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Event Title
Remarks to FDA employees on Generic Drug Science Day
November 28, 2017

Remarks to FDA employees on Generic Drug Science Day - 11/28/2017


Remarks by Scott Gottlieb, M.D.
Commissioner of Food and Drugs
Generic Drug Science Day
November 28, 2017
White Oak, MD

(Remarks as prepared for delivery)

Thank you for the opportunity to share some thoughts in advance of today’s meeting on the science that supports our generic drug program at FDA.

Generic Drug Science Day offers the chance to showcase the evolving scientific and regulatory challenges related to generic drug evaluation – as well as some of the solutions being developed by FDA.

It’s through the work of our scientists that we’re able to develop the tools to fulfill our mission; and enable broader access to advances shaping medical practice.

This is especially true when it comes to generic drugs.

Few areas so clearly demonstrate how the effective application of regulatory science can benefit the public -- in this case by speeding the development and approval of safe, high-quality, and more affordable generic drugs.

The staff of FDA’s Office of Generic Drugs and the Office of Pharmaceutical Quality work hard to strengthen this process, while continuing to improve on our confidence in the quality and safety of the generic drugs we approve. 

Thanks to their work, we’re approving a record number of generic drugs. And because of our substantial and continuing investment in improving this process, we’re seeing faster review and approval times.

This translates into direct benefits for consumers.

FDA requires that a generic firm provide data to show that it can manufacture a drug reliably and it can be substituted for its brand-name counterpart. 

But just as important is that FDA itself must possess the scientific framework to allow the agency to carefully review the data submitted by the generic firm and ensure that it proves what the drug maker is claiming.

Using advanced scientific tools and analytics to evaluate whether an applicant meets these critical requirements directly impacts how quickly applicants can develop – and FDA can review – submissions that lead to approval. Today’s program showcases this science and FDA’s important, advanced research that’s helping to make more generic drug products available.

We’ve made promoting the opportunities offered by generic medicines -- and the access and affordability they enable – one of FDA’s highest policy priorities.

I’ve been especially focused on areas in our regulatory portfolio where the law allows for vigorous competition from generic medicines, and access to more affordable drugs that it enables. But in these cases, for different reasons, that expected competition isn’t materializing.

I’ve bucketed this focus of our attention into three areas. First, sometimes the lack of competition is a result of branded drug makers that game the system, usually in ways that block the ability of generic drug makers to run the studies needed to win FDA approval.

We’ve been focused, in particular, on tactics branded drug makers adopt to block generic drug makers from amassing the physical doses of the branded drug that the generic firms need in order to run the bioequivalence studies that FDA requires for approval.

A second area of focus is on the general throughput of our own approval process. We’ve seen instances where a small number of speculators have bought older medicines that were off patent, but where the drugs didn’t face much, if any competition. Usually this was because these drugs were infrequently prescribed medicines. But for a small number of patients, these drugs were still sometimes critically important.

These speculators would in some cases acquire these drugs, and jack up the price beyond any reasonable measure of the value they generated. You’re probably familiar with some examples.  The speculators knew that they’d be able to play a regulatory arbitrage owing to the time it took to get a new generic application approved. They knew that it could take years before another generic competitor could enter the market.

We’ve taken action to address this behavior and to curb this regulatory arbitrage. We’ve taken steps to make our approval process more efficient at the same time that we vow to expedite the approval of applications for drugs that fall into these categories.

We’ve also recently published a list of off-patent, off-exclusivity branded drugs without approved generics. These are the sort of drugs that the speculators targeted -- off patent and low volume drugs that don’t face a lot of generic competition.

By proactively listing these drugs, and making clear that we’ll expedite approval of any application for one of these medicines, we’ll be helping to reduce the financial incentive to play games with these drugs.

It’s the third category of policy focus that I want to expand on today. That’s our effort to improve the process for developing generic copies of complex drugs.

Complex generic drugs are broadly defined as generic drugs where it’s especially hard to establish therapeutic equivalence, and also difficult to get through the FDA’s ANDA pathway.

Often, these are cases where the drug involves a complex formulation or complex active ingredient.

In other cases, the drug acts locally on tissue, like an inhaled medicine that acts directly on the lung, or an eye drop that acts on the surface of the eye.

In such cases, the drug can’t be easily measured in the blood. Traditional bioequivalence and bioavailability studies aren’t adequate to support approval.

The relevant question, then, is how the drug is directly acting on the tissue.

In some cases, there may not be adequate scientific principles to reliably measure all of these local effects.

During today’s symposia, you’ll hear about different examples of these complex drug products and certain other topical drug products, including transdermal delivery systems and intrauterine systems.

FDA’s ANDA pathway, under Hatch-Waxman, was developed at a time when most drugs were simple small molecules. They were easy to characterize and evaluate through bioequivalence studies.

In most cases, the activity of a drug correlated directly with how quickly it got into the bloodstream, and how long it stayed in the blood so it could have its intended effect on its site of action. In contrast, complex drugs are often hard to formulate or difficult to measure through the blood. There’s often no simple path to approval.

The hurdle to approval can also be higher when the drug is delivered through a complex device like a metered dose inhaler, or an auto-injector. These drugs also fall into the broader category of complex generics.

In these cases, the branded drug maker may still hold IP on certain features of the device. In such a circumstance, the drug can be an old medicine, but the device can be hard to copy since new patents protect its key features. 

A generic competitor may propose differences to the device in an effort to avoid infringing such patents.  However, this may raise complicated scientific and regulatory questions as to whether the generic product will have the same clinical effect and safety profile--and thus be substitutable for--the branded drug product.       

We have taken steps to provide industry with greater guidance on the types of information and analyses generic sponsors that want to copy a branded product, like an auto-injector or a metered dose inhaler, should submit to FDA to support approval of such products, even when the generic versions have some design differences relative to the branded drug they’re copying; and those design differences might correlate with different instructions for use of the two products. 

Specifically, as we currently work to finalize draft guidance that we issued last January, we’re taking new steps in that final guidance to provide parameters to generic applicants in addressing these issues.

The guidance lays out how generic applicants should consider when design differences between a generic version of a branded drug could impact the clinical effect or safety profile of the generic product, and thus the substitutability of the generic medicine.

The final guidance clarifies new policies related to these situations. This includes a principle we’re setting out that allows a generic product to have certain labeling differences from the branded product – if such labeling changes stem from permitted design differences.   

In other words, under this guidance, as long as the generic applicant is able to demonstrate with data, where appropriate, that differences in the design of the generic product do not affect the clinical effect or safety profile when the generic is substituted for the branded product, the generic product can be approved as a competitor to the branded drug where all other requirements for generic approval are met.

Drug-device combinations are just one type of complex drug where we see obstacles to generic competition. 

Many of these drug-device combination products raise complicated scientific issues, with which many of you are very familiar.

Other products raise complicated policy issues.  We’re separately working on many of these policy issues to resolve obstacles that block or delay approval of generic drug-device combination products.

For example, we’re working to develop guidance for industry with the aim of clarifying “sameness” requirements for ANDAs.  We believe that guidance in this area may be particularly helpful for complex generics, including drug-device combination products.

But there are a lot of other complex drugs that lack generic competition even though they don’t have intellectual property blocking generic entrants. In many of these cases, it’s because the scientific principles for proving sameness have not been firmly established.

Going forward, we’ve committed to put out guidance laying out how a generic firm would copy a particular complex drug at least two years in advance of the first potential generic entrant. This will make it easier for generic firms to plan how they can copy complex drugs. But we also need to continue to improve the science for demonstrating sameness in these settings. And gatherings like today’s event help advance these efforts.

Leveraging science is a key part of how we’ll advance our generic drug program. Our goal is to promote generic entry as a way to foster price competition, and improve access to healthcare. So I’m delighted to be able to open today’s event and to support your efforts. It’s a key part of our broader mission to fostering greater access to safe and effective generic medicines.