I spend a lot of time thinking about the intersection of FDA regulation and intellectual property, and I have been constructing a large dataset relating to the patents claiming different types of FDA-regulated products.  Recently, I have also been thinking a great deal about the regulation of food (because Mizzou is now allowing me to teach Food Law & Policy, in addition to Drug & Device Law).  These two areas of interest intersected this past week, giving me some modest insights into premarket review of food additives and some very modest data to contribute to discussions about the (in?)efficiency of FDA’s food additive review process.

How FDA Regulates Food Additives

Food additive regulation can be counter-intuitive the first time through.  To begin with, “food additive” is a surprisingly broad category.  The statutory definition (FDCA § 201(s)) includes substances that most consumers would assume are food additives — direct food additives, the intended use of which results in their becoming a component of food.  Artificial sweeteners are an example.  But the definition also includes substances that are used in the production, manufacturing, packing, processing, and preparing of food, if they could reasonably be expected to indirectly affect the characteristics of food.  These are considered indirect food additives.  Substances that are generally recognized as safe (GRAS) don’t count as food additives, however, and there are other exceptions as well.

Food additives must go through a preapproval process at FDA, but the process is very different from the approval processes in place for new drugs, medical devices, and biological products.  The applicant files a petition instead of an application, and the result is a regulation rather than a license.  The regulation lays out the conditions under which the food additive may be safely added or applied to food.  (For an example, here is the regulation for BHT, which is a preservative.)  What’s in a food additive petition?  Among other things, full reports of the investigations performed to determine whether the food additive is safe for its intended use.  Testing in laboratory animals is the primary way this is done.  (See the Redbook for more information about the principles for safety assessment.)  That said: in 1997, Congress changed the process for food contact substances; many now go through a notification process instead, which results in a no objection letter.

Patent Term Restoration — a Source of Data

The inventor of a new food additive may hold patents claiming the substance or his method of manufacturing the substance.  Because of the food additive approval process, however, the effective term of this patent is shortened.  That is, the inventor typically files for and receives his patent before the testing is complete, the petition prepared, and FDA’s review complete.  By the time the agency approves the food additive for use, a chunk of the 20-year patent term has elapsed.

Congress amended the Patent Act in 1984 to address this issue for several types of product that go through federal regulatory review.  Under this provision, a food additive patent owner is entitled to partial restoration of a portion of one patent covering the food additive.  In other words, a portion of the lost term is added back at the end.  This will be done if the food additive had not been commercially marketed before and the request was timely filed with the U.S. Patent and Trademark Office (PTO).

In these situations, FDA and PTO work together to determine precisely how much time the inventor gets back on the patent.  The process is public.  As a result, there are some useful documents relating to testing and approval of the food additives in question.  I’ve gone through those.

It’s a small pool.  In the 34 years since Congress made this change to the Patent Act, PTO has received patent term restoration (PTR) requests for only 15 food additives.  Eight were direct food additives, and seven were indirect food additives.  We have information from FDA about the regulatory process only for the 11 that received patent term restoration and the one that is still pending.

Three Things We Learn about Food Additive Petitions

First, most of the food additives in the set — 11 of the 15 — were approved in 2000 or earlier.  Only two companies with food additives approved since 2004 have sought patent term restoration.

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Why might this be?  FDA has approved plenty of food additive petitions since 2004 (search here, which has food and color additive final rules by year).  It is possible some companies were not aware of patent term restoration, but the more likely explanation is that: (1) since 1997, most food contact substances have gone through a notification process, which makes them ineligible for patent term restoration, and (2) of the rest of the food additives, only two qualified, because only two represented the first commercial marketing of the additive in question.  In other words, I think, most food additive petitions are not for novel food additives, but rather for new uses.

Second, FDA review of petitions for novel food additives takes a really long time.  As part of the patent term restoration process, FDA reports how long the company studied the food additive and also how long the agency’s review of the petition took.  The statute requires the agency to take action on a submitted petition within 180 days.  The average length of time for FDA to review and approve the twelve food additive petitions for which we have data, however, was 2298 days, or 6.3 years.  For the six direct food additives on which we have data, the average was 2463 days, or 6.75 years.

FDA reports that it takes an average of 24 months to approve a direct food additive petition. But the experience is clearly very different for a company proposing a novel food additive.  Of course, it is reasonable to expect some back and forth between the petitioner and the agency during review of a food additive petition.  But the statute does anticipate a 6-month process.  Does it need to take this long?  Could it be done more quickly?  Some believe the agency applies the statute more conservatively than Congress intended, in light of the fact that the statute does not (and could not) require absolute harmlessness.  Others suggest that FDA’s review of a food additive petition can be hijacked by the petitioner’s competitors (see Lars Noah’s discussion, here).  One of the petitions related to sucralose, for instance, which sat at FDA for eleven years while it considered safety issues that had been raised by third parties.  (The company got only two years of patent life back.)

Third, food additive testing by the companies varies wildly in length.  Some of the 15 products spend less time in testing than they did before FDA for approval, and some spent more time in testing.  Some testing programs lasted two years, and one lasted 12 years.  The direct food additives averaged about six years in testing, and the six sweeteners averaged around seven years in testing.  The fat substitute, Olestra, spent around six years.

And Three Things We Learn about the Patent Term Restoration Itself . . .

First, PTO grants most requests for restoration of food additive patents.  Of the 15 products, 11 have received patent restoration and one is pending (and likely to be granted).  One request, for a slimicide, was denied as not timely filed.  There is a 60-day deadline, and the company was one day late.  Another was denied because the petition did not represent the first permitted commercial marketing of the food additive in question. Although the decision on the third request doesn’t seem to be on the PTO website, it looks like FDA never approved the food additive in the first instance.

Second, about 25 percent of the time companies propose more than one patent for restoration.  PTO rules permit this.  A company may file parallel patent term restoration applications and then elect one patent at the end of the process.  Four of the 15 food additives had more than one patent term restoration application pending at the same time.

Third, the average amount of time restored to a food additive patent is 1031 days (2.8 years).  This is interesting, when you realize that the 11 food additives with restored patents spent an average of 3839 days (10.5 years) getting their patented inventions through the regulatory process!

Why so few days restored?  To begin with a patentee is eligible to recover only half of the days that it spends testing its food additive.  But for this group of food additives, the real issue is that the recovery was capped.  More than half of them were capped at two years, because they were “transition” products.  That is, the patents had issued and testing had begun before the statute was enacted in 1984.  Congress assumed these products would be through the process quickly, and it limited the companies to recovering two years of lost patent life.  As it turned out, these food additives were not approved until considerably later — in some cases the mid to late 1990s!  And they were limited to two years of patent restoration, regardless.  Non-transition products are capped at five years, and this affected two other food additives in the set.

Conclusion

It’s hard to reach any grand conclusions from a set of 15 food additive petitions.  But based on this review, I am inclined to be concerned about the length of time FDA takes reviewing food additive petitions and about the impact of the entire process on patent life.  Some food additives can play an important role furthering the public health (for instance, artificial sweeteners play an important role for diabetics). Without digging further into FDA’s review of these particular food additives, which I have not done, it is hard to say what is causing the delays.  But delays in the interest of chasing down vanishingly small chances of harm, when Congress did not mandate absolute harmlessness, would be concerning.