The WHO defines pharmacovigilance as “The science and activities associated with the detection, assessment, understanding, and prevention of adverse effects or any other possible medication-related problems.
Its scope has recently expanded to cover herbals, traditional and alternative medicines, blood products, biologics, medical devices, and vaccines.
Meaning of Pharmacovigilance:
- Pharmakon (Greek) = drug
- Vigilare (Latin) = to stay alert, keep watch, maintain caution and care, and be vigilant about dangers.
Pharmacovigilance (PV) plays a crucial role in ensuring patient safety and therapeutic efficacy. It is a key component of the healthcare system that monitors, evaluates, and identifies drug interactions and their impact on humans.
While pharmaceutical and biotechnological products are designed to treat, prevent, or manage diseases, they come with inherent risks, particularly adverse drug reactions (ADRs), which can have serious consequences for patients.
For this reason, monitoring ADRs is vital for ensuring medication safety throughout the entire lifecycle of a drug—from pre-marketing stages, drug discovery, clinical trials, to post-marketing surveillance.
It is widely accepted that a drug must undergo multiple phases to demonstrate its safety and efficacy before it is marketed commercially.
However, clinical trials come with several limitations. Strict inclusion and exclusion criteria mean that these trials only involve a highly selective group of patients. In addition, special populations such as children, pregnant women, and the elderly are often excluded from these studies.
Factors such as genetic variability, environmental influences, and drug-drug interactions may also be overlooked during clinical trials. These limitations highlight the importance of continued safety monitoring once a drug is on the market.
Reports of adverse events gathered by PV systems can benefit communities by facilitating communication between reporters and public health professionals, as these systems are both knowledgeable and accessible to the population.
Pharmacovigilance thus supports patients in their recovery and contributes to optimal disease management or even prevention. Ensuring patient safety is a joint responsibility involving pharmaceutical companies, regulators, clinicians, and other healthcare professionals, all of whom aim to enhance public health through PV.
History of Pharmacovigilance:
Pharmacovigilance as a formal practice has evolved over time, prompted by several historical events that exposed the need for better drug safety measures.
Three major incidents have played a critical role in shaping pharmacovigilance practices:
1- Hannah Greener Incident (1848):
On January 29, 1848, a young girl named Hannah Greener from northern England died after receiving chloroform anesthesia during the removal of an infected toenail.
Sir James Simpson had introduced chloroform as a safer and more effective anesthetic. Investigations into her death were inconclusive, though it was suspected that she might have died from a lethal arrhythmia or pulmonary aspiration. This incident is considered an early recognition of the importance of monitoring medical safety.
2- Sulfanilamide Disaster (1937):
Sulfanilamide was sold by the S.E. Massengill company in the United States as a treatment for streptococcal infections like pharyngitis and tonsillitis.
To create a liquid form of the drug, the company dissolved sulfanilamide in diethylene glycol, a toxic solvent. This led to the deaths of 107 people, including many children.
The lack of regulations regarding drug safety at the time contributed to this tragedy. In response, the U.S. government enacted the Food, Drug, and Cosmetic Act of 1938, which required safety testing of drugs before they could be marketed. However, the law focused solely on safety, not efficacy.
3- Thalidomide Tragedy (1950s–1960s):
Thalidomide, a sedative introduced by West Pharmaceuticals in the 1950s, was marketed as a safe and effective sleep aid and was widely prescribed to pregnant women to alleviate morning sickness. However, in 1961, a significant rise in cases of phocomelia—babies born with shortened or missing limbs—was linked to the use of thalidomide during pregnancy.
Dr. William McBride and Dr. Widukin Lenz independently identified the connection between thalidomide and these birth defects. Animal studies confirmed that the drug, once considered safe, was causing severe congenital malformations.
This incident led to the introduction of stricter regulations worldwide, emphasizing both the safety and efficacy of drugs.
Bodies and Procedures Aimed at Monitoring Drug Safety
Following these events, the first bodies and procedures emerged aimed at monitoring the safety of the drug.
The Food, Drug and Cosmetic Act (1938)
The Food, Drug and Cosmetic Act (1938) was established in the United States. This set of laws charged the Food and Drug Administration (FDA), established in 1906, with supervising the safety of foods, drugs, medical devices, and cosmetics, laying the foundations of pharmaceutical legislation.
World Health Organization (1948)
The World Health Organization (WHO) was founded in Geneva to centralize health issues worldwide.
Mandatory Preclinical Studies (1962)
In 1962, following the Thalidomide accident, the Harris-Kefauver amendments were introduced in the United States, mandating the need to conduct mandatory preclinical studies.
Only after evaluating the results of these studies could the clinical trial phase on humans begin. Furthermore, marketing authorization depended on data obtained in the three phases of clinical trials. After marketing, drugs were subjected to post-marketing surveillance.
Yellow Card Scheme (1964)
In the United Kingdom, the Yellow Card, the first form for reporting adverse reactions by doctors, was introduced in 1964.
Program on International Drug Monitoring (PIDM) (1968)
The WHO, in 1968, promoted the Program on International Drug Monitoring (PIDM), an international drug monitoring program aimed at centralizing global data on adverse reactions.
Initially, 10 states were involved. In that same year, the WHO created the global reporting database located in Uppsala, Sweden.
Pharmacovigilance Developments in France and Sweden
In 1973, France inaugurated the first six hospital surveillance centers, where the term “pharmacovigilance” was formally adopted.
The Swedish government and the WHO founded the Uppsala Monitoring Centre in 1978.
European Medicines Agency and EudraVigilance (1995-2001)
In 1995, the European Medicines Agency (EMA) was founded. In 2001, Eudravigilance, the European database for the management of adverse reaction reports, was implemented.
National Pharmacovigilance Network (RNF) in Italy (2001-2006)
In Italy, the National Pharmacovigilance Network (RNF) was created in 2001 to collect reports of adverse reactions at the national level, and in 2003, the Italian Medicines Agency (AIFA) was created.
Since 2006, Italian healthcare companies have been obliged to designate a qualified person responsible for pharmacovigilance activities (QPPV).
Pharmacovigilance Risk Assessment Committee (PRAC) (2012)
With the establishment of the Pharmacovigilance Risk Assessment Committee (PRAC) in 2012, the European pharmacovigilance system was further strengthened, clearly defining roles and responsibilities.
The PRAC is responsible for evaluating and monitoring the safety of medicines for human use and provides recommendations to the relevant committees.
Pharmacovigilance in Arab Countries
The development of pharmacovigilance (PV) in Arab countries began with the formation of national regulatory authorities. These authorities collaborated with international bodies such as the WHO and the Uppsala Monitoring Centre (UMC) to establish PV centers.
Pharmacovigilance in Egypt
Pharmacovigilance in Egypt has emerged as a leader in the Arab world. The country’s journey began in the 1990s, with significant progress following the establishment of the Egyptian Pharmaceutical Vigilance Center (EPVC) under the Egyptian Drug Authority (EDA) in 2009.
In Egypt, national pharmacovigilance guidelines issued by the EPVC under the EDA provide a comprehensive framework for monitoring drug safety, reporting adverse drug reactions (ADRs), and ensuring compliance with local regulatory standards.
Aim of pharmacovigilance:
- To strengthen public protection against new medications
- To assist in the evaluation of the efficacy and risks of medicines.
- To promote healthy communication within communities.
- To encourage the rational and safe use of medications.
- To monitor drug efficacy and side effects.
- To prevent adverse drug reactions through vigilant monitoring.
- To improve public health and safety by raising awareness, education, and clinical training regarding pharmacovigilance.
Need for pharmacovigilance:
- Clinical trial evidence of safety is often insufficient, necessitating further vigilance.
- While medicines are meant to prolong life, deaths caused by drugs, unlike those caused by diseases, are unacceptable.
- The cost of adverse drug reactions (ADRs) can exceed the cost of the drugs themselves.
- Encouraging the rational use of medicines and adherence to guidelines.
- Maintaining public trust in the healthcare system.
- From an ethical perspective, it is immoral to withhold information about harm when others are unaware and at risk.
In summary, pharmacovigilance is vital for safeguarding patient safety and ensuring the effectiveness of medications. By continuously monitoring and evaluating drug safety, contract research organization companies play a key role in helping protect public health and prevent adverse effects. As new treatments emerge, the importance of pharmacovigilance will only grow, highlighting the need for ongoing vigilance in the healthcare system.