AARS Alert: FDA Open Comment Period


FDA Committees Vote in Favor of Ending 19-Day Lockout, Revising Attestations for iPLEDGE

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Modifications aimed at enhancing patient access and minimizing administrative burdens for physicians and patients may be coming to the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) program for isotretinoin.

At the conclusion of a joint meeting of the U.S. Food and Drug Administration (FDA) Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee Meeting last month, a majority of committee members voted in favor of ending the 19-day lockout for patients who can become pregnant and for eliminating the need to document monthly counseling for patients who cannot become pregnant. The vote is non-binding, although FDA historically follows the recommendations of such committees.

In addition to voting on the lockout and counseling requirements, committee members explored the potential to permit the use of non-Clinical Laboratory Improvement Amendments (CLIA)-certified pregnancy testing with iPLEDGE and discussed potential enhancements to the existing pregnancy registry aimed at improving data gathering and analysis.

Representing the American Acne and Rosacea Society (AARS) during the public comment period of the meeting, AARS President Andrea Zaenglein, MD and AARS Director Emmy Graber, MD, advocated for removal of the 19-day lockout, removal of the 30-day waiting period for patients already on long-acting reversible contraception, the use of home pregnancy testing, and enhanced patient education regarding emergency contraception.

“I am very grateful that the FDA allowed for these presentations by me and other dermatologists,” Dr. Graber says. “I appreciate their willingness to listen to our viewpoint. Going forward, I hope that there is further conversation and would welcome a two-way dialogue with members of the committee.”

Calling the 19-day lockout an “excessively punitive requirement,” Dr. Zaenglein notes that, “it does not decrease risk of pregnancy but simply prolongs waiting periods for patients who miss the 7-day window period to pick up their medication, often due to no fault of their own. We are pleased that the majority of FDA panel members recognized the burden that the lockout imposes on patients who already waited 30 days to start treatment and voted in favor of eliminating the 19-day lockout."

Only one member of the committees voted in favor of maintaining monthly attestation for patients who cannot become pregnant. Nearly half of voters favored no attestations beyond the time of therapy initiation. The remaining votes were split between attestation every 120 days or repeat attestation at an interval to be determined.

"Removing monthly attestation would be a tremendous relief of administrative burden for providers. Hopefully, the panel will not dictate a specific timeframe for repeat attestation or counseling and allow for flexible scheduling of these patients based on provider judgment,” Dr. Zaenglein says. “As isotretinoin is slow-acting and subject to 30-day supply limits, drug diversion is not a major concern with very few reports provided by the IPMG. Additionally, blood donation centers stringently screen donors for isotretinoin use during their intake, greatly minimizing this risk."

IPMG is the Isotretinoin Products Manufacturers Group, which is required by FDA to fund the iPLEDGE REMS. The REMS is administered by UBC on behalf of the IPMG.

No vote was held regarding the use of non-CLIA certified pregnancy testing, though robust discussion was held. Comments did not reveal substantial objection to such testing, though committee members seemed to generally agree that more data should be collected to help support a future decision. Committee members seemed to demonstrate greater skepticism regarding the use of at-home testing in the context of telemedicine after the COVID public health emergency period. Discussion focused on potential for falsifying tests, although several dermatologists in clinical practice shared strategies aimed at mitigating such risks.

The joint committee meeting also included discussion of the iPLEDGE pregnancy registry, with an eye toward the potential to expand data collection and analysis. Several committee members noted that it is unclear whether there is active recruitment to the registry or whether modifiable burdens may hinder participation.

In closing, committee members shared additional thoughts on potential improvements to the iPLEDGE program. Multiple comments focused on a need to open lines of communications between stakeholders and IPMG.


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Thoughts on iPLEDGE Modifications

FDA is assessing the iPLEDGE program and potential modifications. The FDA Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee will meet March 28 and 29, 2023, from 10 a.m. to 4 p.m. ET each day.

Comments received on or before March 14, 2023 will be provided to the committees. Comments received until March 27 will be taken into consideration by FDA.

FDA Public Comment    Submit iPLEDGE Stories

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In this AARS Member Highlight Interview, John Barbieri, MD, MBA, FAAD, member of the AADA iPLEDGE Workgroup, discusses concerns about the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) program and proposed modifications. Dr. Barbieri, who is also an Assistant Professor, Department of Dermatology, and Director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital in Boston, MA, offers a look at the history of iPLEDGE and concerns for the more than 350,000 patients treated with isotretinoin in the U.S. each year.

The AADA formed an iPLEDGE Workgroup to discuss solutions with the FDA regarding the web program, which is run by the Isotretinoin Producers Manufacturing Group (IPMG). The AADA Workgroup is comprised of Drs. John Barbieri, Andrea Zaenglein, and Ilona Frieden with AADA staff Stephanie Croney and Chad Appel.

In the past, the Workgroup met with the IPMG and the FDA to advocate for improvements to the REMS program, including removing the monthly physician attestation requirements for patients who cannot become pregnant and removing the 19-day online “lock out” period if a patient misses an initial window period. The IMPG shows more willingness to address patient and physician’s concerns, but the Workgroup has begged for more transparency and communication. The IPMG does not even disclose who its members are, for starters. The AADA has requested a stakeholder meeting with the FDA to work together to fix the issues for patients.

More about public participation for the FDA Meeting of the Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee Meeting

Meeting presentations will be heard, viewed, captioned, and recorded through an online teleconferencing platform. The committees will discuss proposed changes to the iPLEDGE REMS requirements to minimize burden on patients, pharmacies, and prescribers while maintaining safe use of isotretinoin oral capsules for patients.

Interested persons may present data, information, or views, orally or in writing, on issues pending before the committee.

FDA is establishing a docket for public comment on this meeting. The docket number is FDA-2022-N-3071. Please note that late, untimely filed comments will not be considered. The docket will close on March 27, 2023. The https://www.regulations.gov electronic filing system will accept comments until 11:59 p.m. Eastern Time at the end of March 27, 2023. Comments received by mail/hand delivery/courier (for written/paper submissions) will be considered timely if they are received on or before that date.

In the event that the meeting is cancelled, FDA will continue to evaluate any relevant applications or information, and consider any comments submitted to the docket, as appropriate. You may submit comments as follows:

Electronic Submissions

Submit electronic comments in the following way:

  • Federal eRulemaking Portal: https://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https://www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else’s Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov.
  • If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see “Written/Paper Submissions” and “Instructions”).

Written/Paper Submissions

Submit written/paper submissions as follows:

  • Mail/Hand delivery/Courier (for written/paper submissions): Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
  • For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in “Instructions.”

Instructions: All submissions received must include the Docket No. FDA-2022-N-3071 for “Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee; Notice of Meeting; Establishment of a Public Docket; Request for Comments.” Received comments, those filed in a timely manner, will be placed in the docket and, except for those submitted as “Confidential Submissions,” publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.

  • Confidential Submissions--To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states “THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.” FDA will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov. Submit both copies to the Dockets Management Staff. If you do not wish your name and contact information be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify the information as “confidential.” Any information marked as “confidential” will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA’s posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.

Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the “Search” box and follow the prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, 240-402-7500.

Oral presentations from the public will be scheduled between approximately 10:30 a.m. and 12 p.m. Eastern Time on March 29, 2023. Those individuals interested in making formal oral presentations should notify the contact person and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time requested to make their presentation on or before March 6, 2023.