primary mode of action
(1) (A) The Secretary shall, in accordance with this subsection, assign a primary agency center to regulate products that constitute a combination of a drug, device, or biological product. (B) The Secretary shall conduct the premarket review of any combination product under a single application, whenever appropriate. (C) For purposes of this subsection, the term “primary mode of action” means the single mode of action of a combination product expected to make the greatest contribution to the overall intended therapeutic effects of the combination product. (D) The Secretary shall determine the primary mode of action of the combination product. If the Secretary determines that the primary mode of action is that of— (i) a drug (other than a biological product), the agency center charged with premarket review of drugs shall have primary jurisdiction; (ii) a device, the agency center charged with premarket review of devices shall have primary jurisdiction; or (iii) a biological product, the agency center charged with premarket review of biological products shall have primary jurisdiction. (E) In determining the primary mode of action of a combination product, the Secretary shall not determine that the primary mode of action is that of a drug or biological product solely because the combination product has any chemical action within or on the human body. (F) If a sponsor of a combination product disagrees with the determination under subparagraph (D)— (i) such sponsor may request, and the Secretary shall provide, a substantive rationale to such sponsor that references scientific evidence provided by the sponsor and any other scientific evidence relied upon by the Secretary to support such determination; and (ii) (I) the sponsor of the combination product may propose one or more studies (which may be nonclinical, clinical, or both) to establish the relevance, if any, of the chemical action in achieving the primary mode of action of such product; (II) if the sponsor proposes any such studies, the Secretary and the sponsor of such product shall collaborate and seek to reach agreement, within a reasonable time of such proposal, not to exceed 90 calendar days, on the design of such studies; and (III) if an agreement is reached under subclause (II) and the sponsor conducts one or more of such studies, the Secretary shall consider the data resulting from any such study when reevaluating the determination of the primary mode of action of such product, and unless and until such reevaluation has occurred and the Secretary issues a new determination, the determination of the Secretary under subparagraph (D) shall remain in effect.