INTRODUCTION:

the Greek word phannacon, which means drug or medical substance, and the Latin word Vigilare, which means "to keep watch," are included in the historical development of the term "pharmacovigilance^."1. "The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other possible drug-related problem, particularly long- and short-term adverse effects of medicines," is how the World Health Organisation defines pharmacovigilance^”2. Adverse drug responses (ADRs), which are defined as any unwanted and harmful reaction to a medication, including lack of efficacy when used for sickness prophylaxis, analysis, or therapy, or to modify physiological function, are a major focus of pharmacovigilance³. After sulfanilamide elixir, which contains diethyl glycol as the solvent, was linked to over 100 deaths in the United States, the Federal Food, Drug and Cosmetic Act was established in 1938, founding the first governmental organisation dedicated to pharmacovigilance⁴. Maintaining public trust while optimising medicine safety has become a more difficult task. Drug risk must be actively estimated and managed by pharmaceutical and biotechnology businesses at every stage of a product's lifecycle, from development to post-market⁵. ADRs, or adverse drug reactions, are of special importance to PV since they can happen at levels that are typically utilised for illness diagnosis, treatment, prevention, or physiological function alteration⁶To maximise benefits and minimise dangers, it is imperative to continuously monitor pharmacological effects, side effects, contraindications, and overtly adverse effects that could result in a significant degree of morbidity, and in some circumstances, even mortality. When a drug is marketed and prescribed to huge populations both inside and outside of the country, no amount of caution and care throughout the pre-clinical and clinical testing stages can guarantee absolute safety. Less common side effects and adverse drug reactions (ADRs) are frequently unknown at the time a drug enters the market because clinical trials typically involve several thousand participants. Post marketing PV uses technologies such as data mining and investigation of case reports to uncover the links between medicines and ADRs. It is the duty of the drug regulatory bodies to maintain a reliable PV system for tracking adverse drug reactions (ADRs) both during the early stages of drug development and later on in the life of a marketed product⁷. Pharmacovigilance supports safe and appropriate use of drugs by

a) Encouraging the discovery of hitherto undiscovered ADRs and interactions as well as a rise in the frequency of recognised ADRs,

b) Identifying risk factors for the development of ADRs, and

c) Quantitatively assessing benefit/risk analysis components and sharing data to enhance medication prescription and regulation⁸.

The sequential pharmacovigilance developments with special reference to India:

In 1747 to developed Very first known clinical trials by James Lind, proving the usefulness of lemon juice in preventing scurvy.

In 1937 to developed Death of more than 100 children due to toxicity of sulfanilamide.

In 1950 to developed Apalstic anemia reported due to chloramphenicol toxicity.

In 1961 to developed World wide tragedy due to thalidomide toxicity.

In 1963 to developed 16th World Health congregation recognize significant to rapid action on Adverse Drug Reactions (ADRs).

In 1968 to developed WHO research project for international drug monitoring on pilot scale.

In 1996 to developed Global standards level clinical trials initiated in India.

In 1997 to developed India attached with WHO Adverse Drug Reaction Monitoring Program.

In 1998 to developed Initiation of pharmacovigilance in India.

In 2002 to developed 67th National Pharmacovigilance Center established in India.

In 2004 -05 to developed India launched National Pharmacovigilance Program.

In 2005 to developed Accomplishment of structured clinical trials in India.

In 2009 -10 to developed Pharmacovigilance Program (PvPI) started^9,10.

Aims of Pharmacovigilance:

Enhance patient safety and care with regard to medication use and other medical and paramedical procedures.

· Investigate the effectiveness of medications and track their side effects from the lab to the pharmacy and beyond for a number of years.

· Pharmacovigilance monitors any severe side effects from medications.

· Enhance public safety and health in regard to medication use.

· Participate in the evaluation of the risks, benefits, and efficacy of medications, and promote their safe, sensible, and more efficient use, including economical use.

· Promote understanding, education and clinical training in pharmacovigilance and its effective communication to the public.

The procedures used in a drug's clinical development. A medication is legally released for broad public consumption once it is placed on the market, leaving the safe and secure scientific setting of clinical trials. Most medications have only been tried on a small number of carefully chosen people for short-term safety and efficacy at this stage. Rarely will more than 5000 subjects—and often as few as 500—receive the product before it is released.

Generally speaking, more data is required on use in particular population groups, such as children, expectant mothers, and the elderly, as well as regarding the effectiveness and safety of long-term use, particularly when combined with other medications¹¹.

OBJECTIVE:

1. To provide a method for reporting patient safety that is accessible to all.

2. To find and analyse fresh signals in the report cases.

3. To analyse the benefit-threat ratio of sold details.

4. To elicit substantiation-based data regarding the safety of medications.

5. To assist nonsupervisory agencies in making decisions on the use of particulars to encourage drug use that is reasonable¹².

Adverse drug reactions (ADRs)

An unintentional and unpleasant reaction to a health product that occurs at the dosages typically used or tested for the diagnosis, prevention, or treatment of a disease or the modification of an organic function is known as an adverse drug reaction (ADR)^13,14,15. Identifying the causal factor for adverse drug reactions (ADRs) can be challenging as pharmaceutical preparations typically contain multiple substances¹⁶. Adverse drug responses (ADRs) can occur suddenly, gradually, or even after stopping a medicine. Adverse drug responses (ADRs) are not uncommon; in fact, studies in various therapeutic contexts have reported an incidence of 10–25%. These events are particularly frequent in patients undergoing multiple medication therapy^17,18,19.

Adverse drug reactions (ADRs) have been classified in to two ways.

A. Predictable (Type-A) Reactions:

Based on the medication's pharmacological characteristics, such as an increased but quantitatively normal reaction, they include adverse effects, toxic effects, and the effects of drug withdrawal.

B. Unpredictable (Type-B) Reactions:

These include allergies and idiosyncrasies; they are based on the patient's quirks rather than the known activities of the medicine. They are less frequent, frequently unrelated to dosage, typically more severe, and necessitate drug discontinuation^16,17.

Table 1: ADR Monitoring Centre ²⁰

ADR Monitoring Centre	State
Department of pharmacology, All India Institute of Medical Science	New Delhi
Department of pharmacology, PGIMER	Chandigarh
Department of pharmacology, R.G.Kar Medical College	Kolkata
Department of Clinical Pharmacology, Lady Hardinge Medical College	Kolkata
Department of Clinical Pharmacy, JSS Medical College Hospital	Karnataka
Institute of pharmacology, Madras Medical College	Chennai
Department of pharmacology, SAIMS Medical College	Indore –Ujjain

Functions:

1. Identify: Recognising unanticipated, detrimental effects of medications is necessary for identifying adverse drug reactions, or ADRs. When determining the link between a medication and a suspected reaction, causality evaluation frequently makes use of instruments like the WHO causality assessment criteria.

2. Documentation: ADR documentation entails keeping track of pertinent medical history, drug data, reaction description, and patient information. Precise documentation facilitates thorough analysis.

3. Report: It is essential to notify pharmacovigilance centres of ADR regulatory agencies of major adverse drug reactions. This entails submitting thorough reports that support continuous drug safety monitoring and assessment^20.

Table 2: Known drugs adverse effects ²¹

Adverse Drug Reactions (ADRs)	Drug
Phocomelia, Multiple defects	Thalidomide
Discolored or deformed teeth, retarded bone growth	Tetracyclines
nose, eye and hand defects, growth retardation	Warfarin
Foetal goiter, cardiac and other abnormalities	Lithium
Virilization, limb, esophageal, cardiac defects	Androgen
Multiple defects, Foetal death	Methotraxate
Virilization of female foetus	Progestins
Premature closer of ductus arteriosus	Aspirin/ Indomethacin

Drug Controller General of India:

As India's regulatory body, the Drug Controller General of India (DCGI) is in charge of approving pharmaceuticals, including medications and medical equipment. Its pharmacovigilance responsibilities include tracking and evaluating the safety of medications once they are marketed. It makes sure that drug manufacturers follow safety guidelines and looks into negative medication reactions that consumers and medical professionals report. The Central Drugs Standard Control Organisation (CDSCO) was established in 1940, and that is when DCGI's history began.

As CDSCO developed over time, the Drugs and Cosmetics Act of 1961 was passed, giving the organisation the authority to control the import, manufacturing, distribution, and retail of drugs. 2010 saw the creation of the Pharmacovigilance Program of India (PvPI), which was run by DCGI and CDSCO. PvPI seeks to improve drug safety in India by gathering, tracking, and analysing adverse drug reactions (ADRs). DCGI’s involvement in pharmacovigilance shows India’s signifies India’s commitment to ensuring the safety and efficacy of Pharmaceuticals, emphasizing constant monitoring and evaluation even after a medicine is in the market.

Function of DCGI:

1. Regulatory Approval: Before new medications are allowed to reach the Indian market, DCGI must ensure that they meet safety, efficacy, and quality criteria. This entails assessing clinical trial information that pharmaceutical companies submit.

2. WPost Marketing Surveillance: DCGI keeps an eye out for any side effects or safety issues that are reported through pharmacovigilance systems on drugs that have been approved and put on the market. This entails reviewing and evaluating adverse event reports that patients, healthcare providers, and pharmaceutical firms submit

3. Regulation enforcement: In order to uphold standards for public safety, DCGI enforces laws and policies pertaining to the production, labelling, distribution, and marketing of pharmaceuticals.

4. Clinical Trial Oversight: DCGI oversees and controls clinical studies carried out in India to guarantee patient safety, ethical conduct, and compliance with legal requirements.

5. Quality Control: By monitoring production procedures, examining manufacturing facilities, and controlling pharmaceutical imports, DCGI makes sure that medications on the market meet specified quality standards ²²

Adverse Drug Reactions (ADRs) Reporting/Adverse Event (AE) Reporting:

ADRs, or adverse drug reactions Reporting/ Adverse Event (AE) The most common aspect of pharmacovigilance (PV) is reporting, which requires a significant investment of resources from government agencies, drug safety departments in pharmaceutical companies, and drug regulatory authorities²³.Reports from patient support programs, clinical or post-marketing studies, reports from patients or healthcare professionals on the spur of the moment, reports from literature sources, reports from media outlets (including social media and websites), and reports from drug regulatory authorities themselves can all form the basis of adverse event reports (AE reports). In most countries, reporting is required by law^24.

The following are several elements of Adverse Event (AE) Reporting

1. An identifiable patient.

2. An identifiable reporter.

3. A suspect drug.

4. An adverse event^3,25

Pharmacovigilance partners:

The major participants in pharmacovigilance must work closely and efficiently together to address the risks related to medication use. Politicians, health administrators, policy officials, and other relevant parties must work together to predict, characterise, and address the public's and the health professions' ever-growing needs and expectations. However, without reliable and all-encompassing technologies that enable such collaboration, there is little chance that this will occur. Lack of funding, political support, training, and, most importantly, scientific infrastructure are the usual limitations. Comprehending and addressing these are necessary preconditions for the advancement of pharmacovigilance research and practice in the future.

Key partners in the surveillance of medication safety

· Government

· Industry

· Hospitals and academia

· Medical and pharmaceutical associations

· Poisons and medicines information centres

· Health professionals

· Patients

· Consumers

· The media

· World Health Organization^11.

Clinical Trials in India:

India's clinical research space and prospects are highly favourable, which has made it a favourite destination for clinical trials for pharmaceutical companies worldwide^26.

Some of the advantages for clinical trials that India has as are as follows:

· Extensive adherence to international criteria, including US Food and Drug Administration laws and the International Conference on Harmonisation (ICH)/WHO Good Clinical Practice (ICH-GCP).

· The availability of highly skilled, fluent English-speaking researchers, including doctors.

· Constant assistance and collaboration from the state.

· Less expensive than in the West^27.

· The rising incidence of diseases that are prevalent in both developed and emerging nations; • The accessibility of adequate infrastructure.

· Since January 2005, the patent laws have changed.

According to a recent report from the Federation of Indian Chambers of Commerce and Industry (FICCI), some of the growth drivers that have led to the recent transformation of Indian clinical research include scientific feasibility, medical infrastructure, clinical trial experience, regulations, commercialisation potential, and cost competitiveness ²⁸. Indian-born contract research companies (CROs) were able to give the advantages of understanding the Indian scenario better, deliver services at more affordable pricing, and having greater knowledge of Investigator locations throughout the country compared to the newer entries in the industry. India’s current favorable regulatory structure and laws with worldwide standards, increasing knowledge of good clinical practice guidelines and its execution by clinicians are some of the primary causes pushing the growth of clinical research in India^29,30.

Since there was never a concept of medication surveillance in India's past, awareness of ADR surveillance emerged somewhat late in the nation. PV is not new to India, despite its relative youth. It wasn't until 1986 that a small group of doctors, mostly from academic institutions, demanded that more focus be placed on the possible side effects of prescription drugs and the prudent prescription of medications. This resulted in the creation of the first ADR monitoring program, which was a failure and comprised 12 regional centres covering 50 million people apiece³¹. Not much happened until 1997, when India became a member of the WHO Adverse Drug Reaction Monitoring Programme, which is headquartered in Uppsala, Sweden, a decade later. A National Pharmacovigilance Centre in the Department of Pharmacology at the All-India Institute of Medical Sciences (AIIMS), New Delhi, and two WHO special centres in Mumbai (KEM Hospital) and Aligarh (JLN Hospital, Aligarh) were identified as the three centres for ADR monitoring. These centres are primarily located in teaching hospitals. These centres were required to notify India's drug regulatory body of any ADRs. These centres primarily monitored adverse drug reactions (ADRs) to medications sold in India. They were non-functional, though, since prescribers were never informed about the necessity of reporting adverse drug reactions (ADRs) or the operations of these monitoring centres, and government funding was insufficient. Since this endeavour was not successful, on January 1, 2005, the World Bank-funded National Pharmacovigilance Program (NPVP) for India was developed under the sponsorship of WHO³². The National Pharmacovigilance Advisory Committee, housed within the Central Drugs Standard Control Organisation (CDSCO), was tasked with supervising the NPVP when it was founded in January 2005. Information from all over the nation was to be gathered by two zonal centres, the South-West (SW) zonal centre (based in the Department of Clinical Pharmacology, Seth GS Medical College and KEM Hospital, Mumbai) and the North-East (NE) zonal centre (based in the Department of Pharmacology, AIIMS, New Delhi), and sent to the committee and the Uppsala Monitoring Centre (UMC) in Sweden³³. There would be two regional centres reporting to the New Delhi centre and three to the Mumbai centre. Each regional center, in turn, would have numerous peripheral centers (24 in all) reporting to it. There were three main goals for the program. The program's long-term goal was to become a benchmark for international drug monitoring, while its short-term goal was to encourage a reporting culture. The intermediate goal was to involve a significant number of healthcare professionals in the system in information dissemination. But this program wasn't successful either³⁴.

CONCLUSION:

In conclusion, pharmacovigilance plays a critical role in ensuring the safety and efficacy of drugs, both during development and after they enter the market. It serves as a vital mechanism to detect, assess, and prevent adverse drug reactions (ADRs), thus safeguarding public health. Despite the rigorous clinical trials conducted before a drug’s approval, the potential for rare or delayed ADRs underscores the need for continuous post-marketing surveillance. India's journey in pharmacovigilance, marked by the establishment of the National Pharmacovigilance Program in 2005 and the subsequent Pharmacovigilance Program of India (PvPI), has significantly advanced the country’s drug safety standards. Pharmacovigilance efforts not only contribute to identifying new ADRs but also enhance the understanding of drug safety in diverse populations, helping healthcare professionals make informed decisions. Regulatory bodies like the Drug Controller General of India (DCGI) ensure that pharmaceutical companies adhere to safety regulations, thereby fostering a culture of safety and accountability. As India emerges as a key player in global clinical trials, strengthening pharmacovigilance frameworks remains essential to protecting public health and promoting the safe use of medicines. Continuous collaboration among healthcare professionals, government agencies, and pharmaceutical industries will be crucial in addressing the challenges and advancing pharmacovigilance practices in the future.

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Received on 25.10.2024 Revised on 27.11.2024

Accepted on 23.12.2024 Published on 10.03.2025

Available online from March 21, 2025

Research J. Science and Tech. 2025; 17(1):41-47.

DOI: 10.52711/2349-2988.2025.00006

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