PharmExec Blog

Post-Approval Regulatory Priorities: Progress or Pile-Up?

An enduring falsehood about the pharmaceutical industry is that the heavy lifting ends with a successful new drug registration. What comes after is the equivalent of a well-funded retirement, where providers embrace the therapy, payers meet the price, and patients push the boundaries of clinical practice toward lucrative new indications. The reality, however, is starkly different, with FDA approval now only the beginning of a mounting series of post-approval obligations that potentially can match the costs of developing the drug itself.

The most important of these is a shift in risk-bearing responsibility from the regulator to the manufacturer to guarantee the efficacy and safety of his medicine. This now extends to the entire life cycle, including the period beyond patent expiry. Another is the widening of expectations around outcomes, whereby regulatory agencies are overturning previously accepted surrogates for drug approval—in essence, asking companies to update and re-certify the original terms that brought them access to the market. The days when regulatory approval boundaries were fixed and finite, as exemplified by the slogan, “We won, so we’re done,” are clearly over.

The heat is on in terms of squaring these big investments against expectations of strong revenue and profitability performance. This unpredictable spiraling of costs affects the entire product life cycle at a time when growing competition within therapeutic classes has shortened the average duration of market exclusivity, when companies derive most of the returns from their investment in R&D. Costs linked to product support are being borne over a steadily increasing period of time, accentuating the inherent instability of a process that for most companies means their revenues today depend on the outcome of projects launched 15 to 20 years earlier.

Few people in the industry are critically examining the implications of this trend. Harvard Medical School has taken a useful step in the right direction by convening a series of conferences designed to bring together a range of stakeholders—regulators, the industry, patient groups, providers and academia—to scope and analyze what it calls “post-approval” issues.

The most recent was held earlier this month; the target of discussion was comparative clinical and cost effectiveness requirements and how these might add or subtract to the commitments that companies will need to meet in ensuring access to a new medicine. The short answer? Unclear, mainly because regulators are still dancing around the distinction between clinical and cost effectiveness, embracing the former yet expressing skepticism about the latter, despite the fact that in many countries outside the US the two are effectively intertwined. Added Outcome CEO Dr. Richard Gliklich, who chaired the Harvard summit: “On the safety side, while we have grown more comfortable with the regulations requiring post-approval studies, there is still much unease about signals getting ahead of the methods for interpreting them.”

Two other implications of the “post-approval” pile-up are worth noting. First, industry fails to highlight the commitments it is taking on in offering the public a better safety and efficacy proposition. Companies are now conducting expensive post-approval trials designed to address everything from nagging safety concerns to demonstrating efficacy among small sub-populations of patients. These can be hugely complex initiatives; trials cited by Pfizer at the meeting included long-term studies involving upwards of 40,000 patients to prove the clinical relevance and safety profiles of key therapies like Geodon and Celebrex, in disease areas where unmet medical need remains high.

Second, little is said about the ultimate impact of post approval commitments on medicines innovation in general. The question is simple. In a constricted payer environment, will the private sector be able to bear more risk, especially beyond the point of market take-up, where the growing burden of proof around evidence will often limit the size of the treatable patient population? The long time frames for these studies may also mean their conclusions are no longer relevant to the current state of therapy. And how many promising leads will be sidelined by industry as a consequence of the priority it has to give to the regulator, who is increasingly the customer too?

If medicines innovation is one part serendipity and two parts discipline, then there is a potential for losses on both counts. Innovation in industry has always required a strong internal champion; the danger is a process led by the bland, risk-averse and externally-driven “stakeholder” consensus called death by faint praise. Is this really what we mean by “bold partnerships?”

As in all aspects of this industry, trends coalesce slowly and only time will tell. But the stakes for patients and the health system overall are high.

This entry was posted in Regulatory and tagged , , , , , . Bookmark the permalink. Trackbacks are closed, but you can post a comment.


  1. Posted May 27, 2010 at 3:20 pm | Permalink


    Your points are well taken. I would add as well a concern posed by the recent agreement between NICE and the MHRA, which will have NICE involved in pre-approval clinical trial development. A similar scenario is unfolding here in the US with the closer collaboration developing between FDA and CMS. Having the public rather than private sector defining the direction of new drug development is a trend worthy of notice.


  2. rahul goswami
    Posted March 16, 2014 at 12:58 pm | Permalink

    if post approval changes done on drug formulation which is already approved by USFDA then what is procedure to file that change?. Any forms or procedure for filing the changed formulation?

Post a Comment

Your email is never published nor shared. Required fields are marked *


You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>

  • Categories

  • Meta