Anshul Mangal of Project Farma Discusses Policy Strategies to Address the Current Cancer Drug Shortage

Project Farma is a precision for medicine biomanufacturing company that provides strategy and execution management to start-ups, pharmaceutical companies, hospitals, academic facilities, government agencies, financial institutions, contract research organizations/contract manufacturing organizations, not-for-profit organizations, and medical device companies.

This transcript has been edited for conciseness and clarity.

Anshul Mangal, CEO at Project Farma

Anshul Mangal, biotech entrepreneur, attorney, CEO, and founder of Project Farma, addresses the current cancer drug shortage and shares various supply chain and policy solutions to increase manufacturing capacity while maintaining quality and safety of these drugs.

The American Journal of Managed Care^® (AJMC^®): What are the primary reasons for the current cancer drug shortages, and how is Project Farma addressing these challenges?

Mangal: The current cancer drug crisis stems from an incident last fall in November of 2022. The FDA toured a facility in India owned by Intas Pharmaceuticals, where they observed numerous violations due to quality and data integrity. As a result, the plant halted production and it kind of became the first domino that fell in a chain that would lead to a nationwide shortage of cancer therapy drugs.

Before the shutdown, Intas produced about 50% of the US supply of a very common cancer drug used to treat testicular, ovarian, bladder, head and neck, lung, and cervical cancers. And when the plant halted production, other manufacturers were not able to ramp up enough to avoid the current shortage that we have today. Many other manufacturers that could produce did not have the capacity and they didn't have the proper incentives—being a generic drug manufacturer— to produce the medications.

As the drug that Intas produced became scarce, oncologists switched to a different drug, which Intas also produced, unfortunately. As a result, the second drug that the oncologist switched to is also now in short supply. So, that initial plant shutdown just created a ripple effect in the supply chain.

The other thing I've looked at is, why is this all important? Over the years, advances in cancer therapeutics have played a role in reducing the rate of cancer deaths in the United States by over 33% between 1991 and 2020, which translates to about 3.8 million deaths averted. In addition, 14 new anticancer therapeutics were approved by the FDA between August 2022 and July 2023. But these treatments can only make an impact if patients have access to them. Then I found what the supply chain issues were actually causing in terms of hard numbers.

A survey of US Cancer Centers showed in May that 93% of cancer centers experienced a carboplatin shortage; this is a common cancer therapy drug—again, produced by the Intas facility. There's an annual report from the American Association for Cancer Research, and in September, it noted that hospitals nationwide are stating this has been the worst chemotherapy drug shortage crisis that the United States has ever seen. Researchers are estimating that the average drug shortage impacts more than 500,000 patients, and there were over 295 prescription medicines that are in short supply. So, it's extremely dire and pretty severe what I found.

What the shortage means is that some patients with cancer can't access medications that have been maintaining their fight against the disease and other patients can't start their treatment regimens. I did find that novel drugs aren't really the problem for researchers, because pharma companies can usually supply those to investigators. The problem lies with the drugs that doctors often use in comparison or in conjunction with a novel treatment. They're the medicines that doctors currently use to treat patients, and they're often called generic medications, or medications for which patent exclusivity has expired, meaning that any company can legally manufacture.

The next part of the discussion I want to turn to is, what are the causes for the supply chain to be disrupted? Obviously, the facility shutdown of Intas is one reason. There's also been disruptions due to COVID-19 that have affected the supply chain, not just in life sciences, but throughout many industries. There have been shortages in key raw materials. There are also limited economic incentives for additional generics to be made. Generic drugs often price very low due to the absence of patents and exclusivity, so they're not as profitable for manufacturers to produce. As a result, there's little incentives for multiple companies to produce the same generics, for example. This kind of ties into a lack of manufacturing capacity for these drugs, since there's a lack of incentives for there to be multiple manufacturers.

Also, the competitive landscape for generics is very challenging. There's only a few distributors that buy these drugs that have significant negotiating power that enables them to seek the lowest price for these medicines. So, again, there's just not a lot of incentive for people to manufacture and make these types of drugs.

AJMC: Given the recent disruptions in global supply chains, what proactive steps is Project Farma taking to mitigate supply chain risks and ensure a consistent flow of cancer drugs to patients in need?

Mangal: We're doing a lot of different things. We're working with therapeutic developers to ensure they're aware of the items that are in short supply, they know of the relevant timelines for supply chains, and they can identify alternative solutions if there are any present. We're also actively engaged with therapy developers in the United States and abroad to create more manufacturing capacity for cancer drugs, whether that's creating a strategy for additional manufacturing facilities or helping them with boots-on-the-ground support to scale manufacturing and tech ops infrastructure for these lifesaving therapies. We're actively partnering with developers to do that.

We're also actively working with therapeutic developers to ensure the facilities are built to the highest quality standards so that they don't encounter quality issues like the ones Intas did in India. We're also trying to add more automation in facilities so that we can hopefully make production more effective, efficient, and cost-effective. Last but not least, we're helping train and develop the workforce at our partner therapy developers, so that they can manufacture these medicines long after Project Farma is no longer engaged with these therapeutic developers.

There are a lot of other solutions that have been proposed to help with the cancer shortage. One thing that the FDA did was they temporarily authorized a Chinese company to import a generic cancer drug from China into the United States and a Canadian company to act as a US drug distributor. They also relaxed part of the import alert from Intas to allow some of the manufactured products that are in short supply to enter the United States.

Other nonprofits also have stepped up to fill the gap. The Society for Gynecological Oncology worked with the National Comprehensive Cancer Network to issue alternate drug guidelines for cancer care and persuade insurers to cover work-around treatments for the drugs that are running in short supply. Then there are other obvious things the industry has called for that Project Farma is actively working on, such as boosting manufacturing. This could take up the form of artificially increasing the demand for generics enough to sustain multiple manufacturers in the industry. For example, the government could purchase excess capacity by paying for more drugs the market needs.

A more drastic fix could be that the government takes over drug production, either acting as a direct manufacturer or partnering with private companies. There are examples of the government doing so. For example, in March, the government contracted with a nonprofit company called Civica to manufacture insulin for California.

There could also be policy changes that could help us respond to future shortages. We could authorize the FDA to require manufacturers to report anticipated shortages ahead of time or to expand the scope of its list of essential medicines, so that the agency cannot prioritize striking the supply chain of drugs that are essential, both in the event of a shortage or for the longer term. We can also enforce that drug purchases have metrics related to quality; for example, higher grades for manufacturers that have never had quality issues and lower grades for plants that have had manufacturing violations that could be incorporated into purchasing decisions.

Better planning could also help. This is something else that Project Farma has been working with innovators and drug developers on. Current drug shortages are happening with very little warning in the market, so you're forced to react, right? But we could implement systems, like artificial intelligence, that could provide early warning systems for drug shortages to help manufacturers and pharmacies plan ahead. Better supply chain management and better supply chain management tool implementation could help. Project Farma is an expert in supply chain and implementing tools for supply chain. And that's one thing you could do.

Last but not least, a focus on innovation and investment in advanced manufacturing technologies could help. Things like 3D printing of drugs, automated monitoring to identify equipment that's not working properly, and continuous manufacturing rather than batch productions, which is more efficient, could all be ways that could help ensure there's not a shortage in the future. These are all areas that Project Farma has expertise in.

AJMC: How does Project Farma balance the need to increase manufacturing capacity quickly with maintaining the highest quality and safety standards in cancer drug production?

Mangal: Number one, it's not necessarily a balance. I think quality and safety have always had to be met. They cannot be compromised for any drug and specifically cannot be compromised for drugs so critical as those related to cancer. We need to work with drug developers to increase manufacturing capacity while keeping quality and safety top of mind. We need help to help boost manufacturing capacity. Again, one way we could do it is to artificially increase the demand for generics by the government purchasing excess capacity or by paying for more drugs than the market needs.

And then the other things I mentioned, such as ensuring that our drug developers have high quality control standards and that quality is being met every step of the way. Sometimes, drug manufacturers may be tempted to cut corners and reduce quality control measures to reduce costs for generic drugs. But that's not a solution, right? That's just going to exacerbate the problem, like what happened in India with Intas, and lead to facility shut down, shortage of cancer drugs, and an increased cost to remediate those facilities and put the drugs back on the market. All this leads to is more heartache for the patients who need these critical mass medications.

Again, the things that we can help with are to increase manufacturing capacity while maintaining high quality and safety standards in better workforce training and development. Also, ensuring the workforce knows the quality and safety standards that need to be met and how to efficiently manufacture these medicines. Last but not least, using more automation and artificial intelligence in the manufacturing of these medicines, where possible, that could help reduce cost and ensure quality standards are met.

AJMC: How is Project Farma working with regulatory bodies to address regulatory challenges to scaling manufacturing and adopting innovative technologies?

Mangal: I think some of the things already mentioned was working with the FDA to expand the list of essential medicines. By broadening this list, the FDA can prioritize the safeness of the supply chain for a wider range of critical drugs. Hopefully, this will prevent shortages in the future. The proposed Drug Shortage Prevention Act would authorize the FDA to require drug manufacturers to report anticipated drug shortages in advance, by making it mandatory for them to provide early notice of potential shortages. This act can help facilitate a more proactive approach to drug supply challenges. The Drug Shortage Prevention Act is something that Project Farma is a great advocate of that can help us with potential future shortages.

AJMC: Are there any long-term sustainability goals or practices that Project Farma is implementing to ensure a consistent and reliable supply of cancer drugs in the future?

Mangal: We're working with therapeutic developers across the world to ensure that their facilities have the highest quality and safety standards. We are ensuring that those facilities and therapeutic developers have the knowledge that they need, and we have the knowledge that they need to help them scale these manufacturing facilities in a timely manner and within the budgets that they prescribed. We are helping them with training and workforce development, so that long after Project Farma is no longer helping that therapeutic developer, they can stand on their own and continue to manufacture critical patient medicines for the patients in need. And we are leading the industry in ensuring that there's automation and AI and the requisite technologies that are integrated into these facilities, so that we can create more medicines in a more efficient manner.