By Riëtte van Laack –

In May of 2012, Plaintiff Matthew Dronkers filed a complaint in the United States District Court for the Southern District of California, on behalf of himself and other class members against Kiss My Face, LLC (“KMF”) claiming that KMF’s marketing of personal care products labeled as “obsessively organic” was false and misleading.  According to Mr. Dronkers, consumers interpret the term “organic” as applied to personal care products to mean that the product “is derived from fruits, vegetables and other crops that are grown, products, handled, and processed according to strict guidelines.”  Among other things, these “guidelines” include a requirement that the personal care products “must contain no synthetic ingredients.”  The complaint alleged that KMF’s products did not satisfy these criteria.  Plaintiff acknowledged that (“regrettably”) the Organic Food Production Act (“OFPA”) and the National Organic Program’s (“NOP’s”) implementing regulations do not apply to personal care products, but alleges that KMF’s claims did not comply with those standards either.

Somewhat curiously, Plaintiff did not cite or appear to rely on the California Organic Products Act (“COPA”).  COPA prohibits any product handled, processed, sold, advertised, represented or offered for sale in California from being sold as organic unless it is labeled with terminology similar to terminology set forth in the regulations by the NOP.  Under COPA, only personal care products with at least 70 percent organically produced ingredients may be labeled “organic.”  Plaintiff instead, appears to have relied on his own (more narrow) definition of “organic.”  Remarkably, this strategy seems to have worked.

KMF filed a motion to dismiss arguing express and implied conflict preemption because Plaintiff’s claims were (indirectly) premised on the labeling of the personal care products as organic when they did not comport with the requirements of the OFPA and the NOP regulations.  In the alternative, Defendant moved to dismiss the case under the primary jurisdiction doctrine and because of the Plaintiff’s failure to satisfy Federal Rule of Civil Procedure 9(b). 

Judge Houston denied the motion to dismiss.  He held that the OFPA and NOP implementing regulations are for foods and nothing from Congress or USDA to date suggests that federal legislation should preempt state law when it comes to organic claims for personal care products.  Moreover, because there was no evidence that the USDA was considering whether the NOP regulations apply to personal care products, the primary jurisdiction doctrine was inapplicable.  The court further concluded that Plaintiff had met the requirements for the Rule 9(b) heightened pleading standard.  In doing so, the opinion does not address the requisite showing of “falsity” based on what Plaintiff seems to admit is his own definition of “organic.”  The complaint does not appear to allege that Defendant (or anyone else) knew or should have known of Plaintiff’s definition of “organic.”  In other contexts, federal courts, including the Ninth Circuit, have distinguished between false claims and claims that are not true.  See, e.g., Wang v. FMC Corp., 975 F.2d 1412, 1420-21 (9th Cir.1992); (“The phrase “known to be false”  . . . does not mean ‘scientifically untrue’; it means ‘a lie.’”).

In any event, the lawsuit seeking class-action status against Kiss My Face for false advertising will move forward.  As the lawsuit moves forward, we will be watching to see whether Plaintiff’s seemingly home-grown definition of organic remains viable.

By Kurt R. Karst –  

We were reminded earlier today that a new law has gone into effect in the state of Maine permiting the importation of drug products into the state from licensed retail pharmacies located in certain foreign countries.  As we previously reported, in September, the Pharmaceutical Research and Manufacturers of America (“PhRMA”), along with several other trade groups – the Maine Pharmacy Association, Maine Society of Health-System Pharmacists, and Retail Association of Maine – and two pharmacists, filed a Complaint and Motion for Preliminary Injunction against Maine’s Attorney General and Commissioner of Administrative & Financial Services in the U.S. District Court for the District of Maine in an effort to block implementation of the importation law.  Plaintiffs allege in their filings that the Maine importation law is preempted under the Supremacy Clause of the U.S. Constitution (U.S. Const. Art. VI, cl. 2) because federal statutes, like the FDC Act and the 2003 Medicare Modernization Act (“MMA”), “occupy the field and the Maine law conflicts with and obstructs compliance with those statutes.”  Plaintiffs also allege that the Maine law violates the Foreign Commerce Clause (U.S. Const. Art I, § 8 cl. 3) because it “purports to regulate in an area where the federal government possesses exclusive and plenary power.”   That is, the state law violates the requirement that the federal government “speak[] with one voice in the area of international pharmaceutical trade” and discriminates against foreign commerce.

In recent court filings, Maine has opposed Plaintiffs’ Motion for Preliminary Injunction and has moved to dismiss the Complaint.  According to those pleadings, the new state law (referred to as the “2013 Amendment”):

does not affirmatively “authorize” Maine residents to buy prescription drugs from pharmacies located in Canada or any other country, and it does not “aid and abet violations” of the [FDC Act].  Rather, the 2013 Amendment simply restricts the reach of the Maine Pharmacy Act.  No constitutional provision requires Maine as a state to regulate in an area it chooses not to regulate.

Bearing that proposition in mind, Defendants say that “[t]he crux of plaintiffs’ lawsuit is the proposition that they can require a state to affirmatively regulate pharmacies in accordance with plaintiffs’ view of federal law where that state has chosen not to regulate.  No court of which defendants are aware has ever adopted such an extraordinary principle.”  “The 2013 Amendment is a classic example of a state acting to limit the extent of its traditional police powers – deciding not to assert its regulatory authority over certain conduct,” says Maine.  “The State of Maine has every right to take such steps.  To the extent that plaintiffs seek to require the State to enact laws to further the policies underlying the FDCA, plaintiffs run afoul of the Tenth Amendment.”  Under the Tenth Amendment, powers not granted to the federal government by the Constitution, nor prohibited to the States, are reserved to the States or the people.  “Maine is free to choose not to regulate the conduct of pharmacies located in other countries – even if those pharmacies may engage in conduct that violates the FDCA.  There is no constitutional principle that requires that a state regulate pharmacies (or any other industry),” continues Maine.

Moving on to the Foreign Commerce Clause, Defendants say that Plaintiffs’ theories are meritless.  “The foreign Commerce Clause is concerned with state laws that discriminate against foreign commerce or that excessively interfere with foreign affairs. . . .  [P]laintiffs filed this lawsuit because they are upset that the 2013 Amendment allegedly ‘authorizes’ foreign commerce at the expense of in-state commerce.  Even assuming that were true, however, the 2013 Amendment does not violate the foreign Commerce Clause” (citation omitted). 

But these arguments all assume that Plaintiffs have standing to bring the lawsuit in the first place.  They don’t, says Maine: 

This suit should be dismissed because no plaintiff has standing to assert violations of these constitutional provisions.  The 2013 Amendment, which restricts the reach of the Maine Pharmacy Act, does not directly affect plaintiffs.  No plaintiff is a retail pharmacy located outside the United States, and no plaintiff alleges that it plans to provide or facilitate the export of prescription drugs into Maine from a pharmacy located outside the United States.  In short, no plaintiff alleges that it has engaged or plans to engage in conduct covered by the 2013 Amendment.  Plaintiffs seek to enjoin the enforcement of an amendment that does not apply to them.

Moreover, plaintiffs purportedly seek to vindicate the interests of third persons – (A) Maine residents who may decide to purchase less expensive prescription drugs for their personal use from licensed pharmacies located in such places as Canada or the United Kingdom, and (B) pharmacies located in countries other than Canada, the United Kingdom, Australia, or New Zealand.  Plaintiffs’ own alleged injuries from the 2013 Amendment are indirect, remote, and speculative.

Plaintiff’s have requested that Oral Argument on the various motions in the case be scheduled for the week of November 4, 2013.  The court has not yet set a hearing date. 

By Jay W. Cormier –

Notwithstanding the government shutdown, on Tuesday, October 1st, FDA’s Center for Devices and Radiological Health (“CDRH”) issued a final guidance regarding filing for an investigational device exemption (“IDE”) for medical device early feasibility studies.  At the heart of the guidance is that an IDE application for an early feasibility study may be based on less nonclinical data than would be expected for a traditional feasibility or pivotal study.

For purposes of the guidance document, FDA defines an “early feasibility study” as:

a limited clinical investigation of a device early in development, typically before the device design has been finalized, for a specific indication (e.g., innovative device for a new or established intended use, marketed device for a novel clinical application).  It may be used to evaluate the device design concept with respect to initial clinical safety and device functionality in a small number of subjects (generally fewer than 10 initial subjects) when this information cannot practically be provided through additional nonclinical assessments or appropriate nonclinical tests are unavailable.  Information obtained from an early feasibility study may guide device modifications.  An early feasibility study does not necessarily involve the first clinical use of a device.

It is important for our readers to note that the guidance only applies to early feasibility studies for significant risk devices, as defined in 21 C.F.R. § 812.3(m). 

The guidance document discusses how to report prior investigations, establishing the investigational plan for the device, study changes, and design controls for these devices that are defined to be subject to significant changes before final designs have been established.  The guidance document details, with at times extreme specificity, the particular content and format the CDRH expects for these IDE applications.  For example, when discussing prior investigations using the device, FDA asks that sponsors submit such information in a device evaluation table consisting of nine specific columns that each contains pre-specified types of information. 

The upside for sponsors is that CDRH acknowledges that although the basic principles of an IDE apply to all device clinical studies, in these very early studies a smaller amount of supporting data is expected, and data gaps are not necessarily deal breakers for the IDE application.  Additionally, CDRH will be more flexible with how it approaches device and protocol changes during the studies.  Because of the nature of an early feasibility study, CDRH will also allow 5-day notification of five categories of changes that would otherwise not be permitted in a pivotal study.

CDRH notes that, when submitting an IDE for an early feasibility study, sponsors should be able to answer the following six questions with supporting information:

1. What is the clinical condition to be treated or assessed by the device?
2. What is the standard of care for the clinical condition and expected clinical outcomes associated with the standard of care?
3. What are the anticipated benefits associated with use of the study device?
4. Is the information included in the Report of Prior Investigations (Section 6 of the guidance) adequate to support initiation of the study?
5. Does the Investigational Plan include a thorough risk analysis, sufficient risk mitigation strategies, adequate human subject protection measures, and an appropriate clinical study protocol (see Section 7 of the guidance)?
6. Are the potential risks associated with the device use likely to be outweighed by the anticipated benefits of the early feasibility study, that is, is initiation of the clinical study justified based on the clinical need for the device, Report of Prior Investigations and Investigational Plan?

Because there will be less supportive data regarding the benefit-risk calculus, CDRH will, not unexpectedly, take a closer look at the various mechanisms available to mitigate potential risks associated with the device.  These additional risk mitigation strategies may include: more stringent criteria for study site and investigator selection, limiting the size of the study, more timely reporting of serious adverse events, and increased patient follow-up assessments.

Due to the flexibility given to sponsors of IDEs for early feasibility studies in significant risk devices, and because the specific expectations from CDRH will differ depending on the particulars of the study device, CDRH strongly recommends that sponsors consult with them prior to submitting the IDE application via the pre-submission process.  Although the guidance document provides a lot of detail and direction to sponsors, we agree that such pre-submission meetings should be helpful in avoiding unnecessary delays in obtaining IDE approval for these important device studies.

By Kurt R. Karst –      

We’re now entering the second week of the shutdown of the federal government (or “the lapse period” as some have called it), and there does not appear to be an end in sight.  In fact, the environment in Washington, D.C. has been described as “toxic.”  On the FDA front, confusion (both in and out of the Agency) seems to have been the state of affairs for several days last week.  What’s on and what’s off for FDA has been an ongoing topic of discussion since before the shutdown and after FDA issued an initial statement on affected activities (see our previous post here).  

Meanwhile, on Capitol Hill, a bill – H.J. Res. 77, Food and Drug Administration Continuing Appropriations Resolution, 2014 – cleared the House Rules Committee last week that would provide continued funding for FDA under Fiscal Year 2013 levels through December 15th, thereby effectively ending the partial shutdown of FDA (for the time being).  (A score of the bill by the Congressional Budget Office is available here.)  Although the House of Representatives passed the bill by a 235-162 vote Monday evening, the prospects of that bill, along with other bills providing appropriations for targeted government activities, getting past the President’s desk, are slim to none.  In a Statement of Administration Policy, the Office of Management and Budget indicated that “[i]f the President were presented with . . . H.J. Res. 77 [and other other similar resolutions], he would veto the bills.”

Last Friday, the Alliance for a Stronger FDA sent out a helpful list of FDA activities anticipated to be affected by the shutdown.  The list is from a posting on FDA’s website that was taken down later in the day (a copy of the original FDA posting is available here).  On October 7th, FDA reposted an updated version of the list, which we provide below for posterity (because you never know when the next shutdown might occur).  Following FDA's list are some additional notes based on our experience.

Medical Product Activities During the Federal Government Shutdown

This document summarizes the anticipated scope of FDA’s activities beginning on October 1, 2013, and continuing until the date of enactment of an FY 2014 appropriation or Continuing Resolution for FDA (the “lapse period”). Please note that FDA’s anticipated activities are subject to resource constraints on the Agency due to the lapse in appropriations and may change in the event of a protracted lapse period.
 
Overview

• During the lapse period, FDA activities related to medical products generally will be limited to the following:
  • Excepted work involving the safety of human life or the protection of property, including Criminal law enforcement work; and
  • Activities funded by carryover user fee balances, including user fee balances under the Prescription Drug User Fee Act (PDUFA), Generic Drug User Fee Amendments (GDUFA), and the Medical Device User Fee Amendments (MDUFA).
• Carryover user fee balances will be spent on activities for which the fees are authorized under PDUFA, GDUFA, or MDUFA, as applicable.
• FDA will not have legal authority to accept user fees assessed for FY 2014 until an FY 2014 appropriation or Continuing Resolution for FDA is enacted.  This means that FDA will not be able to accept any regulatory submissions for FY 2014 that require a fee payment and that are submitted during the lapse period.
• We do not anticipate that the lapse in appropriations will affect our routine product review process for submissions within the scope of the PDUFA or GDUFA programs, provided that applicable fees were paid before October 1, 2013. We cannot predict whether we will experience delays in these programs in the event of a protracted lapse in appropriations.
• Due to resource constraints, certain review activities for products within the scope of the MDUFA program may be suspended during the lapse period.
• Generally, scheduled advisory committee meetings regarding the approval of, or postmarketing safety issues regarding, products within the scope of the PDUFA, GDUFA, or MDUFA programs may go forward during the lapse period, subject to constraints on resources and travel. Other advisory committee meetings that can be conducted with carryover user fee balances will be handled on a case-by-case basis.

PDUFA

• During the lapse period, FDA will not accept PDUFA applications or supplements that require payment of a fee (e.g., New Drug Applications (NDAs) or certain Biologics License Applications (BLAs)), unless the FY 2014 fee was paid prior to October 1, 2013.  FDA expects to continue to review PDUFA applications and supplements for which all applicable user fees were received prior to October 1. 
  • For example, for an application or supplement that requires a fee, if the FY 2014 fee was received on September 30, 2013, FDA expects to review the application, even if the application or supplement itself is submitted during the lapse period.
  • However, if an application or supplement was received on September 30, 2013 and the fee was received on October 1, then FDA will not review the submission, because it cannot accept the fee.
• During the lapse period, FDA will accept new regulatory submissions for which no fee is required, if the product is within the scope of the PDUFA program.  These types of submissions include, for example:
  • Investigational new drugs applications (INDs)
  • Annual reports
  • Supplements to NDAs and BLAs for which clinical data with respect to safety or effectiveness are not required for approval (this includes most manufacturing and labeling supplements)
  • NDAs or BLAs that only have orphan designated indications, or a supplement for an orphan designated indication
  • Submissions that fall within the exemption for previously filed applications or supplements
  • Applications for which FDA has waived the application fee (e.g., small business waiver)
  • General correspondence
• Sponsors who have not yet paid PDUFA product or establishment fees for FY 2014 should not remit payment during the lapse period, because FDA cannot accept the fees.  Sponsors will not be in arrears for FY 2014 product or establishment fees during the lapse period.  The due date for these fees will be the first business day after enactment of an appropriation for FY 2014 or a Continuing Resolution for FDA.

GDUFA

• During the lapse period, FDA will not accept generic drug submissions that require payment of a fee (e.g., Abbreviated New Drug Applications (ANDAs), prior approval supplements to approved ANDAs).  FDA expects to continue reviewing GDUFA applications and supplements that were submitted on or before September 30, provided that all applicable fees are paid within 20 calendar days of the due date.  (FDA can continue to receive FY 2013 fees, but not FY 2014 fees, during the lapse period).
• During the lapse period, FDA will accept generic drug submissions for which no fee is required, if the product is within the scope of the GDUFA program.  These types of submissions include, for example:
  • Changes Being Effected (CBE) supplements
  • Amendments
  • Annual reports
  • Applications for positron emission tomography drugs
  • General correspondence
• Sponsors who have not yet paid GDUFA facility fees for FY 2014 should not remit payment during the lapse period because FDA cannot accept the fees.  Sponsors will not be in arrears for FY 2014 GDUFA facility fees during the lapse period.  The due date for the facility fee is the first business day after enactment of an appropriation for FY 2014 or a Continuing Resolution for FDA.
• During the lapse period, FDA will accept Drug Master Files (DMFs), including Type II Active Pharmaceutical Ingredient (API) DMFs, intended to be referenced in generic drug applications.
• FDA will not conduct initial completeness assessments on Type II API DMFs for which the fee has not been paid and these new DMFs will not be placed on the Available for Reference List.
  • If a generic drug application references, for the first time after October 1, 2013, a Type II API DMF for which the fee has not been paid, then FDA will notify the applicant that the fee must be paid within 20 calendar days.  If the fee is not paid within 20 calendar days of that notice, FDA will not receive the application.  At this time, FDA has not determined what approach it will take if the 20 calendar day period expires during the lapse period.
• Type II API DMF fees should not be submitted during the lapse period because FDA cannot accept the fees.  Fees that are due during the lapse period may be paid as soon as the lapse period ends.

BsUFA

• FDA does not expect to have access to BsUFA funding during the lapse period.  Accordingly, FDA does not expect to perform any activities with respect to biosimilars, except for emergency work involving the safety of human life or the protection of property.
• FDA will suspend review of any pending regulatory submissions (e.g., INDs, IND amendments, biosimilar initial advisory meeting and Biosimilar Product Development (BPD) meeting requests), unless the submission is:
  • An emergency IND; or
  • An IND amendment that relates to the safety of human subjects (e.g., an IND safety report).
• The 30-day review clock for any pending, non-emergency BsUFA INDs will be suspended during the lapse period.  The clock will resume when the lapse period is over.
• If a sponsor sends FDA a new regulatory submission for a biosimilar during the lapse period, FDA will not consider the submission to have been received by the agency during the lapse period. The only new BsUFA submissions that FDA will consider "received" (and proceed to review) during the lapse period are:
  • New emergency INDs; and New IND amendments that relate to the safety of human subjects (during the lapse period, FDA will screen incoming IND amendments to determine if they are in this category).
• For non-emergency BsUFA INDs submitted during the lapse period, the 30-day review clock will not start until the lapse period is over.

CDER’s Non-PDUFA, Non-GDUFA Drugs

• Certain drugs regulated by CDER are not within the scope of the PDUFA program; accordingly, PDUFA carryover funding is not available to carry out activities with respect to these products.  These drugs include:
  • Over the Counter (OTC) drugs not associated with an NDA, ANDA or supplement (e.g., OTC monograph drugs);
  • Large volume parenteral drug products approved before September 1, 1992; and
  • Drugs that are not for commercial distribution and are sponsored by State or Federal government entities.
• During the lapse period, FDA will not perform any activities with respect to these products except for emergency work involving the safety of human life or the protection of property.  FDA will suspend review of any pending regulatory submissions (e.g., NDAs, ANDA, BLAs, and supplements).

CBER’s Non-PDUFA, Non-MDUFA Biologics

• Certain biological drug products regulated by CBER are not within the scope of PDUFA.  These include whole blood, blood components for transfusion, and allergenic extract products.  Accordingly, PDUFA carryover funding is not available to carry out activities with respect to these products.  During the lapse period, FDA will not perform any activities with respect to these products except for emergency work involving the safety of human life or the protection of property.
• FDA will suspend review of any pending regulatory submissions (e.g., INDs, IND amendments, NDAs, BLAs, supplements), unless the submission is:
  • An emergency IND; or
  • An IND amendment that relates to the safety of human subjects (e.g., an IND safety report).
• The 30-day review clock for any pending, non-emergency IND will be suspended during the lapse period.  The clock will resume when the lapse period is over.
• If a sponsor sends FDA a new IND or IND amendment during the lapse period, FDA will not consider it to have been received by the agency during the lapse period.  The only new INDs and IND amendments for these products that FDA will consider "received" (and proceed to review) during the lapse period are:
  • New emergency INDs; and
  • New IND amendments that relate to the safety of human subjects (during the lapse period, FDA will screen incoming IND amendments to determine if they are in this category).
• If a sponsor sends FDA a non-emergency IND during the lapse period, the 30-day review clock will not start until the lapse period is over.

MDUFA Products Regulated by CDRH and CBER

• FDA expects to continue reviewing regulatory submissions received prior to October 1, 2013.  However, the Agency may suspend work on certain submission types during the lapse period due to resource constraints.
• FDA will not accept new regulatory submissions that require fee payment.  These include:
  • Premarket Approvals (PMA)s;
  • Product Development Protocols (PDPs);
  • Premarket Reports (PMRs);
  • original BLAs and BLA efficacy supplements for medical devices reviewed by CBER;
  • some PMA and PDP supplements (e.g., panel-track, 180-day, real-time, 30-day notice);
  • 510(k)s;
  • 513(g)s;
  • annual reports for PMAs, PDPs, and PMRs; and
  • registration information submitted under section 510 by a device establishment subject to a registration fee.
• FDA can accept and review new regulatory submissions for which no fee is required.  However, the Agency may suspend work on certain submission types during the lapse period due to resource constraints.  Non-fee paying submissions include, for example:
  • Humanitarian Device Exemptions (HDEs) (originals, supplements and reports)
  • Investigational Device Exemptions (IDEs) (originals, supplements and reports)
  • De novos
  • Pre-submissions
  • Special CBE supplements
  • Site change supplements
  • Trade name change supplements
  • Post-Approval Study (PAS) labeling or protocol change supplements
  • PAS reports
  • Submissions for pediatric only indications
  • The first PMA submitted by a small business with gross receipts or sales of $30 million or less

In addition to the above activities, we at the FDA Law Blog have become aware of the following:

• FDA’s Dockets Management Branch remains closed.  Although comments on existing dockets can be submitted via www.regulations.gov, and generally appear on a daily website update, original submissions submitted to the Dockets Management Branch are not being accepted.  The regulations.gov website is currently carrying the following note: “Due to the government shutdown, information on this website may not be up to date. You can still submit comments to agencies using Regulations.gov during the shutdown.”
• Insofar as pending citizen petitions relate to user fee-funded activities, FDA continues to process petition responses and to send responses once complete.  Those responses, however, cannot be uploaded to the regulations.gov docketing system.
• FDA’s electronic Orange Book is being updated with information on new patent listings and generic drug product data.  These updates generally occur daily and are expected to continue during the shutdown.
• FDA’s Office of Orphan Products Development is operating with a reduced staff, but continues to process orphan drug designation requests. 

We also note that the shutdown, if it continues for an extended period, could result in several interesting scenarios under the Hatch-Waxman Amendments vis-à-vis ANDAs and 180-day exclusivity.  As noted above, during the shutdown, FDA will not accept new ANDAs that require payment of a user fee.  That means upcoming so-called “NCE-1” dates could be missed.  Because it is unknown when, exactly, the shutdown will end, and therefore, when an original ANDA can be submitted to and accepted by FDA with a Paragraph IV certification qualifying a company as a “first applicant” eligible for 180-day exclusivity, some generic drug sponsors might consider submitting applications on a serial basis to FDA until an application is accepted.  Following such a strategy, if FDA were to accept it, could increase the likelihood of securing 180-day exclusivity eligibility. 

In other cases, however, sponsors of new, original ANDAs may lose out on 180-day exclusivity eligibility.  Consider, for example, the following scenario, where no patent information is yet listed in the Orange Book for the Reference Listed Drug (“RLD”):  ANDA Sponsor A has a pending ANDA submitted to FDA before the shutdown.  ANDA Sponsor B did not submit its ANDA before the shutdown but had planned to submit it to FDA this week.  If information on a new patent is listed in the Orange Book for the RLD today, then ANDA Sponsor A could amend its application to contain a Paragraph IV certification to that patent and become eligible for 180-day exclusivity.  ANDA Sponsor B would not be permitted to submit its ANDA because of the shutdown, and thus may lose out on eligibility for 180-day exclusivity.  A similar story could play out where there is patent information listed in the Orange Book for an RLD, but no ANDA sponsor has yet submitted a Paragraph IV certification.  ANDA Sponsor A could certify to the patent as an amendment to a pending application, whereas ANDA Sponsor B could not submit an original ANDA.  

By Jeffrey K. Shapiro –

There has been a lot of talk about hostage taking during the recent federal government budget impasse.  But Congress is not the only one taking hostages in Washington.  The recent draft Medical Device Reporting (MDR) guidance reminds us (pp. 4-5) about a long forgotten hostage moldering in FDA’s statutory implementation dungeon. 

To be specific, Section 227 of the Food and Drug Administration Amendments Act of 2007 (FDAAA) amended Section 519 of the Federal Food, Drug, and Cosmetic Act (FDCA) to ease the burden of malfunction MDR reporting by requiring only summary quarterly reporting for most class I and II devices.   

Congress directed that revised malfunction MDR reporting shall be “in accordance with criteria established by [FDA] for reports … which criteria shall require the reports to be in summary form and made on a quarterly basis.”  519(a)(1)(B)(ii).  

This change does not apply to class III devices, class II devices that are permanently implantable, life supporting, or life sustaining, and such other devices as FDA may designate in a “notice published in the Federal Register or letter to the person who is the manufacturer or importer of the device.”  Section 519(a)(1)(B)(i)(III).

Unfortunately, a full six years has passed, and nothing has happened.  In 2011, FDA issued a notice reminding industry that malfunction MDR reporting should continue as usual.  76 FR 12743.  In 2013, FDA has now reminded everyone again in the draft MDR guidance that nothing has changed.

Interestingly, the FDAAA Implementation Chart on FDA’s website does not even show the malfunction MDR reporting change as an item intended for implementation.  There should be a row for Section 227, but the chart skips from Section 226 to 228, with not a word about implementation of Section 227.  

Is this long delay really necessary?  According to the federal register notice, FDA is delaying implementation of the quarterly MDR reporting change until:

1. The agency publishes a federal register notice listing the additional class I and II devices not eligible for quarterly reporting pursuant to Section 519(a)(1)(B)(i)(III) of the FDCA; and
2. The agency conducts a rulemaking to establish the criteria for summary quarterly reporting for most class I and II devices pursuant to Section 519(a)(1)(B)(ii) of the FDCA.

Thus, implementation of the change is being held hostage to the agency’s own inaction.

As to the first item, Section 519(a)(1)(B)(i)(III) was intended to give FDA the regulatory flexibility to designate additional devices ineligible for quarterly reporting.  Nothing in the statute indicates that FDA’s designation of a complete list of such devices is a threshold requirement for implementation of quarterly reporting.  FDA’s failure to issue this list is not a valid basis for holding up implementation of quarterly reporting for the majority of class I and II devices.

As to the second item, keep in mind that even when FDA finally initiates a rulemaking, it typically takes several years until a final rule is issued.  With no rulemaking even begun, FDA appears on track to exceed 10 years in implementing this simple statutory requirement.  This delay is unacceptable.

Furthermore, the statute merely says that quarterly reporting shall be under criteria to be “established” by FDA.  The word “established” does not require a rulemaking, but could be achieved by a guidance.  Given the six year delay, at this point, it would be prudent for FDA to issue a guidance.  Even that process would probably require one to two years.  A benefit to issuing a guidance would be to allow FDA to gain some experience with widespread quarterly reporting before codifying  the requirements in a regulation.  It would also allow the agency to actually implement quarterly reporting inside of a decade.

By the way, Section 226 of FDAAA amended Section 519 to require FDA to establish a system of unique device identifiers.  This provision directs FDA to “promulgate regulations establishing a unique device identification system.”  Thus, Congress knew how to direct FDA to initiate a rulemaking when one was desired.  The absence of a similar requirement to “promulgate regulations” in Section 227 bolsters the interpretation that Congress did not intend for FDA to conduct a rulemaking to establish criteria for quarterly summary MDR reporting.

Congress has made the judgment that quarterly malfunction MDR reporting is sufficient to protect the public health for most class I and II devices.  Six years later, it is long past time for FDA to let this hostage go.

Hyman, Phelps & McNamara, P.C. is pleased to announce that Kermit L. Jones, J.D., M.D. has joined the firm as an Associate.  Prior to joining the firm, Dr. Jones served as a 2012-2013 White House Fellow assigned to the Secretary of Health and Human Services, the Honorable Kathleen Sebelius.  In this role, Dr. Jones briefed the Secretary on issues of importance to senior leadership at the Department of Health and Human Services, such as the arguments and positions in the Supreme Court case, Assoc. for Molecular Pathology v. Myriad Genetics, Inc. (133 S. Ct. 2107 (2013)).  He helped lead the Secretary’s efforts to engage states, licensing bodies and federal government agencies working to secure private sector licensing for military medical personnel. 

Dr. Jones also assisted stakeholders at the NIH, FDA, and within the non-profit and pharmaceutical sectors in evaluating the effectiveness of several recent initiatives that increase private-public collaboration in the rescue and repurposing of therapeutics.   Prior to the White House Fellowship, Dr. Kermit Jones served as a Navy Flight Surgeon with the Marine helicopter casualty evacuation squadron, the HMM-364 Purple Foxes, in Al Habbaniyah, Iraq.  While in Iraq, he provided medical care for U.S. service members and Iraqi citizens. 

Dr. Jones is a graduate of the Columbia University School of International and Public Affairs (2012), and both the Duke University School of Law (2005) and School of Medicine (2005). While at Duke, Dr. Jones was a Mordecai Scholar and spent semesters abroad at the London School of Hygiene and Tropical Medicine and the Christian Medical College and Hospital, in India.  He is conversational in Hindi and Urdu and admitted to practice law in Pennsylvania and medicine in New York.  His application to practice law in the District of Columbia is pending.

By Riëtte van Laack & Ricardo Carvajal –

On September 19, 2013, Cargill entered into a $5 million settlement agreement to dispose of a class action lawsuit regarding its advertising for Truvia® products as “natural.”  Plaintiffs charged that the products are not natural because they contain ingredients that are “‘highly processed,’ synthetic and/or derived from GMOs,” and that the descriptions of the products and their ingredients, namely stevia leaf extract and erythritol, are inaccurate or misleading.  In the agreement, Cargill denies that its marketing, labeling, and advertising violate any legal requirement.

The agreement is intended to address all current and future claims concerning the marketing of the products as natural (for purposes of the settlement, Cargill recognized a nationwide class of consumers).  The agreement consists of four components: 1) the $5 million settlement to cover attorney’s costs (1.59 million) and consumer refunds, 2) an administration fund of 300,000 dollars, 3) modifications to claims on packaging and labels, and 4) modifications to the website.

Interestingly, the parties agreed that Cargill can continue the use of the tagline “Nature’s Calorie-Free Sweetener” on labels, as long as the tagline is linked to a statement referring consumers to FAQs on the website where they can obtain more detailed information on the product’s manufacture (more about that in a moment).  Cargill can also continue to describe erythritol as a “natural sweetener” on labels, but instead of stating that it is produced by a “natural process,” Cargill will state that it is produced by a “fermentation process.”

The FAQs on the website address the processing of stevia leaf in some detail.  In essence, the leaves are harvested, dried, and steeped in hot water, and the extract is then filtered, purified, and dried.  The FAQs also address the production of erythritol.  Notwithstanding the label changes described above, the FAQ agreed to for erythritol states that it is “produced through a natural fermentation process” – a reaffirmation of sorts that fermentation is a natural process.  The FAQs also include the following explanatory text on processing aids:  

Like in other finished foods, including sugar, processing aids suitable for use in food are used in the production of both stevia leaf extract and erythritol. These aids help either extract, isolate or purify components of the ingredients. Under the U.S. Food and Drug Administration regulations, our processing aids are not subject to labeling requirements because they have no technical or functional effect in the finished food and because they are either not present or are present at only insignificant levels in the finished product.

The agreement disclaims any intent to address the merits of the claims, but could still have an impact.  It would not be surprising to see a trend toward greater disclosure with respect to processing methods, especially given the continuing lack of clarity regarding the meaning and scope of “natural.”

The preliminary settlement hearing, in which the Court will consider whether it should approve the proposed settlement, is scheduled for October 23, 2013.

By Jay Cormier & Alan Kirschenbaum –

The Patient Protection and Affordable Care Act made extensive changes to the 340B drug discount program, which we have previously described.  Among other things, the statute expanded the categories of covered entities entitled to purchase drugs at the statutory ceiling price.  It also provided an exemption from the ceiling price for designated orphan drugs when purchased by certain of these covered entities (the so-called “orphan drug exclusion”). 

For readers not familiar with the 340B Program, section 340B of the Public Health Services Act requires drug manufacturers, as a condition of Medicaid and Medicare Part B coverage of their product, to sell outpatient drugs to “covered entities” at a price no greater than a statutory ceiling price.  Congress’ intent was to provide outpatient prescription drug assistance to vulnerable uninsured patients.  The list of covered entities, as expanded by the Affordable Care Act, includes certain federally subsidized clinics and certain safety net hospitals, including disproportionate share hospitals, children’s hospitals, certain free-standing cancer hospitals, critical access hospitals, rural referral centers, and sole community hospitals. 

The orphan drug exclusion in the Affordable Care Act provides that a drug eligible for 340B pricing “shall not include a drug designated by the Secretary under [section 526 of the Federal Food, Drug, and Cosmetic Act] for a rare disease or condition.”  42 U.S.C. § 256b(e).  This exception applies to cancer hospitals, critical access hospitals, rural referral centers, and sole community hospitals. 

In late July, the Health Resources and Services Administration ("HRSA") issued a final implementing rule, codified at 42 C.F.R. § 10.21, providing that the orphan drug exclusion applies only to orphan drugs that are “transferred, prescribed, sold, or otherwise used for the rare condition or disease for which that orphan drug was designated.”  76 Fed. Reg. 44,016 (Jul. 23, 2013) (see our previous post regarding the proposed rule).

As threatened in their comments on the proposed rule, the Pharmaceutical Research and Manufacturers of America ("PhRMA") has filed a complaint and application for a preliminary injunction in the U.S. District Court for the District of Columbia, with supporting memorandum, claiming that HRSA’s orphan drug rule violates the Administrative Procedures Act ("APA").  Specifically, PhRMA alleges that (1) HRSA did not have the authority to promulgate the final rule, and (2), even if HRSA did have such authority, the final rule conflicts with the plain statutory language of the Affordable Care Act, which, according to PhRMA, exempts all uses of designated orphan drugs from the ceiling price, not just those used for the orphan indication.  PhRMA is seeking a declaration that HRSA violated the APA, a preliminary injunction, and an order invalidating and enjoining the enforcement of the final rule.

Will PhRMA prevail on the merits of this case?  That is the question.  We will be following this case during the coming months and will provide you with updates.

The case is Pharmaceutical Research and Manufacturers of America v. US Department of Health and Human Services, et al., Civil Action No. 1:13-cv-01501 (D.D.C.).

By John R. Fleder –

On September 26, 2013, the United States Attorney for the District of Colorado announced that he had filed a six count criminal Information against Eric and Ryan Jensen.  The government alleges that the defendants violated the FDC Act by introducing adulterated cantaloupes into interstate commerce.  The government also alleges that the cantaloupes bore Listeria monocytogenes and 33 people died.  It is quite curious (we are being charitable here) that the government’s press release alleges that 147 people were hospitalized as a result of sales of the cantaloupes, but those allegations appear nowhere in the criminal Information!

The prosecution is a misdemeanor case, and does not allege any criminal “intent” on the part of the defendants.  There is no public indication that the defendants are prepared to plead guilty and/or cooperate with the government against others.  This fact pattern strongly suggests that this case is an old style Park criminal prosecution where the government files criminal charges under the FDC Act against company officials, without allegations that the defendants intended to violate the law and without a plea bargain that a misdemeanor prosecution is a settlement of more serious felony charges.  Our speculation is that a thorough government investigation here failed to turn up evidence that the defendants violated the FDC Act “with the intent to defraud or mislead,” which would be necessary to commence felony charges under the FDC Act.  In fact, the government used a grand jury to investigate this case, even though it can file a criminal Information involving misdemeanor charges without using a grand jury.

The second interesting twist in this case is that arrest warrants were issued for the defendants.  Arresting defendants charged only with misdemeanors was certainly not the norm with regard to old style Park prosecutions.  Typically, the defendants were simply notified of the charges and came to court voluntarily to enter their guilty or not guilty pleas.

By Kurt R. Karst –   

It was not a question of whether, but when FDA would issue its first Warning Letter to a facility covered by the Generic Drug User Fee Amendments of 2012 (“GDUFA”) that failed to self-identify its facility and pay applicable user fees.  That day has come.  In a September 17, 2013 Warning Letter posted on FDA’s website earlier this week, the Agency says that Feldkirchen-Westerham, Germany-based C.P.M. Contract Pharma GMBH & Co. KG (“CPM Contract Pharma”) failed to self-identify its Finished Dosage Form (“FDF”) manufacturing facility and pay applicable user fees.

GDUFA establishes four types of user fees that together generate funding for FDA each fiscal year.  One of the fees – the annual facility fee –  must be paid by both FDF and Active Pharmaceutical Ingredient (“API”) manufacturers.  Facility fees are the most significant of all GDUFA user fees, and FDF facility fees in particular (see our previous post here).  The API and FDF facility fees are based on data submitted by generic drug facilities through the so-called self-identification process (see here and here).  In a draft guidance document titled “Self-Identification of Generic Drug Facilities, Sites, and Organizations,” and in an accompanying Q&A, FDA lays out the so-called “self-identification process.”  As explained in the draft guidance:

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

Facilities that fail to self-identify and pay applicable user fees are subject to some pretty significant penalties:

1. Identification of the facility on a publicly available arrears list, such that no new applications from the person that is responsible for paying such fee, or any affiliate of that person, will be received by FDA;
2. New generic drug submissions to FDA that reference a non-compliant facility will not be received unless the fee is timely paid; and
3. All FDFs or APIs manufactured in such a facility or containing an ingredient manufactured in such a facility are deemed misbranded under FDC Act § 502(aa).

These pentalties apply until the facility fee is paid or until the facility is removed from all generic drug submissions that refer to the facility.  The misbranding penalty is particularly harsh.  It was a point of contention during GDUFA negotiations, but we understand FDA demanded that it be included in the law to give it some teeth.

FDA’s Warning Letter to CPM Contract Pharma pulls out all the stops.  According to FDA:

The above-referenced facility is a drug manufacturing facility as defined under GDUFA.  It was identified as a finished dosage form manufacturer in [REDACTED] on the date for self-identification for fiscal year 2013 and fiscal year 2014 and on the due date for facility fees for fiscal year 2013, but has not self-identified or paid facility fees as required by that law.  Therefore, all finished dosage forms of drugs or APIs, as well as drug containing an API, manufactured at the facility are misbranded.
 
Your facility has been placed on a publicly available arrears list.  Failure to correct these violations promptly may result in regulatory action, including but not limited to seizure or injunction without further notice.  Your facility may also be placed on import alert such that any drug the facility manufactures will be refused admission into the United States.

FDA’s Warning Letter is the latest in a string of events as the Agency continues to ramp up GDUFA implementation.  Not everything FDA has done has been welcomed by the generic drug industry (see our previous post here); however, other aspects are improvements vis-à-vis the pre-GDUFA era.  For example, earlier this week, FDA published a detailed draft guidance, titled “ANDA Submissions – Refuse-to-Receive Standards,” providing helpful insight on the circumstances under which the Agency may refuse to accept an ANDA submission, including failure to pay applicable GDUFA user fees.  

By Ricardo Carvajal & Kurt R. Karst –

According to contingency plans drawn up by the Department of Health and Human Services, 45% of FDA’s nearly 15,000 staff were to be furloughed in the absence of enacted annual appropriations – popularly referred to as a government shutdown.  Now that the shutdown has materialized, the effects will be felt throughout the agency, but the blow is likely to be softened (at least in the near term) for centers that operate programs funded by industry-paid user fees (e.g., drugs and tobacco products).  For those FDA components, carryover balances from user fees previously collected under the Prescription Drug User Fee Act, the Generic Drug User Fee Amendments, the Medical Device User Fee Amendments, the Animal Drug User Fee Act, the Animal Generic Drug User Fee Act, and the Family Smoking Prevention and Tobacco Control Act can be spent – until exhausted – on activities for which the fees are authorized under the statute.

That’s not to say programs funded by user fee carryover balances will escape unscathed.  As indicated in a notice posted on FDA’s website on the first day of the shutdown (referred to as "the lapse period"):

With respect to medical product user fees, during the lapse period, FDA will not have legal authority to accept user fees assessed for FY 2014 until an FY 2014 appropriation for FDA is enacted. This will mean that FDA will not be able to accept any regulatory submissions for FY 2014 that require a fee payment and that are submitted during the lapse period.

Hardest hit is FDA’s foods program, which is generally not funded by user fees.  By all accounts, the majority of activity in that program has ground to a halt.  In particular, notification programs such as those for GRAS uses of substances, food contact substances, and infant formula have ceased operation, leaving a number of submissions in limbo. 

The effects of the shutdown will also be felt in relation to services that are not center-specific.  For example, the Division of Dockets Management is shuttered and will remain so indefinitely.  It is not clear how, in the interim, any submissions that must be made in person at the Division of Dockets Management will be handled (e.g., original citizen petitions).  For routine docket submissions, the regulations.gov website says: "You can still submit comments to agencies using Regulations.gov during the shutdown."

Also, it appears that other operations, such as recall operations, have been significantly curtailed and that remaining resources will be focused as necessary for the protection of human life.

By William T. Koustas & Jessica A. Ritsick –

With California’s electronic pedigree requirement set to take effect in 2015, we have been following recent efforts by Congress to enact a national prescription drug track and trace system (see our previous posts here, here, here, and here).  The House passed a bill in June, H.R. 1919, that would create a national pedigree system and the Senate Committee on Health, Education, Labor, and Pensions (“the Senate Committee”) passed a similar bill, S. 959, in May.  Then, late on September 25, 2013, leaders from the Senate and House committees overseeing health care policy announced that they reached an agreement on bipartisan and bicameral legislation (“bicameral legislation”) that would amend the Federal Food, Drug, and Cosmetic Act (“FDCA”) to address compounding pharmacies and incorporate a national prescription drug track and trace system as well as national standards for prescription drug wholesale distributors (“wholesalers”) and third-party logistics providers (“3PLs”).  The House passed the bicameral legislation, the Drug Quality and Security Act (H.R. 3204), on September 28, 2013 by voice vote.  A detailed outline of the bicameral legislation prepared by Hyman, Phelps & McNamara, P.C. can be found here.

The track and trace system (i.e., pedigree) set forth in the bicameral legislation would preempt state pedigree requirements and eventually create a national interoperable electronic prescription drug track and trace system.  While the bicameral legislation is in many respects similar to the Senate Committee’s bill, it contains some significant differences.

The bicameral legislation provides specific track and trace requirements for manufacturers, wholesalers, repackagers, and dispensers (e.g., pharmacies) of prescription drugs.  Unlike the Senate Committee’s bill, it does not require 3PLs to be responsible for pedigrees.  Under the bicameral legislation, manufacturers would be required to include a product identifier number on each “package and homogeneous case” of prescription drug product they produce within four years of enactment, while repackagers would be required to include it within five years.    In the meantime, the bicameral legislation requires manufacturers, wholesalers, repackagers, to provide and/or receive pedigree by January 1, 2015, while dispensers are required to do so by July 1, 2015.  In addition, wholesalers would be required to accept and distribute only those prescription drug products that include product identifiers within six years, while dispensers would be required to only receive proscription drug products with a product identifier within seven years.  As such, other than for 3PLs, the timelines for incorporating and distributing drug products with a product identifier for manufacturers, wholesalers, dispensers, and repackagers remains unchanged from the earlier Senate Committee’s bill.

In addition to product identifier requirements, the bicameral legislation also mandates that manufacturers, wholesalers, repackagers, and dispensers implement a system to verify that prescription drug products under their control are legitimate (e.g., not counterfeit, diverted, stolen, or otherwise adulterated).  If a “suspect” drug product is determined to be illegitimate, the entity must take the necessary steps to purge it from the supply chain.  Both pieces of legislation allow FDA or any trading partner to request verification from a drug’s manufacturer. 

Both the Senate Committee’s bill and the bicameral legislation initially allow for pedigrees to be transmitted and maintained in either paper or electronic format.  However, both bills mandate that an interoperable electronic system be implemented within 10 years of enactment.  This interoperable electronic system must be able to track and trace prescription drug products at the package level in accordance with standards established through guidance.  As such, FDA would be required to issue guidance documents for each of the following:  1) standards for an interoperable electronic system (within one year of enactment); 2) suspect and illegal products (within 180 days of enactment); 3) unit level tracing (within 18 months of a public meeting); and 4) revisions to the interoperable electronic system guidance (within 18 months of a public meeting).  Some of these guidance documents cannot be issued before a series of public meetings which cannot be held prior to one year after the legislation is enacted.  Both the bicameral legislation and the Senate Committee bill also requires FDA to establish at least one pilot program to “explore and evaluate methods to enhance the safety and security of the pharmaceutical distribution supply chain.”  

The bicameral legislation also sets requirements for the licensing and operation of wholesalers and 3PLs.  This includes the creation of national wholesaler and 3PL licenses in cases where states do not license such entities.  However, similar to the Senate Committee’s bill, the bicameral legislation continues to allow states to collect licensing fees and direct administrative fines for wholesalers and 3PLs licensed by the state.  Additionally, wholesalers and 3PLs are required to submit annual reports to FDA beginning on January 1, 2015.  These reports would include information regarding each state where the wholesaler or 3PL is licensed, the name and address of each facility, and contact information.  Both the Senate Committee’s bill and the bicameral legislation preempt state pedigree requirements. 

The bicameral legislation appears to have the support of congressional leaders from both parties.  With passage secured in the House, it is expected that the full Senate will take up this legislation soon.  A national prescription drug track and trace system is closer to becoming a reality than ever before.

By William T. Koustas – 

We have previously reported (here and here for example) on the litigation between Regenerative Sciences, LLC (“Regenerative”) and FDA.  Regenerative is a Colorado company that owns a medical procedure known as the Regenexx Procedure.  It is a non-surgical procedure by which physicians take bone marrow and blood samples from a patient, culture and process the stem cells, and inject them back into the same patient in order to treat joint, muscle, tendon, or bone pain.  The Regenexx Procedure is exclusively licensed for use by the Colorado clinic where its inventors practice. 

As reviewed in more detail in our prior posts, FDA contends that, among other things, the stem cells processed in the Regenexx Procedure are a drug under the Federal Food, Drug, and Cosmetic Act (“FDCA”) and must therefore only be created pursuant to a New Drug Application and under current Good Manufacturing Practices.  Regenerative responds that the Regenexx Procedure is the practice of medicine, which is outside of FDA’s jurisdiction and the stem cells are not introduced or delivered for introduction into interstate commerce since the entire process is performed in Colorado. 

The U.S. District Court of the District of Columbia ultimately sided with FDA, although it called the decision a “close question.”  The Court found that the stem cells used in the Regenexx Procedure are a drug as defined under the FDCA and that FDA has jurisdiction to regulate this procedure “because a component of the [Regenexx Procedure] shipped through interstate commerce prior to its administration to the patient,” thus satisfying the interstate commerce requirement in the FDCA.

However, with the case now pending before the U.S. Court of Appeals for the District of Columbia Circuit, a new report authored by Richard A. Epstein from the Manhattan Institute’s Center for Legal Policy (“the Report”) calls into question the legal and policy bases for FDA’s regulation of autologous stem cell procedures like the Regenexx Procedure.

The Report, titled “The FDA’s Misguided Regulation of Stem-Cell Procedures: How Administrative Overreach Blocks Medical Innovation,” contends that FDA “has taken the aggressive position that it has oversight authority over any stem-cell procedure that reinjects harvested stem cells into the same person from whom they were removed, so long as those cells were grown and cultured outside the human body.”  Among other things, the Report argues that FDA and the district court incorrectly interpret the interstate commerce provision in the FDCA while also improperly determining that the stem cells in the Regenexx Procedure are drugs rather than part of the practice of medicine. 

With respect to FDA’s position that is has authority to regulate autologous stem cell procedures pursuant to the interstate commerce provision in FDCA § 301(a), the Report contends that the statutory authority provided in the FDCA does not extend as far as the Constitution’s Commerce Clause.  The Report points to the fact that the interstate commerce language in the FDCA pre-dates the Supreme Court’s Wickard v. Filburn, 317 U.S. 111 (1942), decision and is therefore meant to reflect a pre-Wickard reading of interstate commerce.  As such, “the statutory requirement…is not whether a reagent used in the process has moved in interstate commerce but whether the dangerous (‘adulterated or misbranded’) article itself has moved in interstate commerce.”  Therefore, while the Constitution’s Commerce Clause would allow Congress to regulate autologous stem cells due to use of reagents that traveled through interstate commerce, the FDCA’s interstate commerce provision would not. 

In addition, the Report suggests that the “held for sale” language of FDCA § 301(k) only applies to articles that were themselves part of an interstate commerce transaction.  However, the stem cells used in the Regenexx Procedure were never part of an interstate transaction themselves and were therefore not held for sale in an interstate transaction.

The Report also makes the case that the Regenexx Procedure is the practice of medicine rather than the manufacture of a drug as FDA contends.  The Report analogizes the Regenexx Procedure to dental work by noting that, “[t]he process in question would normally be regarded as a provision of services for which the growth of the cells under these highly specified procedures would be regarded as, at most, an ‘incidental’ element to the transaction, just as a dentist who prepares mixtures for fillings is regarded as having supplied services and not as having manufactured and sold a mixture of silver and bonding solutions.”  The report also notes the basic differences between cultivating autologous stem cells and the mass production of drugs, arguing that the “…uniqueness [of the cultivating of stem cells] makes it relatively easy…to engage in the upstream regulation of these products” by state medical boards instead of FDA-approval.  In contrast, the Regenexx Procedure does not lend itself to FDA regulation as the process is slightly different for every patient.

The Report also seeks to rebut FDA’s argument that it is entitled to extensive deference in its interpretation of the definition of “drug.”  It points to the Supreme Court’s decision in FDA v. Brown & Williamson Tobacco Corp., 529 U.S. 120 (2000), in which “the Court pushed back on the FDA when it sought to include cigarettes and tobacco as drugs under the [FDCA]…”  The Report goes on to state that, “…even if it takes great skill to figure out how to regulate drugs, and the government’s broad claims for Chevron deference here should not override the ordinary meaning of ‘drugs’ versus ‘medicine.’”  

Given the arguments laid out in the Report, it will be interesting to see how the case is resolved in the Court of Appeals.     

By Jeffrey K. Shapiro –

As everybody has noticed, FDA finalized its guidance on Mobile Medical Applications earlier this week.  We blogged on the draft version here.

The final guidance is similar to the draft guidance – but with improved clarity.  Hence, it has expanded from 29 to 43 pages.  Most of the additional pages are appendices with examples and other supplementary information.  This guidance is sensible and well written.

FDA’s general approach to mobile medical applications (mobile apps) is to define large swaths of territory that will be either unregulated because they are considered outside of FDA’s jurisdiction or because FDA will simply refrain from regulation on the basis of low patient risk.  When FDA refrains from regulating products within its jurisdiction, it is called an exercise of “enforcement discretion.”

This general approach makes sense, because FDA and industry both have limited resources, so it is realistic to apply the expensive and burdensome FDA regulatory system only to mobile apps that pose a significant risk to patients.  In technical regulatory terms, this approach is known as getting the most bang for the buck.

Because much of the mobile apps industry is not very familiar with FDA regulation, this guidance has an unusually detailed description of the entities, mobile apps, and activities that will not be regulated.  These include:

• Platform products without medical device claims.
• Third party app distributors who do not develop apps.
• Providers of general development tools and hardware/software infrastructure.
• Licensed practitioners who develop their own apps for their own use.
• Mobile apps developed solely for non-clinical research, teaching or analysis and not introduced into commercial distribution.
• Mobile apps that are essential e copies of medical textbooks and reference material.
• Mobile apps used for provider or patient medical training and education.
• Mobile apps used to automate operations in a healthcare setting and not for use in the diagnosis or treatment of disease.
• Mobile apps that are generic aids or general purpose products.

There is also a description of entities and activities for which FDA will exercise enforcement discretion based upon low risk to patients.  Of note, the guidance provides welcome relief for the “health coaching” apps by placing them under enforcement discretion.  There has been a lot of innovation in this area, but also an overhang of regulatory uncertainty.  The enforcement discretion categories are:

• Mobile apps that help patients self-manage their disease or conditions without providing specific treatment suggestions.
• Mobile apps that provide simple tools for patients to organize and track health information.
• Mobile apps that provide easy access to information related to patients’ health conditions or treatments.
• Mobile apps that automate simple tasks for health care providers.
• Mobile apps that enable patients or providers to interact with electronic health records ("EHRs").

A few interesting examples: 

• Mobile apps that help patients diagnosed with psychiatric conditions.  
• Mobile apps that use patient characteristics to provide patient specific screening, counseling and preventive recommendations from well known and established authorities.
• Mobile apps that remind patients about pre determined dosing schedules (medication reminders). 

The last example is especially welcome.  For a number of years, FDA has been actively regulating medical reminders under 21 C.F.R. § 890.5050 (product code NXQ).  The active regulation of these products has created a headache for developers of health and wellness coaching apps, who risked device regulation by including this useful and low risk functionality in their products.  FDA’s decision to exercise enforcement discretion here is wise, and consistent with the overall approach of this guidance. 

The mobile apps that FDA will regulate are called “mobile medical apps.”  What mobile apps fall under this category?  FDA discusses the following broad types:

• Mobile apps that connect to medical devices to control them or to display, store, analyze or transmit patient specific medical device data.
• Mobile apps that transform a mobile platform with device functionality by using attachments, display screens, or sensors.
• Mobile apps that perform patient specific analysis and provide patient specific diagnosis or treatment recommendations.

This last type of mobile medical app looks very much like clinical decision support software (“CDSS”).  However, FDA expressly says that this guidance does not address CDSS.  FDA is expected to issue a draft guidance on that topic in the near future. 

At the same time, it would be odd for FDA to regulate a particular CDSS functionality if provided via mobile app but not if it is on some other platform.  That is especially true because FDA goes out of its way to say in this guidance that its oversight approach to mobile apps is focused on functionality and not platform.

Most likely, the CDSS draft guidance will take a similar approach to the mobile medical apps guidance, subjecting CDSS software with higher risk functionality to regulation while specifying CDSS functionality that is unregulated or under enforcement discretion.  This upcoming guidance will probably apply to CDSS functionality on any platform, mobile or not.

In this guidance, FDA provides only a few examples of mobile apps providing diagnosis or treatment recommendations that will be regulated.  The examples are:  apps that use patient specific parameters to calculate dosage or create dosage plans for radiation therapy; Computer Aided Detection (“CAD”) software; image processing software; radiation therapy treatment planning software. 

These apps are all examples of what FDA describes as “mobile apps that perform sophisticated analysis or interpret data (electronically collected or manually entered) from another medical device” (p. 15).  Unfortunately, FDA does not provide examples of mobile CDSS apps that are not regulated.  We will probably need to wait for the overall CDSS guidance to more fully clarify what mobile CDSS functionality will or will not be regulated.

The awkwardness here is probably due to the fact that FDA geared up development of a guidance for mobile apps before discovering, as the software industry developed, that the focus really needs to be on functionality rather than type of platform.  For anyone who needs to predict the likely regulatory status of stand alone software that is not a mobile app, this guidance should still be a valuable tool.  It is a fair inference that much of the substance here applies when the same type of functionality is placed on a non-mobile platform.

Finally, if a mobile app falls within one of the mobile medical app categories, that is only the beginning of the analysis.  The next step will be to determine its classification (Class I, II or III), because that will drive the determination of what regulatory requirements apply.  This guidance does not directly address the determination of regulatory classification.

By Allyson B. Mullen –

Have you ever heard of an “Immediately in Effect (IIE)” guidance document?  Thanks to a new draft SOP issued by CDRH, you may soon see this new species of guidance on a regular basis.

In section 405 of Food and Drug Administration Modernization Act of 1997 ("FDAMA"), FDA was authorized to issue guidance documents without public comment in certain circumstances.  Specifically, section 701(h)(1)(C) was added to the Food, Drug, and Cosmetic Act (the “Act”) and states that guidance documents “set[ting] forth initial interpretations of a statute or regulation, changes in interpretation or policy that are of more than a minor nature, complex scientific issues, or highly controversial issues” must have prior public participation before implementation “unless the Secretary determines that such prior public participation is not feasible or appropriate.”  (Emphasis added.)

In February 2000, FDA issued proposed implementing regulations.  The preamble to the proposed regulations suggests that FDA deems prior public participation “not feasible or appropriate” if: “(1) there are public health reasons for immediate implementation of the guidance document; (2) there is a statutory requirement, executive order, or court order that requires immediate implementation; or (3) the guidance document presents a less burdensome policy that is consistent with public health.”  65 Fed. Reg. 7321, 7324 (Feb. 14, 2000).  The proposed regulations were finalized in September 2000 and are codified at 21 C.F.R. § 10.115(g)(2). 

Nearly 13 years later, on September 5, 2013, CDRH announced a Draft Standard Operating Procedure ("SOP") “Level 1, Immediately in Effect Guidance Documents on Premarket Data Issues” (the “Draft SOP”).  78 Fed. Reg. 54655 (Sept. 5, 2013).  Some may wonder why FDA would propose an SOP setting forth the process for issuing guidance at this late date.  Could it be because they are intending to make greater use of such a process and implementing more written guidance without prior public participation?

The stated intent of the Draft SOP is to clearly and efficiently communicate changes in CDRH’s expectations and new scientific information that relate to or could impact Investigational Device Exemptions and pre-market submissions (e.g., 510(k)s, PMAs, HDEs).  Draft SOP at 1. The Draft SOP accomplishes this objective by creating a new category of guidance document, called, “Immediately in Effect (IIE) Guidance Documents.”  Id. at 1.  (The Draft SOP replaces CDRH’s earlier attempt in 2011 to establish such a process in its “‘Notice to Industry’ Letters” SOP. 78 Fed. Reg. 54655.)

The Draft SOP proposes a three-pronged assessment to determine if an IIE Guidance Document should be developed: (1) there is new scientific information identified, which raises “new, important safety risk or calls into question the adequacy of currently used test methods or clinical trial design to demonstrate or bear on safety, effectiveness, and/or substantial equivalence of a device type;” (2) as a result of such new information, CDRH needs to change its regulatory expectations  with respect to IDEs and premarket submissions; and (3) “prior public participation is not appropriate or feasible.”  Draft SOP at 2. 

Based on these criteria, it appears as though there could be a high bar for issuance of an IIE Guidance Document.  However, the Draft SOP does not define or put any parameters around what would constitute new scientific information (must it be actual or speculative?) and FDA has previously declined to limit the use of IIE Guidance Documents to “rare and extraordinary circumstances” or “where there is a real demonstrated public health emergency, not just a theoretical emergency.”  65 Fed. Reg. 56468, 56472 (Sept. 19, 2000). 

It seems possible that CDRH could be planning to put this SOP into routine use once finalized since the Draft SOP provides a fairly simple process for issuing IIE Guidance Documents.  The Draft SOP allows for CDRH staff and management to prepare a briefing summary for discussion of proposed IIE Guidance Documents with the Center Science Council ("CSC").  Draft SOP at 3.  The Draft SOP includes a sample (short) format for a briefing summary and states that the briefing summary should include 9 items:

• The new scientific information;
• How the risk/benefit profile of the particular device is changed by the new scientific information;
• The Center’s anticipated changes to regulatory policy in light of the new scientific information;
• Why such changes are necessary;
• The audience who should be made aware of such changes;
• The submission types affected by such changes (future and/or pending submissions) (Yes, you read that correctly – IIE Guidance Documents can impact not only future submissions, but also submissions pending with CDRH at the time the guidance is issued; how will companies keep up?);
• The existing guidance documents impacted by such changes;
• Why an immediate effect guidance document is the “only appropriate method for disseminating this information”; and
• Whether and to whom any further communication regarding the topic at issue is needed.  Id. at 3 & 7.

Based on the discussions facilitated by the briefing summary, the CSC is charged with determining whether the new scientific information warrants a change in the premarket regulatory expectations, whether the change should be communicated through an IIE Guidance Document, and whether additional expertise is needed before making a determination on a particular topic.  Id. at 3-4.

Once the CSC determines that an IIE Guidance Document should be issued, the guidance is drafted and should only be 1 to 2 pages in length, and generally not exceed 3 pages.  Id. at 4.  For information that is critical to industry, such as changing regulatory expectations, it seems that it may be difficult for CDRH to include all of the required elements (e.g., the nonbinding language disclaimer) and still find space in three pages (maximum) to clearly articulate its new expectations.  Once drafted, the IIE Guidance Document must be approved by a number of individuals within CDRH before it is published in the Federal Register.  Id. at 5.  Lastly, the Draft SOP provides for public comment during the 60-day period following issuance of the IIE Guidance Document; and in the 90 days following close of the comment period, CDRH will review the comments and revise the IIE Guidance Document, if necessary.  Id. at 5.
 
Only time will tell how CDRH will utilize this SOP, and whether it will become routine.  However, it appears as though CDRH is establishing a simple process to easily implement guidance without public input and without establishing parameters around critical steps in the process (e.g., what constitutes new scientific information).  Since when does a bureaucracy invest significant effort in developing a regulatory tool and then choose not to use it?  The odds are that you will soon become very familiar with IIE Guidance Documents.