The International Pharmacovigilance (PV) Landscape
By Dr. Arunima Sen, MD, PDCR, ACCR, Sr. Manager, Pharmacovigilance & Medical Affairs
The French playwright Moliere, some hundred years ago had said “to undergo treatment you have to be very healthy, because apart from your sickness you have to withstand the medicine”. It is an undeniable fact even today that, adverse drug reactions (ADR) are the cause for many hospitalizations, significant morbidity and sometimes even death. This is also the basic premise which led to the development of Pharmacovigilance as a science that ultimately aims to prevent adverse drugs reactions and its impact on patients, both in premarketing and post marketing phases of drug development.
The foundation stone for Pharmacovigilance was laid in the 1960s with the launch of WHO’s Program for International Drug Monitoring in 1968. From that time onwards WHO’s relentless work and the rigorous legislations and guidelines by the regulatory agencies of most of the countries have shaped Pharmacovigilance as a domain that has extended beyond the strict confines of detecting new signals of safety concerns and has become a tool for development and marketing of safer medicines.
It is interesting to note some of the evolving country specific legislations and guidelines that has helped shape Pharmacovigilance as it is seen today.
Some important US Legislation by FDA which paved the way of proactive Pharmacovigilance:
FDAAA (FDA Amendments Act)
- Passed in 2007 and effective in 2008, this was the most comprehensive revision bringing sweeping safety reform. Title XI of FDAAA demands REMS (Risk Evaluation and Mitigation Strategy) for identified drugs and also imposes stricter post marketing safety surveillance from marketing authorization holders (MAH).
Some newer FDA Initiatives to enhance the safety of drugs in the developmental stage are:
- Enhanced developmental safety assessment, e.g.- generating industry guidance document for premarketing safety assessment for drug induced liver injury (DILI)
- Safe Use Initiative, 2009: a program aimed at reducing the likelihood of preventable harm from medication use. By this program the FDA aims to collaborate with health care professionals and other stakeholders to identify drugs that are linked to preventable harm and devising mechanism to overcome them.
- IND regulation revision Sep 2010 : On 29 September 2010, FDA released the final ruling and draft guidance for amending Regulation 21 CFR Parts 312 and 320 governing safety reporting requirements for INDs and bioavailability (BA)/ bioequivalent (BE) studies. The new requirements are designed to (i) improve the overall usefulness and quality of safety reporting and the agency’s ability to review critical information, (ii) strengthen FDA’s ability to review critical safety information, (iii) improve safety monitoring of human drug and biological products and (iv) harmonize safety reporting with recommendations made by ICH, CIOMS and EU.
Some EU Legislation that helped the development of Pharmacovigilance
- ‘Risk Management Plan’ was introduced in 2005 as an EU initiative to ensure that the benefits of a particular medicine exceed the risks
- EU Directive 2010/84: (published on 15 December 2010 and will become effective from 21 July 2012) enforces EU coordination of PV activities via coordination group / PV Risk Assessment Committee. Some of the other important areas that this directive talks about is:
- Direct reporting of SAR (suspected adverse reactions)by HCPs and patients
- MAH reporting only suspected adverse reactions (clarification of AE vs. ADR)
- Improved SmPC (Summary of Product Charateristics)of a drug
Some other newer EU initiatives in drug safety:
- ENCePP: European Network of Centres for Pharmacoepidemiology and Pharmacovigilance. This initiative aims to enhance post authorization monitoring of medicinal products by multicentre safety / lack of efficacy studies.
- EU Innovative Medicines Initiative –IMI. This program looks in to Stakeholder collaboration to accelerate development of effective medicines with fewer adverse effects by
- Improved predictivity of safety
- Improved predictivity of efficacy
- Knowledge management
- Education and Training
Newer Pharmacovigilance initiatives in India
Pharmacovigilance Program of India (PVPI) was launched in July 2010 with the goals of monitoring ADRs in Indian population, to create awareness amongst health care professionals, to monitor benefit-risk profile of medicines in India, generate evidence based recommendations and advise CDSCO (Central Drugs Standard Control Organization) for safety related regulatory decisions for medicines. This program is directly under the ministry of health and family welfare and ADR monitoring centers being set up in 40 medical colleges across India.
In conclusion, it can be said that from the time of the ignominious thalidomide tragedy in late 1950s to the more recent rofecoxib and rosiglitazone controversy, the science of Pharmacovigilance has come a long way. From the very “reactive” nature of Pharmacovigilance, which looked in to drug safety as just a mere regulatory requirement on part of the marketing authorization holder to a stage where it proactively can generate safety signals and help get safer drugs to the market, the international landscape of Pharmacovigilance has changed considerably. Right now, Pharmacovigilance is poised to overcome many hurdles in its path to become one of the most important bridges between the patient, the healthcare professionals and the pharmaceutical companies for a safer health care.