Bioprinting: How the Manufacturing of Human Organs Will Disrupt Healthcare
This short article describes how Organovo is using a novel technology called bioprinting to produce liver and kidney tissues that could help reshape the way drugs are tested and organs are transplanted in our days. It also discusses the challenges and potential effects on society.
In recent times, drug development timelines in the US have hovered at about seven and a half years[1]. Part of these timelines are the preclinical trials, which are currently run on animals. There is a new way of doing this and it is the stuff of sci-fi moves. Organovo is currently manufacturing living human liver tissue using additive manufacturing (bioprinting in this case). Researchers believe that it could prove to be more cost efficient in assessing the side effects of new drugs on different human tissues before proceeding to human trials[2]. Anywhere from drug development, transplant needs, and all the way to fully replacing animal testing in labs, the ability to manufacture human tissue (and eventually organs) shows enormous potential benefits for society.
Scientists have been, for quite some time now, growing cells and tissue. But recently, they have been able to tap additive manufacturing (bioprinting) for prototyping fully functional human tissue. The objective is to one day be able to create living functional human organs at scale[2].
Organovo was founded in 2007 and is a for-profit, public (ONVO) biotech company based in San Diego. They are specialized in the developing and commercializing of functional human tissues[3]. The company IPOed in 2012 and raised $46.6M[4]. Organovo is not alone in this developing industry. Companies such as TeVido Biodevices, Cyfuse Biomedical and Regenovo Biotechnologies are competing in this same space today[2].
In the past, research labs have been able to grow cells using tissue or organ culture. However, these techniques have limitations regarding the placement of cells, complexity of the tissue, desired cell density and architectural design. Bioprinting allows for researchers to build specific designs for what is referred to as scaffolding, where cells are deposited and grown. It also allows for multilayered cell placement and provides the ability to computer-design how different variations of the tissue should look like[5]. This increases the company’s ability to speed up prototyping phases for any given tissue prototype.
For Organovo, this has materialized in their efforts in two completed product lines. Through bioprinting they have been able to develop and scale production of ExVive and 3D lines, with human kidney and liver tissues available. They are placing these products in the market as subjects for pharma preclinical testing on developmental drugs[6].
Although sales of their products started in 2014 and steadily increased to $4.6M in 2018, Organovo is still losing money. There are two main problems with the current business model that are especially problematic and are affecting its ability to become profitable [10].
First, it needs to convince the pharma world that testing with bio-printed human tissue is more cost efficient and thus preferable than current processes (i.e. animal testing). However, the FDA still requires extensive animal testing to move on to human trials[7]. In this arena, Organovo has continually been speaking with the FDA to gain credibility of its products as reliable predictors in clinical trials. Until this happens, their value proposition is not materialized, and they cannot scale.
Second, they have yet to develop a fully functional organ to place in the market. They are targeting 2020 for a partial liver transplant using bio-printing technology according to their website[8]. This is, however, contingent on FDA approval.
The company has also been exploring other areas of the rising industry that potentially require less testing such as cosmetics. They have partnered with L’Oreal to use bio-printed skin on their testing phases. This too has a limitation by the FDA that requires animal testing if the company exports to a country that requires it[9].
Organovo needs to speed up revenue streams to generate profit faster. If the FDA will not allow the pre-clinical testing on bio-printed human tissues, then it might be time for Organovo to start looking for traction elsewhere. Europe, Asia and Latin America might be interested in trying out this novel approach.
Important questions to consider in the future regarding bioprinting of human tissue are many. However, the space of ethics jumps right out, since the companies that will be dealing with this will have to respond not only to the pressures of profit as we saw above from investors, but also to the pressures of stakeholders and society at large. Will the development of this technology provide a significantly prolonged life for those who can afford it? And if so, will the rest of the population be condemned to living significantly shorter lives? Who will own the rights to an organ produced by such companies? Will new organs, different from what we see in nature be developed?
[1] “News in Brief.” Nature Reviews Drug Discovery 11, no. 10 (October 2012): 739. doi:10.1038/nrd3865.
[2] Arslan-Yildiz, Ahu, Rami El Assal, Pu Chen, Sinan Guven, Fatih Inci, and Utkan Demirci. “Towards Artificial Tissue Models: Past, Present, and Future of 3D Bioprinting.” Biofabrication 8, no. 1 (2016): 17.
[3] Organovo Holdings Inc. 10-K Form, Securities and Exchange Commission, March 31, 2015 https://www.sec.gov/Archives/edgar/data/1497253/000156459015004951/onvo-10k_20150331.htm
[4] Crunch Base, Organization Overview: Organovo, https://www.crunchbase.com/organization/organovo-holdings#section-overview
[5] Shanjani, Y., C. C. Pan, L. Elomaa, and Y. Yang. “A Novel Bioprinting Method and System for Forming Hybrid Tissue Engineering Constructs.” Biofabrication 7, no. 4 (2015): 045008/1-045008/16.
[6] “Organovo Sponsors Pioneering Research With Amgen and Medikine in Critical Areas of Liver and Kidney Disease.” News Bites US – AMEX (Melbourne), 2017.
[7] The Beginnings: Laboratory and Animal Studies, U.S. Food and Drug Administration, U.S. Department of Health and Human Services, Accessed November, 9th, 2018, https://www.fda.gov/drugs/resourcesforyou/consumers/ucm143475.htm
[8] Organovo Holdings Inc. website, accessed November, 9th, 2018 https://organovo.com/3d-printed-partial-liver-transplants-targeted-2020/
[9] Organovo Inc and L’Oreal Seek Patent for Engineered Three-Dimensional Skin Tissues, Arrays Thereof and Methods of Making the Same.” Global IP News: Beauty & Fashion Patent News, 2018.
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[10] Market Watch accessed November, 10th, 2018, https://www.marketwatch.com/investing/stock/onvo/financials
This is a fascinating article. It seems like under the right regulatory conditions, this technology has the potential to revolutionize the healthcare landscape. However, it seems like Organovo faces significant challenges. As you mentioned, given the potential in this industry, competition is heating up. How does Organovo plan on differentiating itself from the competition? Are there any new types of biological tissue that they could begin producing? To avoid becoming commoditized (e.g., just a printer), should they invest in more creative talent to design new prototypes of printed organs? Finally, would it make sense for Organovo to partner with a pharmaceutical company over the coming years? Organovo’s goal of affecting change within the FDA seems ambitious. Would fighting the good fight – while leveraging a pharma company’s considerable resources and power – help them to achieve their goal?
Thanks for a really interesting piece – healthcare is, in my opinion, the most interesting field to watch in our lifetime – however, as you mentioned the FDA has become a significant bottleneck for bringing scientific advances to the public. The speed of innovation and scientific discovery in healthcare in the last decade has far exceeded the FDA’s ability to process these drugs and the clinical process remains extremely onerous. But these are necessary evils to protect consumers from drugs that could prove to be more harmful than the ailment they are attempting to address. I think printed organs could be a huge advantage for preclinical trials. Especially because so many trials remain in the FDA approval process before treatments can reach consumers – the requirements in preclinical are much more flexible and leave room for a ‘slightly less than perfect’ product that could similarly prove minimal toxicity and safety requirements. I think Organovo has a significant opportunity before it but needs to focus entirely on FDA approval of their printed organs in preclinical trials at this point. Small biotech firms have extremely limited resources and I fear shifting their focus internationally or to cosmetics would constrain them from being able to gain FDA approval in their core product. Currently the majority of drug development remains in the US and cosmetics testing is a limited market with a much smaller budget to spend on testing – the TAM in US preclinical trials is the highest potential For Organovo and I would love to see them continue to focus here – not to mention they would have a huge social (as well as economic) benefit to society by speeding up the incredibly slow FDA process!
To build on Daniel’s comment about the FDA, I find it very interesting to see here how product innovation comes into conflict with regulation. Medicine is such an interesting application for 3D printing, but I wonder if the strict regulatory environment will run companies like Organovo out of business. For instance, they may not be able to secure funding to stay afloat while government agencies adapt their rules to this new category of innovation. It’s still not clear if that will be a short-term or long-term issue for companies like Organovo. For instance, I think product testing will be much faster to accept 3D printing than organ transplants.
Intrigued to learn so much from the future of healthcare with this article.
I would first like to build up in the issue already raised by Daniel and TomGirl about FDA. I have a hard time believing that the FDA will actually approve this approach with tremendous facility. However, I disagree with the article that the society discussion is more in the negative side of the lack of accessibility. I truly believe that actually, society will help accelerate FDAs approval of this approach, because it seems to me it is more political correct than testing in animals. I also believe it might yield closer results to the outcomes of humans. Therefore, I would say that I strongly believe this is happening, and it will happen quick. When society understands the benefit of the long run health for human care, they will probably be in the positive side of the equation. However, I do agree, that it is important that these testings and additive manufacturing should be used to help to develop cheap solutions for it to become accessible to the majority of the population in a more exponential manner than other technologies.
“If the FDA will not allow the pre-clinical testing on bio-printed human tissues, then it might be time for Organovo to start looking for traction elsewhere. Europe, Asia and Latin America might be interested in trying out this novel approach.”
This made my laugh. I know this is a serious matter, but I’m curious about this trend of innovating in growing/under-regulated markets. Is that morally acceptable? Should developed nations use other nations as test subjects? At the same time, I know accelerated development can lead to greater social good… and perhaps the injection of research and capital into less developed economies can be beneficial.
Great example of how additive manufacturing can provide positive societal benefits, but I love the ethical and regulatory questions you posed. To your question about the difference between whether there will be significant differences in who can afford this in the future, do you think this is significantly different than the disparities in health care access today? I could see a world where this makes healthcare more affordable, since speeding up the time and reducing cost of clinical trials could make things like cancer treatment more affordable. I am also curious whether this could help with organ rejection. I could potentially see a world where you grow organs with the person receiving the transplant’s gene, and having this help with rejection.
I share the concerns of the mismatch between the speed of regulation and with innovation. I also fear that regulation could also get push backs from existing players, delaying, even more, the permissions to Organovo. In connection with the company’s need to generate revenue, I would strongly argue against going into cosmetics because I think it will dilute its mission and harm its credibility. I think there are probably many other product lines to develop leveraging on the existing platform (other organs skin, etc). Another way could be to sign contracts with existing companies to develop other organs development. This would not only advance them in terms of product development but also secure a flow of revenues from the partnership.
Very interesting article that brings into questions ethics, regulatory policies and new technologies that have potential to save lives. Hopefully pricing and therefore inequality gaps won’t be much of a problem here if government and insurance is able to subsidize this research. It does so much benefit for not just humans but animals as well to shift towards this type of testing. Waiting for the day that this is the new norm.
RJ – very interesting piece on Organovo and their use of 3D bioprinting. As has been commented, FDA regulations are an important bottleneck in the advancement of bioprinting. However, as all things in medicine, the policies they put in place for animal testing first and clinical trials second exist for the sole safety of the patient. Actually, I would argue that FDA regulation is NOT the limiting factor in the advancement of bioprinting. The limiting factor is the science. It is true that bioprinting will solve many problems in medicine, notably: 1) alleviate the demand for organ transplants, 2) get rid of the need for immunosuppression or risk of transplant rejection, 3) it is a more cost effective option. However, the MAIN limitation of 3D bioprinting of organs is that we can’t get organs to function the way they normally would. Bioprinting is great at making structure (eg, making a liver look like a liver), but has not been successful in function (eg, making a liver work like a liver). There are many reasons for this, a big one being that we can’t get the right blood supply to the organ so the organ will often die. With that said, I still see a bright future for 3D bioprinting, and certainly companies like Organovo will be in the forefront in the advancement of functional organs.
I have been watching the bioprinting space for several years and have had an eye on Organovo specifically for much of that time. It seems like one of the most exciting new technologies that we will are likely reach in our lifetimes — but progress has been frustratingly slow so far. It’s clear that the regulatory issues around 3D printed organs are a major challenge to overcome. While the FDA is right to be cautious and conservative, there tens of thousands of people die each year while waiting for organ transplants in an environment of extreme scarcity. Surely there must be patients who would volunteer to take on the extra risk of testing a potentially life-saving technology like bioprinted tissue. I hope the FDA responds to that grim reality and wish Organovo lots of luck in getting us over the hill.
Thanks for this article RJ – super interesting! I have two main comments.
First, reading a recent article published by MIT Technology Review, I tend to agree with Ricaro that FDA approval is not the main bottleneck for bioprinting to take off. It is an incredibly advanced technology which proves to be more difficult than some have expected. Sharon Presnell, chief scientist of Organovo, is quoted in the article saying: “We all think it [i.e. printing entire organs] is going to be possible at some point in the future. Where we differ is how long it will take.” [1]
Second, you mainly raise ethical questions regarding the full roll-out of this technology. You are afraid this might only be accessible to the super-rich and lead to more inequality. While I totally agree that health care is reaching those boundaries now, I would argue that the current system of organ transplants leads to even more inequality. Researchers have proven wealthy individuals game the system to get access to transplants quicker [2]. While this new technology might be very expensive in the beginning, economies of scale might lead to improving accessibility for all over time.
I am curious to follow the further evolution and continue the discussion.
[1] Antonio Regalado, “Inside the effort to print lungs and breathe life into them with stem cells”, MIT Technology Review, https://www.technologyreview.com/s/611236/inside-the-effort-to-print-lungs-and-breathe-life-into-them-with-stem-cells/, accessed November 2018
[2] Ariana Eunjung Cha, “Inequality in U.S. organ transplants: Researchers detail how the wealthy game the system”, The Washington Post, November 12, 2015, https://www.washingtonpost.com/news/to-your-health/wp/2015/11/11/inequality-in-u-s-organ-transplants-researchers-detail-how-the-wealthy-game-the-system/?noredirect=on&utm_term=.c703fb8d2415, accessed November 2018
Terrific read! Bioprinting makes even the most difficult 3D printing techniques look like a cake walk, but you’ve correctly pointed out that they will be invaluable to the pharmaceutical field. A few thoughts on your questions:
1. Adding “bio” in front of any word automatically increases its complexity, and the question of bio-inequality (coining a new term here) is no different. We see many of the same issues with drug companies today, but the right mix of government and the free market can make medicine more affordable for the masses. When printable organs become a reality, I imagine that price will become a hotly contested issue.
2. The possibility of new organs is especially exciting! Ideally, bioprinting companies would be able to remedy congenital defects.
Thank you for the amazing article. I think ethics is a huge issue in the healthcare, especially when it involves human organs. As you mentioned, it will produce a lot of potential as well as benefits to the overall human health when it gets used in the clinical settings for the drug test. However, I am also worried about who will get the power from this innovation. Not only FDA, but government should play a crucial role in limiting its usage and defining the right use of the technology. Also, as life expectancy increase due to the advancement of technology, government should find a solution to the problem arising from the aging population.
Thanks for the write up! It really is an interesting an thought-provoking dive into the ethics of healthcare. This truly makes me wonder, why has it taken Organovo so long to bring their products to market? The technology seems very promising, but this reminds me of other situations that startups have faced, where the company with the “best” technology hasn’t been the winner. Oftentimes, execution and implementation trumps innovation.
A much needed innovation especially when considering what the current standard of care is. Given current patients wait months and sometimes years for organ transplants, this really will help democratize access in ways we haven’t seen before. However, this space is fraught with failed attempts like Tengion (now defunct). https://www.journalnow.com/business/business_news/local/bankruptcy-court-approves-offer-to-buy-tengion/article_748ff1c4-c431-11e4-8b4c-6f6f7a43c3ed.html
I think the previous comments really hit the nail on the head here about the key risks around FDA approval and the high bar for use in a clinical setting. Partnering with L’oreal was the absolute right move here, since the scientific bar will be significantly lower, and provide the company with much needed time and additional cash infusions to develop clinical solutions.