The US FDA has published six draft guidance documents related to gene therapies. The inclusion of manufacturing guidelines will help modernize the commercialization process to keep pace with the growth technology, say industry groups.

Over the past 12 months, the US food and Drug Administration (FDA) has approved three separate gene therapy products: Novartis’ Kymriah (tisagenlecleucel), Gilead/Kite’s Yescarta (axicabtagene ciloleucel), and Spark Therapeutics’ Luxturna (voretigene neparvovec).

And with a growing number of gene therapies moving through the clinic – there are as many as 600 ongoing trials incorporating gene therapies, BioProcess Insider has been told – the FDA said an inflection point has been reached and has published six draft guidance documents “aimed at fostering developments in this innovative field.”

“These draft guidances will help to ensure that therapeutic developers in this sector have a clear pathway to bring safe and effective gene therapy products to patients as efficiently as possible,” Michael Werner, co-founder and senior policy counsel, Alliance for Regenerative Medicine (ARM) and Partner, Holland & Knight, LLP, told us.

“We were pleased to see that Commissioner Gottlieb reiterated that while it was important to modernize the FDA’s process, it would do so while maintaining its role as the gold standard for safety and effectiveness.”

Six Guidance Docs

Three of the documents are focused on gene therapies for specific disease areas, hemophilia, retinal diseases, and rare diseases.

The other three documents (here, here and here) focus on the manufacture of gene therapies, which Werner – whose organization advocates for progress in gene therapy, cell therapy, and tissue engineering – said replaces outdated guidelines originally implemented in 2006 and 2008.

“ARM expects that the draft guidances related to CMC issues will help to modernize the commercialization process to keep pace with the growth in science and technology in recent years,” he said.

His views were mirrored by Miguel Forte, chief commercialization officer and chair of the Commercialization Committee, International Society of Cellular Therapy (ISCT), a society representing clinicians, regulators, technologists, and industry partners involved in cell and gene therapies.

“This is a clear sign of the growing maturity of the field with finer definition of product characterization and some of the aspects of vector development and safety assessment,” he said, referring to the manufacturing documents.

“Also relating to safety, the sixth document deals with long term follow-up of patients recognizing the need and opportunity to access the long-term safety and benefit aspects of gene therapy,” Forter – who is also CEO of Zelluna Immunotherapy – said.

Supply Chain Management

In the CMC draft guidance, the FDA requests details regarding final mile management of gene therapy products to be included in IND applications. According to Matthew Lakelin, VP of Business Development and Scientific Affairs at TrakCel, this will encourage uptake services from third-party supply chain management firms like his own.

“If this guidance is adopted then human gene therapy developers will have to outline in their IND applications different controls and strategies in their IND applications concerning addressing receipt procedures, dispensing activities – including thawing, diluting and loading into delivery devices – and chain of identity management in the clinic,” he told us.

“This can only be a positive outcome for patients awaiting these treatments, but could potentially put therapy developers under strain if they have not partnered with experienced service partners with regard to logistics and chain of identity control.”