Pharmacovigilance of Medicines for Rare Diseases
Dr. Danica Cvetkovic looks at the issue of pharmacovigilance for orphan or rare diseases. Many issues associated with the sector are challenged by the small patient population. This article looks at the commonly used strategies for evaluation of post-approval safety and the effectiveness of rare and orphan drugs.
What Is An Orphan or Rare Disease?
From a medicines regulatory point of view, in the USA and the European Union (EU) orphan or rare diseases are defined as those that affect less than 200,000 individuals (prevalence <650/million population) and less than 5/10,000 (500/million) respectively . Most patients suffer from even rarer diseases affecting 1 person in 100,000 or more. Approximately 5,000-8,000 distinct rare diseases affect 6-8% of the EU population i.e. between 27 and 36 million people .
Although the regulatory framework for pharmacovigilance does not differentiate orphan drugs, the orphan drugs that have been approved in recent years present major outstanding challenges for pharmacovigilance departments. The pharmacovigilance of orphan drugs presents problems related to the small patient population, and this is further challenged by the fact that many of them are present in the paediatric population [3, 4].
Commonly Used Strategies
In the field of rare diseases, commonly used strategies for evaluation of post-approval safety and effectiveness, such as meta-analyses and review of spontaneous adverse event reports, may not be applicable. Real-world data sources, such as claims databases, electronic healthcare records, and disease and drug registers, show substantial promise in studying orphan drugs .
Long term data collection may be needed to better understand the safety profile in children and particularly to detect any long-term or delayed toxicities in the developing child. All elements and procedures of safety monitoring plans for orphan drugs for rare diseases have to be carefully evaluated and based upon information available about the drugs from all sources, including nonclinical toxicology information, and any data from previous human experience for other indications other than that in the rare diseases.
There are possibilities to increase the speed by which data in the post-marketing period can be generated by better use of data from ongoing formal clinical trials, by early planning of drug or disease registries, and networks to facilitate international research, specifically in rare diseases.
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We are working with several companies on pharmacovigilance projects related to orphan drugs. If you would like to talk to us about your project, please contact us on 00353 52 61 76 706, email: email@example.com, or complete the form below.
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Acorn Regulatory is a leading regulatory, pharmacovigilance and clinical consultancy company headquartered in Ireland. Our Clinical & Medical team works with the largest and the leading companies in life sciences to assist them in bringing their products to market. The team, led by Dr. Danica Cvetkovic, has written extensively on the issue. In the latest e-book from Acorn Regulatory, we look at the best and most popular articles from our Clinical & Medical team.
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1.Richter T, Nestler-Parr S, Babela R, et al. Rare disease terminology and deﬁnitions. A systematic global review: report of the ISPOR Rare Disease Special Interest Group. Value Health 2015;18:906–14.
- European Medicines Agency, Orphan designation. Available at https://www.ema.europa.eu/en/human-regulatory/overview/orphan-designation-overview accessed in May 2020
- Food and Drug Administration. Draft guidance. Rare Diseases: Common Issues in Drug Development. Guidance for Industry. January 2019. Available at: