By Kurt R. Karst & Jeffrey K. Shapiro –      

French company PREVOR has filed a Complaint in the U.S. District Court for the District of Columbia  challenging FDA’s determination that PREVOR’s Diphoterine® Skin Wash (“DSW”) is a drug-device combination product with a “drug” primary mode of action.  Hyman, Phelps & McNamara, P.C. represents PREVOR in the lawsuit.

DSW consists of a liquid substance contained inside a canister.  It is intended to help prevent and minimize chemical burn injuries that occur due to accidental exposure to chemicals and is intended to be used in the industrial setting as a “first response” method.  DSW is sprayed onto the skin to physically and mechanically remove or wash away the offensive chemical from the skin.  A secondary purpose is to neutralize the acids and bases that are washed off the skin.  The Complaint alleges that uncontradicted data show that over 90% of the overall intended purpose of the product comes from a physical washing effect, and that less than 10% of the intended purpose comes from a chemical neutralization effect. 

Under the FDC Act and FDA’s implementing regulations, a product that is a “device” is generally subject to the regulatory authority of FDA’s Center for Devices and Radiological Health (“CDRH”), while a product that is a “drug” is generally subject to the regulatory authority of FDA’s Center for Drug Evaluation and Research (“CDER”).  Some products, termed combination products, contain both drug and device components. 

In October 2009, OCP issued a Letter of Designation to PREVOR in response to the company’s August RFD.  OCP concluded that DSW is a drug-device combination in which the liquid is the “drug” constituent part and the canister is the “device” constituent part. OCP further concluded that DSW has a “drug” primary mode of action and assigned primary jurisdiction of the product to CDER for regulation.  In March 2010, PREVOR requested that FDA’s Office of Special Medical Programs (“OSMP”) reconsider OCP’s October 2009 determination.  More than a year later, however, on April 25, 2011, FDA’s OSMP issued a letter affirming OCP’s October 2009 determination. 

The Complaint states that DSW is a liquid that meets the statutory definition of a “device,” because its primary intended purpose is not chemical, but physical/mechanical, and alleges that FDA’s jurisdictional determination is arbitrary, capricious, and contrary to law under the Administrative Procedure Act.  PREVOR also alleges, among other things, that FDA “erroneously ruled that a product does not meet the definition of a device if there is any chemical action within or on the body of man in achieving its primary effect,” and that FDA’s decision “conflicts with numerous prior decisions by FDA to regulate products as devices because their primary effect is physical, despite having some chemical effect.” 

PREVOR is seeking injunctive relief and a Declaratory Judgment that would vacate FDA’s finding that DSW’s solution is a “drug” and not a “device” and designation of DSW as a drug-device combination product with a “drug” primary mode of action, and that DSW is a “device,” or, in the alternative, that DSW is a drug-device combination product with a “device” primary mode of action.

About 18 months after coming to FDA to serve as Chief Counsel, Ralph Tyler will be leaving the Agency, according to an FDA-wide e-mail sent out on June 30th by FDA Commissioner Margaret Hamburg.  Prior to joining FDA, Mr. Tyler served as Insurance Commissioner of the State of Maryland (see our previous post here).  Mr. Tyler's last day at FDA will be August 5, 2011.  We understand that an Acting FDA Chief Counsel has not yet been named. 

By Kurt R. Karst –      

A recent unpublished decision out of the U.S. District Court for the District of New Jersey presented an interesting public disclosure issue that we think will be of interest to the Hatch-Waxman community.  The case, like so many Hatch-Waxman cases, is complicated.  It involves an ANDA for a generic version of SOLARAZE (diclofenac sodium) Gel, Paragraph IV certifications to six Orange Book-listed patents, a subsequent Paragraph IV Notice Letter with a Detailed Statement, an Offer of Confidential Access (“OCA”), and a Discovery Confidentiality Order (“DCO”) previously entered in the patent infringement litigation.  We’ll spare you a recitation of all of the details of the case, but what’s important is the question the court addressed in its decision: whether the ANDA sponsor’s Paragraph IV Notice Letter, including the appended Detailed Statement, is a confidential document that should be protected from unrestricted disclosure under the DCO. 

Pursuant to the FDC Act (§ 505(j)(2)(B)), as amended by the Hatch-Waxman Amendments and the Medicare Modernization Act, and FDA’s implementing regulations (21 C.F.R. § 314.95), an ANDA sponsor whose application contains a Paragraph IV certification must send notice of such certification to the NDA holder and patent owner.  Such notice must:

(I) state that an application that contains data from bioavailability or bioequivalence studies has been submitted under this subsection for the drug with respect to which the certification is made to obtain approval to engage in the commercial manufacture, use, or sale of the drug before the expiration of the patent referred to in the certification; and

(II) include a detailed statement of the factual and legal basis of the opinion of the applicant that the patent is invalid or will not be infringed.

In addition, FDC Act § 505(j)(5)(C) provides that a Paragraph IV notice letter may include an OCA to provide the NDA holder/patent owner confidential access to certain information from an ANDA “for the sole and limited purpose of evaluating possible infringement of the patent that is the subject of the [Paragraph IV certification] and for no other purpose.” An OCA must “contain such restrictions as to persons entitled to access, and on the use and disposition of any information accessed, as would apply had a protective order been entered for the purpose of protecting trade secrets and other confidential business information.”  Moreover, “[a]ny person provided an offer of confidential access . . . may not disclose information of no relevance to any issue of patent infringement to any person other than a person provided an [OCA].”

In the case before the New Jersey District Court, a dispute arose between the NDA holder/patent owner, on the one hand, and the ANDA sponsor, on the other hand, as to whether the ANDA sponsor’s Paragraph IV Notice Letter, which included an OCA,  should be subject to the restrictions of the DCO previously entered in the case.  The Court directed the parties to file a joint dispute letter setting forth their respective positions on the issue, and based on which the Court made its decision.  The NDA holder/patent owner argued that under controlling authority, all Paragraph IV Notice Letters are public disclosures and that the OCA is not applicable to a Paragraph IV Notice Letter.  The ANDA sponsor argued otherwise, saying that “Plaintiffs have provided no legitimate reason why the Paragraph IV Notice Letter and the OCA’s detailed statement should be exempt from the DCO’s confidentiality provisions entered by the Court.”

In reaching its decision, the Court first addressed “Whether the Detailed Statement is Part of the Paragraph IV Notice Letter, and Whether the OCA Applies to the Detailed Statement.”  On the first part of that issue, the Court said that the Paragraph IV Notice Letter cannot be separated from the Detailed Statement, as a “detailed statement that contains a ‘full and detailed explanation’ is a necessary part of a paragraph IV notice letter,” and that “[p]aginating the OCA and Detailed Statement consecutively does not eliminate the requirement that the Detailed Statement must be part of the Paragraph IV Notice Letter.”  With respect to the OCA’s applicability to a Detailed Statement, the Court commented that “an OCA pertains to access to an ANDA and not to a paragraph IV notice letter,” and that because “an OCA ‘accompanie[s]’ a paragraph IV letter notice, [it] is thus not a part of a notice letter itself or a notice letter’s detailed statement.”  Moreover, “viewing the OCA and the Detailed Statement as one and the same is inconsistent with the FDCA.”  After all, says the Court quoting from the joint dispute letter, “the confidential access provision ‘does not indicate that use of information provided in a paragraph IV notice letter or failure to object to the proposed terms of confidentiality contained in a paragraph IV notice letter constitutes acceptance of such terms.’”

Having decided that the ANDA sponsor’s Detailed Statement is part of the Paragraph IV Notice Letter and that the OCA does not govern them, the Court next addressed “Whether the Paragraph IV Notice Letter Is a Public Disclosure.”  In making its decision, the Court relied heavily on a January 7, 2010 FDA Letter Decision concerning whether certain Paragraph IV notice information included in a Citizen Petition docket (Docket No. FDA-2009-P-0423) – but in a patent infringement case not involving an OCA – is protected from disclosure by FDA.  In its Letter Decision, FDA explained that a Paragraph IV Notice Letter “is an integral part of a public process” and that “the statutory scheme contemplates that the paragraph IV notice letter is the first step in an inherently public process.”  The FDA also noted, however, that in that case, the Paragraph IV Notice Letter and the information in it was disclosed to a member of the public without the ANDA sponsor “taking advantage of the process specifically set forth in § 505(j)(5)(C)(i)(III) for disclosing sensitive information contained in its ANDA.”  Nevertheless, given FDA’s Letter Decision, the New Jersey District Court ruled that the information disclosed by the ANDA sponsor “in its Paragraph IV Notice Letter is now part of ‘an inherently public process’ and therefore constitutes a public disclosure.” 

Having completed the above two-step analysis, the Court ultimately ruled that “[b]ecause the Paragraph IV Notice Letter is not shielded from public view, it is not subject to the [DCO].  The Detailed Statement, as part of the Paragraph IV Notice Letter, is a public disclosure.  The [DCO] does not restrict access to or use of documents that are public,” and therefore, the DCO does not restrict use of the ANDA sponsor’s Paragraph IV Notice Letter.

So, what’s the take-away message for ANDA sponsors?  Be careful what information you disclose in a Paragraph IV Notice Letter and in the appended Detailed Statement, even if you include an OCA.  The disclosed information is not, according to one court, subject to an OCA and could be made available to the world with the click of a mouse. 

By Kurt R. Karst –      

The continuing court battle over a Patent Term Extension (“PTE”) for U.S. Patent No. 5,196,404 (“the ‘404 patent”) covering The Medicines Company’s (“MDCO’s”) ANGIOMAX (bivalirudin) could be derailed if a recent amendment added to the House version of the America Invents Act (H.R. 1249) is accepted when conferees from the House and Senate meet to iron out differences between their respective versions of the bill.  (The Senate-passed version of the America Invents Act is S. 23 and does not include the PTE provision discussed below.) 

The amendment, included in Part B of House Report 112-111 and sponsored by Representative John Conyers (D-MI), would amend the PTE law at 35 U.S.C. § 156 to add at the end of § 156(d)(1) the following flush sentence:

For purposes of determining the date on which a product receives permission under the second sentence of this paragraph, if such permission is transmitted after 4:30 P.M., Eastern Time, on a business day, or is transmitted on a day that is not a business day, the product shall be deemed to receive permission on the next business dy.  For purposes of the preceding sentence, the term "business day" means any Monday, Tuesday, Wednesday, Thursday or Friday, excluding any legal holiday under section 6103 of title 5.

The “applicability” section of the amendment states that language above “shall apply to any application for extension of a patent term under section 156 of title 35, United States Code, that is pending on, that is filed after, or as to which a decision regarding the application is subject to judicial review on, the date of enactment of this Act.”  That, of course, describes MDCO’s situation.

By way of background, FDA approved ANGIOMAX at 5:18 PM on Friday, December 15, 2000, 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.”  The PTO denied MDCO a PTE for the ‘404 patent and MDCO sued.

Currently, and as we previously reported, in February 2011, the U.S. Court of Appeals for the Federal Circuit denied MDCO’s Motion to Dismiss or, in the Alternative, to Bifurcate and Stay in Part ANDA sponsor APP Pharmaceuticals, LLC’s (“APP’s”) appeal related to Judge Claude M. Hilton’s August 3, 2010 decision in which Judge Hilton 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.  The Federal Circuit’s February decision was precipitated by Judge Hilton’s September 13, 2010 decision denying APP’s Motion to Intervene in the litigation without addressing standing (on the basis that APP should have sought intervention earlier, and that allowing intervention at that point would unfairly prejudice MDCO).  APP appealed the decision to the Federal Circuit challenging not only the district court’s September 13th intervention decision, but also the underlying merits decision.  Briefing in the case, in which ANDA sponsor PLIVA filed an amicus brief in support of APP, appears to have been completed.

The Conyers amendment to H.R. 1249 had previously passed by voice vote during a markup of the bill earlier this year by the House Judiciary Committee (see our previous post here), but was subsequently stripped from the bill in a managers amendment.  Rep. Conyers’ H.AMDT.499 (A009) to H.R. 1249 restored the PTE language in the previously passed and stricken amendment.  The amendment was agreed to in an after business hours, recorded vote of 223 to 198 (Roll no. 485) that occurred on June 23rd at 4:58 P.M., Eastern Time.

The Conyers amendment passed after some lively debate on the floor of the U.S. House of Representatives (see Congressional Record pages H4489-4490 here).  Representative Conyers said that the amendment “addresses the confusion regarding the calculation of the filing period for [PTE] applications under the Hatch-Waxman Act,” that “[b]y eliminating confusion regarding the deadline for [PTE] applications, this amendment provides the certainty necessary to encourage costly investments in life-saving medical research,” and that the amendment is consistent with Judge Hilton’s August 2010 decision. 

Rep. Ed Markey (D-MA) echoed Rep. Conyers’ comments and added that the amendment “promotes good government by ensuring that the Patent Office and the FDA adopt consistent interpretations of the very same statutory language.”  Rep. Markey also commented that “[r]ight now, America’s next Lipitor or Prozac could be bottled up at the Patent Office and never made available because of uncertainty regarding the patent term extension process,” and that “[i]n order to uncork American innovation and invention, we need a patent extension process that is clear, consistent, and fair.”  Similarly, Rep. Scott Garrett (R-NJ) commented that the amendment

will clarify that when the FDA provides the final approval after normal business hours, the 60-day clock begins on the next business day.  So by doing this, by ensuring that patent holders will not lose their rights prematurely, what this amendment does is it will not only resolve a longstanding problem but will encourage the development of innovative new drugs as well.

(So does that mean that an after business hours approval by FDA does not become effective until the next business day?)

Not all of the House floor debate was in support of the Conyers amendment.  Rep. Lamar Smith (R-TX) opposed the amendment, saying that it essentially codifies Judge Hilton’s August 2010 decision, “but it ignores the fact that this case is on appeal.”  Rep. Smith further commented that:

We need to let the courts resolve the pending litigation.  It is standard practice for Congress not to interfere when there is ongoing litigation. If the Federal Circuit rules against [MDCO], generic manufacturers of the drug could enter the marketplace immediately rather than waiting another 5 years. This has the potential to save billions of dollars in health care expenses. While the amendment is drafted so as to apply to other companies similarly situated, as a practical matter, this is a special fix for one company.

Instead of including the PTE provision in H.R. 1249, Rep. Smith said that “it would be more appropriate for this to be considered as a private relief bill,” which is a type of bill “designed to provide benefits to a specific individual or corporate entity.”  Such bills have been introduced in the past seeking an extension of a patent term.  For example, in the 111th Congress, H.R. 2508 was introduced to extend the term of U.S. Patent No. 5,180,715 for a period of 2 years.  That patent, now expired, was listed in the Orange Book for ELMIRON (pentosan polysulfate sodium) Capsules.

By Dara Katcher Levy –

Last week, FDA’s Division of Drug Marketing, Advertising, and Communications (“DDMAC”) released an Untitled Letter issued to Novartis on May 31st, which alleges the company made unsubstantiated superiority claims in a detail aid for its ADHD drug, Focalin XR.  Unlike most promotional material that trigger DDMAC letters citing unsubstantiated superiority claims, the promotional claims that were the subject of this letter were based on the statistically significant results of the primary endpoints of two comparative studies.  In addition to the sections of the Federal Food, Drug, and Cosmetic Act, DDMAC cites violations of regulations at 21 C.F.R. § 202.1(e)(6)(ii), (xviii); (e)(7)(1) and (ii).

The Focalin XR detail aid contained the following information, cited by DDMAC:

• Two well-controlled studies confirmed the efficacy of Focalin XR versus Concerta at 2 hours postdose.
• Graph titled, “ADJUSTED MEAN CHANGE IN SKAMP-COMBINED SCORE FROM PREDOSE TO 2 HOURS POSTDOSE,” which compares Focalin XR 20 mg and Concerta 36 mg.
• Focalin XR demonstrated statistically significant superior efficacy versus Concerta 2 hours postdose.
• Conclusion – Two well-controlled studies confirmed the superior efficacy of Focalin XR 20 mg versus Concerta 36 mg at 2 hours postdose.

We note that each claim cited by DDMAC contained the phrase, “2 hours postdose.” 

The DDMAC letter alleges that the claims are misleading in that they imply a general superiority of Focalin XR based on the benefit demonstrated at 2 hours.  DDMAC states that “By focusing on the 2-hour post-dose time point, the studies did not account for the different pharmacokinetic profiles and subsequent efficacy profiles associated with Focalin XR and Concerta over the entire treatment course.”  DDMAC then discusses how each drug is formulated, when each drug’s peak efficacy occurs, and states that the two referenced studies which suggest greater Focalin XR symptom relief at 2 hours also suggest that Concerta may deliver greater symptom relief than Focalin XR from hour nine and beyond.

What is striking is that DDMAC does not take issue with the truthfulness of the statement as written, instead, it focuses on the implication of generalized superiority.  We note the regulatory language in 21 C.F.R. § 202.1(e)(6)(ii) addresses misleading comparative statements that imply greater efficacy “in some particular.”  We would argue that the contextualizing statements of “2 hours postdose” provide that particular.

Further, DDMAC cites to 21 C.F.R. § 202.1(e)(7)(i) and (ii), alleging that the study is inadequate in design, scope, or conduct to furnish significant support for the information, and that the claim has not been demonstrated to have clinical significance or validity.  Presumably, this relates to DDMAC’s allegation that the company failed to analyze the two drugs for a longer period of time (“over the entire treatment course”).  What is interesting, however, is that FDA apparently does give consideration to measures of efficacy at hourly timepoints post dose.  Although not the single pivotal trial, the Focalin XR prescribing information references three additional studies evaluated by reviewers that looked at efficacy in hourly timepoints post dose v. placebo using the same rating scale (SKAMP) as that used in the comparative studies. One study evaluated efficacy 0.5, 1, 3, 4, 5, 7, 9, 10, 11 and 12 hours post dose, and another 1, 2, 4, 6, 8, 9, 10, 11 and 12 hours post dose.  A treatment effect study is also referenced, which evaluated efficacy at .5 hours post dose.  This may undercut DDMAC’s argument that a 2 hour timepoint is not of clinical significance.

We have to wonder whether DDMAC is just picking on Novartis with this one because of its track record.  We’ve witnessed quite a number of comparative promotional pieces currently in the marketplace, supported by a lot less data than a head-to-head study (let alone two!), and these seem to be whizzing under the radar screen over at DDMAC.  Is this more of a general message from DDMAC to industry about the use of comparative promotional claims in general?  We’ll watch and see DDMAC’s continued regulation through enforcement on the issue.

By Ricardo Carvajal –

The New England Journal of Medicine published two articles bound to stoke more controversy in the battle over approaches to countering obesity.  A perspective piece authored by Dr. Kelly Brownell, Director of the Yale Rudd Center for Food Policy and Obesity, and Dr. Jeffrey Koplan, Director of the Emory Global Health Institute and former Director of the CDC, argues that industry’s recently announced front-of-pack labeling initiative, Nutrition Keys, is a “unilateral, unscientific, preemptive approach” that should be shelved pending completion of the IOM’s ongoing review (see our prior posting on the first phase of that review).  Prior criticisms in this vein have been cast as “part of a larger attack on commercial speech” and emblematic of “nanny policy preferences.”

In their perspective piece, Drs. Brownell and Koplan make the following observation:

A mantra of the food and beverage industry is that “there is no bad food.” Even if that were true, there still would be better and worse or more healthful and less healthful foods.

That issue is tackled head-on by an article authored by Dr. Dariush Mozaffarian et al that reports the findings of a 20-year prospective study of 3 cohorts including 120,877 individuals who were not obese at the study’s outset.  Among the results reported by the authors:

Strong positive associations with weight change were seen for starches, refined grains, and processed foods.  These findings are consistent with those suggested by the results in limited short-term trials: consumption of starches and refined grains may be less satiating, increasing subsequent hunger signals and total caloric intake, as compared with equivalent numbers of calories obtained from less processed, higher-fiber foods that also contain healthy fats and protein.  Consumption of processed foods that are higher in starches, refined grains, fats, and sugars can increase weight gain.

Given its potential economic and policy implications, the study is bound to be carefully dissected and its findings hotly debated over the coming weeks.

By Ben Wolf* and Jeff Wasserstein –

Justice Kennedy delivered the opinion of the Supreme Court in today’s 6-3 decision in Sorrell v. IMS Healthcare Inc. (Docket No. 10-779). This decision strikes down a Vermont law prohibiting the sale, disclosure, and use of pharmacy records that reveal the prescribing practices of individual doctors for use in the marketing of drugs.  This data is frequently used by pharmaceutical companies in targetting physicians for detailing and other marketing activities.

Vermont argued that it had enacted the Prescription Confidentiality Law (Vt. Stat. Ann., Tit. 18, § 4631) in an attempt to:

(1) protect medical privacy by reducing the dissemination of physician prescribing information;

(2) avoid harassment when detailers visit the physician’s office by reducing the detailers’ incentive to visit;

(3) preserve the integrity of the doctor-patient relationship by assuaging patient fears that their physicians are being unduly influenced by the drug companies; and

(4) lower healthcare costs by reducing the amount of brand name drugs prescribed. 

However, the Supreme Court found that § 4631 was ineffective in these goals, and impermissibly burdened the First Amendment free speech rights of those seeking to use the IMS prescribing data for sales purposes.

Now that § 4631 has been struck down, companies that obtain prescription data from IMS to analyze for use in drug sales are once again free to use this data in detailing to physicians in the “Freedom and Unity” state.  This decision will spell an end to similar laws in New Hampshire and Maine, which had previously been upheld by the First Circuit.

*Law Student

By Kurt R. Karst –      

Like a young attorney (full of angst) waiting for Bar Exam results to be posted on the Internet, we sat in front of our computer this morning constantly hitting the “refresh” button to update the U.S. Supreme Court’s “2010 Term Opinions of the Court” website waiting for the Court to post its highly anticipated consolidated opinion in PLIVA Inc. v. Mensing (Docket No. 09-993), Actavis Elizabeth, L.L.C. v. Mensing (Docket No.  09-1039), and Actavis, Inc. v. Demahy (Docket No. 09-1501).  It happened at 10:15 AM.

In a 5-4, 20-page landmark majority decision delivered by Justice Clarence Thomas (joined in full by Chief Justice Roberts and Justices Scalia and Alito and and as to all except for Part III-B-2 by Justice Kennedy), the Court invoked the doctrine of impossibility preemption to hold that federal drug regulations applicable to generic drug manufacturers directly conflict with, and thus preempt, state tort-law claims based on drug manufacturers’ alleged failure to provide adequate warning labels for their products (in this case generic metoclopramide).  With this decision, the judgments of the Fifth and Eighth circuits were reversed, and the cases remanded for further proceedings. 

The decision comes a little more than two years after the Court issued its March 4, 2009 decision in Wyeth v. Levine holding that a state tort action against a brand name drug manufacturer for failure to provide an adequate warning label was not preempted.  Wyeth argued that it was impossible for the manufacturer to comply with both state and federal law under FDA’s Changes Being Effected (“CBE”) regulations.

We’re still poring over the nooks and crannies of the decision, but for now, here’s the bottom line:

(1)  The Court finds impossibility here.  If the Manufacturers had independently changed their labels to satisfy their state-law duty to attach a safer label to their generic metoclopramide, they would have violated the federal requirement that generic drug labels be the same as the corresponding brand-name drug labels.  Thus, it was impossible for them to comply with both state and federal law.  And even if they had fulfilled their federal duty to ask for FDA help in strengthening the corresponding brand-name label, assuming such a duty exists, they would not have satisfied their state tort-law duty.  State law demanded a safer label; it did not require communication with the FDA about the possibility of a safer label. Pp. 11–12.

(2)  The Court rejects the argument that the Manufacturers’ preemption defense fails because they failed to ask the FDA for help in changing the corresponding brand-name label.  The proper question for “impossibility” analysis is whether the private party could independently do under federal law what state law requires of it.  See Wyeth, supra, at 573. Accepting respondents’ argument would render conflict pre-emption largely meaningless by making most conflicts between state and federal law illusory. In these cases, it is possible that, had the Manufacturers asked the FDA for help, they might have eventually been able to strengthen their warning label.  But it is also possible that they could have convinced the FDA to reinterpret its regulations in a manner that would have opened the CBE process to them, persuaded the FDA to rewrite its generic drug regulations entirely, or talked Congress into amending the Hatch-Waxman Amendments.  If these conjectures sufficed to prevent federal and state law from conflicting, it is unclear when, outside of express preemption, the Supremacy Clause would have any force. That Clause— which makes federal law “the supreme Law of the Land . . . any Thing in the Constitution or Laws of any State to the Contrary notwithstanding,” U.S. Const., Art. VI, cl. 2—cannot be read to permit an approach to pre-emption that renders conflict pre-emption all but meaningless.  Here, it is enough to hold that when a party cannot satisfy its state duties without the Federal Government’s special permission and assistance, which is dependent on the exercise of judgment by a federal agency, that party cannot independently satisfy those state duties for pre-emption purposes. Pp. 12–14, 17. 

(3)  Wyeth is not to the contrary.  The Court there held that a state tort action against a brand-name drug manufacturer for failure to provide an adequate warning label was not pre-empted because it was possible for the manufacturer to comply with both state and federal law under the FDA’s CBE regulation.  555 U.S., at 572-573.  The federal statutes and regulations that apply to brand-name drug manufacturers differ, by Congress’ design, from those applicable to generic drug manufacturers.  And different federal statutes and regulations may, as here, lead to different pre-emption results.  This Court will not distort the Supremacy Clause in order to create similar pre-emption across a dissimilar statutory scheme.  Congress and the FDA retain authority to change the law and regulations if they so desire.  Pp. 17–20.

In what some might view as the central piece of the decision, the majority says that even assuming that generic drug manufacturers have a duty to propose labeling changes to FDA, there is still preemption, because to hold to the contrary would effectively nullify the Supremacy Clause:

[Plaintiffs] Mensing and Demahy contend that, while their state law claims do not turn on whether the Manufacturers asked the FDA for assistance in changing their labels, the Manufacturers’ federal affirmative defense of pre-emption does. Mensing and Demahy argue that if the Manufacturers had asked the FDA for help in changing the corresponding brand-name label, they might eventually have been able to accomplish under federal law what state law requires.  That is true enough. The Manufacturers “freely concede” that they could have asked the FDA for help.  PLIVA Brief 48.  If they had done so, and if the FDA decided there was sufficient supporting information, and if the FDA undertook negotiations with the brand-name manufacturer, and if adequate label changes were decided on and implemented, then the Manufacturers would have started a Mouse Trap game that eventually led to a better label on generic metoclopramide.

This raises the novel question whether conflict preemption should take into account these possible actions by the FDA and the brand-name manufacturer.  Here, what federal law permitted the Manufacturers to do could have changed, even absent a change in the law itself, depending on the actions of the FDA and the brand-name manufacturer.  Federal law does not dictate the text of each generic drug’s label, but rather ties those labels to their brand-name counterparts.  Thus, federal law would permit the Manufacturers to comply with the state labeling requirements if, and only if, the FDA and the brand-name manufacturer changed the brand-name label to do so.

Mensing and Demahy assert that when a private party’s ability to comply with state law depends on approval and assistance from the FDA, proving pre-emption requires that party to demonstrate that the FDA would not have allowed compliance with state law.  Here, they argue, the Manufacturers cannot bear their burden of proving impossibility because they did not even try to start the process that might ultimately have allowed them to use a safer label.  Brief for Respondents 47.  This is a fair argument, but we reject it.

The question for “impossibility” is whether the private party could independently do under federal law what state law requires of it. . . .  Accepting Mensing and Demahy’s argument would render conflict pre-emption largely meaningless because it would make most conflicts between state and federal law illusory.  We can often imagine that a third party or the Federal Government might do something that makes it lawful for a private party to accomplish under federal law what state law requires of it. In these cases, it is certainly possible that, had the Manufacturers asked the FDA for help, they might have eventually been able to strengthen their warning label.  Of course, it is also possible that the Manufacturers could have convinced the FDA to reinterpret its regulations in a manner that would have opened the CBE process to them. Following Mensing and Demahy’s argument to its logical conclusion, it is also possible that, by asking, the Manufacturers could have persuaded the FDA to rewrite its generic drug regulations entirely or talked Congress into amending the Hatch-Waxman Amendments.

If these conjectures suffice to prevent federal and state law from conflicting for Supremacy Clause purposes, it is unclear when, outside of express pre-emption, the Supremacy Clause would have any force.  We do not read the Supremacy Clause to permit an approach to preemption that renders conflict pre-emption all but meaningless.

The 21-page dissenting opinion delivered by Justice Sotomayor (joined in by Justices Ginsburg, Breyer, and Kagan) says that the majority “invents new principles of pre-emption law out of thin air to justify its dilution of the impossibility standard,” and thus makes the mere possibility of impossibility enough to establish preemption, and that the majority decision “effectively rewrites our decision in [Wyeth].”

Reaction to the decision has been swift.  The Generic Pharmaceutical Association (“GPhA”) promptly issued a press release saying that the organization “believes the High Court has appropriately recognized that current law leaves generic manufacturers with no alternative but to make certain that its products have labeling that is identical to the labeling of the reference brand product.”

And what about Congress?  Will it act to enact legislation intended to curb the Supreme Court’s decision?  In discussing the Wyeth decision, the Court notes that Congress is always free to change the law:

We recognize that from the perspective of Mensing and Demahy, finding pre-emption here but not in Wyeth makes little sense.  Had Mensing and Demahy taken Reglan, the brand-name drug prescribed by their doctors, Wyeth would control and their lawsuits would not be pre-empted. But because pharmacists, acting in full accord with state law, substituted generic metoclopramide instead, federal law pre-empts these lawsuits.  We acknowledge the unfortunate hand that federal drug regulation has dealt Mensing, Demahy, and others similarly situated.

But “it is not this Court’s task to decide whether the statutory scheme established by Congress is unusual or even bizarre.”  It is beyond dispute that the federal statutes and regulations that apply to brand-name drug manufacturers are meaningfully different than those that apply to generic drug manufacturers.  Indeed, it is the special, and different, regulation of generic drugs that allowed the generic drug market to expand, bringing more drugs more quickly and cheaply to the public.  But different federal statutes and regulations may, as here, lead to different pre-emption results. We will not distort the Supremacy Clause in order to create similar preemption across a dissimilar statutory scheme.

As always, Congress and the FDA retain the authority to change the law and regulations if they so desire. [(Internal citations omitted)]

Finally, what does the Supreme Court’s decision mean with respect to decisions like that reached by a California appellate court in Conte v. Wyeth, which held that the manufacturer of a brand name drug could potentially be held liable for an injury allegedly caused by the generic version of the drug?  (See our previous post here.)  This question is almost sure to be answered in due course. 

By Dara Katcher Levy –

Earlier this week, FDA announced the release of a report regarding the increasing globalization of FDA-regulated products that are consumed by Americans, and how FDA intends to improve the safety and quality of these products.  FDA states that the report was prompted by “this rapidly changing environment, and a desire to move from a posture of intercepting harmful products to anticipating and preventing the arrival of such goods.”

The bulk of the report deals with facts and figures about the increasing number of imports and how, if the numbers continue to increase at current rates, the agency, continuing as it has been, will be ill-equipped to ensure the safety and quality these products.  FDA states it plans on transforming itself over the next decade into “a truly global agency fully prepared for a regulatory environment in which product safety and quality know no borders” and will do so with an approach based on four core building blocks:

1. FDA, in close partnership with its foreign counterparts, will assemble global coalitions of regulators dedicated to building and strengthening the product safety net around the world.
2. With these coalitions, FDA intends to develop a global data information system and network in which regulators worldwide can regularly and proactively share real-time information and resources across markets.
3. FDA will continue to expand its capabilities in intelligence gathering and use, with an increased focus on risk analytics and thoroughly modernized IT capabilities.
4. FDA will effectively allocate agency resources based on risk, leveraging the combined efforts of government, industry, and public- and private-sector third parties.

Much of the report is similar to Commissioner Hamburg’s statement to the Subcommittee on Oversight and Investigations, Committee on Energy and Commerce, U.S. House of Representatives given in April of this year.   

While it is laudable that FDA is taking action, reaching out to its foreign counterparts, and issuing this report, this “rapidly changing environment” has not rapidly changed overnight and has been “rapidly changing” for some time.  It’s unclear whether this report truly represents any “new” approach, rather, it appears this is a continuation of FDA's existing approach toward imports.  Although some of the facts and figures may have been updated, the statements in the report are essentially, not new.  Similar statements have been made by the FDA for years.  President Bush established an Interagency Working Group on Import Safety back in 2007, and FDA has provided updates since on its implementation of the “Import Safety Action Plan.”  FDA’s “Enforcement Story” Chapter 9, “Operations in a Global Environment,” provided an extensive look at steps being taken back in FY 08 to ensure import safety.  These steps included "Beyond Our Borders," an initiative to establish an FDA presence in foreign countries as well as partnerships with foreign regulatory agencies that included information sharing.  Further, since 2008, FDA has launched the PREDICT (Predictive Risk-Based Evaluation for Dynamic Import Compliance Targeting) system, software utilized by FDA that tracks historical data on importers, manufacturers, products, and even countries, to determine levels of risk for proposed imports, and to create consistency in FDA's approach towards these imports from port to port. 

Commissioner Hamburg’s prepared remarks for the Center for Strategic and International Studies in February 2010, address almost the identical issues contained in the most recent FDA report, including steps FDA intends to take to address these issues.  One development that could invigorate FDA’s efforts, at least with respect to imported foods, is the recent passage of the Food Safety Modernization Act (“FSMA”).  The FSMA substantially enhances FDA’s authority over imported foods, but also imposes foreign inspection mandates that the agency has indicated are unrealistic – particularly in light of budgetary constraints.

We hope the publication of this most recent report represents additional meaningful progress in implementing FDA’s stated goals.

By Riëtte van Laack –

Although there are currently no federal standards governing the labeling of organic cosmetics, cosmetic products sold in California are subject to the California Organic Products Act of 2003 (“COPA”).  Under this law, cosmetics labeled or represented as "organic" must contain at least 70 percent organically produced ingredients. Cal. Health &  Safety Code § 110838(a).  Cosmetics with “less than 70 percent organically produced ingredients, . . . may only identify the organic content" if each organic ingredient is identified in the ingredient statement as "organic" or if the "product's percentage of organic contents" is indicated "on the information panel."  Id. § 110839.  The percentage of organic material in a cosmetic product must be determined by dividing the weight of the ingredients, excluding water and salt, by the total weight of the product, excluding water and salt. 

COPA gives any person standing to file an action to enjoin a party from violating COPA.  Moreover, in an action for injunctive relief, a plaintiff is not required to show injury or damages.

According to a complaint filed in the Superior Court of the State of California, by the Center for Environmental Health (“CEH”), at least 34 cosmetic companies sell cosmetic products in California that are labeled as organic yet do not contain 70% or more organic ingredients (CEH identifies itself as a non-profit corporation that is concerned about products that are misrepresented as organic).  CEH estimated the percentage of organic ingredients in defendants’ products based on the defendants’ product ingredient statements.  Allegedly, based on the ingredient statements, some of the defendants’ products do not contain any organic ingredients at all.

In addition to a permanent injunction, CEH asks for attorney fees and costs.

By Ricardo Carvajal –

In October 2008, the Natural Resources Defense Council ("NRDC") submitted a citizen petition to FDA asking the agency to repeal regulations that permit food additive uses of BPA, to which FDA tentatively responded with a standard letter stating that “limited availability of resources and other agency priorities” had prevented FDA from rendering a decision on the citizen petition.  When FDA took no further action, NRDC petitioned the DC Circuit Court of Appeals to direct FDA to render a decision.  Among other things, NRDC argued that FDA’s action on the citizen petition would necessitate rulemaking under FDC Act section 409, which vests exclusive jurisdiction in the circuit courts of appeals over any challenge to an order amending or repealing a food additive regulation.

Last week the DC Circuit ruled that it lacks exclusive jurisdiction over the NRDC citizen petition because: (1) NRDC submitted a citizen petition rather than a food additive petition, and “lawsuits involving citizen petitions are regularly heard in the district courts;” (2) agency action under section 409 in response to the NRDC citizen petition is not a foregone conclusion, as FDA can provide a tentative response to the citizen petition or deny it outright – neither of which would require rulemaking under section 409; and (3) 21 CFR Part 10 does not provide for the use of a citizen petition to repeal a food additive regulation. 

NRDC must now decide whether to continue to pursue its case in district court.  FDA action on the citizen petition appears unlikely – particularly in the face of significant cuts to FDA's food safety budget.

By Kurt R. Karst –      

Although many have tried (see, e.g., here), in our experience, few have succeeded in convincing a court to decide to grant a motion to extend a 30-month stay on FDA’s approval of a generic drug application.  (The most recent case we can think of is from 2009, when the U.S. Court of Appeals for the Federal Circuit in Eli Lilly & Co. v. Teva Pharms. USA, Inc. affirmed a district court decision extending a 30-month stay with respect to an ANDA for a generic version of EVISTA (raloxifene HCL) Tablets – see our previous post here.)  It’s even more rare to see such a motion granted under the animal drug Hatch-Waxman counterpart, the Generic Animal Drug and Patent Term Restoration Act (“GADPTRA”).  But that’s what happened in Bayer Healthcare, LLC v. Norbrook Labs. Ltd. when the U.S. District Court for the Eastern District of Wisconsin ruled earlier this month to extend the 30-month stay of approval of Norbrook’s Abbreviated New Animal Drug Application (“ANADA”) for a generic version of Bayer’s Baytril® 100 (enrofloxacin) Injectable Solution, which is covered under New Animal Drug Application No. 141-068 and listed in the Green Book (the animal drug equivalent of the Orange Book) with U.S. Patent No. 5,756,506 (“the ‘506 Patent”), which expires on June 27, 2015. 

Under FDC Act § 512(n)(1)(H), as added by GADPTRA, an ANADA sponsor must submit a certification or statement with respect to each Green Book-listed patent for the reference product.  As under Hatch-Waxman, a timely filed patent infringement lawsuit stemming from a Paragraph IV certification triggers an automatic 30-month stay on ANADA approval.  In that case, “the [ANADA] approval shall be made effective upon the expiration of the [30-month stay] . . . or such shorter or longer period as the court may order because either party to the action failed to reasonably cooperate in expediting the action. . . .” 

In Bayer Healthcare, LLC v. Norbrook Labs. Ltd., Bayer timely sued for patent infringement based on Norbrook's Paragraph IV certification to the '506 Patent, thereby triggering a 30-month stay on ANADA approval that was reportedly originally scheduled to expire on March 29, 2011.  Bayer alleged that Norbrook failed to reasonably cooperate in expediting the patent infringement action by, among other things, changing “its [ANADA] after the close of fact discovery and after the submission of expert reports, just months before trial” (italics in original) as part of a strategy to delay the patent infringement litigation, and by failing to serve “discovery responses for more than three months, not withstanding [sic] that the Federal Rules [of Civil Procedure] mandate a response within 30 days.”  Bayer asked the court to extend the 30-month stay of FDA’s approval of Norbrook’s ANADA through the February 6, 2012 trial date set by the court. 

Norbrook contended, among other things, that “the 30-month stay is not intended to enable the parties to fully resolve their patent disputes before its expiration and that Bayer should file for preliminary injunctive relief if it wants to prevent the FDA from approving Norbrook’s ANADA,” and that the Federal Circuit’s decision in Eli Lilly “does not apply because Norbrook’s ANADA amendment does not change the method for which it seeks FDA approval, whereas in Eli Lilly, the [ANDA] amendment materially changed the product in question.”  Norbrook also cited a recent decision out of the U.S. District Court for the Southern District of New York – Bayer Schera Pharma AG v. Sandoz, Inc. – in which “Bayer contended that a motion to dismiss for lack of personal jurisdiction, which had been pending three months until it was withdrawn, established that the movant had failed to reasonably cooperate in expediting the action,” but the district court did not grant a 30-month stay extension.

Relying heavily on the Federal Circuit’s decision in Eli Lilly where the Court upheld a district court decision extending a 30-month stay because the ANDA sponsor reportedly changed a manufacturing specification eight months before the trial date, Judge Rudolph T. Randa ruled that “Norbrook’s actions – in waiting four months after the close of discovery and only five months before trial to change its ANADA – provide a strong basis for this Court to extend the stay, compared to those of Eli Lilly.”  Judge Randa was not convinced by Norbrook’s contention that Bayer Schera applied and easily dispensed with the case, writing that in Bayer Schera the district court held that “Bayer – the plaintiff – had not sought to expedite the litigation,” whereas in the case at bar, “Norbrook’s December 2010 ANADA amendment has resulted in a delay of the litigation.”

By John R. Fleder –

For over forty years there has been a unit in the Department of Justice dedicated to representing FDA in court actions.  Originally housed in the Antitrust Division under the name “Consumer Affairs Section”, the office was moved to DOJ’s Civil Division in the early 1980’s and called the “Office of Consumer Litigation.”  That office has historically represented the Federal Trade Commission, the Consumer Product Safety Commission, and enforced a number of other federal statutes.  However, since its founding, the office has devoted most of its resources to representing FDA, both in criminal and civil suits that FDA has wanted filed against persons who have allegedly violated the FDC Act, and in suits where persons have alleged that FDA has itself violated that act.

Last Friday, the Civil Division announced that Michael Blume, an Assistant United States Attorney in Philadelphia, will soon be heading that office.  It culminates a series of changes to the office under the Obama Administration’s Assistant Attorney General, Tony West.

First, the office was recently renamed the “Office of Consumer Protection Litigation.”  The name change was clearly not just symbolic.  It reflects Mr. West’s change in focus for the office.  Now, in addition to doing the types of cases described above, Mr. West has been moving the office to focus on matters such as mortgage fraud and immigration services fraud, which are areas of law enforcement that were not within the office’s responsibility until recently.

Mr. Blume comes to the office as its Branch Director without prior service there.  In its forty plus years, no one has ever headed the office who did not previously work in either the office or the division where the office was housed.  Indeed, Mr. Blume is the first person to head the office since the early 1970s who had not previously worked in the office.

Mr. Blume takes over the office from Kenneth Jost who has served as Acting Director for just under two months.  His predecessor was Eugene M. Thirolf, who admirably served as Director for almost nineteen years.  Mr. Thirolf, who retired in April was a clear upgrade over his predecessor.

It is quite unclear what effect Mr. Blume’s selection as Director will have on the office.  His experience as a prosecutor suggests that he will continue AAG West’s efforts to prosecute consumer fraud cases that are wholly unrelated to FDA.  With an expansion of the number of attorneys in the office under Mr. West, we will have to see if the office continues its historical focus as primarily devoting its resources to FDA matters.  Moreover, we will wait to see how this change impacts on the Justice Department’s client agency relationship with FDA.

By Ricardo Carvajal & Riëtte van Laack –

When the FDA Nanotechnology Task Force issued its report in 2007, it declined to adopt precise definitions of the terms "nanoscale materials" or "nanotechnology," opting instead to take an inclusive approach.  FDA has now issued draft guidance on nanotechnology that again shies away from adopting formal definitions.  Rather, the guidance presents “points to consider” with regard to whether a “product contains nanomaterials or otherwise involves the application of nanotechnology,” namely:

1. Whether an engineered material or end product has at least one dimension in the nanoscale range (approximately 1 nm to 100 nm); or



2. Whether an engineered material or end product exhibits properties or phenomena, including physical or chemical properties or biological effects, that are attributable to its dimension(s), even if these dimensions fall outside the nanoscale range, up to one micrometer.

(Emphasis added.)   Notably, the points to consider address only engineered materials or end products, and not “the more familiar use of biological or chemical substances that may naturally exist at small scales, including at the nanoscale, such as microorganisms or proteins.”  This is in keeping with FDA’s interest in “the deliberate manipulation and control of particle size to produce specific properties, because the emergence of these new properties or phenomena may warrant further evaluation” (emphasis in original).  Also worth noting is that the points to consider encompass materials with dimensions beyond 100 nm (usually taken as the upper limit for nanomaterials) to 1000 nm to include agglomerates and aggregates that exhibit dimension-dependent properties relevant to nanomaterials. 

An accompanying FAQ characterizes the guidance as “a first step toward providing regulatory clarity on FDA’s approach to nanotechnology.”  Those who were seeking greater clarity are bound to be disappointed.  The FAQ makes clear that FDA places a premium on flexibility at this early stage, and that the agency has confidence in the adequacy and adaptability of its existing regulatory framework:

FDA’s goal is to develop transparent and predictable regulatory pathways grounded in the best science.  FDA intends to do this with a regulatory approach that is iterative, adaptive and flexible.  FDA does not categorically judge that all products containing nanomaterials or otherwise involving the application of nanotechnology as intrinsically benign or harmful.

FDA is maintaining its product-focused, science-based regulatory policy that allows for variations among product classes and over time as the science evolves.  Products regulated by FDA are subject to different statutory standards for safety, efficacy, or public health impact.  Therefore, acceptable levels of uncertainty and risk may vary among product-classes, even where objective measures of risk are similar.

FDA’s draft guidance was published on the same day as a memorandum from the White House Emerging Technologies Interagency Policy Coordination Committee laying out principles for oversight of emerging technologies that are intended to strike a balance between ensuring safety and encouraging innovation.

Comments on the draft guidance are due by August 14.

By Susan J. Matthees –

On Tuesday, sunscreen finally stepped out of the shadows at FDA.  After years waiting, FDA announced the availability of a number of new documents related to over-the-counter (“OTC”) sunscreen drug products marketed in the US, including a guidance document on enforcement policy for OTC sunscreen drugs marketed without an approved application, a proposed rule on limiting the maximum labeled SPF value for sunscreen products to “50+,” advance notice of proposed rulemaking (“ANPR”) to address difference dosage forms of sunscreen, and a final rule on labeling and testing methods. 

OTC sunscreen drug products have a lengthy regulatory history at FDA.  In 1978, FDA announced an ANPR for sunscreen drug products.  In 1993, FDA published a proposed rule on generally recognized as safe and effective (“GRASE”) conditions for OTC sunscreen drug products and then proposed amendments to that rule in 1996 and 1998.  In 1999, FDA finalized the OTC drug sunscreen monograph, but just a year later FDA delayed the effective date for the final rule.  In 2001, FDA stayed the effective date of the 1999 monograph, and then in 2007, FDA published another proposed rule on sunscreen drug products.  Unfortunately, Tuesday’s announcement of a final rule does not end the sunscreen regulatory saga; FDA is not finalizing the amendments to 21 C.F.R. Part 352 or lifting the stay on that section, and the final rule is not the final monograph for sunscreen drug products.  FDA states that the stay will be lifted when the Agency reaches its final conclusions on conditions under which sunscreen products are GRASE and not misbranded.  In the mean time, those of us in the OTC drug world will have to be satisfied with the final rule, proposed rule, ANPR, and the draft guidance.  Each is summarized below. 

Final Rule:  New Testing Methods, New Labeling

Nearly 5 years and 2,900 comments after publishing the last proposed rule for sunscreen products, FDA has published a final rule, codified in 21 C.F.R. § 201.327, to establish labeling and testing requirements for OTC sunscreen drug products marketed without an approved application.  Because FDA has still not yet made a decision on the conditions under which sunscreen drug products are GRASE, the final rule applies only to those sunscreen products that contain the ingredients specified in the stayed 1999 monograph. 

The final rule provides new test procedures that manufacturers must follow in order to label their products as “Broad Spectrum SPF” protection.  The final rule also requires labels of sunscreen drug products to bear the familiar “Drug Facts” box found on most OTC drugs and prohibits the claims “waterproof,” “sweatproof,” and “sunblock.”  The claim “water resistant” can be made for a sunscreen if the manufacturer follows the test method set forth in the final rule.  Perhaps the most interesting aspect of the final rule is that it resurrects labeling claims that use of sunscreen can prevent skin cancer and skin aging.  In the 1993 proposed monograph, FDA proposed a “sun alert” claim that explained that use of sunscreen could prevent skin cancer and skin damage.  58 Fed. Reg. 28194, 28298 (May 12, 1993).  The 1999 final monograph adopted the sun alert statement, but in 2007, FDA stated that there was insufficient evidence that sunscreen could prevent skin cancer and therefore the Agency was modifying the sun alert statement such that it would only warn consumers that UV exposure could cause cancer, not that sunscreen would prevent cancer.  72 Fed. Reg. 49070, 49089 and 49114 (Aug. 27, 2007).   Now, under the final rule, Broad Spectrum SPF products may bear the explicit claim “if used as directed with other sun protection measures (see directions), decreases the risk of skin cancer and early skin aging caused by the sun.”  Non-Broad Spectrum products, however, may only claim to prevent sunburn. 

The final rule is effective June 18, 2012.  The compliance date for products with annual sales less than $25,000 is June 17, 2013. 

Proposed Rule:  Claims for SPF 50+

The proposed rule seeks to limit the maximum labeled SPF value for OTC sunscreen products to “50+.”  FDA explained that although the Agency received submissions demonstrating the accuracy and reproducibility of SPF tests at values as high as SPF 80, “the record continues to lack data demonstrating that sunscreen products with SPF values above 50 provide additional clinical benefit compared to SPF 50 products.”  FDA does not rule out the possibility that sunscreen could bear SPF values above 50 in the future, but states that the Agency will need data demonstrating a clinical benefit of the higher SPF values.  FDA recommends that parties interested in conducting such studies first contact FDA.  Alternatively, FDA requests comments on whether the Agency should establish a maximum SPF value for sunscreen formulations marketed under the monograph.  FDA explains that if a maximum SPF were established, a product that tests SPF above that value would no longer be permitted because, if having an SPF above 50 does not confer an additional clinical benefit, the risk benefit-assessment for those products may no longer be favorable. 

Comments to the proposed rule are due 90 days after publication. 

ANPR:  Request for Comments on Novel Dosage Forms

The ANPR seeks data to establish monograph conditions for sunscreen products, including specification of certain dosage forms.  In particular, FDA is seeking additional data or information to support adding spray sunscreen products to the monograph. Spray sunscreens have become popular in the past few years, but FDA is concerned that there is a lack of information on how consumers use spray products, how uniformly the sunscreen is applied, how frequently consumers reapply the product, whether consumers follow product directions, how rubbing the product into the skin changes the effectiveness, and how the SPF values as the product is applied compared to those under laboratory conditions.  FDA also is requesting information on the risks associated with inhaling the active sunscreen ingredients and whether toxicology studies are needed for these products.  FDA also states that it does not consider sunscreen wipes, towelettes, powders, body washes, and shampoos currently eligible for review under the OTC monograph process. 

Comments to the ANPR are due 90 days after the date of publication. 

Draft Guidance:  FDA’s Enforcement Policy

The draft guidance document, “Guidance for Industry:  Enforcement Policy- OTC Sunscreen Drug Products Marketed Without an Approved Application,” is intended to guide manufacturers who market sunscreen products that have not been approved via an NDA.  FDA states that the Agency will continue to exercise enforcement discretion for sunscreen drug products that contain active ingredients that are listed in the stayed monograph, do not make claims addressed in the final rule, comply with the requirements for OTC drugs in 21 C.F.R. Part 201 and 330.1, and follow labeling and testing requirements in the new final sunscreen regulation (21 C.F.R. § 201.327).  FDA notes that combination cosmetic/sunscreen drug products are covered by this enforcement policy. 

By 2 years after the publication date of the final rule, FDA will expect that all OTC sunscreen products marketed after publication of the rule will follow SPF testing procedures set forth in 21 C.F.R. § 201.327(i).  Although the final rule sets forth testing procedures for broad spectrum UV claims, FDA states that as long as a sunscreen product does not bear labeling claims for broad spectrum protection, the Agency will not expect sunscreens to have been tested in accordance with the new 21 C.F.R. § 201.327(j). However, FDA will take enforcement action against OTC sunscreens if the products are labeled with an SPF that was generated by a method other than that included in the 2011 final rule, 1999 final rule, or 2007 proposed rule. 

FDA will permit sunscreens to bear SPF values higher than 50 until FDA decides on the proposed rule to limit claims to “SPF 50+.”  FDA also states that while the ANPR on dosage forms is pending, FDA will permit spray dosage forms to be marketed.  However, FDA may take regulatory action against products such as wipes, towelettes, powders, body washes, and shampoos.