New Working Models with Pharma

and OECD have outlined the principles of 3R (Replacement, Reduction and Refinement) framework for performing more humane animal research or do away with animal research completely. Current thinking from opinion leaders and multilateral institutions are strong signals for the imminent shift to “non-animal”methods through the use of NAMs. Current literature describe NAMs using micro-physiological systems (MPS) like organ-on-a-chip, tissue-on-a-chip, organotypic cultures like co-cultures, 3D organoids, in vitro/ in silico toxicity prediction tools, quantitative structure activity relationship (QSAR) computer-based models for toxicity testing. Wide-ranging developments of MPS models using human cells have been developed to improve toxicity and efficacy prediction in humans, and are understandably explored for use in both pre-clinical and drug development stages.

An example of a well-used NAM in vitro method utilising HiPSC is CiPA (Comprehensive in vitro Pro Arrhythmia) assay to predict risks associated with drugs on ion channels. The readouts of CiPA paradigm help profile the risk of candidate drugs before clinical trials are undertaken. Other assays like ALI (in vitro air liquid interface) cell culture model for studying structure and function of organs (including lung, intestine, kidney, lung, and liver) have been developed and validated for commercial applications.

Indian CROs: A Historical Perspective

The ~25-year old Indian CRO industry has done well by achieving US$1.8 billion in revenues in 2021, while growing at double digits over the last decade. However, the performance is mostly attributable to chemistry services. Indian CROs are predominantly offspring of the traditional Indian pharma industry or Indian corporate conglomerates, both financially and expertise-wise. Consequently, the industry is steeped in chemistry skills but less so for biology. Chemistry skills, stemming from the reverse-engineering culture of traditional generics industry, have been well exploited for early research, providing services for synthetic and medicinal chemistry, and also later for large scale manufacturing, where CDMO services have come of age and form significant portions of CRO revenues. However, due to the chemistry-laden heritage, the Indian CRO industry has made only modest strides in biology services. In at least one case a top-10 pharma major, Eli Lilly cancelled an ongoing research services contract with an India CRO, and shifted to Pharmaron in China for access to better biology skills.

More recently (for less than a decade) Indian CROs are incorporating biology services through both organic and inorganic routes. Examples of this include GVK Biosciences acquiring Aragen in 2015, and Intox in 2021. The latter was acquired for the expressed purpose of incorporating animal toxicology services. But even these are mostly geared towards “non-human” cell biology or CDMO-type large scale biologics manufacturing, and not so much innovation and new discovery (intellectual property). To reinforce this take the example of the leading global CRO, Charles River Laboratories, that has played an equal part in the innovation of 70 per cent of the drugs approved by its pharma clients over the last 5 years. In line with this leading international CROs (CRL, Wu-Xi, Pharmaron, Eurofins) are all evolving not only from an increased focus on cell biology but also through embracing human cell biology.

Introducing NAM concept in Safety and Potency Testing Offered as a Solution

Non-clinical safety and potency testing on human MPS models is a reality to practice at industrial scale when digital tools and robotic process automation complement the in vitro system developed. One of the best features of this model is its seamless integration into the user’s workflow. The other advantages like user’s data privacy, access to human MPS based robust testing methodologies integrated in the process to implement in R&D, pre-clinical, clinical and manufacturing stages are totally revolutionary.

Vaccine neurovirulence is a real safety concern of all the vaccines produced for neurotrophic viruses (eg: Polio, Covid19, HIV, Yellow fever, Mumps, Measles) with history of mishaps associated with qualified vaccines in the immunised population. Monkey Neurovirulence Test (MNVT) is the gold standard method practiced for over 50 years to test neurovirulence. Likewise, Human data are generally not available for IND’s neurotoxicity profile, but when they are they take precedence over animal test results.

References are available at www.pharmafocusasia.com

AUTHOR BIO

Subhadra Dravida PhD, Founder CEO Transcell Oncologics that has Transtoxbio (transtoxbio.com) as a dedicated vertical with next gen workstation solutions in offering Safety Efficacy Testing as a Solution to the global pharma, biopharma industry. suba.dravida@tran-scell.com

Vasanthi Dasari PhD, Scientific Officer and experimentalist @Transcell Oncologics with 12+ years of research leadership background

Technological and Regulatory Changes in Pharmacovigilance

Oracle’s safety management systems

Yashi Kant, Vice President, Health Sciences, Asia Pacific, Oracle Corporation

1. Regulatory compliance and pharmacovigilance are undergoing a constant barrage of changes, which Pharma businesses can constantly cope with. How prepared is Oracle to cope with the change? Please share your experiences if any.

Maintaining regulatory compliance in a global marketplace is increasingly challenging as wellestablished regulators and regional local regulators increase their digital capabilities and expectations of Marketing Authorization Holders (MAHs). Oracle has a regulatory intelligence team that tracks global regulations and shares updates within our Safety Consortium, Regulations, and Audits Working Group. Compliance updates are released regularly, with adoption eased by the move from on-premise installations to SaaS cloud.

2. Recent years have seen an increase in the marketing of novel treatments that require specific pharmacovigilance monitoring, frequently following fasttrack approval. Can you tell us about the difficulties and potential growth in this area?

Over time, pharmacovigilance has become more intense – data about adverse events are collected more quickly, more cases are filed, and more questions are being asked about the data that is collected. In fact, according to market intelligence provider IDC, safety caseloads are increasing by an average of 30 to 50 per cent a year1, so pharmacovigilance teams are looking for ways to process cases more quickly and efficiently. Automation and AI are key in this endeavor.

One recent successful automation deployment was seen in the rapid development of the COVID19 vaccines and therapeutics. With more than 10.4 million verified users and 150 million anonymous health records, the v-safeSM health checker created by Oracle and the CDC helps healthcare professionals

1 * IDC MarketScape: Worldwide Life Science Drug Safety Services 2019–2020 Vendor Assessment — Building for Innovation

better understand how people respond to different vaccines—including common adverse effects— and make recommendations based on people’s responses.

The wide-scale adoption of the v-safe platform makes it one of the largest real-world patient data- gathering platforms in the world for a single therapeutic area. The data captured through v-safeSM has been instrumental in building the evidence base to support the safety and efficacy of the mRNA COVID-19 vaccine in pregnant women (who were not part of the original clinical trials) and other vulnerable populations. The data was also critical in securing formal FDA approval for the Pfizer-BioNTech COVID19 vaccine and subsequent booster shots.

Monitoring for new safety signals, which is information on a new or known side effect that may be caused by a medicine, is also challenging for these rapidly adopted new therapies and vaccines. We recently published new research on signal detection of the mRNA COVID-19 vaccine data which demonstrates the capabilities of Oracle Empirica Signal to identify potential signals earlier than historical methods.

3. Could you tell our readers about a few of Oracle Argus' special features?

Argus is a leading SaaS solution for processing, analysing, and reporting adverse event cases originating from pre/post-market drugs, biologics, vaccines, devices, and combination products. Its built-in automation, integration, and usability capabilities reduce manual tasks and maximise efficiency.

Argus can scale from supporting start-up companies with a handful of clinical candidates up through the largest biopharma companies with thousands of products marketed in a hundred or more countries. We are constantly monitoring for changes in global PV regulations and issuing compliance updates as needed.

4. Are regulatory service providers' claims about the potential for AI to revolutionise processes overstated?

No. In fact, with so many new ways to report adverse events, companies today have access to more data on drug safety than ever before. As adverse events arise, it’s critical to have a system in place that can provide fast, high-quality insights at scale to drive the company—and industry—forward. An automated approach allows human experts to focus on the critical cases, so existing resources are used most effectively even as the overall volume of data increases.

5. The current hot topics in the healthcare and life sciences sector are data and AI. How prepared is the pharmaceutical industry for digital transformation concerning drug safety? How is Oracle planning to face uncertainties?

Historically, the pharmaceutical industry has been slow to adopt new innovations, but the pandemic necessitated an acceleration of the adoption of digital technology, including new tools for automating safety case processing.

Key to this transformation understands how tools can be more efficient and effective, both in crunching data and enabling staff to focus on different areas of their jobs that allow them to be more creative and innovative. By applying machine learning and data science approaches, companies can automate mundane, repetitive tasks and quickly gain new information and insights about patients and therapies from the abundance of data.

Focusing on adverse event case intake, AI can be applied to a wide range of data types such as forms with a defined structure to images. It is also possible to extract and analyse data from unstructured sources like journal articles or emails. Once the documents have been automatically structured and processed, they can be separated into ‘routine’ cases that can be handled entirely by software, and ‘high-priority’ cases that require a closer review by safety specialists.

The insights provided by AI also enable safety evaluators to make more informed observations, for example, with new techniques such as neural signal detection, multimodal signal detection, and predictive signal detection.

6. Please give us a brief overview of Oracle Health Sciences Empirica Signal and its significance. With such technological platforms, how do you monitor product safety?

Oracle Empirica is a leading solution for detecting, analysing, and managing safety signals originating in pre- and post-market drugs, biologics, vaccines, devices, and combination products. The platform provides users with a powerful data-mining engine with algorithms that offer flexible signal-management analytics with rich visualisations. With Empirica, pharmaceutical companies can help ensure they are always in compliance with EU GVP Module IX and CIOMS VII. Oracle continually researches, develops,

and advances state-of-the-art data-mining algorithms and statistical techniques used in Empirica solutions.

8. Where does Oracle excel, and what novelties would you like to create going forward for the market for drug safety?

Today, medicinal product safety teams are under enormous pressure to control ever-increasing caseloads, new sources of signal detection data, and changing regulations—all with flat budgets and resources. Cloud-based platforms such as Oracle Argus and Oracle Empirica, coupled with standardisation, have helped lower costs through faster and easier implementations and upgrades. Through the delivery of technology solutions, we are an enabler to allow our customers to process and convert data into information and insights to drive improved patient safety.

9. What potential future business obstacles can pharmaceutical businesses face that Oracle is best equipped to handle?

One of the biggest challenges pharma faces is managing the massive amounts of patient data – and sources of data -- that are available today. There is more data available now than could have ever been imagined nearly a century ago when the first safety protocols were put into effect. Data can show us which patients should be prescribed certain drugs, which drugs are helping people, and which are not.

To process this vast and growing amount of data we will soon see technology used to move beyond augmenting human work to touchless case processing. Oracle Argus can help in this process, including assisting with automating all aspects of the safety process, from intake to report generation. While the touchless approach has not been fully adopted yet, there are certain aspects of safety case processing that are currently more suitable for greater degrees of touchless automation. For example, products that have been in the market for a considerable amount of time and are well understood naturally require less human intervention because the safety profiles are well-known.

As various system capabilities improve over time, more widespread use of touchless processing will become more feasible. Given that, companies can begin to plan for a touchless case processing system. The key is to adopt a stepwise approach, implementing and validating each automation area one at a time, to eventually build an end-to-end automated process with confidence.

10. Where do you look for your company's future?

As we look forward to a new era of pharmacovigilance, cloud and AI technology have provided an opportunity for continued innovation and a way to bring new drug treatments to market faster and serve more people – safely. With so much data – and the technology to analyse it available today – there is no doubt we are evolving from the manual processes used in the early days of drug safety to an era of precision pharmacovigilance – a personalised approach to drug safety that will help maximise the reach of new drugs and minimise the number of adverse events people experience.

11. Any other comments?

While the pharmacovigilance process has traditionally been seen as a cost center, it’s now become a foundational component for any organisation. The information that is gleaned from safety processes is used to achieve the fundamental goal of drug safety –to reduce the risk of adverse events by informing doctors of potential side effects that were previously unknown so they can protect their patients who need the drugs.

AUTHOR BIO

Yashi holds a Bachelor’s Degree in Engineering and a Post Graduate Diploma in Business Management. He has been involved in the IT industry since 1987, working in Sales & Marketing, Business Development, Support and General Management positions. As Vice President, Sales, he is responsible for delivering transformational solutions enabling Pharma, Biotech and CROs to drive innovation and bring drugs rapidly to market to cure disease. As Regional head of the world’s leading Clinical Development & Drug Safety solutions provider, Yashi is passionate about accelerating drug development and research by leveraging the power of modern technologies.

DISTRIBUTED LEADERSHIP AND DECISION-MAKING

The benefits in a multicultural context

Innovation in R&D requires both leadership and effective decision-making at the edges of our current understanding. Despite the advances in translational sciences, overall success rates are still low. In this article, we outline approaches to how decisions can be aligned across organisational and cultural boundaries, adapting to new information as it emerges.

Sherril Kennedy, Organisation Development Practitioner Andrew A Parsons, Experienced Leader, Life Science industry

Navigating the complex challenges of bringing new medicines to the marketplace requires both leadership and effective decision-making. New technologies and the development of translational sciences have created many new opportunities. However, the overall success rates are still low.

In this article we explore different approaches to decision-making and highlight the benefits of a distributed approach to support decision-making across organisational and cultural boundaries. We look at the structure of decision-making bodies throughout the process of bringing a new medicine to market, highlighting the dynamic nature of leadership and decision-making at the different stages of development. All of this is overlaid with the impact of the individual on the decisions taken.