PHARMACOVIGILANCE: A REVIEW

Sangita Fulchand Pawar and Vikram Limbaji Musale M. Pharmacy, Dept. Of Pharmaceutics, Government Collage of Pharmacy, Aurangabad431001. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History Received: 23 November 2019 Final Accepted: 25 December 2019 Published: January 2020

Pharmacovigilance play an important role in the healthcare system through monitoring and interaction of drugs and there effects in the human body. In this article includes good manufacturing practices (GCP) and (ICH) guidelines for pharmaceuticals for human use are examined as an important aspects in the transformation of clinical trial to the objective of pharmacovigilance In pharmaceutical production India becomes third largest country in the world. Nowadays in India pharmacovigilance gives awareness about adverse drug reactions (ADR) and this review gives information about implementation for solving current problems. This article summarized objective and methodology used in pharmacovigilance with their overview of existing in India and their challenges and future expectance.

…………………………………………………………………………………………………….... Introduction:-
Clinical research industry has grown around the world in past years. The main aim of pharmaceutical company is innovate new drugs in market, the company has to conduct clinical trials as per ICH GCP guidelines .pharmacovigilance is integral and important part of clinical trials.1 Pharmacovigilance was officially introduced in December 1961 was publication of a case report in the Lancet by W. McBride, the Australian Doctor who first boosted a causal link between serious fetal deformities (Phocomelia) and thalidomide a drug used during pregnancy: Thalidomide was used as an antiemetic and sedative agent in pregnant women . In1968, the World Health Organization (WHO) promoted the "Programmed for International Drug Monitoring", a pilot project aimed to centralize world data on adverse drug reactions (ADRs). In particular, the main aim of the "WHO Programmed" was to identify the earliest possible PV signals. The term PV was proposed in the mid-70s by a French group of pharmacologists and toxicologists to define the activities promoting "The assessment of the risks of side effects potentially associated with drug.2 Pharmacovigilance is a very important and inseparable part of clinical research. Both clinical trials safety and post-marketing pharmacovigilance potential known as Post-marketing studies or Phase IV clinical trials) are critical throughout the product life cycle. With a reasonably high number of recent Highprofile drug withdrawals, both the pharmaceutical industries as well as various regulatory agencies across the globe have raised the bar. Early detection of signals from the post-marketing surveillance studies and clinical trials in Early phases have now been adapted by major pharmaceutical companies in order to identify the risks associated with their medicinal products as early as possible. If any such risk is present then effectively managing the risks by applying powerful risk management plans throughout the life cycle of the product is acquired. These risk management plans are also widely known as Risk Minimization. PV is particularly concerned with ADRs, which are drug responses that are noxious and unintended, and which occur at doses normally used for the prophylaxis, diagnosis or therapy of disease, or for the modification of physiological function. Continuous monitoring of drug effects, side effects, contraindications and outright harmful effects which could result in a high degree of morbidity 236 and mortality, are essential to maximize benefits and minimize risks. No degree of care and caution at the preclinical and clinical testing stages can guarantee absolute safety, when a drug is marketed and prescribed to large populations across the country and outside. Because clinical trials involve several thousands of patients at most, less common side effects and ADRs are often unknown at the time a drug enters the market. Post marketing PV uses tools such as data investigation of case reports to identify the relationships between drugs and ADRs. The drug regulatory agencies have the responsibility of having a well-established PV system to monitor ADRs during the drug development phase and later during the life time of a marketed drug.

Aims of pharmacovigilance:
1. To Increase public protection from the new drugs 2. To contribute to assessment of benefit efficiency and risk of medicines. 3. Endorse healthy communication to the community. 4. To promote rational and safe use of medicines. 5. Efficacy of drug and their monitoring about adverse effects of drugs. 6. Pharmacovigilance keeps way of any drastic effects of medicines.
Improve public health and safeties in relation to the use of promote understanding, education and clinical training in pharmacovigilance.

List of definations (3): TERM DEFINTION Adverse event
An adverse event is defined as any un toward medical occurrence that may present during treatment with a drug but which does not necessarily have a relationship with its use. Adverse drug reaction An adverse drug reaction (ADR) is any noxious, unintended and undesired effect of a drug, which occurs at a dose used in human for prophylaxis, diagnosis, therapy or modification of physiological function Post marketing surveillance Post-marketing surveillance (PMS) is the practice of monitoring the safety of a pharmaceutical drug or device after it has been released in the market.

Clinical trials
Clinical trials are sets of tests in medical research and drug development that generate safety and efficacy data (or more specifically, information about adverse drug reactions and adverse effects of other treatments) for health interventions (e.g., drugs, diagnostics, devices, therapy protocols).

Safety signals
Safety signal refer to a concern about an excess of adverse events compared to what would be expected to be associated with products use, which can arise from post marketing data and other sources, such as pre-clinical data and events associated with other products in the same pharmacological class. Pharmacoepidemiology Study of the uses and effects of drugs in large populations. Pharmacology Study of the uses, effects and modes of action of drugs 237 Pharmacovigilance The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug related problem. Side effect Any unintended effect of a pharmaceutical product occurring at normal dosage which is related to the pharmacological properties of the the drug. Poly-pharmacy The concomitant use of more than one drug, sometimes prescribed by different practitioners.

Adverse drug reactions (adrs):
An adverse drug reactions (ADRs) can be defined as an unintended and noxious responses to a health product which causes at the doses usually used or tested for the diagnosis, prevention or treatment of a disease or the alteration of an organic function n drugs, this scale fails to identify the offending agent. Advice about reporting: Report adverse experiences with medications: 1. Report serious adverse reaction : Reaction is serious when patient outcome is -Death ,life threatening ,hospitalization ,required intervention to prevent permanent impairment or damage 2. Who can report: Any health care professional (doctors including dentists, nurses, and pharmacists) Where to report: please return the completed form to the nearest Adverse Drug Reaction Monitoring Center or to National Coordinating center. 3. What happens to the submitted information: information provided in this form is handled in strict confidence.
The causality assessment is carried out at ADR monitoring centers by using WHO -UMC scale .the analyses form forwarded to national centers through ADR database. 4. The report are periodically review by national coordinating centers. The information generated on the basis of this report helps in continuous assessment of the benefit risk ratio of medicines.
The information is submitted to steering committee of PvPI constituted by the Ministry of Health and Family Welfare.
A list of some suspected and known drugs associated with adverse effects (5) Clinical trials should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with GCP and the applicable regulatory requirement(s). 2. Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits justify the risks. 3. The rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society. 4. The available nonclinical and clinical information on an investigational product should be adequate to support the proposed clinical trial. 5. Clinical trials should be scientifically sound, and described in a clear, detailed protocol. 6. A trial should be conducted in compliance with the protocol that has received prior institutional review board (IRB)/independent ethics committee (IEC) approval/favorable opinion. 7. The medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of a qualified physician or, when appropriate, of a qualified dentist. 8. Each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective task(s). 9. Freely given informed consent should be obtained from every subject prior to clinical trial. 10. The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirement(s). 11. Investigational products should be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP). They should be used in accordance with the approved protocol. 12. Systems with procedures that assure the quality of every aspect of the trial should be implemented. 13. All clinical trial information should be recorded, handled ,and stored in a way that allow it's reporting, interpretation and verification. A registry is a list of patients presenting with the same characteristics. A) Disease registry eg: registries for blood dyscrasias. B)Specific exposure (Drug registry) Pharmacovigilance methods can be also classified as hypothesis generation methods and hypothesis.

Balanced assessment method:
This method evaluates a case report on various visual analog scale (VAS) models that each criterion is fulfilled individually. It has an added advantage that it considers an alternative causative factor as a possibility and not just as a separate factor. Each case is assessed independently by different assessors and the evaluation depends on the assessor's skills knowledge.

Ciba-Geigy method:
Expert consensus meetings have resulted in Ciba-Geigy method. Experts used their clinical judgment to assess adverse drug events and assign causality on a VAS. This method uses a checklist which is composed of 23 questions, which is split into three sections: (i) History of present adverse reaction, (ii) patient's past adversereaction history, and (iii) monitoring physician's experience. This updated method was found to have a high degree of agreement (62%) when compared with evaluator's assessments.

Loupe et al. method:
This method developed to assess the teratogenic potential of drug. The first sections of the algorithm sanction for the drug to be omitted if not implicated in the inception of the abnormality. The second section weighs the bibliographical data. The three questions consider alternative etiological candidates other than the drug; chronology of the suspect drug and other bibliographical data, to arrive at a conclusion on causality.

Russell Clef causality assessment method:
This method is used in disease states such as liver and dermatological problems. A retrospect assessment of the reproducibility of this method among four experts had showed a 37-99% agreement rate.

Australian method:
Australian method involves the evidence which helps in to draw the conclusion, such as timing, and laboratory information from case reports presented and the antecedent cognizance on the suspect drug profile is deliberately omitted in the assessment.

Role of pharmacist:
1. Participate in spontaneous reporting of adverse events. 2. Review prescriptions 3. Manage the adverse effects of drugs 4. Monitor drug interactions 5. Recommend changes to regimen 6. Pharmacist contributes to the drug safety by preventing, identifying and reporting ADRs report.

Major challenges in pharmacivigilance:
Pharmacovigilance facing the challenges in healthcare delivery because of not getting priority. Biasness of drug in healthcare delivery system is also a big issue (12). Poor staffing, poor funding and mostly political pressures creating barrier in implementing of pharmacovigilance programme. Other challenges are associated with health professionals are few in number but many prescriber. Lack of continuing medical education and difficulties in availability of drug information is another big issue. Some drug use problems contributing to the barriers in pharmacovigilance programme of India are availability of many types of drugs in households and dispensing the drugs by untrained persons (13) Some other drug use problems are wide spread use of injections, high levels of antibiotic use, inadequate treatment guidelines, poor prescribing .Diseases like tuberculosis, HIV/AIDS, malnutrition requires multiple drug therapy and adverse event occurs due to drug interactions and can lead to severe health hazard. Due to the above reasons risk of adverse drug events are very high. So following challenges can be avoided by implementing proper rule and regulation of pharmacovigilance programme strictly everywhere. Improvement of communication regarding pharmacovigilance between public and health professionals creates awareness and adverse occurring can be minimized. Proper knowledge on pharmacovigilance would help to health professionals to understand the effectiveness or risk of medicines that they prescribe and ensure a better healthcare to patient (14).
Following are the few points due to lack of such a point of pharmacovigilance is not attained: 1. Globalization. 2. Web -based sales and information.