A Bangladesh perspective of Pharmacovigilance & NDRA

The main responsibility of any Drug Regulatory Authority is to ensure the quality, efficacy and safety of all marketed products within the country. The first two criteria can be established through data obtained from in vitro testing to ensure compliance with acceptable standard obtained from animal studies, preclinical and clinical trials involving humans. It is a well established fact that premarketing clinical trials do not have the statistical power to detect rare Adverse Drug Reactions (ADRS) nor do they have significant follow up to identify delayed ADRS or effects from long term exposure. Thus pharmacovigilance plays a prominent role in establishing the safety profile of marketed product.

The word Pharmacovigilance is derived from greek pharmakon (Drug) + Latin vigilare (to keep aware or alert or to keep watch). Vigilance basically refers to

• Alert, watchfullness.
• Forbearance of sleep, wakefulness.
• Watchfulness in respect of danger, care, caution.
• The process of paying close and continuous attention

World Health Organization (WHO) defines Pharmacovigilance (PV or PhV) as the science and activities relating to the detection, assessment, understand-ing and prevention of adverse effects or any other possible drug-related problems. Recently, its concerns have been widened to include:

• Herbals
• Traditional and complementary medicines
• Blood products
• Bio logical
• Medical devices
• Vaccines.

Pharmacovigilance is like a sunshade to describe the process for monitoring and evaluating ADR'S and it's a key component of effective Drug Regulation Systems, clinical practice and public health programs.

The aims of PV

• To improve patient care and safety in relation to the use of medicines and other healthcare interventions.
• To improve public health and safety in relation to the use of medicines.
• To detect problems related to the use of medicines, mitigate risks and communicate the findings in a timely manner.
• To contribute to the assessment of benefit, harm, effectiveness and risk of medicines, leading to the prevention of harm and maximization of benefit.
• To encourage the safe, rational and more effective (i.e., cost-effective) use of medicines.
• To promote understanding, education and clinical training in PV and effective communication to the public.

Pharmacovigilance in drug regulation
Sound drug regulatory arrangements provide the foundation for a national ethos of drug safety and for public confidence in medicines. Pharmacovigilance programmes need strong links with regulators to ensure that authorities are well briefed on safety issues in everyday practice that may be relevant to future regulatory action. Regulators understand that pharmacovigilance plays a specialized and pivotal role in ensuring ongoing safety of medicinal products.

Clinical trial regulation
In recent years, there has been a substantial increase in the number of clinical trials in developed and developing countries. In their approval of clinical trials, regulatory bodies look at safety and efficacy of new products under investigation. Safety monitoring of medicines in common use should be an integral part of clinical practice. Education and training of health professionals in medicine safety, exchange of information between national pharmacovigilance centers, the coordination of such exchange, and the linking of clinical experience of medicine safety with research and health policy, all serve to enhance effective patient care. A regular flow and exchange of information in this way means that national pharmacovigilance programmes are ideally placed to identify gaps in our understanding of medicine-induced diseases.

Post marketing safety drug monitoring
These include detection of drug interactions, measuring the environmental burden of medicines used in large populations, assessing the contribution of 'inactive' ingredients to the safety profile, systems for comparing safety profiles of similar medicines, surveillance of the adverse effects on human health of drug residues in animals, e.g. antibiotics and hormones. The Council for International Organizations of Medical Sciences (CIOMS) report on benefit-risk assessment of medicines after marketing has contributed to a more systematic approach for determining the merit of available medicines.

Pharmacovigilance in national drug policy
The provision of good quality, safe and effective medicines and their appropriate use is the responsibility of national governments. Multidisciplinary collaboration is of great importance in particular, links need to be forged between various departments of the ministry of health and also with other stakeholders, such as the pharmaceutical industry, universities, nongovernmental organizations (NGOs) and those professional associations having responsibility for education on rational use of medicines and pharmacotherapy monitoring.

Pharmacovigilance in public health programmes
The monitoring of medicine safety in countries where there is no regulatory or safety monitoring system in place, or in remote areas with little or no health care surveillance or infrastructure, has been identified as a matter of concern. The problems are especially apparent in situations that involve the use of medicines in specific communities, for example, for the treatment of tropical diseases such as malaria, leishrnaniasis and schistosomiasis, and for the treatment of HIV/AIDS and tuberculosis. Pharmacovigilance should be a priority for every country with a public health disease control programs.

ADRM cell responsibilities

• Collect adverse event notification forms/ reports and additional information as needed.
• Maintain Adverse Drug Reaction (ADR) database, including data entry and data quality assurance.
• Analyze data in the database to detect and generate signals.
• Review adverse reaction reports and prepare case summary.
• Submit that summary case report to the Adverse Drug Reaction Advisory Committee (ADRAC) for regulatory recommendations.
• Follow up the implementation of the regulatory decisions made by Directorate General of Drug Administration (DGDA) and Ministry of Health and Family Welfare (MOHFW) based on recommenda-tions from ADRAC.
• Collect current information on safety of medicines and disseminate to health professionals; alert pre-scribers, manufacturers and the general public to emerging risks of adverse events.
• Share adverse event information from Bangladesh with the WHO-UMC (Uppsala Monitoring Centre) Program for International Drug Monitoring.
• Set research priorities and participate in active surveil-lances and other research studies on medicine safety.
• Implement advocacy, training and education activi-ties for health care providers and other health pro-fessional involved in pharmacovigilance activities.
• Communicate medicine safety information through the DGDA website, drug newsletters and bulletins and pharmaceutical journals.
• Promote rational use of medicines and prevention of ADRs.
• Revise and publish the national drug formulary (BDNF).

History of Pharmacovigilance in DGDA, Bangladesh
Understanding the gravity of importance of drug safety, Bangladesh National Drug Regulatory Authority has started pharmacovigilance program like 134 countries of the world. The Directorate General of Drug Administra-tion has formed ADR monitoring cell with the help of SIAPS, an organization funded by USAID. An ADR monitoring cell was formed in the then Directorate of Drug Administration in 1999. ADR reporting form was intro-duced and distributed to eight different medical college hospitals and seminar/workshops were held. Due to lack of required fund, manpower and unwillingness of the health professional the activities of the ADRM cell discontinued. Under the initiative of Major General Md. Jahangir Hossain Mollick, DG, DGDA, ADRM activities started with a new spirit. As a result, a new Adverse Drug Reaction Monitoring cell has been formed on January 1, 2013 comprising six members headed by a Director of DGDA. The Ministry of Health and Family Welfare has declared this ADRM cell as National Drug Monitoring Centre. The Director General is the advisor of this ADRM cell. To continue the activities of this ADRM cell effectively, a new ADR advisory committee has been formed comprising 16 members with DG, DGDA as the chairman, taking experts from different organizations and the matter has been gazetted on 25-04-2013 by the Ministry of Health and Family Welfare.

Activities of the ADRM cell
1.    The modified suspected Adverse Event Reporting form has been approved in the meeting of Adverse Drug Reaction Advisory Committee (ADRAC).
2.    Organogram and activity flow chart of ADRM cell has been prepared.
3.    All drug manufacturers and importers have been directed to submit ADR monitoring report of their manufactured and marketed products after monitoring by own manpower/channel.
4.    Primarily 20 hospital/healthcare provider institutes have been selected for reporting of ADR and one focal point has been selected from each organization.
5.    Training has been provided to this focal point on pharmacovigilance/ ADR reporting.
6.    The pharmacovigilance program has been launched with the help of MSH/SIAPS and the officers of the DGDA have been trained on pharmacovigilance system.
7.    A draft guideline of National guideline for pharmacovigilance has been finalized with the technical assistance from USAID, SIAPS/MSH.
8.    Initiative has been taken to include the pharmacovigilance activity in the present drug act.
9    Initiative has been taken to coordinate the activities of the Directorate General of Drug Administration with the activities of Kalaazar/other diseases control program of DG Health Services.
10.    The DG, DGDA submitted an application to WHO and as a result, National Drug Monitoring Centre, DGDA, Bangladesh has been included as associate member of WHO program for International Drug Monitoring in Uppsala, Sweden.

Conclusion
Pharmacovigilance is an important component of effective drug regulation. The vision of DGDA is to ensure safe, quality and effective medicines to safeguard the health of the people of Bangladesh. The regulatory body, doctors, pharmacists, nurses, pharmaceutical industries, importers and consumers should play their individual role to perform this activity. Allocation of sufficient budget, logistic support and training of manpower at home and abroad is of utmost importance to address this issue properly. There will be a day when the National Drug Regulatory Authority of Bangladesh will be able to perform this noble activity like other developed countries of the world.