Well, here we are in 2020, almost halfway through GDUFA II, and what do we know? We know that the OGD expects approvals to slow down, but original ANDAs to begin to fill up the system again. We have already seen the slowdown in approvals and, according to the OGD, this is likely to continue for the next couple of years. Clearly, this is not really what the industry wants to hear as one of the biggest drivers for industry support of GDUFA fees was supposed to be to get applications approved faster. We are still seeing median approval times well above thirty months, and first-cycle approvals seem to have stalled. So, what do we want from the next iteration of GDUFA?
The ANDA suitability petition process, wherein a firm can obtain permission to make certain limited changes from that of the reference listed drug through an ANDA (dosage form, strength, substitution of one ingredient of the same therapeutic class for another if there is a known equipotent relationship, and route of administration), came to a screeching halt about eight or nine years ago. This mechanism was an effective tool to make a slightly different drug that may serve some useful purpose (e.g., making an intermediate dose so patients did not have to break tablets, making a higher strength so patients did not have to take multiple pills, or changing a dosage form to make taking the product easier for certain patients). The Agency’s lack of action has forced many firms to seek approval of these changes through the 505(b)(2) application process, clogging up the new drug folks with reviews of NDAs for relatively minor changes. The statute requires review of ANDA suitability petitions in ninety days, but currently actions take well over six to seven years (if ever), and that is if you are lucky. Perhaps a fee for review of these petitions will get the ball rolling and allow the Agency to meet its statutory requirements once again.
How do you tackle the first-cycle approval issue? Is there any way under the current review paradigm? What could be done to the fee structure to permit an ongoing continuous review, like with the New Drugs side of the house? Increasing fees for real-time-review teleconferences or meetings might help, but with the volume of ANDAs and the current review process, this is not likely going to happen. Improving first cycle reviews (which will significantly bring down median approval times) is likely one of the most important issues for the industry, yet no solution applied to date has really fixed the problem. New Drugs NDAs have an over 90% first-cycle approval rate. Perhaps you may have some ideas? If you do, I will be happy to publicize them in future posts.
The FDA has removed the supplemental review fee from the GDUFA basket with the advent of the new GDUFA II fee structure. Supplements seem to be moving through the OPQ/OGD very efficiently unless an inspection is needed. Is there anything that could be done to speed the inspection in these instances, for example, a special supplemental inspection fee for expedited inspection? With the world the way it is today, probably not, but just thought I would throw that out there.
More meetings? That has always been a hot button for the industry. How about a better way to communicate than the controlled correspondence (CC) process? There are so many questions being asked of the Agency; perhaps a database of responses to general questions that multiple applicants are asking could be developed and shared online so the same questions don’t keep popping up in CCs. In the long run, this would also lessen the workload in responding to the ever-increasing number of CCs. The FDA could also update the database, perhaps on a quarterly basis, with new responses.
How about the Agency better explaining its decision-making process or, better yet, asking only questions or for information that is based on a “need to know,” rather than information that “nice to know”? This could be accomplished by having more supervisors with the time to parse out the questions asked in information requests, discipline review letters, or complete response letters to be certain that they are actually relevant to and necessary to make an approval decision.
These are some of my ideas. Clearly, the program fee structure should take care of any post-approval application maintenance, but I just wonder where we will be during the negotiations for GDUFA III and whether the industry can get more of what it needs, at a price it can afford.
