3M Health Care (Infection Prevention Division): SoluPrep™

We also acknowledge receipt of your major amendment dated July 31, 2017, which was not reviewed for this action per your request on August 22, 2017, to withdraw the July 31 submission.

The dermal rabbit study (#16-014) submitted on March 3, 2017, does not include a sufficient tissue battery to assess systemic toxicity.

© "As discussed during a teleconference on August 22, 2017, data from a Franz Cell assay does not supplant clinical pharmacokinetic data for informing the animal-to-human exposure margin, or demonstrating minimal absorption of the impurities of concern.

We acknowledge that you have accepted the Agency's recommendation for the drug product impurity levels and updated specifications (dated 21 August, 2017).

We also acknowledge receipt of your amendments dated April 21, 25, and 29, 2016, which were not reviewed for this action.

1. You have failed to demonstrate replicative efficacy in two pivotal clinical simulation studies, based on the previously agreed upon primary endpoints and statistical analyses.

Study EM05-012760 passed on all primary efficacy analyses; however, Study EM-05-013260 did not pass the > 70% responder rate primary endpoint for the inguinal site.

Advice/Information Request, April 17, 2015) that your proposed alternative primary efficacy analyses to be conducted in the event that the positive control fails to meet the 70% threshold are not acceptable.

Conduct a repeat study of the inguinal region with adequate controls that meets the prespecified primary endpoint.

Financial arrangements between investigators and the sponsor can introduce bias in trial data that may be difficult to evaluate.

For any additional clinical trials you conduct for this NDA, ensure that you collect financial disclosure information prior to start of the trial.

You may rely on adequate literature for IPA and CHG/IPA to demonstrate absorption after use as a surgical skin preparation with a similar level of skin coverage to that proposed for the largest size product (26 mL), rely upon FDA's findings of safety for a listed drug(s), or conduct a maximal use pharmacokinetic study with the final, to-be-marketed formulation of your product.

These degradants continue to rise and accumulate in the drug product throughout the shelf-life.

5. The December 9, 2015 submission stated that two samples from the 46 samples were tested for bioburden, whereas the other 44 samples were taken from ampules that were placed in the stability program.

8. Provide English translations of current approved foreign labeling not previously submitted.

3. Describe efforts to minimize or address bias in the small, open-label studies conducted by employees and used to support labeling (e.g., coverage and dry time studies).

The drug product may not be legally markete application is approved.