; and (B) the sponsor submits to the Secretary, not later than 5 calendar days after making the change, a notice of the change. (2) Conditions The conditions specified in this paragraph are that— (A) in the case of developmental changes to an in vitro clinical test, including manufacturing changes, the changes— (i) do not constitute a significant change in design or in basic principles of operation; (ii) do not affect the rights, safety, or welfare of the human subjects involved in the investigation; and (iii) are made in response to information gathered during the course of an investigation; and (B) in the case of changes to clinical protocols applicable to the test, the changes do not affect— (i) the validity of data or information resulting from the completion of an approved clinical protocol, or the relationship of likely patient risk to benefit relied upon to approve a product; (ii) the scientific soundness of a plan submitted under subsection (c)(3)