By Wes Siegner –
 
Dan Fabricant has now left FDA.  In his short tenure as FDA division head and spokesperson on dietary supplement matters, the agency devoted more resources to dietary supplement enforcement matters. Moreover, the industry was routinely criticized for failing to file new dietary ingredient notifications ("NDINs") and serious adverse event reports ("SAERs"), as well as, most recently, for widespread “noncompliance” with good manufacturing practices ("GMPs").  In each case, FDA used numbers to illustrate what the agency perceived to be a problem — but there were also obvious problems with FDA’s numbers:   

• NDINs – The high numbers of “expected” NDINs that FDA has repeatedly cited was based on FDA’s controversial interpretations of DSHEA that were published in a draft guidance in July, 2011.  Comments from all of the industry trade associations, from Congress and from this firm uniformly criticized FDA’s interpretations as untenable and urged FDA to withdraw the draft guidance.  Although FDA has tacitly acknowledged problems with the draft guidance and committed to issuing a new draft, FDA is still basing its accusations of failure to comply with the NDIN requirements on the number of notifications FDA would expect to receive if industry complied with the disputed guidance.
• SAERs – FDA, in advocating passage of the law requiring these reports, argued that the burden on industry would be light because, consistent with the safety of these products, very few reports of serious adverse events would need to be filed.  Nonetheless, FDA now points to the low numbers of SAERs to support claims of widespread noncompliance.
• GMPs – FDA’s recent statements on percentages of industry “noncompliance” apparently refer to inspections that result in one or more “observations” by an FDA investigator that a GMP regulation has been violated.  Such “observations” are not FDA “findings” of a violation, but are merely the view of one individual FDA employee.  FDA’s regulations state that such individual views are not binding on the agency.  Rather, these written “observations” are meant to begin a discussion between the inspected company and FDA, and to encourage voluntary corrections when needed.  Further, for any FDA-regulated industry, receipt of a 483 is far from exceptional, particularly in cases, as is true with dietary supplements, where an entire industry is subject to new and very detailed GMP regulations, which FDA inspectors are still struggling to understand and apply in a consistent manner.

Companies that choose to ignore the rules deserve to be singled out.  However, FDA should not use misleading raw numbers to unfairly stigmatize the entire dietary supplement industry, or any FDA-regulated industry.  We hope that future FDA numbers relating to dietary supplement industry compliance will be more balanced. 

By Kurt R. Karst –

The battle over New Chemical Entity (“NCE”) exclusivity for Fixed-Dose Combination (“FDC”) drugs continues to heat up.  In a recent Petition for Reconsideration and Petition for Stay (Docket No. FDA-2013-P-0119), Ferring Pharmaceuticals, Inc. (“Ferring”) requestes that FDA reconsider its denial of NCE exclusivity for PREPOPIK (sodium picosulfate, magnesium oxide and citric acid) for Oral Solution.  Ferring also requests that FDA stay application of a new interpretation of the FDC Act to award NCE exclusivity to certain newly approved FDCs until the issues Ferring raises are resolved.

As we previously reported, on February 21, 2014, FDA denied three Citizen Petitions requesting that the Agency award NCE exclusivity to three previously approved FDCs containing an NCE and a previously approved drug.  Those petitions concern STRIBILD (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate) Tablets (Docket No. FDA-2013-P-0058), PREPOPIK (Docket No. FDA-2013-P-0119), and NATAZIA (estradiol valerate and estradiol valerate/dienogest) Tablets (Docket No. FDA-2013-P-0471).  On the same day FDA issued its petition response, the Agency announced that upon finalization of a draft guidance document, the Agency would reinterpret the NCE exclusivity provisions of the FDC Act to award NCE exclusivity for a newly approved FDC containing an NCE and a previously approved drug.  FDA refused to apply its new interpretation to previously approved drugs, such as PREPOPIK.  The 60-day comment period on FDA’s draft guidance document expires on April 25th, but it is unclear how quickly FDA will act to finalize the draft guidance. . . . and whether or not there will be a legal challenge to FDA’s reinterpretation of the statute.

Ferring is the second company to request that FDA reconsider its denial of NCE exclusivity.  As we recently reported, Gilead Sciences, Inc. (“Gilead”) submitted a Petition for Reconsideration asking FDA to rethink its position with respect to STRIBILD, and to refuse to accept any ANDA or 505(b)(2) application for a drug product containing either of the two NCEs in STRIBILD – elvitegravir and cobicistat – under the rules governing NCE exclusivity.  According to Gilead, none of the reasons FDA cites in its petition response, such as recognizing NCE exclusivity would burden sponsors with pending applications, fit the circumstances surrounding STRIBILD.

Ferring raises some of the same points in response to FDA’s petition denial as Gilead does in its reconsideration request.  According to Ferring:

• The Commissioner’s statutory interpretation of the five-year exclusivity provisions for fixed-combinations with at least one novel drug substance is the only correct interpretation, and must be applied to all relevant applications.  No change in the Agency's regulations is required legally or technically.
• The Commissioner failed to adequately consider all points raised in the original Citizen Petitions, including wildly inconsistent exclusivity results under its umbrella policy and the support in the legislative history for five-year exclusivity for fixed-combinations with novel ingredients.
• Due Process and fairness require that five-year exclusivity be recognized for all applicable drug applications with remaining exclusivity, particularly Ferring’s Prepopik.
• The Commissioner should adopt Petitioners’ statutory interpretation immediately.  The Commissioner’s decision to implement the interpretation prospectively at some indefinite future date (i.e., through final guidance) is arbitrary and capricious action that cannot be considered reasonable when all relevant factors are considered.

Among other things, Ferring highlights an alleged “irrational and arbitrary nature” of FDA’s application of the Agency’s “old rules” concerning NCE exclusivity for FDCs containing a new and a previously approved drug, and cites FDA’s recent approval of NDAs for alogliptin as a prime example.  As we previously reported, in the case of alogliptin, FDA approved three NDAs on the same day – one NDA for single-entity alogliptin (NDA No. 022271), and two NDAs for FDCs containing alogliptin and a previously approved drug (NDA Nos. 022426 and 203414).  FDA was careful to note that single-entity alogliptin (NDA No. 022271) was approved first in the day, thereby preserving NCE exclusivity for NDA No. 022271, and allowing that NCE exclusivity to apply under the Agency’s “umbrella exclusivity policy” to the other two approved NDAs.  According to Ferring:

This concocted process [] clearly shows the arbitrary nature of FDA’s current interpretation of the [statute’s] exclusivity provisions.  Based on FDA’s current (i.e., pre-Citizen Petition) policy on exclusivity, if either of the combination products had been deemed to have been approved first, none of the products would have been able to obtain five years of exclusivity, regardless of the fact that the same amount of effort would have been involved in the drug development process.  These conclusions produce precisely the type of result that courts have feared, whereby exclusivity periods are based on the order of NDA approval rather than any scientific, technical, economic, or other rationale.  Interpretation of the statute in a manner that permits such outcomes, when there is an alternate valid interpretation (one which FDA acknowledges in its decision), is arbitrary and capricious in violation of the Administrative Procedures Act (“APA”).  FDA’s approach here highlights the fears raised by the courts about the Agency juggling or manipulating the timing of approvals to accomplish a preconceived goal that affects intellectual property (here, market exclusivity) rights.  In fact, it raises those fears by orders of magnitude.

Ferring also objects to FDA’s decision to announce a new interpretation of the FDC Act’s NCE exclusivity provisions in guidance.  According to Ferring, that decision was legally incorrect and creates significant regulatory uncertainty:

This decision to issue draft guidance for public comment was legally incorrect because draft guidance is not binding, does not create or confer rights, is intended to help industry carry out its obligations, and may be deviated from in appropriate circumstances.  FDA’s change in statutory interpretation here is in fact binding, does create rights, is meant to help FDA (not industry) carry out an obligation, and cannot be departed from lest individual FDA reviewers decide to award exclusivity however they see fit.  Guidance is therefore not the appropriate legal means to implement FDA’s change in statutory interpretation with respect to NCE exclusivity for fixed-combination drug products. [(Emphasis in original)]

Instead, says Ferring, FDA should have regulated directly from the statute and immediately implemented its new interpretation of the NCE exclusivity provisions. 

Clearly, the battle over NCE exclusivity for FDCs is far from over.  To date, there has been verly little comment on FDA’s proposed reinterpretation of the FDC Act’s NCE exclusivity provisions.  Docket watchers will be looking closely at the docket this week as the 60-day comment period draws to a close.  And speculation on the timing of a final guidance will likely begin to grow.      

 By Kurt R. Karst –  

When we first heard about the Complaint and Motion for Preliminary Injunction Zogenix, Inc. filed against Massachusetts Governor Deval Patrick, among others, alleging that the Commonwealth’s ban on FDA-approved ZOHYDRO ER (hydrocodone bitartrate) Extended-release Capsules is unconstitutional because the ban violates the Supremacy Clause of the U.S. Constitution (as well as the dormant Commerce Clause and the federal Contracts Clause), we thought Zogenix would have a pretty good shot at a quick win on preemption grounds.  But we were concerned about the implications a win for the Commonwealth could have on FDA’s stamp of approval – would it undermine FDA and the drug approval process? (See our previous post here.)  

As it turns out, after some briefing by the parties (see here, here, and here), the U.S. District Court for the District of Massachusetts does not think Governor Patrick has much of a case.  Earlier this week, the court allowed Zogenix’s motion for preliminary injunctive relief and enjoined, until April 22, 2014, the Commonwealth from taking any action to implement or enforce Governor Patrick’s March 27, 2014 Declaration of Emergency and the March 27th order of the Commissioner of the Department of Public Health banning the sale and distribution of ZOHYDRO ER. 

The court nicely teed up the preemption issue and swung through to a conclusion that the U.S. Constitution does not allow the Commonwealth to second guess FDA drug approval decisions:

The FDA endorsed Zohydro ER’s safety and effectiveness when it approved the drug.  When the Commonwealth interposed its own conclusion about Zohydro ER’s safety and effectiveness by virtue of DPH’s emergency order, did it obstruct the FDA’s Congressionally-given charge?

I conclude that it did.  The FDA has the authority to approve for sale to the public a range of safe and effective prescription drugs—here, opioid analgesics.  If the Commonwealth were able to countermand the FDA’s determinations and substitute its own requirements, it would undermine the FDA’s ability to make drugs available to promote and protect the public health.  See Geier v. Am. Honda Motor Co., 529 U.S. 861, 881 (2000).  The Commonwealth’s emergency order thus stands in the way of “the accomplishment and execution of” an important federal objective.  Hines, 312 U.S. at 67.  The Constitution does not allow it to do so.

Governor Patrick relied on the U.S. Supreme Court’s decision in Wyeth v. Levine, 555 U.S. 555 (2009), to support the Commonwealth’s position that the Court not only rejected so-called “obstacle preemption” with respect to the FDC Act, but that consistent with Wyeth, federal regulation (here, FDA drug approval) is a floor and not a ceiling.  That is, according to the Commonwealth, states can regulate over and above FDA.  But the district court rejected the Commonwealth's reliance on Wyeth for both points.  After noting that “obstacle preemption” is alive and well with respect to the FDC Act and that “Wyeth simply concluded that Congress did not view state tort suits as an obstacle to achieving the FDA’s purposes,” the district court continued with respect to the Commonwealth's second use of Wyeth:

Wyeth is a drug labeling case, and defendants present no evidence or persuasive argument that its reasoning should control in this different context.  Furthermore, Wyeth assumed the availability of the drug at issue and analyzed whether stronger state labeling requirements obstructed the FDA’s objectives.  Here, the obstruction is clearer because the drug Massachusetts wants Zogenix to adopt—Zohydro ER with an “abuse-resistant formulation”—has not been approved by the FDA.  To satisfy the Commonwealth, Zogenix would be required to return to the FDA and seek approval of a drug different from the one the FDA has already deemed safe.

Thus far things are looking well for Zogenix.  And they are likely to stay that way . . . at least in Massachusetts.  Whether or not the recent ruling in Massachusetts will now prompt federal lawmakers to push forward on legislation to withdraw the approval of ZOHYDRO ER (i.e., S. 2134 and H.R. 4241) remains to be seen.  There has not been much action on either bill since they were introduced on March 13, 2014. 

By Riëtte van Laack –

Legislation that would require labeling of genetically engineered or bioengineered foods (generally referred to as “GMOs”) has been proposed in various states.  If enacted, these state laws may expose companies to a patchwork of different GMO labeling requirements. 

On April, 10, 2014, Representatives Mike Pompeo (R-KS) and G. K. Butterfield (D-NC) introduced legislation that would nullify the efforts in multiple states to require labeling of GMOs.  H.R. 4432, the “Safe and Accurate Food Labeling Act of 2014” (“SAFLA”), would amend the FDC Act to include a provision preempting any state requirement regarding the sale, distribution, or marketing of a bioengineered organism intended for food use or application, and regarding food products from, containing, or consisting of a bioengineered organism.  We note that this clause does not appear to allow state laws that are identical to the federal law. 

SAFLA would require premarket review the safety of GMOs.  A company would be required to submit a premarket biotechnology notification to FDA at least 210 days before introduction into commerce of a GMO.  This notification would provide FDA with information about the notifier’s determination that food produced from or containing the GMO is as safe as the food from the non-GMO variety.  FDA would get 30 days to inform the notifier that the notification is complete or identify missing information.  Once FDA has informed the notifier that the notification is complete, the Agency would get 180 days for substantive review of the notification.  If FDA decides that the GMO variety is safe but materially different from the non-GMO variety and that disclosure of this material difference is necessary to protect the health and safety of consumers or to prevent the labeling from being false and misleading, FDA may require specific labeling for the GMO variety.

Although the bill essentially would prohibit mandatory GMO labeling unless FDA determines that such labeling is necessary, it specifically would allow “non-GMO” claims.  Such claims would be permitted only if the ingredients are subject to certain supply chain process controls and meet certain limits for the presence of inadvertent GMOs.  FDA is to promulgate regulations that specify a maximum level of inadvertent GMOs that would be permissible in non-GMO foods.

The bill also addresses natural claims.  It would require that FDA issue regulations defining “natural” within 12 months after enactment of the law.  FDA has previously declined to address the term for courts (see our prior post here), but was recently petitioned to promulgate a regulation.

By Ricardo Carvajal & Diane B. McColl –

When GAO issued its 2010 report criticizing FDA’s oversight of the GRAS exception, we were motivated to respond first in short form in a blog post, and then in long form through a Washington Legal Foundation Legal Backgrounder.  In the years since, attacks on the GRAS exception have grown increasingly shrill and detached from reality, so we thought it would be a worthy exercise to begin cataloguing the principal errors and mischaracterizations underpinning those attacks.  Even if one presumes that FDA’s oversight of the GRAS exception needs to be improved, knowing which improvements would be beneficial would require an accurate diagnosis of where problems might lie.  Many of the diagnoses offered thus far are based on unwarranted assumptions, erroneous analyses, and factual misrepresentations.  The catalogue of such flaws has grown so vast that we don’t aim to complete our task in a single blog posting – thus the designation of this posting as Part 1 of a series that we’ll continue in the coming weeks.

We begin with the report that the Natural Resources Defense Council ("NRDC") released earlier this week, Generally Recognized as Secret: Chemicals Added to Food in the United States.  That report contends that the GRAS exception is “the loophole that swallowed the law.”  According to the revisionist history of the Food Additive Amendments of 1958 ("FAA") offered in the report:

The 1958 law exempted from the formal, extended FDA approval process common food ingredients like vinegar and vegetable oil that are “generally recognized as safe” (GRAS). It may have appeared reasonable at the time, but that exemption has been stretched into a loophole that has swallowed the law. . . .

Congress concluded that the FDA would make all safety decisions, except in the most obvious situations in which a chemical’s use in food was “generally recognized as safe.”  This is known as the GRAS exemption.  Examples include such common food ingredients as oil and vinegar.

The suggestion that the GRAS exception was intended only for common household food ingredients like oil and vinegar is repeated on NRDC’s website, both in text and video formats (see here).  That suggestion is, at the least, misleading.

In passing the FAA, Congress was well aware that numerous substances other than common food ingredients would be eligible for GRAS status.  That is evident in FDA’s first GRAS list, which was published shortly after the law’s passage.  In publishing that list, FDA stated: 

It is impractical to list all substances that are generally recognized as safe for their intended use. However, by way of illustration, the Commissioner regards such common food ingredients as salt, pepper, sugar, vinegar, baking powder, and monosodium glutamate as safe for their intended use.  In addition, the following lists include some substances that, when used for the purposes indicated, in accordance with good food manufacturing practice, are regarded by the Commissioner as generally recognized as safe for such uses. [(Emphasis added.)] 

The lists compiled by FDA included dozens of substances in the categories of buffers and neutralizing agents, sequestrants, antimycotics, antioxidants, nonnutritive sweeteners, and emulsifying agents, among others.  The existence of FDA’s first GRAS list is known to the authors of the NRDC report because they cited to it in one of their earlier PEW publications (see Navigating the U.S. Food Additive Regulatory Program, at 347).  Evidently, acknowledging the variety and nature of the substances on the first GRAS list has grown inconvenient, as it undermines one of the NRDC report’s central claims – namely that both FDA and industry have perverted the original purpose of the law.

Even a cursory reading of the FAA’s legislative history makes clear that the law was intended to achieve two principal purposes, only one of which was to ensure the safety of substances added to food.  The other principal purpose, increasingly ignored by critics, was to avoid unnecessarily impeding innovation in the food supply.  In that respect, the GRAS exception has played a pivotal role, and its continuing utility should come as no surprise given the increasingly sophisticated analytical tools available to experts in the field of food toxicology.  The flexibility afforded by the GRAS exception is such that FDA relied on it with great success in developing its regulatory paradigm for bioengineered foods – a technological advance that certainly was not on the Congressional radar in 1958.  In summary, continued reliance on the GRAS exception is perfectly consistent with the twin purposes of the FAA, and has yielded the added benefit of enabling both industry and FDA to direct their food safety resources to areas where those resources can yield a greater return on investment – a significant benefit given the anticipated costs of implementing FSMA.

Another of the report’s central claims is that GRAS determinations are plagued with conflicts of interest because companies have a financial incentive to sell their products, and the fear of legal liability and damage to reputation are insufficient to counter that incentive.  In support of that contention, the report states:

The FDA has acknowledged that a company’s potential liability and its interest in protecting its brand are insufficient to ensure that food is safe.  In 2013 the agency said, “Because the demand for many manufactured or processed foods may not be sufficiently affected by safety considerations, incentives to invest in safety measures from farm to fork is diminished. Consequently, the market may not provide the incentives necessary for optimal food safety.”  “Even in cases where consumers are aware that their illness was contracted from a specific food,” the FDA explained, “it is often difficult to determine who is ultimately responsible for their illness, since the particular source of contamination is not known in many circumstances.”  It concluded that “it is unlikely that the existence of brands in the food sector creates the optimal level of safety for society.”

As a supporting reference, the report cites to FDA’s Preliminary Regulatory Impact Analysis for the Proposed Rules for Current Good Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for Human Food.  However, a review of that document reveals another inconvenient fact.  The quoted statements were made in the context of unintentional contamination of food.  In that context, it stands to reason that tracing an illness back to a specific product manufactured by a specific company is very challenging, and therefore the likelihood that the responsible company would be held accountable is diminished.  That logic does not apply in the context of the intentional use of an ingredient that is declared on a product’s label.  Indeed, NRDC had no difficulty identifying specific ingredients, products, and companies to target in its current report.

The relative ease with which a product can be identified is not the only factor that distinguishes the food ingredient context from the unintended contaminant context.  In the food ingredient context, FDA doesn’t have to show that the ingredient actually caused harm in order to challenge its use as an unapproved food additive; it is enough for FDA to show that general recognition of safety of the use of the ingredient is lacking.  The power of FDA’s enforcement tools in that context is amply demonstrated by some of the agency’s recent activities.  For example, FDA has issued warning letters to distributors of foods that contain melatonin (see here and here). The letters contend that FDA is unaware of any basis to conclude that the use of melatonin as a food ingredient is GRAS, and therefore the product in question is adulterated by virtue of containing an unapproved food additive.  FDA does not assert that the products in question actually caused injury because the agency doesn’t have to make that showing.

Similarly, when FDA announced its intent to investigate the safety of caffeine in food products, the mere expression of FDA’s concern was sufficient to prompt a number of companies to stop distribution.  That announcement followed on the heels of FDA’s prior warning letters targeting certain caffeinated alcoholic beverages, which the manufacturers subsequently stopped distributing.  These actions and industry’s response thereto give the lie to any claim that FDA’s ability to address potentially unlawful uses of food ingredients is hampered by the agency’s inability to show harm.  If anything, the challenge FDA faces in exercising its food additive authority lies in doing so judiciously, as illustrated by the agency’s recent, sweeping proposal to revoke the GRAS status of partially hydrogenated oils.

In closing out Part 1, we note that, whereas some critiques of the GRAS exception have been intended to enlighten, the current critique appears primarily intended to frighten.  The narrative is simple – profit-hungry companies are using unsafe chemicals in food to pump up their bottom lines, under the lazy eye of an agency that relies on outmoded science and an antiquated law.  While that narrative might provide a nice fund-raising platform for an NGO, it contributes little to the reasoned discourse needed to evaluate whether and how the existing system might be improved, and which improvements might yield benefits commensurate with their costs.  In that vein, we note that industry is stepping up to the plate with the establishment of a Center for Research on Ingredient Safety ("CRIS") in conjunction with Michigan State University.

By Riëtte van Laack –

In 2006, the American Beekeeping Federation and honey industry groups petitioned FDA (Docket No. FDA-2006-P-0207) to adopt a standard of identity for honey.  In 2011, FDA denied this petition because it concluded that no standard of identity was needed.  FDA asserted that existing enforcement tools could achieve petitioners’ goals. 

On April 9, 2014, FDA announced the availability of a draft guidance on the proper labeling of honey and honey products.  According to FDA, this draft guidance addresses the labeling issues relevant to the 2006 petition and reinforces existing laws and regulations to the industry.

FDA broadly defines honey as “a thick, sweet, syrupy substance that bees make as food from the nectar of flowers and store in honeycombs.”  The guidance does not address whether honey that has been subjected to ultrafiltration, removal of pollen, etc., qualifies as honey.  Instead it focuses on the labeling of honey with added sweeteners and other substances, and on the possible contamination with illegal pesticides.

The draft guidance includes a list of questions and answers including how and when to declare the floral source of honey, how to label products that contain honey and a sweetener, or honey and another ingredient such as natural flavors.

FDA notes that it has a “long-standing” import alert for surveillance of honey for adulteration with cane or corn sugars. The imported products are not admitted until FDA determines that they are not misbranded.

Although anyone can comment on any guidance at any time, to ensure that FDA receive and consider comments before finalizing the guidance, comments should be submitted by June 9, 2014.

By James C. Shehan –

The Generic Pharmaceuticals Association (“GPhA”) opened a new front in its ongoing battle to shape the approval process for biosimilars, while also calling for more cooperation between the US and the EU in their oversight of traditional generic drugs.  In a joint letter to the European Commission’s Trade Commissioner and the US Trade Representative, GPhA and the European Generic medicines Association (“EGA”) made recommendations that “regulatory convergence” be included in the negotiations for the Transatlantic Trade and Investment Partnership (“TTIP”).  TTIP is a prospective trade agreement that is currently being negotiated between the European Union and the United States.  It is intended to remove trade barriers in a wide range of economic sectors to make it easier to buy and sell goods and services between the EU and the US.

The GPhA/EGA letter makes five specific recommendations for inclusion in TTIP:

1. Implement a single development and approval pathway for biosimilars, via adoption of appropriate  guidelines/guidances by both regulators and facilitated by work of the existing FDA-EMA “cluster” group that currently exchanges information on biosimilars; 
2. Implement a single development and approval pathway for traditional generic medicines, again via adoption of appropriate  guidelines/guidances by both regulators and facilitated by establishment of a new FDA-EMA cluster that would meet regularly to exchange information; 
3. Mutually recognize cGMP inspections; 
4. Allow manufacturers to make generic and biosimilar products during the periods of US patent term extension and EU Supplementary Protection Certificates, so that (i) generic products made in the US and the EU can be exported for sale to the rest of the world prior to patent expiration and (ii) generic products can launch in the US and the EU immediately after patent expiration; and
5. Reject any suggestion to harmonize the US and EU  intellectual property regimes, specifically by rejecting any alignment of the periods of data and market exclusivity enjoyed by innovators.

It’s worth noting that in the context of TTIP, there is a difference between “convergence” and “harmonization.” Convergence refers to making separate systems work more smoothly together, while harmonization refers to adoption of the same system.  The European Commission’s website specifically notes that harmonization is “not on the agenda” for TTIP.  There may be some difficulties in squaring “no harmonization” with a “single development and approval pathway.”   

Interestingly, the GPhA/EGA letter is silent on one of most robustly debated biosimilar topics – how those products will be named in the US (see our previous posts here, here, and here).  Under the EU system, biosimilar products have names that are distinguishable from innovator reference product, either by use of a unique brand name or by attaching the company name to the generic name of the active ingredient.  GPhA has opposed proposals to require US biosimilars to have distinguishable nonproprietary names.  At a January meeting with FDA, however, GPhA, indicated that it may be willing to accept attaching a company name to the non-proprietary name, provided that the requirement also applies to brand name companies. GPhA also indicated at that meeting that its members would commit to the using brand names, even though FDA may not have the authority to require brand names.    

TTIP negotiators hope to finish their work in 2015.

By Kurt R. Karst –

When FDA announced on February 21, 2014 that the Agency would, upon finalization of a draft guidance document, reinterpret the New Chemical Entity (“NCE”) exclusivity provisions of the FDC Act to award NCE exclusivity for a newly approved Fixed-Dose Combination Drug (“FDC”) containing an NCE and a previously approved drug, FDA also issued a Consolidated Response denying the three Citizen Petitions submitted to the Agency in 2013 that led the Agency to its new interpretation in the first place.  Those petitions concerned STRIBILD (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate) Tablets (Docket No. FDA-2013-P-0058), PREPOPIK (sodium picosulfate, magnesium oxide and citric acid) for Oral Solution (Docket No. FDA-2013-P-0119), and NATAZIA (estradiol valerate and estradiol valerate/dienogest) Tablets (Docket No. FDA-2013-P-0471).  Now one of the petitioners – Gilead Sciences, Inc. (“Gilead”) – is asking FDA in a Petition for Reconsideration to rethink that decision with respect to STRIBILD, and to refuse to accept any ANDA or 505(b)(2) application for a drug product containing either of the two NCEs in STRIBILD – elvitegravir and cobicistat – under the rules governing NCE exclusivity.

As we previously reported, FDA decided to apply its new interpretation prospectively upon finalization of the draft guidance.  FDA explained in the Consolidated Response the Agency’s rationale for this decision and the bases for not granting the three petitions and awarding NCE exclusivity:

Exclusivity runs from the date of approval of a drug product.  At the time of approval of the drug products at issue here (i.e., Stribild, Natazia, and Prepopik), our existing interpretation of the relevant statutory and regulatory provisions was in effect.  We have decided not to recognize 5-year NCE exclusivity based on our new interpretation of these provisions, which we had not announced prior to the approval of these products . . . .

First, although the relevant statutory and regulatory provisions are ambiguous, our existing interpretation of these provisions is longstanding and has been consistently applied in many prior cases presenting similar facts.  Second, the new interpretation we are proposing represents a departure from our past interpretation, and we wish to avoid any unnecessary disruption to regulated industry.  Third, if the new interpretation were to be applied to products for which ANDAs already have been filed, it could impose a burden on the ANDA sponsors, who relied on our existing interpretation in filing their applications.

In addition, we do not believe that applying our new interpretation to the Petitioners’ products would advance the goals of the Hatch-Waxman Amendments.  Although we recognize that the Hatch-Waxman Amendments contain incentives to reward the development an approval of novel drugs, these particular products already have been developed and approved.  Recognizing additional exclusivity in this case is not necessary to encourage the development of novel drugs.  We believe that changing our interpretation going forward will foster Congress’s goal of encouraging the development and approval of novel drugs.  (Emphasis in original.)   

But according to Gilead, none of these reasons fit the circumstances surrounding STRIBILD.  First, with respect to FDA’s concern that recognizing NCE exclusivity would burden sponsors with pending applications, Gilead says that to its knowledge FDA has not yet even accepted an ANDA or 505(b)(2) application citing STRIBILD as the listed drug relied on for approval.  Second, as to FDA’s rationale that the STRIBILD approval was made when the “old” rules were (and still are) in effect, Gilead says that “the date of approval is not the relevant date . . . because FDA made the decision to defer the exclusivity determination for STRIBILD.”  Moreover, says Gilead, the company “raised the 5-year NCE exclusivity issues early during STRIBILD’s NDA process,” and “requested 5-year NCE exclusivity at the time of submission of the STRIBILD NDA and reiterated its request in a letter submitted to the agency immediately following STRIBILD’s approval.”  Third, FDA’s Hatch-Waxman goals remark misses the mark, says Gilead.  “Gilead developed the new active moieties in STRIBILD with the expectation that they would have 5-year NCE exclusivity,” writes the company.  The STRIBILD NDA was submitted to FDA before the NDAs for elvitegravir and cobicistat because “Gilead recognized during development that pursuing the combination product first would be more beneficial to patients and scientifically feasible.”  Finally, as to FDA’s comment that recognizing NCE exclusivity for an approved FDC would amount to “additional exclusivity,” Gilead says that “nothing additional or gratuitous is being requested,” and that “[a]warding the exclusivity in this instance represents the appropriate statutory recognition for having developed these novel drugs.” 

As to Gilead’s request that FDA refuse to accept any ANDA or 505(b)(2) application for a drug product containing either elvitegravir and cobicistat, the company argues that two key points of interpretation that predate the Consolidated Response require FDA to recognize NCE exclusivity for each active moiety. 

The statutory provisions governing NCE exclusivity – FDC Act § 505(j)(5)(F)(ii) (and its sister provision at Section 505(c)(3)(E)(ii)) – contain both an “eligibility clause” and a “bar clause.”  Under the “eligibility clause,” a drug is eligible for 5-year NCE exclusivity if it is “a drug, no active ingredient (including any ester or salt of the active ingredient) of which has been approved in any other [505(b)] application.”  Under the “bar clause,” the submission of any ANDA (or 505(b)(2) application) that “refers to the drug for which the [505(b)] application was submitted” is prevented for 5 years (absent a Paragraph IV certification).  Under FDA’s revised interpretation as described in the Consolidated Response, the term “drug” in the “eligibility clause” of the statute (and in the regulatory definition of NCE at 21 C.F.R. § 314.108) refers to drug substance, not drug product.  But what about the statutory “bar clause”?

According to Gilead, FDA agreed in the Consolidated Response that under the “bar clause” the term “the drug” has historically been interpreted under FDA’s so-called “umbrella policy” to mean a particular active moiety rather than a drug product.  Under that policy, described in various places in the preamble to the 1989 proposed regulations implementing the Hatch-Waxman Amendments, FDA interpretes NCE exclusivity:

to cover any subsequent approval of an application or supplemental application for a different ester, salt, or other noncovalent derivative, or a different dosage form, strength, route of administration, or new use of a drug product with the same active moiety.  Any modification to the product will be protected for the period of exclusivity remaining on the original application, unless the change occurs after or toward the end of the initial 5 years of exclusivity and independently qualifies for exclusivity under another exclusivity provision. [54 Fed. Reg. 28,872, 28,898-99 (July 10, 1989)]

“In light of that clear and appropriate interpretation, it is not plausible that the term ‘a drug’ in the [eligibility] clause . . . could mean something different,” says Gilead.  “Here, the meaning specifically adopted by the agency is that the ‘drug’ at issue in the exclusivity provision is a specific active moiety,” and not a drug product.

Furthermore, FDA long ago incorporated this active moiety-specific interpretation of the “bar clause” into the Agency’s implementing regulation at 21 C.F.R. § 314.108(b)(2), argues Gilead.  That regulation prevents for 5 years (absent a Paragraph IV certification) the submission of an ANDA or 505(b)(2) application that references “a drug product that contains a new chemical entity” (emphasis added).  “A drug product cannot ‘contain’  another drug product; it may contain drug substances and moieties, but not other drug products.”  Thus, argues Gilead, FDA’s bar regulation “is designed to provide the same scope of protection – namely, moiety-specific protection – as the bar clause in the statute, based on FDA’s clear and reasonable interpretation of the statute.”

By Riëtte van Laack –

Does the same standard that applies when regulators require label statements that “correct a deception,” such as false advertising, also apply when they require label statements for other purposes based on the interests of the government?  This issue will be before the United States Court of Appeals for the District of Columbia Circuit (“D.C. Circuit”) en banc in the rehearing of the appeal by American Meat Institute and others (“AMI”) challenging the U.S. Department of Agriculture’s (“USDA’s”) regulations requiring mandatory country of origin labeling (“COOL”) statements.  (See our previous posts here, here, and here.) 

AMI had argued that the government does not have a good enough reason to override the industry’s free speech rights and force them to make statements against their will.  According to AMI, the more demanding test of Central Hudson Gas & Electric v. PSC of New York, 447 U.S.56 (1980) ought to apply rather than the lesser standard of Zauderer v. Office of Disciplinary Counsel, 471 U.S. 626, 651 (1985), because the COOL regulation was not an anti-deception regulation.  Under Zauderer, a commercial speaker has only a minimal First Amendment interest in not providing purely factual information with which it does not disagree, as long as the mandatory disclosure is reasonably related to the state’s interest in preventing or correcting deception.  The three judge panel of the D.C. Circuit, in a unanimous decision decided to follow other circuits that held that the Zauderer standard applies to more than disclosures that correct deception.  For example, in reaching its decision, the panel noted that the Second Circuit had extended it to “government interests in telling buyers that mercury-containing light bulbs do contain mercury and may not be disposed of until steps have been taken to ‘ensure that [the mercury] does not become part of solid waste or wastewater.’” The Court determined that previous D.C. Circuit decisions that AMI cited in its favor did not apply because those cases did not involve purely factual and uncontroversial information.  However, in a footnote it suggested that the full court hear the case en banc to provide a clear ruling on the issue.

Rehearings en banc are relatively rare.  The D.C. Circuit’s Handbook of Practice and Internal Procedures notes “Federal Rule of Appellate Procedure 35(a) expressly states that en banc hearings are not favored and ordinarily will not be ordered except to secure or maintain uniformity of decisions among the panels of the Court, or to decide questions of exceptional importance.”  Under the Circuit procedures, “[t]he Court sitting en banc consists of all active judges, plus any senior judges of the Court who were members of the original panel and wish to participate.”  Of the court’s senior Judges, only Judge Williams was a member of the original panel. 

On April 4, 2014, the D.C. Circuit issued an order setting the case for rehearing en banc.  Parties are to file supplemental briefs by April 21, 2014 addressing “[w]hether, under the First Amendment, judicial review of mandatory disclosure of ‘purely factual and uncontroversial’ commercial information, compelled for reasons other than preventing deception, can properly proceed under Zauderer . . . or whether such compelled disclosure is subject to review under Central Hudson.”  Oral argument before the en banc court is scheduled for 9:30 a.m. on Monday, May 19, 2014.

By Kurt R. Karst –    

Shortly after Massachusetts Governor Deval Patrick issued a press release on March 27, 2014 announcing a Declaration of Emergency and that the Governor had directed the Massachusetts Department of Public Health (“DPH”) and its Commissioner, Cheryl Bartlett, RN, to take several actions to combat opioid overdose, including granting DPH “emergency powers” to, among other things, ban the prescribing and dispensing of ZOHYDRO ER (hydrocodone bitartrate) Extended-release Capsules, rumors began to swirl that the manufacturer of the drug, Zogenix, Inc. (“Zogenix”), would take legal action.  Those rumors intensified when later on March 27, 2014 the DPH Commissioner Bartlett and the Public Health Council approved an Emergency Order stating: “No registered individual practitioner shall prescribe or order, and no one shall dispense or administer any hydrocodone bitartrate product in hydrocodone-only extended-release formulation until the Commissioner has determined that adequate measures are in place to safeguard against the potential for diversion, overdose and abuse.” 

Less than two weeks after Governor Patrick’s announcement, and now that other states are considering (or taking) similar action (e.g., Vermont recently issued an emergency rule that will reportedly make it more difficult for physicians to prescribe the drug within state limits), Zogenix is taking a stand.  Earlier this week, Zogenix filed a Complaint and a Motion for Temporary Restraining Order and Preliminary Injunction in the U.S. District Court for the District of Massachusetts alleging that the Commonwealth’s ban on ZOHYDRO ER is unconstitutional because the ban violates the Supremacy Clause, the dormant Commerce Clause, and the federal Contracts Clause of the U.S. Constitution:

To put it in plain terms: the Order banning Zohydro™ ER is unconstitutional.

To begin with, it is preempted by federal law.  FDA, not Governor Patrick and not the State DPH, has the authority to approve new drugs, to determine the formulations that are safe and effective for use, and to authorize their introduction into the interstate market.  And after extensive consideration, FDA approved Zohydro™ ER in its current formulation, finding it safe and effective for use in treating patients with chronic pain for whom their physicians conclude Zohydro™ ER is indicated.  Neither Governor Patrick nor the state DPH has the authority or the ability to countermand that determination and declare Zohydro™ ER unsafe in its current formulation.  The Order also runs afoul of the dormant Commerce Clause, which prohibits a state from taking a regulatory action that has impact outside its borders, or if which replicated would result in the effective dismantlement of a national regulatory scheme.  And it violates the federal Contracts Clause, because the Order undoes private contracts between Zogenix and other contracting parties for services in Massachusetts, all without sufficient justification. 

FDA approved ZOHYDRO ER on October 25, 2013 under NDA No. 202880 after an extended review cycle for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.  ZOHYDRO ER is manufactured without an abuse-deterrent formulation, and that fact has made the approval controversial.  Indeed, several members of Congress have sent letters to FDA protesting the approval, and legislation has been introduced to withdraw the NDA approval (S. 2134 and H.R. 4241).  Nevertheless, ZOHYDRO ER remains an approved medication.  And as Zogenix points out in its lawsuit:

In rendering a considered decision that the benefits of Zohydro™ ER outweighed the drug’s potential risks, the FDA satisfied Congress’s dual mandate of promoting and protecting public health by classifying Zohydro™ ER as “safe and effective,” consistent with its obligations under 21 U.S.C. § 393(b)(2)(B).  That determination reflects the FDA’s expert conclusion that public access to the drug “promote[s]” the public health.

Thus, Zogenix argues that the Commonwealth’s ban on ZOHYDRO ER:

stands as an impermissible obstacle, in two ways, to the FDA’s mandate to make particularized drug approvals for the protection and promotion of the public health.  First, . . . state drug prohibition decisions contrary to those of the FDA – such as the Massachusetts ban here – would harmfully undermine the authoritative character of federal safety decisions designed to have national effect. . . .  Second, the Massachusetts order plainly conflicts with the scientific predicates supporting the FDA’s approval of the same drug Massachusetts wants banned – and thus with Congress’ objective to promote public health by facilitating access to important treatments.

Zogenix is seeking, among other things, declaratory and injunctive relief.  Specifically, Zogenix seeks a declaration that Governor Patrick’s and DPH Commissioner Bartlett’s conduct in effectuating a ban on ZOHYDRO ER violates the U.S. Constitution, and final order enjoining Massachusetts from implementing or enforcing the Declaration of Emergency, the Emergency Order (or any other action banning the prescription, ordering, dispensing, and administration of ZOHYDRO ER), or an order vacating those actions.  A hearing was held on April 8th regarding Zogenix's Motion for Temporary Restraining Order and Preliminary Injunction.  Judge Rya W. Zobel granted a continuance to allow the parties some additional time.  A hearing is now scheduled for April 14th at 9:00 AM.

Massachusetts’ action banning ZOHYDRO ER, and Zogenix’s response to that action, seems to be a case of first impression.  We’re not aware of another lawsuit like it.  A decision in favor of the Commonwealth could set the stage for future state action against particular drug products, and could undermine FDA’s drug approval authority.  During the April 8th hearing, however, Judge Zobel reportedly indicated that she will likely strike down the ban, presumably on preemption grounds. 

By Jennifer M. Thomas & James P. Ellison –

Hyman, Phelps & McNamara, P.C. (HP&M) filed comments on April 7 concerning FDA’s Guidance document, Investigational New Drug Applications (INDs) — Determining Whether Human Research Studies Can Be Conducted Without an IND (the “Guidance”).  HP&M has previously blogged on this Guidance (here, here, here, and here).

HP&M’s comments on the Guidance focus on the legal issues that the Guidance raises.  Most important, through the Guidance FDA seeks to impose on food, medical food, dietary supplement and cosmetics the same pre-study requirements that the law properly authorizes for drug studies.  However, FDA has no legal authority to impose these requirements on non-drug studies, as HP&M’s comments make clear.  The negative public health impacts of FDA’s unauthorized Guidance, while not the primary focus of these comments, would be profound.  HP&M’s comments point out that the only appropriate solution is for FDA to remove references to foods and cosmetics from the Guidance and to revise the Guidance to make it consistent with the authority granted to FDA under the Federal Food, Drug, and Cosmetic Act.

Spring is here!  How do we know?  Is it the cherry blossoms in peak bloom in Washington, DC?  Is it the daffodils emerging from hibernation?  No – we know it’s Spring because the annual American Conference Institute (“ACI”) “Paragraph IV Disputes” conference is right around the corner. 

That’s right, ACI will be holding its 8th annual “Paragraph IV Disputes” conference from April 28-29, 2014 at the Conrad New York in New York City.  The 2014 conference is a special one with the 30th Anniversary of the Hatch-Waxman Amendments later this year (September 24, 2014).  Attendees will get to hear from a virtual “who’s who” of Hatch-Waxman litigators and industry decision makers.  Hyman, Phelps & McNamara, P.C.’s Kurt R. Karst will be speaking at a session assessing implementation of the Generic Drug User Fee Amendments and other recent developments that affect Paragraph IV litigation.

FDA Law Blog is a conference media partner.  As such, we can offer our readers a special $200 discount off the current price tier.  The discount code is: FDA200.  You can access the conference brochure and sign up for the event here.  We look forward to seeing you at the conference.  

The American Bar Association’s Section of Ligation (specifically the Food and Supplements Subcommittee of the Products Liability Committee) just announced its Fourth Annual Food & Supplements Workshop, scheduled for June 5 in the Minneapolis area.  Among the topics to be addressed:

• Emerging Issues: Surveying the Regulatory and Litigation Horizon
• Ethical Issues Arising from Governmental Investigations and Potential Criminal Charges Under the Park Doctrine
• FSMA New Developments
• Consumer Fraud Class Actions—Litigation and Settlement Strategy
• Anatomy of a Recall
• Litigation Risks: How In-House and Outside Counsel Can Work Together to Identify and Preemptively Address Potential Lawsuits Targeting Food and Supplement Products

Hyman, Phelps & McNamara, P.C.’s Ricardo Carvajal will participate in discussion of key issues raised by the latest proposed regulations issued under the authority of the Food Safety Modernization Act.  Additional information and a link to registration are available here.  

By Karla L. Palmer –

The Energy and Commerce Committee’s Subcommittee on Health (chaired by Representative Joe Pitts (R-PA)), has scheduled a hearing for Monday, April 7, 2014, at 3:00 p.m. in room 2123 of the Rayburn House Office Building.

The hearing is titled “Improving Predictability and Transparency in DEA and FDA Regulation.” Industry and government witnesses include, among others, Janet Woodcock, M.D. (Director CDER, FDA), Mr. Joseph T. Rannazzisi (Deputy Assistant Administrator, Office of Diversion Control, DEA);  Dr. Nathan B. Fountain (Chair, Medical Advisory Board, Epilepsy Foundation), and Mr. John M. Gray (President and CEO, HDMA).

Subcommittee members will review three bills described below: H.R. 4299, “Improving Regulatory Transparency for New Medical Therapies Act,”; H.R. 4069, “Ensuring Patient Access and Effective Drug Enforcement Act;” and H.R. 4250, the “Sunscreen Innovation Act”.

H.R. 4299, blogged about here, would amend the CSA to improve efficiency of the DEA’s process for scheduling new drugs approved by the FDA. Introduced by Representative Pitts (R-PA) and Ranking Subcommittee Member Frank Pallone (D-NJ), the bill would require DEA to make a final determination within 45 days after receiving FDA’s scheduling recommendation for a new drug.  Additionally, it would generate more transparency in the drug application process for clinical trials by requiring that DEA make a final determination within 180 days or provide the applicant with details about what outstanding issues remain unresolved.

H.R. 4069, introduced by Vice Chairman Marsha Blackburn (R-TN), Rep. Tom Marino (R-PA), would improve enforcement efforts regarding controlled substance drug diversion and abuse.  The legislation would help prevent controlled substance abuse and diversion, yet ensure patient access to necessary medications by creating a collaborative partnership between drug manufacturers, wholesalers, retail pharmacies and federal enforcement and oversight agencies.  

The bill also seeks to better define standards set forth in the CSA including the definition of “consistent with the public health and safety” as having a “substantial relationship” to the CSA’s “purpose of preventing diversion and abuse of controlled substances.”  In addition, the legislation would further define “imminent danger” as meaning “a significant and present risk of death or serious bodily harm that is more likely than not to occur in the absence of an immediate suspension order.” (Emphasis added.)   This enhanced definition of “imminent danger” may be a fallout from DEA decisions to issue immediate suspension orders against at least two drug distributors and at least one nationwide retail pharmacy in the past few years where the subject of those immediate suspension orders involved conduct that occurred — and typically had resolved – well prior to DEA’s serving of the immediate suspension orders, causing the parties to challenge the DEA’s definition and interpretation of what constitutes “imminent danger.” 

The legislation would also require employers (specifically distributors and manufacturers of schedule I though V drugs)  to obtain as a condition of the registration criminal background checks and drug testing for employees with access to controlled substances. The employee background checks must be obtained periodically (not more frequently than every two years) and at the time of hiring (if hired after the date of the enactment of the legislation). Those that fail to comply with the background check provision would be subject to civil penalties. 

The legislation would also permit registrants the opportunity to submit a corrective action plan prior to revocation or suspension of a registration under 21 U.S.C. § 824(c).  Specifically the amendment would require the DEA to provide notice to the registrant of the grounds for revocation or suspension including the citation to specific violations, and give the registrant an opportunity to submit a corrective plan within a reasonable period of time to demonstrate how the registrant plans to correct the grounds for revocation or suspension.  The DEA would then make a determination whether in light of the plan, revocation or suspension proceedings should be discontinued or deferred or additional changes need to be made to the corrective plan. 

Finally, the legislation would also establish the “Combat Prescription Drug Abuse Working Group” to include not more than 20 members (pharmacy, patient groups, manufactures, distributors, hospitals and health care providers, law enforcement, DEA representatives, states attorneys general representatives, and public policy experts, among others).  The (non-paid) Working Group members would, among other things, review and report to Congress on efforts to reduce prescription drug abuse and diversion, examine recommendations for transfer of controlled substances between schedules, and make specific recommendations to reduce diversion and abuse of prescription drugs.  The Working Group would also be responsible for various reports and recommendations for FDA, DEA and various other federal and state agencies on several topics identified in the legislation. 

H.R. 4205, introduced by Representative Ed Whitfield (R-KY) and Rep. John Dingell (D-MI), would expedite the FDA’s approval process for new sunscreen ingredients while maintaining strict safety standards. The FDA has not approved a new sunscreen ingredient in almost two decades. As we previously reported, the legislation would attempt to streamline the drug approval process for sunscreens and provide transparency – through regular reports to Congress. The legislation would require that pending applications are completed within eight months and that new applications reviewed within 11 months.

By John A. Gilbert, Jr. – 

A new bill introduced in Congress, H.R. 4299 (titled “Improving Regulatory Transparency for New Medical Therapies Act”), would significantly streamline the drug scheduling process for new medical therapies and reduce the potential for unnecessary delays in the availability of these needed medicines.  The bill would also require the Drug Enforcement Administration (“DEA” or “Agency”) to make a decision on new registration applications for the manufacturing and distribution of drugs and substances used in clinical trials.  A hearing on the bill is scheduled before the House Energy and Commerce Committee on April 7, 2014.   

As reported here and here, the recent example of the long delay in DEA’s scheduling of Eisai’s FYCOMPA (perampanel) – more than a year after it was approved for marketing by the FDA – highlights the need for a change in the process.  The bill would amend the Controlled Substances Act (“CSA”) to require DEA to issue an interim final scheduling rule within 45 days of receiving a recommendation from the Department of Health and Human Services (“HHS”) to schedule a new drug or substance not previously marketed or scheduled in the United States.  The bill would require DEA to take such action pursuant to the “good cause” exception to issuing a notice of proposed rulemaking under the Administrative Procedures Act (5 U.S.C. § 553(b)(3)(B)).  The interim final rule would be made immediately effective pursuant to 5 U.S.C. § 553(d)(3).

As we discussed previously, scheduling based on the HHS recommendation is reasonable and rational for a new medicine where the drug has not been marketed in the United States and thus there is no actual abuse data available.  Under such circumstances, the HHS and FDA scientific and medical review of the drug is the best source of abuse potential, so scheduling a new drug on this basis is consistent with the public interest.  It also avoids the issue previously reported where Eiasi faced losing a significant period of its patent exclusivity solely because it had to await DEA’s scheduling notice for the newly approved drug.

The bill would also amend the CSA to put a time limit on DEA’s review of an application for a DEA registration to be used only for the manufacture or distribution of a controlled substance for clinical trials.  The DEA would be required to make a decision within 180 days of receiving the application.  If the Agency does not make a decision on the application within this time, the Agency would have to give written notice to the applicant as to any outstanding issues that must be resolved in order to make a final decision on the application and the estimated date on which a decision would be made. 

Neither the CSA nor DEA regulations currently impose any time limits on DEA to decide on whether to grant or deny new applications for any DEA registration.  Imposing such time limits could be beneficial to all applicants – not just manufacturers or distributors for use in clinical trials.  We would like to see such limits imposed on all DEA applications for registration; not just in the narrow context expressed in the bill.  There are some obstacles where the 180-day time limit may be difficult, e.g., where DEA is required to publish a notice in the Federal Register for applications for bulk manufacturing of narcotic drugs; however, in most cases requiring DEA to act on an application within, for example, six months would not likely be an unreasonable burden on the Agency.