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protocol deviations may also be acceptable. If the change in the mechanisms of investigational product distribution is then included in a protocol amendment, such a change may be part of a “cumulative” amendment that includes a number of changes that accrue, rather than an urgent protocol change.14 Q8. How can the sponsor ensure proper disposal of unused investigational drug product if the participant cannot return to the study site? FDA regulations outline sponsor and investigator responsibilities for storage conditions and accountability of investigational drug products, including disposition of unused investigational products (IPs). 15 Under 21 CFR 312.59, the sponsor shall assure the return of all unused supplies of the investigational drug from each individual investigator. The regulation further provides that the sponsor may authorize alternative disposition of unused supplies of the investigational drug provided this alternative does not expose humans to risks from the drug. The procedure for disposition is generally considered part of the investigational plan and is normally described in the study protocol as a study-specific plan for handling the IPs. In most protocols, such plans involve the participant bringing the unused IP to the clinical trial site and then the investigator returning the unused IP to the sponsor or its designee. During the COVID19 public health emergency, if appropriate, a pre-paid shipping package can be used for the participant to return IP back to a central location where it can be accounted for and disposed of per the protocol, but this approach is not the only way to satisfy the regulatory requirements for disposition of unused IP. Regardless of the chosen disposition method, sponsors and investigators must maintain adequate records regarding the disposition of the IP.16 Sponsors may consider adopting alternative procedures for disposition of IP that permit sponsors and investigators to fulfill their requirements for maintaining adequate records of IP disposition (including documenting dates, quantity, and use by particpants), provided such procedures do not expose humans to risks from the IP.17 For example, it may be possible to provide the participants with a way to dispose of IP at their home (such as with a drug disposal pouch) and document such disposal through photo or video that can be transmitted to the investigator or sponsor. FDA does not endorse a particular approach, but the risks involved (e.g., environmental considerations) with specific IPs should be considered when selecting a method for disposal. FDA has provided a consumer update Where and How to Dispose of Unused Medicines18 that provides recommendations to consumers about how to safely dispose of unused FDA-approved medication at home. Sponsors can consider whether any of those recommended methods of disposition are appropriate for approved drugs being studied for a new use in a clinical 13 See 21 CFR 312.30(b) and 812.35(a). 14 See 21 CFR 312.30(b), 812.35(a), and 812.150(a)(4). 15 See 21 CFR 312.57, 312.59, 312.60, and 312.62. 16 See 21 CFR 312.57 and 312.62. 17 Sponsors should consider whether an information amendment should be submitted pursuant to 21 CFR 312.31. 18 See https://www.fda.gov/consumers/consumer-updates/where-and-how-dispose-unused-medicines. Contains Nonbinding Recommendations 14 investigation. As noted in the consumer update, FDA only recommends flushing medications that are on the FDA flush list, which currently does not include unapproved IP. Investigators proposing alternative disposition methods must obtain authorization of those methods from the sponsor of the trial.19 Additional restrictions may apply to IPs subject to the Controlled Substances Act.20 Q9. If patients are currently receiving an investigational product infusion at the clinical trial site, can a sponsor switch to home infusion? Sponsors should consider the safety risk to trial participants who would miss an investigational product infusion because of the inability to come to the clinical trial site. If a sponsor is considering providing alternative arrangements for administration of the investigational product (e.g., home nursing or alternative sites by trained but non-study personnel), the sponsor is expected to perform a risk assessment that considers the nature of the investigational product and the potential risks to both the trial participants and the health care providers responsible for administering the product at the alternative site. This risk assessment should include assessment of risk mitigation strategies. Based on this risk assessment, sponsors should consider whether consulting the appropriate FDA review divisions regarding plans for alternative arrangements for administration of investigational products that are usually administered in a health care setting is warranted. Consulting FDA is strongly advised for complex investigational products (e.g., cellular therapy and gene therapy products), where potentially altered storage and handling conditions could adversely affect product stability. In all cases, applicable requirements for maintaining required investigational product storage conditions (prior and after reconstitution), investigational product reconstitution specifications per the Investigator’s Brochure, and 

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