Before the life-saving drug enters a patient’s vein or bloodstream, it travels through one of the most complex logistical networks on Earth. From Swiss or Indian manufacturing plants to clinics in sub-Saharan African countries, the pharmaceutical cold chain is a temperature-controlled miracle. One dose of antibody drugs may pass through multiple countries, requiring multiple-language customs clearance and passing through climate-controlled warehouses, where a two-degree rise in temperature could render a $1 million supply useless. Firms such as Pfizer, Moderna, and the Serum Institute of India have teams of supply chain engineers who do nothing but make sure a cancer treatment leaves one facility in Massachusetts and comes to Manila in a state to be used. This invisible infrastructure is as important as the chemistry it delivers – it is these things that make the world’s most ingenious drugs just costly liquids in cracked glass.
Regulatory Labyrinths and Regional Realities
Each country has its own regulatory landscape for pharmaceuticals, which affects the availability of medicines on their territory and therefore the health of patients globally. The pipelines for drug approval are also different for each jurisdiction: FDA, EMA and WHO, and this may result in a delay of years to access a drug approved in one jurisdiction. This regulatory split has given rise to a full-blown medical travel industry, where patients travel to receive care that is approved on the other side of the border. Healthcare hubs have grown in the Middle East, serving international patients who typically visit for specialized treatments, and some of them have been looking into certain treatments like steroids in Dubai as part of a wider study of treatments in areas with different pharmaceutical availability systems. The gaps in the legislation bring with them fundamental ethical issues: Can a drug which is safe in Europe be denied to people in Southeast Asia just because tests are still underway there? Companies are under pressure from organisations such as the Access to Medicine Foundation to act quickly to register medicines, but there is a fundamental tension between the need to verify safety and the urgency to provide medicines to patients.
Who lives and who doesn’t depends on patent cliffs and exclusivity periods. After the pharmaceutical company wins a patent for a new breakthrough therapy, they enjoy a market monopoly for 20 years, half of which is spent on clinical trials before the drug can be sold in pharmacies. As a result, during this period of time, prices can go to crazy extremes: CAR-T cell therapies for leukemia have been priced at over $450,000 per treatment; orphan drugs for rare diseases can cost more than $2 million per year per patient. Some call this extortion; others say it is a price that must be paid, given the fact that nine out of 10 candidate molecules fail during drug development, and it takes one billion dollars. When patents expire, a second life-saving mechanism occurs – generic competition. In 2011 when patent protection of Lipitor expired, global access to cholesterol management grew by leaps and bounds and the price plummeted 95%. The boom and bust dynamics in pharmaceutical economics is the main tension in global drug policy.
Antimicrobials – the drugs that no longer work!
Today the greatest danger to modern medicine is not just the lack of medicines, but the fact that they are becoming obsolete. Antimicrobial resistance (AMR) happens when bacteria, viruses and fungi become so resistant to antimicrobials that infections become untreatable and fatal. AMR could be a bigger killer than cancer, causing 10 million deaths worldwide by 2050, the World Health Organization estimates if the current trend continues. The economic incentives behind this crisis are perverse: a new antibiotic might only be used a few times, and therefore produce little income, before it loses its efficacy, but a chronic disease drug could be used for decades every day, producing a much greater income. As a result, drug firms have almost stopped researching antibiotics. The pipeline of new antibiotics is dangerously low—just a few new classes are found in the last 30 years. The AMR Action Fund and the “Netflix models” of antibiotic procurement are desperate measures in a field of medicine that is rapidly coming to the end of its rope before common procedures such as surgery and chemotherapy become too risky.
Biologics and the Personalized Revolution
Moving the frontier of life saving therapeutics from small molecule chemicals to biologics, or complex proteins, antibodies and cellular therapies that are made in living systems and not chemical reactors. In the early days, insulin was extracted from the pancreas of pigs and cows, but now it is made by genetically modified bacteria. With diseases such as autoimmune disorders now treatable with a drug called adalimumab (Humira), a monoclonal antibody, and terminal cancer now becoming manageable chronic illness for some patients thanks to drugs known as checkpoint inhibitors, these are just some of the fields where molecular biology has gone a long way in recent years. The extreme form of this is personalized medicine, or therapies tailored specifically to each person’s genome. CAR-T therapy is a three-part process that extracts a patient’s own immune cells, modifies them in the lab to become “living drugs” that target cancer, and then puts them back in the patient. For some, these therapies are incredibly effective, and incredibly costly to make. The making is more in the nature of artisanal craft than of factory production, and each item is made for one individual.
Who Decides Who Lives? The Human Element.
An underlying moral dilemma is involved in every drug policy saving lives. In the midst of the COVID-19 pandemic, countries that already have vaccines in their possession are confronted with difficult choices regarding vaccine prioritization: healthcare workers first, elderly second, essential workers third, but what about those who are immunocompromised, or in overcrowded prisons, or communities of color who are disproportionately impacted? Such triage decisions reveal the very politics of drug distribution. In low-income countries, the absence of manufacturing capability resulted in the world’s wealthier countries vaccinating their people while the local doctors were burying patients who could have been saved. The move to temporarily waive some IP rights for COVID-19 vaccines, as proposed in the TRIPS agreement, set off a debate that went global, between the encouragement of innovation and immediate survival. The same issues occur with gene therapies with one-time life-changing prices that can bankrupt families and organ transplant medications that require a life-long commitment of immunosuppression, and come with a multimillion dollar price tag. The art of saving life is as perfect today as the ethics of its distribution are unsolved.
