The draft guidelines – which were published this month – set out how manufacturers and clinical investigators should whether their candidate protein drugs elicit dangerous immune responses and how they should develop risk-mitigation strategies.
The US Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research told in-Pharmatechnologist.com: “Immune responses to therapeutic protein products may pose problems for both patient safety and product efficacy.
The organisation explained that in addition to being dangerous for patients immunological adverse events “have caused sponsors to terminate the development of therapeutic protein products or limited the use of what might otherwise be effective therapies.
“This draft guidance is the first step towards encouraging industry to continue development of therapeutic protein products by identifying risk factors for immune responses and proposing mitigation strategies.”
The proposals – which are open for comment – are the first to cover risk management related to therapeutic proteins and – according to the CDER – should be considered in combination with draft guidance on assay development for protein therapeutics issued in 2009.
The CDER declined to comment on the likely cost implications of the testing recommendations, but did say that it has already received some industry comment which it will publish in the Federal register in due course.
The general advice is that developers take a risk-based, case by case approach.
Recommendations include that developers create immunoassays as part of the overall product development programme and use clinical trials to establish baseline antibody responses to protein drug candidates for comparison with later stage trials.
Similarly, “elucidation of a specific underlying immunologic mechanism for related adverse events is encouraged, because this information can facilitate the development of strategies to help mitigate the risk of clinically significant immune responses.”