Orphan, Combo, Pediatric Products Would See More Influence In Proposed US FDA Reorg

Reorganization also may force change to commissioner succession plan.

US FDA Commissioner Scott Gottlieb intends to elevate the voice of orphan, combination and pediatric product stakeholders as part of his proposed agency reorganization.

The plan announced July 19 would eliminate the directorate system, including the Office of Medical Products and Tobacco (OMPT), which had been in place since 2011. Gottlieb wants to flatten the organization and officially mandate all center directors and several office directors report directly to him. (See sidebar.)

Among the 16 centers and offices with direct access to Gottlieb would be the new Office of Clinical Policy and Programs (OCPP), which will include the Office of Orphan Products Development, Office of Combination Products and Office of Pediatric Therapeutics. (See graphic below.)

They now are housed in OMPT's Office of Special Medical Programs.

Gottlieb intends for the new office to "support cross-cutting clinical programs that serve key functions across the agency's medical product centers," according to a memo to staff.

The changes, which Gottlieb wants to implement in October assuming they are approved by HHS, should further boost the stature of FDA's combination products, pediatrics, and orphan products programs. Their interests and needs will have fewer barriers to reaching the commissioner.

Orphan products continue to grow in popularity with the advancement of precision medicine and gene therapy. OOPD has seen orphan designation requests and designations issued rise substantially in recent years.

The office now is confronting how to handle designation requests for biomarker- and histologically-targeted products in cancer. (Also see "Orphan Designations For Cancer Drugs: US FDA Urged To Distinguish Tissue-Agnostic From Tumor-Specific Diseases" - Pink Sheet, 10 May, 2018.) It also is dealing with how to make orphan designation decisions for gene therapies. (Also see "US FDA's Acting Orphan Products Development Director Has Gene Therapy Background" - Pink Sheet, 6 May, 2018.)

Orphan products also are gaining influence in the drug review areas of FDA. The prescription drug user fee renewal included language requiring FDA's rare disease staff to be integrated into review teams for rare disease development and application review. (Also see "Rare Disease Integration Into FDA Reviews Will Grow Under PDUFA VI" - Pink Sheet, 18 Jul, 2016.)

The Office of New Drugs reorganization, which is separate from the reorganization Gottlieb announced, also would create a new office for rare diseases, pediatrics and women's health. (Also see "US FDA's Rare Diseases Program Not Expected To Change With Drug Office Reorg" - Pink Sheet, 27 Jun, 2018.)

Pediatric and combination product issues also have become priorities recently. The agency issued guidance recently intent on ending the use of orphan designation system to avoid conducting pediatric studies for non-orphan indications. (Also see "Not A Loophole? BIO Concerned About Limiting Orphan Designations For Pediatric Subsets of Common Diseases" - Pink Sheet, 5 Mar, 2018.)

FDA also is working to streamline the combination product review system, which has a history of problems (Also see "Combo Product Review Pilot At US FDA Will Offer All Applications Intercenter Consults" - Pink Sheet, 20 Dec, 2016.), and recently announced a proposed rule adjusting the combination product designation process. (Also see "US Combo Product Designation Appeal Process Limited In Proposed Rule" - Pink Sheet, 18 May, 2018.)

Provider Affairs To Join Sister Patient Affairs Programs

OCPP also will house new patient and provider outreach programs.

Gottlieb wrote that he intends to formally establish health care provider and patient affairs programs within the office "to enhance our engagement with these important external stakeholder groups."

FDA has previously announced its intentions to create a patient affairs office, which was to be a central point of contact for patients, advocates and other stakeholders. To avoid the long official process, the agency decided to create a staff instead within OMPT. (Also see "US FDA's Patient Affairs Office Is An Office … In Spirit" - Pink Sheet, 17 Nov, 2017.)

The provider affairs staff appears intent on boosting the status of FDA efforts to engage that group in some of its public health efforts, such as the opioid epidemic.

Gottlieb has said he wants to work with medical societies to create opioid prescribing guidelines, which could be used to mandate packaging standards in labeling. (Also see "Opioid Packaging Standards Could Emerge From Dosage Guidelines in Labeling" - Pink Sheet, 11 Dec, 2017.)

The Center for Drug Evaluation and Research's Professional Affairs and Stakeholder Engagement (PASE) staff had been part of the agency effort to reach out to patients and other groups. CDER announced July 19 that PASE Director John Whyte will leave FDA at the end of August to become chief medical officer at WebMD.

PASE's efforts included creating the stakeholder meeting request system for non-industry groups. (Also see "US FDA Sets 'Low Bar' For Meetings With Patients " - Pink Sheet, 25 Apr, 2018.)

Sherman Will Once Again Oversee Orphan, Combination, Pediatric Product Programs

OCPP would be led by Nina Hunter, who now is deputy director for medical programs in OMPT.

Hunter, who joined FDA in 2008 as a scientific reviewer in the Center for Devices and Radiological Health, is a molecular biologist who now works on policy and processes. She was part of a team that streamlined the orphan designation process and helped launch a combination product review pilot program.

Gottlieb also said in the memo to staff that Principal Deputy Commissioner Rachel Sherman would have delegated oversight of OCPP, in addition to the Office of Operations, Office of Chief Scientist, and Oncology Center of Excellence.

When Sherman was Deputy Commissioner for Medical Products and Tobacco, she oversaw the orphan products, pediatric therapeutics and combination products offices, as well as the Oncology Center of Excellence and drug, biologic, device and tobacco centers. She was promoted to that position in 2016 before Gottlieb made her principal deputy commissioner in 2017. (Also see "Gottlieb Adds A No. 2: Sherman Is US FDA Principal Deputy Commissioner" - Pink Sheet, 21 Aug, 2017.)

Who Would Replace Gottlieb In New Structure?

The reorganization also would seem to change the agency's succession plans should Gottlieb resign or otherwise leave office.

Existing FDA policy, which dates to 2016, states that the Deputy Commissioner for Foods and Veterinary Medicine is to become acting commissioner should the commissioner leave office, followed by the Deputy Commissioner for Medical Products and Tobacco. With the directorates eliminated, the policy for who is next in line would need to be updated.

The commissioner also may designate the next in line from a list of senior officials, according to the policy.

FDA told the Pink Sheet that the policy remains in place because the reorganization is only a proposal and there is no further information.

Sherman would seem to be the logical choice to take over, given she is the agency's second in command. But it an important question that might need to be answered soon. Political appointees often choose to depart following a mid-term election, although Gottlieb has made no such announcements.

In his capacity as deputy commissioner for foods and veterinary medicine, Stephen Ostroff has served as acting commissioner twice – when Margaret Hamburg left in 2015 and when Robert Califf left in 2017.  (Also see "US FDA Might Be Temporarily Headed By Ostroff As Califf Sets His Departure" - Pink Sheet, 5 Jan, 2017.)