Table 4.

Mechanisms for unapproved biologics in the US and the EU.

Category	US FDA expanded access program	ATMP hospital exemption (EU)
Regulation	21 CFR 312.305 21 CFR 312.310 21 CFR 312.315 21 CFR 312.320	Article 28 of Regulation 1394/2007
Safety reporting regulation	21 CFR 312.32	Article 28 of Regulation 1394/2007
Common criteria	1)The patient or patients to be treated have a serious or immediately life-threatening disease or condition, and there is no comparable or satisfactory alternative therapy to diagnose. 2)The potential patient benefit justifies the potential risks of the treatment use and those potential risks are not unreasonable in the context of the disease or condition to be treated. 3)Providing the investigational drug for the requested use will not interfere with the initiation, conduct, or completion of clinical investigations that could support marketing approval of the expanded access use or otherwise compromise the potential development of the expanded access use.	1)Preparation on a non-routine basis. 2)Preparation according to specific quality standards (equivalent to those for ATMPs with a centralized marketing authorization). 3)Use within the same Member State. 4)Use in a hospital. 5)Use under the exclusive responsibility of a medical practitioner. 6)Comply with an individual medical prescription for a custom-made product for an individual patient.
Population	Based on each regulation of each mechanism	Individual patient
When can it be used	Based on each regulation of each mechanism	Before or after initiation of clinical trial
Prior regulator approval	Required	Required
Examples of products (ClinicalTrials.gov identifier)	GX-051 (NCT02079324)	DCVax-L (not applicable)

The US: the United States, CFR: Code of Federal Regulation, FDA: Food and Drug Administration, the EU: the European Union, ATMP: Advanced Therapy Medicinal Product.

ATMP Criteria Source: Flory E, Reinhardt J. European regulatory tools for advanced therapy medicinal products. Transfus Med Hemotherapy 2013;40:409–12. doi:10.1159/000356364.

Source: ClinicalTrials.gov by the U.S. National Institutes of Health https://clinicaltrials.gov/.

Source: DCVax-L <http://www.nwbio.com/nw-bio-announces-two-german-approvals-hospital-exemption-for-early-access-program-with-dcvax-l-and-eligibility-of-dcvax-l-for-reimbursement/>.