I have written before about insulin – a simple biologic with arguably the least stringent regulatory requirements for registration as a biosimilar, yet with no or little interest by companies in the biosimilars space – both locally and in countries with large pharmaceutical markets and industries. Gan & Lee, one of the largest insulin manufacturers in China, produced human insulin in 2021 when it had a government tender, but when it lost the tender in 2022, the company shut down its human insulin manufacturing line (personal communication). In the USA, diabetics can pay as much as $450 per month for insulin1. The high price led to several patients rationing their insulin use, often with disastrous consequences to their health as many developed diabetic ketoacidosis that proved fatal for some2, 3.
The high cost of insulin in the USA market has been ascribed, not to patents (the original patent was sold for $1 dollar to the University of Toronto by its discoverer Frederick Banting in 1921), but to lack of competition from biosimilars because of regulations that make development and marketing of biosimilar insulin, expensive4. The cost of developing a biosimilar is estimated at around 250 million dollars, and may explain why biosimilars are only about 15 to 20% cheaper than the innovator reference product5.
In many developing countries, human insulin is regarded as a low-value product by especially foreign manufacturers because of high production and shipping costs, small volumes and the low prices offered by national health departments6. This accounts for the limited availability of human insulin in many Southern African countries. This mix of high prices and limited availability and accessibility has prompted hobby scientists with a wide geographic footprint to launch an initiative known as the Open Insulin Foundation with the goal of creating community-scale systems that can produce quality and affordable insulin7. Such an ecosystem will still be subject to regulations, however, and consequently will require investment to develop the insulin as a biosimilar. The cost to the patient will nevertheless be substantially lower because these community systems are non-profit organisations.
Many of us are familiar with how the computer industry in the eighties that was dominated by expensive mainframe computers was disrupted by Apple, Microsoft, and Hewlett-Packard whose founders started these companies in their garages8. Today we seem to have a parallel in the biopharmaceutical industry as advances in biotechnology have made once complex, expensive and time-consuming techniques, such as making transgenic bacteria, DNA sequencing and gene editing accessible to the ordinary citizen who has some training in the biological sciences. Multipurpose portable versions of expensive standalone equipment that can fit into a laptop bag and which can be used anywhere (i.e., a portable DNA laboratory) are available online to the general public (https://bento.bio/product/bento-lab/). Similarly the reagents, cells, labware, and methods necessary to perform the experiments can be purchased as kits online (https://www.the-odin.com). Designs are also freely available to manufacture highly specialised and precision instruments such as microscopes that can be built using a 3D printer, a Raspberry Pi microprocessor and cell phone9. What all this means is that the technology and knowledge are already in the hands of patients to manufacture their own biological medicines – a reality that will become increasingly possible as the cost of these medicines skyrocket out of the reach of most patients. The biggest concern will be the safety of these “homebrewed” remedies. A solution must, therefore, be found involving all role players – companies, regulators and patients – to make these products accessible to everyone who needs them before patients are driven to make their own medicines. Regulators can set the tone by drastically reducing requirements for biosimilar registration based on cumulative quality, safety and efficacy information since the first biosimilar, Omnitrope® (biosimilar recombinant human growth hormone) was approved in Europe in 2006. In this regard I can reveal that SAHPRA has finally set a date (15 December) for the review of the Biosimilars guideline.
References
- The absurdly high cost of insulin explained. https://www.vox.com/2019/4/3/18293950/why-is-insulin-so-expensive.
- Gaffney A, Himmelstein DU, Woolhandler S. Prevalence and Correlates of Patient Rationing of Insulin in the United States: A National Survey. Ann Intern Med. 2022 Nov;175(11):1623-1626. doi: 10.7326/M22-2477. Epub 2022 Oct 18. PMID: 36252243.
- Herkert D, Vijayakumar P, Luo J, et al. Cost-Related Insulin Underuse among Patients With Diabetes. JAMA Intern Med. 2019;179(1):112–114. doi:10.1001/jamainternmed.2018.5008
- White J, Wagner A, Patel H. The impact of biosimilar insulins on the diabetes landscape. Journal of Managed Care & Specialty Pharmacy 2022 28:1, 91-98
- Mark McCamish & Gillian Woollett. Worldwide experience with biosimilar development, mAbs 2011, 3:2, 209-217, DOI: 10.4161/mabs.3.2.15005.
- Leng H, Dong J. A snap survey among insulin manufacturers to determine their reasons for not participating in the 2019 WHO Expression of Interest call for the prequalification of human insulin: Implications for the continued availability of low-cost insulin (in preparation).
- Gallegos JE, Boyer C, Pauwels E, Kaplan WA, Peccoud J. The Open Insulin Project: A Case Study for ‘Biohacked’ Medicines. Trends Biotechnol. 2018 Dec;36(12):1211-1218. doi: 10.1016/j.tibtech.2018.07.009. Epub 2018 Sep 13. PMID: 30220578.
- 7 Startups that started in a garage. https://pakwired.com/7-startups-that-started-in-garage/
Diederich, B., Lachmann, R., Carlstedt, S. et al. A versatile and customizable low-cost 3D-printed open standard for microscopic imaging. Nat Commun11, 5979 (2020). https://doi.org/10.1038/s41467-020-19447-9