Express Pharma (Vol. 19, No. 5) April 2024

IT@PHARMA

Harness data to unleash power of Indian pharma industry REGULATIONS

Impact of the new Annex1 on sterile filling

INDIA'S FOREMOSTPHARMA& BIOTECH MAGAZINE SINCE 1994APRIL2024,` 40

Chairman of the Board

ViveckGoenka

Sr.Vice President-BPD

Neil Viegas

Vice President-BPD

Harit Mohanty

Editor

Viveka Roychowdhury*

Editorial Team

Lakshmipriya Nair

Kalyani Sharma DESIGN

Art Director

Pravin Temble

Senior

Rekha Bisht

Senior Artist Rakesh

Marketing Team

Rajesh Bhatkal

Ashish Rampure

Debnarayan Dutta

Production Co-ordinator

DhananjayNidre

Scheduling

Pushkar

EDITOR’S NOTE

A step towards global harmonisation of GMP inspection protocols

In a letter dated March 21, the US FDA India office country director Sarah McMullen said that four states (Gujarat, Telangana, Goa and Karnataka) had been 'sensitised to FDA's inspection process and, as such, are eligible for inclusion as observers for relevant inspection in their respective states.' The letter goes on to mention, 'We would appreciate relevant opportunities being made available to state inspectors to attend as observers as practical.'

US FDA’s ''Observed Inspection Program‘ involves interaction between the USFDA India office and State Drug Control Authorities, with the former inviting the latter as observers during inspections. As the letter indicates, 'FDA has shared best practices and inspectional protocols in regulatory forums with several states.'

It is logical that the US FDA would now turn to replicate these efforts in other states, especially those with many FDA-registered facilities, like Maharashtra, for instance, and explore the possibility of adding to this list.

While increased cooperation between regulatory authorities will promote standardisation and global harmonisation of regulatory protocols, there is a steep learning curve. For both state regulators as well as regulatory affairs personnel in pharma companies.

The concerns are many. Firstly, pharma companies have manufacturing facilities in multiple states, some might be on the observed inspection programme and others might not be on this list. Will this impact the results of US FDA inspections and state drug controllers? Pharma companies are ideally supposed to ensure that all manufacturing facilities follow the same procedures, but this is not always the case. Such observed inspection programmes could take them one step closer to this reality. State regulators should share learnings from such observed inspections with each other more systematically for the programme to reap multiple benefits.

Looking ahead, are we looking at having such an observed inspection programme with other global inspection agencies like UK MHRA, EU EMA, etc? As head of Gujarat's state drug regulatory body, Dr HG Koshia, Commissioner, Food and Drug Control. Administration (FDCA) Gujarat recounts that for a short time, a couple of years back, his team did have a similar informal

Linking purchase of electoral bonds to inaction on questionable quality standards is yet another warning to all pharma companies to get their act together

arrangement with the UK MHRA and were invited as observers on a few MHRA inspections in Gujarat. He says such a programme opens a world of different experiences to state inspectors and results in an improved quality consciousness.

The vexing issue of varying levels of manufacturing quality among India's pharma facilities has surfaced during the analysis of electoral bonds. Media groups investigating the source and recipients of these bonds are joining the dots. In some cases, the purchase of these bonds by pharma companies is linked to IT raids and GST evasion. As per an Indian Express report, (Facing GST heat | A telling pattern: In pharma, different firms buy electoral bonds on same days) just on November 10, 2022, major pharma companies including Cipla, Dr Reddy’s, and Ipca Laboratories purchased bonds totalling close to Rs 50 crore. Glenmark Pharma and Mankind also purchased bonds a day in several tranches worth over Rs 30 crore. And, three days later, on November 14, Alembic Pharmaceuticals, Alkem Laboratories and Piramal bought bonds worth over Rs 20 crore.

In other cases, the pharma companies' manufacturing units were pulled up by overseas regulators for poor GMP practices. Reports allege that they resorted to buying electoral bonds to prevent follow-up inspections from state regulators. As an open letter to pharma CEOs points out, (An open letter: Concerns on electoral bonds and pharma industry) as consumers of medicines, we are all at risk if these alleged substandard medicines are still on chemists' shelves, not just in India but across the world.

Linking the purchase of electoral bonds to inaction on questionable quality standards is yet another warning to all pharma companies to get their act together. The US FDA's observed inspection programme is yet another sign that slowly but surely, local inspection procedures and processes will need to work up to global best practices. It follows that pharma companies will also have to up their quality game.

VIVEKA ROYCHOWDHURY, Editor viveka.r@expressindia.com

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Harness data to unleash power of Indian pharma industry

Saransh Chaudhary,President,Global Critical Care Division,Venus Remedies,and CEO,Venus Medicine Research Centre details how data analytics and data science can potentially revolutionise the entire pharma value chain by improving efficiencies and outcomes

The Indian pharma industry is one of the largest and most dynamic in the world, supplying affordable and quality medicines to millions of people globally. However, the industry also faces several challenges like increasing competition, regulatory hurdles, pricing pressures and rising R&D costs. To overcome these challenges and achieve sustainable growth, the pharma industry needs to leverage the power of data science and data analytics, which can provide insights, solutions and innovations across the entire value chain.

The disciplines of data science and data analytics use scientific methods, algorithms and systems to extract knowledge and insights from structured and unstructured data. They can help the pharma industry in various ways to improve efficiencies and outcomes.

An analysis by McKinsey has projected that on account of broader adoption of these technologies, the EBIDTA earnings of the Indian pharma industry will go up by 45-75 per cent in the next 10 years. Furthermore, viewing it from a global perspective, artificial intelligence (AI)-enabled automation and advanced data analytics will result in a 60-70 per centreduction in process timelines and a 30% reduction in operational costs, according to another study conducted by PwC.

The Big Pharma in India has already taken a lead by adopting a range of technologies like artificial intelligence, machine learning and cloud computing to advance drug discovery, optimise clinical trials, improve supply chain management and accelerate product development.

Boost for research

Data science and data analytics can accelerate and enhance the research process by enabling faster and more accurate identification of drug targets, biomarkers and pathways, as well as better understanding of disease mechanisms and patient subgroups. For example, AI-assisted clinical management can help researchers design and execute more efficient, faster and effective clinical trials through predictive modelling, reducing the time and cost of drug development. Similarly, molecular design can rely on machine learning algorithms to generate novel and optimised drug candidates and, in turn, reduce the need for extensive screening and testing.

Drug discovery

Data-driven technologies can revolutionise the drug discovery process by enabling the discovery of new drugs, repurposing of existing drugs and optimisation

of drug properties. For example, drug repurposing can use data mining and network analysis to identify new indications for approved or failed drugs, thus saving time and resources. Toxicity prediction can employ computational models to predict the potential toxicity of drug candidates and hence reduce the risk of adverse effects and attrition.

Drug development

These new-age technologies can improve the drug development process by enabling faster and more reliable validation, optimisation and scale-up of drug candidates. For example, material waste reduction can use datadriven methods to optimise the process parameters and reduce the material consumption and environmental impact of drug production. Process intelligence can utilise data visualisation and analytics to monitor and control the quality and performance of drug manufacturing processes

so as to ensure compliance and consistency. A leading multinational is aptly using AI systems to build clinical decision-making tools to develop personalised medicine for cancer patients.

Supplychain management

Data technologies can optimise the supply chain management of the pharma industry by enabling better forecasting, planning and coordination of drug demandsupply dynamics. For example, forecasting of patient flow and demand can use data modelling and simulation to predict the future demand for a particular drug or medicine, helping pharma companies adjust their production and inventory accordingly. Supply chain logistics can use data optimisation and automation to improve the transportation and distribution of drugs, reducing costs and delays. These advancements are also enhancing traceability and end-to-end visibility in the supply chain across manufacturing, warehouse and distribution centres, besides combating counterfeit drugs.

Impetus to marketing

These advanced technological interventions can give an edge to the marketing efforts of the pharma industry by enabling more effective and personalised communication, promotion and engagement of customers and stakeholders. For instance, segmentation analysis can use data clustering and classification to identify and target different customer segments based on their needs, preferences and behaviours. Social media analytics can use data mining and sentiment analysis to monitor and analyse the online reputation and feedback of pharma brands, products and services to achieve the

end objective of improving customer satisfaction and loyalty.

Cost management

Data-enabled technologies can reduce the costs of the pharma industry by enabling more efficient and economical use of resources, assets and processes. For example, data prediction and prevention can be used in preventive maintenance to anticipate and prevent the breakdown of equipment and machinery, thus reducing downtime and repair costs. The pharma industry can also use data analytics as a tool to assist sales representatives in taking optimal decisions regarding pricing, discounts and incentives in order to maximise revenue and profits.

Make the most of it

The Indian pharma industry has a huge potential to leverage data science and data analytics for improved business outcomes as it has access to a large and diverse pool of data, talent and technology. However, in order to realise this potential, the industry also needs to overcome barriers like data quality, security and privacy, data integration and interoperability, data literacy and culture, and data governance and regulation. The industry also needs to collaborate with other stakeholders like academia, government and healthcare providers to create a datadriven ecosystem that fosters innovation and value creation.

Data analytics and data science are the key enablers of Pharma 4.0, which signifies the next wave of digital transformation in the pharma industry. By harnessing the power of data, the pharma sector can become more efficient, competitive and quality-oriented, which will in turn improve health outcomes.

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EXPRESS PHARMA

The Sikkim Pharma Summit 2024,organised by Express Pharma,united key stakeholders fom the mountain state to drive innovation and growth in India Pharma Inc.This event brought together industry experts,thought leaders,and innovators for discussions and knowledge exchange on a diverse range of topics such as innovations in drug discovery and development,evolution of pharma packaging,building a future-ready workforce,potential of digital transformation in pharma operations etc.

Apart from knowledge exchange,the event also offered myriad opportunities to network and engage with peers and colleagues as well as foster partnerships and initiatives in the pharma sector.

Thus,the Sikkim Pharma Summit 2024 served as a platform for industry leaders to exchange ideas, address challenges,and strategise for a thriving pharma landscape.

Here is a review of the sessions from the event.

Innovations in drug discoveryand development

Vinay Chaturvedi from Zuventus presented on the innovations transforming drug discovery and development across its phases: Discovery, Preclinical Studies, Clinical Development, and Market Approval.

Chaturvedi's presentation shed light on the transformative innovations driving drug discovery and development, underscoring the importance of AI, patient-centric approaches, synthetic biology, computational methods, 3D cell culture, cybersecurity, and emerging solid oral dosage form technologies

It highlighted Artificial Intelligence (AI) and Data Analytics as pivotal in accelerating drug discovery processes. It pointed out that AI algorithms and data analytics expedite the identification of potential candidates and predicting their efficacy.

VinayChaturvedi,VP-Operations,Zuventus Healthcar

Chaturvedi also emphasised the importance of patient-centric trials, and addressed how advancements such as virtual trials, wearable devices, and remote monitoring enhance

patient experience and streamline data collection.

Another innovation highlighted was

ACG Lab: Process development and optimisation made easy

The session on ‘Process development and optimisation made easy’, led by Prashant Deshpande, provided invaluable insights into interconnected facets of pharma development. The session delved into the essential strategies and methodologies crucial for success in the pharma industry, with a focus on enhancing product yield, reducing manufacturing costs, and ensuring regulatory compliance.

The session highlighted the distinction between product development and process development. Product development revolves around the formulation and design of the drug product such as dosage form, excipient selection, and quality standards. Process development entails optimising the processes required for commercialscale production such as technology selection, equipment optimisation, and process parameter refinement.

Synthetic Biology with its potential in engineering biological systems for creation of novel compounds and innovative therapies.

High-Performance Computing (HPC) was another trend covered during the presentation for its role in accelerating drug discovery.

3D Cell Culture methods was underscored for their ability to provide better understanding of drug responses and toxicity.

Cybersecurity measures were emphasised as crucial for safeguarding sensitive patient data and research findings throughout the drug development process, ensuring data integrity and privacy.

Furthermore, emerging technologies in solid oral dosage forms were covered to explore advancements in formulation and delivery methods.

Thus, it was a very comprehensive and insightful presentation with several pertinent takeaways.

Key strategies for process optimisation were discussed, with an emphasis on reducing manufacturing costs, increasing production efficiency, and achieving faster time-to-market while maintaining product quality and regulatory compliance. The speaker also informed how regulatory guidelines from USFDA, EMA, ICH, and WHO underscore the importance of process validation, understanding critical parameters, and ensuring product quality and safety throughout the product lifecycle.

Practical approaches to improving product yield were discussed, including equipment qualification, process simplification, and continuous improvement through data analysis and training initiatives. Deshpande concluded the session with an assurance that ACG’s expertise can help pharma companies navigate complexities and achieve success in their endeavours.

Prashant Deshpande,Head - Process Technology& Support,ACG

Digital transformation in the pharma industry

Sasikanta Hotta, VP Technical & Operations-Site Head of Micro Labs, gave an eloquent presentation on the need for digital transformation in the pharma industry at Sikkim Pharma Summit 2024. The session shed light on the crucial role of digitalisation in enhancing profitability, progress, and quality within the pharma landscape. Hotta stressed that in a milieu of dynamic market demands and stringent regulatory frameworks, digitalisation can drive efficiency, productivity and adaptability.

Outlining various facets of digital transformation within the pharma sector, and the impact of robotics and automation to streamline manufacturing processes, the session underscored how machine-to-machine communication and machine learning can help companies achieve seamless operations, corrective actions, and predictive maintenance, thereby minimising downtime and

Hotta,VPTechnical

enhancing overall efficiency. Digitalisation can also help fortify quality

control measures, ensure regulatory compliance, and mitigate financial and reputational damages arising from product recalls.

Hotta shared practical examples of digital transformation initiatives, ranging from smart quality management systems to electronic document management and learning management systems. He pointed out that adoption of advanced technologies underscores the industry's commitment to safety and security.

The session underscored the potential of digitalisation in reshaping the pharma landscape. A key takeaway was that by embracing digital transformation initiatives, companies can navigate evolving market dynamics, enhance operational resilience, and deliver superior products while upholding the highest standards of quality, safety, and compliance.

Evolution and revolutions in pharma packaging

Vijay Kumar Mangla, Glenmark Pharmaceuticals gave an insightful session that delved into the evolution and revolutions in pharma packaging, led by globalisation, technological advancements, and evolving consumer needs. Mangla also highlighted how factors such as growing export markets, stringent regulatory requirements, digital technology and heightened competition are driving impactful changes in pharma packaging.

He accentuated that pharma packaging's evolution encompasses packaging materials, labelling technologies, and automation processes driven by digitalisation. He cited notable examples including inn ovations in blister packaging, cartoning, aseptic filling technology, and logistics solutions for cold chain packaging . He showcased shifts towards child-resistant packaging and personalised medicine packaging as significant developments. He gave some great real life examples such as the transition of in-

VijayMangla,GM and Plant Head,GlenmarkPharmaceuticals

sulin injections from glass vials to prefilled syringes and pumps, adaptation of Crocin tablets through brand extensions and color-coated primary packs, Amrutanjan Balm's shift from glass bottles to plastic, to illustrate his points.

The session emphasised patientcentric approaches with simplified dosing instructions, color-coding for enhanced adherence, and safety measures. The session also explored advancements like smart packaging solutions like electronic monitoring devices, importance of driving environmental sustainability in pharma packaging through adoption of biodegradable materials, tamper-evident packaging solutions etc.

Thus, the session highlighted the dynamic landscape of pharma packaging, driven by innovation, regulatory compliance, and consumercentricity. The presentation gave a comprehensive understanding of the evolving trends shaping the future of pharma packaging.

Sasikanta

& Operations-Site Head of Micro Labs

Kilian E 710 Smart Tablet Press

Sunderraj Konar, GM-Sales & Marketing - Processing Division, Romaco India shed light on the evolving landscape of the pharma industry and offered a comprehensive overview of Romaco's technical prowess and cuttingedge solutions for the industry's evolving needs. The sesson particularly focussed on KILIAN E 710 Smart, a double-sided rotary press designed for high-volume production. With an output of up to 1,020,000 tablets per hour, the KILIANE 710 Smart boasts of features such as a changeable die table for enhanced flexibility, deep-drawn process areas to prevent product penetration, and a unique bellow system to ensure black-spot-free tablets.

The session also highlighted that the equipment's other features such as fill shoe, tablet chute, and tablet scraper etc were designed for optimal performance, easy dismantling, and minimal product loss. In conclusion, Konar's session provided attendees with a comprehensive understanding of Romaco's solutions, emphasising efficiency, reliability, and adaptability to meet the evolving de-

Sunderraj Konar,GM-Processing,Romaco India

KILIAN E 710

Smart,a doublesided rotary press designed for highvolume production gives an output of up to 1,020,000 tablets per hour

mands of the pharma industry.

Furthermore, attendees gained insights into the E 710 Smart's userfriendly design, with features like a paperless batch reporting system, remote assistance capabilities, and seamless integration into existing processes.

Overall, Konar's session gave a comprehensive overview of Romaco's solutions and capabilities.

Future-readyworkforce in the pharma industry

The session, led by Amit Sharma, Head-Quality, Lupin, focused on the technological advancements in the pharma industry and examined future job opportunities in this evolving landscape. The presentation emphasised that pharmaceutical workforce needs to skill, unskill and reskill for transforming times and addressed strategies for creating a skilled and competent task force.

Sharma emphasised the importance of restructuring academic courses to align with industry needs, and ensure that new entrants possess the relevant skills and competencies demanded by the pharma sector. Collaboration between academia and industries was highlighted as essential for bridging the gap between theoretical knowledge and practical appli-

Amit Sharma,Head-Quality,Lupin

cation. He also recommended facilitating internships, collaborative research projects, and guest lectures by industry experts.

The session highlighted the need for a shift from classroom-based learning to practical demonstrations, enabling students to gain hands-on experience and real-world insights. The speaker also stressed on the significance of integrating new learning tools such as VR to enhance engagement and knowledge retention among students, thereby creating a dynamic and immersive learning environment for skill development.

The session offered crucial insights into strategies required by organisations to ensure their workforce is equipped with the necessary skills and competencies to thrive in the digital age.

Global market access and evolving regulatory landscape in pharma

In a thought-provoking session, Dr Nirmal Kumar, VP-Quality, Alkem Labs covered the critical aspects of global market access and the evolving regulatory landscape in the pharma industry. Detailing its role in facilitating product approval, marketing, and integration into national healthcare systems and formularies, Dr Kumar underscored the growing importance of global market access against the backdrop of projections indicating a significant expansion in both the Indian and global pharma markets by 2030. The session highlighted the immense economic opportunities presented by effective market access strategies.

Throughout the session, Dr Kumar elucidated the multiple facets of market access such as product development, pricing, regulatory compliance, and intellectual property rights (IPR) protection. Participants gained insights on the complexities associated with pricing negotiations and regulatory requirements across different markets.

Nirmal Kumar,VP- Quality,Alkem Laboratorie

Volume to value leadership in pharma

Dr Ranjit Mohapatra, Site HeadSun Pharma, Sikkim spoke on the imperative shift from volume to value leadership within the pharma industry. The session delved into the aspects required to drive this transformation, such as quality, innovation, compliance, and strategic partnerships.

During the session, Dr Mohapatra highlighted the critical need for regulatory simplification to streamline processes, reduce bottlenecks, and foster innovation. He said that by aligning regulatory frameworks with industry needs, the pharma sector can accelerate progress.

He said that quality is at the core of the transformation from volume to value leadership. Dr Mohapatra emphasised the importance of an innovative mindset within

Dr Ranjit Mohapatra,Site Head-Sun Pharma,Sikkim

One of the key highlights of the session was the discussion on intellectual property rights (IPR) and its role in safeguarding pharma innovations. Dr Kumar stressed the importance of patent protection in driving innovation, economic growth, and consumer protection within the pharma industry.

The session also highlighted the challenges faced while entering new markets such as increasing demand for cost-effectiveness, intensifying competition, evolving healthcare landscapes, and changing regulatory requirements. Dr Kumar outlined the necessity for a comprehensive market access strategy, encompassing activities such as market research, value proposition development, regulatory compliance, and stakeholder engagement.

The session provided several takeaways for companies looking to maximise market access opportunities and ensure the delivery of innovative healthcare solutions to patients worldwide.

organisations to improve processes, enhance efficiency, and minimise waste.

He also recommended integrating process analytical technology (PAT) to design, analyse, and control manufacturing processes more effectively, leading to improvements in quality, productivity, and resource utilisation.

The session also underscored the role of learning and development in driving organisational transformation. The speaker stressed on the need to align training with job roles, and on fostering habit change, particularly in communication, through feedback sessions.

The session served as a reminder for the industry to rethink their approaches to succeed in the journey towards value-driven leadership in the pharma sector.

GLIMPSES OFSIKKIM CONCLAVE 2024

GLIMPSES OFSIKKIM CONCLAVE 2024

EXPRESS PHARMA

GLIMPSES OFSIKKIM CONCLAVE 2024

Impact of the newAnnex1 on sterile filling

The new Annex 1 of the EU Good Manufacturing Practices for the production of sterile medicinal products came into force on August 25,2023.The document has far-reaching consequences for sterile filling operations. Dr Johannes Rauschnabel,Director-Advanced Technology Development,Syntegon explains the factors that pharma manufacturers need to consider – and how can equipment suppliers like Syntegon help with the implementation

15 years after the previous version came into force, the new Annex 1 ‘Manufacture of Sterile Medicinal Products’ of the EU GMP guidelines1 has become effective on August 25, 2023. Its scope alone suggests numerous implications for sterile manufacturing processes.

The document now comprises 58 pages instead of previously 16, while the size of the chapter on barrier technology has even quadrupled. Long before its publication, the new Annex 1 was the source of controversial discussions that continue to this day. On the one hand, the document leaves room for interpretation; on the other hand, many players in the pharma industry fear overregulation.

EU guidelines with global consequences

Overall, the new Annex 1 sends a clear signal in direction of the highest possible product quality. Its primary objective is to prevent product contamination.

The transition period of one year shows that implementation is not easy; for the loading and unloading of freeze dryers, this period even amounts to two years. However, these relatively long deadlines also underline the expectations on the part of the authorities: the changes should not only be planned or considered; they should also be implemented in practice – both for the installation of new plants and for retrofitting existing ones.

Although Annex 1 is an EU guideline, the document has consequences for the global pharma industry. For one thing, the specifications affect the manufacturing processes of drugs imported into the EU. For another, the coordination of the document between EMA, WHO and PIC/S and the publication of equivalent documents by these organisations underscore its global relevance. Accordingly,

REGULATIONS

Annex 1 has created a stir throughout the world. Inspectors from all regions derive the requirements for their market –and are confronted with the same questions regarding their implementation.

Focus on barrier technology

One rationale of the new Annex 1 is the separation of the aseptic process area from the operator environment. For the first time, the document clearly recommends the use of appropriate barrier technologies – isolators and Restricted Access Barrier Systems (RABS) are considered equal. Pharma manufacturers will therefore require at least RABS for the approval of new products; new approval on

existing cleanroom lines will only be possible in exceptional cases.

In the year following the pub-

lication of the guideline, the industry witnessed a veritable ‘run’ on RABS upgrades of existing clean room lines, which

continues to this day. The aim is to fulfill the requirements of Annex 1 for the operation of RABS as completely as possible –which is quite a challenging task. Pharma manufacturers must decide whether to retrofit an existing clean room line for a new product or invest in new filling equipment that runs with isolator (or RABS). Isolator technology will become the new ‘normal’, as automatic biodecontamination processes and the pressure difference from the operator environment provide additional safety. RABS is more likely to come into play for frequent product changes and with experienced operators.

Aquestion of sterility

To establish and maintain steril-

ity as required by Annex 1, pharma companies must conduct a contamination risk analysis and document it with measures in the form of a Contamination Control Strategy (CCS). Advanced equipment makes an important contribution here. In the second chapter of Annex 1, automation and robotic systems are highlighted under the heading “Appropriate technologies”. By using these technologies, gloves and human intervention in barrier systems can be reduced to an absolute minimum or even eliminated.

The issue of gloves presents many challenges, which are acknowledged in separate paragraphs. For example, gloves are to be additionally tested in operation during longer

April 2024 30

One rationale of the entire newAnnex1 is the separation of the aseptic process area from the operator environment.For the first time,the document clearlyrecommends the use of appropriate barrier technologies

From nowon,pharma manufacturers require barrier technologies for the approval of new products; newapproval on existing cleanroom lines will onlybe possible in exceptional cases

Syntegon’s fullyautomated,gloveless Versynta microBatch production cell fills between 120 and 500 containers per hour with virtuallyno product loss

Advances in automation and the use of robotic systems will enable further optimisations in sterile filling in the future

REGULATIONS

campaigns – which is not possible with the glove testing equipment used to date without risking the integrity of the sterile room.

In fact, the new Annex 1 requires high level disinfection as soon as the gloves have been exposed to the RABS environment. Besides the aseptic setup situation, this also concerns the intervention involving door opening during production. This makes the disinfection process very demanding, as the final steps must be performed with the doors closed. At the same time, the disinfection reagents should not affect packaging materials, components, and unsealed products. A switch to gloveless systems with robotics that handle these manipulations represents the “grail of solution scenarios”. One example is Syntegon’s new Versynta microBatch2 for processing very small batches. The fully automated isolator production cell fills between 120 and 500 containers per hour with virtually no product loss and 100 percent in-process control. Glove interventions are no longer necessary in this solution.

‘First Air’as major challenge

Annex 1 also sets clear requirements for air flow: unidirectional air flow (UDAF) is mandatory for open isolators and RABS in all class A areas and should not be interrupted between the air inlet and the open product. The air velocity (0.45 m/s +/- 20 per cent) and its measurement are located ‘at working position’. This does not refer to the vertical position (working height), but the area of the critical, quality-relevant processes on the machine, such as filling, stoppering, and gassing. UDAF has the task of carrying any potential residual particles away from the product. This can also be achieved well at lower air speeds at product height.3

However, especially the ‘First Air’ principle, which is addressed for the first time in a European GMP guideline, poses new challenges for manufacturing companies. First Air refers to a flow of filtered air that must not be interrupted prior to

contact with exposed product and product-contacting surfaces. This ensures that the air reaches the product without turbulence or contamination. Yet this uninterrupted flow is not possible everywhere. A typical exception is the filling needle together with the filling

needle holder, which must be positioned exactly above the open, pre-sterilised packaging material in order to achieve loss-free filling. It is expected that these components are aerodynamically designed to minimise turbulences and that these items can be sterilised

separately and installed aseptically.

Considering QRM and CCS from the start

Further important topics covered in the new Annex 1 are Quality Risk Management (QRM) and the aforemen-

tioned CCS, which are intended to provide pharma producers with more options for defining the optimal manufacturing process for their products. Overall, the new guideline has a stronger focus on a holistic, risk-based approach. CCS not only addresses the working

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practices in the immediate production process to prevent microbial, particulate, and endotoxin/pyrogenic contamination in the final product. It also includes the entire manufacturing chain from raw material to components and packaging materials to the finished drug.

When it comes to QRM, however, machine manufacturers also have their responsibilities. Good design of the machine, equipment, and process is crucial for Annex 1-compliant production. Suppliers such as Syntegon offer extensive support in this regard: in accordance with QRM principles, potential quality risks can be proactively identified, scientifically evaluated, and controlled. Qualification and validation measures confirm that both the

The new Annex 1 will change sterile filling significantly.In the early phase after the guideline has come into force,the main objective for all players – from pharma companies to inspectors to equipment suppliers – is to remain in close exchange and to learn from each other.One thing is certain: the new Annex 1 has come to stay

design and the procedures have been implemented correctly and meet expectations.4

Outlook

The new Annex 1 will change sterile filling significantly. Many new, mandatory details require inn ovative solutions, while advances in automation

enable further optimisations. In addition, the introduction of CCS and QRM in the document also opens up regulatory space for product-specific solutions. In the early phase after the guideline has come into force, the main objective for all players – from pharma companies to inspectors to equip-

ment suppliers – is to remain in close exchange and to learn from each other. After all, one thing is certain: the new Annex 1 has come to stay. And despite certain challenges and contradictions, it has a clear intention: to provide patients around the world with the highest quality medicines.

References

1. EudraLex: The Rules Governing Medicinal Products in the European Union Volume 4 EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary UseAnnex 1 Manufacture of Sterile Medicinal Products (2022), https://health.ec.europa.eu/system/fi les/2022-08/20220825_gmpan1_en_0.pdf

2. https://www.syntegon.com/ solutions/pharma/microbatch-processing/

3. Air Speed Qualification: At Working Position or Working Level?Pharmaceutical Engineering, September/October 2023, https://ispe.org/pharmaceutical-engineering/september-october-2023

4. https://www.syntegon.com/ services/expert-services/qualificationand-validation/

April 2024 32

AI in packaging and labelling processes

Prabir Das,Pharma Expert explains how AI is revolutionising packaging and labelling processes by offering augmented intelligence,enhancing productivity,quality,and regulatory compliance while minimising variability and optimising resources across the supply chain,paving the way for advanced digital management systems in the industry

Artificial Intelligence (AI) is an emerging digital technology-driven tool to support various processes from design and development to distribution and delivery of goods and services with improved quality, safety, security and punctuality, thereby helping to enhance consumer satisfaction and boost the trust-building process. Since there is no artificial or arbitrary element in it and the level of intelligence is enhanced in this programme, I call it Augmented Intelligence. Packaging and labelling, being an integral part of the products, are also transforming by adopting such contemporary technologies to remain at par with the industry standards across the globe.

AI is a hybrid form of programming, which is built on numerous micro-level data and various information with multiple in-built logics. It is a customised intelligent program and can be compared with a cluster of PLCs, where multiple logics are used for processing and analysing data and information to take a decision or an action. Often various machine learning data are also ingrained for AI programming to make it suitable for controlling different equipment and their functionalities. Ergonomic and demographical data derived from human nature and behaviour are also used to develop multiple logics for analysing data internally. All these helps to behave the program as close as the human brain, but in a much quicker and smarter manner, eliminating subjectivity and variability. AI has inputs from multiple processes, data from various unit operations and a lot of logical information which helps to make rational decisions and appropriate actions, mimicking the human brain. The critical part of human intelligence is reasoning or judgement-based decisionmaking and actions. This is quite natural or spontaneous and

PACKAGING

varies from person to person depending on individual intellect, wisdom and many external factors. Since the level of understanding, reasoning and intelligence varies from person to person, the quality of judgement also varies while making a decision or taking an action. Secondly, the time spent to take a decision or an action varies from person to person because of this difference in level of understanding and intelligence. It also varies from time to time depending on individual physical and mental status and a set of external factors. Perception, understanding, interpretation and reasoning varies from person to person along with their rational and analytical capabilities.

AI is developed for maintaining consistency with quality and swift actions with rational decisions to mitigate this risk of variability and to eliminate the human factor, especially in large scale processes and operations.

AI primarily works on data, information and logic, something similar to our mind which works on thoughts, feelings and emotions. Our decisions and actions are derived from our thoughts, feelings and emotions which is the result of internal churning within our minds. Developing an AI programme is a complex process and data is one of the critical ingredients to develop it. Data capture, data transform, data storage, data processing, data analysis, data transfer, data exchange to data retrieval all are

part of the programme and primarily responsible for its functionality. Hence data hygiene and data integrity are very much essential for its effective functioning. The same is true for the information and logic, which should be authentic and rational for the successful development and functioning of any AI programme.

Even though packaging and labelling are widely spread across various industries to protect the product and secure its stability, quality and safety across the entire supply chain, the majority of it is still under the MSME sector and often most of them cannot afford a costly and complex tool like AI in their operations. However, packaging and labelling users (relatively larger industry houses) can explore a few areas to optimise the productivity and quality of their goods and services. The major role of packaging and labelling is

brand protection and brand promotion, establishing connectivity of the product with the people and supporting the entire operation and supply chain system. There are a few areas where AI programme can be customised to deploy in optimising the packaging design from primary packaging level to palletisation. It can also help to enhance productivity, minimise process cycle time, improve accuracy and maintain consistency. It is also helpful for quality and regulatory compliance.

During the packaging design and development phase, AI can help select the right containerclosure system (primary pack) or a better pack option with optimum volume and maximum level of protection. Similarly, it can also help in optimising dimensions of secondary and tertiary packs to maximise pallet capacity. It can also help in designing the packaging process

through process mapping with minimum floor space utilisation and process cycle time. However, to develop the program lot of product data, packaging material data and data from each unit operation will be required, along with other allied information to analyse internally for an optimal workable option through its built-in logics.

AI can also help in standardising, harmonising and optimising material specifications and process parameters for consistent results through automation, wherever feasible. Artwork and Artwork Management System (AMS) are part of labelling which is an integral part of packaging. Nowadays these are mostly being managed digitally for speed, accuracy and quality. The entire AMS can be well managed through AI to eliminate variability across multiple sites of operations. AI can also help in managing a large volume of work with multiple languages for any global business. Generic updates, applicable to multiple product labelling, also can be managed well through an AI program. Checking of artworks, proofs and commercial supplies of printed packaging materials can also be automated through AI tools. A well-programmed AI can also manage local and regional languages along with a common global language and its translation as per the end user's requirement.

Digital features on labelling, coupled with AI tool can change

the entire landscape. Quality function associated with packaging materials, packaging operations and finished packs can also be considered for managing through AI tools to minimise or eliminate variability due to human factor. This can result uniform quality of a product pack while reaching the end users. AI can also be deployed in areas like rejection analysis, process control, demand-supply management, forecasting, scheduling and planning, warehouse management, vendor management, etc. However, before deploying AI for any process, basic data, information and logics need to be made part of the URS for the successful development of the program. We have seen the growth of pharma industry from small scale manual operations to large scale automated operations to cope up with the business need and speed. Application software like ERP / SAP, TRACKWISE, DOCUMENTUM, LIMS, and GLAMS / AMS are now integral parts of a globally successful pharma business. Similarly, AI also will make inroads in coming years and become an integral part of the process. Even though AI has the potential to bring transformation in every level of our society, thoughts, feelings and emotions are still in the precious possession of human beings and that is why people are continuously working on various advanced tools to enhance the quality of goods and services to satisfy our necessities.

April 2024

RESEARCH

Clearing the air on liposomes and LNPs in drug delivery

Arun Kedia,MD,VAVLipids looks at some significant differences between liposomes and LNPs that extend beyond their intended applications,encompassing variations in morphology, composition and manufacturing processes

Lipid-based formulations have been pivotal in advancing drug development and facilitating the delivery of therapeutic biomolecules and genes. However, a widespread misconception exists regarding the interchangeability of terms like liposomes and lipid nanoparticles (LNPs).

True enough, the use of liposomes and LNPs as carriers for highly specialised drug and biologic payloads, notably mRNA therapies, has experienced remarkable growth—notably, the initial SARS-CoV-2 vaccines authorised for use employed LNPs as delivery mechanisms for

mRNA payloads.

So, in that sense, both are effective in drug delivery. However, it is essential to recognise that though they share some similarities, they differ significantly in composition and function. In this article, we look at some significant differences between liposomes and LNPs that extend beyond their intended applications, encompassing variations in morphology, composition and manufacturing processes.

Deep dive into differences:

Liposomes vs.LNPs

Morphology: In technical terms,

LNPs encompass nanoparticles incorporating lipids, with liposomes falling under this category. Within the scientific literature, the term LNP specifically denotes a distinct particle type differing from liposomes in morphology, size, and composition. Unlike liposomes, LNPs lack an entrapped aqueous volume.

Instead, they feature a core containing lipids and nucleic acids such as mRNA, siRNA, or DNA. Their structure reveals a multi-layered core comprising contracted rings of lipids and nucleic acids interspersed between lipid layers. Compared to conventional liposomes, the di-

verse morphological features of LNPs result from the specific composition and ratios of individual lipid components within them.

Composition: In their composition, LNPs and liposomes share similar main components, encompassing lipids and cholesterol. However, a notable distinction arises regarding ionisable lipids, which are essential in the formulation of LNPs, whereas liposomes lack strict lipid type requirements.

Despite this commonality, a significant difference lies in the component ratios, particularly the cholesterol content.

RESEARCH

Cholesterol, representing upto 40 per cent of the LNPs structure, contributes to formulation rigidity, stability and controlled release owing to its hydrophobic properties.

For instance, the classic liposomal product DOXIL follows a ratio of HSPC:CHOL:DSPEPEG2000=3:1:1. In contrast, the components of the two prominent mRNA COVID-19 vaccines feature cholesterol content at 42.7 per cent and 38.5 per cent, respectively—levels significantly higher than those observed in liposomes.

Manufacturing contrast

The manufacturing processes for liposomes and LNPs differ significantly in the upstream stages but share similarities in downstream processing steps. In the case of conventional liposomes, the initial step involves forming crude liposomes using processes like solvent dilution. Subsequently, particle size reduction is achieved through extrusion or homogenisation to meet the desired size distribution range. Purification follows, utilising systems like Tangential Flow Filtration (TFF), and the final stage involves terminal sterilisation.

For LNPs, the process commences with preparing a lipid stock solution in solvents like ethanol and nucleic acid in an acidic buffer. Particle formation and size reduction are typically managed using high-efficiency microfluidic mixing systems to achieve a narrow polydispersibility index (PDI). This

Choosing high-quality lipids is paramount for both LNPs and liposomal-based products.Lipids must adhere to GMP,with meticulous control over impurities,mastery of complex analytical techniques,and comprehensive evidence of longterm stability

mixing step increases the overall process volume, necessitating reduction through TFF to a more manageable level. A buffer exchange via diafiltration may be performed to attain a neutral buffer, and a cryoprotectant can be optionally added. The final step, terminal sterilisation, mirrors the liposome process, completing the LNP formulation.

Howmicro-mixing systems facilitate nucleic acid LNPcreation

Various micro-mixing technologies contribute to the generation of LNPs. In a typical system, two vessels house lipids and nucleic acid in a buffer. Two sets of pumps are then converged through a mixing unit. The quality of LNPs is intricately linked to the geometry of the micromixing unit. The pumps must operate without pulsations, as any pulsation may increase the size polydispersity of the LNPs and impact the dependable encapsulation of the payload.

Microfluidics is in a continual state of advancement, aligning with the progress of nucleic-

acid therapeutics. The overarching goals include achieving high flow rates and minimising processing times in a linearly scalable manner conducive to industrial deployment.

Primarychallenges in LNP manufacturing

The multitude of operational parameters poses a significant challenge in optimising the LNP manufacturing process. The selection of lipids and various manufacturing steps can impact critical factors such as particle size, polydispersity, active loading, and encapsulation efficiency (EE), also known as the percentage of encapsulation.

Micromixing equipment exhibits variability, generating diverse outcomes. Careful calibration of temperature, hold times and flow rates during the mixing process is essential as it significantly influences the final product. Temperature control postinitial particle formation is crucial to enhance nanoparticle stability.

Another crucial consideration involves the sterile filtration and fill-finish process. Tradi-

tional filling processes at room temperature are deemed unacceptable. Given the limited stability of LNPs at room temperature, the duration for performing aseptic fill-finish must be brief, at low temperatures. Subsequently, a swift transition to temperature-controlled long-term designated chambers or storage rooms is imperative.

Advantages of lipids and essential factors in selection

Lipid-based formulations play a pivotal role in drug discovery and delivery, enhancing bioavailability by controlling therapeutic compounds' solubility, permeability, absorption, distribution, and metabolism. Notably, these nanoparticles exhibit minimal toxicity, extend drug duration by prolonging half-life, and regulate drug release. Lipid nanosystems, incorporating modifications like gangliosides or polyethylene glycol (PEG), evade immune detection and enhance the therapeutic index (passive targeting). Additionally, pH-sensitive formulations enable controlled drug

release in acidic environments, while antibody associations like folic acid enhance tumour targeting. These nanodrugs synergise with other therapeutic strategies, offering multifaceted benefits for improved patient responses.

Choosing high-quality lipids is paramount for both LNPs and liposomal-based products. Pharma-grade lipid manufacturing technology demands specific core competencies, and only a few global producers cater to this market. Lipids must adhere to Good Manufacturing Practices (GMP), with meticulous control over impurities, mastery of complex analytical techniques, and comprehensive evidence of long-term stability.

Parting thoughts

Lipid-based formulations tailored for drug delivery exhibit immense promise in overcoming the constraints associated with conventionally formulated drugs, ultimately augmenting their therapeutic efficacy.

Particularly noteworthy is their potential in genetic medicine, where critical applications such as gene editing, vaccine development, immuno-oncology, and various genetic therapies hinge on the efficient delivery of nucleic acids into cells. The versatility and capabilities of these nanoparticles position them as a promising avenue for advancing therapeutic interventions and addressing the evolving landscape of medical treatments.

POST EVENT

TransChem Pharma,in collaboration with BASF, organises seminer on excipient innovation

Themed “Formulator’s Forum: Exchange on Excipients Innovation”,the event aimed to unravel the intricacies of excipient utilisation for superior product outcomes

TransChem Pharma, in collaboration with BASF, organised a seminar on March 15, 2024 at the JW Marriott Mumbai.

Themed ‘Formulator’s Forum: Exchange on Excipients Innovation’, the event aimed to unravel the intricacies of excipi-

ent utilisation for superior product outcomes.

Distinguished speakers Dr Felicitas Guth and Dr Rainer Dobrawa, representing BASF Pharma Solutions, Germany, shared their insights into excipient inn ovati on and the multifaceted applications of

Soluplus. Umakanth Kanna from BASF Singapore explored the potential of Sustained Release Polymers, while Dr Rajkiran Narkhede and Atish Sawant from BASF Pharma solutions, India led a discussion on Kollicoat Smartseal polymers.

The seminar had over 125+ participants who lauded the organisers for its content and expressed a keen interest in further technical engagements. The organisers attributed the event's success to the leadership of Managing Directors Zubin Zaveri and Shiv-

ang Zaveri. The collaborative effort between BASF Pharma Solutions and TransChem Corporation Pharma emphasises a commitment to pushing the boundaries of pharma formulations with renewed vigour and collective expertise.

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VIVAPHARM® HPMC: Cellulose based polymer for film coating,wet granulation and hard capsule manufacturing

Hydroxypropyl methylcellulose (HPMC) is a cellulose ether widely used in drug formulations due to its biocompatibility, uncharged nature, solubility in water and thermoplastic behavior.1

Manufacturing process

VIVAPHARM® Hydroxypropyl Methylcellulose (HPMC) is produced through the etherification synthesis process of cellulose. Initially, cellulose undergoes milling and activation using caustic soda. The activated cellulose is then subjected to reactions with methyl chloride and propylene oxide, resulting in the formation of HPMC. Methylcellulose (MC) is produced through the reaction of cellulose with methyl chloride. Throughout the etherification synthesis, methanol, water, and sodium chloride (NaCl) are generated as primary byproducts. Water-soluble byproducts are eliminated through a heating/condensation system, while NaCl is removed via subsequent washing

stages. Any residual sodium hydroxide (NaOH) is neutralized with citric acid during the washing process if necessary.

Following the washing stage, a conditioning step ensues, involving the addition of

hot or cold water to achieve the appropriate moisture content for subsequent milling and drying operations. Viscosity reduction is accomplished by subjecting HPMC to high temperatures and hydrogen peroxide treatment until achieving a viscosity of less than 50 mPas. pH adjustments are made using sodium bicarbonate.

Physicochemical properties of VIVAPHARM® HPMC

At low temperature HPMC are highly hydrated, H bonding between the HPMC hydroxyl groups and water favors hydration, water molecules close to HPMC hydrophobic methyl groups for water cages. At high temperatures water cages are disrupted, increasing the mo-

bility of water molecules and facilitating the hydrophobic association of methyl groups (shown in blue).

The viscosity of the polymer solution is directly proportional to the polymer average molecular weight.

In accordance with the current United States Pharmacopeia (USP) monograph as of 2023, USP Hypromellose is delineated as a methyl and hydroxypropyl mixed ether of cellulose. It is characterized by calculated proportions, based on the dried substance, of methoxy (–OCH3: 31.03) and hydroxypropoxy (–OC3H6OH: 75.09) groups, adhering to specified limits corresponding to various types of Hypromellose (hydroxypropyl methylcellulose) as outlined in the provided

table. The former official nomenclature for hypromellose was "hydroxypropyl methylcellulose" or "HPMC."

Conversely, the USP elucidates hypromellose by its substitution type, denoted by a four-digit numerical code appended to the non-proprietary name. The initial two digits signify the approximate percentage content of the methoxy group, while the latter two digits indicate the approximate percentage content of the hydroxypropoxy group, both calculated on a dried basis. 3

come this issue is inserting chemical groups by specific reactions with hydroxyl groups at C2, C3 and C6. If all available hydroxyl groups on each repeated unit are substituted the degree of substitution (DS) is three; if in average two hydroxyl groups per repeated unit are substituted, then the DS is two, and so on. Particularly for HPMC, the degree of substitution (DS) refers to the number of moles of methyl groups per repeated unit, whereas the molar substitution (MS) reports the number of moles of hy-

Degree of substitution

The intra- and intermolecular H bonds among the hydroxyl groups and van der Waals interactions hamper the solubility and process ability of cellulose. One way to over-

droxypropyl groups per mole of repeated unit. 1

The hydrophilic/hydrophobic character of HPMC can be tuned by the DS and MS values; samples with high DS and MS values

Fig.1 Manufacturing process of VIVAPHARM® HPMC

Fig.3 Graphical representation of Viscosityof different grades of VIVAPHARM® HPMC

Fig.2 Rheologyof VIVAPHARM® HPMC

PHARMA PULSE

tend to be more hydrophobic, whereas, samples with low DS and high MS are more hydrophilic. 1

Low molecular weight HPMC samples have higher entropy of dissolution than high molecular weight HPMC samples; therefore, the drug release is faster from a low molecular weight HPMC matrix than from a high molecular weight HPMC matrix. 1

Regulatoryoverviewof

VIVAPHARM ® HPMC

Drug Master Files (DMFs) have been submitted for VIVAPHARM® HPMC to the United States Food and Drug Administration (FDA), citing the manufacturing sites Derivados Macroquimicos S.A. de

C.V., Mexico, and Microcellulose Weissenborn, Germany. The assigned DMF number for all types of VIVAPHARM® HPMC is 24926.

Regarding compliance with Chinese regulations, VIVAPHARM ® HPMC has obtained registration in the Chinese Drug Master File (cDMF) system for the manufacturing site Microcellulose Weissenborn, Germany, under registration number F20200000411.

Furthermore, the suitability of VIVAPHARM® HPMC monographs according to the European Pharmacopoeia standards has been certified for the manufacturing site Microcellulose Weissenborn, Germany. The certification registration number is R1-CEP

2007-321-Rev 01, effective as of 03-04-2014.

Food Compliance of VIVAPHARM® HPMC

Europe:

VIVAPHARM® HPMC adheres to EU regulations as an approved food additive, meeting the specifications outlined in Directive No. 231/2012/EC, as detailed in the E464 monograph for "Hydroxypropylmethylcellulose." We ensure compliance with country-specific regulations governing food additives.

USA:

VIVAPHARM® HPMC products are recognized as Generally Recognized as Safe (GRAS) by the US Food and Drug Administration. Our Hydroxypropyl Methylcellulose is

listed under section 21 CFR 172.874 as GRAS. Additionally, it conforms to the standards set forth in the Food Chemical Codex Monograph for Hydroxypropyl Methylcellulose (INS: 464, CAS: [9004-65-3]).

Pharmacopoeia compliance of VIVAPHARM® HPMC

all specified parameters and limits delineated in these compendial monographs.

Moreover, VIVAPHARM® HPMC variants, such as E3, E5, and E6, are generally aligned with the standards set forth by the Chinese Pharmacopoeia (ChP) and conform to the prevailing Hypromellose monograph within the ChP 2020 edition.

References

1) Tundisi L.L, Mostaco G.B, Carricondo P.C, Petri D.F.S. Hydroxypropyl methylcellulose: Physicochemical properties and oculardrug delivery formulations. Eur.J.Pharm Sci. 159 (2021)

2) www.jrspharma.com/ pharma_en/products/coatings/v ivapharm-hpmc

3) https://online.uspnf.com/ uspnf/document/1_GUID6A0B0F3C-FA70-433C-AD552020BBC64718_4_en-US

Suyesh

VI-

VIVAPHARM® HPMC adheres to Pharmacopoeial standards as outlined in the current editions of the European Pharmacopoeia (Ph. Eur.), United States Pharmacopeia (NF), and Japanese Pharmacopoeia (JP). This compliance encompasses the respective monographs for "Hypromellose" in these compendia.

VAPHARM® HPMC satisfies

PHARMA PULSE

METTLER TOLEDO Launches NewGeneration of LaboratoryBalances

With the introduction of the new Advanced and Standard Balance portfolio,including MX,MR,MA and LAlines,METTLER TOLEDO positions itself at the forefront of laboratory weighing when it comes to simplicity,performance and robustness.The new balances provide customers with even greater resilience,even better measurement performance,and an even simpler user interface and smart features for a smooth,ergonomic and sustainable weighing experience

METTLER TOLEDO

announces the launch of four new laboratory balance lines. Starting today, laboratories from large enterprises, medium-sized companies, and startups worldwide will have a more comprehensive and superior selection of balances to ensure accurate weighing.

Customers will benefit from a broad range of balance models that meet the needs of every user, industry and workplace, from advanced weighing requirements to the most essential weighing needs. The new portfolio is engineered for enhanced user experience, designed with sustainability in mind and built with the highest quality materials for trusted, long-lasting performance.

"Our customers rely on accurate weighing results for all their applications, and with the new portfolio users can benefit from reliable performance and trusted results, simple operation, advanced technology, and service expertise available worldwide. The new portfolio covers readabilities ranging from 1 g down to 0.01 mg and capacities from 220 g up to 32 kg, including large platforms and compact portable models. Our ultimate goal is to provide our customers with the peace of mind they need for accuracy and reliability and meet the requirements of all their weighing needs," says Claas Boerger, Head of Laboratory Balances.

The new lines also feature highly efficient materials and usage.

“METTLER TOLEDO is committed to sustainability,

and we are proud to share that these new Advanced and Standard balances feature both power-saving capabilities and

more sustainable use of materials," says Stefan Heiniger, Head of Laboratory Division. “We are pleased to continue to

expand our portfolio of highquality solutions with new products that incorporate Design for Environment principles.”

The MX balances boast weighing performance, effortless data management, and user-friendliness. With innovative engineering these balances provide an ergonomic weighing experience and satisfy advanced weighing requirements. Highly intuitive and with a multitude of smart features, such as ErgoDoors, SmartPan, StatusLight, LevelControl and advanced routine testing functions, these balances simplify your weighing tasks. To easily comply with GxP regulations, they offer user management and activity log traceability.

MR balances deliver consistently accurate results even in the harshest weighing environments. Thanks to their robust construction, these balances are the perfect choice whether you weigh in a busy lab or the challenging conditions of a production setting. A range of built-in applications and connectivity options make MR balances highly versatile.

To make every day weighing easy, MA balances are designed with a focus on valuable, practical features, and they deliver quality without compromise. Touch control on a bright LCD screen, simple menus, guided applications and easy result documentation make weighing a breeze. These balances are also available in a compact portable design with battery operation that saves valuable space on your workbench and enables you to easily

transport your balance.

With the LA balances, you can experience affordable quality with all the basic functions you need for essential weighing tasks. LA balances feature a bright LCD display for optimal reading in all conditions. With an RS232 interface, you can connect to a printer, secondary display, or other device. Each balance has three integrated applications (weighing, dynamic weighing, and piece counting).

To learn more about the new Advanced and Standard Balance portfolio, visit http://mt.com/new-lab-balances

About METTLER TOLEDO

METTLER TOLEDO is a leading global supplier of precision instruments and services. We have strong leadership positions in all of our businesses and believe we hold global number-one market positions in most of them. We are recognized as an innovation leader and our solutions are critical in key R&D, quality control, and manufacturing processes for customers in a wide range of industries including life sciences, food, and chemicals. Our sales and service network is one of the most extensive in the industry. Our products are sold in more than 140 countries and we have a direct presence in approximately 40 countries. With proven growth strategies and a focus on execution, we have achieved a long-term track record of strong financial performance.

For more information, please visit www.mt.com.

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PRIME NEO: High-performance door from Gandhi Automations

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Gandhi Automations presents the multi-composites, high-performance door PRIME NEO for clean environments.

Complete washable, greater sealing and pressure resistant.

When it comes to pharmaceutical facilities and laboratories, clean rooms’ hygiene and protection from environmental contamination are the most important factors to consider.

Gandhi Automation's PRIME NEO High Speed Doors are designed to provide superior sealing and resistance to pressure differences for clean rooms. And the added advantage is that it is absolutely washable.

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Safety: PRIME NEO reduces the risk of accidents and damage. The free, flexible, and soft bottom edge minimizes hitting impact. The radar detector and

inbuilt photocells reopen the door at the slightest impact.

Windows: The transparent material allows people to see coming traffic. Long-term transparency is assured, as the material is anti-fatigue PVC fabric.

Multi-Composite Structure:

The toughness of the side guides and their ability to absorb an impact avoid high repair costs. PRIME NEO is anticorrosion and paint-free, which ensures durability in corrosive and aggressive environments.

Auto-reset: The door is equipped with auto-reset technology. In the event of an accidental crash, the curtain sets itself again. This unique system avoids time loss and reduces the risk of high repair costs.

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