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Ethical, Regulatory and Scientific Challenges in Paediatric Drug Development

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Abstract

Drug development is a complex process that calls for the balancing of the requirements of a number of interests, including those of the pharmaceutical industry, regulatory authorities, science, ethics, politics and, not least, the patient. Originally the domain of academia, drug development is now performed by the pharmaceutical industry and controlled by regulatory authorities. It has created its own global frameworks, culminating in the International Conference on Harmonisation (ICH) regulations; for example, on good clinical practice (GCP) standards.

Over the last few decades, the demand for a stronger focus on drug treatment in children has developed from the voices of just a few paediatricians into action by governments and regulatory authorities.

The pendulum of scientific and ethical consensus has swung away from emphasizing the need to protect children against research. Children will always need protection in research; however, research to improve child health is now perceived as an ethical obligation and delays in passing benefits from pharmaceutical progress as unethical. The ethics of using child research to guide risk assessment in balance with the potential benefit to the single child, and children in general, is constantly evolving.

In 1997, the first successful paediatric legislation was introduced in the US and reduced the paediatric off-label use of medications primarily developed for adults. As part of the US Food and Drug Administration (FDA) Modernization Act (FDAMA) it offered an added period of patent protection to reward paediatric research. It was further complemented in 2003 by the Pediatric Research Equity Act (PREA) that made it a mandatory requirement for pharmaceutical companies to take children into consideration during the drug development process. FDAMA was re-authorized in 2002 as the Best Pharmaceuticals For Children Act (BPCA), and both acts, mandatory PREA and voluntary BPCA, were re-authorized in 2007 under the FDA Amendments Act (FDAAA) that also enacted new paediatric medical device provisions.

After many years of deliberation, an EU paediatric regulation came into force in 2007 that combines voluntary and mandatory aspects. Even more so than the US laws, this legislation emphasizes the need for the inclusion of children at an early stage of the drug development process. There is also increasing cooperation between the regulatory authorities in the US, EU and Japan with regard to the use of medicines in children.

Research into rare childhood diseases is facilitated by paediatric and orphan drug legislation. In addition, the health of children in the developing world is gaining higher visibility with the new World Health Organization campaign to “make medicines child size”. Paediatric drug development is evolving as a complex process on the background of the globalization of trade, transport, travel, science, culture and politics. Continuing the dialogue between all partners in healthcare will be essential if an appropriate balance between risks, resources and benefits is to be reached.

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Table I

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Notes

  1. 1A ‘Written Request’ is a document in which the US FDA explains the research expected for a specific drug. Once the company has declared its agreement to the Written Request and submitted the generated data, it is entitled to 6 months of paediatric exclusivity.

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Acknowledgements

The author is an employee of F. Hoffman-La Roche Ltd, Switzerland and owns shares in Roche and Novartis. The opinions expressed in the manuscript are the personal opinions of the author and are not the official opinion of Roche. No sources of funding were used to assist in the preparation of this review.

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  1. Department of Pharmaceutical Development, F. Hoffman-La Roche Ltd, Basel, CH-4070, Switzerland

    Klaus Rose

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Rose, K. Ethical, Regulatory and Scientific Challenges in Paediatric Drug Development. Pharm Med 22, 221–234 (2008). https://doi.org/10.1007/BF03256707

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