Generics

The book Generic by Greene is best described as a history of the early days of the introduction of generic therapeutics. The approval of any new therapeutic by the FDA has been an evolving process. The current process is in a simple manner a three step process in humans, which itself occurs after in vitro and animal testing . Phase I typically examines the safety of the drug. Phase II looks at efficacy. Namely does it work. Phase III examines clinical effectiveness. The FDA process does not look at such things as comparative effectiveness and post approval there is no standard requirement for monitoring, and thus many effects that may result from usage are at best reported and catalogued.

Overall the process tries to limit harm while attempting to deliver drugs which do what they are purported to do. The question however is: just what is the drug being tested? The drug is often an active ingredient which may be patented. The active ingredient may then be patented but the actual drug tested and approved, under a non-disclosure agreement with the FDA, may have inactive or even compounding ingredients that facilitate the activation and utilization of the patented drug. Thus the actual drug sold by the initial holder of the patent is the publicly identified chemical structure, plus other elements that may facilitate the utilization and assist in the overall efficacy. Such things may be the delaying of the breakdown of the prime element until well within the digestive tract or the enabling of timed release.

Now along come the generics. A generic is a copy of the prime patented molecule after the patent has expired. The other proprietary elements are not necessarily there, since they have never been disclosed. Thus if the drug only works by getting it to the small intestine and the NDA protected elements facilitate that, the exclusion of those elements may make the drug generic ineffective. Thus generics are same "but for" the key proprietary ingredients which are secret to the original patent holder and the FDA, never to be disclosed.

How does a generic get approved ? The FDA requires the following:

The generic drug is "pharmaceutically equivalent" to the brand.
The manufacturer is capable of making the drug correctly.
The manufacturer is capable of making the drug consistently.
The “active ingredient” is the same as that of the brand.
The right amount of the active ingredient gets to the place in the body where it has effect.
The "inactive" ingredients of the drug are safe.
The drug does not break down over time.
The container in which the drug will be shipped and sold is appropriate.
The label is the same as the brand-name drug’s label.
Relevant patents or legal exclusivities are expired.

Note, it does not require the same inactive ingredients. It does require "pharmaceutically equivalent". Now just what does that mean? The FDA notes:

generic drug needs to show that it is the same type of product (such as a tablet or an injectable) and uses the same time release technology (such as immediate-release, meaning for immediate effect of the drug, or extended-release, meaning one that is intended to slowly release the active ingredient over time).

There may be many issues here as well. But there are several interesting questions. First, not that these are the current 2019 FDA rules and generics have been around for quite a long time. Thus do these rules apply to all those previous generics? If not, what has been the evolution process? What risks if any do generics pose? Are generics the panacea for explosive pricing on all therapeutics? And the list goes on.

Green presents a history of the generic movement. It clearly is a battle between and amongst the members of Congress as well as the major Pharmas and they growing generic makers. The book presents the growth of this industry in a readable fashion and one can see the issues from the Mylan controversy going back decades not just of recent times.

Words like substitutability and similarity are examined in the context of the generic battle. The major Pharmas roles are presented and the development of various generic entities discussed.

The main weakness of the book in my opinion is that it lacks structure and seems to be limited to the earlier days of the generic introductions. The structure issue is that there is a going back and forth over the same ground and no linear temporal progression of the topics. The temporal issues in my opinion is the discussion of the early days and a lack of discussion of the more recent period.

One of the concerns we should have in my opinion is the outsourcing of generic drug production in China, India, and other countries. Although the FDA alleges it does maintain quality controls these controls can often be circumvented. Thus generics like levothyroxine could readily be adulterated by various means and since 10% ore more of the US population is exposed this could be a massive threat. Add all the generics together and the global outsourcing of production and we could have a major threat to US security, well in excess of any cyber threat.

Thus it would have been useful in my opinion of this tale had been equally focused on current times as well. Yet, overall this is a highly useful and timely presentation of a topic needing more effective consumer education.