The US Food and Drug Administration (FDA) has released recommendations covering the development of gene therapy programmes, through to the investigational new drug (IND) application process.
The draft guidance on Chemistry, Manufacturing, and Control (CMC) information for human gene therapy INDs, for example, offers the FDA’s current thinking on IND preparation with respect to quality and manufacturing, as well as documentation for drug substances and drug products.
According to WCG (WIRB-Copernicus Group) senior scientific advisor for gene therapy, Daniel Kavanagh, the guidance highlights the need for broad, interdisciplinary expertise.
Industry requires proficiency in “biochemistry, molecular biology, genetics, and microbiology, to successfully manufacture new investigational drug products for gene therapy applications,” he told us.
While much of the advice is also generally applicable to other categories of INDs, Kavanagh said the FDA’s current thinking on drug substances will be of interest to gene therapy developers, “including the need for structure information to include annotated genetic sequences and viral and cellular components.”
A complex process
According to Kavanagh, the FDA documents respond to an industry need for gene therapy-specific recommendations: “Some simple gene transfer projects may be synthesised by a relatively straightforward process. However, many of these products involve production of one or more molecular, viral, bacterial, and cellular components for which standard chemical manufacturing standards do not apply,” he explained.
“By setting expectations for documentation of items such as the importance of sourcing of sera and media, as well as establishment of cell banks, the guidance should help sponsors understand what is needed to facilitate IBC [Institutional Biosafety Committee] allowance,” he added.
Open-source manufacturing?
What more could be done to advance the development and manufacturing of gene therapies? Manufacturing techniques could be openly shared between stakeholders, said Kavanagh.
“A major challenge at present is that technical know-how for complex manufacturing steps is being developed by multiple sponsors in parallel and classified as trade secrets. The more that optimised techniques enter the public domain, the quicker the field can advance,” he told us.
“This challenge goes hand in hand with the need to automate complex manufacturing techniques that are currently the domain of highly-skilled scientists and technicians,” he added.
The Agency also released draft guidance documents with a clinical trial design-focus, which cover its current thinking on preclinical considerations, and surrogate endpoints that could be used by sponsors to accelerate the approval of gene therapies.