By James R. Phelps –

According to recent reports concerning the widely reported “whistleblower” scandal at FDA’s Center for Devices and Radiological Health (“CDRH”), in 2009, the CDRH dissidents involved in the affair, while still employed at FDA, filed a “secret” Federal False Claims Act suit against 15 medical device manufacturers.  (Under the Federal False Claims Act, defendants are not immediately apprised of the existence of the “whistleblower” suits, which are not made public during the pendency of an investigation by Department of Justice officials, who decide whether the suits are to be prosecuted by the government or the individuals themselves.)  In this kind of suit, called a qui tam action, there are allegations that false claims were made in the delivery of services or products, resulting in damages when the government made payments for their use.  Because CDRH employees brought this suit while working as reviewers at the agency, it must be assumed that data submitted to the FDA form a part of the allegations made in the lawsuit. 

These qui tam suits can make a “whistleblowing” plaintiff very wealthy; the idea is that, while the government will recover penalties for purchases when there have been “false claims,” the “whistleblower” who brings the suit will take a cut of the money recovered.  It appears that the suit filed by the FDA dissidents would, if successful, bring them a rich reward.  According to the unsealed Complaint filed in the U.S. District Court for the District of Colorado back in 2009, “Defendant Manufacturers are each liable to the United States for treble the United States’ damages, and an additional amount of $5,500- $11,000 for each false claim.”  That means quite a potential jackpot for the “whistleblowers.”  Indeed, plaintiffs in successful qui tam lawsuits have often received millions of dollars each for serving as plaintiffs in the lawsuits, and, occasionally, tens of millions of dollars.

There was a time, before Hatch-Waxman, and before FDA began collecting fees for its activities, when FDA personnel were not so close to matters of money.  To be sure, they were aware that the regulated companies were paid for their products and services, but the agency was not so directly involved in the financial aspects of the healthcare business, and FDA personnel had no reason to see themselves as participants in financial matters.  That has certainly changed, and it appears that this may have contributed to an environment in which FDA’s review personnel are being distracted from their primary mission.

Within recent memory, an FDA reviewer was convicted of trading stock based on confidential, FDA-sourced information.  And this reported qui tam lawsuit, filed by FDA personnel working inside the agency’s review process, powerfully signals that data submitted for approvals are not being held confidential, as they should be. 

Although the qui tam lawsuit was dismissed after the government declined to intervene, the fact that it could happen undoubtedly does much to erode confidence that submissions are being handled properly.  If such a suit were to proceed, then confidence in FDA’s ability to manage valuable and confidential information will be greatly compromised.

The lawsuit suggests that FDA’s management might well have had reason to believe that the reviewers who filed the qui tam lawsuit were not respecting the law as regards confidentiality, which could serve as justification to be monitoring their e-mails.  However, under the circumstances, it is incumbent upon FDA to advise the public fully concerning the steps it is taking to preserve the statutory framework, within which submissions are made and evaluated, by protecting confidential information. 

Hat tips to BioCentury (Steve Usdin), Forbes (Jon Entine), and The New York Times (Erc Lichtblau & Scott Shane) who first reported on the qui tam lawsuit.

By John R. Fleder –

We have previously reported about the Federal Trade Commission’s (“FTC”) case against POM Wonderful, the maker of pomegranate juice (here, here, here, and here). In the world of FTC advertising cases, this litigation is certainly “big league” litigation.

On September 27, 2010, the FTC filed an administrative complaint against POM Wonderful LLC (“POM”), its sister corporation and three officers of POM (collectively “Respondents”).  The FTC asserted that the Respondents had violated the FTC Act in connection with years of advertisements.  The Commission asserted that POM’s advertising was false and misleading because it made unsubstantiated disease claims.  The FTC sued POM even though it was undisputed that Respondents had invested considerable resources in clinical studies to try to substantiate the claims made in the advertisements.

At the risk of mixing up sports, one is reminded of what former Washington Redskins owner Edward Bennett Williams said about his then Coach and General Manager, George Allen:  “George was given an unlimited budget and he exceeded it.”  In the POM case, we have no doubt that both sides exceeded any budgets they may have allocated to the case.  The filing of the FTC’s Complaint has led to a titanic struggle between the FTC and the Respondents.  They participated in a hotly-contested hearing before an FTC Administrative Law Judge (“ALJ”) that included testimony from many experts on both sides.  The parties also submitted hundreds and hundreds of pages of briefs.

On May 21, 2012, the ALJ issued an “Initial Decision” that made neither side happy.  He ruled that some, but not all, of the ads challenged by the Commission were unlawful.  He issued a cease and desist order against the Respondents.  However, he rejected two key arguments advocated by the FTC, namely that Respondents must possess two double blinded studies before making certain claims and that they should only be permitted to make certain claims if those claims have been precleared by another federal agency, namely FDA.

Both sides appealed that ruling to the five member Federal Trade Commission.  Further briefing ensued.  Once that briefing had been completed, the regular season ended.  It was on to the playoffs.

The next event was a fascinating hearing held at the FTC in Washington on August 23, 2012, presided over by the five FTC Commissioners, all of whom have been nominated by a President and confirmed by the United States Senate. The hearing had all the atmospherics of an appellate court argument.  The FTC’s hearing room was packed with people anxious to hear what is a rare event—a formal hearing before the FTC where the Commissioners function as judges in an adjudicatory proceeding.

The Commissioners entered the room together, taking their seats on a podium above the litigants.  When the hearing ended, the Commissioners got up from the podium, went down to the area where the litigants were seated and shook their hands.  This is a custom that one sees rarely in court cases.  This writer has only seen it in the United States Court of Appeals for the Fourth Circuit.  However, that courtesy by the Commissioners demonstrated how seriously everyone involved took this proceeding.  Indeed, on a number of occasions Edward Lazarus, POM’s Counsel referred to an FTC Commissioner as “Your Honor.”  These references led to a number of comments by the Commissioners indicating that they appreciated the reference.

The argument lasted almost two hours.  POM’s Counsel argued first.  His first argument was that the advertisements at issue did not make the implied claims that the FTC Staff asserted had been made.  Commissioners Rosch and Brill immediately disagreed, saying that it was clear to them that a number of POM’s advertisements had made implied disease claims.  They indicated that they can examine the ads de novo, meaning that they are not bound to give any deference to the ALJ’s analysis of those advertisements.  They also indicated that they can decide the meaning of the ads without needing to examine extrinsic evidence as to the ads’ meaning.

POM then argued that it is legally entitled to say anything that is true.  This comment elicited an immediate response from Commissioner Rosch, who stated that “no you are not,” if POM is making deceptive claims by implication.

There was a substantial discussion about whether the FTC can require POM to substantiate certain of its ads by requiring two adequate and well-controlled clinical studies, which are referred to in this case as RCTs, short-hand for randomized clinical trials.  POM asserted that the FTC has never required RCTs in any litigated case.  Commissioner Rosch disagreed, stating that the FTC required RCTs many years ago in  Thompson Medical Co., 104 F.T.C. 648, 842-43 (1984), aff’d, 791 F.2d 189 (D.C. Cir. 1986), cert. denied, 479 U.S. 1086 (1987) (see here).  POM then sought to distinguish that case from the POM situation.

There was a fascinating exchange between Commissioner Brill and POM’s Counsel with regard to the distinction under the FTC Act between foods and drugs.  POM’s position is that its product is an all-natural food product.  Commissioner Brill indicated that the ALJ erred in his discussion of the characterization of POM’s product.  Commissioner Brill stated that a food product can be deemed a drug product under the FTC Act based on an analysis of the product’s “intended use.”  She said that water can be a drug if it is marketed to cure a disease.

POM argued that it had generated and relied on a huge number of studies and experts to support the claims at issue in this case.  POM argued that in a close case, the case law decided under the First Amendment requires that a “jump ball” goes to the Respondents.  None of the Commissioners explicitly agreed with that position.

However, POM’s argument led to a series of questions and statements by Chairman Leibowitz with regard to POM’s numerous unpaid appearances on television.  Chairman Leibowitz first asked if the FTC Act even applies to statements and claims made by a company official when the company has not paid for the television appearance.  He also asked if POM contended that there is an absolute First Amendment protection for the Respondents in those situations.  POM’s position is that there is First Amendment protection.

FTC Counsel Heather Hippsley addressed the First Amendment issue in some detail.  She asserted that, with regard to liability, there is no First Amendment issue in this case.  She stated that because this is an enforcement action involving allegedly deceptive advertisements, the Respondents have no First Amendment protections for their claims.  She also stated that the unpaid-for appearances were preceded by a substantial marketing campaign by POM designed to give itself free advertising by promoting its products on television shows such as one hosted by Martha Stewart.

The Commissioners engaged FTC Counsel in a discussion regarding one aspect of Staff’s appeal, namely whether the FTC should require that POM can only make certain claims if those claims have been approved by FDA.  FTC Counsel relied on prior FTC Consent Orders as precedent for that proposition.  Commissioner Rosch indicated that he is unaware of any prior litigated precedent for that requirement.  FTC Counsel agreed.  Commissioner Rosch expressed grave concern about relying on prior FTC Consent Orders as precedent for this requirement.  Commissioner Ramirez weighed in on this topic asking whether FDA preclearance was too harsh and would violate the First Amendment.  Commissioner Rosch then suggested that it may not be appropriate for the FTC to tie itself too closely to FDA, adding that the FTC had earlier distanced itself from FDA requirements in the Daniel Chapter One case (see here).  FTC Counsel vigorously defended the Staff’s request to have an order entered with this preclearance requirement.  She contended that the content of POM’s advertisements demonstrated that the FTC could not trust POM to decide even when two RCTs would be required to substantiate a claim.

Commissioner Brill asked if someone other than the FDA should be entrusted to preclear POM’s claims.  FTC Counsel responded that if the Commission is unwilling to impose a requirement that POM get FDA preclearance, the Commission should require two RCTs.

So what happens now?  Under the Commission’s rules, we can expect a decision by early December 2012.  If the decision goes against the Respondents, they can challenge the FTC’s ruling in a Court of Appeals.  My guess is that this challenge will be filed in the United States Court of Appeals for the District of Columbia Circuit.  That case will likely be the World Series of FTC advertising cases.

Making accurate predictions about the result of cases is a dicey proposition based on an oral argument.  Nevertheless, many of our readers may be curious as to what I think will happen based on what was said and not said during this oral argument.
My record on making such predictions has been historically poor.  Nevertheless, here is my prediction based on this hearing:

(1) The FTC will issue a decision that will find that all the Respondents generated advertisements that made disease claims as to POM’s products;

(2) The FTC will find that at least some of those advertisements were false and or misleading in violation of the FTC Act;

(3)  The FTC will issue a cease and desist order against all five Respondents;

(4) The FTC will not impose an FDA-preclearance requirement with regard to any POM advertisement;

(5) The FTC will require POM to have 2 RCTs for at least some of the claims that POM may make in the future.  I suspect that the Commission will impose this requirement in a fact-based analysis that will continue to leave open the general question of when the FTC will require RCTs;

(6) The FTC decision will have a detailed analysis of the First Amendment.  I will not venture a guess as to whether the FTC will rule that POM has First Amendment protections for any of the ads they have run or the appearances that POM officials made on television; and

(7) The FTC will issue a fascinating ruling on the lines between food and drugs, including the extent to which a food product can be deemed a drug.

By Kurt R. Karst –      

In a pair of Federal Register notices (here and here) set for publication on August 27, 2012, and in a pair of draft guidance documents released ahead of their announcement in the Federal Register next week (here and here), FDA moves full-bore ahead with efforts to implement the Generic Drug User Fee Amendments of 2012 (“GDUFA”).  GDUFA, which was enacted as part of the FDA Safety and Innovation Act (“FDASIA”) in July 2012 (see our FDASIA summary and analysis here), is set to go into effect on October 1, 2012 – the start of Fiscal Year (“FY”) 2013.  The August 2012 notices and draft guidances cover myriad GDUFA topics, but are primarily intended to notify industry of certain obligations that need to be timely completed so that FDA can get the ball rolling come October 1, 2012.  One notice announces a September 21, 2012 public meeting to discuss GDUFA implementation.

GDUFA establishes four types of user fees that together will generate $299 million in funding for FDA in FY 2013, and adjusted annually thereafter.  Application fees, which account for 30% of total user fee revenue each FY, include an original ANDA fee and a Prior Approval Supplement (“PAS”) fee, which is one half of the ANDA fee, and a Type II Drug Master File (“DMF”) “first reference fee.”  Both the original ANDA fee and the PAS fee together account for 24% of the total revenue amount.  The Type II DMF fee accounts for 6% of total revenue amount.  An application containing information concerning the manufacture of an Active Pharmaceutical Ingredient (“API”)  at a facility by means other than reference to a Type II DMF, must pay, in addition to an application fee, a special “API fee” to be determined by FDA if “a fee in the amount equal to the [Type II DMF] fee . . . has not been previously paid with respect to such information.”  An annual facility fee, which accounts for 70% of total fee revenue each FY, must be paid by both Finished Dosage Form (“FDF”) and API  manufacturers.  FDF facility fees account for 80% of facility fee revenue (56% of the total revenue amount), and API facilities account for 20% of facility fee revenue (14% of the total revenue amount).  There is a fee differential of not less than $15,000 and not more than $30,000 for foreign FDF and API facilities, which is intended to reflect the added costs of foreign inspections conducted by FDA.

GDUFA also establishes a one-time ANDA backlog fee that will be assessed in FY 2013 for ANDAs pending on October 1, 2012.  Under GDUFA, an ANDA that is “pending” on October 1, 2012, is an application “that has not received a tentative approval prior to that date.”  That fee will be calculated by dividing $50 million by the number of ANDAs in the backlog.  FDA began the process of determining what ANDAs will be included in the backlog in June 2012.  In a notice, FDA announced the Agency’s intention to deem to be withdrawn certain incomplete ANDAs as to which the applicant has not communicated with FDA since July 8, 1991 (see our previous post here).

Below is a table we borrowed from one of FDA’s draft guidance documents, and to which we made some modifications, providing a summary of GDUFA user fee requirements.  Additional information on each fee is detailed in the draft guidance titled “Generic Drug: User Fee Amendments of 2012: Questions and Answers.”

With respect to the backlog and facility fees, FDA is seeking information to facilitate the fee calculation.  In the draft guidance document titled “Self-Identification of Generic Drug Facilities, Sites, and Organizations,” FDA lays out the so-called “self-identification process.”  As explained in the draft guidance:

Self-identification is required for two purposes.  First, it is necessary to determine the universe of facilities required to pay user fees.  Second, self-identification is a central component of an effort to promote global supply chain transparency.  The information provided through self-identification will enable quick, accurate, and reliable surveillance of generic drugs and facilitate inspections and compliance.

In a separate Federal Register notice, FDA implores ANDA applicants to promptly withdraw any pending ANDAs to avoid assessment of the backlog fee.  FDA is separately sending out letters to ANDA applicants making the same request.  Written notification must be received by FDA by Friday, September 28, 2012, because October 1, 2012 (when the backlog is solidified) is a Monday; however FDA encourages applicants to submit notification by September 15, 2012.

ANDA applicants should keep in mind that the penalties for failing to pay GDUFA user fees are stiff.  Failure to pay the backlog fee will result in placing the ANDA sponsor on a public arrears list, such that no new ANDAs or supplements will be received (submitted by the applicant or its affiliates).  Failure to pay the Type II DMF fee within 20 calendar days of the due date results in the Type II API DMF not being deemed available for reference, and an affected ANDA will not be received unless the fee has been paid within 20 calendar days of FDA notification of the failure to pay the fee.  Failure to pay the application fee within 20 calendar days of the due date will result in the application not being received by FDA until the fee is paid.  (Keep in mind that ANDA receipt date is particularly important when 180-day generic drug exclusivity is at stake.)  Finally, failure to pay a facility fee within 20 calendar days of the due date will result in the several consequences, including that all FDF or API products manufactured at the facility and all FDFs containing APIs manufactured at the facility will be deemed misbranded.

By Ricardo Carvajal & Diane B. McColl –

Back in April, FDA’s Center for Veterinary Medicine ("CVM") notified industry of its decision to extend the agency’s Memorandum of Understanding ("MOU") with the Association of American Feed Control Officials ("AAFCO") for one year (the MOU was scheduled to expire on September 1, 2012).  As of September 1, 2013, CVM intends to “transition from being the active reviewers of individual Ingredient Definition submissions to serving as a liaison and advisor to the Ingredient Definition Committee.”  However, CVM intends to “stop accepting requests to review new Ingredient Definition submissions” much sooner, specifically as of February 2013.  This means that the window of opportunity to petition for a new or revised Ingredient Definition through AAFCO is now down to six months.

The February deadline is intended to give CVM time to finish pending Ingredient Definitions, and to redirect the “increasing resources needed to address food additive petitions and [GRAS] notices.”  However, a cursory review of CVM’s inventory of GRAS notices reveals that none are pending.  Since CVM started receiving GRAS notices in 2010, a total of 13 notices have been filed.  Of those 13 notices, 3 received no objection letters, 4 received objection letters, and the remaining 6 were withdrawn.  Query whether the low rate of submissions is in part a function of these discouraging statistics.

By Kurt R. Karst –   

The decades-long saga over the withdrawal of approval of certain uses of certain classes of antibiotics in food-producing animals is likely to continue for some time given an August 8, 2012 decision from the U.S. District Court for the Southern District of New York.  The decision stems from a 2011 lawsuit filed against FDA by the National Resources Defense Council (“NRDC”) and three other member groups of “Keep Antibiotics Working.” 

As we previously reported (here, here, and here) the NRDC et al. sued FDA and initially sought to compel the Agency, by a court-ordered deadline, to withdraw approval of all subtherapeutic uses of penicillin in animal feed and nearly all subtherapeutic uses of tetracyclines (oxytetracycline and chlortetracycline) in animal feed and to issue final responses to two Citizen Petitions relating to hearing notices FDA issued in 1977 on the Agency’s withdrawal proposals.  FDA subsequently denied the petitions and took other action, and the Plaintiffs supplemented their lawsuit.  In a March 22, 2012 decision, Magistrate Judge Theodore H. Katz granted Plaintiffs’ Motion for Summary Judgment on their first claim for relief – that FDA withheld agency action in violation of both the Administrative Procedure Act (“APA”) and the FDC Act (§ 512(e)) by failing to implement withdrawal proceedings – and requested additional briefing on a schedule under which FDA must act.  FDA has appealed that decision to U.S. Court of Appeals for the Second Circuit (Case No. 12-2106).  In a June 1, 2012 decision, Magistrate Judge Katz denied FDA’s Motion for Summary Judgment and granted Plaintiffs’ Motion for Summary Judgment on another claim concerning the denial of the aforementioned Citizen Petitions.  Magistrate Judge Katz found that FDA violated the APA and the FDC Act when the Agency denied the two petitions.  FDA has not appealed that decision.

The August 8th decision from Magistrate Judge James C. Francis IV (who was assigned the case upon the retirement of Magistrate Judge Katz) concerns FDA’s proposed schedule pursuant to the Court’s March 22nd Order, as well as the Agency’s Motion for Stay requesting that the court stay the March 22nd Order pending resolution of the appeal (or impose an interim stay), and Plaintiffs’ Motion to Strike certain documents FDA submitted to the record.  The meat of the decision deals with FDA’s proposal and motion, so that’s where we’ll focus as well.

FDA proposed a timeline that would require reissuance of the hearing notices within 11 to 17 months, and an additional period of 41 months to complete the withdrawal process, including administrative appeals, but nevertheless asked the court to refrain from imposing a deadline because doing so would impermissibly re-order the Agency’s priorities.  Plaintiffs contended that FDA’s proposed schedule should be given a buzz cut so that the Agency would be required to reissue hearing notices within 125 days of commencement of the process and complete withdrawal proceedings within an additional two years. 

In deciding whether there has been unreasonable delay meriting the court’s the imposition of a schedule, Magistrate Judge Francis looked to the six so-called “TRAC” factors from the U.S. Supreme Court’s decision in Telecommunications Research & Action Center v. FCC, 750 F.2d 70 (D.C. Cir. 1984), and that the U.S. Court of Appeals for the District of Columbia Circuit laid out in In re Barr Laboratories, Inc., 930 F.2d 72 (D.C. Cir. 1991).  In Barr Laboratories, the Court refused to issue a writ of mandamus compelling FDA to act on ANDAs within the statutory 180-day period because “a judicial order putting [one ANDA sponsor] at the head of the queue simply moves all others back one space and produces no net gain.”   In finding that “FDA’s unreasonable delay merits the imposition of a schedule for compliance with the March 22 Order,” Magistrate Judge Francis distinguished the case at hand from the D.C. Circuit’s decision in Barr Laboratories:

In Barr Laboratories, the writ of mandamus would have effectively controlled the agency’s generic drug approval process, benefitting one enterprise at the expense of others, failing to improve the efficiency of the process of approving (or disapproving) generic drugs, and having no effect on human health and welfare.  Here, the FDA has utterly failed in its duty to initiate congressionally-mandated withdrawal proceedings.  Requiring it to do so promptly is not reordering the FDA’s priorities; it is correcting the agency’s misprision of its duty.  In Barr Laboratories, the court found that the contemplated order would have no effect on human health and welfare.  Here, in contrast, compelling the FDA to timely fulfill its obligations will speed adjudication on the issue of whether the non-therapeutic use of certain antibiotics in animal feed threatens human health and, if the sponsors or other interested parties cannot demonstrate the drugs’ safety, accelerate their compulsory withdrawal.

Moving on to the schedule for compliance with the March 22nd Order, Magistrate Judge Francis ultimately adopted FDA’s proposed 17-month (hearing reissuance) and 41-month (hearing process) timetable, saying that FDA “is in the best position to analyze the issue and propose a realistic schedule that is not based on unsupported assumptions, but rather on its expertise, and it has done so.”

FDA was not so fortunate, however, with its Motion to Stay the district court’s March 22nd Order pending the Second Circuit’s decision on its appeal (or, in the alternative, a stay pending the Second Circuit’s resolution of FDA’s planned application for a stay in that Court).  In denying the motion (for both a stay and an interim stay), Magistrate Judge Francis found that FDA did not show that it will be irreparably harmed if a stay is not granted, and that “given the substantial harm that further delay of withdrawal proceedings could visit on the plaintiffs and the public, the balance of the equities would not ‘weigh heavily in favor’ of a stay even if the Government had shown irreparable harm.”

The NRDC touted the district court decision as good news and commented that “FDA needs to move forward as rapidly as possible with the regulatory proceedings to address this pressing health threat and to rectify its decades-long neglect of this issue.”  In other related news, a baker’s dozen of U.S. Senators sent a letter to FDA commending the Agency for releasing a guidance document proposing voluntary reductions in the use of antibiotics in food-producing animals, but urging FDA to further strengthen the guidance. 

By Kurt R. Karst –      

Just before Congress recessed for the month of August, and less than a month after the July 9th enactment of the FDA Safety and Innovation Act, several FDA-related bills were placed in the hoppers in the U.S. Senate and U.S. House of Representatives.  With an election on the horizon and several other non-FDA-related issues to handle, it seems highly unlikely that Congress will be poised to tackle the FDA bills this year; however, they may provide some insight into some of the issues that will be debated in the 113th Congress come 2013.

H.R. 6272 – The Trial and Experimental Studies Transparency (“TEST”) Act of 2012

According to a press release from the primary sponsor of the bill, Rep. Ed Markey (D-MA), the TEST Act would close certain “clinical trial loopholes and bring certainty and transparency to life-saving research studies.”  Among other things, the bill would amend the definitions of “applicable device clinical trial” and “applicable drug clinical trial” at PHS Act § 402(j)(1)(A) to require that “all interventional biomedical studies on humans” be registered at ClinicalTrials.gov “before the first participant is enrolled in the trial.”  Although current draft guidance on clinical study registration explains that certain studies conducted outside of the United States do not need to be reported on Clinicaltrials.gov, the TEST Act specifically applies to “any interventional study of a [drug or device] conducted outside of the United States the results of which are submitted to the Secretary in support of” a marketing application, including a PMA and 510(k) notification for devices, and an IND, NDA, BLA, or ANDA for drugs and biologics.  (Applications for biosimilars under PHS Act § 351(k) are not specifically mentioned in the bill, but the broad reference to PHS Act § 351 presumably includes them.)  An “interventional study” is defined in the bill to mean “a study in human beings in which individuals are assigned by an investigator, based on a protocol, to receive specific interventions to evaluate their effects on biomedical or health-related outcomes.”  Support for the TEST Act has already appeared in the pages of The New England Journal of Medicine (see here).

H.R. 6288 – The Patient Choice Act of 2012

According to Rep. Brian Bilbray (R-CA), who introduced H.R. 6288 (see here), the bill is intended to “speed up the approval process of drugs used in therapies and treatments of patients fighting life threatening diseases.”  It would do so by establishing a “provisional approval” system for a product designated by FDA as a “fast track” product under FDC Act § 506.  (FDASIA made several amendment to FDC Act § 506 – see here.) In order for FDA to grant a request for provisional approval, the Agency would have to determine that a product is “adequately safe.”  This term is defined in the bill to mean that “for at least one population, the risk of death or morbidity caused directly by an adverse effect of the drug, as determined in one or more safety studies or through other data that the Secretary determines are sufficient, is unlikely to be greater than the combined direct and secondary risks of death or morbidity, as established in the literature or historical data” of the target disease, among other things.  The bill also contains provisions on the requirements for products granted provisional approval, and on the timing of the start of marketing exclusivity.

H.R. 6342 – The Compassionate Freedom of Choice Act of 2012

The Compassionate Freedom of Choice Act of 2012 was introduced by Rep. Ron Paul (R-TX) (see here) and is intended to allow the importation, distribution, and sale of investigational drugs and devices by terminally ill patients if their physicians certify: “(i) such patients have no other treatment options; and (ii) the patient executes written, informed consent that they are aware of any potential risks from the drug, device, or treatment.”  According to one advocacy group, H.R. 6342 “would substantially limit FDA’s ability to second-guess treating physicians’ decisions concerning the standard and methods of care available to terminally ill patients.” 

S. 3506 – The Ethical Pathway Act of 2012

S. 3506 was introduced by Sen. Bernie Sanders (I-VT) and is intended to “eliminate requirements to undertake duplicative clinical testing of new pharmaceutical drugs, vaccines, biological products or medical devices, when such duplication is inconsistent with relevant ethical norms” (e.g., the Declaration of Helsinki).  To do this, the bill, if enacted, would require FDA to establish a mechanism by which an applicant may request a cost-sharing arrangement with the owner of existing regulatory test data.  The bill is in line with other legislation introduced by Sen. Sanders to create a prize-based system for new drugs, instead of one with patent and non-patent exclusivity incentives (see here and here). 

Hyman, Phelps & McNamara, P.C.’s Diane McColl will present at USP’s 2012 Science & Standards Symposium, which is dedicated to functional foods and dietary supplements.  The conference will address scientific and regulatory issues from an international perspective, and will feature speakers from USP and NIH’s Office of Dietary Supplements.  The conference is scheduled for September 18-20 in Boston, MA.  A copy of the conference brochure and registration information is available here.

Ricardo Carvajal will present the ASQ Food, Drug, and Cosmetic Division's 23rd West Coast Conference on Dietary Supplement Global Strategies.  The conference will address numerous issues of interest to dietary supplement manufacturers and distributors, including GMP’s, advertising claims, and new dietary ingredient notifications.  The conference will feature presentations by senior FDA and state officials. The conference is scheduled for September 14 in Anaheim, CA.  Conference registration information is available here.

Mr. Carvajal will also present at the European Food Law Association’s 19th International Congress, which will examine the evolution from agricultural to food law, with particular attention to regulation of food quality and safety.  The congress is scheduled for September 20-21 in Seville, Spain. A copy of the conference brochure and registration information is available here.

By Jennifer D. Newberger –

Perseverance can be an admirable quality, except when it is misguided.  So it seems to be with Representative Edward Markey and Senator Jeff Merkley, who seem intent on convincing the public that devices cleared through the 510(k) process pose great risks that must be remedied.

We previously posted on a bill introduced by Rep. Markey and Senator Merkley, the Safety of Untested and New Devices (“SOUND”) Act of 2012.   As we noted in that post, the bill seemed to be presenting a solution in search of a problem.  The latest efforts by Rep. Markey and Senator Merkley continue to search for a chimera: badly designed devices, cleared through the 510(k) process, regularly causing death and serious injury. 

On August 15, the congressmen sent a letter to Dr. Jeff Shuren, Director of the Center for Devices and Radiological Health (“CDRH”), expressing their concern “about weaknesses in the premarket review process used to evaluate most medical devices.”  To fix these “weaknesses,” the congressmen request CDRH “overhaul and streamline its Recalls and 510(k) Premarket Notification databases to provide publically available and easily searchable information regarding the safety of devices that rarely undergo clinical trials in humans prior to being sold on the market.”  Their premise is that the 510(k) process is substantially flawed.

Yet, when the Institute of Medicine released its report on the 510(k) process last summer (see here), one finding was very clear: there is not a “public-health crisis related to unsafe or ineffective medical devices.  Although the safety and effectiveness of preamendment Class II devices have not been systematically reviewed, their continued use in clinical practice provides at least a level of confidence in their safety and effectiveness.”  It would seem that this committee of experts—a committee notably lacking any industry representatives—is better qualified to assess the risks posed by 510(k)-cleared devices than the two congressmen.

Nevertheless, they will not let their cause go undeterred.  In the letter to Dr. Shuren, the congressmen assert that “thousands of patients have been harmed – in some cases grievously and irrevocably – by medical devices that were modeled after recalled devices.”  To remedy this purported “problem,” they believe FDA’s authority should be expanded “to enable it to reject clearance if a device repeats design flaws that have led to the voluntary recall of early products.”  Such expanded authority was proposed in the SOUND Act, which appears to be stalled in the House of Representatives.  Given the failure to move that bill forward, the congressmen sent the letter to Dr. Shuren, proposing ways to increase “transparency” about “devices recalled for serious design flaws.”

Specifically, the letter proposes the following measures:

• Update the 510(k) database to reflect if the device was the subject of a recall “because of a serious design flaw that negatively affected safety of [sic] effectiveness.”  It asks that FDA update the database within 30 days of learning that a “flaw triggering the recall was a serious one that could adversely affect safety or effectiveness.”

• Update the 510(k) database to reflect whether the device “was cleared on the basis of a predicate recalled for a serious design flaw that negatively affected safety or effectiveness.”

• The database should provide “a link to information about the predicate’s adverse event reports and recall, so that consumers and doctors can determine the nature of the earlier problem.”

• The database “should be updated retrospectively to reflect previous recalls due to serious design flaws, to the extent that reliable information about older recalls is available.”  It does not specify how many years back the database should be updated, but notes that if the database “does not include serious recalls going back at least several years, its usefulness to companies attempting to ascertain which predicates to avoid will be severely limited.”

The letter also suggests that if a new device “repeats the same serious design flaw that caused the predicate to be recalled,” FDA should notify the sponsor in writing that the failure to fix the design flaw “puts the device at risk of being deemed misbranded or adulterated[.]”  This notion is particularly misguided, since it implies that FDA would be willing to clear a device that it knows, prior to clearance, would be misbranded or adulterated by virtue of its design. 

The letter also asks that FDA revise the 510(k) database to indicate whether a device “repeats the same design flaw that caused a predicate’s recall,” and “develop a mechanism for identifying certain 510(k) entries to reflect instances where a device’s clearance traces back to a predicate recalled for a serious design flaw adversely impacting its safety, even if the original problematic device is not the immediate predicate.” 

Our conclusion stated in the prior blog post remains true: Congress, industry, and FDA should all consider how to best assure that marketed devices are safe.  However, the proposals in this letter (and the SOUND Act) do nothing to further that goal.

By Kurt R. Karst –      

Efforts to include a 12-year period of exclusivity for biological products in the Trans-Pacific Partnership (“TPP”) agreement chapter on intellectual property rights are alive and well as folks ramp up for the 14th negotiating round of the TPP, which will take place in Leesburg, Virginia from September 6-15, 2012 (see here).  Such a move would align the TPP agreement with the 12-year period of reference product exclusivity provided by the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”).  As we previously reported (here and here), the TPP is a free trade agreement being hammered out among the United States – specifically, the United States Trade Representative (“USTR”), Ron Kirk – and several other partners, and is intended to further liberalize the economies of the Asia-Pacific region.  The TPP, which has been controversial and shrouded in secrecy, has also been touted as a model for all future U.S. trade and investment agreements. 

Although copies of the draft intellectual property chapter had previously been leaked and posted in the Internet, Representative Darrell Issa (R-CA), who is chairman of the House Oversight and Government Reform Committee, “officially leaked” the draft intellectual property chapter in May 2012.  Article 9 of the draft chapter (from February 2011), titled “Measures Related To Certain Regulated Products,” covers pharmaceutical products and includes placeholders for “provisions related to data protection for pharmaceutical products” and “provisions related to patent term/data protection relationship.”  Another leaked version of selected provisions of the chapter from September 2011 includes some additional details on Article 9, but still has a placeholder for specific provisions applying to biologics. 

In June 2012, Teresa Stanek Rea, Deputy Director of the U.S. Patent and Trademark Office, testified before the House Judiciary Subcommittee on Intellectual Property, Competition and the Internet and commented that the Obama Administration was seeking a period of 12-year exclusivitity for biologics in the TPP agreement.  This is contrary to the Obama Administration’s 2013 budget proposal, which seeks to reduce the 12-year exclusivity period under the BPCIA to 7 years.  According to Knowledge Ecology International, Ms. Rea subsequently retracted her comments and the USTR issued a statement that it has “not proposed a specific term for data exclusivity for biologics” and that “discussions on issues relating to biologics are continuing.”

Perhaps as a result of the flap in testimony, and in anticipation of the next round of TPP negotiations, a new round of letters have been sent to President Obama by several Members of Congress.  In a July 12th letter, Senators Patty Murray (D-WA) and Maria Cantwell (D-WA) say that “the TPP negotiations must ensure consistency with U.S. law, which provides 12 years of data protection for biologics,” and that 12-year exclusivity is “vitally important” and “an important foundation for a vibrant U.S. biopharmaceutical industry and workforce.”  Similarly, several members of the Massachusetts delegation – Representatives Edward Markey (D), Richard Neal (D), John Olver (D), James McGovern (D), John Tierney (D), Stephen Lynch (D), Niki Tsongas (D), and William Keating (D) – state in a July 13th letter that “[a]n agreement that reflects U.S. law on biologics exclusivity standards will help Massachusetts companies continue to expand and compete in the global economy.”  In the most recent letter from earlier this month, Senator Claire McCaskill (D-MO) says that TPP negotiations “should sustain the high standards on intellectual property rights that are the hallmark of U.S. law,” and that it is “especially important that the negotiations protect the 12 years of exclusivity that U.S. law now provides” for biologics.

By Kurt R. Karst –      

It’s been nearly nine years since the enactment of the Medicare Modernization Act (“MMA”), which, among other things, changed the regime for 180-day generic drug marketing exclusivity from a “patent-by-patent” approach (under which shared exclusivity can exist for cross-Paragraph IV filers to different patents) to a “first applicant to any patent” approach.  Yet, the lawsuits against FDA involving pre-MMA 180-day exclusivity keep popping up.  Last year, there was the controversy over generic LIPITOR (atorvastatin calcium) Tablets.  Earlier this year there was the case involving generic PROVIGIL (modafinil) Tablets (see here).  The latest case, filed on August 15th in the U.S. District Court for the District of Columbia by Watson Laboratories, Inc. (“Watson”), involves generic versions of Takeda Global Research & Development Center, Inc.’s (“Takeda’s”) diabetes drug ACTOS (pioglitazone HCl) Tablets, 15 mg, 30 mg, and 45 mg.  Watson, through its Complaint and Motion for a Temporary Restraining Order and a Preliminary Injunction, seeks to enjoin FDA from granting final approval (or causing or allowing final approval to be granted) to any ANDA for generic ACTOS prior to granting final approval to Watson’s ANDA No. 076798, or, alternatively, to require FDA to approve ANDA No. 076798 if FDA grants final approval to any other ANDA for generic ACTOS.

Like almost all pre-MMA 180-day exclusivity cases, this case is complicated; but we’ll try to be brief.  FDA approved ACTOS on July 15, 1999 under NDA No. 021073 and granted a period of 5-year new chemical entity exclusivity.  At the time the first ANDA containing a Paragraph IV certification could be submitted to FDA on July 15, 2003, the Orange Book listed several patents for ACTOS.  One of those patents expired in 2006, and the others, which are referred to by Watson in its court filings as the Composition Patents and the Combination Therapy Patents, expire in 2016. 

Watson, and apparently Mylan (ANDA No. 076801) and Ranbaxy (ANDA No. 076800), all submitted ANDAs to FDA on July 15, 2003 containing Paragraph IV certifications to the Composition Patents and to the Combination Therapy Patents.  Prior to “receiving” (i.e., filing) the Watson ANDA on September 9, 2003, FDA instructed Watson (and presumably the others ANDA sponsors as well) to amend its proposed labeling and to change its Paragraph IV certifications to the Combination Therapy Patents to section viii statements (i.e., for labeling carve-out purposes).  Watson disagreed with FDA’s position, but made the certification change. 

After FDA received ANDA No. 076798, Watson provided notice of the Paragraph IV certifications as to the Composition Patents to Takeda and was sued for patent infringement, as were other ANDA sponsors.  Ultimately, the patent infringement litigation was settled and Takeda granted Watson, Mylan, and Ranbaxy a non-exclusive license to the Composition Patents and to the Combination Therapy Patents as of August 17, 2012.  Under FDA’s regulation at 21 C.F.R. § 314.94(a)(12)(v), “if the [ANDA] is for a drug or method of using a drug claimed by a patent and the applicant has a licensing agreement with the patent owner,” the application must contain a Paragraph IV certification as to that patent “and a statement that it has been granted a patent license.”  All three ANDA sponsors apparently amended their respective ANDAs to include Paragraph IV certifications Combination Therapy Patents.  But it is unclear when this happened exactly.  Timing is, of course, critical for 180-day exclusivity purposes.

According to Watson, “[b]ased on the simultaneous filing of the Watson ANDA with Mylan and Ranbaxy’s ANDAs, Watson has expected to share the period of 180-day exclusivity with Mylan and Ranbaxy (as well as with a fourth generic manufacturer, Teva Pharmaceuticals (‘Teva’), that has been granted a license by Takeda).”  In August 2012, however, Watsons says that “FDA informed Watson for the first time that approval of the Watson ANDA would be delayed.  FDA informed Watson it had reached a decision to award another filer or filers a period of 180-day exclusivity, to the exclusion of Watson’s ANDA, and to delay approval of Watson’s ANDA until the expiration of that exclusivity period.”  In other words, FDA presumably determined that one (or more) ANDA sponsor was first to convert its section viii statements to the Combination Therapy Patents to Paragraph IV certifications as a result of the settlement agreement, and that Watson subsequently converted.

Watson argues in its court papers that at the very least the company is entitled to shared exclusivity.  Watson’s primary arguments, however, are that FDA’s decision in this case that Watson’s ANDA cannot be approved as a result of another sponsor’s 180-day exclusivity “(i) contravenes the plain language of the statute and regulations, which only bars approval of later filed applications; and (ii) is contrary to FDA’s regulations and past practice, which deny exclusivity to any ANDA applicant for patents that are the subject of withdrawn or amended Paragraph IV certifications” (emphasis in original).  Accordingly, Watson says that the company is “entitled to an order requiring FDA not to approve any other pioglitazone ANDAs before it approves Watson’s ANDA.”

The case number is 12-cv-01344-ABJ. A hearing has been scheduled for August 15th.  We'll update this post with additional information.

UPDATE:

• August 15, 2012 Minute Entry: "Motion Hearing held on 8/15/2012 re [3] MOTION for Temporary Restraining [Order]; Motion heard and denied without prejudice."
• August 17, 2012 Minute Order: "As stated by the Court in its August 16, 2012 oral ruling, plaintiff's renewed motion for a temporary restraining order is denied. To demonstrate entitlement to a temporary restraining order or preliminary injunction, a litigant must show 1) a substantial likelihood of success on the merits; 2) that it would suffer irreparable injury if the injunction is not granted; 3) that an injunction would not substantially injure other interested parties; and 4) that the public interest would be furthered by the injunction. See Mova Pharm. Corp. v. Shalala, 140 F.3d 1060 (D.C. Cir. 1998) (setting forth standard for a preliminary injunction); Sterling Commercial Credit–Michigan LLC v. Phoenix Indus. I, LLC, 762 F. Supp. 2d 8, 78 (D.D.C. 2011) (stating that the same standard applies to temporary restraining orders and preliminary injunctions). For the reasons explained at the August 16, 2012 hearing, the Court finds that plaintiff did not show a substantial likelihood of success on the merits in its motion for a temporary restraining order concerning its abbreviated new drug application ("ANDA") for generic pioglitazone hydrochloride 15 mg, 30 mg, and 45 mg tablets ("Generic Pioglitazone"). Specifically, plaintiff was told by the Food and Drug Administration ("FDA") on August 15, 2012 that its application was deficient and that it was required to submit additional information. The Court denied plaintiff's initial motion for a temporary restraining order without prejudice in view of the FDA's request. Plaintiff then responded to the FDA's request and renewed its motion. During the August 16 hearing on plaintiff's renewed motion, the FDA informed plaintiff that it had not submitted sufficient information in response to the August 15 request. Accordingly, at that time, plaintiff's application was still deemed deficient by the FDA and plaintiff was unable to demonstrate a likelihood of success on the merits; indeed, plaintiff's counsel conceded that the Court could not grant injunctive relief if its application was deemed deficient. Even if plaintiff had provided sufficient information to the FDA prior to the August 17, 2012 release date of Generic Pioglitazone, however, the Court finds that plaintiff did not present the Court with any case law or other legal authority that would persuade the Court that it has the authority to compel the FDA to immediately process and approve Watson's ANDA under the facts of this case. Plaintiff's alternative requests for relief also fail. Plaintiff requested, inter alia, that the Court enjoin the FDA from approving any other company's ANDA for Generic Pioglitazone if the FDA were not to approve Watson's ANDA on August 17, 2012. This request fails because such relief would plainly cause substantial injury to the other providers of Generic Pioglitazone who would have been approved on August 17, 2012. Furthermore, the public interest would not be furthered by an injunction that prevents approved companies from selling a generic drug. Accordingly, for the reasons stated by the Court on August 16, 2012 and for the reasons explained above, plaintiff's motion for a temporary restraining order is DENIED. Signed by Judge Emmet G. Sullivan on August 17, 2012."

By Riëtte van Laack –

The Organic Food Products Act of 1990 (“OFPA”) established national standards for the marketing of certain agricultural products marketed as organically produced.  It directed USDA to issue regulations specifying the requirements for certification and labeling of organic agricultural products.  In promulgating the NOP regulations, the USDA decided that the labeling of cosmetics was outside the scope of the OFPA.  Although the USDA’s position appears to have changed over time, USDA has not amended its NOP regulations to apply to organic claims for cosmetics.

The California Organic Products Act of 2003 (“COPA”) prohibits any product handled, processed, sold, advertised, represented or offered for sale in California from being sold as organic unless it is labeled with terminology similar to terminology set for in the regulations by the National Organic Program (“NOP”). COPA specifically applies to cosmetic products sold or labeled as organic or made with organic.  Under COPA, cosmetics with organic claims must contain at least 70 percent organically produced ingredients.  Unlike OFPA, which may be enforced only by USDA, COPA is enforceable by any person who may bring an action for injunctive relief.

In 2011, R. Brown et al. filed a complaint against The Hain Celestial Group, Inc. (“Hain”), claiming that Hain sold organic cosmetics in violation of COPA because these cosmetics did not contain 70% or more organic ingredients.  Hain filed a motion to dismiss arguing that COPA’s requirements for cosmetics are expressly preempted by the federal OFPA.

Judge Beeler of the U.S. District Court for the Northern District of California disagreed, however, in a decision from earlier this month.  Although the title of the OFPA may suggest otherwise, the Court concluded that OFPA covers cosmetics that use agricultural products.  However, the court held that OFPA only expressly preempts a narrow set of state certification requirements and does not bar state law labeling provisions that do not conflict with OFPA’s and NOP’s provisions.  In the alternative, even if (contrary to the Court’s interpretation) OFPA does not extend to agricultural cosmetics, USDA has approved COPA.  In either case, COPA’s provisions regarding organic claims for cosmetics are not preempted.  Therefore, the Court denied the Hain’s motion to dismiss.

By Jennifer D. Newberger –

On August 10, 2012, FDA issued a draft guidance, “Refuse to Accept Policy for 510(k)s.”  This draft guidance largely mirrors the recently issued draft guidance for premarket approval applications, “Acceptance and Filing Review for Premarket Approval Applications (PMAs),” on which we previously commented here. 

The draft guidance includes checklists for traditional, abbreviated, and special 510(k)s, based largely on the regulatory requirements for 510(k)s outlined in 21 C.F.R. § 807.87.  Included in the checklist are elements that will not necessarily be applicable to all devices, e.g., biocompatibility testing.  If a submitter believes that a particular element is not relevant to the submission, it should provide a justification for not including the information.

Within 15 days of receipt of the submission, FDA must inform the submitter if the submission is administratively complete, or, if not, identify the missing elements.  The submitter may then respond by providing the missing information, and FDA will then have another 15 days to perform the acceptance review.  The submitter should provide the information under the originally assigned 510(k) number.  FDA will not require a complete new submission, nor will the submitter be required to pay a new user fee upon providing the missing information.

The guidance states that if FDA fails to complete the acceptance review within 15 days, the submission should be considered accepted, but “FDA may ask for any information during the substantive review that may have been unintentionally overlooked during the acceptance review.”  The review clock for MDUFA goal purposes will not begin until FDA determines that the submission is administratively complete.  This review does not assess whether the contents of the application are substantively sufficient to make a substantial equivalence determination. 

The guidance contains certain principles that it suggests reviewer and submitters should heed in determining whether a 510(k) submission is complete:  1) acceptance should not be based on a substantive review of the submission; 2) reviewers should consider any justifications provided by the submitter as to why certain elements are not included, and; 3) submitters should review any applicable guidance or standards to ensure the submission contains all necessary information for that device type.

The guidance provides preliminary questions to be addressed by the reviewer prior to determining whether the submission contains all elements in the checklist.  These questions include:  (1) Is the product a device? (2) Is the submission within the correct center (e.g., CDRH or CBER)?  (3) Is a 510(k) is the appropriate regulatory submission?  (4) Is there a pending PMA for the same device with the same indications?  (5) If clinical data are submitted, is the submitter subject to the Application Integrity Policy (AIP)?  Though most of these questions could be easily answered during a preliminary review, determining whether the 510(k) path is appropriate could require a more substantive review, and may not always easily be determined.  For some products, it also may not be as clear as to whether the product is a device (see, e.g., here).  If a submitter is unsure of the appropriate regulatory path prior to providing a submission to FDA, it should consider submitting a 513(g) to determine FDA’s likely regulatory approach. 

It’s that time of year again when we at FDA Law Blog turn to our loyal readers and ask for your help.  The American Bar Association (“ABA”) announced that it is now accepting nominations for the 2012 Blawg 100 (the top 100 legal blogs – or “blawgs” – in the blogosphere).  With your help we made the top 100 list in 2009 and 2010, and we would really like to do so again in 2012!  We’d like another merit badge to add to the growing “Awards and Honors” collection posted on our blog. 

We ask that FDA Law Blog readers use the ABA’s Blawg 100 Amici Form – available here – and nominate the FDA Law Blog!  Although it’s called a “friend-of-the-blawg brief,” filling out the form will take only a couple of minutes.  In fact, you only have 500 characters to say why you’re a fan of the blog (something pithy).  Remember, when you complete the nomination form, our URL is www.fdalawblog.net.  Friend-of-the-blawg briefs are due no later than Friday, September 7th.

ABA editors make the final decisions about what’s included in the Blawg 100.  We hope they’ll be impressed with what our readers have to say about us.  Thank you!

By Kurt R. Karst –      

That’s the picture conjured up when we plugged some dates into the new model for calculating forfeiture of 180-day generic drug marketing exclusivity for certain ANDAs – what we are calling “window ANDAs” – covered by Section 1133 of the recently enacted FDA Safety and Innovation Act (“FDASIA”).

FDASIA § 1133 concerns FDC Act § 505(j)(5)(D)(i)(IV), which is one of the six 180-day generic drug exclusivity forfeiture provisions added to the FDC Act by Title XI of the 2003 Medicare Modernization Act.  Under FDC Act § 505(j)(5)(D)(i)(IV), 180-day exclusivity eligibility is forfeited if:

The first applicant fails to obtain tentative approval of the application within 30 months after the date on which the application is filed, unless the failure is caused by a change in or a review of the requirements for approval of the application imposed after the date on which the application is filed.

The 2007 FDA Amendments Act clarified FDC Act § 505(j)(5)(D)(i)(IV), such that if “approval of the [ANDA] was delayed because of a [citizen] petition, the 30-month period under such subsection is deemed to be extended by a period of time equal to the period beginning on the date on which the Secretary received the petition and ending on the date of final Agency action on the petition (inclusive of such beginning and ending dates) . . . .” FDC Act § 505(q)(1)(G). 

FDASIA § 1133 covers two cohorts of ANDAs – one under subsection (a) and another under subsection (b).  For both sets of ANDAs covered by FDASIA, the intent of the law is two-fold.  First, FDASIA accounts for FDA’s growing median ANDA approval time – about 32-33 months today – which has led to many companies forfeiting 180-day exclusivity eligibility.  Second, FDASIA § 1133 addresses FDA’s strict interpretation of FDC Act § 505(j)(5)(D)(i)(IV), such that when an ANDA sponsor who amends a long-pending ANDA to include a Paragraph IV certification to an Orange Book-listed patent and qualifies as a “first applicant,” that sponsor may simultaneously forfeit 180-day exclusivity eligibility for failure to obtain timely tentative approval.  This has happened because FDA counts 30 months from the ANDA submission date rather than from the first Paragraph IV certification date (see our previous post here).

FDASIA § 1133(a) covers ANDAs submitted to FDA between January 9, 2010 (actually, January 11, 2010, because January 9th is a Saturday) and July 9, 2012 initially containing a Paragraph IV certification to a patent listed in the Orange Book for the Reference Listed Drug (“RLD”), or that is amended between January 9, 2010 and July 9, 2012 to first contain a Paragraph IV certification to a patent listed in the Orange Book for the RLD.  It provides that the time to obtain timely tentative approval (or final approval if tentative approval is not warranted) is 40 months during the period of July 9, 2012 and September 30, 2015, and not 30 months.  During the period beginning on October 1, 2015 and ending on September 30, 2016, the period is 36 months and not 30 months.

FDASIA § 1133(b) covers ANDAs first amended after July 9, 2012 to contain a Paragraph IV certification.  Specifically, this subsection provides that for an ANDA submitted to FDA prior to July 9, 2012 that is first amended on July 10, 2012 and up to September 30, 2017 to contain a Paragraph IV certification to a patent listed in the Orange Book for the RLD, the date of the amendment starts to 30-month tentative approval forfeiture period instead of the original ANDA submission date. 

While all seems well with the FDASIA § 1133(b) window ANDAs, there appears to be a problem with the FDASIA § 1133(a) window ANDAs.  In particular, the 36-month extension date is inapplicable (absent an applicable 505(q) citizen petition, or some change in review that occurs during the last 6 months of the 36-month period making the forfeiture provision irrelevant).  By the time this provision takes effect on October 1, 2015, the youngest ANDA to which it could apply – i.e., an ANDA submitted to FDA on July 9, 2012 – will be nearly 39 months old.  If such an ANDA is tentatively approved on September 30, 2015 when the tentative approval period is still 40 months, there would not be a forfeiture.  If, however, that same ANDA is tentatively approved one day later, on October 1, 2015, there would be an automatic forfeiture.

In addition, we note that the youngest window ANDA to which FDASIA § 1133(a) can fully apply (i.e., an ANDA that could potentially enjoy the full 40-month period absent an applicable 505(q) citizen petition) is an ANDA submitted on May 30, 2012 and tentatively approved on September 30, 2015.  Such an ANDA would be tentatively approved within the 40-month period (depending on what it means to be tentatively approved “within” the specified timeframe – see our previous post here.)  An ANDA submitted after May 30, 2012 would not enjoy the full 40-month period. 

By Larry K. Houck –
 
The Drug Enforcement Administration (“DEA”) recently amended its regulations to allow practitioners to issue electronic prescriptions for controlled substances (“EPCS”) in lieu of hardcopy paper prescriptions.  See 75 Fed. Reg. 16,236 (March 31, 2010).  DEA requires that any electronic prescription application or pharmacy application used for EPCS must be reviewed, tested and determined by a third party to meet all of the required technical specifications.  21 C.F.R. § 1311.300(a).  As an alternative to the third party audit requirements of 21 C.F.R. §§ 1311(b)-(d), an electronic prescription or pharmacy application may be verified and certified as meeting DEA requirements by a certifying organization whose certification process has been approved by DEA.  21 C.F.R. § 1311.300(e).  DEA stated that it would notify registrants of any approved third party certifications on its website.  75 Fed. Reg. 16,243.

DEA announced on August 1, 2012 that it has approved the certification processes developed by two certifying organizations (77 Fed. Reg. 45,688 (Aug. 1, 2012)) and has posted relevant information about those approvals, and about an earlier approval, on the DEA Diversion Control website.