he integration of pharmacovigilance (PV) with traditional medicine systems is an important yet underexplored area. As regulatory science, pharmacovigilance has grown considerably in the past two decades, predominantly focusing on modern medicinal products. However, the world of Alternative Medicine—comprising Ayurveda, Yoga, Unani, Siddha, and Homeopathy (AYUSH)—offers a vast array of health solutions that are used by millions globally. Despite their popularity, these systems have not yet been subject to the same level of scrutiny from a safety and efficacy standpoint as modern pharmaceuticals.

During the DIA India Annual Meeting 2024 in Mumbai, we explored this very topic. Our session, titled Ayurveda and Unani Medicine from a Pharmacovigilance Perspective, sought to highlight the safety challenges and regulatory nuances associated with AYUSH products. This article encapsulates these insights and offers a fresh perspective on pharmacovigilance as it applies to herbal and traditional medicines.

A Growing Demand for Pharmacovigilance in Traditional Medicine

Most AYUSH medicines are herbal-based, relying heavily on centuries-old traditional knowledge rather than the rigorous experimental processes typical in modern medicine. Despite this, the widespread usage of these products, particularly for example in India, necessitates a thorough understanding of their benefit-risk profiles. There is a common misconception that being “natural” is equivalent to being “safe.” However, this equivalence does not always hold.

The increasing global use of these products calls for a critical evaluation of their safety, especially considering the diverse patient populations that rely on them for primary healthcare needs. This is where the role of pharmacovigilance becomes indispensable, monitoring, assessing, and ensuring that these traditional therapies do not inadvertently harm public health.

Industry Perspective on AYUSH Pharmacovigilance

Herbal and alternative medicines saw exponentially increased consumption throughout the COVID-19 pandemic, raising concerns about their safety. Unlike synthetic medicines, herbal medicines are typically chemically rich and complex products and not isolated single active substance. The geographic origin, which includes the soil, climate, and photoperiod (exposure to the sun), genotype, and parts of the plant (leaves, stems, root, root bark, etc.) can all have an impact on the chemical profile, both qualitatively and quantitatively.

Products may be made from the same plant, but their phytochemical composition will vary depending on the plant component and the concentration of one or more active substances. Adulteration, pesticides, heavy metals, toxicity (excess dose), microbial pathogens, and standardization/batch-to-batch variation are among the concerns that healthcare professionals (HCPs) raise regarding the quality of herbal medicines.

Hence, the same product from two different companies might not be similar, compared to what is the case for modern medicinal products. The safety risks with herbal products need to be taken seriously because of the absence of industry standards and their recent exponential growth.

The identification of adverse effects in herbal products poses several challenges, including inadequate pharmacovigilance training in academia and industry, challenging causality assessment due to confounding factors, and a lack of expertise in causality analysis of herbal medicine.

Paths forward to support AE reporting for herbal medicine include herbal drug safety studies (pre-clinical studies, toxicity studies, and phase 1 through 4 clinical trials), mandatory reporting of AE to regulatory bodies, validation scales for the assessment of causality of adverse reactions reported for herbal products, easy access to unbiased herbal drug information, and pharmacovigilance training and related programs in the curriculum of both undergraduate and postgraduate life sciences.

Industry’s objective should be to establish a standardized, well-regulated system for herbal pharmacovigilance, in line with modern medicine, to assess the safety and efficacy of all herbal products. This is because the moral responsibility of product safety lies with the herbal manufacturers to set up post-marketing surveillance and PV systems.

Safety Myths and Realities

One of the basic myths and realities surrounding the safety of alternative medicines is the common belief that ASU (Ayurveda, Siddha, and Unani) drugs are naturally prepared, cost-effective, and nutritious. Since these drugs are derived from natural sources, they are thought to align well with human physiology, resulting in fewer side effects or none at all. This leads to the perception that they are safer compared to modern therapies, and that adverse drug reactions (ADRs) are associated only with modern therapies. Some practitioners even argue that all herbal remedies are safe due to their historical use. However, when adverse events occur, they often attract sensational media attention, creating a negative impression instead of focusing on the underlying causes.

In traditional medicine, the types of ADRs are not clearly defined, and rare adverse events or delayed effects may not be easily recognized, even with longstanding use. Symptoms such as irritability, depression, fatigue, headaches, joint and muscle pain, or gastrointestinal issues are often dismissed or not taken seriously. These seemingly unrelated symptoms are frequently attributed to food or other medications rather than to the herbal treatments. Additionally, they may be overlooked as psychological or emotional issues. Diagnosing ADRs is challenging and time-consuming, requiring expertise from individuals with a specific interest or from a dedicated traditional medicine Causality Assessment Committee.

Factors leading to the under-reporting of ADRs related to traditional medicine (TM) include a lack of scientific correlation between specific TM products and their adverse effects. Patients often discontinue TM once they start feeling better or unwell, and both modern and AYUSH practitioners may be unaware of patients’ use of herbal medicine because many individuals do not view herbal and nutritional products as “medicines” and fail to disclose their use. Additionally, both physicians and patients may not realize that herbal ADRs should be reported. Pharmacovigilance reporting (PSUR) was not mandatory in India for ASU manufacturers, due to the emerging nature of the national pharmacovigilance system for AYUSH medicine, until the national pharmacovigilance program for AYUSH (AyushSuraksha) was unveiled in 2017-2018.

Compared to modern drugs, pharmacovigilance for traditional medicine products faces unique challenges. The complexity of herbal products, along with their chemical variability and lack of standardization, complicates the assessment of their safety. The World Health Organization (WHO) highlights the importance of incorporating traditional medicines into pharmacovigilance systems and has published guidelines on the safety monitoring of herbal medicines within these frameworks.

The current Materiovigilance program in India does not encompass AYUSH devices, highlighting the need for proper documentation, systematic classification of Ayurvedic devices, and the establishment of an Ayurveda Materiovigilance (AMv) system.

Conclusion

In an era where patient safety is paramount, and more patients have the opportunity to pursue alternative treatments, pharmacovigilance must expand beyond modern medicine and into the domain of traditional and alternative therapies. With millions relying on AYUSH systems for their healthcare needs, ensuring the safety of these treatments is a crucial step in the global healthcare ecosystem.

This article consolidates perspectives shared at the DIA India Annual Meeting 2024, but the conversation on pharmacovigilance and alternative medicine is far from over. The authors hope that this discussion will encourage further exploration into the safety of traditional medicines and help establish more robust regulatory frameworks for these widely used products.