Posted: 29 Jan 2017 04:24 PM PST
By Alexander J. Varond –
FDA recently put forth its first interpretation of the Regenerative Advanced Therapy (“RAT”) designation program, which was established by section 3033 of the 21st Century Cures Act. Although it consists of just a few short paragraphs on FDA’s website (here), the guidance confirms that FDA will use its standard definitions found in its Expedited Programs Guidance for terms like “serious or life-threatening,” and it signals that FDA has begun the lengthy process of implementing the new designation program. For a healthy dose of nostalgia, recall a simpler time, when breakthrough therapy designation was the newest tool in FDA’s expedited programs kit (here).
Section 3033 of the 21st Century Cures Act provides that a drug is eligible for RAT designation if:
Given the definition of RAT, it’s useful to recall that, per 21 CFR 1271.10(a), 361 human cells, tissues, or cellular or tissue-based products (“HCT/Ps”):
In practice, many of the HCT/Ps in regenerative medicine that do not qualify as 361 HCT/Ps are regulated as biologics subject to section 351 of the PHS Act and approved via a biologics license application (BLA). The BLA process is perhaps the most burdensome and lengthy premarket review process that FDA imposes. To address this, Congress created the RAT designation.
Evolving Definition of Regenerative Therapy
The definition of RAT established by 21st Century Cures is considerably broader than the one recently provided by FDA in a presentation on regenerative medicine and regulatory science. In a October 2016 presentation, FDA stated that regenerative medicine products are generally for repair, replacement, or regeneration and usually are a combination of a biological product with a medical device (e.g., a 3D, cell-scaffold product).
Instead of focusing on function, a la “repair, replacement, or regeneration,” the 21st Century Cures definition puts greater emphasis on product type (e.g., whether it is a therapeutic engineering product), as opposed to intended use. After all, a RAT need only be “intended to treat . . . a serious or life-threatening disease or condition.” (Emphasis added.) This intended use is in no way unique to regenerative medicine, and the Agency may seek to narrow the intended uses that qualify as RATs in future guidance.
RAT Designation Process
Requests for RAT designation can be made concurrently or at any time after submission of an IND. FDA is required to respond within 60 days. If CBER’s Office of Tissues and Advanced Therapies (“OTAT”) determines that a RAT designation request is incomplete or that the drug development program does not meet the criteria for designation, it will inform the sponsor and include a written description of the rationale for its determination. FDA’s RAT website also provides that:
RAT designation affords the following benefits to sponsors:
The new postapproval requirements are a key differentiating factor from the breakthrough therapy designation. Sponsors of RAT-designated products approved via the accelerated approval pathway have additional options to meet post-approval requirements beyond the standard, controlled clinical trial. Post-approval requirements can be met through:
The new designation, therefore, encourages FDA to further develop and utilize the Subpart H/accelerated approval pathway. For a comprehensive review of FDA’s use of accelerated approval, refer to our paper, here.
Notably, the January 2015 House version of 21st Century Cures at section 2041 addressed regenerative medicine from a different angle. It directed FDA to issue a guidance document on surrogate and intermediate endpoints for accelerated approval of regenerative medicine products. Although this original approach was less ambitious, it also highlighted the need for accelerated approval to bring to market products in the budding field of regenerative medicine.