Three times in the last two weeks, I have found myself explaining to someone that the Hatch-Waxman Amendments did not create the abbreviated new drug application for generic drugs.  For that matter, there were generic drugs long before 1984, and there was a generic industry long before 1984.  And that’s not even the most interesting part; at one point, FDA drafted a regulation for an ANDA pathway that would apply in the future to new NDAs and that would provide a 17-year exclusivity period.

This blog entry explains a little of the history.

There were generic drugs even in the 1940s.

Congress enacted the FDCA in 1938, requiring that every “new drug” have an effective new drug application (NDA).  A drug that was “generally recognized as safe” under the conditions described in its labeling wasn’t a “new drug” – so it could be marketed without submission of an application.  After the law was enacted, some companies marketed copies (the equivalent of a today’s generic) without applications, by reasoning that their drugs were “generally recognized as safe” because someone else had submitted a new drug application.  The 1938 law had grandfathered pre-1938 drugs if certain conditions were met, and copies of these drugs also didn’t need applications.  Sometimes FDA issued an opinion that a particular drug was old and didn’t need an application, and copies of those drugs didn’t require applications.

There were generic drugs after the 1962 amendments.

In 1962, Congress amended the statute, requiring that every new drug have an approved application and requiring that applications contain evidence of effectiveness.  Now, a drug was exempt if it was “generally recognized as safe and effective” under the conditions described in its labeling.  There was another grandfather clause for the really old drugs.

But FDA withdrew all of the opinions it had issued. At this point, a generic company had two choices:  (a) it could reach the decision internally that its drug was generally recognized as safe and effective, because of another company’s NDA, and thus not subject to the NDA requirement, or (b) it could file an application with the agency.  But the only type of application was a full application, like the innovators filed — with trials showing safety and effectiveness.

FDA created ANDAs through rulemaking in 1970.

In the late 1960s, FDA developed the “abbreviated new drug application” (ANDA) pathway through a rulemaking.  The final rule was published in April 1970.  This application – like today’s ANDA – was supposed to prove the generic drug was the same as and bioequivalent to a reference product.  FDA fleshed out the concept of bioequivalence, as well.

The ANDA regulation was available to any generic company seeking to copy a pre-1962 product.  (Lest you think nothing important came to market before 1962: many drugs on the WHO’s list of essential medicines were the subject of NDAs in the 1950s.)   It did not apply to copies of post-1962 products, which meant that there were a lot of newer drugs that couldn’t be the basis of copies through ANDAs.

The 17-year exclusivity period proposal.

When President Carter took office, the new Administration wanted to address the issue of generics through legislation.  A bill was introduced in March 1978, which would have prohibited approval of a generic copy for five years, and it was reported out of committee with a seven-year exclusivity period and actually passed the Senate in 1979 with that language.  But it didn’t go any further.

FDA then turned to solving the issue administratively.  The Bureau of Drugs (now the Center for Drug Evaluation and Research) sent a memorandum to the Commissioner in February 1982, recommending a 17-year period before ANDAs could be approved.  There was a draft regulation attached to that memorandum, with a lengthy preamble.  The drug center explicitly based this length of time on the need for incentives to innovate and on the length of the patent term at the time.  They envisioned 15 years before a designation that ANDAs were suitable and then another two years (estimated) for generic companies to prepare their applications and FDA to review them.  This history, and more details, can be found in a July 1983 hearing report (# 98-67) from a House subcommittee.

Why was Hatch Waxman needed?

The old-drug versus new-drug debate wasn’t entirely over.  FDA said in 1976 it would take action against any generic drug marketed without an approved application, effectively saying that approval of an NDA did not render the underlying drug generally recognized as safe and effective. The generic industry took a different view, and the courts divided on the question whether generic drugs required applications.  The Second Circuit ruled one way in 1980 (applications needed), and the Fifth Circuit ruled the other way in 1981 (no application needed).

In early 1983, FDA was still mulling an administrative solution for copies of pre-1962 drugs, but the generic industry strongly opposed the 15-year period that had been floated.  And there was some concern that the regulation would be vulnerable to challenge by the innovative companies.  Then the Supreme Court ruled in March that generic drugs are “new drugs” and require approved applications.  This brought to end several decades of uncertainty about whether it might be possible for the generic industry to bring their copies to market simply by citing previously approved products.

It meant that the only relief would be the rulemaking at FDA – or legislation more favorable to the generic industry.

In July 1983, Congressman Waxman introduced a placeholder bill (H.R. 3605) that would evolve into the Hatch-Waxman Amendments.  Its purpose was “to amend the Federal Food, Drug, and Cosmetic Act to authorize an abbreviated new drug application under section 505 of that Act for generic new drugs equivalent to approved new drugs.”  And it contained only one provision.

Section 505(b)(1) of the law at the time described the contents of innovator applications.  Congressman Waxman’s first draft simply stated:

“Clause (1) of the previous sentence shall not apply in the case of an application for a drug for which a previous application has been approved in accordance with subsection (c), if the drug with respect to which such subsequent application is filed meets appropriate standards of identity, strength, quality, purity, stability, bioavailability, and bioequivalence in relation to the drug approved in the previous application.”

Put another way, once an NDA was approved, a generic application for a copy would be approvable.  The final legislation in the fall of 1984, of course, looked nothing like that.

FDA’s draft regulation was never published in the Federal Register.  And the question whether FDA could have proceeded by rulemaking for copies of post-1962 innovative products was never addressed by a court.