Pharma Machines & Technology Magazine-vol 16 - 2022 by Pharma Machines

Vol - 16 / Issue - 5 / Dec 2021 - Jan 2022

Common mistakes while answering questions in INSPECTION Microbiology meets AI: Pushing the boundaries of pharmaceutical science

How Automation-Digitalization-Communication in uenced and improved Product-Packaging-Labelling

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Vol - 16

Issue - 5

Dec 2021 - Jan 2022 PUBLISHER & EDITOR

Dear Pharma Pals,

Harjit Singh Dhaul

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Artificial intelligence is increasingly becoming an important component of microbiology within the pharmaceutical field. Researchers, microbiologists, laboratorians, and diagnosticians are interested in artificial intelligence based testing and analysis. The article by Dr. Tim Sandle looks at some recent applications of artificial intelligence, taking place in 2021, within microbiology and as applied to pharmaceuticals.

Printed & Published by: Harjit Singh Dhaul on behalf of Global Vision and printed at Hariom Printers, C/70, Akurli Industrial Estate, Akurli Road, Kandivali East, Mumbai 400 101, and published at 26-B, Rebellow Cottage, Gaon Devi Road, Poinsur (E), Kandivli 400 101. Editor Harjit Singh Dhaul.

Being of the prime importance to pharmaceutical companies, regulatory inspection creates a tense environment both for the persons working at floor level as well as higher management and company's owners. This tense environment usually becomes a primary reason for mistakes being made either in execution of activities or while answering questions to an auditor during the course of inspection. In the article in this issue by Dhavalkumar Surti, we will understand the reasons for mistakes being made while answering questions to an auditor.

DEPUTY EDITOR Byju Bhaskaran

Harjit Singh Dhaul

CONTENTS

EDITORIAL ASSISTANT Ravlin Kaur

Publisher & Editor

EXCLUSIVE

Common mistakes while answering questions in inspection Dhavalkumar Surti pinpoints the mistakes and the reasons

MATERIAL PROCESSING • Global expertise in material processing technologies

REVIEW

Articles

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Microbiology meets AI: Pushing the boundaries of pharmaceutical science Dr. Tim Sandle does it again with this article

How Automation-DigitalizationCommunication influenced and improved Product-Packaging-Labelling Article by veteran packaging professional Prabir K Das

INFOCUS CONDOR 300: Contemporary, high-speed tube filler

Regulars INDIA PHARMA 8 GLOBAL PHARMA 12 DID YOU KNOW? 16 TECH NEWS 66

INDIA PHARMA

API sector seen three-fold increase in investments India's active pharmaceutical ingredients (API) sector has seen a three-fold increase in investments in 2021 compared with a year ago. Three private equity-led investment platforms have been created specifically targeting the API space, while at least half a dozen transactions are in various stages of negotiations, according to bankers and fund managers.

India pharma to grow 9-11% in 2021-22 According to ratings agency ICRA, the Indian pharma industry is estimated to grow at 9-11 per cent in 2021-22 and in the next few quarters. Revenue growth was moderate at 6.4 per cent in the second quarter of FY22, down from 16 per cent in the first quarter of 2021- 22. The normalisation of the base and pricing pressures in the US market were the major reasons for slowing growth momentum in Q2 FY22, even as growth under domestic and emerging markets remained healthy. While the US business is expected to remain muted, in the domestic market, a combination of steady normalisation in hospital footfalls and field force operations, given the relatively lower restrictions on account of Covid-19, continued traction in acute therapies and better pricing supported healthy revenue growth across companies.

ICMR designs kit to detect Omicron in 2 hours The Indian Council of Medical Research (ICMR) in Dibrugarh, Assam, has designed a testing kit that will be able to detect the virus in two hours time. It was a real concern for the authorities to quickly detect the variant. It used to take three to four days time to detect the Omicron variant with the help of the kits currently available in the market. The hydrolysis probe-based real-time RT-PCR assay for detection of the new Omicron variant (B.1.1.529) SARS-CoV-2 (COVID-19) can detect the new variant within 2 hours. The kit is now being produced on a bulk basis by a 100 per cent made in India, a Kolkata-based company, GCC biotech on a public-private partnership (PPP) model.

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Dec 2021 - Jan 2022

These include Carlyle Group's $300-million platform with former Mylan India CEO Hari Babu, Advent's $400-million platform with RA Chem and Hong Asia-focused PE firm PAG's $200-million platform with Samara Capital and CX Partners. M&A and PE transactions in API space more than doubled during 2021 to $800 million compared with $293 million in 2020 and just $30 million in 2019. According to EY, API constitutes more than one-third of the overall M&A activity in the pharma space in 2021.

Centre to encourage research in pharma sector The central government is formulating a policy to encourage research in pharmaceutical sector for patented drugs, and is also trying to widen the reach of generic medicines, Union Health Minister Mansukh Mandaviya has said. "The government has eased the policy for research in the pharmaceutical sector, and the time taken for giving permission to a company to carry out research has been reduced. But the country should not limit itself to manufacturing generic medicines, it should also conduct research and sell patented drugs to the world market," he said. "One out of four generic tablets taken in the US, and one out of six in the world, is manufactured in India. We are making generic medicines available to the world, and we are ourselves consuming branded medicine to increase our treatment cost," he said, adding that the Centre's schemes will encourage use of generic medicines in the country.

INDIA PHARMA

All set to roll out cheapest coronavirus drug

Drug maker forays into diagnostics

Mankind Pharma is all set to launch the cheapest molnupiravir, the Covid-19 antiviral drug, at 35 per capsule. The full treatment of Molulife (brand name) is expected to cost 1,400.

Drug maker Lupin has announced the launch of its diagnostics business in India as part of diversification. The company launched operations with 11 labs including a 45,000 square feet national reference lab in Navi Mumbai and 200 collection centres in West and East India.

The recommended dose of the molnupiravir is 800 mg twice a day for five days. A patient needs to take 40 capsules of 200 mg dosage form. The oral pill will be manufactured by 13 Indian pharmaceutical companies including Torrent, Dr Reddy's, Mylan and Hetero. The drug is approved for restricted use under emergency situation for treatment of adult patients who have a high risk of progression of Covid-19. Molnupiravir developed by MSD and Ridgeback Biotherapeutics was approved by the UK Medicines and Healthcare products Regulatory Agency (MHRA) and USFDA for the treatment of mild-to-moderate Covid-19 at high risk of developing severe disease. In the coming days Cipla, Sun Pharma and Dr Reddy's Laboratories will also be launching molnupiravir capsules.

Orphan drug status for novel malaria drug Zydus Cadila's antimalarial drug ZY19489 (MMV253), currently in development together with Medicines for Malaria Venture (MMV), has received orphan drug designation from the USFDA. The orphan drug status makes the potential drug eligible for certain development incentives, including tax credits for qualified clinical testing, prescription drug user fee exemptions and sevenyear marketing exclusivity upon USFDA approval. ZY19489 is a novel antimalarial compound active against all current clinical strains of P. falciparum and P. vivax, including drug resistant strains. The Phase I study of the drug has demonstrated long half-life and potential for a single-dose cure for malaria. ZY19489 is a potent, first in class molecule, originally discovered and elaborated in India.

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Dec 2021 - Jan 2022

The drug maker plans to open over 100 labs and 1000 collection centres across India in the next three years. About 90% of collection centres will be run by franchisees. Lupin said it wants all its labs to be NABL accredited within 18 months of their launch. Lupin labs would not just be offering routine diagnostic tests, but specialty ones such as a range of tests such as molecular diagnostics, cytogenetics, flow cytometry, microbiology, serology, histopathology, immunology, hematology, among others.

Snapdeal to promote 'National Health ID' programme E-commerce platform Snapdeal has said the company is leveraging its pan-India reach, especially across smaller cities and towns, to promote the National Health Authority's 'National Health ID' programme. The company will leverage its digital presence including the website, mobile application, and social media accounts to increase awareness about the scheme and offer information on how users can create their own Health ID. As part of this initiative, Snapdeal is initially running a series of banners to provide information about the benefits of the scheme and providing a link to the NHA's page where they can generate their Health ID. The information will also be shared through Snapdeal's social media properties in English, Hindi and in other Indian languages. In an increasingly digital world, easy access to digital health records will be of immense use to citizens.

admission or mortality and for whom substitute Covid-19 therapy options are not available or suitable clinically. As per the EUA, 800mg molnupiravir every 12 hours for five days should be given soon after detecting Covid-19 and within five days of symptom development. The FDA EUA is based on results from the Phase III MOVe-OUT clinical trial of molnupiravir in adult individuals with Covid-19 in the non-hospital setting. Findings showed that the pill lowered hospitalisation or mortality risk with 6.8% subjects treated with molnupiravir were hospitalised or died versus 9.7% in the placebo arm. Fast track designation to Alzheimer's therapy USFDA has granted fast track designation to Eisai and Biogen's experimental drug, lecanemab, to treat early Alzheimer's disease (AD). An anti-amyloid beta (Aβ) protofibril monoclonal antibody, lecanemab also obtained breakthrough therapy status from the FDA in June this year. It specifically attaches to soluble, toxic Aβ aggregates, thereby neutralising and removing them. These protofibrils are claimed to lead to the neurodegenerative process in AD. In December 2007, Eisai gained international rights from BioArctic to develop, produce and commercialise lecanemab for AD. Eisai collaborated with Biogen to develop and market lecanemab later in March 2014. Breakthrough therapy and fast track status from the FDA aids in speeding up the new drug development for serious ailments with an unmet medical need, such as AD. According to data from the Phase IIb trial, lecanemab offered a greater Aβ plaque reduction and showed clinical decline across various goals. EUA for oral Covid-19 antiviral molnupiravir USFDA has granted Emergency Use Authorization (EUA) for Merck (MSD) and Ridgeback Biotherapeutics' oral antiviral, molnupiravir, for adult patients with mild to moderate Covid-19. The treatment is intended for use in patients who are at greater disease progression risk, including hospital

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Dec 2021 - Jan 2022

In the placebo arm, nine cases of deaths were noted with one in the molnupiravir arm. Diarrhoea, nausea and dizziness were the most common side effects linked to molnupiravir reported in the trial. To develop nanosized Covid-19 antibodies BiondVax Pharmaceuticals has entered definitive agreements with the Max Planck Society and the University Medical Center Göttingen in Germany to develop and market novel Covid-19 nanosized antibodies (NanoAbs). Under the proposed collaboration, nanoAbs will also be developed for various other ailments with greater market sizes that use their unique binding affinity, stability at increased temperatures and potential for a convenient mode of administration. NanoAbs have a higher affinity to the target, neutralising SARS-COV-2 virus in-vitro at levels that are 100 times lower than those needed by existing monoclonal antibodies. This could offer improved effectiveness, fewer adverse events and permit reduced production expenses. The reduced size and hyper-thermostability at 95°C of NanoAbs could aid inhaled administration, extended shelf life and avoid the requirement for cold chain storage and shipping. Furthermore, NanoAbs have shown robust neutralisation of key viral variants including Alpha, Beta, Gamma and Delta at reduced concentrations in in-vitro studies.

EUA for Covid-19 oral antiviral Paxlovid USFDA has granted an emergency use authorization (EUA) for Pfizer's oral antiviral Paxlovid to treat mild-to-moderate Covid-19 in adults and paediatr ic individuals aged 12 years and above. The oral drug is indicated for patients who are at increased risk for advanced to severe disease, including hospital admission or mor tality. Paxlovid comprises nirmatrelvir that hinders the SARS-CoV-2 main protease (Mpro) required by the virus for replication and ritonavir, which decelerates the breakdown of nirmatrelvir. The treatment is given as two tablets of nirmatrelvir and one tablet of ritonavir together twice a day for five days. The EUA is based on results from the Phase II/III EPIC-HR clinical trial of Paxlovid in high-risk adult Covid-19 patients in the non-hospital setting . Further Phase II/III trials are underway in adult participants at standard risk of disease progression as well as those exposed to Covid-19.

To develop and manufacture bispecific antibody ImmuneOncia Therapeutics has signed an MoU with WuXi Biologics to develop and manufacture bispecific antibody, IOH-001. As part of the collaboration, the company will use WuXi Biologics' integrated ser vices in cell culture development, bioassay development, cell line development, and biologics manufac turing to develop the bispecific antibody that tar gets PD-L1 and CD47. Additionally, WuXi Biologics will help the company on the IOH-001's CMC studies for Investigational New Drug (IND) application. Chinese biologics technology platform, WuXi Biologics provides end-to-end solutions to support companies to discover, develop, and produce biologics from concept to commercial manufacturing.

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Dec 2021 - Jan 2022

.Therapy for severe asthma treatment USFDA has granted approval to AstraZeneca and Amgen's Tezspire (tezepelumab-ekko) as an add-on maintenance therapy for severe asthma in adults and paediatric individuals of the age 12 years and above. Tezspire is a human monoclonal antibody that potentially hinders the activity of thymic stromal lymphopoietin ( TSLP), an epithelial cytokine. The approval comes after the FDA granted priority review for application seeking approval for Tezspire and is based on data from the PATHFINDER trial programme. The filing also comprised data from the Phase III NAVIGATOR trial where the Tezspire plus standard treatment showed superiority across all primary as well as key secondary goals in severe asthma patients versus placebo.

Approval to CMA variation for antiviral Veklury The European Commission (EC) has granted approval to the Conditional Marketing Authorization (CMA) variation for Gilead Sciences' antiviral Veklury (remdesivir) to include adult Covid19 patients who do not need supplemental ox ygen and are at greater disease progression risk. A nucleotide analog discovered by Gilead, Veklury is the standard of care to treat Covid-19 hospitalised people. The approval comes after the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) provided a positive recommendation to expand the indication for the treatment. In July last year, Veklury obtained CMA from the EC to treat Covid-19 in adults as well as adolescents of the age 12 to 18 years with pneumonia needing supplemental oxygen. The EC based its decision on data from a randomised, placebo-controlled, double-blind Phase III trial.

DYK

DID YOU KNOW? Indian pharma and healthcare industry has supplied 60 per cent of the global Covid-19 vaccine requirements. AstraZeneca-Serum are currently the main suppliers to COVAX, a worldwide initiative aimed at equitable access to Covid-19 vaccines. Pfizer's drug Paxlovid, a combination of antiviral drugs nirmatrelvir and ritonavir tablet is most awaited in the world. WHO leads the collective “United Against Rabies” to drive progress towards "Zero human deaths from dogmediated rabies by 2030. Over the past three years, millions of blood pressure pills that contain a probable carcinogen have been recalled around the world. Of the 118.5 million blood donations collected globally, 40% of these are collected in high-income countries, home to 16% of the world's population. A growing number of infections – such as pneumonia, tuberculosis, gonorrhoea, and salmonellosis – are becoming harder to treat as the antibiotics used to treat them become less effective. Researchers have estimated that each year there are 1.3 to 4.0 million cases of cholera, and 21 000 to 143 000 deaths worldwide due to cholera. An estimated 295,000 newborns die within 28 days of birth every year, worldwide, due to congenital anomalies – heart defects, neural tube defects and Down syndrome. Diarrhoeal disease is the second leading cause of death in children under five years old. Each year diarrhoea kills around 525 000 children under five. WHO estimates that 296 million people were living with chronic hepatitis B infection in 2019, with 1.5 million new infections each year. Every year there are an estimated 20 million HEV (hepatitis E virus) infections worldwide, leading to an estimated 3.3 million symptomatic cases of hepatitis E. Cervical cancer is the fourth most common cancer among women globally, with an estimated 570,000 new cases in 2018. In 2020, there were an estimated 241 million cases of malaria worldwide. The estimated number of malaria deaths stood at 627 000 in 2020. Meningitis remains a major global public-health challenge with a high case fatality rate and leading to serious long-term complications. Mercury is considered by WHO as one of the top ten chemicals or groups of chemicals of major public health concern.

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Dec 2021 - Jan 2022

ARTICLE

Regulator y Inspection

Common mistakes while answering questions in

INSPECTION In this speci c article we will understand about common mistakes made by personnel facing audit while answering questions asked by auditors during a regulatory inspection.

Regulatory inspection is important to pharmaceutical companies doing business in regulated market and inspection by auditors is an important tool by which related country's food and drug administration ensures that the drug products supplied to their

18 PHARMA machines & technology

By Dhavalkumar Surti

respective countries are meeting the required standards and are safe to use for their citizens.

remains a tense aﬀair for everyone whether or not he/she is involved or not involved in an audit.

Being of the prime importance for the company's business, regulatory inspection creates a tense environment both for the persons working at oor level as well as higher management and company's owners. No one wants to make mistake nor wants to be a reason for failure during regulatory inspection. Hence an inspection

And this tense environment usually becomes a primary reason for mistakes being made either in execution of activities or while answering questions to an auditor during the course of inspection. In this article, we will understand the reasons for mistakes being made while answering questions to an auditor.

Dec Sep -2021 Oct 2021 - Jan 2022

ARTICLE

Regulator y Inspection

1. First common mistakes is, 'To start answering even before question is completed by an auditor'. So what actually happens is that, an auditor asks a question and the person responsible to provide answer starts his answer even before the auditor completes his question. This happens usually because we assume the entire question just based on pre x of question, we assume the possible question based on our experience, or based on our common understating about speci c topic or based on knowledge gained by common inspection trends within industry. However, even with all good intention about giving a correct answer to the auditor, this is not a correct way to answer. The correct way to answer is rst to allow the auditor to complete his question. Auditor may have some diﬀerent thoughts in his/her mind while asking a speci c question, which may not be the usually asked question. So the best way to answer a speci c question is to rst listen the entire question, and then start with your answer. 2. Second common mistake is, 'To answer the question without completely understanding the question'. This happens because of basic human nature to immediately answer the question without any delay to show our preparedness, our readiness, our willingness to answer all questions asked by auditors during a regulatory inspection to create a very good image of company, show best intent of company to provide

20 PHARMA machines & technology

prompt answers, to provide detailed information in order to display about knowledge, our abilities and capabilities. It is agreed that our intentions are correct, but we need to be patient and rst understand the question, understand what is being asked. You can take a 3 to 5 seconds time/pause to understand and digest the question completely. There is nothing wrong in taking this valued time to understand the question, it is better to take some time to understand the question and give correct answer rather than answering question in a hurry just to display our promptness and provide with an incorrect answer which will cause more harm than taking some time to answer. As a company, we are not willing and we don't want to provide incorrect information to an auditor. We are doing correct things in our daily activities within company and we need to convey the same to auditor that our procedures and practices are adequate and in compliance to products meeting the acceptance criteria. In order to do that, it is important to understand the question before we provide with our answer.

Dec 2021 - Jan 2022

3. Third common mistake is, 'Assumption about question and answering to our assumption rather than answering to question'. So what actually happens that based on our experience, we assume that the question is being asked because of a speci c reason. This assumption comes through our previous experience, based on our interactions with industry friends about common queries during regulatory inspections. In such scenario, we answer to our assumption about the question rather than to actual question being asked. Probably auditor might not have said anything about intent of the question, but we assume that, this speci c question is being asked because of some speci c reason, and auditor wants to get some information which is not directly relevant to question, auditor wants to dig out something. We think that auditor has something else in his/her mind and we try to justify that assumption, and while doing so, we end up answering to assumption rather than the question. Ultimately, this results in providing a non-relevant

ARTICLE

Regulator y Inspection

or incorrect answer and auditor may not like and may think we are wasting time by not providing the required answers, we are trying to hide the real information. The key to avoid this situation is to don't answer based on your assumption, even don't assume anything. Simply provide 'To the Point' answer to the question being asked by rst listening to the full question and understanding the question completely. 4. Fourth common mistake is, 'Providing too much of information while responding to question'. For example, if the auditor asks 'Do you have a SOP (Standard Operating Procedure) for handling of incidents/deviations?', the simplest and to the point answer to the question is 'YES', because every company has a SOP for handling of incidents/deviations/nonconformities. The terminology may be diﬀerent, the title may be diﬀerent, but SOP for handling deviations is always available. But what people do mistake while answering such question is that they start with an elaborative answer stating that, “Yes, we have a SOP, we have very good SOP, SOP title is this, in SOP we have de ned how to handle deviations thoroughly, we have de ned categories of deviations based on criticality, the criticality is de ned based on impact on product. We have de ned critical, major and minor categories of deviation based on impact assessment. We are handling incidents thoroughly, we log incident on same day it happens, we immediately start

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investigation, etc., etc.”

To summarize, the below points must be kept in mind while answering questions during regulatory inspection:

Such detailed information is practically not asked by the auditor, he/she had only asked about • Allow the auditor to complete having a SOP for handling of the question deviations/incidents and simple answer to that question is either • Understand the question before 'Yes' or 'No'. Provide that answer and you start your answer wait for next question. • Don't answer 'To your Of course, we have to provide the assumption' about question information asked by auditors, but don't give too much of information • Provide 'To the Point' and 'Speci c' answer to the question, in response to question which is don't provide 'Too much of not even asked by auditor. Even the Information' which even auditor load of information is not will not appreciate. demanded by auditor, they don't want to waste their time or your Hope this article will help you to time in getting the information understand about answering the which is not required by them. They questions during a regulatory will ask further questions if more inspection in order to have a information is required, and as a successful outcome for both good practice, we should wait for company as well as auditors. more questions rather than volunteering the information which will not help auditor or company. Auditors have very limited time to complete the inspection and we should not waste the time by providing the details which are not asked, giving the lengthy, timeconsuming answers which are not helping auditors and not even required by them. Auditors want speci c information and we should comply with that requirement without wasting time of either one. We should understand that as a company we are not doing anything wrong in our daily practices and we follow good business ethics and this baseline understanding should always be kept in mind. We need not be too much worried about what will happen if we remain speci c and to the point.

Dec 2021 - Jan 2022

Dhavalkumar Surti has more than 18 years experience in injectable manufacturing, validation, quality assurance and new facility projects. He is with pharmaceutical industry in India from 2003, working with reputed companies like Dr. Reddy's, Sun Pharmaceuticals, Zydus Pfizer Oncology, Emcure Pharmaceuticals and Aculife Healthcare. He has core experience in aseptic technique, freeze drying, sterilization validation, smoke studies, SOP writing, investigations, training and media fills.

ARTICLE

Microbiology

Microbiology meets AI: Pushing the boundaries of pharmaceutical science By Tim Sandle Arti cial intelligence is increasingly becoming an important component of microbiology within the pharmaceutical eld. Researchers, microbiologists, laboratorians, and diagnosticians are interested in arti cial intelligence based testing and analysis. This is for a variety of reasons, connected to drug analysis, pinpointing microbial weaknesses, improving the turnaround time, quality, and costs of testing, and so on. In addition, arti cial intelligence has aided the prediction of drug targets, diagnosing microorganisms causing infectious diseases, classifying drug resistance against antimicrobial medicines, predicting disease outbreaks and exploring microbial interactions. Perhaps of greatest signi cance is where researchers are using machine learning algorithms for optimization of the best treatment indications for developing new medicines and as information sources to monitor and document the quality and impact of pharmaceuticals interventions. This review article looks at some recent applications of arti cial intelligence, taking place in 2021, within microbiology and as applied to pharmaceuticals.

Bacterial sensors to improve mental health Microbiome research, which has advanced through the development of microbial sequencing methods, has paved the way for novel drug treatments (1), with inference drawn from arti cial intelligence. High-

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throughput sequencing technology has resulted in generation of an increasing amount of microbial data and this requires the application of approaches like machine learning to interpret it. For example, future treatments for gastrointestinal diseases and disorders such as irritable bowel

Dec 2021 - Jan 2022

syndrome, in ammatory bowel disease and slow transit constipation, among others, have been advanced through advances in computational research and machine learning (2), both supervised learning and unsupervised learning. Many of these are types of personalised (or

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ARTICLE

Microbiology

'precision') medicines, targeting for speci c patients or smaller groups of patients rather than being targeted for the population at large. Furthermore, it has been established for several years that the bacteria living in the gut can synthesize some of the neurotransmitters (chemicals that transmit signals from nerve cells to target cells), that are responsible for a person's nerves, anxiety, and euphoria. An imbalance of the bacterial population, in relation to the types of species, leads to changes with the levels of hormones and consequently a person's mental health can suﬀer. For example, 95 percent of the hormone serotonin is synthesized by bacteria in the gut. Serotonin is the key hormone that stabilises a person's mood, feelings of wellbeing, and happiness. This hormone enables brain cells and other nervous system cells to communicate with each other. Serotonin also plays a role in relation to sleeping, eating, and digestion. Researchers at McKelvey School of Engineering at Washington University in St. Louis have demonstrated how genetically

engineered bacteria that can monitor chemical production from inside a person's gut and x any imbalances (3). This is based around engineering bene cial bacteria, in the form of a probiotic, speci cally aimed at protecting people from the negative health eﬀects of adrenaline surges. Probiotics are live bacteria and yeasts promoted as having various health bene ts. The monitoring of the imbalance was established through the development of a "bacterial sensor" that can detect certain chemicals in a person's gut. The sensors detect variations in temperature, pH, oxygen levels, light, pollutants and other disease-related chemicals, each of which can signal the eﬀects of a bacterial imbalance. An

ARTIFICIAL INTELLIGENCE Applications for the Clinical Microbiology

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example is with genetically engineered Escherichia coli Nissle 1917 (EcN). E. coli strain Nissle 1917 (trade names Muta or® or ECN) is a Gramnegative microorganism with probiotic properties that has been successfully used for the treatment of intestinal in ammation, especially in patients suﬀering from ulcerative colitis. Through the use of arti cial intelligence, with the recent study, it was possible to develop computer modelling to explore how mutations would aﬀect the pathway's sensitivity. Through this, the researchers were able to develop a sensor pathway that was sensitive to the molecules they were interested in (and for the sensor to be speci c only to the molecules of interest). With the EcN sensor, the modi ed bacteria become “precision hunters”. Taking a genetic disease example, the organisms can discriminate between phenylalanine and tyrosine, which are two structurally similar molecules associated with the disorders like type 2 tyrosinemia. For the neurotransmitter application, the objective is that when the levels are too high, the bacteria will produce

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ARTICLE

Microbiology

an enzyme that degrades the target chemical. Conversely, if it is too low, the bacteria produce an enzyme that can synthesize more of the neurotransmitter. Developing drugs to reduce bio lms on drug delivery systems When investigating the key proteins in bio lms of the fungus Candida albicans, to understand how the proteins control, how the organism resists antifungal drugs as well as how the proteins aid the dispersal of the fungus throughout the human body, researchers pinpointed the sticky, armour-like structures that build a bio lm matrix (4). The bio lm acts to encase clusters of disease-causing organisms, providing protection from antifungal drugs. Such research is of pharmacological importance, given that there are no approved antimicrobials to treat bio lms. The only way to treat a bio lm is to physically remove it from the body.

sensitive fungal mutants remained susceptible to uconazole, reducing fungal populations down by 30-fold or more. An additional signi cance is that because bio lms shape the lifecycle of the organisms contained within them, body-wide dispersal is The researchers used a machinedecreased by reducing the scope of learning algorithm to screen the bio lm and the types of Candida through hundreds of proteins to contained within the slime-like identify likely candidates involved in structures. This arises since the bio lm production and function. identi ed proteins also play Through the analysis, the scientists identi ed 63 proteins to investigate complex roles in bio lms (5). further. The investigations involved Detecting disease likelihood developing Candida mutants that Insights into how bacterial proteins were unable to make speci c work as a network to take control of Candida is an enigmatic organism. proteins. This stage revealed 13 human cells could help predict The fungus often makes its home in variants of the fungus became infection outcomes and develop and on healthy people, to no ill more susceptible to the antifungal new treatments. Pathogenic effect. However, it can readily infect uconazole. Following laboratory bacteria use miniature molecular immunocompromised individuals. studies, animal models to test drug The newly identi ed proteins from syringes to inject speci c agents resistance were created using the research provide potential drug (called effectors). These injections rodents and venous catheters. are often made into the cells that These catheters, inserted into large keeps the gut healthy. These veins, are often left in place for effectors take control of our cells, months to help deliver drugs, such overwhelming their defences and as during chemotherapy treatment. blocking key immune responses, Because they spend a long time in allowing the infection to take hold. the body, catheters are prone to becoming sources of infection, and Researchers at Imperial College London and The Institute of Cancer hence the catheter was of importance in terms of bio lms and Research, London have studied drug delivery systems. Through the whole sets of effectors in different combinations. These involved rat models, four of the 13 drug-

28 PHARMA machines & technology

targets to impair a pathogen's antimicrobial defences. The study demonstrated that Candida could not make some of these proteins were much more sensitive to the existing antifungal uconazole.

Dec 2021 - Jan 2022

ARTICLE

Microbiology

experiments conducted using mice infected with Citrobacter rodentium, which injects 31 effectors (the bacterium is a mucosal pathogen of mice that shares several pathogenic mechanisms with enteropathogenic E. coli). The results show how effectors work together as a network, allowing them to colonise their hosts even if some effectors are removed. The investigation also revealed how the host's immune system can bypass the obstacles the effectors create, triggering complementary immune responses. The researchers suggest that knowing how the makeup of effector networks in uences the ability of infections to take hold could help design interventions that disrupt their effects. This leads the research team to predict how a cell will respond when attacked by different combinations of bacterial effector proteins. Such insights will help scientists to better understand how cells, the immune system and bacteria interact, and this can be applied to understanding and pharmacologically treating diseases

like cancer and in ammatory bowel disease. These are diseases where bacteria in the gut play an important role. During the experiments, the research group was able to remove different effectors when infecting mice with the pathogen, tracking how successful each infection was. This showed that the effector network produced by the pathogen could be reduced by up to 60 percent and still produce a successful infection.The researchers collected data on more than 100 different synthetic combinations of the 31 effectors. These data points were used to build an arti cial intelligence algorithm.The AI model was able to predict the outcomes of infection with C. rodentium expressing different effector networks, which were tested with experiments in mice (6). As it is impossible to test in the lab all the possible networks that 31 effectors can form, employing an arti cial intelligence model is the only practical approach to studying biological systems of this complexity. Such combinations

would not be obvious from our experimental results alone, opening the possibility of using arti cial intelligence to predict infection outcomes. Moreover, going forwards the data can be built upon by other researchers with an interest in using arti cial intelligence and synthetic biology. This will be useful in allowing microbiologists to ascertain which cell functions are essential during infection. In turn, this will enable future scientists to nd ways to ght the infection not by killing the pathogen with antibiotics, but instead by changing and improving our natural defence responses to infection. Machine learning to identify likelihood of gene transfer as an antibiotic resistance mechanism One of the primary mechanisms for antibiotic resistance is the consequence of the ability of bacteria to pass genes to each other through horizontal gene transfer. To attempt to exploit any weakness in this process, Cornell University researchers used

ARTIFICIAL INTELLIGENCE

30 PHARMA machines & technology

Dec 2021 - Jan 2022

www.pharmachsystems.com www.osdpharmachsystems.com

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Contacts: +91 98678 39902 / +91 96190 07977

ARTICLE

Microbiology

machine learning to sort organisms by their functions and use this information to predict how genes are transferred between them. This is an approach that could be used to reduce the spread of antibiotic resistance (7).

is micro uidics, which involves moulding polymer chips to create The association between microscopic channels for the microorganisms and precise manipulation of uids. The pharmaceutical processing is not second technology is cell-free always about nding ways to kill protein synthesis, this takes only cells, for valuable compounds can those crucial pieces of biological be extracted from microorganisms machinery required for protein This is through understanding and used within biotechnological production and combines them which organisms bacteria were processing. An example is with into a soupy extract that can be exchanging and hence to unravel enzymes, the protein molecules used to create enzymes the driving factors that implicate comprised of chains of amino acids synthetically, without requiring organisms in this transfer. By that act to speed up, or catalyse, the living cells to serve as incubators. gaining a deeper insight into how conversion of one kind of molecule this happens could lead to the (substrates) into another (products). Since the vast amount of data that development of drugs to control HT-MEK generateswould require In so doing, enzymes enable these processes. For this, machine many months to process at a time, reactions such as digestion and learning was used to assess bacteria fermentation to happen far more computational approaches and genomes and their various machine learning algorithms are quickly and hence allow functions in order to identify therapeutic compounds of value to being developed in parallel. These signatures that indicate the types of be produced to scale. are designed to deduce an bacteria that were swapping genes enzyme's complicated 3D shape With enzymes, details surrounding from its amino acid sequence alone. and the form of the networks of how their forms connect to their exchange. To do so took several Since each tiny chamber within the functions, and how they function machine-learning models in order with such extraordinary speed and HT-MEK contains only a thousandth to assess different phenomena of a millionth of a litre of material, embedded in a vast array data. The speci city, are still not well the scientists can engineer understood. To gain an insight, output enabled the researchers to thousands of variants of an enzyme scientists from the University of identify multiple networks of in a single device and study them in different antibiotic resistance genes, Stamford have developed a technique called High-Throughput parallel. By tweaking the DNA and across strains of the same instructions in each chamber, they Micro uidic Enzyme Kinetics (HTorganism. The model was tested can modify the chains of amino MEK) (8). This technique allows out on bacteria isolated from soil, acid molecules that comprise the thousands of enzyme experiments plants, and humans. enzyme. In this way, it's possible to to be performed simultaneously. The research succeeded in nding systematically study how different The process deeply probes beyond that the network of bacterial gene modi cations to an enzyme affect the small "active site" of an enzyme exchange -- speci cally for its folding, catalytic ability and where substrate binding occurs, to antibiotic resistance is predictable. ability to bind small molecules and reveal clues about how more This means by examining the other proteins. It is hoped the HTdistant parts of enzymes work genomes of pathogens, predictive MEK process will accelerate an models can be constructed. This together to achieve their reactivity. approach to drug development includes antibiotic resistance One application of HT-MEK is to termed allosteric targeting, which transfers between humanaims to increase drug speci city by associated bacteria and pathogens explore bacteria, speci cally engineered bacteria designed to targeting beyond an enzyme's that have yet to be observed. This produce a particular enzyme. This is active site. Enzymes are popular should researchers to select a through HT-MEK combining two pharmaceutical targets because of speci c antibiotic, depending what existing technologies to rapidly the key role they play in biological is observed in a speci c patient's gut. speed up enzyme analysis. The rst processes. However, some enzymes

32 PHARMA machines & technology

Extracting compounds of value

Dec 2021 - Jan 2022

ARTICLE

Microbiology

are considered "undruggable" because they belong to families of related enzymes that share the same or very similar active sites and targeting them can lead to side effects. The idea behind allosteric targeting is to create drugs that can bind to parts of enzymes that tend to be more differentiated, like their surfaces, but still control particular aspects of catalysis. HT-MEK may even allow scientists to reverseengineer enzymes and design bespoke varieties of their own. This shares parallels with the application of arti cial intelligence in other elds of pharmaceutical science. For example, AI can assist in structurebased drug discovery by predicting the 3D protein structure because the design is in accordance with the chemical environment of the target protein site, thus helping to predict the effect of a compound on the target along with safety considerations before their synthesis or production.

Summary This article has presented ve applications of arti cial intelligence and the subset machine learning to the eld of microbiology, citing examples that are, or have the potential to, reshape pharmaceutical production. In each case, the underlying driver is to the use of automated algorithms to perform tasks which traditionally rely on human intelligence. Through this new or faster insights can be made, and these can be used to either speed up drug discovery, or disease diagnosis, or to nd faster means to combat pathogens in the fast-changing situation of antimicrobial resistance. Future treatments for gastrointestinal diseases and disorders such as irritable bowel syndrome, in ammatory bowel disease and slow transit constipation, among others, have been advanced through advances in computational research and machine learning, both supervised learning and unsupervised learning. References 1. Wilder, C., Sandle, T. and Sutton, S. (2013). Implications of the Human Microbiome on Pharmaceutical Microbiology, American Pharmaceutical Review, 16 (5): pp17-21 2. Vicentini, F., Keenan, C., L. et al. Intestinal microbiota shapes gut physiology and regulates enteric neurons and glia. Microbiome, 2021; 9 (1) DOI: 10.1186/s40168-021-01165-z 3. Rottinghaus, A., Xi, C., Amrofell, M. et al. Engineering ligand-speci c biosensors for aromatic amino acids and neurochemicals. Cell Systems, 2021; DOI: 10.1016/j.cels.2021.10.006 4. Abd El-Baky RM, Sandle T, John J, Abuo-Rahma GE, Hetta HF (2019) A novel mechanism of action of ketoconazole: inhibition of the NorA eﬄux pump system and bio lm formation in multidrug-resistant Staphylococcus aureus, Infection and Drug Resistance, 12: 1703-1708 5. Zarnowski, R., Noll, A., Chevrette, M. et al. Coordination of fungal bio lm development by extracellular vesicle cargo. Nature Communications, 2021; 12 (1) DOI: 10.1038/s41467-021-26525-z

Tim Sandle is the author of the book Digital Transformation and Regulatory Considerations for Biopharmaceutical and Healthcare Manufacturers, Volume 1: Digital Technologies for Automation and Process Improvement, available via the PDA Bookstore: https://www.pda.org/bookstore/pro duct-detail/5897-digitaltransformation-volume-1

34 PHARMA machines & technology

6. Ruano-Gallego, D., Sanchez-Garrido, J., Kozik, Z., et al. Type III secretion system eﬀectors form robust and exible intracellular virulence networks. Science, 2021; 371 (6534): eabc9531 DOI: 10.1126/science.abc9531 7. Yarmarkovich, M., Marshall, Q., Warrington, J. et Cross-HLA targeting of intracellular oncoproteins with peptide-centric CARs. Nature, 2021; DOI: 10.1038/s41586-021-04061-6 8. Markin, C., D. Mokhtari, A., Sunden, F. Revealing enzyme functional architecture via high-throughput micro uidic enzyme kinetics. Science, 2021; 373 (6553): eabf8761 DOI: 10.1126/science.abf8761

Dec 2021 - Jan 2022

EXCLUSIVE

IDEX India is a leading manufacturer of highly engineered industrial products and technologies under the wellknown brand names of Fitzpatrick, Matcon, Micro uidics, Quadro and Steridose.

I am proud to know that every day we live the IDEX philosophy of 'Trusted solutions improving lives', helping our customers to create eﬃcient, eﬀective manufacturing systems that provide life-saving and lifeenhancing pharmaceuticals to our nation.”

We believe our success comes from relentless focus on our vision and values and the fact

DHIRAJ PANDIT

is Managing Director of MPT Asia responsible for supporting customers in Asia region

36 PHARMA machines & technology

that we care about the “how” as much as the “what”, as we lead and run our businesses.

Dec 2021 - Jan 2022

IDEX India

Global Expertise in Material Processing Technologies IDEX India is a subsidiary of the IDEX Corporation which was founded in 1987 and has become a global leader in applied solutions, with presence in ve continents, and more than 6,800 dedicated employees helping customers around the world. The products produced by the companies in the corporation touch our “We are able to not only provide customers with global products and system solutions, but we also have the autonomy to design and develop solutions that are speci c to our local

lives every day - whether it's a life-saving rescue operation, creating lifeenhancing pharmaceuticals or fuelling aircraft, IDEX is a leader in creating enabling technology used in many of the most common everyday activities. “We believe our success comes from relentless focus on our vision and values and the fact that we care about the “how” as much as the “what”, as we lead and run our businesses.” The team in India is based in a world class facility of 1,50,000 sq ft in Savli, Vadodara, India. The facility incorporates a highly eﬀective, teamoriented environment that integrates design, engineering,

market and local

manufacturing, administration, and the industry's latest technology. “We

customer requirements.”

are able to not only provide customers with global products and system solutions, but we also have the autonomy to design and develop solutions that are speci c to our local market and local customer requirements.” The team comprises front-end sales, technical and service team who are highly quali ed. They are fully supported and networked with their colleagues located around the world, which helps everyone to keep in touch with not only the local needs, but global trends too. IDEX has a network of channel partners who further help it to support its local customers. IDEX team is just a call away – 1800 267 9955 (toll free).

37 PHARMA machines & technology

Dec 2021 - Jan 2022

EXCLUSIVE

Fitzpatrick and Quadro introduce one of the world's most advanced milling and screening platforms The SLS – Scalable Lab System™ is a unique benchtop laboratoryscale powder milling and screening platform that provides ve powder processing solutions from one base unit. Oﬀering conical milling, hammer milling, high energy milling and screening technology, this is an ideal platform for reliable and repeatable testing, as well as for research within an R&D lab or start-up.

38 PHARMA machines & technology

Dec 2021 - Jan 2022

When it comes to scalable milling and powder processing technology, IDEX MPT technology is hard to beat. With solutions for the labscale investigative stage, the proof-ofconcept stage and full-scale production, there is a compatible solution that will grow with your company's success.

Milling & Screening

SLS – Scalable Lab System™

When it comes to scalable milling and powder processing technology, IDEX MPT technology is hard to beat. With solutions for the labscale investigative stage, the proof-of-concept stage and fullscale production, there is a compatible solution that will grow with your company’s success. The SLS – Scalable Lab System™ is a unique benchtop laboratoryscale powder milling & screening platform that provides ve powder processing solutions from one base unit. Offering conical milling, hammer milling, high energy milling and screening technology, this is an ideal platform for reliable and repeatable testing, as well as for research within an R&D lab or start-up. When it comes to scaling up and proof of concept work, the newly launched Mid-Size SDx™ Series affords provides the easiest path from research & development through to full production. Offering multiple milling and screening technologies on a single, common drive it offers a cost effective, space saving solution to commercial scale up. The Mid-Size SDx™ improves on-target PSDs by 30 – 50% over similar technologies. It is the rst conical mill and security screener with a greaseless gearbox in the pharmaceutical milling industry that safeguards batches for enhanced operator and product safety. Proprietary Comil® screen designs can improve processing efficiencies over comparable equipment. And now, with the introduction of the patented high-efficiency screens – capacity throughput can be increased by up to 50% and milling temperatures lowered by as much as 30%, depending on product and equipment set-up. This cutting-edge technology on a single common drive affords effective, reliable, efficient & scalable powder processing technology.

Mid-Size SDx™ Series

Production-Scale SDx™ Series

The Production-Scale SDx™ Series platform offers three distinct powder processing solutions on one common drive, providing the ability to easily transfer between conical milling, security screening and hammer milling, improving production efficiency and removing bottlenecks. Once again this platform has a greaseless gearbox offering reassurance of performance. All the platforms use SMARTdetect™ Technology which instantly recognizes the head being installed and automatically makes the necessary RPM modi cations, ensuring the equipment operates within the pre-set minimum and maximum RPM for each speci c technology. This enables the user to easily navigate between the various heads without the need of resetting complicated parameters.

Reduced Capital Investment & Cost of Ownership comes from the fact that each model oﬀers multiple functionalities on a single common drive platform, oﬀering the lowest long-standing cost when compared to the purchase of individual units. To learn more, visit https://www.idexindia.in/quadro/milling/ or give a call on 18002679955(Toll Free) or drop an email on info.fmt@idexcorp.com.

39 PHARMA machines & technology

Dec 2021 - Jan 2022

EXCLUSIVE

High Shear Mixers

Quadro Liquids Solving Processing Challenges

Quadro® Liquids group designs and manufactures single-pass, inline, high Furthermore, there is less degradation for speci c APIs. This all helps to improve eﬃciency and improve the performance of the downstream equipment. These models are fully scalable and have a variety of tooling available to handle the speci c requirements of both the lab and production environments.

shear mixer technology that is used for powder incorporation and

rotor-stator technology, for top quality results and reliability year after year.

One of the recent high volume applications was to help in the ght liquid-into-liquid mixing against Covid by supplying Quadro and homogenizing. High Shear Mixers for manufacturing Hand Sanitizer. To nd out more about the story visit: Bringing decades of knowledge https://www.quadroliquids.com/blo and applications experience to the Quadro® liquid blending and g/how-to-manufacture-handcustomer problem, Quadro® Liquids emulsi cation equipment is chosen sanitizer-using-high-shear-mixers. prides itself on being the mixer time and again due to its higher manufacturer that provides shear output compared to other solutions that other businesses cannot. dispersion into liquids,

Quadro® Liquids is solving the processing challenges of manufacturers involved in particle size reduction of API slurries. The Z Emulsi er and HV Emulsi er can improve particle and droplet size distribution, increase product yield and reduce milling time by reducing the number of passes.

40 PHARMA machines & technology

Dec 2021 - Jan 2022

EXCLUSIVE

Case Study

Know how a leading API customer signi cantly improved their product milling process OBSTACLES IN THE PROCESS User was running the Comil U30 machine without continuous feeding Granule size was large and its nature was hard Lot of heat was being generated API was sticky, leading to choking of screen holes

HOW WE SOLVED THEM Quadro team recommended not to stop Comil U30 during entire milling process Also the infeed was made controlled and continuous. This allowed the Comil for longer run and reduced the occurrence of screen holes blinding

“With the help of Our Quadro Team the API customer witnessed a signi cant improvement The existing process (404 kg) took 5 hours and now the new process took only approx. 45 minutes without screen choking and zero dusting”

41 PHARMA machines & technology

Dec 2021 - Jan 2022

Witness How Our Maharashtra Based API Client Achieved UNITERRUPTED MILLING Through QUADRO L4 SERIES CONICAL MILL !

Quadro L4 Series Conical Mill !

Challenges Faced by Customer

Quadro Solution - L4 Series Cone Mill

Local Conical Mill was being used

Achieved out-put of 600kg/hr (3 times of the old mill)

Out-put was low (around 200kg/hr)

Achieved required PSD in single pass. Eliminated extra step of Classi cation sifting

Didn’t get required PSD in single pass, and hence they had to do classi cation process and re-milling of the coarser material

Saving of time due to elimination of Classi cation sifting

Choking of screen while milling with 0.5mm size

Uninterrupted milling. No choking found in 0.5mm screen

EXCLUSIVE

IBC Systems

Matcon considers the challenges you face both up and downstream and help you to install a system that will set you up for the future, increase the production output of granulation process equipment and improve pro tability.

MATCON

sets you up for the

FUTURE 43 PHARMA machines & technology

Dec 2021 - Jan 2022

For a pharmaceutical OSD producer, commonly the focus of attention is on the processing stages of granulation, compression, coating and packing. Often overlooked, or not considered early enough in the facility design process, is “How are the materials moved from one process step to another?” “What is the best way to do this?”

EXCLUSIVE

IBC Systems

Without fully considering these fundamental questions when designing a facility, the manufacturer not only risks compromising the productivity of a given product line, but also limiting future potential for expanding capability and capacity. Of course, there is not a 'one size ts all' solution to materials handling, but Matcon IBC systems are extensively used in the Indian and worldwide pharmaceutical sector for transferring powders, granules and tablets. The patented Cone Valve within each IBC can control even the most free- owing powders, right through to sticky materials, such as metformin, ensuring that the nished product contains the correct measures of ingredients. The valve opens, closes or shuts oﬀ the ow, regulating the amount of powder being discharged into the process below. If a problem occurs downstream, production doesn't need to stop, or batches changed.

· Are these methods cost and time eﬀective? · Are you able to cope with uctuating future industry changes and demands? Now is the perfect time to reevaluate your pharmaceutical manufacturing operations and start preparing for your future.

a consistent, reliable feed of granules allows us to produce between 15-20% more from the Matcon fed lines as compared to the others.“ In the 40+ years' experience helping its customers remain competitive, Matcon has a unique understanding of the challenges you face in what is an everchanging industry. Matcon considers the challenges you face both up and downstream and help you to install a system that will set you up for the future, increase the production output of granulation process equipment and improve pro tability.

One of its esteemed Indian pharmaceutical clients recently commented: “We have been using To meet the pressures of consumer Matcon on our site since 2014 and and supplier demand, it is remain very happy with it. We have important to be agile if you're going two identical process units in to compete. Assess your current adjacent buildings, one which we facility processes by asking yourself: use Matcon IBCs to feed our · Are you using updated compression machines and one To nd out more visit technologies and exible which uses a conveying system. The https://www.idexindia.in/matcon/ equipment? ability of the Matcon IBC to provide

44 PHARMA machines & technology

Dec 2021 - Jan 2022

EXCLUSIVE

Case Study

INCREASE PLANT VOLUME by solving powder handling issues This case study is from a senior executive from one of the largest ARV manufacturer in the world

CHALLENGES Flow Issue: Issues with powder ow, downtime and waste Bridging Issue: Due to butter y valve, product would regularly bridge in the container; Operators had to hammer the bins to stimulate powder ow Intermittent Flow: Intermittent powder ow to tablet compression: this regularly choked the butter y valve Required Cleaning: Regular cleaning was required following each batch resulting in larger downtime Additional Manpower: Operators were diverted from core tasks onto cleaning duty

OUR SOLUTION IBC with CONE VALVE TECHNOLOGY Consistent Flow: Stimulated consistent powder ow to tablet press Reduced Handling: Reduced manual handling so that operators time is well used Eliminate Bridging Issues: Powder recipe was stopped from bridging in the container, no need of hammering Increased Production: The speed of tablet production was increased

45 PHARMA machines & technology

Dec 2021 - Jan 2022

EXCLUSIVE

Fluid Processors

Microﬂuidics USP TOP PRODUCTS

Micro uidizer® processors are more than simply high-shear uid processors – they are designed speci cally for the pharma & biotech industries to create advanced biopharma and pharmaceutical products. Currently, some of our customers are using Micro uidizer® technology to produce cuttingedge vaccines with advanced adjuvant production and LNP delivery systems particularly for Covid-19 vaccine development. In Covid vaccine production, LNPs exhibit strong eﬃcacy and functionality in their ability to deliver fragile mRNA intact and to its target site. Micro uidizer® technology is a proven technology in LNP production because of its ability to achieve precise particle size control. By reducing the particle size from the micron to the nano range scale, LNPs are able to achieve an eﬃcient drug delivery so particles can be quickly released into the target site. As an injectable drug, these mRNA vaccines are required to be sterile

47 PHARMA machines & technology

which can be a costly process. Through Micro uidizer's® technology, very narrow particle size nanoparticles are created and can pass through sterilizing lters without losing product or clogging the equipment which hinders production. For vaccine production, the ability to achieve desired results in the laboratory is successful only if the results can be repeated and produced for global distribution. Micro uidizer® technology is scalable by aligning microchannels in parallel within the Interaction Chamber™, with a single output reservoir. This ensures that the entire product stream experiences identical shear, resulting in consistent quality. Therefore, the same results are repeatable batchto-batch. As an example of how Micro uidics oﬀers a scalable solution in RNA delivery, watch our recent webinar (https://www.micro uidicsmpt.com/blog/a-scalable-solutionfor-the-creation-of-lipidnanoparticles-for-rna-delivery) and see how our customer achieved revolutionary, repeatable results on

Dec 2021 - Jan 2022

our M110P and pilot processors and will ultimately scale to our M700 production series. Last year, we installed an M815 Micro uidizer® processor in India for the production of Liposomal Amphotericin B to produce emergency doses to cure mucormycosis, using this powerful, intravenous anti-fungal medicine. The M815 was selected due to its ability to create on-target nanoparticles with a narrow particle size distribution, which is critical for producing consistent, reliable product. A further application of Micro uidizer® technology is in the production of nab paclitaxel. As this requires precise particle size control the uniform high shear generated during processing produces repeatable results, a high quality nanoemulsion and tight particle size distributions. If you would like to nd out more: (https://www.micro uidicsmpt.com/applications/nanoparticl e-albumin-bound-nab-drugdelivery

EXCLUSIVE

Testimony

SUCCESS Story

In 2011, Gennova purchased an Aseptic M110EH30, Serial No. 2011106 processor. Since then, in times of need, MF team (both USA and India) has provided excellent support whenever needed, even repeatedly ying factory engineers to site to resolve issues earlier this year.

“We are thankful and appreciate Micro uidics for their commitment & continuing supports extended to us, and highly recommend them to the other customers looking for an aseptic solution”. - Swarnendu Kaviraj Vaccine Formulation and Research Center Gennova Biopharmaceuticals Ltd.

Micro uidizer® processor 48 PHARMA machines & technology

Dec 2021 - Jan 2022

When creating nanoemulsions for intravenous therapeutics, a target nanoparticle size and narrow particle size distribution is critical for achieving consistent results.

Micro uidizer® technology is compliant with cGMP regulations and has been found to be both fast and eﬃcient in the reduction of liposome vesicles.

Micro uidizer® processors deliver uniform high shear during processing. This controlled precision allows for repeatable results regardless of volume size.

EXCLUSIVE

FITZPATRICK

Powder processing innovation excellence

Committed to improving the performance and pro tability of its customers' powder processing operations, The Fitzpatrick Company continually invests in customer-driven innovative solutions.

For over 80 years, Fitzpatrick has consistently achieved powder processing innovation excellence. They have designed, manufactured, and supplied the CCS and IR range of roller compactors as well as FitzMill™ milling equipment and hammer mills, to the

50 PHARMA machines & technology

pharmaceutical, chemical and food sectors worldwide. Committed to improving the performance and pro tability of their customers' powder processing operations, they continually invest in customer-driven innovative

Dec 2021 - Jan 2022

solutions and provide long-term support via their highly technical customer service and spare parts network.

The available 20 kN/cm roll pressure is equivalent to productionscale systems and matches the requirement for most pharmaceutical blends, so the results you achieve are a true re ection of a powder's suitability for dry granulation.

CCS1025

For more information go to https://www. tzpatrickmpt.com/products/benchtop-dry-granulation

CCS520

Manufactured with Fitzpatrick's high-precision, twin feed screw system, the LCS processes powders using the same mechanism as larger production-scale systems. This capability produces a compact that is comparable to that produced on full-sized models, which ensures your development projects can progress to production with con dence.

CCS720

Introducing the newest model in the roller compaction range LCS – Lab Compaction System, a scalable benchtop, high performance model for R&D and trial batch production. With capacities ranging from 10g to 6 kg/hr, the new LCS is ideal for proof-of-concept work or for smallest volume production.

CCS320

CCS220

LCS

Powder Processing

51 PHARMA machines & technology

Dec 2021 - Jan 2022

EXCLUSIVE

Powder Processing

LAB COMPACTION SYSTEM (LCS) Ideal for proof-of-concept or smallest volume production. Bene ts Manufactured with Fitzpatrick high-precision, twin feed screw system 20 kN/cm roll pressure equivalent to production-scale systems Complete disassembly of all contact parts enables thorough cleaning that is quick & easy Touchpad control of all independent feed & compaction variables Consistent compaction mechanism ensures easy scale-up to larger production machines Design optionally available for containment systems Documentation available for cGMP software option Choice of roller styles for maximum exibility

Features at a glance ROLL DIMENSIONS ROLL FORCE MINIMUM CAPACITY CAPACITY

52 PHARMA machines & technology

Dec 2021 - Jan 2022

1.5 X 12 cm 20 kN/cm 10 g 6 kg/hr*

EXCLUSIVE

Why customers value

STERIDOSE MAGNETIC MIXER Steridose Magnetic Mixer has become the trusted solution for demanding hygienic and sterile applications such as those involving serums, vaccines, plasma fraction, bacteria and cell cultures and APIs. Steridose have utilized over 4 decades of manufacturing experience to produce the most dependable and advanced solutions for its customers. The mission is to employ its technical understanding and application knowledge to develop equipment that surpasses the growing demands of both biotech and pharmaceutical manufacturers.

applications such as those involving serums, vaccines, plasma fraction, bacteria and cell cultures and APIs. Magnetic mixers have become the

The Sterimixer is ideal for demanding hygienic and sterile

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trusted solution for applications where sterility cannot be compromised – all the liquid is contained and isolated.

Magnetic Mixer

High levels of Containment and Isolation · Increased yields with mixing to the last drop · Easy cleaning processes using standard CIP and SIP procedures · Compact design – no overhead equipment needed · Simple maintenance – safe and easy impeller and drive unit removal. · Gas entrainment and foaming is greatly reduced by the oﬀset mixer mounting. The Sterimixer Magnetic Coupled mixer has the highest number of installations around the world. One of its customers is a contract manufacturer producing a wide variety of cough syrups. As their business steadily grew, they needed four new tanks. Instead of doing things the same old way, they were looking for a way to make their

55 PHARMA machines & technology

process more hygienic. They approached Steridose to help them design an upgrade of their mixing process. Like any contract manufacturer, they needed exibility - they may be making a 200 centipoise cough syrup today and they may get a contract for a 500 centipoise cough syrup tomorrow, the speci c gravity varying with each recipe.

· Simple maintenance – safe and easy impeller and drive unit Steridose's engineers used the data removal. provided by the customer to arrive · Gas entrainment and foaming is at a mixer selection that provides greatly reduced by the oﬀset mixer the customer with not only a mounting. solution for their new tanks, but one that added in a reasonable The Sterimixer Magnetic Coupled amount of mixing in reserve, so that mixer has the highest number of they are future-proofed for installations around the world. One continued growth and expansion. of its customers is a contract To nd out more about this story go to: https://www.steridose.com/blog/m aking-cough-syrup-with-magneticcoupled-mixers.

Dec 2021 - Jan 2022

manufacturer producing a wide variety of cough syrups. As their business steadily grew, they needed four new tanks. Instead of doing things the same old way, they were looking for a way to make their

C M Y K

Open Size width 8.5"

GLOBAL EXPERTISE

Open Size height 12.045"

in Material Processing Technologies

HIGH SHEAR FLUID PROCESSORS

SOLID DOSAGE POWDER / GRANULE, TABLET HANDLING SOLUTIONS HIGH SHEAR MIXER MANUFACTURER

PHARMA POWDER PROCESSING & SIZE REDUCTION EQUIPMENT

ROLL COMPACTION & DRY GRANULATION EQUIPMENT

Toll Free:1800 267 9955

26 PHARMA machines & technology

Oct - Nov 2021

info.fmt@idexcorp.com

STERIDOSE MAGNETIC MIXER

www.idexindia.in

ARTICLE

Packaging

How Automation-Digitalization-Communication in uenced and improved Product-Packaging-Labelling By Prabir K Das

The Product-PackagingLabelling relationship is analogous to AutomationDigitalizationCommunication relationship, practically inseparable from each other.

The product-people connectivity is very important in trust building process and success of a brand is largely dependent on this trust building. The packaging-labelling eﬀectiveness is largely responsible to establish this connectivity with its communicative features. While some of the features on packaging and labelling are visible and readable, there are features which are invisible and require diﬀerent tools to make it visible or readable to know the desired information. The purpose of including these features in packaging-labelling is either to promote the brand or to

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protect the brand or both. The basic packaging and its in-built design prevent product spillage, leakage, breakage and spoilage. Adverse external environmental conditions and external threats like theft, diversion, and cloning are very common. Apart from internal operational controls, there are many external logistics controls too, to protect the product from these threats and challenges. Similarly, labelling helps to comply various regulatory guidelines through instructions for identi cation, storage, handling, dispensing and disposal. There are

ARTICLE

Packaging

elements for branding too through text, color and graphics. A combination of packaging-labelling design and features take care of all these requirements to support brand promotion and brand protection. Over the years industry has experienced diﬃcult situations and responded with stronger designs and features to sustain and survive in the competition. Now, in this fenceless global business, when multiple technologies are available for easing the process of globalization, industry has responded well to compete in the global market. Quantity, quality and strict regulatory complianceare the need of the hour. Evolution in industrial automation and digitalization are strongly supported with revolution in communication systems. Most of the advanced features in productpackaging-labelling became feasible because of this automation-digitalizationcommunication system. This is how they are analogous to each other and also inseparable from each other.

These advanced value-added features are primarily two types: Static / standalone / oﬀ-line category – Pilfer-proof / tamperevident feature, covert / overt anticounterfeit feature, brand promotion feature, animated and digital graphic design features, etc.

Packaging (primary, secondary and tertiary) decides the substrate and its speci cations. Substrates provide the base for the texts and graphics. While the text is for the brand / Dynamic / connecting / on-line product identity and statutory category – Serialization / compliance, graphics is for the aggregation (track & trace) feature, product positioning or brand SMS / Web based veri cation identity. Fonts, colors, embossing, feature, User interactive feature, etc. hot stamping, diﬀerent types of Most of these features are adopted surface nish are common. through advanced technologies – Packaging and Labelling also automation and digitization, contains many value added features wireless communication and hybrid to facilitate speci c functions like technologies. ease in display, dispensing and disposal. Such features combinedly Brand promotion features promote branding. Text, Graphics, Decorative and Tamper evident features Technical design features to enhance consumer appeal. Every Design or device to prevent product needs the packaging for pilferage or theft of the product protection from the external from the original pack. Tamper environment and needs the evidence is already an existing labelling to communicate with the system, primarily to prevent theft external world. It also facilitates and pilferage. There are 3 common brand positioning and brand systems currently being used for tamper evidence: promotion.

Brand promotion features Text, Graphics, decorative and Technical design features to enhance consumer appeal. TAMPER E

PACKAGING & LABELLING

ANTI-COUNTERFEIT NTICA TION

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Tamper Evident features Design or device to prevent pilferage or theft of the product from the original pack.

VIDENCE

TRACK & TRACE

AUTH E

Packaging and Labelling are complements to each other. Labelling has 3 basic elements – Text, Graphics & Substrate.

Track and Trace features A tool or system to control and ensure supply chain security and assure consumer safety

Anti-counterfeit features Design or device which prevents to replicate or cloning of the original product-pack.

Dec 2021 - Jan 2022

Authentication features A tool or system to verify genuineness of the product and its ownership.

TRUST BUILDING

ARTICLE

Packaging

1) Use of tamper evident stickers, 2) Use of hot or cold glue, and 3) Mechanical locking of the pack which leaves sign / proof when opened.

changing security inks / lm, security graphics, random serialization, on-product imaging or numbering.

Anti-counterfeit features

3. Other features: RFID, biological taggants, micro taggants, secured web link, special (diﬃcult to copy) printing / embossing on products (solid doses).

2. Covert Technologies (invisible It also has challenges like use of an features): These are not visible with additional sticker or glue and naked eyes – invisible printing, light related application units on the sensitive printing, embedded packaging lines. Industry is using it images, digital watermark, antifor years to prevent theft or copying copy or anti scan design, laser of the product-packs. codes.

Design or device which prevents to replicate or cloning of the original product-pack. Some of the common anti-counterfeit features on product-packaging are: 1. Overt Technologies (visible features): These are visible but diﬃcult to imitate – customized holography, micro text, color

Authentication features A tool or system to verify genuineness of the product and its ownership. This is the last action of an end-to-end solution

wherein the end user participates to close the loop. Some of the common authentication features are intricate design stickers / holograms, microprinting, use of diﬀerent electronic tags / chips, SMS based communication link, web link through Wi-Fi connectivity, biometric codes, speci c light sensitive prints / codes, mobile application-based codes, scratch and scan codes, and so on. Product level authentication features are also available, especially on solid dose formulations. These features are often used as a single technology or as a blend of diﬀerent technologies, involving other value-added features like, anti-counterfeiting, tamper evidence or even serialization. However, in all these cases

PACKAGING AND LABELLING Optics and Electronics

Virtual Imaging

Track & Trace

Block Chain Digital Graphics

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Dec 2021 - Jan 2022

Automation & Robotics Interactive Packaging

Augmented Reality Arti cial Wireless Intelligence Communication Personalized Branding Nano Tech IoT

ARTICLE

Packaging

customer education and awareness building is must through physical demonstrations or printed instructions.

wise aggregated) is pushed to the network for veri cation and authentication by the regulators and agencies involved in the supply chain of the products.

and improved every stage of operations in the industry and it has been adapted to our changing lifestyle as well.

· Evolution to Revolution: Local to Despite initial challenges, it has Global – Large wholesale pack to A tool or system to control and been broadly accepted and Small consumer pack. ensure supply chain security and adopted by pharma industry not · Scaling Up: Quantity with Quality assure consumer safety. The Track only to ensure supply chain – Consistency and and Trace feature was primarily security, but also to control Reproducibility. introduced to monitor and control counterfeit, pilferage and diversion. the movement of the goods across Pharma industry across the globe is · Manufacturing and Packaging: the entire supply chain. Testing and Releasing – Data now aligned to make it a success management and with various cost eﬀective, compact This GTIN based technology uses Documentation. and compliant solutions. unique serial number on each trade · Promotion and Protection: unit / saleable pack. The GTIN and Automation-DigitalizationCloning and Counterfeiting – batch speci c data (packaging level Communication has in uenced Track and Trace features

Internal Necessities

LOGISTICS

TECHNOLOGY

BRANDING

REGULATOR

Packaging & Labelling

PROCESS PRODUCT

I N T E R N A L E X T E R N A L

External Mandates

•PRODUCT •PROCESS •BRANDING •LOGISTICS -

COMPETITOR CUSTOMER

Category of product, Physical, Chemical and Organoleptic properties, shape, size, colour, Fragility, sensitivity level, Bulk density, Viscosity, Flow properties. Design, Flow, Scope of Automation, Standardisation and Harmonisation. Pack Design, Graphic Design, Use of Smart Features. Storage, Handling & Distribution, Mode of Transportation, Excursion Study, Shipment Study.

•CUSTOMER -

Domestic or Export, Demography, Convenience, Dispensing ease, Disposal ease, Authenticity. •COMPETITOR - Bench marking, Cost sensitivity, Uniqueness (USP). •REGULATOR - Local rules & regulations, Environment friendliness, Child protection, Supply chain safety & security. •TECHNOLOGY - Availability & Adaptability, Cost-bene t analysis, Feasibility for hybridizing, Sustainability.

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Dec 2021 - Jan 2022

Making FFS & BFS Affordable

ARTICLE

Packaging

Theft and Diversion. · Storage, Handling and Transport: Logistics and Distribution – Safety, Security and Traceability. · Digitalization is a great support to Automation and Communication systems through Data and Information Capture, Data Transform, Storage, Processing, Transfer, Exchange, Retrieval, Integrity, Transparency and Compliance. · These help to optimize cycle time, space utilization and convenience. It enhances speed to all the business processes. Quality and Compliance are well ensured with Transparency and Integrity. It also strengthens the Communication system. There are many basic tools to support this AutomationDigitalization-Communication relationship. Over the period these tools have been ne-tuned for their practical applicability. Such tools help to build diﬀerent custommade programs, which directly or indirectly facilitate the operations, conversions, controls and communications. This is how Product-PackagingLabelling relationship is strengthened with the help of advanced tools and technologies. Often multiple tools and technologies are blended to get a customized hybrid model, which are more powerful than a single technology. Across the world packaging professionals always try to nd customized solution to support brand protection and brand promotion with their knowledge in

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material science, conversion technologies, application feasibility and exibility. Basic packaging materials vary from simple paper to complex composites, inclusive of metals, glass, plastics, and many more options. Accordingly, their conversion technologies also vary to nalize the design and process options. While doing so it is always ensured basic safety and security of the product-pack is maintained. There are logistics challenges as well which covers multiple options like roadways, railways, airways, ropeways, pipelines and water routes. Each of these has their own hazards and challenges. Similarly, there are many external mandates like compliance to regulatory guidelines, benchmarking with competitors, obsoletion of technology, change in consumer behaviors, etc. Hence a good balance is required while designing and developing a product-pack which can sustain and survive longer in competition.

Dec 2021 - Jan 2022

Prabir K Das, is one of the rst batch alumni (1985 – 87) from Indian Institute of Packaging, Mumbai (India), and a 30+ yearsexperienced pharmaceutical packaging professional, currently taking care of the Indian operations for one of the large and renowned global pharmaceutical service providers based in US. He is actively involved in development, execution and post commercialisation life cycle management which involves technology transfer, new product-pack launch, packaging validation, change management, quality and COGS improvement projects, automation, standardization and harmonization projects, track and trace project, and any kind of innovative packaging development project considering patient safety and compliance.

Technology Updates

TECH NEWS

Single-use microbial impactors The BioCapt Single-Use (BCSU) microbial impactors from Particle Measuring Systems (PMS) are now available for use with applications at 100 Litres Per Minute (LPM), expanding the range of uses the active air microbial impaction plates can be used for. The BCSU 100 is a ready-to-use, lightweight and integrated microbial impaction plate designed for both portable and fixed monitoring systems in remote sampling settings. PMS brings you these innovative active air microbial sampling plates for analytic measurement of viable contamination in critical areas. The flexible new BCSU 100 is designed to be used with the Particle Measuring Systems' MiniCapt® Mobile microbial active air sampler.

To assist biopharma, med device, cell and gene markets

To fill-finish more than 500 million doses per year

ILC Dover, a leading designer and manufacturer of high-performance materials for life critical and primarily life sciences-based applications, has announced the acquisition of KSE Scientific, a sterile solutions manufacturer which specializes in the production of Water for Injection (WFI) and related media and buffer solutions for biopharma, cell and gene therapy, tissue banking and medical device end-markets.

Fareva and ApiJect Systems, Corp. has announced a 10-year licensing agreement to install three Blow-FillSeal production lines that when operational will be able to fill-finish more than 500 million doses per year of vaccines and other large molecule injectable drugs using ApiJect's innovative prefilled injector technology.

Founded in 2000 and headquartered in Durham, North Carolina, KSE has transformed into a leading supplier of sterile consumable products and will continue to operate under its own brand. ILC and KSE have highly complementary product offerings and the combination creates significant growth opportunities by offering a broader and more integrated workflow solution to customers. Following the transaction, ILC will be able to provide custom cellculture and bioprocess solutions within its own liquid bag containment solutions to better serve its customers within biopharma, cell & gene therapy, and related life sciences end markets.

Following the acquisition of Flexan earlier this year, KSE is the third BioCapt Single-Use can easily acquisition ILC Dover has comreplace any existing microbial pleted since announcing a partnersampling head, whether attached to a mobile instrument or installed in a ship with New Mountain Capital in remote location. Multiple mounting early 2020. The acquisition will continue to grow ILC Dover's life accessories allow it to connect to sciences solutions for its global new or existing environmental customer base. monitoring systems.

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Fareva intends to invest more than €50M (US$ 56.5M) for these three manufacturing lines, with support from the Government of France, through the “France Relance” industry initiative and the Investments for the Future Program. The three manufacturing lines and ApiJect's technology utilize the Blow-Fill-Seal (BFS) aseptic packaging process. BFS has demonstrated its ability to package certain vaccines and large molecule formulations, and ApiJect is helping to expand BFS's capabilities to additional drug products, including temperature sensitive pharmaceuticals. When cleared by regulators, ApiJect will provide the necessary needle hub and other attachable components to convert finished BFS single-dose containers from these lines into easy-toassemble, ready-to-use prefilled injectors. By investing in these three BFS lines and installing ApiJect technology, Fareva is helping to increase Europe's high-speed, high-volume fill and finish capacity by potentially more than 500 million doses per year.

Technology Updates

Mixers with solids/liquid injection manifold technology Ross VersaMix Multi-Shaft Mixers with Solids/Liquid Injection Manifold (SLIM) Technology enable fast and efficient large-scale powder dispersion into lowviscosity liquids including resins, oils, melted waxes, emulsions, and aqueous solutions.

out and dramatically minimizes issues like agglomeration (fisheyes), floating powders and dusting.

The second agitator is a Two-Wing Anchor equipped with hinged Teflon scrapers for consistent heat transfer across the vessel sidewalls and bottom which could be jacketed for temperature control. After the powder induction step, the VM-600 can handle a significant VersaMix Model VM-600 is a 600-gal increase in viscosity because the capacity dual-shaft mixer designed combined mixing action of Anchor for deep vacuum levels. Featuring a and High Shear Mixer ensures High Shear Mixer with SLIM adequate turnover. Technology, the rotor/stator Software solution provider hits assembly of the VM-600 creates a $100 million ARR powerful suction that draws solids MasterControl, a global provider of sub-surface, directly into the highshear zone. This method of material software solutions for life sciences and other regulated industries, has addition accelerates powder wet-

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Dec 2021 - Jan 2022

reached $100 million in annual recurring revenue (ARR). Just this year, more than 120 companies have chosen MasterControl as their quality and manufacturing systems partner and, to date, nearly half of the top 50 pharmaceutical and medical device companies use MasterControl solutions. Additionally, the company continues to expand globally with significant growth in the EMEA and APAC regions. MasterControl's manufacturing solutions are used by leading Covid-19 vaccine developers and manufacturers and have been integral to the scale and delivery of these advanced therapeutics.

Technology Updates

Expanded Microsoft Azure Machine Learning support Seeq Corporation, a leader in manufacturing and Industrial Internet of Things advanced analytics software, has announced additional integration support for Microsoft Azure Machine Learning. This new Seeq Azure Add-on, announced at Microsoft Ignite 2021, an annual conference for developers and IT professionals hosted by Microsoft, enables process manufacturing organizations to deploy machine learning models from Azure Machine Learning as Add-ons in Seeq Workbench. The result is machine learning algorithms and innovations developed by IT departments can

70 PHARMA machines & technology

be operationalized, so frontline OT employees can enhance their decision making and improve production, sustainability indicators, and business outcomes. Seeq customers include companies in the oil & gas, pharmaceutical, chemical, energy, mining, food and beverage, and other process industries. Investors in Seeq, which has raised over $100M to date, include Insight Ventures, Saudi Aramco Energy Ventures, Altira Group, Chevron Technology Ventures, and Cisco Investments.

With the new Azure Machine Learning integration, data science teams can develop models using Azure Machine Learning Studio and then publish them using the Seeq Azure Add-ons feature. Using Seeq Workbench, frontline employees with domain expertise can easily access these models, validate them by overlaying near real-time operational data with the model results, and provide feedback to the data science team.

This enables an iterative set of interactions between IT and OT Seeq's strategy for enabling employees, accelerating time to machine learning innovations insight for both groups, while creating the continuous provides end users with access to algorithms from a variety of sources, improvement loop necessary to including open source, third party sustain the full lifecycle of machine and internal data science teams. learning operations.

Dec 2021 - Jan 2022

REVIEW

IPE 2021

Indian Pharma Expo 2021 Indian Pharma Expo 2021 was held on 10th and 11th December at Pragati Maidan, New Delhi with complete Covid-19 guidelines, adding success and setting the benchmark. The 10th edition of Indian Pharma Expo was inaugurated by Dr. Sushil Kumar Gupta - Member of Parliament, Rajya Sabha, Aam Admi Party, Shri Surendra Rathi - Member National Council, Aam Admi Party and Shri Ashok Shrivastav - Senior Journalist, Doordarshan News along with Mr Joe Thomas Business Director - India Operations, Mr. Alok Sharma - Assistant Vice President, Events & B2B Pharma, Mr. Vikram Singh - Head HR India and Mr. Vikas Kashid - Head Finance & Accounts at CIMS Medica India Pvt. Even in challenging times like these, Indian pharma experts showed spirit and enthusiasm by

attending the Indian Pharma Expo and making it memorable. As the pandemic has changed the

PacMac

dynamics of the pharmaceutical industry as a whole, this event helped the industry to understand

First to Market : A fully synchronized ointment filling line.

Aptitude for perfection

SINGLE HEAD TUBE FILLING

CARTONER MACHINE

End to end ointment filling machine solution Wide range (60 to 200 tubes per minute)

Best ointment filling line available in India. Almost 100 % repeat order from all the buyers.

PacMac Solutions Pvt. Ltd. A-109, Dadra Industrial Estate, Opp. Dadra Check Post, Silvassa, U.T. of Dadra & Nager Haveli. Tel: +91 9819950900/9427468575 Email: thakkar@pacmac.co.in Website: www.pacmac.co.in

70 PHARMA machines & technology

Dec 2021 - Jan 2022

www.pacmac.co.in

REVIEW

IPE 2021

the challenges and changes, unique ideas, innovation and execution, cost-effective production techniques, procurement, logistics and more interesting things.

Director, Indian pharmacopeia commission and Shri Atul Nasa - Head of Office/Controlling & Licensing Authority and Deputy Drugs This year's Indian Pharma Expo too Controller with Drugs played an ideal platform to witness Control Department, and appreciate the latest advanceGovernment of NCT ment and innovation in of Delhi along with Manufacturing, Research and Development, Packaging Solutions, Mr. Joe Thomas. Supply Chain Management, The Business Excellence Awards Franchising, Distribution and many felicitates the business that brought other domains. Additionally, this innovation and freshness in the Expo has contributed to helping pharma industry. The winners are eminent stakeholders of the selected in the fields of Research pharma industry to build new and Development, Active business leads and boost revenue Pharmaceutical Ingredients, potentials. Formulations, Manufacturing, Packaging, Distribution, Marketing, The Business Excellence Awards was held on 10th December in the Franchising, Outsourcing, Supply chain and Logistic Management, presence of Dr Rajeev Singh Raghuwanshi – Secretary/Scientific and other Support Services.

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Dec 2021 - Jan 2022

Indian Pharma Expo along with the Business Excellence Awards helps businesses of all sectors under the pharmaceutical sector to showcase their innovation, share ideas for successful innovation and get recognised for innovation. Such an event helps us understand the latest trends, updates and newness in the pharmaceutical industry, helping to identify and learn the changing dynamics of our industry.

www.targetinnovations.com An ISO 9001:2015 Quality Company

MAXIMIZE QUALITY and Protect Your

BRAND

REPUTATION

METAL DETECTION

Detection Perfection

Manufacturers of : Metal Detection and Separation Systems, Checkweigher, Pouch packing machines, Liquid lling, capping & Labeling machines and all types of Special purpose packing machines.

Pharmaceutical Metal Detector

Micro Scan Metal Detector

Pharmaceutical Metal Detector with De duster 9 Tray

Gravity Feed Metal Detectors

Micro Scan Metal Detector Analog Version for Packets Inspection

Micro Scan Metal Detector for Packets with Rejection

Visual Inspection Belt Conveyor for Grains and Nuts

Regd. Ofce: 13, Chase International, P.E. Jose Vaz Road, Vasco Da Gama, Goa, INDIA 403802, Tel: +91 832 2510840 , 65483119, 2555830, Mumbai Factory: R 380, TTC MIDC, Rabale Industrial Area, Navi Mumbai, Maharashtra, INDIA, Tel: +91 22 20876543, +91 22 20878685, Goa Factory: D 1/3, Sancoale Industrial Estate, Zuarinagar, Goa, INDIA 403726 Tel: +91 832 2555630 , +91 832 2556801,

Email: sales@targetinnovations.com

IN FOCUS

Tube Filler

CONDOR 300

As the fastest tube filler in SUBNIL's range, it has the capacity to produce about 100,000 tubes per shift.

CONTEMPORARY, HIGH-SPEED TUBE FILLER

The CONDOR 300 is high-speed tube filler with a capacity to produce about 100,000 tubes per shift.

out either into a collection container or to a tube-transfer system to link to the downstream MERLIN 300XC cartoner.

The tubes have to be first manually transferred from the tube box to the cassette provided on the machine. In turn the tubes are loaded into the tube holders through intermediate tube loaders. First the tubes are centered and oriented and then filled. They are then closed depending on the type of tube.

Options for completely automatic robotic tube loading is also available.

tools Ÿ Vision systems for checks like

right packaging for SKU, illegible printing by ink-jet, bad seal, etc. Ÿ All-around guarding, with

minimum access to moving parts

Features

Ÿ Saddle Fold

Ÿ Easy Changeover

Ÿ Multi-colour filling

Ÿ Bottom-up / dive-down filling

Ÿ Profiled Sealing / Euro-slot

with shut-off nozzle. Blow-off for string-like characteristic

Ÿ Vertical dosing for ease in suction In case of metal tubes, the tubes are flattened and crimped twice (or Ÿ Standard features include even thrice). In case of laminate / product level sensor, detection of plastic tubes, they are first heated reverse tubes, jammed tubes, unon the inside periphery and then filled tubes and un-oriented tubes sealed. Batch details are then coded Ÿ Heating from hopper to nozzle, on the crimp (or seal) with metal for balm-like products stereos and the tubes are ejected

74 PHARMA machines & technology

Ÿ Adjustment with bare minimum

Dec 2021 - Jan 2022

Ÿ Nitrogen flushing Ÿ Compliance to CE, UL & cGMP

norms For more details contact: Avish Machines Pvt. Ltd F/3-4, Prime Estate, Sagpada, Deodal, Kaman, Naigaon - East, Dist. Palghar – 401 208. Tel: 96079 40379, Email: hello@avishmachines.com

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