Final FDA Guidance on Product Development under the Animal Rule

In the Oct. 28 Federal Register, the FDA announced the availability of a final guidance document titled “Product Development under the Animal Rule.” When human efficacy studies are not ethical and field trials are not feasible, the FDA may rely on adequate and well-controlled animal efficacy studies to support approval of a new drug or licensure of a new biological product under the Animal Rule. Adequate and well-controlled animal efficacy studies are required under the Animal Rule. The guidance document is intended to help potential stakeholders in industry and academia (as well as the government) understand the FDA’s expectations for product development under the Animal Rule. This guidance makes final a June 3, 2014, revised draft guidance of the same name. The FDA reviewed 26 comments on the draft received; the comments may be read at the website identified below.

Interested parties may submit comments on final guidance documents at any time. The FDA may consider those comments for future revisions. Submit electronic comments at www.regulations.gov. Comments submitted electronically, including attachments, will be posted to the docket exactly as submitted; do not include confidential information in electronic comments. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville, MD 20852. The notice includes detailed instructions on how to submit written comments with confidential information; if applicable; these instructions should be followed carefully. Identify comments with Docket No. FDA-2009-D-0007.

FDA Seeks Comments on Using Technologies and Innovative Methods to Conduct FDA-Regulated Clinical Investigations of Investigational Drugs

In the Oct. 29 Federal Register, the FDA announced the establishment of a public docket to solicit input from a broad group of stakeholders on the scope and direction of the use of technologies and innovative methods in the conduct of clinical investigations. Specifically, the FDA seeks information to understand individual and industry experiences with the use of such technologies to more efficiently conduct clinical research. FDA is interested in identifying new opportunities to study medical products, as well as receiving comments on barriers, challenges, and relevant considerations that may affect a medical product clinical investigation that uses these technologies and methods.

The clinical trial enterprise continues to evolve and become more complex, and the scientific and infrastructure challenges of conducting clinical investigations affect the cost and timeliness of medical product development. Challenges in recruiting and retaining sufficient numbers of trial participants to conduct an adequately powered investigation in a reasonable amount of time may contribute to the cost and complexity. Creative uses of technology in conducting clinical investigations have emerged over the previous decade and include advances that have the potential to improve recruitment, participation, and retention of trial participants.

New technology and communication infrastructure allow for collection of data and communication wherever the trial participant is located, including at his or her healthcare provider’s location, creating opportunities to overcome geographical and logistical barriers that otherwise might prevent a potential trial participant from participating in a clinical investigation, as well as facilitating the integration of research with clinical care. In addition to potential convenience for the trial participant, these tools and technologies may present sponsors with the opportunity to capture data more frequently and efficiently than would be feasible if data collection were only conducted when the trial participant visited the study site. This may enhance the sponsor’s ability to understand the safety and effectiveness of drugs, biologics and medical devices; increase additional meaningful data gathering; minimize missing data; and maximize trial participation and retention.

Some of these technologies and methods may be used regardless of the trial participant’s location and may include, for example, mobile health technology, telemedicine, and remote sensors. Use of these technologies and methods allows for more flexibility for the sponsor and clinical investigator in the oversight of clinical investigation conduct, data collection, and monitoring of trial participants and clinical sites. Other elements that may be incorporated into clinical investigations to improve trial participant recruitment include online/Web-based eligibility screening, informed consent, and communication between investigators and participants.

In addition to the general solicitation above, the FDA is interested in obtaining information and public comment on the following specific issues:

1. What technologies, communication infrastructure, or innovative methods are being used to conduct clinical investigations? The FDA requests feedback on experiences with methods or models such as mobile technology and remote methods for data collection (for example, lessons learned), as well as information supporting the use of any suggested technologies, methods or models, including any characteristics that would make the technology more or less desirable for use in clinical trials.
2. What are ways the FDA could encourage adoption of these technologies and innovative methods in the conduct of clinical investigations?
3. Identify clinical, cultural, business, regulatory or other barriers perceived by stakeholders that serve as a disincentive to the use of technology to facilitate the conduct of clinical investigations. What are challenges in adopting these technologies or methods? Are there challenges in complying with regulatory requirements for clinical investigations that use such technologies or methods? What are the perceived barriers or challenges to obtaining and documenting informed consent or obtaining institutional review board review, approval and oversight for clinical investigations utilizing these technologies or methods?
4. The FDA is interested in obtaining information on potential trial-participant acceptance, privacy and human-subject-protection issues that may occur as a result of the use of technologies and innovative methods. The FDA is interested in potential trial participants’ interest, tolerance, concerns and willingness to participate in clinical investigations that involve nontraditional settings or use new technologies. What are factors that affect trial participant awareness, acceptance, enrollment, and retention for these investigations? Are there specific patient groups or therapeutic areas that could particularly benefit from these types of technologies or methods? What new opportunities are created through the use of continuous or intermittent remote monitoring and data collection? What are the risks and benefits to trial participants that may occur as a result of using these technologies or off-site methods in clinical investigations? Are there challenges to using these types of technologies or methods because of breach-of-privacy concerns? Are there concerns relating to the integrity of data collection or encryption or the secure transmission of information? Are there unique considerations for ensuring integrity of the source data, for example, authenticity and reliability? How should validation of participant-operated mobile devices be addressed? What are the challenges presented when data are collected using the Bring Your Own Device (BYOD) model where trial participants use their own smartphones or tablets for data collection? What are the perceived barriers to pooling data collected from different devices provided by individual participants, as well as pooling data from the BYOD model with data collected at the investigational site or on paper forms? How should situations such as mid-study user device switches be handled? What are the challenges or special considerations with recruiting and/or retaining potential trial participants with low levels of computer literacy or individuals who may have limited or no access to mobile technologies, computer devices, or the Internet? How can these challenges or special considerations best be addressed?

Submit electronic or written comments by Dec. 28 as instructed above and identify them with Docket No. FDA-2015-N-3579. 

The Regulatory Update is excerpted from Research Practitioner, Volume 16, Number 6, November-December 2015.