3. History and evolution of Pharmacovigilance

Pharmacovigilance started about 170 years ago, although it was not yet named as such at that time. The historical phases help us to understand why pharmacovigilance helped us to achieve such important results for man’s health and for pharmacology itself, and to identify the challenges that await Pharmacovigilance in future years. In this blog we will see the milestones that led to the evolution of Pharmacovigilance activities in the last century.

1848 – 15 year old patient died in course of routine anaesthesia with chloroform. The patient had problem of ingrown nail of toe; and was given chloroform to remove it and it caused fibrillation of ventricles which resulted in patient death.

1893 – Lancet initiated foundation of a commission and starting collection of notifications about side effects

1936 – USA-s 107 lethal cases after sulphanilamides (diethylene glycol was used to solubilize); 

1938 – US Federal Food and Drug Act – required, that the pharmaceuticals should be “pure” and “free of any contamination” (nothing about the efficacy)

THE THALIDOMIDE TRAGEDY (1957-1961) – Thalidomide first entered the German market in 1957 as an over-the-counter remedy, based on the maker’s safety claims. They advertised their product as “completely safe” for everyone, including mother and child, “even during pregnancy,” as its developers “could not find a dose high enough to kill a rat.” By 1960, thalidomide was marketed in 46 countries. Around this time, Australian obstetrician Dr. William McBride discovered that the drug also alleviated morning sickness. He started recommending this off-label use of the drug to his pregnant patients, setting a worldwide trend. Many children in the 1960’s, like the kindergartner, were born with phocomelia as a side effect of the drug thalidomide, resulting in the shortening or absence of limbs.

1961 – Dr William McBride (Australia) reported 20% increase in foetal abnormalities and phocomelia in relation with thalidomide use, later numerous reports from other countries (more than 4000 cases)

1962 – USA Kefauver-Harris amendment to the law (requirement to prove safety and efficacy before issuing MA)

1963 – resolution WHA 16.36 reaffirmed the need for early action in regard to adverse drug reactions

1964 – UK started “yellow cards” system

1965 – European Union issued EC Directive 65/65 – first European pharmaceutical directive. The directive was a reaction to the Thalidomide tragedy in the early 1960s, and aimed to establish and maintain a high level of protection for public health in Europe.

1968: World Health Organization Pilot Project started to pool adverse drug reactions from multiple countries 

1997: ICH E2B adopted Electronic reporting standard agreed worldwide 

1999: Revised MedWatch, draft MedDRA 

1999: Institute of Medicine – report on errors and risk issues Introduction of risk management concepts 2001: Post marketing safety reporting guidelines – FDA Guidance on how to report adverse events in post marketing phase 

2002: PDUFA III – Prescription Drug User Fees Acts allowed FDA to charge fees 

Allowed FDA to monitor risk post approval, requires companies to monitor risks 2 yrs post approval 

2003: The “Tome” 

– 94 pages of proposed rules on adverse event reporting Pre-marketing section finalised in 2010 

2004: Draft risk management guidelines 

2005: Final risk management guidelines 

– Specifies how to perform signal detection, risk assessment and risk mitigation 

2007: FDA Amendment Act
2008: Volume 9A in EU
2010: New IND Reporting Rule
2010: European PV legislation passed 

2011: Volume 10 (Eudravigilance) 

– Detailed guidance on the collection, verification and presentation of adverse event/reaction reports arising from clinical trials on medicinal products for human use (‘CT-3’) , (2011/C 172/01) 

2012: European PV legislation effective (UK SI 2012 No 1916) 

2014: MHRA Good Pharmacovigilance Practice for Medicines (Dec 14)