After every few days, we all come across the headlines about rising or falling values of ‘Bitcoin’ followed by torrents of predictions about the global economy and future of financial market. Though his true identity is unknown, Satoshi Nakamoto – a mysterious inventor of Bitcoin, is a renowned figure in the world of cryptocurrency. Bitcoin or cryptocurrency is just the tip of an iceberg. This technology was essentially developed to solve the huge problem associated with the centralisation of power which may become corrupt intentionally or unintentionally. Thus, blockchain technology, also known as distributed ledger technology (DLT), is a decentralised way of maintaining a track/ledger of every transaction associated with the system, which makes it practically impossible to falsify any information. As explained in simple words by Quazi Mamun, a blockchain is a time-stamped series of permanent data records managed by a collection of computers that are not owned by any entity.
This groundbreaking technology has enormous applications in almost every walk of life and it is not surprising that the healthcare industry, being a high-asset and knowledgeintensive industry, is amongst the top few sectors to experience its great potential and benefits. The ability to treat previously untreatable diseases, with remarkable efficacy and safety, marks biopharmaceuticals as one of the most sophisticated achievements of modern science and technology. Biopharmaceuticals account for the rapidly growing segment of prescription drugs and are forecasted to reach the global market share of approximately US $400 billion by 2025. With the emergence of 3D bio-printing, stem cell technologies, CART cell therapy, etc., we are at the cusp to witness the next therapeutic revolution that is striding from single cell component (current protein, mRNA based therapeutics) to a whole cell-based therapies. Apart from these scientific vertical of innovations, the healthcare industry is intensifying horizontally, especially due to integration of technological advancements such as machine learning, artificial intelligence, cloud computing, internet of things (IOT), quantum computing, virtual and augmented reality and blockchain technology.
Decentralised distribution of information can reshape the pharma and biopharma industry by offering streamlined processes, reduced operational costs, removal of fraud and duplicity, providing trust, and enabling data integration in a sharing-based economy. Blockchain technology can be applied to numerous facets of drug discovery and development, such as for clinical trials, data management, ensuring drug authenticity, intellectual property, licensing and royalties, supply chain compliance, etc.
The unprecedented global pandemic due to COVID-19 exposed some of the fragilities in healthcare ecosystem, especially in clinical trials and supply chain management. Many world class hospitals and vaccine manufacturers struggled due to shortages of basic personal safety equipment (such as masks, face shields, gowns, etc.), and more advanced requirements like diagnostic kits and essential therapeutics. This shortage led to pitching and distribution of many counterfeit drugs, fraudulent testing kits and other biomedical supplies. This situation was an eye-opener for the healthcare ecosystem to understand the urgent need to expedite the adoption of advanced technologies such as blockchain, automation, digitisation, etc., to improve the robustness of supply chain management. With blockchain technology, organisations with competing interests can safely work together in a shared permanent ledger, without giving up the system control or revealing the critical information. The cryptographic principles and codes of blockchain technology will enable organisations to work together as teams to expose frauds, reduce frictions in the raw material supplies and ensure product authenticity at a speed never experienced before.
In order to evaluate blockchain as a solution to meet the requirements of the ‘Drug Supply Chain Security Act of 2023’, a pilot project was supported by the United States food and drug administration (US-FDA) in 2019. This consortium focused on pharma supply chains and included several global pharma leaders such as Genentech, Amgen, Pfizer, etc. Underlying blockchain technology was provided by Chronicled. The first solution that this consortium seeks is to establish a product verification system to verify the authenticity of the returned drug product. In an article published in Harvard business review, Alison McCauley has highlighted that approximately 60 million units of saleable drugs are returned annually as per a healthcare distribution alliance. Blockchain can also ensure the legitimacy of surplus drugs procured by wholesalers before they are re-sold. Currently, without a strong method to verify drug authenticity, these drugs are either returned to the manufacturing companies (which destroy them, resulting in a waste of resources) or the wholesalers contact manufacturers to track down serial numbers. The whole process of tracing and tracking down the serial number of drugs has many practical flaws and can take up to 48 h. Using blockchain and digitisation, wholesale distributors can make use of barcode scanners to perform such verifications within fraction of seconds and quickly put back the product into commercial distribution. Manufacturers can also maintain control of their data simultaneously with such transparent and traceable transactions. This rapid system of product verification can be very helpful for hospitals and pharmacies as well. Counterfeiters could still copy barcodes in an attempt to pass drugs off as legitimate — but the ledger will flag and permanently record suspicious activity.
In clinical trials, blockchain can help handle the trial’s subject identity better, including electronic health records, without losing privacy or security. Blockchain technologies could translate into a set of solutions that may improve patient participation and relevant processes, leading to better health outcomes. All clinical trial participants: patients, clinical investigators, coordinators, and primary physicians would be touching different parts of the same ledger. Moreover, public registries could be created, which will provide an access to the results of clinical trials to all the stakeholders, and in turn could further re-shape drug R&D. This healthcare ecosystem of the future will thus have an access to the same, synchronous version of the truth.
A similar synchronous version of truth is essential for all research laboratories and commercial biopharmaceutical manufacturers. The journey of a prospective new drug begins from research laboratories, which generate raw (output files from the instruments) and sophisticated (human readable and interpretable) data, that serves as a proof of experimental findings. Cautious review of literature and citation of relevant data is very essential during drug discovery because loss of critical data may lead to huge loss of investments into new drugs. Thus, right from the clone section or sample collection, every small or big process and analysis could be recorded by researchers with blockchain-enabled electronic laboratory notebooks (ELN). These records could be encrypted to avoid unauthorised access and obviate any conflicts about the date of creation of the material and about its creator. This traceability offered by blockchain can ensure authenticity of published data and help to protect the integrity of scientific information. This could increase the operational confidence and excellence, with additional benefits of saving a significant amount of time and resources around inoperable and/or deceitful reports/literature. Integrating other technologies, such as artificial intelligence, machine learning, internet of things, etc. will offer rapid data mining and analysis of existing literature. Thus, the future research and development (R&D) ecosystem will have advantages of intellectual property protection, with opportunities for most effective utilisation and revenue generation from new research findings.
Authenticating the experience of medical professionals can be a timeconsuming and wasteful endeavor by phone calls and snail mails. Cryptographic protocols can help in tracking the experience of medical professionals, which will not only help to streamline the hiring process for healthcare organisations but also help patients to take decisions on where and from whom to receive treatment. Due to poor communication network and technology, healthcare payments by individuals or insurance companies are the major pain-points of healthcare ecosystem. Pre-authorisation process required by certain insurance companies and enquiries into a certain expense being covered by a member’s insurance policy can be extremely slow due to involvement multiple stakeholders and manual processes. Use of blockchain for pre-authorisation can offer various benefits such as improving cash flow due to faster claim settlements, appropriate payment to the healthcare providers, reduced administrative costs, timely patient treatments, etc.
Beyond these peripheral applications, blockchain technology can also be applied to understand and/or address fundamental biological issues. Alfred Chin in frontiers in blockchain journal has outlined the application of blockchain principles to study and model biological mechanism. He suggests that retrospectively reconstructing cell lineage information is valuable for understanding human diseases as experimental manipulation is not possible. Naturally occurring mutations, such as single nucleotide variants, LINE-1 transposition, copy number variation, microsatellite mutation, mitochondrial DNA mutation etc., can moonlight as endogenous lineage barcodes. These barcodes could serve as a starting point for reconstructing the cancer history blockchain. Incorporating current genetic methods that probe biological memory with a blockchain model may expand the extensiveness and efficacy of retrospective lineage tracing. ‘Smart contracts’ are the protocols that get automatically implemented upon accomplishment of certain conditions and enjoy all the prime features of blockchain technology. These smart contracts as well as Boolean logic gates are both based on the principle of conditionality. Trust in blockchain technology may develop confidence that the biological Boolean logic gates function appropriately, which may be collectively employed to create a ledger of state of a particular cell. This valuable fundamental understanding may further facilitate engineering of dynamic and multiplexed biochemical circuits.
Though this technology has numerous benefits to offer, there are significant research gaps and lack of attention on actual technological aspects since 2008. Lack of thorough knowledge and a legal framework to support smart contracts makes it difficult for companies to fully embrace and implement blockchain technology in business. In a global blockchain survey conducted by Deloitte in early 2019, 29% of the respondents identified lack of understanding of the underlying technology as a key obstacle in adopting blockchain for real-time applications. In fact majority of the research continued surrounding the Bitcoin rather than understanding the infrastructure that Bitcoin uses. The major factors behind reluctance for adopting blockchain in healthcare ecosystem (including pharma and biopharma manufacturers) may include –i) lack of experts and extremely high cost to hire the available experts who can assist in implementation of this technology ii) building softwares capable of handling such great complexities may cost at least US $800,000 or more for the developers iii) linear flow of material and data across manufacturing and supply chain (i.e. data flows linearly one partner up and one partner down) iv) Powerful incumbents and off-chain transactions v) ideological push backs, privacy concerns and lack of faith such as thefear of losing proprietary data and trade secrets.
Biopharma and pharma giants will need to avoid operational silos and develop clear business implementation plans for new technologies in order to experience the benefits of large scale implementation of blockchain technology. Associations among healthcare and life-science sector competitors and regulatory bodies (FDA) would be needed to foster mass adoption. To summarise in simple words, with an increasing interest of industry players and rapid growth in blockchain technology, it will be interesting to watch how the technology contributes to discovery and development process for biologics and pharmaceuticals in the upcoming years.
REFERENCES:
[1] Q. Mamun, Blockchain technology in the future of healthcare, Smart Heal. 23 (2022) 100223. https://doi.org/10.1016/j.smhl.2021.100223.
[2] T.A. Hemphill, Biologics regulation, second-to-market competition, and the use of blockchain technology: an opportunity for the FDA to support responsible biotechnology innovation, J. Responsible Innov. 7 (2020) 689–696. https://doi.org/10.1080/23299460.2020.1807669.
[3] Bijoylaxmi Ghosh, The applications of blockchain technology in drug discovery and development, Biotech Connect. Singapore. (2019). https://www.biotechconnection-sg.org/the-applications-of-blockchain-technology-in-drug-discovery-and-development/.
[4] Alison McCauley, Why Big Pharma Is Betting on Blockchain, Harv. Bus. Rev. (2020). https://hbr.org/2020/05/why-big-pharma-is-betting-on-blockchain.
[5] A.C. Chin, Blockchain Biology, Front. Blockchain. 3 (2020) 1–4. https://doi.org/10.3389/fbloc.2020.606413.
[6] P. Tagde, S. Tagde, T. Bhattacharya, P. Tagde, H. Chopra, R. Akter, D. Kaushik, M.H. Rahman, Blockchain and artificial intelligence technology in e-Health, Environ. Sci. Pollut. Res. 28 (2021) 52810–52831. https://doi.org/10.1007/s11356-021-16223-0.
Amita Puranik is PhD research scholar at Nano-medicine research group, Institute of chemical technology, Mumbai. She has received prestigious Prime-minister’s fellowship for the doctoral research from government of India, cosponsored by Lupin Ltd., a renowned pharmaceuticals and biopharmaceuticals manufacturing company. Her PhD research work is focused on development of LC-MS based multi-attribute-method (MAM) for characterisation of biopharmaceuticals. She has two first author research papers and two scientific review papers published in international peer reviewed journals.
Prajakta Dandekar Jain is UGC Assistant Professor at DPST, ICT, Mumbai. She completed her Ph.D. in Bioprocess Technology from the same department in 2010,following which she was the first women researcher to receive the RESPIRE long-term fellowship from the European Respiratory Society (ERS)-MarieCurie Co-fund, to conduct research in siRNA delivery systems for all eviating lung infections. She conducted this research at the Helmholtz Institute of Pharmaceutical Sciences, Saarland, Germany for two years. Currently, her research work is focused in the areas of nanofibers and tissue engineering, upstream bioprocessing, 3Dcell culture technology and green technology. She has guided 5 Ph.D. students and over 25 masters’ students.
Ratnesh Jain is Associate Professor in Department of Biological sciences and Biotechnology at Institute of Chemical Technology, Matunga, Mumbai. Dr. Jain is heading “National Facility for Analytical Characterization of Biopharmaceuticals” being setup by Department of Pharmaceuticals, Govt. of India in addition to the existing Biologics Characterization Lab at ICT. From 2012, Dr. Jain has taken various initiative towards biosimilar characterisation and educational initiative e.g. Biosimilar-Workshop to support biopharmaceutical sector related to skill development, infrastructure development and entrepreneurship. He has more than 55 publications and 150 presentations.
