The Institute of Food Technologists (“IFT”) is requesting proposals for its March 28-29, 2012 annual Wellness Conference, which will explore new trends and examine recent scientific, technological, and business information in the health and wellness sector of the food industry.  The conference will cover a variety of topics related to consumer lifestyles and demographics, health issues, and weight management.  Submission Guidelines and topical priorities can be viewed here.  The deadline for submissions is August 18, 2011.  Hyman, Phelps & McNamara, P.C.’s Cassandra Soltis, a Wellness 2012 Advisory Panel Member, will moderate some of the sessions. 

By Cassandra A. Soltis & Anne Marie Murphy –

The Department of Health and Human Services, Office of the Secretary, along with the Office of Science and Technology Policy, has issued an advance notice of proposed rulemaking (“ANPRM”) requesting comments on how to update current regulations on the protection of human subjects who participate in research. 

Existing regulations on human research have been in place for decades with little significant change.  Thus some have dubbed the current initiative “historic.”  The impetus to modernize the regulations is in part a result of the way human research has evolved over the years.  Changes in the way human research is conducted include an increase in multi-site clinical trials and observational studies; research in the social and behavioral sciences; research using databases, the Internet, and biological specimen repositories; and perhaps most significantly the use of advanced technologies, such as genomics.  Other factors motivating change include criticism of the existing regulatory scheme by government bodies (e.g., Government Accountability Office) and academics.  A recent Executive Order also charges Federal agencies to review and update existing significant regulations to ensure that objectives are being met in the most efficient manner.  Improving Regulation and Regulatory Review, January 18, 2001. 

The ANPRM addresses a host of concerns over the “Common Rule,” which is codified at 45 C.F.R. part 46, subpart A, and has been adopted by about 15 Federal departments and agencies.  The Common Rule generally requires that Federally funded investigators obtain and document the informed consent of research subjects and describes, among other things, the requirements for membership, function, operations, research review, and recordkeeping of institutional review boards (“IRBs”).  Regulations to protect human subjects involved in FDA-regulated research include the provisions set forth at 21 C.F.R. parts 50 (informed consent), 56 (IRBs), 312 (investigational drugs), and 812 (investigational medical devices).  FDA’s regulations on informed consent and IRBs are separate from, but largely track, the provisions of the Common Rule.  The proposed rulemaking notes that other regulatory schemes, such as FDA regulations and the HIPAA Privacy Rule, will be affected and “will need to be harmonized.”

Seven primary categories of concern are highlighted in the ANPRM:
 
(1) Ensuring that the rules relate to the magnitude of risk to study subjects.  For example, IRBs have been criticized for spending too much time reviewing studies that involve minimal risk or overestimating foreseeable risks to subjects, particularly in the context of social and behavioral research.

(2) Streamlining IRB review of multi-site studies. 

(3) Improving informed consent.  Particularly in biomedical research where risks can be significant, there is value in ensuring that the consent process conveys the information needed for a potential subject to make an informed decision in a manner that the subject can understand.  At the same time, a rigid requirement to obtain written informed consent for certain types of research, e.g., surveys or interviews, has been questioned. 

(4) Strengthening data protections to minimize information risks.  For example, where genetic information is collected and stored, study subjects incur the risk of accidental or unauthorized disclosure of personal information.  HIPAA requirements address such risks in part, but apply only to covered entities. 

(5) Collecting information that would better allow evaluation of the system and how well human subjects are protected.

(6) Extending the scope of the Common Rule to include research studies conducted at institutions that receive any Federal funding, even if not specific to the study at issue.  This responds in part to those who have called for legislation to expand the Common Rule to cover all human subjects research conducted in the United States, regardless of the source of funding.

(7) Clarifying and harmonizing regulatory requirements and guidance across Federal agencies.

The ANPRM requests public comment on these issues and asks for responses to more than 70 specific related questions.  Barring an extension, comments must be submitted by 5 p.m. on September 26, 2011.

By Ricardo Carvajal –

FDA announced fee rates for reinspections of domestic and foreign facilities, importer reinspections, and noncompliance with a recall order – all authorized by the Food Safety Modernization Act ("FSMA").  The fees kick in on October 1, 2011.  The hourly fee rate is $224 ($335 if foreign travel is required).  FDA can be expected to collect fees under the following circumstances:

• Reinspection after a previous inspection that was classified as Official Action Indicated (meaning that significant objectionable conditions or practices were found and regulatory action is warranted to address non-compliance), and where non-compliance was materially related to food safety requirements (meaning the food is adulterated under FDC Act § 402 or misbranded under § 403(w)).  For domestic facilities, fees will be collected from the responsible party (the person who submitted the food facility registration required under § 415).  For foreign facilities, fees will be collected from the U.S. agent.  The fee will be based on the number of hours FDA spends on the reinspection.  Those hours could add up quickly, given that FDA can include time spent on physical surveillance, travel, preparation of reports, and sample analysis.

• Import reinspection/reexamination after a refusal under § 801(a) (including refusal pursuant to an import alert for detention without physical examination) that is materially related to food safety requirements.  Fees will be collected from the importer.  The fee will be based on the time spent on the activity in question (e.g., evaluation of a request for, and supervision of, reconditioning; review of evidence regarding admissibility, under some circumstances; evaluation of a request for removal from import alert, under some circumstances). 

• Recall activities performed by FDA as the result of noncompliance with a recall order.  The fee will be collected from the person who received the recall order, which would be the responsible party (in the case of domestic facilities) or the importer.  Again, the hours could add up quickly, considering the time spent on audit checks, inspections, and monitoring of disposition, among other things.

For the first year, there will be no formal mechanism for fee reductions for small business because FSMA requires notice and comment rulemaking to implement such fee adjustments.  In the interim, to help develop proposed guidelines, FDA published a separate notice requesting comment on the burdens imposed by the fees on small business, and whether FDA should alleviate those burdens.  FDA will also “consider waiving in limited cases some or all of an invoice fee based on a severe economic hardship, the nature and extent of the underlying violation, and other relevant factors.”

By Kurt R. Karst –     

Each year around this time, some of us at our firm participate in a version of The Price Is Right Showcase Showdown in which folks “bid” on what they think the PDUFA application user fee rate will be set at for the next Fiscal Year (“FY”).  (There’s always that one person who goes a dollar over the previous highest bid.)  Bids are placed based, in part, on previous FY application user fee rate increases and other historical information.  For example, for FY 2011, FDA set the full application fee at $1,542,000, a 9.7% (or $136,500) increase over the FY 2010 fee of $1,405,500.  This year, nobody anticipated that FDA would increase the application fee as high as it did – by a dollar amount higher than any and previous increase in the history of PDUFA, and at a rate higher than any fifth year of a PDUFA cycle. 

In a Federal Register notice scheduled for publication on August 1st, FDA will announce the Prescription Drug User Fee Act (“PDUFA”) user fee rates for Fiscal Year (“FY”) 2012.  (In separate notices, FDA will announce the FY 2012 user fee rates for animal drugs, animal generic drugs, medical devices, and fees under the Food Safety Modernization Act domestic for foreign facility reinspections, recall, and importer reinspection.)  The FY 2012 PDUFA application user fee rates is set at $1,841,500 for an application requiring “clinical data,” and one-half of a full application fee ($920,750) for an application not requiring “clinical data” and a supplement requiring “clinical data.”  (The term “clinical data” for PDUFA user fee purposes is explained in an FDA guidance document available here.)  Annual establishment and product fees have been set at $520,100 and $98,970, respectively.  The FY 2012 fees go into effect on October 1, 2011.

The first table below shows the percent increase since the previous FY for each of the five FYs under PDUFA IV (for each fee type), and should be used with the table from our previous post, which tracks PDUFA user fees rates since the inception of PDUFA.  The next three tables show the historical trend for each PDUFA user fee.

 
  
 
When it was enacted in 1992, PDUFA was hailed by some as an unprecedented accord among FDA, the pharmaceutical industry, and Congress.  In exchange for the promise of a speedier drug review system, the industry agreed to pay user fees.  Over the years, the cost to the industry for FDA’s promise of improved performance has increased considerably (as shown in the above tables). 

So, is industry getting what it is paying for?  Some, would say no.  At a recent Senate hearing on PDUFA V, Senator Richard Burr (R-NC) criticized FDA for delays in approval decisions.  According to FDA Commissioner Hamburg, who testified at the Senate hearing, except for FY 2008-09, “FDA has maintained strong performance in meeting the PDUFA application review goals.”  Dr. Hamburg’s testimony included the following table on application review performance metrics.

By Jennifer D. Newberger –

On July 29, 2011, the Institute of Medicine ("IOM") released its long-awaited report, “Medical Devices and the Public’s Health, The FDA 510(k) Clearance Process at 35 Years.”  Both industry and FDA were likely surprised by the IOM’s recommendation: do away with the 510(k) process as quickly as possible, and put in its place “an integrated premarket and postmarket regulatory framework that effectively provides a reasonable assurance of safety and effectiveness throughout the device life cycle.” 

The IOM reached this decision based on a consideration of two questions posed to it by FDA:

1. Does the current 510(k) clearance process optimally protect patients and promote innovation in support of public health?
2. If not, what legislative, regulatory, or administrative changes are recommended to optimally achieve the goals of the 510(k) clearance process?

The IOM stated that it was difficult to answer those questions, since it found that the 510(k) process was not intended to determine whether a new device provides a reasonable assurance of safety and effectiveness or whether it promotes innovation.  Rather, according to the IOM, it was intended only to determine whether the new device is substantially equivalent to an already marketed (predicate) device, and there was therefore an inherent conflict between the legislative framework of the 510(k) program and the FDA’s stated goals.

On first glance, this might look good for industry.  If FDA does not have the statutory authority to request information about safety and effectiveness (except to support the safety and effectiveness of technological changes), then the report could have concluded that FDA should just stick to its statutory mandate to determine whether a new medical device is substantially equivalent to a predicate.  In fact, the first conclusion of the committee is that the 510(k) process “cannot be transformed into a premarket evaluation of safety and effectiveness as long as the standard for clearance is substantial equivalence to any previously cleared device.”  But, rather than simply telling FDA that it is going beyond its statutory mandate in trying to use the 510(k) process as a premarket evaluation of safety and effectiveness, and rather than proposing ways to “fix” the 510(k) process, the IOM stated that it “does not believe that further investment in the 510(k) process is a wise use of the FDA’s scarce resources and is not recommending specific changes in the 510(k) clearance process itself.  Instead, it believes that the FDA’s resources would be put to better use in obtaining information needed to develop a new regulatory framework for Class II medical devices and addressing problems with other components of the medical device regulatory framework.”

The IOM did not, however, propose how FDA might use its “scarce resources” to obtain the information necessary to completely overhaul the entire medical device premarket approval program.  The report repeatedly noted that the 510(k) clearance process is “not a stand-alone program, but a component of the larger medical device regulatory framework.”  If FDA were to adopt the IOM’s recommendation to scrap the 510(k) program altogether (which is extremely unlikely), this raises the obvious question of whether changes would be made not only to the premarket pathway for Class II devices, but for Class and I and Class III as well.

Although it did not describe a specific regulatory framework, the report does provide what the IOM committee considers to be an “ideal regulatory framework”:

• The process should be based on sound science.
• The process should be clear, predictable, straightforward, and fair.
• The process should be self-sustaining and self-improving.
• The process should facilitate innovation that improves public health by making medical devices available in a timely manner and ensuring their safety and effectiveness throughout their lifecycle.
• The process should apply relevant and appropriate regulatory authorities and standards throughout the life cycle of devices to ensure safety and effectiveness.
• The process should be risk-based.

These elements are broad and far-reaching, and not very controversial.  However, they do not appear to provide FDA with any solid ground upon which to move forward with the IOM recommendation to conjure an entirely new pathway for medical device premarket review (which would, of course, need to be enacted by Congress).  But perhaps that won’t matter, since FDA has already stated in response to the report that it “believes that the 510(k) process should not be eliminated,” but that it is “open to additional proposals and approaches for continued improvement of our device review programs.”  

The committee also declined to comment specifically on whether the 510(k) process has an effect, for better or worse, on medical device innovation over the years.  It  concluded that “[i]nformation that would allow an understanding of the extent to which the 510(k) clearance process either facilitates or inhibits innovation does not exist.”  It further noted:  “The 510(k) process does not require a moderate-risk device to be innovative, nor does it reward innovation. However, the 510(k) process can facilitate innovation by making new devices available to consumers in a timely manner. It is unclear—and the committee concludes that it is indeterminable, given current information—whether the 510(k) process over the last 35 years has had a positive or negative effect on innovation. To answer this question, the FDA should commission an assessment to determine this effect.”  Perhaps that is what FDA thought it was doing when it commissioned the IOM to address this issue, but apparently it was mistaken. 

One subject on which the report does provide some detailed discussion is that of improving FDA’s postmarket surveillance system.  The report states that FDA should give priority to postmarket surveillance as an “invaluable investment” in both short- and long-term oversight of medical device safety and assessment of device effectiveness.  It also notes that although FDA stated that its postmarket authorities have “important limitations,” the committee did not seem convinced that such limitations exist, and the report encourages FDA to identify and address any such limitations.

One area that both industry and FDA are interested in improving is the de novo review process, an area on which the committee was to provide suggestions.  Rather than specifically describing how the de novo process itself may be improved, however, the report states a “pilot program of a modified de novo process would allow the FDA to determine its feasibility as a replacement for the 510(k) clearance process.”  The report does not indicate what that “modified” de novo process would look like, apart from expediting development of special controls, developing guidances, and adopting standards for devices.

So where does all this leave us?  Though hard to say, there a couple conclusions that seem reasonable.  First, the IOM committee specifically states that it “is not suggesting that all, many, or even any medical devices cleared through the 510(k) process and currently on the market are unsafe or ineffective. The continual use of many of these devices in clinical practice provides reason for a level of confidence in their safety and effectiveness.”  Perhaps this will provide more confidence that most devices on the market are safe and effective for their intended uses, even if cleared through the 510(k) process.  Second, FDA has already stated it does not think the 510(k) program needs to be completely scrapped and an entirely new medical device review program put in place.  It wants to work within the framework that already exists.  While IOM’s recommendation to get rid of the 510(k) process certainly gives FDA the ammunition to do just that if it wants to, the likelihood of that happening is low.  Perhaps this means that industry need not worry about sweeping overhauls taking place any time soon, at least based on recommendations from the IOM.

FDA has already stated that it will be opening a public docket to receive comments on the report.  Given the sheer breadth of the report, there may be many areas that will attract comments.  So, for better or worse, perhaps the most reasonable conclusion is simply that nothing is bound to change for a good, long while, and it is no more clear today than prior to release of the report what those changes are likely to be.

By Ricardo Carvajal –

A federal district court dismissed with prejudice a claim that Bayer’s labeling of gummy vitamins violated the Arkansas Deceptive Trade Practices Act.  Plaintiff alleged that the brand name “ONE A DAY” is misleading because the daily serving size for the vitamins is two gummies.  Acknowledging that plaintiff’s claim “carries a logical appeal” and “is not silly,” the court nonetheless ruled that no reasonable consumer would be deceived when the label is considered as a whole.  The label stated the dosage three times, as well as the number of servings in the container.  Further, plaintiff failed to allege that he was deceived. 

By Susan J. Matthees –

FDA recently denied a 2006 citizen petition submitted by Wyeth Consumer Healthcare (“Wyeth”) requesting that FDA withdraw a 2005 Notice of Proposed Rulemaking (“NPRM”) that would reclassify phenylpropanolamine (“PPA”) from Category I (generally recognized as safe and effective) to Category II (not generally recognized as safe and effective).  Wyeth alleged that FDA’s proposal to reclassify PPA was based on one flawed study of PPA and that the NPRM incorrectly described the safety status of PPA.  FDA disagreed, stating that the weight of evidence indicates that PPA’s safety has not been demonstrated. 

PPA has a relatively long history of use in the United States.  The ingredient was synthesized in the early 1900s and by the early 1940s was used in OTC nasal decongestant products.  Beginning in the 1970s, PPA was marketed as an appetite suppressant in OTC weight control drug products.  According to FDA, a 1991 review of adverse event reports from 1977 to 1991 and published studies on PPA suggested that PPA might be associated with an increased risk for hemorrhagic stroke.  In 2000, FDA’s Nonprescription Drugs Advisory Committee evaluated data on PPA and concluded that PPA should not be generally recognized as safe.  That same year, FDA conducted its own analysis of PPA data and requested that manufacturers voluntarily discontinue marketing products containing PPA.  In 2005, FDA proposed the reclassification of the ingredient from Category I to Category II. 

Wyeth objected to the proposed reclassification, alleging that FDA based its proposal to reclassify PPA on the findings of one flawed study, the Yale Hemorrhagic Stroke Project (“HSP”).  According to Wyeth, the HSP study is not a reliable study because the findings were based on a small number of cases and that there were a number of errors in the study, including errors in determining subject eligibility and classification and confounding factors that could undermine the validity of the results. 

FDA disagreed that the HSP study was fatally flawed, saying that Wyeth failed “to present convincing evidence that the HSP study is irreparably compromised.”  FDA also explained that the Agency’s proposal to reclassify PPA was based on all available data for the drug and the totality of the evidence suggested that the drug’s safety has not been demonstrated.  FDA reviewed 20 years of adverse event reports for PPA and the published results of a Korean study that was similar to the HSP.  Although Wyeth had criticized the Korean study, FDA concluded that the study provides “additional supportive evidence.”  FDA also stated that the adverse event reports for PPA are consistent with known biological effects of PPA on blood pressure. 

On July 26, 2011, Hyman, Phelps & McNamara, P.C. filed a request for a one-year comment period to allow affected businesses adequate time to respond to a lengthy and controversial draft guidance on New Dietary Ingredient ("NDI") notifications that FDA issued earlier this month.  Our previous post on the draft NDI guidance is available here. 

By Jennifer D. Newberger –

On July 27, 2011, the Center for Devices and Radiological Health ("CDRH") announced the issuance of a Draft Guidance titled “510(k) Device Modifications: Deciding When to Submit a 510(k) for a Change to an Existing Device.”  When finalized, this guidance document will replace that of the same name issued in January 1997. 

At first glance, the 2011 Draft Guidance does not appear to be too different from its 1997 predecessor.  For instance, both claim to focus on the meaning of whether a modification may “significantly affect” the safety or effectiveness of the device; both pose questions, categorized by modification category, that are to be analyzed for each change individually as well as collectively since the last 510(k) clearance; and both emphasize that, when determining whether the modifications may significantly affect safety or effectiveness, the modified device may only be compared to the most recently cleared device, not to another device made by the manufacturer or another manufacturer. 

But don’t get too comfortable too soon.  While much of the Draft Guidance is not too drastically different from the 1997 version, some of the changes that the Draft Guidance does include make fairly substantive changes to existing policy and practice.  Most importantly, these changes all flow in one direction:  more 510(k)s.  Changes that, in the past, may have been addressed via a letter to file may now require a new 510(k).  There do not appear to be any situations in which a change that previously required a 510(k) may now be addressed via a letter to file.

Labeling Changes.  Let’s start with labeling.  In the 1997 guidance, the labeling section notes that the threshold for whether a new 510(k) will be required is whether the modification affects the indications for use.  The 2011 Draft Guidance, however, does not appear to be so limiting.  Of particular interest is that the Draft Guidance notes that “it is important to keep in mind that the term ‘labeling’ includes more than just the instructions for use,” and may include things such as promotional materials.  Presumably, this means that when a manufacturer changes its promotional materials, it will need to go through the labeling analysis in the Draft Guidance and determine whether that change necessitates a new 510(k).  If a manufacturer determines no new 510(k) is needed, it will need to document that decision.

In addition to including promotional materials in the types of labeling covered by the Draft Guidance, the labeling section states that CDRH will now require a new 510(k) for changes that were specifically called out as not requiring a new submission in 1997.  For instance, the 1997 guidance notes generally that if a device is cleared for three indications and the manufacturer decides to market the device only for two of those indications, no new 510(k) is needed.  The Draft Guidance, however, modifies this condition in a manner sure to create confusion, stating that no new 510(k) would be needed in that situation only if the indication was removed “due strictly to marketing reasons” (emphasis in original).  In other words, if the market demand changed, resulting in a decision by the manufacturer to pull one of the indications, no new 510(k) would be needed.  However, “if a firm decides to market the devices for only two of those [three] indications due to other reasons, for example, changes that have been made to the device that affect the removed indication or because of complaints or corrective actions, FDA would generally consider the removal of the indications for use to be a ‘major change’ that requires a new 510(k).”  Yes, you read that right.  If the manufacturer makes a modification to a device that affects a use no longer claimed in the labeling, it may still need to submit a 510(k) for that modification unless the deletion was for marketing reasons.

The Draft Guidance also changes CDRH’s position regarding clinical versus home use.  CDRH has become increasingly focused on home-use products recently, so this change may not be a complete surprise.  Nevertheless, it does revise the 1997 position.  In 1997, the guidance stated:  “Many prescription devices are used in the home with increasing frequency and the Agency believes that 510(k)s are not necessary to add home-use labeling.”  This belief is no more.  The 2011 Draft Guidance states:  “[C]hanges from prescription use in a clinical setting to prescription use in a home setting” require a 510(k).

Manufacturing Process Changes.  One other area of particular import is that the Draft Guidance discusses manufacturing changes, a section not contained in the 1997 guidance.  Some of the questions asked in the manufacturing section (related to packing or expiration dating and changes to sterilization) were present in the 1997 guidance in a different section.  The primary difference is that the Draft Guidance now asks the manufacturer to consider whether manufacturing processes were part of the original 510(k).  If not, you’re in luck—the Draft Guidance says if manufacturing process changes were not part of the original 510(k), chances are any changes to the manufacturing process won’t necessitate a 510(k).  But if they were part of the original 510(k), “changes to manufacturing processes that could affect device specifications will likely require submission of a new 510(k).”

Technology, Engineering, and Performance Changes.  As expected (or, perhaps, hoped), the Draft Guidance also addresses more types of technology used by medical devices than does the 1997 version.  With regard to nanotechnology, the Draft Guidance notes that FDA has not adopted nanotechnology-specific criteria to assist manufacturers in determining when changes require a new 510(k), so instead CDRH asks manufacturers to consult it regarding any nanotechnology-related changes.

Many of the technology-related updates in the Draft Guidance conclude that a new 510(k) would be required for most technology-related changes.  For instance, the Draft Guidance concludes that “all changes in fundamental scientific technology could significantly affect safety or effectiveness,” and therefore all such changes require the submission of a new 510(k).  The Draft Guidance also more specifically addresses whether the change has the potential to alter performance characteristics or specifications, and concludes that such changes directly impact the performance, and potentially the safety and effectiveness, of the device, “and a new 510(k) with comparative testing should be provided for such modifications, whether the performance characteristics are improved or worsened.”  Another area with a sweeping requirement for a new 510(k) is changes that affect how the device receives, transmits, or displays electrical signals or data.  The Draft Guidance does not contain much discussion of this topic, but nevertheless concludes that most changes of this nature have the potential to significantly impact safety or effectiveness by altering data communication quality, and therefore require a new 510(k).  An example provided includes a case of diagnostic software that typically displays images on a monitor in a clinical setting that is being modified to output the image to a portable hand-held device that can be used to view the images from any location.  The Draft Guidance states that this change “could result in new risks, such as the inability to discern certain data due to a smaller hand-held screen, lower picture resolution, or loss of data during transmission, that could significantly affect the safety and effectiveness of the software.” 

Finally, the Draft Guidance includes an area into which FDA generally at least attempts to tread lightly:  the practice of medicine.  One of the questions posed in the Draft Guidance is whether the change will affect how the device is likely to be used in practice.  What is particularly interesting about this question is that it cites a little-used statutory provision related to FDA’s ability to consider potential off-label uses of products under review.  According to this provision, if FDA concludes there is a “reasonable likelihood that the device will be used for an intended use not identified in the proposed labeling” and that “such use could cause harm,” FDA may require the submitter to include a statement in the labeling providing “appropriate information regarding” the off-label use of the product.  According to the Draft Guidance, if a manufacturer makes a change to the product that may result in off-label use that could cause harm, even if the manufacturer does not intend to change the labeling, a 510(k) may be needed “to enable FDA to evaluate whether ‘appropriate information’ in the labeling about a use not currently identified in the labeling is necessary.”

It’s hard to say whether industry will find the Draft Guidance provides the clarity missing from the 1997 guidance, or whether the proposal only increases the areas of ambiguity.  The only thing that appears certain is that CDRH believes many more modifications necessitate a new 510(k) than had been the case.  There are no changes where 510(k)s that were needed are no longer required, but there are many changes for which companies would have used a letter to file that would now need a 510(k).

By Kurt R. Karst –

Late last week, the U.S. District Court for the Eastern District of Virginia granted the U.S. Patent and Trademark Office’s (“PTO’s”) Motion for Summary Judgment in a challenge mounted by the Genetics & IVF Institute (“GIVF”) to the PTO’s August 2010 denial of a Patent Term Extension (“PTE”) for U.S. Patent No. 5,135,759 (“the ‘759 patent”), which covers a method to preselect the sex of offspring and is owned by the U.S. Department of Agriculture (“USDA”).  As we previously reported, GIVF, as the exclusive licensee of the (now-expired) ‘759 patent, sued the PTO under the Administrative Procedure Act, and asked the court to, among other things, vacate and set aside the PTO’s August 2010 decision and to declare that the PTO has the discretion to extend the term of the ‘759 patent for the full period required under 35 U.S.C. § 156.

The case involves the interim PTE provisions at 35 U.S.C. § 156(d)(5), under which the PTO may grant an interim patent extension while a Premarket Approval application (“PMA”) is undergoing FDA review if the patent owner (or his agent) “reasonably expects that the applicable regulatory review period . . . that began for a product that is the subject of such patent may extend beyond the expiration of the patent term in effect.”  To request an initial interim PTE, the owner (or his agent) submits an application to the PTO “during the period beginning 6 months, and ending 15 days before such term is due to expire.”  The statute provides that a total of 5 interim PTEs may be granted.  After the initial interim PTE is granted, 35 U.S.C. § 156(d)(5)(C) provides that “[e]ach such subsequent application shall be made during the period beginning 60 days before, and ending 30 days before, the expiration of the preceding interim extension” (emphasis added).

The ‘759 patent was set to expire on August 4, 2009; however, the USDA requested and the PTO granted an interim PTE for a period of one year, through August 4, 2010.  Just days before the interim PTE was going to expire, the USDA, on July 27, 2010 petitioned the PTO for an extension of time to file a second interim PTE and also a request for a second subsequent interim PTE.  On August 2, 2010,  the PTO denied both the USDA’s petition and request for a second subsequent interim PTE, saying that “[b]ecause the relief that petitioner seeks is from a statute, the USPTO, without any statutory authority to grant such relief, cannot excuse failure to comply with the statutory timing requirement of § 156(d)(5)(C) . . . .”  Unsatisfied with this decision, GIVF decided to take the matter to court.

GIVF argued in its Motion for Summary Judgment that the PTO’s decision that the Office lacked discretion to consider the USDA’s untimely application, because § 156(d)(5)(C) uses “shall,” fails because “shall” is sometimes discretionary,  the PTO’s decision is “inconsistent with how the USPTO views Section 156 and how the law views the other timing provisions in federal patent law,” and because  “allowing the USPTO’s decision to stand will result in a harsh, absurd, and
unfair result.”

In a 31-page opinion, Judge James C. Cacheris granted the PTO’s Motion for Summary Judgment.  Noting that although in the proper context “shall” may be permissive, in 35 U.S.C. § 156(d)(5)(C), the court said, “shall”  is mandatory:

The relevant language provides that “[e]ach such subsequent application shall be made during the period beginning 60 days before, and ending 30 days before, the expiration of the preceding interim extension.”  35 U.S.C. § 156(d)(5)(C).  This language is unqualified.  The application “shall be made” in the relevant period, full stop.  Without any qualifying language, “[n]othing in the language of the statute states or suggests that the word ‘shall’ does not mean exactly what it says.”  Thus, “shall” has its ordinary meaning denoting a mandatory requirement or obligation.  [(Citation omitted)]

This was not the end of the inquiry for the court, however: 

That “shall” in § 156(d)(5)(C) has its ordinary meaning does not end the inquiry.  That mandatory requirement or obligation applies to the applicant for the Extension, and not the USPTO.  That is, § 156(d)(5)(C) speaks to when a patent holder must file an application for an Extension, and does not, by its terms, address anything the USPTO must do.  Put simply, saying that Plaintiff had a mandatory requirement or obligation to file its application within a certain period does not, in and of itself, address whether the USPTO had discretion to consider a tardy application. [(Italics in original)]

Turning to whether § 156(d)(5)(C) speaks to the PTO’s discretion, independent of imposing a mandatory obligation on GIVF, the court said that “[n]othing in that statute, or in § 156 generally, answers the question of whether the USPTO has discretion to consider a tardy application under § 156(d)(5)(C).”  There are several other provisions in the patent laws that expressly grant the PTO  with discretion when administering time periods or deadlines; however, Judge Cacheris, relying on the canon of statutory construction against superfluity, wrote that if the PTO  “has discretion regardless of the mandatory requirement placed on the patent holder . . .  and without the statute’s granting discretion, then Congress would not have needed to provide for that discretion in the other provisions . . . .  Thus, all of that discretionary language would be unneeded and superfluous.”

Finally, addressing the remedial nature of the PTE statute and the allegedly “harsh” result it produced here, Judge Cacheris stated that even “[a] liberal reading of ‘shall’ in § 156(d)(5)(C) is not enough to get to where Plaintiff would have this Court go.  The Court would also need to add language to the statute to add discretion where Congress stated none.  The Court will not do so.”  GIVF had sought to rely on the district court’s so-called “liberal-reading-of-a-remedial-statute rule” in Medicines Co. v. Kappos, 731 F. Supp. 2d 470 (E.D. Va. 2010), to support its position.   But Judge Cacheris was not convinced, saying that in Medicines Co. Judge Hilton “reasonably applied one of two alternative common definitions for a term,” but that GIVF, in contrast, “is effectively asking the Court to rewrite, or at least add, whole-cloth, language to § 156(d)(5)(C).”

By Carmelina G. Allis –

The FDA’s “Draft Guidance on Mobile Medical Applications” is applicable to software products (or “mobile apps”) intended for use on mobile platforms that are handheld in nature, such as, for example, the iPhone® and Android® phones.  “Mobile medical apps” are defined as software applications that meet the statutory definition of a “device” under Section 201(h) of the Federal Food, Drug, and Cosmetic Act, and are either used as an accessory to a regulated medical device, or transform a mobile platform into a regulated medical device.

The FDA plans to exercise regulatory oversight over those mobile medical apps that are associated with current device classifications.  Thus, the guidance document focuses on mobile apps that perform functions that either have been traditionally considered medical devices, or that affect the performance or functionality of a currently regulated medical device.  Examples include mobile apps that are an extension of one or more medical devices by connecting to such device for storing or displaying patient-specific medical data (e.g., an app that displays medical images directly from a PACS server), or mobile apps that allow the user to input patient-specific information and uses algorithms to obtain a patient-specific results or diagnosis (e.g., apps that collect patient-specific data and compute the prognosis of a particular disease).

FDA also identifies the categories of mobile medical apps for which it will apply regulatory oversight.  Those categories are:

• displaying, storing or transmitting patient-specific medical device data in its original format;
• controlling the intended use, function, modes, or energy source of the connected medical device;
• transforming or making the mobile platform into a regulated medical device; and
• creating alarms, recommendations or creating new information (data) by analyzing or interpreting medical device data.

The guidance document clarifies that mobile apps that are electronic copies of textbooks, reference materials or teaching aids; that are used to make decisions regarding general health and wellness; or that only automate general office operations, such as billing, are not considered mobile medical apps.

This document also clarifies that a mobile platform is not a “device” simply because it can be used to run a mobile medical app.  However, if the platform is being marketed with a medical device intended use, then it would meet the definition of a “device.”

Although this guidance document provides much needed clarification on how the agency intends to regulate mobile medical apps, it still leaves uncertainty in some areas.  For example, FDA intends to exercise “enforcement discretion” against those mobile apps that do not meet the definition of a “mobile medical app” but may meet the statutory definition of a “device.”  This approach will create uncertainty for industry.  Moreover, there are other mobile apps that FDA will “monitor” and “determine whether additional or different actions are necessary to protect the public health.”  Examples of mobile apps that FDA will “monitor” are products that may meet the definition of a “device” and also automate common clinician’s diagnostic and treatment tasks, or allow individuals to self-manage their disease.  Because the agency has not defined its regulatory position on those apps that it will “monitor,” FDA seems to suggest that manufacturers should consider complying with device regulatory requirements for these types of apps.  This position will generate further uncertainty and unnecessary expense.

FDA is seeking comments on this draft guidance document.

By Kurt R. Karst –      

FDA has been asked for a fourth time to provide an advisory opinion on compliance with the Hatch-Waxman Orange Book patent listing requirements for a patent that claims a drug delivery device integral to the administration of the active ingredient, but where the patent does not recite the active ingredient.  The latest Advisory Opinion Request (Docket No. FDA-2011-A-0363), submitted on behalf of Forest Laboratories, Inc. (“Forest”) (and with respect to a drug product under an NDA – NDA No. 202-450 – that apparently has not yet been approved), follows almost identical Advisory Opinion Requests filed in January 2005 by GlaxoSmithKline (Docket No. 2005A-0015), in August  2006 by AstraZeneca (Docket No. 2006A-0318), and in June 2007 by AstraZeneca (Docket No. 2007A-0261).  Forest’s Advisory Opinion Request raises the issue of whether a patent with certain characteristics should be submitted to FDA for Orange Book listing; specifically, where:

a)  the patent claims a drug delivery device: (i) whose use is integral to the administration of the active ingredient subject of the NDA, (ii) whose approval, therefore, is part of the approval of the active ingredient subject of the NDA, and (iii) that is recited in the “Indications and Usage” section of the Prescribing Information for the active ingredient subject of the NDA (“label”); and

b)  the claims in the patent do not recite the active ingredient subject of the NDA.

As we previously reported, the advisory opinion requests previously submitted to FDA were apparently prompted by FDA’s response to comments stated in the preamble to the Agency’s June 2003 final rule implementing the FDC Act’s patent listing provisions.  Those comments sought clarification as to whether patents claiming delivery devices or containers “integral” to a drug product should be submitted to FDA for Orange Book listing.  FDA did not directly address the issue, but rather stated that the key factor in determining whether a drug product patent must be submitted for Orange Book listing is “whether the patent being submitted claims the finished dosage form of the approved drug product.” 

FDA’s failure to provide clear statements on the issue has led some companies to interpret the law and FDA’s patent listing regulations at 21 C.F.R. § 314.53 to require patent submission and Orange Book listing if such patents claim an integral part of an approved drug product rather than merely packaging (patents claiming packaging may not be submitted for Orange Book listing).  Indeed, GlaxoSmithKline, apparently tired of waiting for a response from FDA to its Advisory Opinion request, informed FDA in February 2009 that “in the absence of further guidance from the FDA, [the company] has modified its Orange Book listing practice to list those patents whose claims read on the drug product subject to FDA approval, including those patents that claim all or a portion of integrated drug-device products, regardless of whether the approved drug substance is specifically mentioned in the claims of such patents.” (See our previous post here.)  Other companies have apparently followed suit, as there are now several patents listed in the Orange Book that could be characterized as drug delivery device patents. 

Forest says in its Advisory Opinion Request that the FDC Act “imposes a duty on an NDA applicant to submit a patent for listing when the patent claims a drug product that can be asserted against a generic manufacturer in an infringement action,” and that:

In Forest’s view, that duty exists when the patent claims a drug delivery device that is an integral part of the administration of the active ingredient to a patient, especially when the approval of the drug product NDA is conditioned on the concurrent approval of the drug delivery device.  This duty should exists irrespective of whether the patent recites the active ingredient in the claims.  This is because the patent would be, in either case, a patent with respect to which a claim of patent infringement could reasonably be asserted under the conditions recited in the statute.

Moreover, says Forest, there are two reasons that “strongly suggest that the FDA accepts the practice of submitting drug delivery device patents that do not recite the drug substance in the claims for listing in the Orange Book.”  First, “the FDA has not condemned the practice publicly, even after given the explicit opportunity to do so via the three requests for an advisory opinion cited above.”  Second, “the FDA accepts the submissions of such patents and later lists them in the Orange Book.”

The Orange Book listing of one patent alleged to be a drug delivery device patent has already led one company to assert in court the patent delisting counterclaim provisions at FDC Act §505(c)(3)(D)(ii)(I) added to the statute by the Medicare Modernization Act (“MMA”) available to 505(b)(2) NDA sponsors.  (The MMA also added a parallel counterclaim provisions at FDC Act §505(j)(5)(C)(ii)(I) applicable to ANDA sponsors.)  As we previously reported, Intelliject, Inc. alleges in a court filing from earlier this year that U.S. Patent No. 7,794,432 (‘the ‘432 Patent”), which is listed in the Orange Book for EpiPen and EpiPen Jr Auto-Injectors (epinephrine injection) solution, 0.3mg/ml and 0.415/0.3 ml (NDA No. 19-430), must be delisted from the Orange Book, because “the ‘432 patent does not claim either the drug for which Meridian’s NDA was approved or an approved method of using the drug.”

By Kurt R. Karst –      

Suppose FDA approves a New Drug Application (“NDA”) – NDA No. 1 – and grants a period of 5-year New Chemical Entity (“NCE”) exclusivity, but there are no patents listed in FDA’s Orange Book for the NDA, and therefore, there is no opportunity for a generic drug sponsor to submit to FDA an ANDA containing a Paragraph IV certification on the so-called “NCE-1 date.”  Suppose further that a couple of years after the approval the NDA No. 1, FDA approves a second NDA from the same sponsor – NDA No. 2 – for a drug product containing the same active moiety as in NDA No. 1, but perhaps in a different dosage form, but the NDA sponsor does submit to FDA for listing in the Orange Book a patent for NDA No. 2.  While the remainder of the period of NCE exclusivity granted for the approval of NDA No. 1 would apply under FDA’s “umbrella policy” to NDA No. 2, does the fact that NDA No. 1 is not listed in the Orange Book with a patent preclude an NCE-1 Paragraph IV ANDA submission for the drug product covered under NDA No. 2?  It’s an interesting scenario – and probably quite rare – but one we thought should be tackled. 

The statutory 5-year NCE exclusivity provision at FDC Act § 505(j)(5)(F)(ii) applicable to ANDAs (there is a slightly different parallel provision at FDC Act § 505(c)(3)(E)(ii) applicable to 505(b)(2) applications) governing the scope of NCE exclusivity states in relevant part:

If an application submitted under subsection (b) for a drug, no active ingredient (including any ester or salt of the active ingredient) of which has been approved in any other application under subsection (b), is approved after the date of the enactment of this subsection, no application may be submitted under this subsection which refers to the drug for which the subsection (b) application was submitted before the expiration of five years from the date of the approval of the application under subsection (b), except that such an application may be submitted under this subsection after the expiration of four years from the date of the approval of the subsection (b) application if it contains a [Paragraph IV certification]. [(Emphasis added)]

Is the emphasis in this statutory provision on the phrase “the drug” (subsequently clarified by FDA to mean “active moiety”), which would argue in favor of an NCE-1 Paragraph IV ANDA submission for NDA No. 2, or on “the subsection (b) application,” which would seem to argue otherwise?

FDA’s regulation at 21 C.F.R. § 314.108(b)(2) implementing FDC Act § 505(j)(5)(F)(ii) sheds some light on this statutory provision and states, in relevant part, that:

If a drug product that contains a [NCE] was approved after September 24, 1984, in an application submitted under section 505(b) of the act, no person may submit a 505(b)(2) application or [ANDA] under section 505(j) of the act for a drug product that contains the same active moiety as in the [NCE] for a period of 5 years from the date of approval of the first approved [NDA], except that the 505(b)(2) application or abbreviated application may be submitted after 4 years if it contains a [Paragraph IV] certification . . . .[(Emphasis added)]

This regulations seems to say that the decisive factor in determining the scope of NCE exclusivity is the active moiety.  Indeed, if FDA intended the reference to “the subsection (b) application” in FDC Act § 505(j)(5)(F)(ii) to be the decisive factor in determining the scope of NCE exclusivity, then 21 C.F.R. § 314.108(b)(2) presumably would not emphasize the active moiety as it does.  Thus, if FDA were presented with the scenario above, it seems that the Agency would determine that NCE exclusivity prevents the submission of an ANDA for a proposed drug product containing the protected active moiety for 5 years – whether that protected active moiety is in a drug product approved under NDA No. 1 or under NDA No. 2 – unless an ANDA for a generic version of the drug product covered under NDA No. 2 protected by the umbrella NCE exclusivity stemming from the approval of NDA No. 1 contains a Paragraph IV certification to an Orange Book-listed patent.  In other words, an ANDA for a generic version of the drug product covered by NDA No. 2 could be submitted on the NCE-1 date if it contains a Paragraph IV certification.

Such an interpretation of FDC Act § 505(j)(5)(F)(ii) seems to be consistent with FDA’s NCE exclusivity “umbrella policy.”  Under that policy:

[W]hen exclusivity attaches to an active moiety or to an innovative change in an already approved drug, the submission or effective date of approval of ANDA’s and 505(b)(2) applications for a drug with that active moiety or innovative change will be delayed until the innovator’s exclusivity has expired, whether or not FDA has approved subsequent versions of the drugs entitled to exclusivity, and regardless of the specific listed drug product to which the ANDA or 505(b)(2) application refers.

FDA, Proposed Rule, ANDA Regulations, 54 Fed. Reg. 28,872, 28,897 (July 10, 1989) (emphasis added). 

Thus, NCE exclusivity protects the active moiety in subsequent NDA approvals made within the 5-year NCE exclusivity period; however, that exclusivity would seem to apply separately with respect to each approved drug product, particularly when there is a patent listed in the Orange Book covering NDA No. 2 in our scenario but not for the original NDA No. 1 approval from which the NCE exclusivity flows. 

By Kurt R. Karst –

On July 19th, President Obama announced his intent to nominate Maureen K. Ohlhausen as a Commissioner of the Federal Trade Commission (“FTC”).  Ms. Ohlhausen is currently a partner at Wilkinson Barker Knauer LLP, where she specializes in privacy, data protection, and cybersecurity.  Ms. Ohlhausen previously worked at the FTC from 1997 to 2008.  From 2004 to 2008, she served as Director of the Office of Policy Planning, where she supervised the development of reports, amicus briefs, and advocacy filings on competition and consumer protection topics, principally focusing on e-commerce, advertising, and technology issues.  Additional background information is available here.

If confirmed by the Senate, Ms. Ohlhausen would serve a 7-year term on the 5-member board, which currently includes Commissioners Jon Leibowitz, J. Thomas Rosch, William E. Kovacic, Edith Ramirez, and  Julie Brill.  Ms. Ohlhausen would be replacing William E. Kovacic, whose term expires in September.

By Ricardo Carvajal –

The integration of federal and state food safety systems is one of the goals of the Food Safety Modernization Act.  To that end, FDA recently announced the availability of grant funding to help with the “design, development, delivery, and maintenance of a national food/feed training program” to ensure “a competent workforce doing comparable work at all levels of the integrated food system.”

Budgetary realities suggest that the effort might not go smoothly.  Minnesota, generally regarded to be in the vanguard of states that prioritize food safety, was recently forced to designate critical services that would continue to be provided during that state government’s shutdown. Food safety and disease outbreak investigation and response made the cut, albeit “with limited staff.”  Conditions could be similarly grim in other states, particularly given that the playing field was not level even before the economic downturn.

Doubtless FDA will push forward.  An Agenda for Strengthening State and Local Roles in the Nation’s Food Safety System was laid out by Deputy Commissioner for Foods Michael Taylor before he assumed that mantle at FDA – and when the FSMA was just a gleam in the eyes of its sponsors.