Pharmacist ESIC, Ministry of Labour & Employment
Govt. Of India
When you type the word Pharmacovigilance in Goggle you will find the meaning as ‘the practice of monitoring the effects of medical drugs after they have been licensed for use, especially in order to identify and evaluate previously unreported adverse reactions”. As per the World Health Organization (WHO) definition, Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem.
To understand the word “Pharmacovigilance” the roots of the word are: pharmakon (Greek- drug) and vigilare (Latin- to keep watch). For safety of medication, Adverse Drug Reactions (ADRs) monitoring is required for each medicine throughout its life cycle, during pre-marketing (Phase I, II & III clinical trials) and post-marketing (Phase IV clinical trial or PMS).
In a nutshell, Pharmacovigilance plays a key role in the healthcare system through assessment, monitoring and discovery of interactions amongst drugs and their effects in humans. Thus, the aims of Phamacovigilance are to enhance patient care and patient safety in relation to the use of medicines.
Need of Pharmacovigilance:
Some people may wonder why we need of pharmacovigilance when drugs are already available in the market and heavily studied before becoming available. To understand the need for ongoing monitoring of adverse drug reactions/effects long past a drug is officially approved, it is important to understand the limitations of clinical trials in predicting the unseen drug interaction among real world.
It would be unfair if we do not mention here about the thalidomide disaster, 1961 in West Germany. The drug thalidomide was sold against nausea to alleviate morning sickness in pregnant women which led to 5000 to 7000 infants born with phocomelia (malformation of the limbs) as a result of unsafe medicine promoted for use by pregnant mothers.
As we know, pharmacovigilance is an important and integral part of clinical research. Both clinical trials safety and post-marketing, pharmacovigilance are critical throughout the product life cycle. With a number of recent high-profile drug withdrawals, the pharmaceutical industry and regulatory agencies have raised the bar. Early detection of signals from both clinical trials and post marketing surveillance studies have now been adapted by major pharmaceutical companies in order to identify the risks associated with the medicinal product and effectively managing the risks by applying robust risk management plans throughout the life cycle of the product. Signal detection and risk management has added a new dimension to the field of pharmacovigilance and as an evolving discipline; it requires ongoing refinement in order to increase its applicability and value to public health.
Reason 1: Limited experience prior to marketing of a drug;
Before medical products can be introduced onto the market or into public health programmes, they must undergo a series of investigations designed to evaluate safety and efficacy of the drug. During the clinical research and development process, most medical products will only have been tested for short-term safety and efficacy on a limited number of carefully selected individuals. In some cases, as few as 100, and rarely more than 5000 subjects will have received the product prior to its approval for marketing. It would not be justified to predict the unseen adverse drug reactions in such a small clinical study population as compare to real world population.
Reason 2: Drug withdrawals;
There are thousands of drugs which have been withdrawn or banned from the market world widely because of their hazardous health issues or adverse drug reaction. Recently, the Government of India has prohibited 328 Fixed Dose Combinations (FDCs) for manufacturing, sale or distribution as these FDCs may involve risk to human beings.
Reason 3: Increased health care costs;
The cost of drug-related morbidity and mortality is also an important issue. The un-necessary drug related adverse reactions increases the cost of health as it increases the staying in hospitals. If the physician is already known the drug related reactions, he may take the different way to treat the patients so as to avoid the un-necessary financial burden over them.
Aim of Pharmacovigilance:
Major aims of pharmacovigilance are:
1. Early detection of hitherto unknown adverse reactions and interactions
2. Detection of increases in frequency of (known) adverse reactions
3. Identification of risk factors and possible mechanisms underlying adverse reactions
4. Estimation of quantitative aspects of benefit/risk analysis and dissemination of information needed to improve drug prescribing and regulation.
The ultimate goals of pharmacovigilance are:
the rational and safe use of medical drugs
the assessment and communication of the risks and benefits of drugs on the market
educating and informing of patients
Clinical Trials in India:
Clinical trials are part of a clinical study. In clinical trials, human volunteers or participants or subjects receive specific medical products or drugs. Clinical trials used in drug development are sometimes described by phases.
Phase I Clinical Trials: Human Pharmacology Trials
Phase II clinical Trial: Therapeutic Exploratory Trials
Phase III Clinical Trial: Therapeutic Confirmatory Trials
Phase IV Clinical Trial: Post Marketing Trials
As per the Drugs & Cosmetics Acts, for a new drug approval in India, Phase I, II & III clinical trials are required. However, post marketing trials (Phase IV) may not be considered necessary at the time of new drug approval but may be required by the regulators. Also, post marketing trials (Phase IV) is different from the Post marketing surveillance.
Post Marketing Surveillance:
To closely monitor the clinical safety of a new drug once marketed, a Periodic Safety Updated Reports (PSURs) are required to be submitted to drug regulators.
Pharmacovigilance in India:
Pharmacovigilance in India started back in 1986. A formal Adverse Drug Reactions (ADR) monitoring system was initiated with 12 regional centers, each covering a population of 50 million. However, no noteworthy growth was made. Afterward in 1997, India joined the World Health Organization (WHO) and Adverse Drug Reaction (ADR) scrutinizing program based at Uppsala, Sweden.
The National Pharmacovigilance Programme (NPP) was launched in India in 2004 with World Bank funding till 2009. It was built on the structure recommended by WHO in a document titled “Safety Monitoring of Medicinal Products- Guidelines for Setting up and Running a Pharmacovigilance Centre”.
In 2010, the Pharmacovigilance Programme of India (PvPI) was initiated by the Government of India with AIIMS, New Delhi as National Coordination Centre (NCC) for monitoring ADRs in the country. The NCC was shifted from AIIMS to Indian Pharmacopoeia Commission (IPC), Ghaziabad on 15th April 2011.
Indian Pharmacopoeia Commission (IPC) is an autonomous institution of the Ministry of Health and Family Welfare, Government of India and functioning as National Coordination Centre (NCC) for Pharmacovigilance Programme of India (PvPI). The main responsibility of NCC is to monitor all the adverse reactions of medicines being observed in Indian population and to develop and maintain its own pharmacovigilance database for patient safety with respect to use of medicine in India so that regulatory interventions can be made based on Indian population.
Current status in India:
Currently there are 250 Adverse Drugs Reaction Monitoring Centres (AMCs) established in government and non-government hospitals throughout in India operating under the NCC-IPC, Ghaziabad. These AMCs are responsible for collection of Adverse Drugs Reactions from their respective centers and send to the NCC-IPC through VigiFlow.
To guide Marketing Authorization Holders (MAHs) on reporting ADRs and establishing a sustainable PV system at their respective sites, the PvPI in collaboration with CDSCO has released the “Pharmacovigilance Guidance Document for MAHs of Pharmaceutical Products”, the Guidance Document for MAHs lays down the role and responsibilities for MAHs of pharmaceutical products to have a pharmacovigilance system in place for collecting, processing and forwarding report/s on ADRs emerging from the use of any medicine manufactured or marketed by the applicant in the country, to the licensing authority.
Subsequently, the PvPI is responsible for collection of ADR reports from all over the AMCs and from MAHs to generate the signal detection and provides the timely drug alerts. PvPI also recommends to CDSCO for regulatory changes in the particular drug label or package insert as per the signal detection generated.