Philipp Hofmann, MD, Director of Pharmacovigilance and Global QPPV, Navitas Life Sciences.

In the winter of 2022/2023, many pediatricians complained about a shortage of antipyretics. Unfortunately, it is not better this year, as a lack of availability for fever medications and certain antibiotics left many parents upset.

Many authorities, including the German Federal Institute for Drugs and Medical Devices, list over 500 supply bottlenecks. Drugs currently not available due to shortage include antibiotics for children, eye drops, antidepressants for young people, and medicines for the chronically ill and patients with cancer.

From raw material to tablet

In the fall of 2022, the infection rates for seasonal flu rose sharply. At that time, cough and fever medicines for children were in short supply. Some attributed supply problems to the ongoing impact of the COVID-19 pandemic. In some cases, lockdowns in China led to production stops.

But this is only a small part of a larger story, as drug shortages have been occurring for more than 10 years. The COVID-19 pandemic has only blatantly exposed shortcomings and geopolitical dependencies suddenly became apparent.

The problem of scarcity goes back much further in time, and it is multi-layered. Where do the problems originate? The production sites for active ingredients are now mostly in Asia, especially in China and India.

For these supply chains, the chemical raw material for painkillers or antibiotic tablets often comes from China and production then takes place over several stages in India. The finished medicinal product is transported to other regions of the world. For example, in the European Union, the product reaches wholesalers via warehouses and—finally—to pharmacies.

There are many risks involved, such as a factory fire, blockade of the Suez Canal, or even another pandemic, all of which could lead to shortages. A second development has increased the cost pressure on health insurance companies and pharmaceutical companies. Generics are coming onto the market after patents expire.

Because of the price spiral, there are fewer and fewer manufacturers; however, at the same time, demand has increased, which leads to a supply bottleneck.

When drugs disappear or are not approved

A recent case is the lung cancer drug capmatinib, which treats a small number of patients, primarily those with a non-small cell form of carcinoma. According to health authorities, the “additional benefit” of the lung cancer drug is not given.

Thus, capmatinib was withdrawn from the market. Other examples include a manufacturer that stopped selling a drug for psoriasis or refrained from selling a new HIV drug in certain countries.

Possible solutions

One solution to shortages could be to create financial incentives to bring production back to other continents to expand focus from China or India. Regulations should be designed flexibly so that it’s possible to use a medicine with a foreign language on the packaging. Countries that are often the first to stop receiving supplies because of low sales prices may benefit from this.

In the European Union, the European Commission is also planning to jointly procure essential medicines. To this end, a list of essential medicines is to be drawn up by the end of the year to join forces and avoid drug shortage.

Pharmacovigilance and drug shortage

How is pharmacovigilance involved in drug shortage? For patients, drug shortage usually leads to changes in medications or involuntary discontinuation that may compromise their safety due to a lack of efficacy, occurrence of a medication error, or an adverse drug reaction (ADR). These instances have been reported in the context of drug shortages involving anti-cancer drugs, anesthetic products, and anti-infective drugs.

A retrospective study on the French National Pharmacovigilance on ADR related to drug shortage by Bourneau-Martin et al., showed the clinical impact of drug shortages in terms of ADRs, medication errors, and inefficiency. This applies for the drug in shortage and the replacement drug. These findings support statements made by pharmacists and health authorities regarding the necessity of health policy that prevent drug shortages and strengthen the information given to patients and healthcare providers regarding drug shortages to reduce the likelihood of ADRs and medication errors.

About the Author

Philipp Hofmann, MD, Director of Pharmacovigilance and Global QPPV, Navitas Life Sciences, strives to drive excellence in drug safety and regulatory compliance on a global scale. He is a seasoned professional with extensive expertise in pharmaceutical medicine and commitment to patient safety. He began his journey as a medical writer, rapidly advancing through positions such as Medical Manager and Director of Global Safety, and ultimately assuming leadership in Pharmacovigilance and QPPV.