While Covid-19 had a serious impact on many countries’ healthcare supply chains, including in South Africa, the global industry was in trouble long before that, experts say, with the drug and medical device shortages expected to worsen.
“Shortages and supply chain issues don’t just happen during a public health emergency,” said Tammy Beckham, associate director of the US Food and Drug Association’s (FDA’s) Resilient Supply Chain Programme at the Centre for Devices and Radiological Health (CDRH).
Speaking at this month’s MedCon 2023, sponsored by the Association of Food and Drug Officials, the Regulatory Affairs Professional Society, and the FDA, she added: “We’ve seen these before Covid, and we’re continuing to see these moving into the future. Many of the issues we’re facing are becoming much more complex and more systemic.”
Drug shortages are at a five-year high in the US for a variety of reasons. Sometimes a big supplier has a quality problem and other makers of a given drug aren’t able to quickly fill the gap. Other times there are spikes in demand for certain drugs, but companies don’t have space or resources to keep up. Consolidation among the companies that buy generics is also forcing prices lower and driving manufacturers to stop making the drugs.
Problems that have plagued the industry for years, including scarce raw materials, sole-source suppliers, a concentrated market, quality problems and product recalls, labour issues, geopolitical conflict, and natural disasters, won’t go away with the end of the Covid-19 public health emergency, added Beckham.
Global crisis
Europe – with many other regions of the world – is also struggling with maintaining a steady flow of drugs like antibiotics and generic medicines, reports CIDRAP News.
This month, 19 European Union (EU) member states issued a four-page report on a steady increase in drug shortages since 2022. The report cites problems such as increased demand, manufacturing and quality problems, factory closures, and supply-chain bottlenecks.
“In addition to these problems, the EU is becoming increasingly dependent on imports from a few manufacturers and regions for its medicines supply, adding a security dimension to the question,” the authors wrote.
The EU has already instigated some actions, such as creating legislation designed to improve national and European Medicines Agency oversight and mitigation of drug shortages, establishing a steering group to track the causes of shortages and monitor supply, and proposing the Critical Medicines Act to support the domestic manufacturer of drugs, active pharmaceutical ingredients, and intermediates, for which the EU depends on one country or just a few manufacturers.
Generic, brand-name products affected
Drug shortages and the quality problems that often cause them aren't limited to generic products, as evidenced by ongoing shortages of Adderall, Wegovy, Pluvicto, and others.
Recently, the FDA has reported a slew of quality problems at both foreign and domestic plants that produce both generic and brand-name drugs.
“The FDA is finding problems in manufacturing quality whether the site is new or old, whether it is producing brand or generic drugs, or whether it is run by the product sponsor or their contractor.”
For example, on 26 April, the FDA issued an eight-observation report listing quality-unit failures and controlled-document oversight at Iceland’s Alvotech facility, which manufactures the rheumatoid arthritis drug Humira. After a March inspection, the FDA released a 10-observation report on Lupin’s Pithampur, India, facility that cited unreported out-of-specification results and critical equipment breakdowns.
Based in the same Indian city, in March, Cipla received an eight-observation report on its manufacturing plant related to microbiological contamination, power failures, and patient complaints. In Germany, Rentschler Biopharma SE’s intermediate manufacturing plant in Baden-Wurttemberg was cited for inadequate prevention of microbial contamination and too-infrequent endotoxin monitoring of some point-of-use equipment.
In the US, Eli Lilly’s Technology Centre in Indianapolis was given a three-observation report citing insufficient aseptic technique and surface sanitisation done with soiled wipes.
Lack of transparency
In 2022, the World Health Organisation (WHO) reported that Indian manufacturer Maiden Pharmaceuticals sold cough syrups that contained the deadly poisons ethylene glycol and diethylene glycol, which are used to make antifreeze, brake fluids, and other products.
The contaminated cough syrups were linked to the deaths of more than 70 children in Gambia, most of them under five, who died of acute kidney injury.
Now, it has been reported that an unnamed middleman in Mumbai sold a crucial raw material used to make the cough syrups. Corrupt people can substitute these adulterants for propylene glycol, a key ingredient in syrupy medications, because they can be less than half as expensive.
In December, India's drug regulator told the WHO that the propylene glycol used to make the cough syrups were supplied by Delhi-based Goel Pharma Chem, which imported it from South Korea’s SKC. Goel Pharma owner Sharad Goel said he bought the ingredient in sealed barrels from a Mumbai importer who procured it from SKC, but couldn’t name the importer, according to Reuters.
Unfortunately, the Maiden Pharmaceuticals poisoning was not unique.
“In fact, the death of more than a hundred patients in the US in the 1930s due to diethylene glycol contamination led to the creation of the Food, Drug and Cosmetic Act, which requires proof of safety for new drugs on the market,” said David Margraf, PharmD, PhD, pharmaceutical research scientist at the Resilient Drug Supply Project (RDSP).
RDSP is part of the University of Minnesota’s Centre for Infectious Disease Research and Policy (CIDRAP), publisher of CIDRAP News.
“The lack of transparency in the global drug supply chain is a major concern that impacts drug shortages and life-threatening quality issues,” he said. “It is essential to identify vulnerabilities within the supply chain to ensure safe and effective drugs.”
This month, the FDA updated its guidance on testing for dangerous compounds, including diethylene glycol and ethylene glycol.
“Regulators, policymakers, and companies in the healthcare industry need to prioritise the health of patients and work towards greater transparency in the drug supply chain to ensure that drug shortages and quality issues are identified and addressed before they become bigger problems,” Margraf said.
Meanwhile, Israel-based Teva Pharmaceutical plans to cut back generic drug production, even as shortages intensify, intending to focus on new, branded products to fuel growth, it says, citing low profitability.
The announcement comes as shortages are intensifying and makers of these medicines are struggling to stay in business.
Teva is one of the world’s largest makers of generic drugs, but has been contending with high debt as prices shrink across the board. Some nine out of 10 prescriptions filled in the US are for generic drugs. The industry has been under increasing pressure, leading to a scarcity of crucial medicines like antibiotics and cancer treatments.
As part of a plan to improve its finances – the company has debt of more than $20bn – Teva will stop producing some older generic drugs and reduce the number of new generics it develops, said CEO Richard Francis.
Bloomberg reports that Francis declined to specify which drugs would be dropped and said the changes will not be concentrated among therapies for any specific disease.
“The drugs we’re pulling out of are drugs that are low-margin,” he said, adding that Teva would drop medicines manufactured by as many as 10 or 15 other drugmakers. Other companies should be able to compensate for the decreased supply from Teva, he said, and this would free up his company’s resources for other products.
The effect of Teva’s cuts would depend on which drugs the company stops making, said Erin Fox, who runs the University of Utah’s drug information service that tracks shortages. If Teva cuts a drug for which it is a major supplier, that might lead to shortages, but if they stop producing a drug they produce only in small numbers, there might not be an impact.
Teva is acutely aware of this problem. The company makes the antibiotic amoxicillin and attention-deficit/hyperactivity disorder drug Adderall, both of which have been in short supply for more than six months.
Teva’s changes are part of a long-term plan announced last week, which focuses more on innovative products and biosimilars, copycats of expensive biologic drugs. Both categories are more lucrative than the simple generics that have sustained the company for years.
While Teva still makes much of its revenue from generics, the company also sells some branded drugs that pull in hundreds of millions of dollars annually. The company has biosimilar drugs on the market and in development, but recently struggled to launch a biosimilar to AbbVie Humira, a treatment for arthritis and other immune diseases that is one of the top-selling medicines in the US.
In the future, Teva intends to focus on complex generics, such as drug-device combinations and long-acting injected drugs
“Generics are a contracting business, and Teva will need to focus elsewhere to find growth to support its large debt load,” said Ann-Hunter van Kirk, a Bloomberg Intelligence analyst.
Meanwhile, companies are struggling to stay afloat. Two major generic drugmakers have filed for bankruptcy in recent months, adding to concern about the health of the industry. Akorn Operating Co. went out of business in February and recalled all of its drugs, including an albuterol product used for hospitalised children that’s in short supply, and Lannett filed for bankruptcy earlier this month.
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See more from MedicalBrief archives:
Sub-standard generic medicines killing children globally
Big pharma backlash against EU’s drug law updates
WHO probes raw materials link in lethal cough syrups
UK drug shortages putting patient safety at risk
SA stocks of diabetes drug drained after global weight loss frenzy
Critical shortage of ADHD medication in US and demand rises