by José Luis Cárdenas Tomažič

Adapted from the Spanish column originally published in El Economista on June 27th, 2024 (Medicamentos Genéricos Complejos: ¿Por qué es necesario mejorar su acceso?)

Complex generics are generic versions of innovative medicines that feature complex structures, novel formulations, or more sophisticated delivery systems. Unlike traditional generics, which replicate simple chemical structures, complex generics involve intricate active ingredients, device combinations, and/or unique formulations.

Complex generics help contain and reduce healthcare expenditures. By offering alternatives to costly medicines, they promote competition and ease the financial burden on patients and healthcare systems, as they represent the final stage in the lifecycle of a medicine. In this regard, one study estimated that generic competition in the United States, for just seven complex products analyzed, could generate annual savings ranging from USD 600 million to USD 1.7 billion, with a median estimate of USD 1.3 billion.

These medicines are used to treat a variety of serious conditions. One example is respiratory diseases, where inhalers and nebulizers are used for asthma and chronic obstructive pulmonary disease (COPD). They are also used in dermatology, through topical formulations for psoriasis, eczema, and other skin conditions. Likewise, they are important in the treatment of mental health disorders such as schizophrenia, where such alternatives are needed to improve therapy adherence, among other aspects. They also play an important role in the management of chronic pain. Finally, in oncology, they are used in complex injectable formulations.

In 2022 in the United States, while 25% of all approved reference (innovative) medicines were considered complex products, only 13% of all approved generic medicines had this characteristic, highlighting the ongoing difficulty in bringing them to market. This gap has several potential causes.

One of these is the regulatory requirements for approving complex generics, which demand continuous dialogue with regulatory agencies. In this sense, the U.S. Food and Drug Administration (FDA) has been actively developing guidance to establish specific standards for different types of complex generics. Additionally, collaboration between the FDA and the European Medicines Agency (EMA) is helping advance greater regulatory convergence and harmonization in relation to complex generics, which is key to enabling their development and ensuring patient access.

However, as is also the case with biosimilar medicines—on which I have previously commented in these columns—obtaining regulatory approval from medicines agencies is not sufficient for complex generics to reach patients. There are other key factors essential to capturing their full value for healthcare systems.

One of these factors is education about what complex generics are and the benefits they offer, both for healthcare professionals and patients. While several studies have focused on identifying the information and strategies needed to increase acceptance of generic medicines overall, there is virtually no research addressing complex generics specifically. For these purposes, and as noted earlier, complex generics are more similar to biosimilars than to simple generics. Therefore, dialogue by medicines agencies and health authorities should not be limited to developers and manufacturers seeking to register these medicines, but should also target healthcare professionals and patients, ensuring they have the confidence needed to use them and avoiding misinformation that could hinder access to these alternatives.

Another relevant factor is public procurement, which can either encourage or hinder the entry of complex generics. Governments and healthcare systems must be consistent in their efforts to establish regulatory requirements for the registration of complex generics and their subsequent use. In this regard, procurement processes and tender models should promote the adoption of complex generics as soon as they become available following registration, provided that they deliver financial benefits to the healthcare system.

Finally, payers and health insurers can play a more active role in driving the use of complex generics in healthcare systems, given their strong interest in cost containment.

As can be seen, there is still much to be written about complex generics. They have been less prominent in public discussion, yet they are poised to make a decisive contribution to improving access to medicines for serious and costly diseases. Therefore, it is imperative to raise their visibility and encourage both public and private stakeholders to reflect on and address the barriers to entry these important medicines face, for the benefit of healthcare systems and patients.