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David A. Kessler, M.D - Food and Drug Law Institute

This is a draft of the prepared remarks. The actual speech may vary.

David A. Kessler, M.D.
Commissioner of Food and Drugs
U.S. Food and Drug Administration
Food and Drug Law Institute
Annual Meeting

Washington, D.C.
December 10, 1996
Thank you and good morning. This is the seventh, and as most of you know, the last time that I will come before you as the Commissioner of Food and Drugs. There is a time to say goodbye and there is a time to thank all of you for your help during my time as commissioner. And that time is almost here.

But rather than focus on that today, I want to focus on one of the most fundamental questions that faces the Food and Drug Administration: How well do we do in getting important new therapies that are safe and effective to patients who need them. This speech is going to focus heavily on data. While you are going to see a lot of numbers, and while it is easy to get lost in the numbers, remember that these numbers really do make a difference to patients who need therapy.

The one number that has, over the years, been an important symbol is the number of new molecular entities approved in a given year. Let me give you the definition of a new molecular entity. That's the scientific definition. In essence, a new molecular entity is "an active ingredient that has never been marketed in this country." The number of NMEs is a sign of hope.

Let's go back to the passage of the Kefauver-Harris amendments in 1962, and review the number of new molecular entities that have come on the market each year. The average number of NMEs in the 1960s was 13.7. In the 1970s, that went up to 17.3 In the 1980s, the average was 21.7, and in the first half of this decade, the average is 25.6. The calendar year 1996 is not over, but fiscal year 1996 is complete. In fiscal year 1996, FDA approved 46 new molecular entities, which is almost double the annual rate of years past. If one looks at calendar year 1996, 41 new molecular entities have been approved to date, and, again, the year is not over. And these drugs were approved in record speed.

Look at the last decade. Here are the median total times to approval since 1986.In the late 1980s, median times to approval approached 30 months. The median time to approval for the 41 drugs approved so far in calendar year 1996 is 15.1 months, nearly half the time it took in the late 1980s.

In a critical editorial in Fortune magazine this year, Joanna Siegel and Marc Roberts of Harvard were quoted as saying that "the changes (at FDA) do not constitute basic reforms ... They are instead departures for exceptional circumstances, carefully targeted to AIDS and other life-threatening illnesses." It is true that we have given priority drugs priority treatment. But they are wrong to say that the changes at FDA apply only to priority drugs. When the total time to approval is half of what it used to be for all new molecular entities, that does constitute basic reform.

I want to make sure that everyone is focused on the important numbers. Forty-six new molecular entities approved in fiscal year 1996, 41 new molecular entities approved and counting in calendar year 1996. A median time for new molecular entities approved in either calendar year or fiscal year 1996, 15.1 months. Fifteen-point-one months, for new molecular entities. But new molecular entities make up about a third of all new drug applications submitted to the agency.

In fiscal year 1996, 121 NDAs were approved. The median time to approval for these 121 NDAs was 15.0 months. But there is another important number. As you know, FDA divides drug applications into priority drugs and standard drugs. In calendar year 1996, there have been, so far, 27 priority NDAs approved through Nov. 30. The median total time to approval for these 27 priority drugs was 7.8 months. I have just gone through the data for drugs approved in 1996. Those are drugs whose approval decision was made in 1996. They could have come in anytime over the last several years.

But there are other ways to look at our progress in drug review. Let's move to the performance goals set out in the Prescription Drug User Fee Act in 1992. Under PDUFA, new drug and biologic applications are organized into groups and named for the fiscal year in which they were submitted. Unlike the previous data that I showed you, in which drug applications were grouped by the year in which they were approved, PDUFA groups applications, and sets review performance goals, based on the year that they were submitted. Last year, here at FDLI, I showed you our performance for the fiscal year 1994 PDUFA group. Those applications were submitted in fiscal year 1994, and acted on in either 1994 or 1995, depending on when they came in.

Let me tell you about the data for the fiscal year 1995 group of applications. Data for the fiscal year 1996 PDUFA group of applications will not be ready until next year. I can say that so far, none of the applications in the 1996 PDUFA group are late. The major PDUFA goal is for the agency to review and rule on an application in 12 months unless the company makes significant changes to the application in the last three months of the review cycle. When such modifications are made, FDA gets an additional three months to review the application.

So far, we have reviewed 95 percent of the 1995 group on time. We expect that number to get even higher by year's end. We won't reach 100 percent, however, because we did make a mistake; we misread a deadline on a computer printout and we missed one deadline by three days. Every other application has been reviewed on-time, and the three still pending are expected to be reviewed by the final deadline at the end of this month. The PDUFA goal for the fiscal year 1995 group called for only a 70 percent on time record. The 95 percent performance more than doubles the pre-PDUFA on-time level of around 40 percent.

Whether you are a critic of the agency, or a supporter, whether you are a consumer or a pharmaceutical manufacturer, everyone can take pride in a 95 percent performance record.

The credit goes to the men and women at CDER and CBER who do the hard work, and to the leadership at both of those centers. They deserve our applause. Moreover, when you look at the applications that are part of the PDUFA fiscal year 1995 group, you find that the median total time to approval of priority applications approved thus far is 6.9 months. There are other PDUFA goals.

PDUFA gives FDA 12 months to review and act on efficacy supplements. These are requests from companies to add a new indication or a new group of patients to be treated with an already approved drug.

FDA received 87 efficacy supplements in fiscal year 1995, and PDUFA required the agency to review 70 percent of them on time. The agency reviewed 93 percent on time. This is a substantial improvement over fiscal year 1993's 42 percent on-time rate and fiscal year 1994's 77 percent on-time rate. So far, for fiscal year 1996, none of the efficacy supplement applications are late, but, again, we won't have final figures on those until the end of next year.

When companies want to make a significant change in the way an approved drug is made or decide they want to make it in a new facility, they submit a manufacturing supplement. Under PDUFA, FDA has six months to review these supplements, and the PDUFA goal for fiscal year 1995 requires FDA to review 70 percent of them on-time.

The agency received 1,519 manufacturing supplements in fiscal year 1995, and it reviewed 89 percent of them on-time. This is a significant improvement over fiscal year 1993's performance of 51 percent, and fiscal year 1994's performance of 69 percent. Because the PDUFA review goal for manufacturing supplements is six months, we have an early indication of how FDA is doing in fiscal year 1996.

The agency received 1,492 manufacturing supplements in fiscal year 1996, and the goal for this group is 80 percent on-time review. So far for fiscal year 1996, FDA is at 96 percent on-time review, an improvement over fiscal year 1995 which I just told you was 89 percent. Similarly, we are doing well on resubmissions. These are responses provided by a pharmaceutical company to questions or deficiencies raised by FDA in an approvable or not approvable letter on an original application. Like the manufacturing supplements I just talked about, FDA has agreed, under PDUFA, to review and act on resubmissions in six months. Of the total 71 resubmissions in fiscal year 1995, FDA has reviewed 96 percent of them on time. The goal is 70 percent.

Again, we substantially exceeded expectations. And fiscal year 1996 looks just as promising. So far, the combined CDER-CBER performance for the first six month period in fiscal year 1996 is 98 percent; the goal is 80 percent.

Again, final statistics will not be available until the end of March, but the centers are doing a tremendous job. PDUFA also appears to have improved the communication between FDA and the pharmaceutical industry as to what should go in a new drug application. This has produced better applications that get accepted and reviewed more quickly.

For example, in fiscal year 1993, 34 of the new applications that came into FDA were sent back to the company because they were poorly prepared or missing critical information. These have gone down steadily until in fiscal year 1996, only six applications were refused for these reasons, a more than five-fold improvement. What's more, the rate at which applications received a positive response during the first review has gone up 40 percent.

In fiscal year 1994, 48 percent -- about half -- of applications received a positive response during the first review. In fiscal year 1995, that went up to 67 percent -- about two-thirds. This is another strong indication that FDA and the companies are working closely together so the manufacturers understand what needs to be in an application before its submitted.

All of this suggests that American patients are getting the medications they need faster and more efficiently. Despite all the progress FDA has made in speeding up the review and approval of new drugs, we still have our share of skeptics.

Last year, we answered those skeptics. Here at FDLI, we released comparative data, showing that patients in the U.S. had access to important new drugs as soon as -- and often sooner -- than patients in the United Kingdom, Japan and Germany.

We submitted the data to the Journal of the American Medical Association for peer review. That article -- based on the data first shared with you -- is being published in this week's JAMA.

Let me share some even newer international data. We have looked at the new centralized drug approval process of the European Union -- the system that is said by some to be better than ours.

We have looked at the 15 new drugs approved both by both the FDA and the EU centralized procedure. The U.S. is faster than the EU. The median time for FDA review and marketing approval in the U.S., for those 15 common drugs, is 5.8 months. The median time for review by the Committee for Proprietary Medicinal Products and final EU authorization for a company to sell those 15 common drugs in Europe is 12.2 months. Now, we all know that drugs are not submitted at the same time, and so the U.S. could be faster and American patients still be waiting. But that's not the case either for these 15 drugs. In 11 instances, the drugs were first approved in the U.S. In one instance, EU authorization came three days ahead of the FDA approval, and in three instances, the EU authorization came first. It is fair to say that FDA is a world leader in drug review any way you look at it. Forty-six NMEs in fiscal year 1996, 41 NMEs in calendar year 1996, approval time for all drugs; 15 months, priority drugs; 7 months. Ninety-five percent of all applications were approved on time and we're faster than EU. Those are the numbers. FDA has been making substantial progress in its other centers as well. For example, the Center for Devices and Radiological Health has sped up its premarket approval in the last three years even as it eliminated the backlog of 510(k) applications.

Let's look at the PMA approvals first. In fiscal year 1996, CDRH approved 43 PMAs, a six year high. In the three years before that, we tended to approve between 25 and 30 PMAs. Some of these recently approved PMAs were quite old, so the average review times are long. But eight were reviewed start to finish in one year or less. In fact, eight of 15 PMAs, more than half of the PMAs submitted in the first half of fiscal year 1996, received a first action within the 180-day deadline. That's up from 30 percent in fiscal year 1995, and less than 20 percent in fiscal year 1994. Even though we are approving more PMAs, and we have improved the time to first action, the PMA approval time is coming down only slowly. It still takes too long, more than two years, to get a device through the process.

The center and the agency are ready, willing, and able to bring down the PMA review times, just as we brought down the review times for NDAs, if resources are made available.

In 1994, we did devote additional resources to the 510(k) process, not through user fees, but through appropriated dollars. Because of those resources and the center's hard work, there is no backlog for 510(k) applications. The percent of 510(k)s receiving a first action within 90 days has risen steadily until they are over 90 percent on-time. And for those 510(k) devices that are receiving approval, the time it takes has gone down steadily.

In fiscal year 1996, the median review time for 510(k) devices that received approval was 85 days, down from a peak of 144 days in 1993. The average review time in fiscal year 1996 was 110 days, down from the peak of 184 days in fiscal year 1994.

Overall, CDRH has done a remarkable job in solving review problems that had plagued the center for several years. We have worked on review times without sacrificing the increased scientific and medical rigor of the reviews.

I have presented a lot of numbers. Many are records for the agency. But that is not what is important. What is important is that those numbers are attached to specific therapies.

Here are the names of some of the priority products that were approved in the last year or so. Many of the products often approved in record time are important new therapies.

We approved six for AIDS, nine for cancer, and new agents also became available for difficult to treat conditions such as Lou Gehrig's disease and Alzheimer's.

We have approved six new vaccines, a dozen important diagnostic tests, and some of the most advanced biological therapeutics.

We have approved new lasers to treat esophageal cancer and nearsightedness; devices to make PAP smears easier and assist devices for failing hearts.

It has been an unprecedented year for new therapies, highlighted by the historic efforts of a handful of pharmaceutical firms to develop the protease inhibitors that are used to treat AIDS. It is an amazing achievement.

The companies involved in developing the protease inhibitors; Abbott's team led by Andre Pernet; Roche's team led by Wajen Suh; Merck's team led by Ed Scholnick; Agruron's team led by Barry Quart, and FDA's team led by David Fiegal including Jeff Murray, Stanka Kukuich, Rachel Berman, Steve Gitterman, Paul Lu, Chi-wan Chen, and many others deserve special recognition and our gratitude in getting those protease inhibitors to patients in record time.

It is a historic accomplishment.

While these new drugs--the protease inhibitors--do not represent the ultimate goals that must be reached in the battle against AIDS, they do provide an entry into the next level of therapy.

Why has this been such a productive year? Many factors are involved, but when you look at these new drugs, you quickly realize that they came to fruition because of the scientific seeds that were sown years ago.

The new protease inhibitors resulted not only from an understanding of the biology of the virus, but also because of the knowledge that came from other fields -- the study of hypertension and renal physiology.

New anti-depressants and anti-psychotics have been developed because of a better understanding of the shape of receptors in the brain.

Drugs to treat rare metabolic diseases were approved this year because metabolic pathways were elucidated years ago.

Safer vaccines to treat old diseases such as pertussis have resulted from a better understanding of the biology of the organism that causes the disease.

Our insights into cell biology and replication contributed to the development of an anti-cancer drug that is a dramatic example of an agent that results in the death of rapidly proliferating acute leukemia cells.

And all of this has been done with the highest safety and efficacy standards in the world. Not a single drug, not one biologic has been withdrawn from the market in this country during this last year because it is unsafe or ineffective.

Today, I have talked a great deal about the centers that review and approve drugs and devices.

FDA's other centers are moving forward with important programs as well. You will be hearing about some of these in the next month or so.

FDA will soon be releasing a proposed regulation on labeling for over-the-counter drugs, and within days we will receive and need to act on the final report from the steering committee set up to develop criteria and guidelines for what kinds of information patients should receive about their medicines when they fill a prescription.

And, the Center for Food Safety and Applied Nutrition will soon release a study that compares the nutritional information reported on a food label to the actual nutrition of the product. And there is a great deal of work going on in the area of food safety.

All of us can be enormously proud of what FDA employees have accomplished. After all, this is the most important consumer protection agency in the world.

Thank you.