Clinical research is integrated and important with regard to pharmacovigilance.[1]

Throughout the product lifecycle, pharmacovigilance and clinical trials safety are critically important. Pharmacovigilance is responsible for monitoring and assessing the safety of the product. “defined as the pharmacological science relating to the detection, assessment, understanding and prevention of adverse effects, particularly long term and short term adverse effects of medicines.”. Clinical trials safety and post-marketing pharmacovigilance are critically assessed throughout the product lifecycle Not much has been achieved in India with regard to major advancements in the field of pharmacovigilance . Pharmacovigilance has a significant impact on the life cycle of a product, emphasizing the necessity of recognizing its importance. Good pharmacovigilance practices will be integrated into the process and procedures through this, helping ensure regulatory compliance and enhancing clinical trials safety and post-marketing surveillance. Numbers have been going on with Pharmacovigilance in India instead of Pharmacovigilance not being new to India.[2]

History: It is detailed in the account of the significant events in pharmacovigilance.

 Thalidomide Tragedy (1950s-1960s): Thalidomide severe birth defects were caused in   thousands of infants by Thalidomide, originally prescribed as a sedative and antiemetic. Systemic monitoring of drug safety was highlighted by this catastrophe. Increased awareness of the potential harm drugs could cause during pregnancy resulted from the aftermath. .

1. Formation of WHO Program(1968) The International Drug Monitoring Program was established by WHO in the aftermath of the thalidomide incident. A global network of pharmacovigilance centers was founded by this program, promoting collaboration in the collection and analysis of data on adverse drug reactions (ADRs).
2. FDA and AERS (1970s): The FDA initiated the Adverse Event reporting system (AERS) in 1970s. The FDA uses the AERS to collect, manage, and analyze  data on adverse events related to drugs, making it a crucial instrument for monitoring and regulating drug safety in the United States.
3. ICH Guidelines (1990s): A crucial role was played by the international conference on harmonization (ICH) in standardizing pharmacovigilance practices globally. Safety data could be collected and exchanged harmoniously among regulatory authorities through ICH guidelines like E2B.
4. EU Pharmacovigilance system (2005): The European Union introduced a comprehensive pharmacovigilance system. The European Medicines Agency (EMA) coordinated safety assessments and risk management strategies to strengthen monitoring and supervision of medicinal products.
5. Periodic safety update reports (PSURs): PSURs become a standard requirement for marketing authorization holders. Regulatory authorities continuously evaluate the safety profile of drugs through the submission of regular safety data in these reports.     
6. Digital Age and Signal Detection (21 century): Technological advancement in 21 century supported the inclusion of big data and digital platforms for pharmacovigilance. Large datasets were enhanced in efficiency for identifying potential safety concerns through the use of algorithms and data mining by the automated signal detection system.    
7. Global collaboration (current): Global collaboration is a component of a new modern pharmacovigilance. A country's individual case safety reports (ICSRs) are standardized and exchanged cross-country through the global system established by the World Health Organization (WHO). Through the approach, monitoring and safe use of medicinal products are participated in by regulation agencies, pharmaceutical companies, health professionals, and patients.[3]

Importance and Scope of Pharmacovigilance:

    Importance: Throughout the product lifecycle, pharmacovigilance is crucial and essential for ensuring safety. Post marketing surveillance and clinical trial safety are both vital components of this process. Pharmacovigilance is not advanced in India, and limited information is available on the topic. In contrast, the western countries have made substantial progress. Pharmacovigilance significantly affects a product’s life cycle by ensuring its significance is understood. Best practices for pharmacovigilance can be incorporated into the procedures and processes to assure regulatory compliance, improve clinical trial safety, and monitor products once they are on the market, making it possible for these activities to be carried out effectively. After India’s decision to join the Upasla centre for adverse event monitoring in 1998, adverse events have been monitored through pharmacovigilance in that country. Pharmacovigilance is highlighted by withdrawals, regulatory bodies, the media, and increased consumer awareness of medications’ advantages and risks.[4]

The importance of pharmacovigilance is as follows:

1. Pharmacoepidemiological trials.
2. safety monitoring of pharmaceuticals.
3. Case reports.
4. case series development.
5. case series analysis.
6. data mining to find product-event combinations.
7. spontaneous reporting.[5]

Scope:

These healthcare products should have their safety measures and regulatory oversight enhanced.[6] The Drugs and Cosmetics Act of 1940 and subsequent rules of 1945 have established the Pharmacovigilance Program of India (PV PI). The Central Drugs Standard Control Organization (CDSCO), India’s apex regulatory body for pharmaceutical and medical devices, exercises jurisdiction over the program. Several key objectives are pursued by PV PI, with a primary focus on ensuring patient safety by monitoring adverse drug reactions (ADRs). The National Coordinating Centre (NCC) is responsible for overseeing the program’s functioning as its central coordinating body. ADR reports are received from various sources, including healthcare professionals, consumers, and pharmaceutical companies, in a pivotal role. Strategically located across the country are the Regional Adverse Drug Reaction Monitoring Centres (AMCs), which facilitate efficient data collection and analysis. The NCC receives and processes ADR reports from these AMCs, forwarding the relevant information to it. Various stakeholders can access the reporting mechanism, which includes an online platform established by the CDSCO, making it user-friendly for healthcare professionals and the public. Pharmaceutical products undergo systematic evaluation with both statistical and clinical assessments to identify potential safety signals in the process of signal detection and analysis. Emerging risks are promptly recognized and addressed through a rigorous approach. Communication and dissemination of safety information are emphasized in PvPI. Healthcare professionals and the broader public are made aware of regular newsletters, safety alerts, and educational programs. Informed decisions-making and a culture of safety within the healthcare community are supported by this approach. Domestically, PvPI collaborates with international pharmacovigilance networks. Pharmacovigilance is strengthened through the proactive stance of this collaboration, which enables the sharing of information and best practices, contributing to global drug safety initiatives. In India, PV PI focuses on enhancing awareness and reporting capabilities among healthcare professionals through training programs and workshops, which are an integral part of its capacity building strategy for infrastructure development. [7] These healthcare products should have their safety measures and regulatory oversight enhanced. [8]

Objectives of Pharmacovigilance.

1.. A public-wide system for patient safety reporting can be established to produce reports.

2. New signals can be identified and dissected from report cases.
3. The benefit-threat rate of retail specifics can be dissected.
4. Grounded information on the safety of drugs must be induced to substantiate it.

5.A nonsupervisory agency must be supported in the decision-making process on using specific drugs rationally.[9]

 An important parameter for enhancing patient care and safety in relation to the use of medicines with medical and paramedical interventions remains unchanged. The adverse effect profile of drugs is monitored by pharmacovigilance to demonstrate their efficacy for many years, from the lab to the pharmacy, Drugs' use in public health and safety are being monitored for any drastic effects. Efforts are made to promote safe, rational, and cost-effective drug use, In pharmacovigilance, we work to promote understanding, education, and clinical training. We also strive for effective communication with the general public. [10]

Aim of Pharmacovigilance:

• Enhance patient care and safety with regard to medication use and all other medical and nonmedical treatments.
• Study the effectiveness of medications and keep track of any negative side effects by following them from the lab to the pharmacy and beyond for a long time.
• Pharmacovigilance monitors any severe side effects of medications.
• Boost public safety and health with regards to the use of medications.
• Encourage the safe, intelligent, and more effective (including cost-efficient) use of medicines by helping to analyse their benefits, harms, effectiveness, and risks. Promote public awareness, knowledge, clinical training, and effective communication of pharmacovigilance. [11]
• Finding instances of improper medication administration.
• A product's pharmacological/toxicological features are clarified more, and the way that it causes negative drug reactions.
• The identification of important drug-drug interactions in co-therapy and novel products.
• A market with agents already established, which might only be discovered during extensive application.
• The comparative profile of negative medication reactions among drugs belonging to the same therapeutic class.[12]

ROLES OF PHARMACOVIGILANCE

The role of pharmacovigilance in observing the risks associated with drugs has been widely accepted. A concerned small ratio of population is used for testing all medicines before they are approved for post-marketing surveillance. Various roles have been assigned to pharmacovigilance, including identification, quantification, and documentation of drug-related problems. It contributes towards minimizing the risk of such problems in healthcare systems. Factors and mechanisms responsible for drug-related injuries are enhanced, leading to a deeper understanding and knowledge of these issues. [29]

Politicians at national, regional, and local levels have required interactions and influence in fulfilling various roles of pharmacovigilance, healthcare administrators; drug regulatory authorities; pharmaceutical companies; Drug regulatory authorities, healthcare administrators, pharmaceutical companies, academic institutions, and healthcare professionals carry out various roles in the healthcare industry. Media representatives are contacted by various sources,  Health insurance companies issue policies and regulations, Lawyers represent clients in court, Patient groups advocate for their members’ health concerns. [30]

Minimizing Risks and Maximizing Benefits

 In healthcare, it is a principle that gives room to minimizing risk while maximizing the benefit, especially in drug management. The principle seeks to "achieve the greatest beneficial and minimized harms of treatment, including avoiding harm of adverse drug reactions, noncompliance, and drug interactions." Healthcare professionals utilize a risk-benefit assessment when trying to ensure patient safety. The risk versus the expected therapeutic benefit is weighed to know if there is a balance between the risk and the overall gain. [31]

The principle then extends to other varieties of RMS, which include careful patient screening, dose adjustment, and therapeutic drug monitoring especially to cases at risk like the elderly or those suffering from multiple comorbidities. This principle makes its way as paramount in pharmacovigilance and guides safe prescription practices. [32]

One of the successful strategies is the RMP that is implemented in almost all countries, EMA and FDA-regulated. RMPs also insist on the drugs' continuous assessment of their safety profile during the lifecycle, which basically translates to periodic reevaluation of their benefits and risks. Updating the risk profiles also requires post-marketing surveillance and real-world evidence, which help to keep healthcare providers informed of the best course of action for their patients. [33].

Early Detection of Adverse Drug Reactions (ADRs)

Essential for enhancing patient safety and improving therapeutic outcomes of medications is the early detection of Adverse Drug Reactions (ADRs).  Hospital stays, increased healthcare costs, and sometimes severe morbidity or mortality are caused by ADRs being among the leading causes. [34].

 The Yellow Card Scheme and the FDA’s MedWatch are typically used for the early detection of Adverse Drug Reactions through passive pharmacovigilance, Healthcare professionals and patients can report suspected drug-related adverse events. [33].

ADR detection has been significantly contributed to by technological advancements such as electronic health records (EHRs) and clinical decision support systems (CDSS). EHRs allow for the aggregation of patient data and can identify patterns of ADRs by cross-referencing medical records, laboratory results, and prescribed medications. [37]

CDSS can alert healthcare providers in real-time to potential ADRs based on a patient’s current medication regimen and health status, enabling quicker intervention.[35]

Another approach to the early detection of ADRs is the use of biomarkers. Biomarkers can help identify individuals who are more susceptible to certain adverse effects, thus allowing for personalized medicine approaches to minimize drug toxicity (World Health Organization, 2020).[36] Furthermore, large-scale observational studies and databases, such as the WHO’s Vigibase, provide global ADR reporting and detection, facilitating the identification of rare or unexpected ADRs across diverse populations. [36]

Public Health Implications

The public health implications of ADRs and risk-benefit assessments are profound, as they directly affect the safety and efficacy of medical treatments at a population level. ADRs contribute significantly to the global burden of disease, leading to avoidable hospitalizations, disability, and death (Kumar & Sinha, 2019). Public health initiatives aimed at minimizing ADRs and maximizing therapeutic benefits include implementing national pharmacovigilance programs, educating healthcare providers, and increasing public awareness of the safe use of medications. [36]

Vaccination programs provide an illustrative example. Despite the overwhelming benefits of vaccines in preventing infectious diseases, rare but severe ADRs can occur, and public health systems must continuously monitor these risks. In doing so, they reassure the public of the overall safety of vaccines while ensuring that appropriate measures are taken when adverse events are detected. [31]

 Additionally, large populations are further minimized from risks by public health policies that promote rational drug use, such as restricting over-the-counter availability of potentially harmful drugs. [32]

Public health organizations like the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) play vital roles in disseminating information on drug safety and ADRs, guiding policies that protect public health (World Health Organization, 2020)[36]. Moreover, healthcare systems need to adapt to emerging challenges, such as polypharmacy in aging populations, by fostering systems that can handle the complexities of drug safety on a broader scale. [37]

1. Key Concepts in Pharmacovigilance

Adverse Drug Reactions (ADRs)

A health product can cause an undesirable and harmful reaction, known as an adverse drug reaction (ADR), even at the usual dosages or a disease or organic function is tested for diagnosis, prevention, or treatment. [23-25]

Two ways adverse drug reactions (ADRs) are classified;[26]

A.Predictable (Type A) Reactions

The pharmacological characteristics of the drug cause increased and typical reactions, including adverse effects, toxic effects, and withdrawal symptoms.

1. Unpredictable (Type-B) Reactions

These are based on patient quirks rather than the known effects of the medicine; examples include allergy and eccentricity. They are less frequent, frequently not dose related, typically more dangerous, and call for drug discontinuation.[27,28]

Side Effects vs. Adverse Effects

In pharmacology, side effects and adverse effects are two terms often used to describe unintended effects of drugs, but they differ in their nature and impact. Side effects refer to unintended but often predictable reactions that occur at therapeutic doses and are generally mild and manageable. For example, drowsiness from antihistamines is a common side effect (Nebeker, Barach, & Samore, 2004)[38]. These effects are not necessarily harmful and may resolve with continued use or dose adjustment.

Adverse effects or adverse drug reactions (ADRs) are experienced as unwanted, harmful effects during the use of a drug. These effects can range from mild to severe and may require discontinuation of the drug or medical intervention (World Health Organization, 2020).[39] Adverse effects are considered more serious as they may cause significant harm, such as organ damage, allergic reactions, or even death. [40]

Serious vs. Non-Serious ADRs

Serious Adverse Drug Reactions (ADRs) can lead to life-threatening conditions, hospitalization, disability, or death. Non-serious ADRs do not have such severe consequences. These require immediate medical attention, and in some cases, permanent cessation of the drug. For instance, anaphylactic shock caused by penicillin is a serious ADR.[38]

Conversely, non-serious ADRs may involve minor symptoms like nausea, headache, or mild skin reactions, which do not require hospitalization and often resolve with continued use or dose modification. These reactions are less life-threatening but still affect patient compliance and treatment outcomes. [41]

Causality Assessment

Causality assessment in pharmacovigilance refers to the process of determining whether a particular drug is responsible for an observed adverse reaction. Several methods are used to assess causality, including clinical judgment, algorithms (e.g., Naranjo scale), and probabilistic methods. The Naranjo algorithm is widely used to quantify the likelihood of a drug causing a specific adverse effect by assigning scores based on factors like temporal association, alternative causes, and the presence of prior reports. [42]

Causality assessment is crucial in pharmacovigilance to distinguish true ADRs from coincidental occurrences of symptoms due to other factors such as underlying diseases or drug interactions. [39]

1. Global Pharmacovigilance Systems

Global pharmacovigilance systems aim to monitor, detect, assess, and prevent adverse effects from medicines on a worldwide scale. These systems play a critical role in ensuring drug safety and protecting public health.

World Health Organization (WHO) Programme for International Drug Monitoring

The WHO Programme for International Drug Monitoring (PIDM), established in 1965, is cornerstoned by global pharmacovigilance in the role of the primary institution. The program facilitates collaboration between member countries, helping them to monitor ADRs and share data through VigiBase, a global database managed by the Uppsala Monitoring Centre (UMC). [39]

 This program enables early detection of ADRs, particularly for new drugs or rare adverse events, by pooling data from countries around the world.

Through this collaboration, low- and middle-income countries can access advanced pharmacovigilance tools and training, making it possible for even smaller healthcare systems to contribute to global drug safety efforts. [40]

Pharmacovigilance in Developed Countries

In developed countries, pharmacovigilance systems are more advanced due to well-established regulatory frameworks and resources. Robust pharmacovigilance mechanisms are in place in the U.S. Food and Drug Administration (FDA) through its MedWatch program and in the European Medicines Agency (EMA) with its EudraVigilance system. [44]

These agencies require rigorous post-marketing surveillance and reporting of ADRs by healthcare professionals and pharmaceutical companies. The systems in these countries are often supported by large-scale electronic health records (EHRs), real-world evidence (RWE), and advanced technologies like artificial intelligence (AI) that enable the early detection of ADRs and enhance drug safety monitoring. [43]

Pharmacovigilance in Developing Countries

In developing countries, systems of pharmacovigilance may be more immature due to the scarcity of infrastructure as well as paucity of resources and awareness among the medical professionals. Most countries fail to have proper ADR reporting systems, and underreporting of ADRs remains a big issue. [42]

However, the WHO Global Training Network has been providing education, tools, and support to health professionals of developing countries to better pharmacovigilance activities (World Health Organization, 2020)[39]. India as well as South Africa have shown leadership by establishing national programs, but there is still a difference between developing and developed countries as system changes are very sturdy. [41]

Challenges in Global Harmonization

One of the major challenges in global pharmacovigilance is the harmonization of data collection, reporting, and assessment procedures. Different countries use various systems, tools, and standards for ADR monitoring, which can lead to inconsistencies in data quality and reporting. Disparities still exist in creating common standards for pharmaceuticals for human use through the International Council for Harmonisation of Technical Requirements (ICH). [40]

Moreover, legal and regulatory differences between countries can slow down the global response to emerging safety issues. Addressing these challenges requires enhanced collaboration, sharing of resources, and continued support for countries with emerging pharmacovigilance systems. [42]

Regulatory Framework

A robust regulatory framework is essential to enhance the safe use of medicines and to minimize risks associated with adverse drug reactions (ADRs). Regulatory agencies worldwide collaborate to create consistent standards and frameworks for pharmacovigilance.

Role of Regulatory Agencies

Drug safety is ensured by regulatory agencies through enforcing regulations and guidelines on the monitoring and reporting of Adverse Drug Reactions. These agencies ensure that pharmaceutical companies comply with post-marketing surveillance and report any safety concerns promptly. [46].

  In the U.S., the FDA monitors drug safety through programs like MedWatch, where healthcare professionals and the public can report adverse effects.[47]. Similarly, the European Medicines Agency (EMA) oversees pharmacovigilance in Europe through its EudraVigilance system, ensuring that any emerging safety issues are addressed swiftly. [46]

International Guidelines (ICH, CIOMS)

International guidelines help harmonize drug safety practices across countries. Standardized protocols for the evaluation and monitoring of drug safety are provided by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). These protocols include Good Pharmacovigilance Practices (GVP). [48]

Similarly, the Council for International Organizations of Medical Sciences (CIOMS) develops global guidelines on drug safety, risk management, and causality assessment to facilitate cooperation between countries in addressing ADRs. [45]

National Regulatory Bodies and Their Role (e.g., India, USA, Europe)

2. Pharmaceutical products are ensured to be safe for public use by regulatory bodies such as the Central Drugs Standard Control Organization (CDSCO) in India, the FDA in the U.S., and the EMA in Europe. These agencies require pharmaceutical companies to conduct post-marketing surveillance, report ADRs, and take corrective actions when necessary. [46]
3. In India, the Pharmacovigilance Programme of India (PvPI), under the CDSCO, coordinates ADR reporting and drug safety monitoring across the country. [49]
4. Methods and Tools in Pharmacovigilance

Several methods and tools are used by pharmacovigilance to detect, assess, and manage adverse drug reactions and ensure drug safety.

Spontaneous Reporting Systems (SRS)

Voluntary reports of Adverse Drug Reactions (ADRs) are submitted to Spontaneous Reporting Systems (SRS) by healthcare professionals and patients. Systems like VigiBase, managed by the Uppsala Monitoring Centre, and MedWatch, operated by the FDA, are examples of such systems. These systems are invaluable for detecting rare and unexpected ADRs that may not have been discovered during clinical trials. [51]

Cohort Event Monitoring

New drugs' safety is monitored through cohort event monitoring, which is a reactive approach. Instead of initiating the process, we follow a group of patients who have been exposed to a specific drug and document any adverse events that occur. This method provides more comprehensive data on ADRs compared to spontaneous reporting, as it systematically tracks patients over time. [52]

Case-Control Studies

Adverse events are compared between patients in case-control studies used in pharmacovigilance. Some patients experienced an adverse event (cases), while others did not (controls). These studies are useful for identifying risk factors associated with specific ADRs and for assessing causality between drug exposure and adverse outcomes. [46]

Signal Detection and Management

Potential safety issues are identified from large databases of ADR reports through the use of data mining and statistical algorithms in signal detection, which are then assessed to determine if further investigation is needed. Effective signal management is critical for preventing widespread harm caused by unsafe drugs. [45]

Pharmacovigilance Databases (e.g., VigiBase, MedWatch)

5. Pharmacovigilance databases like VigiBase (WHO), MedWatch (FDA), and EudraVigilance (EMA) serve as repositories for ADR reports. These databases enable regulatory agencies to detect patterns in ADRs and take appropriate action to protect public health. For example, VigiBase consolidates data from more than 150 countries, allowing for global monitoring of drug safety. [51]
6. The Role of Healthcare Professionals and Public in Pharmacovigilance

Healthcare professionals and the public play crucial roles in the success of pharmacovigilance programs by actively participating.

Reporting Adverse Events

Regulatory bodies are often reported ADRs  by healthcare professionals, such as doctors, nurses, and pharmacists, who are the first to encounter them and play a critical role in doing so. Prompt and accurate reporting of ADRs helps in the early detection of drug safety issues, thereby preventing further harm. [49].

Encouraging Patient Participation

Adverse effects experienced by patients while taking medications are reported in pharmacovigilance. Regulatory agencies, including the FDA, provide platforms like MedWatch for patients to directly report Adverse Drug Reactions (ADRs).  Encouraging patient participation is vital, as many ADRs may go unreported if healthcare professionals are not directly involved. [47]

Responsibility of Pharmacists, Doctors, and Nurses

Pharmacists, doctors, and nurses have a collective responsibility in pharmacovigilance. Pharmacists are often responsible for counseling patients about potential ADRs and ensuring the safe dispensing of medications. Doctors are responsible for prescribing drugs safely and monitoring patients for any adverse reactions. Nurses are key in monitoring patients and administering medications, making them well-positioned to observe and report ADRs. [50] Together, these professionals form the backbone of pharmacovigilance systems and contribute to overall drug safety.

Pre-Marketing Surveillance

Early in the drug development pipeline, potential Adverse Drug Reactions  of a prospective drug  are predicted or assessed.  Preclinical in vitro Safety Pharmacology Profiling (SPP) is applied by testing compounds using biochemical and cellular assays. ADRs (adverse drug reactions) may occur in humans if a compound binds to a certain target. However, detecting these reactions experimentally remains a challenging task due to cost and efficiency constraints. Numerous research activities have been devoted to predicting potential adverse drug reactions using preclinical characteristics of compounds or screening data. The approaches in most of the existing research can be categorized as protein target-based or chemical structure-based, while some have explored the integrative approach. [13]

Risk Management Plans (RMP)

Many ADRs (adverse drug reactions) may be missed even after a drug undergoes extensive screening by the Food and Drug Administration (FDA). This is because clinical trials are often small, short, and biased, excluding patients with comorbid diseases. Post-market surveillance is important for ensuring that premarketing trials accurately reflect actual clinical use situations for various populations, including inpatients. The Pharmacovigilance (PV) system plays an essential role in post-market analysis of newly developed drugs. [14,15].

A complex research and development process is undergone by pharmaceutical companies before launching a new drug into the market, with competition and rigorous regulatory evaluation procedures in place. Post marketing PV can draw from several unique data sources being made available.[16]

Signals in PV research are defined as undisclosed assertions by the World Health Organization (WHO) on direct relationships between effects on the human organism and a drug, inducing adverse events. [17]

Spontaneous reporting systems (SRSs) are used by clinicians and researchers to generate comprehensive signal datasets. These systems are already implemented electronically in some European countries and the United States.  Other solutions, such as analyzing general practitioners’ databases, conducting post-market studies, and prescription monitoring, among others, are being thoroughly explored for finding alternatives. Severely limiting signal detection, the majority of data is not available to the public for researchers. [18-20]

Drug events are reported to drug companies by clinicians, lawyers, or patients. The detection process largely depends on the ability of physicians to recognize a given trait as a drug adverse event. The problem of collecting and filtering ADR data from multiple distributed nodes has been studied in the past, the data and other post-drug administration inputs are pursued relentlessly by researchers in order to uncover the most effective strategies. [21].

Millions of electronic medical records are scavenged using data and text-mining techniques, and PV researchers are now faced with the problem of delivering knowledge-oriented tools and services that exploit this data.  These data will ultimately pave the way for improved drug evaluations, which are critical for pharmaceutical companies, regulatory entities, and researchers. [22]

Risk Management Plans (RMPs) are integrated into the process to ensure the safety of pharmaceutical products after authorization for use. Risks associated with a medicinal product are identified, assessed, and minimized throughout its life cycle by these plans.[54] The safety profile of a drug is continuously monitored to ensure that its benefits outweigh its risks by RMPs .

Post-Authorization Safety Studies (PASS)

7. Safety studies (are conducted as part of the risk management process) after a drug has been approved for market use, are known as Post-Authorization Safety Studies (PASS). In the broader population, risks of a drug may be identified and assessed, which were not apparent during clinical trials. [53]  Rare or long-term adverse effects may not be detected unless PASS is employed.
8. Current Challenges in Pharmacovigilance

Pharmacovigilance faces several challenges that limit its efficiency in detecting and managing adverse drug reactions.

Underreporting of ADRs Underreporting remains one of the most significant issues in pharmacovigilance. Many adverse drug reactions (ADRs) go unreported, particularly mild or moderate ones, leading to incomplete safety data. Factors such as lack of time, fear of legal consequences, and the assumption that mild ADRs are not serious contribute to this underreporting. [56]

Lack of Awareness Among Healthcare Professionals

A lack of awareness about pharmacovigilance among healthcare professionals also hampers its effectiveness. In many developing countries, medical and nursing curricula do not emphasize the importance of ADR reporting, resulting in healthcare providers being ill-equipped to contribute to pharmacovigilance systems. [59]

Data Management and Analysis

The increasing volume of ADR reports creates challenges in data management and analysis. Processing this data to detect meaningful safety signals requires advanced tools and systems, which many national pharmacovigilance centers lack. Inadequate data infrastructure can lead to delays in identifying and addressing drug safety issues.v[58]

Global Harmonization Issues

Global harmonization remains a critical issue, as pharmacovigilance regulations and practices vary widely between countries. Despite international efforts like those of the ICH and CIOMS, differences in regulatory requirements and reporting standards pose challenges to creating a truly unified global pharmacovigilance system. [53]

9. Technological Advances in Pharmacovigilance

Advances in technology are helping to overcome some of the challenges in pharmacovigilance.

Role of Artificial Intelligence and Machine

Artificial intelligence (AI) and machine learning can revolutionize pharmacovigilance by automating data analysis and signal detection processes. Vast amounts of data can be quickly and accurately sifted through by these technologies, identifying patterns and potential risks that might be overlooked by humans. [55]

Electronic Health Records (EHR) in ADR Detection

Electronic Health Records (EHR) systems are increasingly being used to detect ADRs in real time. EHRs can provide immediate access to patient data, helping healthcare professionals detect ADRs earlier and report them more efficiently. The integration of EHR systems with pharmacovigilance databases can enhance real-time monitoring of drug safety. [59]

Mobile Health Applications

Mobile health (mHealth) applications are gaining traction in pharmacovigilance, allowing patients and healthcare professionals to report ADRs more easily. Apps that facilitate ADR reporting make it easier for patients to report side effects directly to regulatory bodies, thereby improving data collection. [57]

Big Data and Real-World Evidence in Pharmacovigilance

Big data and real-world evidence (RWE) are increasingly being used in pharmacovigilance. Data is analysed from various sources, such as insurance claims and electronic health records, In the real world, regulatory bodies and patient registries can gain a more comprehensive understanding of a drug's safety profile, as opposed to the controlled environment of clinical trials. [54]

10. Pharmacovigilance and Public Health

Unsafe drugs are identified and communicated safety measures are ensured by Pharmacovigilance to safeguard public health.

Drug Withdrawals and Recalls

One of the most significant public health impacts of pharmacovigilance is the ability to prompt drug withdrawals and recalls. Regulatory agencies can take swift action to withdraw a drug from the market or issue a recall when it is found to cause serious harm. [58]

Public Safety Alerts and Communication

Regulatory bodies rely on pharmacovigilance systems to issue public safety alerts when new information about a drug's safety becomes available. Effective communication is critical for ensuring that healthcare providers and the public are informed about potential risks and can take necessary precautions. [55]

Impact on Public Health Policies

The data collected through pharmacovigilance not only influences drug safety but also shapes public health policies. Governments and health organizations use pharmacovigilance data to make informed decisions about drug regulation, healthcare guidelines, and treatment protocols, ultimately improving patient safety and healthcare outcomes. [53]

Future Directions of Pharmacovigilance

The challenges to manage drug safety efficiently and to adhere to regulatory requirements create the strong impression that widespread adoption of pharmacovigilance is inevitable. As an instrument of reform, pharmacovigilance has attributes that ensure its attractiveness to many groups in a politically and economically divided health care system that is struggling with seemingly insurmountable problems of cost and quality and post marketing clinical studies as well. Regulatory bodies such as FDA and European Medicines Agency (EMEA) are intensifying safety regulations, therefore boosting the adoption rates of pharmacovigilance systems by biopharmaceutical firms.16 However, the apparent certainty of pharmacovigilance adoption needs to be co 12.1.Precision Medicine and Pharmacovigilance:

12.2.Role of Pharmacogenomics:

Pharmacogenomics plays a vital role in understanding individual responses to drugs based on their genetic makeup. By identifying genetic factors that predispose individuals to adverse drug reactions (ADRs), pharmacogenomics helps personalize medicine, reducing the likelihood of harmful side effects. Tailoring drug therapies based on genetic information can improve safety and efficacy, making ADR management more proactive than reactive. [60]

 For example, genetic testing for certain enzyme deficiencies, such as CYP2C19, can guide dosing of drugs like clopidogrel, preventing ADRs in patients who metabolize the drug poorly. [63]

12.3. Improving ADR Reporting Systems:

Improving Adverse Drug Reaction (ADR) reporting systems is crucial for enhancing drug safety. Many countries are implementing measures to streamline the reporting process, making it more accessible for healthcare professionals and patients alike. Digital tools, such as mobile apps and online portals, have made reporting faster and more efficient. Simplified reporting forms and integrating ADR reporting into existing electronic health record (EHR) systems can help overcome the issue of underreporting (Gibbons, 2012)[61]. Moreover, training healthcare professionals on the importance of ADR reporting and reducing the complexity of the process can lead to more consistent and reliable data collection. [65]

12.4. Enhancing Collaboration Between Stakeholders:

Enhancing collaboration between stakeholders in pharmacovigilance—regulatory bodies, healthcare providers, pharmaceutical companies, and patients—is essential for a more comprehensive and effective ADR monitoring system. Multi-stakeholder engagement ensures the timely flow of information, from ADR detection to regulatory actions such as drug recalls or safety warnings. Collaborative efforts, such as public-private partnerships and international cooperation, can harmonize pharmacovigilance practices across borders and address global drug safety concerns (U.S. FDA, 2022)[64]. Such collaborations also help share knowledge and resources, especially in developing countries where pharmacovigilance infrastructure may be limited. [62]

13.1. Summary of Key Points:

This review explored the multifaceted aspects of pharmacovigilance, including the importance of risk management, the role of healthcare professionals, the evolving technological landscape, and the impact of pharmacogenomics. We also examined the current challenges, such as underreporting, and the strategies to improve ADR reporting systems, with a focus on enhancing global collaboration.

13.2. The Future Outlook of Pharmacovigilance:

 As pharmacovigilance continues to evolve, the integration of advanced technologies like artificial intelligence (AI) and machine learning will likely improve the detection and analysis of ADRs. These technologies, combined with genetic insights from pharmacogenomics, will push pharmacovigilance toward a more personalized approach to drug safety (FDA, 2022)[64]. Moreover, greater emphasis on real-world evidence (RWE) and big data analytics will further refine our understanding of drug safety and efficacy in broader populations (Shah et al., 2015)[63].

13.3. The Need for Continued Vigilance and Reporting:

Despite advancements, the need for continued vigilance and reporting cannot be overstated. A robust pharmacovigilance system depends on timely and accurate ADR reporting from all stakeholders—healthcare professionals, patients, and regulatory bodies alike. Ongoing education and awareness initiatives are critical to fostering a culture of safety in drug use. Ensuring consistent global standards and improving collaboration between regulatory agencies will be key to addressing future challenges in drug safety.

1. Pipasha, B. , Arun , K.B. Setting standards for proactive pharmacovigilance in India : The way forward‟, Indian J pharmacol , 2007; 39(3): 124-128.
2. Kumanan, R., Sudha, S., Vijayashre, P., Charumath, S., Gowridevi, K.C., Mahesh, M. imperative Approach on pharmacovigilance in Indian systems of medicines‟, International journal of pharma sciences and Research (ijpsr), 2010; 1(9): 378-390.
3. R Dr history And Development of pharmacovigilance110.
4. Linezolid (Zyvox) : severe optic neuropathy.
5. Hall M, Mc Cormack P, Aurthur N, Feely J. The spontaneous reporting of ADRs by. British journal f clinical pharmacology, 1995; 40: 173-175.          
6. DK Tripathi S Shiv Pharmacovigilance (Nirali Prakashan)2017262.
7. S Nimesh Pharmacovigilance program of review article Acta scientific S Nimesh Pharmacovigilance program of review article Acta scientific pharmaceutical sciences2022 sciences 2022 .
8. DK Tripathi S Shiv Pharmacovigilance (Nirali Prakashan)2017262.
9. S Nimesh Pharmacovigilance program of review article Acta scientific pharmaceutical sciences2022.
10. WHO Pharmacovigilance: ensuring the safe use of medicines, Geneva: WHO 2004.
11. Drotrecogin alfa (activated) (Xigris): risk benefit in the management of sepsis.
12. Moore N. The role of clinical pharmacologist in the management of ADRs. Drug safety, 2001; 24(1): 1-7.
13. Whitebread S, Hamon J, Bojanic D, Urban L. 2005. Keynote review: in vitro safety pharmacology profiling: an essential tool for successful drug development. Drug Discov 10, 1421-33
14. McClure DL. 2009. Improving Drug Safety: Active Surveillance Systems Should be paramount. Pharmaceutical Medicine. 23, 127-30. http://dx.doi.org/10.1007/BF03256760.
15. Shibata A, Hauben M. Pharmacovigilance, signal detection and signal intelligence overview. Proceedings of the 14th International Conference on Information Fusion (FUSION-2011).
16. Lopes P, Nunes T, Campos D, Furlong LI, Bauer-Mehren A, et al. 2013. Gathering and Exploring Scientific Knowledge in Pharmacovigilance. PLoS ONE. 8(12), e83016.
17. Stahl M, Edwards IR, Bowring G, Kiuru A, Lindquist M. 2003. Assessing the Impact of Drug Safety Signals from the WHO Database Presented inSIGNAL': Results from a Questionnaire of National Pharmacovigilance Centres.
18. Lazarou J, Pomeranz BH, Corey PN. 1998. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 279, 1200-05.
19. Meyboom RHB, Lindquist M, Egberts ACG, Edwards IR. 2002. Signal Selection and Follow-Up in Pharmacovigilance. Drug Saf. 25, 459-65.
20. De Bruin ML, Van Puijenbroek EP, Egberts AC, Hoes AW, Leufkens HG. 2002. Nonsedating antihistamine drugs and cardiac arrhythmias– biased risk estimates from spontaneous reporting systems? Br J Clin Pharmacol. 53, 370-74.
21. Coloma PM, Schuemie MJ, Trifirò G, Gini R, Herings R, et al. 2011. Combining electronic healthcare databases in Europe to allow for largescale drug safety monitoring: the EU-ADR Project. Pharmacoepidemiol Drug Saf. 20, 1-11.
22. Härmark L, van Grootheest AC. 2008. Pharmacovigilance: methods, recent developments and future perspectives. Eur J Clin Pharmacol. 64, 743-52.
23. Bhosale Uma, Jaiswal Shruti, Yegnanarayan Radha and Godbole Gouri, “A Pharmacovigilance Study of Antiasthmatic Agents in Patients of Bronchial Asthma at a Tertiary Care Hospital”, Journal of Clinical & Experimental Research, 1, May-August 2013, 26-30.
24. Sharma Sanjeev, Phadnis Pradeep and Gajbhiye Sapna“Pharmacovigilance: Its Awareness and Impact Care Teaching Medical College in Central India Impact- Study ina Tertiary care Teaching Medical College in Central India”, International Journal of Pharmaceutical Research and Bio-Science (IJPRBS), 2, 2013, 234-247.
25. Padmavathi G. V., Beere Nagaraju, Divakara P., Suresh Kumar P., Surendranath A. and Sunil R. Patel, “Screenplay of pharmacovigilance among nursing staff in Bangalore”,2, February 2013, 365-370.
26. P, Prudence A Rodrigues and Georgy Archana,“Pharmaovigilance: Perspectives and Future Challenges in Indian Scenario”, Asian Journal of Pharmaceutical and Clinical Research, 4, 2011, 01-04.
27. Rohilla Ankur, Kumar Vipin, Sharma Mohit Kumar, Dahiya Amarjeet and Kushnoor Ashok, “Pharmacovigilance: Needs and Objectives”, Journal of Advanced Pharmacy Education & Research, 2, Oct-Dec 2012, 201-205.
28. Maiti Bodhisattwa, N. B.P., Singh Rambir, Kumar Pragati and Upadhyay Nishant, “Recent Trends in Herbal Drugs: A Review”, International Journal of Drug Research and Technology, 1, 2011, 17-25.
29. Mann RD, Andrews EB, eds. John Wiley & Sons Ltd, Chichester, 2002.
30. The Importance of Pharmacovigilance, WHO 2002.
31. Council for International Organizations of Medical Sciences. (2020). Practical approaches to risk minimization for medicinal products. World Health Organization. https://cioms.ch/publications/product/practical-approaches-to-risk-minimization-for-medicinal-products/.
32. European Medicines Agency. (2017). Good pharmacovigilance practices (GVP). https://www.ema.europa.eu/en/human-regulatory/post-authorisation/pharmacovigilance/good-pharmacovigilance-practices
33. (2022). MedWatch: The FDA safety information and adverse event reporting program. U.S. Food and Drug Administration. https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-reporting-program.
34. Kumar, A., & Sinha, K. (2019). Pharmacovigilance and adverse drug reaction reporting: A review on worldwide and Indian scenario. Journal of Pharmacovigilance, 7(3), 67–75. https://doi.org/10.4172/2329-6887.1000263.
35. Nebeker, J. R., Barach, P., & Samore, M. H. (2004). Clarifying adverse drug events: A clinician's guide to terminology, documentation, and reporting. Annals of Internal Medicine, 140(10), 795–801. https://doi.org/10.7326/0003-4819-140-10-200405180-00009
36. World Health Organization. (2020). Pharmacovigilance: Ensuring the safe use of medicines. https://www.who.int/medicines/areas/quality_safety/safety_efficacy/pharmvigi/en/
37. Zhou, Y., Boudreau, D. M., & Freedman, A. N. (2017). Pharmacovigilance in the era of big data. Frontiers in Pharmacology, 8, 494. https://doi.org/10.3389/fphar.2017.00494
38. Nebeker, J. R., Barach, P., & Samore, M. H. (2004). Clarifying adverse drug events: A clinician's guide to terminology, documentation, and reporting. Annals of Internal Medicine, 140(10), 795–801. https://doi.org/10.7326/0003-4819-140-10-200405180-00009
39. World Health Organization. (2020). Pharmacovigilance: Ensuring the safe use of medicines. https://www.who.int/medicines/areas/quality_safety/safety_efficacy/pharmvigi/en/
40. Zhou, Y., Boudreau, D. M., & Freedman, A. N. (2017). Pharmacovigilance in the era of big data. Frontiers in Pharmacology, 8, 494. https://doi.org/10.3389/fphar.2017.00494
41. Kumar, A., & Sinha, K. (2019). Pharmacovigilance and adverse drug reaction reporting: A review on worldwide and Indian scenario. Journal of Pharmacovigilance, 7(3), 67–75. https://doi.org/10.4172/2329-6887.1000263
42. Council for International Organizations of Medical Sciences. (2020). Practical approaches to risk minimization for medicinal products. World Health Organization. https://cioms.ch/publications/product/practical-approaches-to-risk-minimization-for-medicinal-products/.
43. European Medicines Agency. (2017). Good pharmacovigilance practices (GVP). https://www.ema.europa.eu/en/human-regulatory/post-authorisation/pharmacovigilance/good-pharmacovigilance-practices
44. (2022). MedWatch: The FDA safety information and adverse event reporting program. U.S. Food and Drug Administration. https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-reporting-program
45. Council for International Organizations of Medical Sciences. (2020). Practical approaches to risk minimization for medicinal products. World Health Organization. https://cioms.ch/publications/product/practical-approaches-to-risk-minimization-for-medicinal-products/
46. European Medicines Agency. (2017). Good pharmacovigilance practices (GVP). https://www.ema.europa.eu/en/human-regulatory/post-authorisation/pharmacovigilance/good-pharmacovigilance-practices
47. (2022). MedWatch: The FDA safety information and adverse event reporting program. U.S. Food and Drug Administration. https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-reporting-program
48. (2020). ICH guideline E2E on pharmacovigilance planning. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. https://www.ich.org/page/guidelines
49. Kumar, A., & Sinha, K. (2019). Pharmacovigilance and adverse drug reaction reporting: A review on worldwide and Indian scenario. Journal of Pharmacovigilance, 7(3), 67–75. https://doi.org/10.4172/2329-6887.1000263
50. Nebeker, J. R., Barach, P., & Samore, M. H. (2004). Clarifying adverse drug events: A clinician's guide to terminology, documentation, and reporting. Annals of Internal Medicine, 140(10), 795–801. https://doi.org/10.7326/0003-4819-140-10-200405180-00009
51. World Health Organization. (2020). Pharmacovigilance: Ensuring the safe use of medicines. https://www.who.int/medicines/areas/quality_safety/safety_efficacy/pharmvigi/en/
52. Zhou, Y., Boudreau, D. M., & Freedman, A. N. (2017). Pharmacovigilance in the era of big data. Frontiers in Pharmacology, 8, 494. https://doi.org/10.3389/fphar.2017.00494
53. Council for International Organizations of Medical Sciences. (2020). Practical approaches to risk minimization for medicinal products. World Health Organization. https://cioms.ch/publications/product/practical-approaches-to-risk-minimization-for-medicinal-products/
54. European Medicines Agency. (2017). Good pharmacovigilance practices (GVP). https://www.ema.europa.eu/en/human-regulatory/post-authorisation/pharmacovigilance/good-pharmacovigilance-practices
55. (2022). MedWatch: The FDA safety information and adverse event reporting program. U.S. Food and Drug Administration. https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-reporting-program
56. Kumar, A., & Sinha, K. (2019). Pharmacovigilance and adverse drug reaction reporting: A review on worldwide and Indian scenario. Journal of Pharmacovigilance, 7(3), 67–75. https://doi.org/10.4172/2329-6887.1000263
57. Nebeker, J. R., Barach, P., & Samore, M. H. (2004). Clarifying adverse drug events: A clinician's guide to terminology, documentation, and reporting. Annals of Internal Medicine, 140(10), 795–801. https://doi.org/10.7326/0003-4819-140-10-200405180-00009
58. World Health Organization. (2020). Pharmacovigilance: Ensuring the safe use of medicines. https://www.who.int/medicines/areas/quality_safety/safety_efficacy/pharmvigi/en/
59. Zhou, Y., Boudreau, D. M., & Freedman, A. N. (2017). Pharmacovigilance in the era of big data. Frontiers in Pharmacology, 8, 494. https://doi.org/10.3389/fphar.2017.00494
60. Aspinall, M. G., & Hamermesh, R. G. (2007). Realizing the promise of personalized medicine. Harvard Business Review, 85(10), 108-117. https://hbr.org/2007/10/realizing-the-promise-of-personalized-medicine
61. Gibbons, R. (2012). Improving the systems for ADR reporting: A focus on pharmacovigilance. Journal of Pharmacovigilance, 10(1), 45–52. https://doi.org/10.1093/pharm/v2012p02
62. Graham, D. J., Campen, D., Hui, R., Spence, M., Cheetham, C., Levy, G., Shoor, S., & Ray, W. A. (2012). Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective NSAIDs: Nested case-control study. The Lancet, 365(9458), 475–481. https://doi.org/10.1016/S0140-6736(05)17810-4
63. Shah, R. R., Smith, R. L., & Jones, R. (2015). Personalized medicine: Challenges and opportunities. British Journal of Clinical Pharmacology, 79(3), 321–336. https://doi.org/10.1111/bcp.12532
64. S. FDA. (2022). Pharmacovigilance for improving drug safety and quality: The evolving role of stakeholders. U.S. Food and Drug Administration. https://www.fda.gov/safety/pharmacovigilance
65. World Health Organization. (2020). Pharmacovigilance: Ensuring the safe use of medicines. https://www.who.int/medicines/areas/quality_safety/safety_efficacy/pharmvigi/en/