FDA guidance on drug development for rare diseases

We take a look at the new guidance from the US FDA

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The US FDA has released draft guidance on drug development for rare diseases. The development process of drugs for rare diseases and drugs for common diseases are by and large very similar, but the key differences are important. One of the major themes of the guidance, is that the FDA expects the sponsor of development to have a thorough understanding of every stage of the process.

The focus areas of the guidance are laid out at the beginning of the document:

  • Adequate description and understanding of the disease’s natural history
  • Adequate understanding of the pathophysiology of the disease and the drug’s proposed mechanism of action
  • Nonclinical pharmacotoxicology considerations to support the proposed clinical investigation or investigations
  • Reliable endpoints and outcome assessment
  • Standard of evidence to establish safety and effectiveness
  • Drug manufacturing considerations during drug development

The FDA places a particular emphasis on natural history studies of the disease in question, dedicating a chapter of the guidance to it and saying “a well-designed natural history study may help in designing an efficient drug development program.” Understanding how the disease progresses and which morbidities are important to patients will allow for the better selection of a sensitive endpoint for studies. This might seem like a reasonable practice for any drug development program, but the FDA place a particular focus on it in the case of rare disease “because there is substantial phenotypic variability in many rare disorders.” Furthermore in these natural history studies, it is important to “include patients across as wide a spectrum of disease severity and phenotypes as possible.”

As the word “guidance” would suggest, the recommendations are not requirements, rather the document exists to assist sponsors in the creation of the next generation of drugs for rare diseases. They say themselves “FDA does not require sponsors to study the biochemical basis of a disease, but sponsors should seek to understand the pathophysiology of a disease as fully as possible at the outset of drug development.”

On the manufacturing front, the FDA underlines some particular challenges which are faced in the manufacture of drugs for rare diseases. One specifically highlighted, is any change in manufacturing quality (impurities, changed drug characteristics etc.) caused by the up scaling from trials to manufacture.

This FDA guidance lays out the path from early stages of drug development through to manufacture with the aim that sponsors should have a thorough understanding of every step to smooth interactions with the regulatory body.

You can read the whole document here.

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Gerald PJ Clarke

Contributor, FSG

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