GDUFA implementation is proving to be an extremely difficult lift, but FDA said it will not be shouldering all the weight alone. It also has expectations for industry.

FDA is cognizant that the clock is counting down to the start of the Generic Drug User Fee program’s third year, when a cohort of submissions will arrive with designated review goals. A white board posted in the Office of Generic Drugs is updated daily with the number of days remaining.

But if FDA is to be ready to meet those review goals, along with all the other ambitious responsibilities and improvements mandated in GDUFA, industry will have to change along with the agency, said acting OGD Director Kathleen Uhl.

“This is a shared responsibility. We have to have a shared sense of urgency,” Uhl told the Generic Pharmaceutical Association/FDA Fall Technical Conference. “We are accountable for this program collectively and I’m hoping that we have a shared commitment to make this a successful program.”

In an Oct. 30 speech which closed the two-day conference, Uhl outlined a number of improvements that industry must undertake in order for FDA to have a chance to meet its goal of reviewing 90% of all ANDA submissions arriving in FY 2017 within 10 months.

Chief among them is improving application quality and cutting down on multiple review cycles. The plea should be a familiar one for firms with brand drug divisions. It was a prime topic of prescription drug user fee reauthorization negotiations in 2010 and 2011 Also see "Buying Time: Industry Sacrifices Early To Gain Later With PDUFA V Review Model" - Pink Sheet, 1 October, 2012..

The idea adds another layer to the agency’s campaign to improve the overall quality of the generic industry. Most of the emphasis in the recent past has been on manufacturing and bioequivalence issues Also see "Hamburg Trumpets Potential Rewards Of Quality Improvement For Generic Industry" - Pink Sheet, 23 February, 2013..

Now with application and inspection goals on the horizon, FDA is making clear industry must improve its practices beyond timely payment of user fees in return for the massive expansion of the generic drug program.

“What are you doing differently because of GDUFA … and how is that going to get us to meet these goals?” Uhl asked the audience. “And if you aren’t doing anything differently, how [is] that, lack of change, going to get us to meet these goals?”

FDA is in the midst of redesigning and updating its review and other processes to better handle the generic application workload, thanks to about $300 million in new annual use fee revenue. The agency reached all of its program goals and exceeded its hiring goal in the first program year ([A#00130930007]).

ANDA approvals declined in FY 2013, compared to the previous fiscal year, but not as much as Uhl thought. More than 425 ANDAs were cleared in FY 2013, compared to about 500 in FY 2012. Another about 90 temporary approvals were issued, compared to about 100 in FY 2012, Uhl said.

“It’s much less of a hit than I expected considering the impact of new hires and training new hires,” she said. “I think most of you know that your productivity takes a hit when you get a whole lot of new people.”

Supplement approvals increased from about 260 in FY 2012 to more than 560 in FY 2013. “Complete response” letter volume also increased (see chart).

Many industry officials expected FDA operations would struggle while GDUFA was implemented, but were optimistic benefits were coming ([A#00130930015]).

Title Change Coming?

OGD also is on the verge of becoming a “super office” within the Center for Drug Evaluation and Research as a result of GDUFA and the role generics play in the U.S. health care system Also see "Generic Drugs Gain Status Boost Within CDER" - Pink Sheet, 7 September, 2012..

Final plans for the reorganization are awaiting sign-off, said CDER Director Janet Woodcock.

It remains unclear who will head the new super office, but it appears Uhl is a candidate. She was named acting OGD director in March, following the resignation of Gregory Geba Also see "FDA Generics Office Gets Third Director In Three Workdays; Uhl Brings Policy, Pharmacology Experience" - Pink Sheet, 20 March, 2013..

Woodcock said she cannot appoint a permanent OGD director until the reorganization package has been approved. Uhl would not say whether she would be awarded the role, saying it was not her decision, but has not removed her name from consideration.

However, based on her presentation at the conference, Uhl seems to be acting like she may expect to be named the permanent director or is at least auditioning for the position.

The tone of her presentation outlining the necessary industry and FDA changes under GDUFA was authoritative and confident. She also spent a few minutes at the start describing her background, including her nickname, “Cook,” which has been with her since childhood. It has nothing to do with her cooking skills, she said.

Uhl also talked about her career as a physician, and how she was exposed to generic drugs during clinical work in the military. She called herself “a staunch advocate for the importance of generic drugs in this country,” which drew applause.

FDA, especially in a period of transition and temporary leadership at OGD, would want to project confidence and strength to the generic industry. Still, the biographical statements and tone were an attempt to let industry and stakeholders get to know her better, which could be advantageous if she expects to continue in the position for an extended period.

Uhl is FDA’s fifth OGD director in less than four years. Long-time office head Gary Buehler left the position in early 2010 and joined Teva Pharmaceutical Industries Ltd. shortly thereafter. He was succeeded at OGD on a temporary basis by Keith Webber, who also recently left the agency ([A#14130919006]).

Geba was named permanent director in July 2012, but left in March 2013 Also see "FDA’s Generics Office Loses Another Director As Geba Makes Quick Exit" - Pink Sheet, 14 March, 2013.. Uhl was named acting director a few days later, with Woodcock assuming the role in the interim.

Read The Commitment Letter, Uhl Implores

All of the recent OGD directors, as well as Woodcock and other FDA senior leaders, have highlighted industry quality issues, mostly focusing on manufacturing problems.

Submission quality also will have to improve, especially when review goals begin to take effect in FY 2015. The industry practice of “filing first and developing later,” where it was more important to have an application on file at FDA than for it to be complete, is an inefficient use of GDUFA resources, Uhl said.

Submissions with missing or inadequate elements risk receiving a refuse-to-receive action, which would result in loss of first-to-file incentives. That should force a behavior change, she said.

“It’s going to be a risk assessment on their side,” Uhl said.

Among the application upgrades Uhl requested from sponsors was designation of a central point of contact for FDA questions and correspondence about a submission. That mirrors the agency’s submission review process change, where project managers were designated the sole contact for sponsors to obtain information about an application.

Sponsors also were asked to ensure their contract manufacturers and sites are registered with the agency and that confidentiality agreements are in place so FDA can talk with a sponsor about a site’s inspection status or other issues that arise, if necessary.

In addition, sponsors were told submissions should be mostly electronic and drug master files should arrive well before the ANDA that will be referencing them so the completeness assessment can be finished.

Uhl also implored those attending the conference to read the GDUFA commitment letter that industry and FDA negotiated in 2011 and understand what is expected. She has made the same request of OGD employees multiple times, she said.

Many of the requested changes were outlined in the letter or are an outgrowth of the policies contained in it Also see "Generic User Fee Agreement Includes FDA Pledge To Determine Best Use Of Foreign Regulator Inspections" - Pink Sheet, 7 December, 2011..

“It is imperative to understand what are the terms of GDUFA to then recognize why there is the need for so much change to happen,” Uhl said. “There is probably not one thing in that commitment letter that was something that OGD or FDA did prior to GDUFA … We have to redesign the entire generic drug program.”

GDUFA Metrics
Submissions
Type	FY 2013	FY 2012
ANDA approvals	More than 425	About 500
Prior Approval Supplement approvals	More than 560	About 260
Temporary approvals	More than 90	About 100
“Complete response” letters issued	About 1,250	Less than 50
CR letters with inspections	About 560	N/A
CR letters without inspections	About 690	N/A
Backlog Action in FY 2013
Total First Actions	More than 1,600 in FY 2013 (about 35% of the GDUFA ANDA and supplement backlog)
Guidances Issued in FY 2013
New bioequivalence guidances	About 60
Revised bioequivalence guidances	About 40
Regulatory Science in FY 2013
Grants	20
Contracts	8
Total spent	$20 million
Source: FDA presentation slides

GDUFA Success Depends On Industry Changes As Much As Review Improvements, FDA Says

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