By Ricardo Carvajal –

Researchers report that in vitro and in vivo experiments conducted with polystyrene nanoparticles indicate that nanoparticle exposure can disrupt iron transport in the gut, and may possibly disrupt absorption of other minerals, as well as vitamins.  The in vivo experiments, which were conducted in chickens, further indicate that chronic exposure can result in remodeling of intestinal villi to increase surface area so as to increase absorption, thereby compensating for the disruption in nutrient transport.   Chickens were chosen for the experiments in part because of similarities between their gastrointestinal tract and that of humans. 

The significance of these findings may be difficult to assess until additional studies on the effects of nanoparticle exposure on the gut have been conducted.  Nonetheless, they should be of interest to food ingredient developers, given the researchers’ observation that dietary particles in certain food additives have been thought to potentially have adverse health effects.   The findings should also be of interest to drug developers, given the utility of nanoparticle carriers for drug delivery.

By Jamie K. Wolszon & Jeffrey N. Gibbs –  

On February 15, 2012, Hyman, Phelps & McNamara, P.C. (“HPM”) submitted supplemental comments to FDA’s June 1, 2011 draft guidance (see our previous post here) that would limit the sale and distribution of Research Use Only (“RUO”) products.  HPM’s supplemental comments highlight FDA’s discussion of the draft guidance in a recent government brief submitted in federal court in a case related to drug off-label information.  The government’s description to the court of the draft guidance is inconsistent with the position in the draft guidance itself that RUO manufacturers should cease sales to a customer if they have knowledge of that customer’s diagnostic use.

On October 14, 2011, Par Pharmaceutical, Inc. (“Par”) sued FDA for allegedly violating the First Amendment by improperly restricting the flow of truthful information (see our previous post here).  The government filed its brief opposing Par on January 11, 2012. 

In its brief, the government states that mere knowledge that an RUO is to be used diagnostically is insufficient to establish a new intended use. 

Looking beyond § 201.128 for proof that FDA equates knowledge that a drug is being prescribed for unapproved uses with intent to create a new intended use, Par quotes selectively from a draft FDA guidance document regarding in vitro diagnostic devices approved for investigational and research uses.  Compl. ¶ 69.  The draft guidance says that “FDA may consider a manufacturer’s knowledge of the purposes for which its customers offer and use its IVD [in vitro diagnostic] product, and the manufacturer’s provision of technical support for those activities, to be evidence that the IVD product is intended to be used for such purposes” (emphasis added).  The emphasized language, which Par omits, makes clear that it is the combination of manufacturer knowledge “and” technical support for the customer’s use, not bare knowledge by itself, that may be taken as evidence of the device’s intended use.

Government’s Brief at 28-29. (Emphases in original.)

HPM previously submitted comments to FDA on the Draft Guidance on August 30, 2011, and supplemental comments on September 22, 2011.

By Kurt R. Karst – 
 
Following the Federal Circuit’s recent precedential decision in AstraZeneca Pharms. v. Apotex et al. (Case No. 2011-1182) (in which the Court held that an ANDA sponsor who submits a “section viii” statement with respect to an Orange Book-listed method-of-use patent and does not seek approval for the patented use cannot be found liable under 35 U.S.C. § 271(e)(2) for patent infringement – see Orange Book Blog and Patent Docs posts), and as we all patiently await a decision from the U.S. Supreme Court in the patent use code counterclaim case, Caraco Pharmaceutical Laboratories, Ltd. v. Novo Nordisk A/S (Docket No. 10-844) (see our previous post here), we thought we’d tee up another case, pending before the Federal Circuit, that represents a middle ground of dispute of sorts between AstraZeneca and Caraco: Bayer Schering Pharma AG v. Lupin, Ltd. et al. (Case No. 2011-1143; Oral Argument held Dec. 7, 2011).  

The case involves U.S. Patent No. 5,569,652 (“the ‘652 patent”), which is listed in the Orange Book for the contraceptive drug YASMIN (drospirenone 3 mg/ethinyl estradiol 0.03 mg) Tablets (NDA No. 021098; approved on May 11, 2001) with a “U-1” patent use code defined as “PREVENTION OF PREGNANCY.”  

Depending on who you ask, Bayer Schering Pharma AG v. Lupin, Ltd. et al. is either a run-of-the-mill Hatch-Waxman patent infringement dispute under 35 U.S.C. § 271(e)(2), or a high-stakes case with significant implications for future Hatch-Waxman infringement litigation concerning method-of-use patents.  The question before the Federal Circuit is whether the U.S District Court for the Southern District of New York erred when it granted, in September 2010, a Judgment on the Pleadings in favor of the ANDA sponsors (Defendants-Appellees) determining that the ‘652 patent does not claim an FDA-approved use for YASMIN because the patented use does not appear in the “Indications and Usage” section of the YASMIN labeling, but rather in the “Clinical Pharmacology” section of the labeling. 

Claim 11 of the ‘652 patent, which is at the center of the dispute, asserts the following method-of-use claim for YASMIN:

A method of simultaneously achieving, during pre-menopause or menopause, a contraceptive effect, an anti-androgenic effect, and an antialdosterone effect in a female patient in need thereof comprising administering an effective amount of dihydrospirorenone and an effective amount of an estrogenic compound, wherein said effective amount of dihydrospirorenone is effective to simultaneously achieve a gestagenic effect, anti-androgenic effect, and an anti-aldosterone effect in said female patient.

Plaintiffs-Appellants argue that FDA approved the ‘652 patent’s claim of simultaneous gestagenic, anti-androgenic, and anti-aldosterone effect, and that that approval is found in the “Clinical Pharmacology” section of the YASMIN labeling, which states in relevant part:

Drospirenone is a spironolactone analogue with antimineralocorticoid activity.  Preclinical studies in animals and in vitro have shown that drospirenone has no androgenic, estrogenic, glucocorticoid, and antiglucocorticoid activity.  Preclinical studies in animals have also shown that drospirenone has antiandrogenic activity.

Based on Federal Circuit precedent – i.e., Warner-Lambert Co. v. Apotex Corp., 316 F.3d 1348 (Fed. Cir. 2003) and Allergan Inc. v. Alcon Labs., 324 F.3d 1322 (Fed. Cir. 2003), which have been used to support the proposition that a method-of-use patent infringement claim against an ANDA sponsor cannot stand where that use is not approved by FDA – district court precedent – i.e., Alcon Labs. v. Allergan, Inc., 256 F. Supp. 2d 1080 (C.D. Cal. 2003) – and FDA’s labeling regulations at 21 C.F.R. § 201.57(c), which state in part that “[i]ndications or uses must not be implied or suggested in other sections of the labeling if not included in this section,” the New York District Court determined that “the FDA-approved use of a drug is governed by the “Indications and Usage” section of its label. . . .”

In their briefs (here and here), Plaintiffs-Appellants argue that the district court ignored basic principles of administrative law in coming to its September 2010 decision.  Citing FDA’s Hatch-Waxman patent listing regulations, Plaintiffs-Appellants argue that the court’s ruling is in direct conflict with those regulations.  Those regulations “confirm that a patented method need not appear just in the Indications section.”  Moreover, write Plaintiffs-Appellants, “[c]onsistent with these regulations, the Orange Book contains numerous [patent] use codes sourced outside of the Indications section.  The district court’s holding would render unenforceable in Hatch-Waxman proceedings the method of use patents underlying these use codes.”  Plaintiffs-Appellants also argue that the district court ignored other evidence of FDA approval of the ‘652 patented method, including DDMAC’s pre-clearance of certain promotional pieces “featuring the ‘652 patented method,” and a declaration from a former FDAer responsible for the clinical review of YASMIN. 

Defendants-Appellees argue in their brief that the district court got it right when it concluded that the only approved use for YASMIN included in the product’s labeling is contraception.  They counter that Plaintiffs-Appellants go too far in characterizing the scope of the district court’s decision.

Bayer repeatedly mischaracterizes the District Court’s opinion as going far beyond its actual holding that the FDA approved Yasmin for contraception only. . . .  Bayer insists that the District court held, far more broadly, that “a patentee can only assert method patents if those methods appear in the Indications section of the approved labeling.”  Bayer does not even attempt to cite to specific language in the District Court’s opinion in order to support its mischaracterization of the breadth of the court’s holding.  Rather, it simply sets up a straw man argument, and then devotes many pages of briefing to knocking it down.  In fact, the District Court’s holding was appropriately limited to the ‘652 patent claims, the scope of the FDA’s approval of Yasmin, and the consequences vis-a-vie Appellees’ ANDAs for their respective generic versions of Yasmin.  The court’s decision from which Bayer appeals . . . is a straightforward, narrow ruling, and is amply supported by the record.

Hatch-Waxman junkies will surely be watching this case closely.  Clearly, the Federal Circuit’s decision will be an important one regardless of how the Court ultimately rules.  Indeed, the case is so important that even PhRMA filed an amicus brief. 

By Ricardo Carvajal –

According to press reports, Senator Charles Schumer (D-NY) has prevailed on FDA to examine the regulatory status of Aeroshot, a product labeled as a dietary supplement that claims to contain “a unique blend of caffeine and B vitamins in a fine powder that dissolves quickly in your mouth.”  According to the manufacturer, each Aeroshot provides 100 mg of caffeine (roughly equivalent to a large coffee) and delivers 4 to 6 “puffs,” which users are directed to swallow.  Sen. Schumer first attacked the product last December, describing it as “nothing more than a club drug.”

Although readers might be reminded of FDA and FTC’s joint action against caffeinated malt beverages (see our previous post here), those products raised the question of whether the intended use of caffeine was generally recognized as safe, or GRAS – the standard applicable to the use of an ingredient in conventional foods when that use of the ingredient has not been the subject of a food additive approval.  Because Aeroshot is marketed as a dietary supplement, it will be evaluated under the definitions and safety standards applicable to those products.  That said, it bears watching whether FDA takes account of the manufacturer’s marketing practices, and of whether the product is associated with “adverse behavioral effects” – factors that the agency cited in support of its conclusion that the use of caffeine in caffeinated malt beverages such as Four Lokos is not GRAS.

Given that Aeroshot appears intended to dissolve in the mouth and be swallowed, it’s not clear what makes it “breathable.”  In any case, the concept of “breathable” food has been on the table for at least 10 years, albeit in a more rarified form.  Intriguing, but no substitute for a good bowl of gumbo.

By Kurt R. Karst –

Following a long court battle in which a three-judge panel of the U.S. Court of Appeals for the Tenth Circuit affirmed a November 2010 decision from the U.S. District Court for the District of Wyoming granting FDA’s Motion to Dismiss a lawsuit brought by Cody Laboratories, Inc. and Lannett Co., Inc. (collectively “Lannett”) concerning the alleged grandfather status of Lannett’s marketed unapproved Morphine Sulfate Solution, Lannett has submitted a citizen petition to FDA seeking the Agency’s determination on the subject.  As FDA Law Blog readers might recall, the Lannett lawsuit came about as a result of FDA’s March 2009 Warning Letters to Cody and Lannett (among other companies) to stop manufacturing certain unapproved narcotic drugs, including morphine sulfate oral solutions.  At that time, FDA concluded that marketed unapproved morphine sulfate products are “new drugs [under the FDCA] and not grandfathered and that manufacturing and marketing of these products without an approved application constituted a violation of the Act.”  Lannett ultimately submitted and obtained approval of a marketing application (NDA No. 201517) for Morphine Sulfate Oral Solution, 100 mg per 5 mL (20 mg per mL), which is subject to PDUFA user fees.

Although the Tenth Circuit agreed that the approval of NDA No. 201517 did not moot Lannett’s grandfather drug claim, because “[b]y prevailing on its grandfathering claim, Cody could still obtain meaningful relief in the form of freedom from [certain user fee and labeling]  burdens,” the Court refused to reach the merits of Lannett’s grandfather drug claim.  Importantly, the Court stated:

Mootness aside, we cannot reach the merits of [Lannett’s] grandfathering claim unless the FDA has engaged in “final agency action” under the APA. . . .  [Lannett’s] failure to avail itself of available administrative remedies [(i.e., use of the citizen petition process)] defeats its claim even if we were inclined to hold that the FDA’s action [(i.e., Warning Letters)] were otherwise final. . . .  Given that grandfathering status hinges on the fact-intensive history of the drug’s marketing and use, we do not anticipate that the agency will blindly refuse to consider evidence submitted by [Lannett].  Accordingly, we decline to consider [Lannett’s] grandfathering claim prior to exhaustion of the company’s administrative remedies.

The recent Lannett citizen petition would appear to be an attempt to obtain final agency action, perhaps on which to base a future lawsuit.  The citizen petition requests that FDA affirm, pursuant to the 1938 “grandfather clause” of the FDC Act, the grandfather status of morphine sulfate, which is marketed for the relief of severe acute and severe chronic pain.  In addition, FDA is asked to acknowledge that, in light of a grandfather affirmation, Lannett’s Morphine Sulfate drug product is not a “new drug” subject to premarket approval and PDUFA user fees.

Under the 1938 “grandfather clause,” a drug “shall not be deemed a ‘new drug’” requiring FDA approval if: (1) the drug was subject to the 1906 Food and Drugs Act at any time prior to June 25, 1938, when the FDC Act was enacted; and (2) “if at such time its labeling contained the same representations concerning the conditions of its use.”  The 1938 “grandfather clause” is different from the 1962 “grandfather clause,” which exempted manufacturers of pre-1962 drugs from the requirement to demonstrate effectiveness, in addition to safety under the 1938 FDC Act.

Lannett contends in its petition that morphine sulfate meets both of the 1938 “grandfather clause” requirements.  Along the way, Lannett addresses certain interpretations of the 1938 and 1962 “grandfather clauses” that might otherwise lead FDA to conclude that Lannett’s Morphine Sulfate drug product is not a grandfather drug.  For example, Lannett argues that:

The fact that a specific manufacturer’s morphine sulfate drug product was not introduced into interstate commerce in the United States prior to the enactment of the Act in 1938 does not disqualify its drug product from “grandfather” status.  The language of the first prong of the “grandfather clause” requires only that a drug be subject to the 1906 Act, not a specific manufacturer’s drug.  A more restrictive reading would preclude any other entity from marketing a drug that was on the market prior to 1938, with the same conditions of use, and claim that it was “grandfathered.” (Emphasis ion original)

Moreover, acknowledging that the labeling for its Morphine Sulfate drug product is not identical to that of pre-1938 product labeling, and that FDA and some courts have narrowly (and perhaps incorrectly) interpreted the 1938 “grandfather clause,” Lannett argues that the correct inquiry under the 1938 “grandfather clause” is whether the drug product contains “the same representations concerning the conditions of its use.”

The 1962 “grandfather clause” calls for a comparison of the drug products’ conditions of use, 
composition and labeling, while the 1938 clause focuses only on a comparison of their conditions of use.  Any attempt by FDA to impose the same requirements with respect to the applicability of the 1938 “grandfather clause” and the 1962 “grandfather clause”— despite the clear differences between the language used in the two provisions—is unsupported by the statutory language and is contrary to the above mentioned canons of statutory construction.

In that connection, says Lannett, FDA has incorrectly relied on its grandfather drug hearing regulations at 21 C.F.R. § 314.200(e) to establish the burden of proof necessary to qualify for grandfather status under the 1938 “grandfather clause.”  Those regulations, which Lannett says are related to the 1962 “grandfather clause,” state, in part, that “[a] contention that a drug product is exempt from part or all of the new drug provisions of the act under the exemption for products marketed before June 25, 1938, contained in section 201(p) of the act, or under section 107(c) of the Drug Amendments of 1962, is required to be supported by evidence of past and present quantitative formulas, labeling, and evidence of marketing.”  According to Lannett, however, the text of the FDC Act “sets forth the standard for when a drug product is not subject to the new drug requirements, and does not require FDA approval of such a claim before such old drugs can be marketed.  FDA cannot override or add to the unambiguous requirements of the statute. . . .  FDAs continued reference to §314.200(e) is misplaced and beyond its regulatory authority.”  For one example of where FDA has raised the Agency’s hearing regulations when faced with a 1938 “grandfather clause” issue, see FDA’s December 2000 response to a citizen petition concerning cannabis-containing drugs.

By Kurt R. Karst –      

Just days after FDA announced the release of three draft guidances on biosimilar product development (see our previous post here), and on the same day FDA officially noticed their availability in the Federal Register (here, here, and here) (as well as a proposed collection on § 351(k) biosimilar applications), FDA denied the outstanding requests in two citizen petitions submitted to the Agency in April 2003 (Docket No. FDA-2003-P-0003) and April 2004 (Docket No. FDA-2004-P-0214) by the Biotechnology Industry Organization (“BIO”) and Genentech, Inc. (“Genentech”), respectively.  Both petitions were submitted to FDA well before the March 2010 enactment of the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”), which amended the Public Health Service Act (“PHS Act”) to, among other things, create an approval pathway for biosimilar and interchangeable versions of reference products (§ 351(k) biosimilar applications).  As such, the petitions primarily pertain to the submission and approval of 505(b)(2) applications under the FDC Act for “biotechnology-derived products” (i.e., therapeutic drug or biological products developed by biotechnology methods) or “follow-on therapeutic proteins” (i.e., polypeptide therapeutic products, including recombinant versions of therapeutic protein products, not submitted to FDA with a full complement of clinical data).

FDA had previously addressed most of the issues raised in the petitions in the Agency’s October 2003 and May 2006 petition responses (here and here); however, two outstanding requests remained:

(1) that FDA decline to publish a draft guidance regarding the “similarity” or “sameness” of a “biotechnology-derived product” or “therapeutic protein” that relies on confidential or trade secret information; and

(2) that FDA provide advance notice and a pre-deprivation hearing if FDA does decide to issue such a guidance using trade secret or confidential information.

Genentech broadly requested in its petition that FDA “refrain from publishing a draft guidance document setting forth standards for the ‘similarity’ or ‘sameness’ of biotechnology-derived products. . . that relies, directly or indirectly, on Genentech’s trade secret and confidential commercial data.”  FDA says in its 2012 petition response that Genentech “suggests that any guidance document FDA creates on this subject impermissibly will be infused with protected confidential and trade secret information.”  Any such argument must fail, however, says FDA, because the Agency’s “mandate is to protect the public health in the areas within its purview – including biotechnology-derived products – and it may, among other things, create guidance to industry regarding the laws it administers.”  With respect to the draft biosimilars guidances issued on February 9, 2012, FDA comments that they “do not violate any protections available to applicants by relying, either ‘directly or indirectly,’ on Genentech’s or any other entity’s confidential information. . . [,] do not disclose any trade secret or confidential information, and [that] FDA did not impermissibly use or rely upon any such information in developing them.”

BIO more specifically requested in its 2003 citizen petition that FDA “refrain from preparing, publishing, circulating, or issuing any new guidance for industry, whether in draft or final form, concerning follow-on applications for therapeutic proteins, particularly human growth hormone or insulin, under [FDC Act § 505(b)(2)] which was intended simply to codify FDA’s earlier ‘paper NDA’ policy.”  Insofar as BIO’s request is limited to guidace involving 505(b)(2) applications for therapeutic proteins, FDA comments in the Agency’s February 2012 response that FDA has general authority to issue guidance and notes that “if FDA deems such an exercise of its authority appropriate or necessary, the Agency may prepare, publish, circulate, or issue new draft or final guidance for industry concerning applications for therapeutic proteins (or any other subset of products) eligible for approval under [FDC Act § 505(b)(2)].”  Insofar as BIO’s petition more generally requests that FDA refrain from issuing guidance on class-specific biological products, FDA points to the text of the BPCIA, which permits the Agency to issue “specific” guidance “with respect to the licensure of a biological product under [PHS Act § 351(k)].”  Perhaps signaling future guidance, FDA comments that while the Agency “thus far has not published draft guidance on the subject of product class biological products, the [BPCIA] clearly contemplates that the Secretary may issue this type of guidance.”

Genentech specifically requested in its citizen petition that FDA provide advance notice and a pre-deprivation hearing if the Agency decides to issue guidance on biotechnology-derived product/therapeutic protein similarity/sameness issues using trade secret or confidential information.  In FDA’s February 2012 petition response, the Agency declined to address Genentech’s Constitutional and trade secret law arguments, and instead reasserted that that Agency “acts within its authority when it issues guidance documents in its areas of scientific expertise for purposes of executing its mandate as an agency.”  Moreover, says FDA, the draft biosimilars guidances “do not implicate, disclose, or rely upon Genentech’s (or any other company’s) confidential commercial or trade secret information.”

By Kurt R. Karst & David B. Clissold –   

Three House lawmakers (Reps. Henry Waxman(D-CA), Ed Markey (D-MA), and Diana DeGette (D-CO)) sent letters (here and here) to FDA Commissioner Dr. Margaret Hamburg and NIH Director Francis Collins earlier this week expressing their concern over a recent report published in the British Medical Journal (“BMJ”) documenting the underreporting of results of clinical studies on ClinicalTrials.gov.  According to the article published in the January 2012 issue of the BMJ, titled “Compliance with mandatory reporting of clinical trial results on ClinicalTrials.gov: cross sectional study,” a database search of trials registered on ClinicalTrials.gov which completed in 2009 and that are covered by the 2007 FDA Amendments Act (“FDAAA”) showed that “[o]f the 738 trials that were classified as subject to mandatory reporting, 163 (22%) had reported results.  In comparison, 76/727 (10%) trials covered by the FDAAA but not subject to mandatory reporting had reported results . . . . ”

Section 801 of FDAAA amended PHS Act § 402 to expand the clinical trial registry data bank created by Section 113 of the Food and Drug Administration Modernization Act of 1997.  FDAAA § 801 expanded the clinical trial data bank (i.e., ClinicalTrials.gov) in two ways.  First, a broader range of “applicable” clinical trials must now be registered at ClinicalTrials.gov.  Second, certain results information from applicable clinical trials must now be submitted to the clinical trial registry data bank.

An “applicable drug clinical trial” is defined in PHS Act § 402(j)(1)(A)(iii) to mean “a controlled clinical investigation, other than a phase 1 clinical investigation, of a drug subject to [FDC Act § 505] . . . .”  An “applicable device clinical trial” is defined in PHS Act § 402(j)(1)(A)(ii) to mean “a prospective clinical study of health outcomes comparing an intervention with a device subject to section 510(k), 515, or 520(m) of the [FDC Act] against a control in human subjects (other than a small clinical trial to determine the feasibility of a device, or a clinical trial to test prototype devices where the primary outcome measure relates to feasibility and not to health outcomes); and a pediatric postmarket surveillance as required under [FDC Act § 522].”  In March 2009, NIH posted a revised draft document on its website concerning FDAAA and clinical trial registration.  The document provides more detailed information on applicable clinical trials, including defining such trials to include certain in vivo bioequivalence studies used to support the approval of a generic drug under an ANDA (see our previous post here).

Under PHS Act § 402(j)(2)(C), the responsible party of an applicable clinical trial that is initiated after September 27, 2007, or that is ongoing on December 26, 2007, must submit to NIH certain required information for inclusion in the clinical trial data bank by December 26, 2007, or 21 days after the first patient is enrolled in the clinical trial, whichever is later.  The only exception to this rule is that if the clinical trial was ongoing on September 27, 2007 and was not for a serious or life-threatening disease or condition, the information must have been submitted by September 27, 2008. 

PHS Act § 402 also requires the submission of certain results information of applicable clinical trials to the clinical trial registry bank.  FDA, NIH, and the responsible parties for applicable clinical trials all have responsibilities under the law.  Among other things, NIH is responsible for maintaining the public database of trial results on ClinicalTrials.gov, and FDA is responsible for enforcing the statutory requirements.  (FDA and NIH were supposed to have, by September 27, 2010, expanded the results database by rulemaking to possibly include a summary of the clinical trial and its results, the full protocol, and other information.  That rulemaking has not yet been issued, but it might happen soon, according to the Fall 2011 DHHS Unified Agenda.)  Responsible parties for applicable clinical trials are responsible for, among other things, submitting certain results information to the basic results section of ClinicalTrials.gov. 

Subject to specified exceptions, the general rule is that as of September 27, 2008, the responsible party for an applicable clinical trial must submit the basic results information no later than 1 year “after the earlier of the estimated complete date of the trial . . . or the actual date of completion” (PHS Act § 402(j)(3)(E)).  One important exception is that if the trial is completed before the drug is approved or the device is cleared, the responsible party can delay submitting the results information until no later than 30 days after the drug or device is approved (PHS Act § 402(j)(3)(E)(iv)).  If the manufacturer of a drug or device or sponsor of an applicable clinical trial is seeking approval for a new use of the drug or device, the same information must be submitted on the earliest of 30 days after approval, 30 days after FDA issues a not approval letter or a not substantially equivalent letter, or 30 days after the application is withdrawn without resubmission for no less than 210 days (PHS Act § 402(j)(3)(E)(v)). 

The failure of a responsible party to submit the required clinical trial information under PHS Act § 402(j) is a prohibited act (FDC Act § 301(jj)) that could result in significant penalties of up to $10,000 per day (FDC Act § 303(f)(3)).  FDA has not, to our knowledge, taken any enforcement action with respect to PHS Act § 402(j). 

The February 14th letters from the trio of lawmakers to FDA and NIH raise both common concerns (e.g., “publication delays may allow ineffective or dangerous drugs to remain on the market, resulting in significant harm to patients and waste in the health care system”) and agency-specific concerns, such as “whether FDA is adequately enforcing the law requiring such reporting” and “whether NIH is adequately implementing the law requiring such reporting” (emphasis added).  The letters also contain requests specific to FDA and NIH to help the lawmakers better understand the issue.  FDA is asked to provide answers to the following questions:

1) Do the findings of the [study reported in the BMJ] correspond with FDA‘s internal data on compliance with the reporting requirements of Section 801 of the FDAAA?  Please summarize FDA‘s internal compliance data.

2) Has FDA issued any warning letters, imposed any fines, or otherwise initiated any enforcement actions related to these reporting requirements?

3) Does FDA have adequate resources and authority to enforce these reporting requirements?

4) Does FDA believe additional statutory changes are necessary to address the issues of underreporting of clinical trial data and non-compliance with the reporting requirements in Section 801 of the FDAAA?

NIH is asked to provide answers to the following questions:

1) Do the findings of the [study reported in the BMJ] correspond with NIH‘s internal data on compliance with the reporting requirements of Section 801 of the FDAAA?  Please summarize NIH‘s internal compliance data.

2) Does NIH have adequate resources and authority to implement these reporting requirements?

3) Does NIH believe additional statutory changes are necessary to address the issues of underreporting of clinical trial data and non-compliance with the reporting requirements in Section 801 of the FDAAA?

Depending on how FDA and NIH respond to the inquiries – particularly the queries regarding whether additional statutory changes are necessary – it is possible that we could see even more proposed legislation that might be taken up this year alongside the various user fee bills. 

An interesting finding of the BMJ paper was that the source of funding for the clinical trials greatly influenced the reporting of results.  Industry-funded studies were far more likely to report results (40%) than were studies “not solely industry funded“ (9%).  Of note, the latter category included studies funded solely by NIH and other government agencies.  This suggests that even NIH and FDA are not in compliance with their own reporting requirements, which would surely complicate enforcement and any attempted legislative correction.  Further, the “source of funding“ used by the BMJ authors does not necessarily reflect the “responsible party.”  As permitted under the statute (PHS Act § 402(j)(1)(A)(ix)), even industry-funded studies can designate “the principal investigator” as the party responsible for the submission of clinical trial information.  Before rushing to portray these findings as another example of “industry“ not in compliance with the law, it would seem prudent to know how many NIH employees designated as either the “sponsor“ or the “responsible party“ have failed to meet these reporting obligations.

By Jeffrey K. Shapiro –

This post is the second in an occasional series that will examine significant or interesting warning letters involving medical device companies. 

As a reminder, FDA issues warning letters to allege violations of the Federal Food, Drug, and Cosmetic Act and/or implementing regulations.  A warning letter is a statement of FDA’s enforcement position and a threat to pursue legal remedies if the target does not comply.  On occasion, FDA issues a warning letter that reveals a new or little known enforcement position.  This type of warning letter will be our critical focus.

On December 27, 2011, the Philadelphia district issued a warning letter focused on Medical Device Reporting ("MDR") issues. 

This warning letter has a fascinating comment about the presumption that a malfunction is likely to contribute to a serious injury or death if it were to recur.  Essentially, FDA criticizes the target company for following the agency’s own written guidance on this issue.

As background, under the MDR regulation, a malfunction is reportable if a recurrence would likely cause serious injury or death.  21 C.F.R. § 803.50(a).  The question is, if a malfunction actually causes a serious injury or death, must the manufacturer presume that subsequent occurrences of the malfunction are “likely” to do so as well?  In 1997 guidance, FDA said:

“FDA believes that once a malfunction has caused or contributed to a death or serious injury, a presumption that the malfunction is likely to cause or contribute to a death or serious injury has been established. This presumption will continue until the malfunction has caused or contributed to no further deaths or serious injuries for two years, or the manufacturer can show, through valid data, that the likelihood of another death or serious injury as a result of the malfunction is remote.”  (Emphasis added.)

The target of the warning letter apparently had incorporated the foregoing “two year presumption” in its warning letter procedure.  FDA did not approve.  The warning letter admonishes:

Also, your firm states in [redacted] that malfunctions causing or contributing to a death or serious injury will be reported to FDA until the malfunction has not caused or contributed to further deaths or serious injuries for two years. The guidance document “Medical Device Reporting for Manufacturers,” dated March, 1997, contains a discussion of malfunctions and reportability. The guidance advises that malfunctions should be reported until valid data shows that the likelihood of another death or serious injury occurring as a result of the malfunction is remote and references a two year period. The guidance is intended to assist industry with interpreting the requirements of the MDR regulation, 21 CFR Part 803. However we currently recommend that manufacturers who wish to stop reporting a malfunction contact the MDR Policy Branch for further discussion at 301-796-6670 or by email at MDRPolicy@fda.hhs.gov.

Stepping past the District's misleading characterization of the guidance document, the warning letter is troubling on two levels.  First, it appears that FDA is disavowing the “two year presumption.”   Apparently, FDA now wishes to adjudicate the expiration of the presumption on a case by case basis.  This policy change is unfortunate.  The two year presumption has been a rare “bright line” rule among a welter of MDR reporting elements that are mostly subjective and difficult to apply in the real world.  It has been in place for 16 years with no apparent ill effect.  The decision to now require case by case adjudication of the presumption will increase the cost and uncertainty of MDR reporting.  There does not seem to be an obvious benefit to doing so.

Second, many firms have relied upon FDA’s published guidance to incorporate the two year presumption in their MDR procedures.  To our knowledge, FDA has not publicly modified the guidance.  Therefore, it seems reasonable for firms to rely upon the guidance in formulating their MDR procedures.  Yet, the warning letter suggests that firms are no longer safe in doing so. 

It is arbitrary and capricious for an administrative agency to modify published guidance via individual warning letters.  This is the opposite of transparency.  If FDA wishes to alter the two year presumption, it should follow its own Good Guidance Practices.

The terminology of the warning letter creates even more confusion.  It couches the directive to consult the MDR Policy Branch as a “recommendation.”  So, is it now violative to have a two year presumption in an MDR procedure, or not?  Must firms proactively revise their procedures?  Or should they simply wait until an inspector criticizes the procedure or issues a Form 483 observation?  Perhaps this enforcement position is unique to the Philadelphia district?  It is hard to know.

What we do know is that this warning letter has taken the helpful certainty of the two year presumption and thrown it to the wind.

REMINDER: HP&M is hosting FDA Appeals – Improving Your Odds of Success: Trends, Expectations, Strategies, a webinar on March 21, 2012, 12:30 – 2:00 p.m. ET.  Click here to register.

By Kurt R. Karst –      

Last week, Representative Bobby Rush (D-IL) announced the introduction of H.R. 3995, the Protecting Consumer Access to Generic Drugs Act of 2012.  The bill is the latest piece of legislation that attempts to stymie so-called pay-for-delay patent settlement agreements.  In January 2011, Senator Herb Kohl (D-WI) introduced S. 27, the Preserve Access to Affordable Generics Act (see our previous post here), and in November 2011, a group of bi-partisan Senators introduced S.1882, the Fair And Immediate Release of Generic Drugs Act, or the “FAIR GENERxICS Act” (see our previous post here), which also seeks to pull 180-day exclusivity into the mix by making some significant changes to the FDC Act’s exclusivity provisions.

The latest bill – H.R. 3995 – is different than the currently pending legislation, but harkens back to an older version of the Preserve Access to Affordable Generics Act introduced as S. 369 in February 2009, both in terms of substance and length.  Gone from new legislation is the controversial presumption that an agreement, if challenged by the Federal Trade Commission, is anticompetitive and unlawful unless it can be demonstrated by clear and convincing evidence that the procompetitive benefits of the agreement outweigh the anticompetitive effects of the agreement.  Instead, the Protecting Consumer Access to Generic Drugs Act of 2012 simply says that:

It shall be unlawful for any person to directly or indirectly be a party to any agreement resolving or settling a patent infringement claim in which – (1) an ANDA filer receives anything of value; and (2) the ANDA filer agrees not to research, develop, manufacture, market, or sell, for any period of time, the drug that is to be manufactured under the ANDA involved and is the subject of the patent infringement claim.

There are, of course, some exceptions.  For example, the bill would not prohibit agreements in which the value received by the ANDA sponsor includes no more than the right to market the drug product before the expiration of certain patents and non-patent marketing exclusivities.  The FTC may also promulgate regulations to further implement the exceptions included in H.R. 3995.

As in previous versions of legislation addressing patent settlement agreements, H.R. 3995 would amend the 180-day exclusivity forfeiture provision at FDC Act § 505(j)(5)(D)(i)(V) (the so-called “Collusive Agreement Forfeiture Provision”) to make a violation of the Protecting Consumer Access to Generic Drugs Act of 2012 a forfeiture-triggering event. 

H.R. 3995 has been referred to the House Judiciary and Energy and Commerce Committees.  There, it will join a growing number of FDA-related bills that have recently been introduced in the current wave of FDA legislation as folks gear up for user fee creation and reauthorization – see our Legislation Tracker.  

By Nisha P. Shah –

On February 9, 2012, FDA released a new guidance document called, “Guidance For Sponsors, Investigators, and Institutional Review Boards – Questions and Answers on Informed Consent Elements, 21 CFR § 50.25(c).”  The guidance is intended to help small businesses understand the new informed consent requirements described in 21 C.F.R. § 50.25(c), which requires that informed consent documents and processes for “applicable clinical trials,” initiated on or after March 7, 2012, include a specific statement that clinical trial information will be entered into the clinical trial registry databank maintained by the National Institutes of Health/National Library of Medicine.  That statement is, “A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time.”

In the guidance, FDA clarifies that if an IRB has approved any informed consent documents for the applicable clinical trial before March 7, 2012, then the trial will be considered “initiated” prior to the compliance date, and the new statement will not be required in the informed consent documents.  Guidance, p. 4.  FDA also explains that any applicable clinical trial, including those conducted outside of the United States, must include the new statement in informed consent documents.  Regarding waiver of documentation of informed consents, the agency affirms that, “the trial participant still provides consent and the statement is required during the oral presentation of the research and/or in the written statement regarding the research, if required by the IRB under 21 CFR § 56.109(d).”  Guidance, p. 5.  Finally, according to the guidance, if an informed consent document fails to properly include the statement, then the IRB should be notified and a revised consent form containing the statement should be provided to the IRB for review and approval. 

By Ricardo Carvajal –

In a decision sure to bring joy to the U.S. Department of Agriculture (“USDA”), the D.C. District Court granted the government’s motion for summary judgment in a lawsuit challenging a USDA regulation that requires domestically produced almonds to be treated for Salmonella.  The regulation was issued in the wake of Salmonella outbreaks associated with raw almonds, and it is credited with eliminating the domestic market for raw almonds.  The regulation was issued in part under the authority of the Agricultural Marketing Agreement Act of 1937 (“AMAA”).  The AMAA authorizes the issuance of marketing orders that dictate the “grade, size, or quality” of a commodity sold in a particular region of the U.S. 

Plaintiffs alleged that USDA had exceeded its authority because the regulation was a food safety measure, and not a quality measure.   The court noted that “quality” is not defined in the AMAA, and concluded that the term is ambiguous based in part on its dictionary definition (“[a]n attribute, property; a special feature or characteristic,” or “[a] particular class, kind, or grade of something, as determined by its character, esp[ecially] its excellence”).  The court further concluded that USDA’s interpretation of the AMAA as authorizing a food safety measure was reasonable, in that the AMAA “specifically contemplates interventions relating to ‘quality’” that are needed to “respond to both general market conditions and external threats, such as the Salmonella outbreaks…, which have the potential to cause significant market disruption.”

Curiously, in concluding that “quality” encompasses “safety,” the court did not delve into the definition of “safety” – and we won’t either.  However, we note that robust discussions of the distinction between safety and quality has taken place in other food-related contexts (see, e.g., the preamble to the dietary supplement GMP final rule). 

It’s not yet clear whether plaintiffs will appeal the court’s decision.  If so, they may also have to overcome the government’s argument that plaintiffs waived their claims by not raising them during the comment period preceding issuance of USDA’s final rule.  This potential hurdle highlights the importance of submitting timely comments during agency rulemaking.

By Jennifer D. Newberger –

On Wednesday, February 8, Representatives Mike Rogers (R-MI) and Ed Markey (D-MA) introduced H.R. 3975, The Pediatric Medical Device Safety and Improvement Reauthorization Act of 2012.  The bill would put into effect a rule previously withdrawn by FDA regarding the inclusion of pediatric information in certain medical device submissions to FDA, notwithstanding the requirements of the Administrative Procedure Act ("APA") to obtain and consider public input prior to implementing a final rule. 

A little background to the withdrawn rule is helpful in understanding the intent of this bill.  On April 1, 2010, FDA issued a proposed rule along with a direct final rule “that was intended to make noncontroversial amendments to existing regulations which would require the submission of readily available pediatric medical device information as a part of premarket approval applications, requests for humanitarian use device exemptions, and any product development protocols.”  Although the rule was intended to be noncontroversial, the agency received “significant adverse comment” and therefore withdrew the direct final rule on July 19, 2010. 

The withdrawal of the direct final rule due to receipt of significant adverse comment indicates that the APA worked precisely as intended—to allow for public participation in the rulemaking process.  This seems to be of no matter to the sponsors of this bill, which would have the withdrawn direct final rule take effect on January 1, 2013, notwithstanding the APA “and any other provision of law.” 

Certainly, just as Congress created the APA, it can create exceptions to the APA.  Before doing so, however, it should consider whether it truly wants to force upon the public a rule much of the public explicitly decried. 

REMINDER: HP&M is hosting FDA Appeals – Improving Your Odds of Success: Trends, Expectations, Strategies, a webinar on March 21, 2012, 12:30 – 2:00 p.m. ET.  Click here to register.

By Kurt R. Karst –      

Within moments of FDA’s (Dr. Janet Woodcock) announcement during the February 9th House Energy and Commerce hearing on generic drug and biosimilar user fees that the Agency would issue draft guidance on biosimilar product development later in the day, Twitter was, well . . . . all atwitter with the news.  Release of the draft guidances, which perhaps have been overpromised as “coming soon” since last summer, was officially announced by FDA just a couple of hours later. 

FDA issued three draft guidances, which provide the Agency’s current thinking on key scientific and regulatory factors involved in submitting applications for biosimilar products to FDA pursuant to the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”).  The BPCIA amended the Public Health Service Act (“PHS Act”) to, among other things, create an approval pathway for biosimilar and interchangeable versions of reference products (so-called § 351(k) applications) and establish a 12-year exclusivity period for reference products licensed under PHS Act § 351(a).  FDA’s three draft guidances are pretty dense and take into consideration comments the Agency received in response to a November 2010 public hearing on BPCIA implementation, as well as FDA’s experience thus far in meeting with sponsors of biosimilar products.  (It was recently reported that FDA has held 21 Pre-IND sponsor meetings, has received 35 Pre-IND meeting requests for proposed biosimilars to 11 reference products, and has received 9 INDs.)

Draft Guidance No. 1 – Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009:  This draft guidance document is intended to provide answers to common questions from sponsors interested in developing proposed biosimilar products.  The Q&As are grouped into three categories: (1) Biosimilarity or Interchangeability; (2) Provisions Related to Requirement to Submit a BLA for a “Biological Product;” and (3) Exclusivity (presumably carefully worded to avoid another tussle over “market” versus “data” exclusivity – see our previous post here). 

Many of the questions are drafted to elicit an initial proposed answer of “yes” or “no,” which is then futher explained and modified.  For example, FDA answers "yes" to each of the following burning questions:

• Can a proposed biosimilar product have a delivery device or container closure system that is different from its reference product?
• Can an applicant obtain licensure of a proposed biosimilar product for fewer than all routes of administration for which an injectable reference product is licensed?
• Can an applicant obtain licensure of a proposed biosimilar product for fewer than all presentations (e.g., strengths or delivery device or container closure systems) for which a reference product is licensed?
• Can an applicant obtain licensure of a proposed biosimilar product for fewer than all conditions of use for which the reference product is licensed?
• Can a sponsor use comparative animal or clinical data with a non-U.S.-licensed product to support a demonstration that the proposed product is biosimilar to the reference product?
• Can an applicant extrapolate clinical data intended to support a demonstration of biosimilarity in one condition of use to support licensure of the proposed biosimilar product in one or more additional conditions of use for which the reference product is licensed?

Among other things, the draft guidance provides FDA’s interpretation of the category of “protein (except any chemically synthesized polypeptide)” in the amended definition of “biological product” in PHS Act § 351(i)(1).  FDA defines the term “protein” to mean “any alpha amino acid polymer with a specific defined sequence that is greater than 40 amino acids in size,” and the term “chemically synthesized polypeptide” to mean “any alpha amino acid polymer that (1) is made entirely by chemical synthesis; and (2) is less than 100 amino acids in size.”  FDA goes on to note that the Agency considers “any polymer composed of 40 or fewer amino acids to be a peptide and not a protein.”  Therefore, says FDA, “unless a peptide otherwise meets the statutory definition of a 'biological product'“, it will be regulated as a “drug” under the FDC Act.

Draft Guidance No. 2 – Scientific Considerations in Demonstrating Biosimilarity to a Reference Product:  This draft guidance – the longest of the three draft guidances – is where FDA lays out the Agency’s approach to determining biosimilarity.  “FDA intends to consider the totality of the evidence provided by a sponsor to support a demonstration of biosimilarity, and recommends that sponsors use a stepwise approach in their development of biosimilar products” (italics in original) says FDA.  Under the risk-based, “totality of the evidence” approach, FDA will consider “the totality of the data and information submitted in the application, including structural and functional characterization, nonclinical evaluation, human PK and PD data, clinical immunogenicity data, and clinical safety and effectiveness data.”  Under the stepwise approach, biosimilar sponsors should evaluate at each step “the extent to which there is residual uncertainty about the biosimilarity of the proposed product and identify next steps to try to address that uncertainty,” and should start with an “extensive structural and functional characterization of both the proposed product and the reference product.” 

Draft Guidance No. 3 – Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product:  The final draft guidance is intended to provide recommendations to biosimilar applicants on the scientific and technical information of the CMC section of a 351(k) application, and includes an overview of analytical factors to consider when assessing biosimilarity between a proposed therapeutic protein product and a reference product.  FDA notes in the draft guidance that although it applies specifically to therapeutic protein products, “the general scientific principles may be informative for the development of other proteins, such as in vivo protein diagnostic products.” 

Under the PHS Act, as amended by the BPCIA, the terms “biosimilar” or “biosimilarity” mean that “the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components,” and that “there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product” (emphasis added).  FDA’s draft guidance provides a list and discussion of various factors to consider when assessing whether products are, in fact, highly similar.

We’re likely to see quite a bit of commentary submitted to FDA on the draft guidances in the coming weeks and months.  We’ve also heard that FDA might be scheduling a public hearing to elicit further comments on and discussion of the draft documents and the Agency’s approach to biosimilarity laid out therein.   

By Kurt R. Karst –      

In music, “coda” is a term used primarily to designate a passage that brings a piece (or a movement, which may be part of a symphony – an extended musical composition) to an end – the “fine.”  A coda can be as simple as a few measures, or as complex as an entire section.  These musical terms serve as a nice metaphor for The Medicines Company’s (“MDCO’s”) decade-long battle (multi-movement symphony) to obtain a Patent Term Extension (“PTE”) for U.S. Patent No. 5,196,404 (“the ‘404 patent”) covering ANGIOMAX (bivalirudin). 

As most folks know by now, FDA approved ANGIOMAX at 5:18 PM on Friday, December 15, 2000 under NDA No. 020873, and MDCO submitted its PTE application to the U.S. Patent and Trademark Office (“PTO”) on February 14, 2001 – 62 days after NDA approval, including the December 15, 2000 date of approval.  Under 35 U.S.C. § 156(d)(1), the submission of a PTE application must occur “within the sixty-day period beginning on the date the product received permission under the provision of law under which the applicable regulatory review period occurred for commercial marketing or use.”  (For additional background, see our previous post here.) 

In August 2010, Judge Hilton of the U.S. District Court for the Eastern District of Virginia (Alexandria Division) granted MDCO’s Motion for Summary Judgment and ordered the PTO to consider timely filed MDCO’s PTE application for the ‘404 patent under a next business day interpretation of the PTE statute, making December 18, 2000 the operative date for beginning the 60-day period instead of December 15, 2000.  The government decided not to appeal the decision, and the PTO proceeded to request that FDA determine the regulatory review period with respect to MDCO’s PTE application for the ‘404 patent.  FDA issued a notice in December 2010 with its determination. 

ANDA sponsor APP Pharmaceuticals, LLC (“APP”) attempted to intervene in the PTE litigation before Judge Hilton; however, APP’s Motion to Intervene was denied.  APP appealed the decision to the Federal Circuit challenging not only the district court’s intervention decision, but also the underlying merits decision.  

In the meantime, Congress passed the Leahy-Smith America Invents Act (“AIA”) (Pub. Law No. 112-029).  Section 37 of the AIA, titled “Calculation of 60-Day Period for Application of Patent Term Extension” and referred to by some as “The Dog Ate My Homework Act” or the “Medco fix,” amended the PTE statute at 35 U.S.C. § 156(d), and was intended to legislatively resolve MDCO’s PTE battle.  (There were several failed attempts in Congress to pass “The Dog Ate My Homework Act” going back to 2006.)  There was a post-AIA attempt in Congress to effectively nullify Section 37, but that effort failed – see here.

Shortly after the enactment of the AIA, MDCO sent a letter to the Federal Circuit notifying the Court of the enactment of Section 37 and asserting that it resolves the merits of the ongoing ‘404 patent PTE litigation with APP.  APP vigorously disagreed that Section 37 resolved the case, however, and argued that Section 37 cannot constitutionally be applied and that Section 37 does not take effect for one year after the AIA‘s enactment (i.e., September 16, 2012).  The parties brief the issues and oral argument was held on November 15, 2011 – see our previous post here. 

Before the Federal Circuit could issue its decision on AIA Section 37, MDCO and APP entered into a settlement agreement that includes APP’s agreement to dismiss its appeal of Judge Hilton’s August 2010 decision, as well as another Hatch-Waxman patent infringement lawsuit brought in the U.S. District Court for the District of Delaware over  two other Orange Book-listed patents for ANGIOMAX – see our previous post here.  The Federal Circuit dismissed the case on January 24, 2012.

Exiting the last movement of the ANGIOMAX Symphony and moving on to the coda, the PTO issued a Notice of Final Determination on January 31, 2012 saying that the ‘404 patent is entitled to a PTE of 1,728 days that expires on December 15, 2014 – 14 years to the clendar day that FDA approved NDA No. 020873, but three days earlier than the December 18, 2000 next business day date MDCO was determined to have received notification of the approval.  Although not necessary, MDCO promptly notified the PTO on February 3, 2012 of its acceptance of the 1,728-day PTE.  While the ‘404 PTE battle has taken numerous twists and turns throughout the years and has touched all three brances of government, we expect the coda here to be short.  All that seems to be left now is for the PTO to issue a Certificate of Extension (which will look something like this) and publish the information on the Official Gazette – fine!  Adieu ANGIOMAX PTE battle.

By Kurt R. Karst –      

It’s about that time of year again when we do some number crunching and take stock of the year that was in orphan drug designations and approvals.  And what a year it was!  FDA not only approved a record 26 marketing applications for products for orphan (i.e., rare) diseases and conditions, but FDA’s Office of Orphan Products Development (“OOPD”) granted a record 199 orphan drug designation requests.   OOPD also received 306 orphan drug designation requests in 2011, which is only second to the record of 323 designation requests set in 2010 (see our previous post here).  Of the 3,659 orphan drug designation requests submitted to FDA since the enactment of the Orphan Drug Act in 1983, OOPD has granted 2,507 of them, or about 68.5%. 

The tables below show OOPD’s designation and FDA’s orphan drug approval track record.  (Additional historical information on the year-by-year designation/approval numbers since the enactment of the Orphan Drug Act in 1983 is available here.) 

 
In addition to the record numbers of orphan drug designations and approvals, 2011 also saw a change in OOPD leadership with the installment of Gayatri Rao, M.D., J.D. as Acting Director (see our previous post here), and the first U.S. Conference on Rare Diseases and Orphan Products.  At the conference, Chairman of the NORD Board of Directors and Hyman, Phelps & McNamara, P.C. Director, Frank J. Sasinowski announced the release of a landmark report he authored on the flexibility in FDA’s review of potential treatments for patients with rare diseases (see our previous post here).  Shortly thereafter, FDA issued a proposed rule intended to clarify regulatory provisions and make minor improvements to address issues that have arisen since the Agency promulgated its orphan drug regulations in December 1992 (see our previous post here).  FDA also issued a report to Congress with findings and recommendations to improve the current regulatory/scientific armamentarium to facilitate the development of products for rare and neglected diseases (see our previous post here). 

The 2011 orphan drug designation and approval numbers may be difficult marks to beat; however, FDA appears to be off to a decent start in 2012 with 8 designations and 2 approvals in January.

REMINDER: HP&M is hosting FDA Appeals – Improving Your Odds of Success: Trends, Expectations, Strategies, a webinar on March 21, 2012, 12:30 – 2:00 p.m. ET.  Click here to register.