRS, FMedSci, Statutory Professor of Pharmacology, University of Clinically Meaningful Oxford commented, “GM2 Gangliosidosis (Tay- Sachs and Sandhoff disease) is a devastating disease Improvements in the Use that has never had any available treatment. We are very excited that IB1001 is the first drug that is of IB1001 for Treatment of effective for this disorder and will improve the lives of so many patients and their families. Given what GM2 Gangliosidosis (Tay- is known about IB1001’s mechanism, and its multiple successful clinical trials, we will continue Sachs and Sandhoff to investigate this drug for other rare genetic neurological diseases and for more common disease) neurodegenerative diseases prevalent in society with large unmet medical needs.” Source: IntraBio In a joint statement, Rick Karl, President of the Cure Tay-Sachs Foundation and Dan Lewi, Chief IntraBio Inc today announced positive data Executive Officer of the Cure Action for Tay-Sachs from its multinational clinical trial of IB1001 Foundation, commented: “This treatment is a (N-acetyl-L-leucine) for the treatment of major breakthrough for the GM2 Gangliosidosis GM2 Gangliosidosis (Tay-Sachs and Sandhoff community that includes Tay-Sachs and Sandhoff. disease). It is the first drug to offer hope to the patients and IB1001 demonstrated a statistically significant and families affected by these devastating diseases. clinically meaningful improvement in symptoms, They are progressive, life-threatening conditions functioning, and quality of life in both the primary with no approved medicinal treatments. There is and secondary endpoints for pediatric and adult an urgent need for this effective treatment to be patients with GM2 Gangliosidosis. approved and made available for patients in our The trial met its primary endpoint, the Clinical community before the window of therapeutic Impression of Change in Severity (CI-CS), which opportunity is lost.” was assessed by blinded, centralized raters (professors of neurology with expertise in movement and neurological disorders). The trial also met secondary endpoints including the Scale for the Assessment and Rating of Ataxia (SARA), the Modified Disability Rating Scale (mDRS), the Investigators’, Caregivers’, and Patients’ Clinical Global Impression of Change (CGI-C) assessment. IB1001 was observed to be safe and well-tolerated, with no drug- related serious adverse events. “The results of this study are hugely important for the GM2 community,” said Dr. Susanne Schneider, Principal Investigator and Professor of Neurology from Ludwig Maximilian University of Munich. “IB1001 is the first drug to demonstrate a statistically significant and a clinically meaningful effect for the treatment of GM2 Gangliosidosis. Microbioz India, September 2021 Edition | 34

Business News The positive results of this IB1001-202 study are reinforced by the efficacy and safety profile of IB1001 already demonstrated in IntraBio’s successful IB1001- 201 study for Niemann-Pick disease Type C (NPC). As is the case in the IB1001-202 clinical trial for GM2 Gangliosidosis, IB1001-201 was the first clinical trial to demonstrate statistical significance and a clinically meaningful effect in patients with NPC. These results provide further momentum for the broad clinical development program the employees of Sakura. They are the key to the strong brand Sakura Finetek Europe is today. I will planned for IB1001 which will address high unmet focus on extending our solid culture of innovation, teamwork, and customer centricity to be able to medical needs for treatment of both rare and empower pathology professionals, now and in the common neurological disorders. future.’ Chris Koeman, General Manager at Sakura Mateo Iglesias Vice Finetek Europe: ‘We look forward working together with Mateo. We believe he has the experience and drive to President Marketing & enable the ambitious plans Sakura has. His progressive and human approach is what makes him the ideal candidate to Sales Sakura Finetek help us bring Sakura to the next level.’ More about Sakura Finetek Europe Europe At Sakura Finetek Europe we advance cancer diagnostics by providing integrated solutions for Source: Sakura Finetek anatomic pathology and patients through best-in- class innovations, quality and customer care. This Sakura Finetek Europe appointed Mr. Mateo is how Sakura became the original manufacturer of Iglesias as Vice President of Marketing & Tissue-Tek®, Cyto-Tek®, Tissue-Tek VIP® and Sales EMEAI. Mateo starts September 1st Tissue-Tek Xpress®, today’s industry standards. and will be responsible for all marketing and sales With headquarters based in Alphen aan den Rijn activities for Sakura’s fast-growing markets. (NL) and seven regional locations in Europe we Mateo has over 20 years of experience with empower pathology professionals in the whole (bio)medical companies. For the last fifteen years, EMEAI region. For more information visit he worked for Agilent Technologies, as Associate www.sakura.eu, follow us on LinkedIn, or contact Vice President EMEAI. His proven leadership us via [email protected]. capabilities and marketing & sales experience will be a massive benefit in this new role. Focus on people and culture The new Vice President is honoured and thrilled of his appointment and has a clear vision: ‘I believe in Microbioz India, September 2021 Edition | 35

Product Showcase Silicone tubing especially designed for dairy industry! Milk contributes more than 60 per cent Our Platinum Cured transparent silicone Tubing of the total livestock production and known for its ultra-smooth bore to prevent any accounts for nearly 67.69 per cent of particle entrapment, reduces the chances of the value of the output of the livestock sector’s butterfat occurrence and it can also help to contribution to the national GDP. To alleviate eliminate the probability of Microbial growth the labour involved in milking, much of the within the milk transfer line and ensures smooth milking process has been automated but still they transfer of milk. face many challenges during milk processing in dairy Industry which leads to loss of money, loss Features and Benefits of time, loss of quality and much more. 1. Superior Flexibility, Kink Resistance First and foremost, kink resistance is very properties. important - In Dairy Industry kink resistance 2. Clear Transparency allows easy visual properties plays a vital role as kinking can happen Inspection of Milk during process. when a cow stucks in tubing or it moved around 3. Smooth bore to ensure less during Installation which can cause leaking and contamination and resists butterfat build-up. loss of milk - A huge messss!!! 4. Water repellent properties allow easy cleaning and complete soakaway. Secondly, Tubing must be weather resistance so 5. Excellent Weather resistance properties. that it doesn’t become stiff especially during 6. Non-toxic, non-haemolytic. winter season as stiffness can lead to delay in 7. Free of plasticizers like production since it takes much time and becomes phthalate/Bisphenol-A very difficult during installation. 8. Higher Shelf life Also Tubing should be flexible but still retains its 9. Free of any heavy metals and hazardous elasticity of feeding retention and not become substances. too easily stretched out. Additionally, tubing 10. Sterilisable by using different techniques must have tear resistance ability as it can be like autoclaving, Ethylene oxide, Gamma torned on / off feedings, dropped on floor or a radiation. cow steps on it that’s why tubing with tear 11. Dimension range 1mm ID – 3000mm resistance ability very crucial to avoid constant ID dimensionally accurate & excellent repair. workmanship and finish It also must have resistance to milk fat 12. Customized Colour, dimension and absorption which can attract dirt and negatively hardness available on demand. infect hygiene as milk fat build-up softens the 13. Good flex fatigue resistance enhances tubing and reduces its strength or even cause Milking peristaltic pump life & Milking discoloration. Dosing Pump Life. After examining all this challenges and to overcome it, we at Ami Polymer Pvt Ltd come- Major Applications up with one stop solution and here we are Introducing Platinum Cured Silicone Tubing 1. For Raw milk transfer. which ensures milk processing or transfer of milk 2. For Bulk milk transfer. must be safe, hygienic and high performance. 3. For Rotary Milking Parlour line. Platinum cured silicone Tubing is designed for 4. For Milking Dosing Pumps. the application in Automatic milking system / 5. For Milking Peristaltic Pumps. rotary milking parlour/ robotic milking / Peristaltic Pumps. Microbioz India, September 2021 Edition | 36

Product Showcase Physical Properties. Authored by: Simran Singh Designation – Sr. Executive International Sales & Marketing Compliances About Amipolymer Pvt Ltd: Manufactured and packaged in clean room of class 10000 facility audited by TUV Nord. AMI POLYMER PVT. LTD., Established in 1998 at Silvassa in FDA 21 CFR 177. 2600 Dadra and Nagar Haveli, is leading Exporter of silicone tubes, USP CLASS VI silicone gaskets in India. AMI POLYMER PVT. LTD. is one of Trade TSE/BSE FREE India's verified and trusted sellers of listed products. With their PHATHALATE FREE extensive experience of supplying and trading Platinum Cured ROHS COMPLIANCE Silicone Bi Color Tube/ Color Coded, AMI POLYMER PVT. LTD. DMF #26201 has made a reputed name for themselves in the market with high quality Platinum Cured Silicone Bi Color Tube/ Color Coded, \"The Company believes in “Be in business with Silicone Corks & Stopper etc. Focusing on a customer centric ethics” and assure Quick Development, approach, AMI POLYMER PVT. LTD. has a Pan-India presence Fastest Delivery, Ultimate Quality and also very and caters to a huge consumer base throughout the country. Buy Competitive Rates\" silicone tubes in bulk from AMI POLYMER PVT. LTD. at Trade India quality-assured products. Visit us at www.amipolymer.com Take a sneak-peak look at our advanced facility AV https://www.youtube.com/watch?v=V51mA1nOYQM. Feel the best ever purchasing experience with Ami Polymer Pvt Ltd- GET An OFFER NOW! Email: [email protected] / [email protected] Microbioz India, September 2021 Edition | 37

Product Showcase All You Need to Know About the Zebrafish Model in Biomedical and Applied Research Zebrafish (Danio rerio) are increasingly used Predation pressure led to the development to address key questions raised in basic of shoaling behaviour, believed to reduce and applied research including, but not stress and aggression among fish held in limited to, biomedicine, toxicology, small groups. Of course, while conditions environmental science, biotechnology and in the wild can vary considerably, attempts aquaculture.1 Zebrafish have proven well-suited have been made to provide stable to large-scale genetic screening, whether in husbandry conditions in laboratory search of models for human disease or for settings. It is important to emphasise that when control mechanisms related to natural or pathological differentiation of cells and tissues, implementing lessons from fish in their natural studies which are more difficult to carry out in habitats, some caution is warranted: laboratory mammalian model organisms because of their strains have been maintained in research facility long in-utero gestation periods. aquaria for at least 25 years (c. 100 generations). A long list of established zebrafish models aids in understanding the mechanisms behind diseases, During this time, diverse adaptations and and novel toxicology models have been domestication steps have arisen, for example developed for endocrine disruptor studies. Many concerning mechanisms of sex determination. In clinically relevant biochemical pathways are addition, a vast quantity of internet-based conserved between fish and human, but cannot resources is available to aid both beginners and be reliably investigated in vitro, in unicellular more experienced researchers using the zebrafish organisms, or in invertebrates. model (zfin.org). Worldwide, more than 1000 laboratories use zebrafish as a research model (zfin.org). In Europe, the tightly interconnected zebrafish scientific community consists of more than 350 laboratories (eufishbiomed.eu) that would benefit from guidelines for standardised husbandry conditions at the European/international level. The guidelines provided here are meant to constitute a framework for European zebrafish research groups, and a basis and reference point for future welfare relevant studies. The biology of zebrafish Zebrafish are native to South Asia where they are found in streams, ponds and other slow-flowing water bodies including rice fields. The range of environmental conditions under which zebrafish live includes water bodies with temperatures ranging from below 10℃ up to 40℃, clear or turbid water, pH from 6 to just below 10, conductivities from 10 to 271 µS/cm, depth from surface level down to 60 cm, a wide range of bottom substrates (primarily silt), presence or absence of vegetation and elevations ranging from sea level to over 1500 m altitude (Figure 1). Microbioz India, September 2021 Edition | 38

Product Showcase Figure 1. Temperatures and pH levels measured Two recent international surveys on zebrafish at 35 natural zebrafish habitats at altitudes husbandry practices from over 100 facilities in between 14 m and 1576 m above sea level (blue five continents showed that parameters like dots). Ranges recommended for zebrafish physical housing, nutrition, pathogen status, housing systems (pH 6.5–8 and 24–29℃; green water conditions and holding densities can be area) and values commonly referred to in highly variable. literature being optimal for reproduction (pH In addition, international zebrafish resource 7.4–7.5 and 28℃; red circle) are indicated. centres and several single facilities have recently published husbandry procedures that lay the The Directive 2010/63/EU groundwork for educated discussions for a The 3Rs (Refinement, Reduction and gradual standardisation of zebrafish protocols. Replacement) are an intrinsic part of the EU Although less common in earlier literature, there Directive 2010/63 on the protection of animals is now an increasing trend towards including used for scientific purposes and apply to all non- detailed information about the husbandry human vertebrate animals, including parameters used in studies in the Materials and independently feeding larval forms (Article 1). Methods section of publications. With the notion However, fish are not elaborated on and specifics that parameters like feeding, temperature, dark– for zebrafish are not provided at all. This light period etc. may affect results from motivates the work on common European experimental research, it is recommended to guidelines for ensuring sound husbandry and always include a detailed description of the high standards of welfare for zebrafish. zebrafish husbandry parameters used. Important A key issue within the Directive is the time point factors for dissemination of experiences and when fish larvae can be regarded as skills are national/regional/international training independently feeding and free-living, thus initiatives with theoretical and hands-on courses. falling under the scope of the legislation. The The major application of Zebrafish in development of poikilothermic animals is Biomedical Research involved in: temperature dependent, and for zebrafish this Recommendations for housing and critical time point is 120 hours post fertilisation husbandry (hpf) at 28.5℃. The guidelines provided here address and suggest International exchange of experience and recommendations for: transportation and best practices reception, safe introduction into facilities, During the last few years, dedicated husbandry housing systems and environmental conditions sessions have become mandatory at international (temperature, dark–light cycle, water quality, zebrafish conferences.6 stocking density, environmental enrichment, feeding), breeding, identification and nomenclature as well as sanitisation of equipment. View larger version Transportation and reception Exchange of fish between laboratories usually poses three main challenges: organising safe shipment of fish, ensuring compliance to fish welfare as well as to national and international legislations, and finally avoiding spreading pathogens between laboratories. For genetically modified zebrafish lines, regulations related to a transgenic or genetically modified organisms (GMO) biosafety and restrictions must also be fulfilled. If available, documentation of health monitoring and relevant husbandry parameters used for the originator population should precede the shipment. Microbioz India, September 2021 Edition | 39

Product Showcase Quarantine for biosecure introduction of Stocking density new strains/fish Embryos hatch around 60 hpf and settle over the After safe reception of embryos or fish, the next bottom of the Petri dish/tank until roughly 5 challenge is to avoid the spread of potential days post fertilisation (dpf) when the swim pathogens into the main section of a facility. bladder has developed sufficiently to allow swimming. Body mass, rather than numbers of While egg surface disinfection (bleaching) animals, sets the limits for fish/l density strongly improves biosecurity, it does not suffice recommendations. Thus, the density of juveniles to safeguard against dissemination of intracellular can be higher than the corresponding figures pathogens. It is strongly recommended to keep given for adults. and breed newly imported animals under Environmental enrichment quarantine containment to limit the risk of In general, observing normal behaviour patterns pathogen dissemination into the main facility. and the absence of any signs of illness or stress Water and housing systems among the fish suggests that well-being is Decades of experience have proven that maintained. Two commonly used laboratory maintaining zebrafish is a relatively measures for animal welfare are reproductive straightforward task. In most cases, commercially success and plasma (or water) cortisol levels. available tank systems are used, which come fully Changes in the D–L cycle, water conditions (e.g. integrated with filter systems, germicidal rise in ammonia levels) or presence of parasites irradiation (UVC) and light and temperature (e.g. nematodes) are associated with reduced egg control units. production. Temperature Feeding Fish are poikilothermic and the zebrafish is a It is generally accepted that a combination of live tropical species (although many natural habitats feeds and processed dry feeds improves growth, are temperate, Figure 1). The commonly used generation time and reproductive performance, references to developmental stages relate to hpf all positive indications of well-being. Dry feed determined by the speed of development at diets are generally assumed to be nutritionally 28.5℃. Temperature influences water chemistry complete, whereas live feed and the associated and animal physiology. fish prey-capture behaviour have an enrichment Dark–light cycle effect. Formulated diets simplify feed delivery, In nature, light conditions vary with seasons and storage and preparation. weather. Modern laboratory facilities present the Breeding, identification, nomenclature fish with a static dark–light (D–L) cycle Among the attributes that make the zebrafish a (commonly 10 hours dark, 14 hours light, great model species is its high fecundity. A female optionally with gradual decrease and increase in can spawn hundreds of eggs per single mating. It light intensity mimicking dusk and sunrise). is however recommended to set up fish for Water quality spawning with a recovery period of at least one Depending on the local water supply used for week to allow for sufficient regeneration and recirculating water systems, some laboratories maturation of new ova. can use tap water without major amendments. Sanitisation of equipment and hygiene Chlorine still needs to be removed, as levels safe A clean environment is essential for maintaining for humans (c. 0.1 mg/l) are toxic for fish. a high standard of animal health and welfare. Constant stirring and aerating of the water for 24 hours prior to use is sufficient to remove For more information: chlorine, whereas water sanitised with Girish Nair chloramine (which is less volatile) needs to be Founder, Director filtered through active charcoal. Biolinx India Pvt Ltd In most facilities, the water chemistry needs to be [email protected] adjusted before use. Microbioz India, September 2021 Edition | 40

Microbioz India, September 2021 Edition | 41

Product Showcase High-Throughput Mannose Glycans Screening of Crude and Purified mAb and Non-mAb Protein Sample – Sartorius Octet® GlyM Kit You can Download application note on Mannose Glycans Content Screening for Human-mAb Samples Using the Octet® GlyM Kit. G lycosylation, an important post- Reliable data at this early stage supports shorter translational modification, is a key lead times and prevent later failures. Assay critical quality attribute (CQA) that Workflow the GlyM Kit utilizes mannose specific influences product safety and efficacy and should lectin which is immobilized onto the biosensor be monitored when developing new biological surface (Figure 2). This surface binds to mannose drugs. Among various glycan structures, mannose structures in the sample. is especially important as it affects a protein’s plasma The secondary amplification steps increase the clearance and binding signal from protein of interest (POI) and reduces its in negates the minimal signal from host cell proteins vivo half-life, (HCPs). This increases assay sensitivity, facilitating negatively the analysis of crude cell culture samples without impacting drug the need for purification or enzymatic digestion. efficacy. This essentially eliminates the need for any sample preparation beyond a dilution step, simplifying the While process mannose screening workflow for users. conditions, Additionally, the GlyM Kit reduces time to results media and feed and increases sample analysis throughput. As a formulations result, 96 clones can be screened in under 1 hour are critical on the Octet® RH96 system. factors in the optimization of protein mannosylation, optimal cell line selection can be a limiting step; early screening for mannose content can facilitate the selection of clones that produce proteins with favorable glycan profiles during cell line development (CLD). The Octet® GlyM Kit enables high-throughput mannose content screening in crude cell culture samples during early clone selection stages in the CLD process. When combined with titer analysis, it expedites the selection of the top performing cell lines producing proteins with the most favorable glycan (mannose) profile (Figure 1). Only clones which are the most suitable will move downstream for further optimization. Microbioz India, September 2021 Edition | 42

Product Showcase The GlyM Kit comes with the biosensors and The Octet® GlyM Kit is designed to provide cell reagents required to screen mannose content in up line development and upstream bioprocessing to 96 samples and is compatible with Octet® groups with a ready to use kit for the rapid relative systems with at least 4 channels. Relative Mannose mannose content screening of both purified and Content Screening the GlyM Kit enables the cell harvest antibody samples. Unlike traditional screening and ranking of crude samples based on techniques, the Octet® platform can also monitor the relative mannose content in the POI. The kit other functional critical quality attributes (CQAs). provides ranking results for samples with mannose content that differs by 4% or more (Figure 3, see The ability to view and choose from desired titer samples with 3% vs. 8% and 10% vs. 14% Mannose and mannose levels at the same time provides more content). Users can assign all screened clone in-depth knowledge that facilitates more informed samples into groups depending on the mannose decisions in the early selection of optimal clones content (e.g., high, medium or low) and focus during cell line development.In this application further development effort on the desired group of note, a novel approach for relative mannose clones only. Data Analysis Octet® Analysis Studio content screening and ranking of human software combines titer data with mannose content monoclonal antibody (mAb) samples is showcased; data for more in-depth analysis that facilitates using a well characterized mAb from the National selection of the best clones. Institute of Standards and Technology (NIST) as well as samples developed at Novartis. Source: Octet RED384 System (sartorius.com) Mannose Glycans Content Screening for Human- mAb Samples Using the Octet® GlyM Kit Microbioz India, September 2021 Edition | 43

Pharma News Dr Reddy’s gets DCGI gesture to lead stage 3 trial of Sputnik Light in India Dr Reddy’s Laboratories was granted approval by the drugs regulator to conduct Phase III trials of single- dose COVID-19 vaccination Sputnik Light. According to Hindustan Times, the subject expert committee (SEC), of the Central Drugs Standard Control Organisation CDSO (CDSO), had recommended to the Drugs Controller General of India(DCGI) that approval be granted to conduct Bridging Studies in India in order to support Sputnik Light. RDIF has partnered up with Dr. Trials in the United States at that time were paused on reports of rare blood clots. Reddy’s Labs in order to distribute the first The drugmaker’s withdrawal comes as India 250,000,000 doses of the Russian vaccination tackles legal challenges with manufacturers over indemnity issues, with its junior health minister and conduct the necessary trials in India for saying last week that a team had been formed to engage with vaccine makers. regulatory approval. “This team is in continuous dialogue with Pfizer, Moderna and Johnson & Johnson to discuss and address In July, the Subject Expert Committee of various issues including the issue of indemnity,” Bharati Pravin Pawar had said. CDSCO had denied authorisation for emergency Johnson & Johnson and the Central Drugs Standard Control Organisation (CDSCO) did use to Sputnik-Light. This ruling ruled out the not immediately respond to Reuters’ requests for comments on why the company withdrew its necessity of conducting the phase III Russian application. As of July 31, Johnson & Johnson is yet to vaccine trial in the country. request a full approval for its shot with the U.S. FDA, while Pfizer Inc , BioNTech SE, and India says Johnson and Moderna Inc have already sought full approval of their vaccines with the FDA. Johnson pulls out proposal In India, the drug regulator had given emergency use authorisation to Moderna’s vaccine in June. for quick COVID-19 vaccine approval Source: Reuters India’s drug regulator said on Monday that Johnson & Johnson withdrew its proposal seeking accelerated approval of its COVID- 19 vaccine in the country, without giving additional details. The U.S.-based company had said in April it was seeking an approval to conduct a bridging clinical study of its Janssen COVID-19 vaccine candidate in India. Microbioz India, September 2021 Edition | 44

Microbioz India, September 2021 Edition | 45

Pharma News Aleor Dermaceuticals gets USFDA gesture for generic antibacterial gel Source: PTI Drug firm Alembic Granules India and Pharmaceuticals on Monday said Jubilant Cadista Recall its joint venture Aleor Products in US Market Dermaceuticals has received approval from the US health regulator for generic Metronidazole Source: PTI gel, used in the treatment of inflammatory lesions Granules India and Jubilant Cadista, two generic of rosacea. drug manufacturers, are recalling several goods in Aleor Dermaceuticals Ltd has received final the United States, the world’s largest market for approval from the US Food & Drug medicines, for various reasons. According to the Administration (USFDA) for its abbreviated new latest Enforcement Report issued by the US drug application (ANDA) for Metronidazole gel Food and Drug Administration (USFDA), USP, 1 per cent, Alembic Pharma said in a Granules India’s US-based unit is recalling over regulatory filing. 1.14 crore Naproxen Sodium tablets, a non- The product is a generic version of Galderma steroidal anti-inflammatory drug used to treat Laboratories LP”s Metrogel gel 1 per cent, it pain, menstrual cramps, and inflammatory added.According to IQVIA, Metronidazole Gel, diseases such as rheumatoid arthritis, gout and USP 1 per cent, has an estimated market size of fever. USD 29 million for twelve months ending June 2021, Alembic Pharma said. The product is indicated for the topical treatment of inflammatory lesions of rosacea. Aleor had previously received tentative approval for this ANDA, it added. The company has a cumulative total of 149 ANDA approvals (132 final approvals and 17 tentative approvals) from USFDA, Alembic Pharma said. Shares of Alembic Pharmaceuticals were trading at Rs 783 per scrip on BSE, up 1.10 per cent from its previous close. PTI AKT BAL Microbioz India, September 2021 Edition | 46

Pharma News According to USFDA, the company’s US-based Aurobindo Pharma gets USFDA gesture for unit is recalling the affected lot due to ‘Current malignancy treatment injection Good Manufacturing Practice (CGMP) Source: PTI deviations’. Drug firm Aurobindo Pharma on Friday The affected lot has been manufactured at said its arm Eugia Pharma Specialities has received approval from the US Granules India’s Telangana-based plant. The lot health regulator for Cyclophosphamide injection, used in the treatment of several types of cancer. has been distributed in the US by New Jersey- The company”s subsidiary “Eugia Pharma Specialities Ltd has received a 505(b)(2) NDA based Granules USA, Inc, the report stated. approval from the US Food & Drug Administration (USFDA) for its Granules initiated the Class II voluntary recall on Cyclophosphamide Injection 500 mg/2.5 mL and 1 g/5 mL vial,” Aurobindo Pharma said in a 11th August this year. regulatory filing. The product will be available in ready-to-use As per USFDA, a Class II recall is initiated in a injection preparation, it added. “The product shall be launched in the US market situation in which use of, or exposure to, a in the near term and will be manufactured in Eugia”s manufacturing facility in India,” violative product may cause temporary or Aurobindo Pharma said. medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote. USFDA further said US-based Jubilant Cadista Pharmaceuticals Inc is recalling 14,544 bottles of Donepezil HCL Tablets, which is used to treat mild to moderate dementia in Alzheimer’s disease. The company is recalling the affected lot due to it being ‘subpotent,’ it added. Jubilant Cadista Pharmaceuticals is a fully-owned subsidiary of Cadista Holdings Inc, which is a part of the Noida-based Jubilant Life Sciences Company. The affected lot has been produced by Jubilant Generics in India and marketed in the US by Salisbury-based Jubilant Cadista Pharmaceuticals, Inc. Jubilant commenced the Class III recall in the US on 20th August 2021. As per USFDA, a Class III recall is initiated in a ‘situation in which use of, or exposure to, a violative product is not likely to cause adverse health consequences.’ According to industry estimates, the US generic drug market was estimated to be around USD 115.2 billion in 2019. It is the largest market for pharmaceutical products. Microbioz India, September 2021 Edition | 47

Pharma News According to IQVIA, the approved product has an addressable market size of USD 170 million for the twelve months ending June 2021, it added. Cyclophosphamide Injection is indicated for malignant lymphomas, multiple myeloma, leukemia, mycosis fungoides, neuroblastoma, adenocarcinoma of the ovary, retinoblastoma and carcinoma of the breast, the filing said. This is the 19th product to be approved (including 3 tentative For this purpose, a joint venture company shall approvals) for Eugia. Aurobindo now has a total be incorporated with an aim to enter the respiratory biosimilars space. of 482 abbreviated new drug application (ANDA) approvals (453 final approvals and 29 Under the terms of the agreement, the joint tentative approvals) from the USFDA, it added. venture will leverage Cipla and Kemwell’s complementary strengths for end-to-end product Shares of Aurobindo Pharma were trading at Rs development, clinical development, regulatory 709 per scrip on BSE, up 1.56 per cent from its filings, manufacturing and commercialisation of biopharmceutical products. Cipla’s respiratory previous close. PTI AKT BAL prowess combined with Kemwell’s expertise in BAL biologics will accelerate bringing these essential products to market. Cipla and Kemwell Umang Vohra, Managing Director & Global Chief Executive Officer of Cipla, said: “This Biopharma announce development reinforces our strength as leaders in respiratory therapy and is in line with our aspiration of execution of a joint venture global lung leadership. Guided by our purpose of ‘Caring for life’ our partnership with Kemwell will help serve agreement for developing, unmet needs of patients across the globe.” Anurag Bagaria, Chairman and Chief Executive manufacturing and Officer of Kemwell, said: “We are very excited commercialising about combining the strengths of Cipla’s expertise in development and commercialisation biosimilars of respiratory products and Kemwell’s biologics capabilities. Through this JV, we aim to make Source: Cipla cost-effective biotherapeutics available to more patients globally.” Cipla Limited (BSE: 500087 | NSE: CIPLA EQ, hereafter referred to as “Cipla”), a leading global pharmaceutical company and Kemwell Biopharma Private Limited, a leading biopharmaceutical Contract Development and Manufacturing Organisation (CDMO), announced execution of a joint venture agreement to develop, manufacture and commercialise biosimilars for global markets. Microbioz India, September 2021 Edition | 48

Microbioz India, September 2021 Edition | 49

Guest Post Mack PharmaTech: Devoted to excellence, care, safety & A Matchless Solution for Environmental Testing F ound in 1999 by group of visionary MACK PharmaTech having Young, dynamic, professionals, MACK PHARMATECH talented, pool of professionals engaged in is a vision translated into reality. Founders experience, expertise & vision in the field of Showcasing wide range of products in domestic as Pharmaceutical Equipment rendered Mack well as international market and continues to PharmaTech to be the youngest face to emboss the promote brand awareness. mark in India and abroad. MACK PharmaTech provides complete set of We are relentlessly engrossed in benchmarking our documentation including the following: product and services against globally recognized quality standards. Mack PharmaTech as one of the  Design Qualification (DQ) leading Manufacture & supplier of Laboratory  Installation Qualification (IQ) equipment in India & international market in  Operational Qualification OQ) accordance with GMP guidelines. All the  Performance Qualification (PQ) equipment manufactured by us are as per FDA, GMP regulation & ICH guideline. Mack offer the following service backup for all Laboratory Equipment’s: We add one more feather in our cap by being 1st company in India to provide CE (Compliance to European Standard) certified lab equipment. All equipment’s are PLC controlled with Safety, Automation, Password Protection, and Event Recorder & Data Acquisition. 21 CFR Part 11 Compliance software for monitoring & Recording of data from Chamber at your computer. We are an ISO 9001:2015 organization certified by BSI for the scope of Design, Manufacture and Servicing of Environmental testing equipment of Pharmaceutical industry & Laboratory. We are serving to the sectors like Pharmaceutical, Food, Chemical, Medical, Government Research Institutes and Other industries. Mack even successfully implant their footprints in more than 20 countries across the Globe in territories like Asian, South East Asia, Gulf, West Africa, Canada etc. Mack always committed our standards & ethics with all integrity. In discharging our responsibilities, we never prefer professional or ethical shortcuts. Microbioz India, September 2021 Edition | 50