Food and Drug Administration
Department of Health and Human Services
5630 Fishers Lane, Rm. 1061
Rockville, MD 20852
Re: Docket No. FDA-2018-N-3017 for “Prescription drug-use-related software; Establishment of a public docket; Request for comments.”
ASHP is pleased to submit comments regarding a proposed framework for regulating software applications disseminated by or on behalf of drug sponsors for use with one or more of their prescription drug products (the “notice”). ASHP represents pharmacists who serve as patient care providers in acute and ambulatory settings. The organization’s nearly 50,000 members include pharmacists, student pharmacists, and pharmacy technicians. For more than 75 years, ASHP has been at the forefront of efforts to improve medication use and enhance patient safety.
ASHP thanks the Food and Drug Administration (FDA) for the opportunity to comment on this notice. We commend the FDA for its proactive approach in proposing a regulatory framework for the use of digital technology software with prescription medications. Although ASHP opposes direct-to-consumer pharmaceutical advertising in any form, including software applications, we understand that the software at issue may provide benefits to patients as well as their caregivers and clinicians. We recognize the need to foster innovation in this rapidly evolving area while maintaining appropriate oversight.
ASHP appreciates FDA’s efforts to structure a regulatory framework for prescription drug-use-related software that utilizes existing regulations and guidances to the extent possible. Recognizing that the proposed regulatory framework is speculative, we offer our feedback on FDA’s questions and pose some additional questions for the agency’s consideration.
- Submission Review: It is unclear how FDA anticipates software applications will be submitted. In cases where the software is released in tandem with the medication it supports, it seems likely that the software would be reviewed at the same time as the drug application. However, when new software is submitted to the agency outside of the drug application process, does FDA intend to conduct a preliminary review to determine whether it would fall into the FDA-required labeling category, or will drug sponsors pursue the pathway of their choice? Given the variation in potential software designs, does the agency intend to develop new risk assessment criteria for software applications reviewed as promotional labeling? Will software applications be tracked via MedWatch or other post-marketing surveillance tools?
- Multifunctional Software Applications: FDA suggests that sponsors will be allowed to split up the component elements of software applications to be reviewed separately under the FDA-required labeling and promotional labeling pathways. Again, we question whether FDA or the sponsor will determine the appropriate review pathway. Given the complexities of multifunctional software applications, we also question why the agency does not review the entire application at the higher level of scrutiny associated with FDA-required labeling. FDA furthersuggests that in cases of split review, sponsors could be required to include disclosures that certain software functionalities have not been evaluated by FDA. How would such disclosures be communicated to patients?
- Reliability: Regarding software reliability, FDA notes that “it would be expected that prescription drug-use-related software output submitted by a drug sponsor to the Agency…would be reliably produced by the software.” Will FDA require any data or demonstration of reliability? Unlike drugs, which are produced under controlled conditions and undergo rigorous scrutiny, software applications are inherently mutable. Depending on the software’s usage, patients could be placed at significant risk. For example, FDA cites a program that “allows a healthcare provider to program a patient-adjusted weight-based dosing schedule for an immunosuppressant medication and then reminds patients to take their doses” as software it would consider promotional labeling. A mistake in the software’s dosing algorithm could seriously harm a patient.
Software reliability can be impacted by everything from a relatively benign update to criminal actions such as hacking or introduction of ransomware. Although we recognize that it is inherently in a drug sponsor’s interest to protect patients, the novelty of many software applications may warrant an initial period of more aggressive oversight. We encourage FDA to provide detail on how it proposes to address reliability issues.
ASHP also encourages FDA to seek input from the Digital Therapeutics Alliance. The Alliance seeks to identify best practices and standards in digital therapeutic products. In a recent report, they outline digital health technology policies to ensure safety and quality over clinical validation, regulatory status, and marketing authorization that may be beneficial to consider in the context of prescription drug-use-related software.
- Addressing Benefit Claims: As noted above, ASHP opposes direct-to-consumer patient advertising. If software outputs include benefit claims, we assume that FDA will vet those claims as it would any other promotional advertising. Benefit claims should be balanced with relevant risk disclosures to ensure that end users, whether patients, clinicians, or caregivers, receive all information necessary for safe use of the drug.
- End-User Access to Software Applications: The proposed regulatory framework does not include any detail regarding how drug sponsors will disseminate software. At minimum, prescription drug-use-related software should not prevent or delay patient access to prescription medications. Direct and indirect costs associated with the software should not be borne by the patient, pharmacist, or any other member of the healthcare team or organization.
The proposed regulatory framework applies solely to drug sponsors, which raises the possibility that third-party companies could create unregulated applications to accompany certain drugs. These competing applications could easily create patient confusion. Does FDA plan to regulate or otherwise address third-party applications? At minimum, ASHP would expect the use of safeguards to ensure a sponsor’s software application is readily identifiable.
- Timely Generic Competition: ASHP encourages FDA to prevent sponsors and manufacturers from placing proprietary restrictions on software that may prevent generic or biosimilar agents from entering the market. Specifically, changes to software applications should not be grounds for patent evergreening nor should software licensing be a means to block generic competitors. ASHP is a member of the Campaign for Sustainable Rx Pricing (CSRxP) which seeks to advance market-based solutions to promote transparency, competition, accountability, and value in prescription medications. We urge FDA to maintain a dialogue with CSRxP, patients, and other healthcare providers to ensure that software applications do not stifle generic and biosimilar competition.
Again, ASHP appreciates this opportunity to provide FDA with feedback on the notice. We look forward to working with the agency to produce a regulatory framework that protects patients and ensure safe medication use. Please contact me if you have any questions on ASHP’s comments. I can be reached by telephone at 301-664-8696 or by email at email@example.com.
Jillanne Schulte Wall, J.D.
Director, Federal Regulatory Affairs