FDA Expects More Than 200 new INDs for Cell Therapy Products Next Year
[Thursday, January 17, 2019 ]
In a news release this week, FDA leaders announced that they are forging ahead with increased enforcement of IND and BLA rules on cell therapy companies and expect to receive hundreds of new INDs within months. FDA estimates that by next year it will receive more than 200 new INDs for such products each year, and that by the year 2025 it will be approving about 10-20 new BLAs for cell therapy products every year. To accommodate the extra workload, FDA plans to hire 50 new reviewers. These numbers seem overtly ambitious and need to be put in context. This is an ongoing effort by FDA to regulate so-called “stem cell” companies. The announcement puts gene therapy and CAR-T companies in the same category as unregulated stem cell companies, which may be an over-simplification of the issue. While the IND and BLA route of regulation is unequivocally established for traditional gene therapy and CAR-T therapies, there is lack of clarity if the same is true for many of the autologous cell therapies and other mixed cell therapies offered by physicians to their patients. Almost all the non-regulated cellular therapy providers, use autologous protocols where a patient’s cells harvested from one part of the body are re-implanted in the same individual for therapeutic purposes. Most such cellular preparations involve various kinds of techniques to harvest the cells but does not involve genetic manipulations such as that involved in CAR-T or gene therapies. In fact, almost none of the players in the unregulated space claim gene therapy but regenerative treatment. FDA’s past efforts to regulate autologous therapies faced strong resistance from public, physicians and even several State regulators. Even FDA’s past initiatives have added to the confusion. While on one hand, FDA has released Guidance documents that provide a very restrictive perspective on regulation of such therapies, its leaders have said that they would take selective enforcement decisions on a case-by-case basis. There is no doubt that all cell therapies, irrespective of the technology involved in creating such products, ought to be regulated but it cannot be one size fit all approach. This FDA announcement muddies the waters by combining therapies with established regulations (such as gene therapies, CAR-T therapies, and other cellular therapies), for which there are about 800 active INDs, with the unregulated mostly autologous therapies, for which practically there is no IND. To predict that from 800 current INDs, FDA would have an additional thousand new INDs for cellular therapies in the next five years is ambitious, if not unrealistic. Most of the small autologous therapy companies, most of which are individual physicians, may simply close shop instead of embarking on an expensive IND/BLA route. It may be FDA’s intention anyway to have unregulated cell therapies off the market. But with no alternative similar, relatively inexpensive treatment options, it may not be a wise decision. Rather FDA should create clear, pragmatic directions based on logic, pubic benefit, and cost of the treatment. There is need for two regulatory pathways, one that involves IND and BLA, and another that allows most low risk options with a goal to establish reliability via real world evidence. This is an opportunity for FDA to take leadership in this area; so far FDA has not shown that it wants to take it.