By Kurt R. Karst –

Further cementing FDA’s position that a generic applicant can forfeit 180-day exclusivity after patent information is "withdrawn" by the NDA holder, FDA ruled earlier today that Hi Tech Pharmacal Co., Inc. (“Hi Tech”) forfeited 180-day exclusivity after the information on  two exclusivity-qualifying Orange Book-listed patents covering the ophthalmic drug product COSOPT (dorzolamide hydrochloride; timolol maleate) had been withdrawn by the NDA holder, Merck & Co., Inc. (“Merck”).  FDA’s ruling was issued in the U.S. District Court for the District of Columbia around 10:00AM this morning, after the Court decided earlier this month not to grant Hi-Tech’s preliminary injunction motion seeking to prevent FDA from granting final ANDA approval to any subsequent ANDA applicant during Hi-Tech’s period of 180-day exclusivity.  Hyman, Phelps & McNamara, P.C. has represented Hi-Tech in its efforts – thereby explaining our decision not to address, until now, this case on the FDA Law Blog.  Apotex, Inc., a subsequent ANDA applicant, is an Intervenor-Defendant in the case, and Teva Pharmaceuticals USA, Inc., also subsequent ANDA applicant, filed an amicus brief in the case supporting Hi-Tech’s position.

We will spare you all of the details of the case.  Instead, we will focus on FDA’s Letter Decision.  But first, some quick facts . . . .  

Hi-Tech submitted the first ANDA to FDA containing a Paragraph IV certification to three patents listed in the Orange Book covering COSOPT.  This qualified Hi-Tech as a “first applicant” eligible for 180-day exclusivity.  Merck challenged Hi-Tech on one of those patents – U.S. Patent No. 4,797,413 (“the ‘413 patent”) – and Hi-Tech lost.  The ‘413 patent expired on April 28, 2008, but was subject to a period of pediatric exclusivity that expired on October 28, 2008.  Merck did not challenge Hi-Tech on the remaining two patents – U.S. Patent Nos. 6,248,735 (“the ‘735 patent”) and 6,316,443 (“the ‘443 patent”).  Instead, on April 26, 2006, Merck sent a letter to FDA requesting that information on the ‘735 and ‘443 patents be delisted from the Orange Book.  The patents have continued to be listed in the Orange Book, even today. 

Then along comes FDA’s May 2008 Letter Decision concerning 180-day exclusivity for generic PRECOSE (acarbose) Tablets.  In that case, FDA ruled that a request to withdraw patent information from the Orange Book is a forfeiture event under the “failure to market” provisions at FDC Act § 505(j)(5)(D)(i)(I), which were added to the law in December 2003 by the Medicare Modernization Act (“MMA”).  (See our May 11, 2008 post for a discussion of FDA’s acarbose decision.)  Hi-Tech then sent a letter to FDA arguing that the company could not forfeit 180-day exclusivity, and requesting that FDA make a prompt exclusivity decision to allow Hi-Tech to seek judicial relief in case of an adverse FDA decision.  FDA refused to make a decision before October 28, 2008, when the period of pediatric exclusivity on the ‘413 patent expired, and Hi-Tech sued FDA to get an exclusivity decision.  FDA subsequently opened a public docket, and, as mentioned above, the District Court, denied Hi-Tech’s motion for preliminary injunction, but instructed the parties to meet in court at 10:00AM on October 28, 2008 when FDA would issue its Letter Decision. 

FDA’s 16-page COSOPT Decision Letter concludes that Hi-Tech forfeited 180-day exclusivity on April 11, 2008, which is 30 months after Hi-Tech submitted its ANDA, and is also the “later of” date under the FDC Act § 505(j)(5)(D)(i)(I) “failure to market” forfeiture analysis.  In FDA’s January 2008 Letter Decision concerning 180-day exclusivity for generic KYTRIL (granisetron), the Agency determined that there must be both an item (aa) and an item (bb) forfeiture event under FDC Act § 505(j)(5)(D)(i)(I) for the Agency to determine a “later of” forfeiture date.  With respect to generic COSOPT, the item (aa) date was April 11, 2008, and the item (bb) event was, according to FDA, July 10, 2006 – 75 days after Merck withdrew information on the ‘735 and ‘443 patents (FDC Act § 505(j)(5)(D)(i)(I)(bb)(CC)).  With respect to Hi-Tech’s argument that FDC Act § 505(j)(5)(D)(i)(I) requires a failure on Hi-Tech’s part (and that Hi-Tech did not “fail” to do anything it was required to do), FDA ruled that the “failure to market” forfeiture provisions “must be read as establishing a ‘no-fault’ forfeiture when an applicant fails to market by one of the identified dates.”  Hi-Tech also argued that the 180-day exclusivity tolling provisions under the Best Pharmaceuticals for Children Act (FDC Act § 505A(m)) should prevent a forfeiture.  FDA, however, ruled that FDC Act § 505A(m) applies only in the pre-MMA context, where 180-day exclusivity could be triggered by a court decision of patent invalidity, non-infringement, or unenforceability. 

FDA’s position for not providing an early exclusivity decision with respect to generic COSOPT – and in other cases as well – is that “[m]aking and advance decision on generic exclusivity . . . would result in FDA making decisions in piecemeal fashion, and FDA could be inundated with such requests from ANDA sponsors.  In addition, FDA would be unable to fully explain the basis for an advance exclusivity decision since many details of ANDAs are non-public until approval, and judicial review would thus be similarly circumscribed.”  FDA also notes that a policy of not making advance decisions “is also consistent with Congress’s choice to vest FDA with the authority to take and give effect to its actions, such as approving drugs, subject to subsequent challenge under the Administrative Procedure Act.”  Notwithstanding these concerns and points, and as we stated in court today, and the judge has articulated on several occasions, such a system leads to unnecessary court fire drills, and, more importantly, can preclude meaningful judicial review of FDA decisions.  FDA would do well to rethink its exclusivity decision-making process.  A status conference on the case has been scheduled for November 7, 2008.

By Anne Marie Murphy —
 
We recently posted on the Consumer Product Safety Improvement Act of 2008 (“CPSIA”), which makes a number of changes to the laws enforced by the Consumer Product Safety Commission (“CPSC”). 
 
Section 102(a)(1) of CPSIA amends the Consumer Product Safety Act (“CPSA”) to require each manufacturer (including an importer or private labeler) of any product that is subject to any CPSC rule, ban, standard, or regulation to issue a certificate that the product complies with such CPSC requirements.  This certification requirement applies to products manufactured after the effective date, which is November 12, 2008.  The certificate must “accompany” each product or shipment of products covered by the certificate.  A copy of the certificate must also be “furnished to each distributor or retailer of the product.”  The CPSA states that a product offered for importation “shall be refused admission” if it is not accompanied by a certificate.
 
On Friday, October 24, 2008, the CPSC posted on its website a “Sample General Certification of Conformity.”  The sample form includes the same information that was presented at a CPSC public meeting on October 2, 2008.  Instructions for completing the certification and a brief list of “frequently asked questions” are also posted.  The CPSC information is available here.

Hyman, Phelps & McNamara, P.C.’s John R. Fleder has now appeared in a Washington Legal Foundation “Legally Brief” YouTube video.  In the 6-minute video Mr. Fleder notes the recent increase in federal False Claims Act cases initiated by private whistleblowers based on alleged “off-label” use promotional activities involving pharmaceutical companies, and explains why recent court rulings have dismissed such cases, and cast doubt on the viability of any off-label use “qui tam” action.

Earlier this month, European drug makers called on the European Union (“EU”) to act on the issue of parallel trading of pharmaceuticals by confining prices for drugs to the specific EU member country they are initially sold.  Drug makers argue that some form of price control is necessary to prevent such a practice, yet was missing from recently endorsed recommendations by the EU.  This issue is not unique to Europe.  In the United States, the debate continues as to whether Americans should be allowed to re-import prescription drugs from Canada or Europe at lower prices than they may be purchased domestically.   

As European law currently stands, suppliers in a lower priced country may purchase excess of a drug product from the drug maker and then re-sell that excess for a higher price in another country without the authorization of the drug company, which results in depriving the original manufacturer of a substantial amount of potential profit.  European drug makers argue that they recognize the problems associated with the rising cost of pharmaceuticals and would like to voluntarily offer different price points to different countries based on their financial capacity.  However, without legal protection from parallel trading, they are reluctant to do so. 

European drug makers’ renewed calls for the EU to step in and reduce or eliminate parallel trading came after a recent ruling by the European Court of Justice which permits drug companies to reduce trading in their own products only if they receive orders for larger than ordinary requirements.  This result has left drug makers seeking greater rights against parallel traders. 

By Bill T. Koustas

Last week, I presented at the Center for Business Intelligence’s Pharmaceutical Congress on Paragraph IV Disputes with Geoff Levitt of Wyeth on citizen petitions.  The focus of my talk was on new FDC Act § 505(q) – “Petitions and Civil Actions Regarding Approval of Certain Applications” –  which was added to the FDC Act by § 914 of the FDA Amendments Act (“FDAAA”).  A copy of my presentation is available here.

Briefly, FDC Act § 505(q) provides that FDA shall not delay approval of a pending ANDA or 505(b)(2) application as a result of a citizen petition submitted to the Agency pursuant to 21 C.F.R. § 10.30 or § 10.35, unless FDA “determines, upon reviewing the petition, that a delay is necessary to protect the public health.”  Under the new law “[FDA] shall take final agency action on a petition not later than 180 days after the date on which the petition is submitted.”  FDA may not extend the 180-day period “for any reason,” including consent of the petitioner.  FDC Act § 505(q) does not apply to all citizen petitions.  Excluded from the new law are petitions that relate “solely to the timing of the approval of an application pursuant to subsection (j)(5)(B)(iv)” (i.e., 180-day exclusivity), and petitions that are made by an ANDA or 505(b)(2) sponsor “that seeks only to have [FDA] take or refrain from taking any form of action with respect to that application.”  Petitions subject to FDC Act § 505(q) must include a specific certification identified in the new law, and petition supplements and comments must include a specific verification statement. 

As I noted during my presentation, there are several unresolved issues with the new law.  For example, how is “intent to delay” determined by FDA?  FDA’s failure to respond to a citizen petition within 180-days is not a petition denial, but rather “final agency action.”  What does this mean for challenging such “final agency action,” particularly if there is little to nothing in the administrative record from FDA? 

Notwithstanding a growing list of questions about the new law, FDA has begun to provide some guidance.  For example, FDA is reportedly interpreting FDC Act § 505(q) to apply to petitions that are submitted after an ANDA or a 505(b)(2) application is submitted to the Agency.  Why?  FDC Act § 505(q)(1)(A) refers to a “pending application.”  Because FDA will not reveal to a petitioner whether an application is pending, however, a petitioner will not know if the 180-day deadline applies – unless, of course, a generic applicant publicly states it has submitted an ANDA or a 505(b)(2) application or FDA’s ANDA Paragraph IV Certification List provides that notice.  Therefore, if a petition is submitted too soon, the 180-day FDA response deadline would not apply. 

Also, in a recent petition response concerning the approvability of a pending 505(b)(2) application, FDA notes that while FDC Act § 505(q) requires the Agency to take action on a petition within 180 days, the Agency cannot make any final decisions concerning the approvability of NDAs.  Specifically, FDA states in an October 10, 2008 petition response that:

There is no evidence that in enacting section 505(q) of the Act, Congress intended to vitiate an NDA applicant’s procedural rights by requiring that the Agency make decisions that constitute final Agency action regarding the approvability of aspects that are specific to a pending application (e.g., specific claims proposed in a drug product’s labeling) on a piecemeal basis outside of the process established under the Act and regulations.

As the number of citizen petitions subject to FDC Act § 505(q) mounts, we thought it would be useful to provide a mechanism by which to track them.  Hence, the creation of the “FDC Act § 505(q) Citizen Petition Tracker.” The Tracker is an Excel spreadsheet with links to petitions and petition decisions that will appear on the right-hand side of FDA Law Blog.  We will update it as new petitions are submitted and petition decisions are made.  According to information we were able to cull from Regulations.gov, 28 petitions with the FDC Act § 505(q) certification have been submitted to FDA since FDAAA’s enactment.  FDA has thus far denied 11 petitions and granted/denied in part 2 petitions.  Fourteen petitions are pending and one has been withdrawn; however, one of the pending petitions concerns 180-day exclusivity (i.e., FDA-2008-P-0117; Clopidogrel Bisulfate), and FDA presumably does not consider it subject to FDC Act § 505(q).  Another petition – a petition for reconsideration submitted under 21 C.F.R. § 10.33 – was submitted after FDA denied the original petition submitted pursuant to 21 C.F.R. § 10.35, and is presumably not subject to FDC Act § 505(q).  (FDC Act § 505(q) defines a “petition” to mean a written request submitted pursuant to 21 C.F.R. § 10.30 or § 10.35.)

As of today, FDA’s track record in meeting the 180-day response deadline is encouraging.  According to available information, only one pending petition is outside the deadline – FDA-2008-P-0185 concerning Minocycline HCl (SOLODYN). We are not aware of any action yet to litigate FDA’s failure to timely respond to that petition.

By Kurt R. Karst    

On October 20, 2008, FDA announced the availability of a highly anticipated draft guidance document, titled “Tropical Disease Priority Review Vouchers.”  The draft guidance discusses FDA’s implementation of FDC Act § 524 – “Priority Review to Encourage Treatments for Tropical Diseases” – which was added to the law by § 1102 of the FDA Amendments Act (“FDAAA”) to encourage the development of new drug and biological products to treat certain tropical diseases for which there are no or few available treatments by offering a new transferable voucher incentive for obtaining FDA approval for products for such diseases.  FDA is also reportedly planning to hold a public meeting to discuss the new voucher program. 

We first posted on the so-called “treat and trade” program in May 2007 when FDAAA was still being debated.  Briefly, FDAAA amended the FDC Act to create a new transferable priority review program in which applicants for new chemical entities for “tropical diseases” that have received priority review receive a “priority review voucher” entitling the holder to a 6-month FDA review of another application that would otherwise be reviewed under FDA’s standard 10-month review clock. The priority review voucher may be used or sold by the company granted the voucher for an application “submitted after the date of the approval of the tropical disease product application.” The tropical diseases that can qualify an applicant are enumerated in new FDC Act § 524(a)(3), and include “infectious disease[s] for which there is no significant market in developed nations and that disproportionately [affect] poor and marginalized populations, designated by regulation by [FDA].” Applicants that use a priority review voucher are required to pay FDA a priority review user fee in addition to other required user fees, and no such fee may be waived, reduced, or refunded. FDA will establish the amount of the priority review user fee before the beginning of each fiscal year, but has not yet done so for Fiscal Year 2009. 

The idea to stimulate tropical disease drug development by offering a voucher system was first proposed in a 2006 Health Affairs article authored by Duke University professors David Ridley, Henry Grabowski and Jeffrey Moe.  (See additional background information here.)  Since then, there has been significant speculation as to the price such a voucher would fetch on the market.  Some have speculated that a voucher could bring $300 million or more; however, given FDA’s recent willingness to let PDUFA goal dates slip, it is unclear how much money a company might be willing to invest in such a voucher that might not carry with it the initially intended benefits.  But we might find out soon.  Novartis’ orphan drug-designated malaria treatment COARTEM (artemether; lumefantrine) (currently under FDA review with a December 2008 action date) and Vioquest Pharma’s orphan drug-designated LENOCTA (sodium stibogluconate) for the treatment of cutaneous leishmaniasis are two drugs that might qualify for a voucher.  The success of the tropical disease voucher program could also determine whether interested parties might pursue expanding the law to apply to other types of products, including counterterrorism products.

FDA’s draft voucher guidance is largely styled as a question-and-answer document, and is presumably based on inquiries FDA received on § 524 and related discussions with sponsors.  FDA anticipates that the Agency will receive approximately 5 voucher requests annually from 5 sponsors and 5 notifications of intent to use a voucher from 5 sponsors annually. FDA notes in the draft guidance that sponsors should notify the Agency of their intent to use a priority review voucher (including the date on which the sponsor intends to submit the application) at least 1 year before use.  Each transfer should be documented with a letter of transfer.  Although FDC Act § 524 allows for only a single actual transfer of the voucher from the original recipient to another sponsor, FDA notes in the draft guidance that “contractual arrangements such as the use of an option or transfer of the right to designate the voucher’s recipient could comply with the terms of the statute.”   

By Kurt R. Karst

Hyman, Phelps & McNamara, P.C. is very pleased to announce that Anne Marie Murphy and Michelle L. Butler have been named Directors of the firm, and that Larry K. Houck has been named Of Counsel.  Ms. Murphy’s practice focuses on drug development issues. She serves on the Human Subjects Research Board for George Mason University.  Ms. Butler’s practice focuses on pharmaceutical, medical device, and healthcare law, including civil litigation, and related matters involving the Federal Trade Commission and the Consumer Product Safety Commission.  Mr. Houck’s practice area encompasses controlled substances and regulated chemicals as well as state licensing/registration compliance issues.

FDA’s Office of Combination Products (“OCP”) recently released a draft guidance entitled “New Contrast Imaging Indication Considerations for Devices and Approved Drug and Biological Products.”  The draft guidance permits diagnostic imaging device makers to expand labeling for use with a contrast agent or radiopharmaceutical even if there is no change in the labeling for the imaging drug.  This document was released as part of an effort to “ensure timely and effective review” of imaging devices used with contrast agents or radiopharmaceuticals, as mandated in the 2007 Medical Device User Fee Amendments commitment letter.

OCP’s draft guidance is addressed to the problem of how to bring to market an imaging device intended to take advantage of a new indication for a previously approved imaging drug, when the drug manufacturer is not inclined to seek a change in its own labeling or otherwise cooperate in the clearance or approval process for the device.

The draft guidance is the first ever to implement a so-called “umbrella” approach to the imaging device labeling as a potential resolution of the problem. It permits the new indication for the imaging drug to be added to the imaging device labeling even if the indication is not added to the drug labeling.

OCP has, however, included significant restrictions. First, the umbrella device labeling would likely be developed through the more burdensome PMA process rather than the 510(k) process.  Second, the sponsor would likely be required to conduct a clinical trial employing both the drug and device to support the new indication.  Finally, the new indication would have to be consistent with the drug labeling and could not require any change in the formulation, dose, rate and route of administration of the drug. If the latter type of changes were required, then the umbrella device labeling approach would not be permitted under this guidance.

Despite these restrictions, OCP’s draft guidance represents a promising step forward toward resolution of the vexing issues created by innovation in devices that have an impact on the use of previously approved drugs.  This draft guidance, in the circumstances when it applies, should enable the imaging device manufacturer to promote a new indication for an imaging drug in conjunction with its device, even if the drug manufacturer does not seek a change in the drug labeling.

By Jeffrey K. Shapiro

FDA recently published a new draft guidance document on potency tests for cellular and gene therapy (“CGT”) products.  The FDC Act requires that all biological products meet agency requirements for safety, purity, and potency before such products will be approved, but historically the agency and IND sponsors have faced challenges in establishing appropriate standards for potency testing for these complex types of products.  In the early years of CGT development, some pivotal clinical studies for CGT products were placed on clinical hold for lack of appropriate potency tests.  In the ensuing years, FDA and industry have learned a great deal about developing such tests for these products.  The draft guidance seeks to provide sponsors with the benefit of this learning.

The draft guidance makes clear that FDA recognizes that measuring potency of CGT products is a complex and evolving process.  Thus, the draft guidance recommends “an incremental approach to product characterization testing, including the development of potency assays,” and explains that the potency measurement “may change significantly” as the product is developed.  Although clinical study data “is not a practicable quantitative measure of potency,” FDA states that a manufacturer may use clinical study results “to establish a correlation between the product’s clinical efficacy and a potency measurement.”  FDA further recommends that manufacturers begin considering potency early and gather and evaluate data throughout the preclinical and clinical development of the product in order to determine the best method for measuring potency. 

The guidance also provides recommendations for determining what criteria to use to measure potency and the types of methods that may be able to make these measurements.  First, FDA states that manufacturers should develop potency measurements that “reflect the relevant biological attributes” of the product.  FDA uses a gene therapy vector to illustrate this recommendation, explaining that potency tests for a gene therapy vector should incorporate both the measure of “the ability to transfer a genetic sequence to a cell and the biological effect of the expressed genetic sequence.”  Second, FDA outlines three possible assays for measuring potency, including biological assays, non-biological analytical assays, and an assay matrix, and provides details on the types of data that should be gathered for those assays.   

Adequate potency testing becomes a critical issue for manufacturers in Phase 3 of CGT product development.  The draft guidance states that a manufacturer’s “potency assay design and acceptance criteria should be sufficient to assure that a well-characterized, consistently manufactured product was administered during your pivotal study(ies).”  Therefore, it is important that manufacturers develop appropriate potency testing.      

Although the draft guidance does not create any new regulations and “does not operate to bind FDA or the public,” it is evidence of FDA’s current thinking on CGT product approval.  The draft guidance applies only to CGT products that are reviewed by FDA’s Office of Cellular, Tissue, and Gene Therapies, but it signals FDA’s increasing comfort with for these products.  With luck, this draft guidance will help more manufactures bring these important products to market.

By Susan J. Matthees

In an effort to eliminate rogue pharmacies from dispensing controlled substances over the Internet, Congress passed legislation amending the Controlled Substances Act (“CSA”).  The Ryan Haight Act (H.R. 6353), which honors a teenager who died of an overdose of controlled drugs obtained over the Internet, awaits President Bush’s signature.  The legislation follows the recent Drug Enforcement Administration (“DEA”) crackdown on Internet pharmacies and distribution of controlled substances to those pharmacies.   

The Act would permit DEA to register only certain pharmacies meeting specific criteria to dispense controlled substances over the Internet.  In summary, the Act would prohibit dispensing controlled substances by means of the Internet unless:

1.  The patient has a “valid prescription;”

2.  DEA has modified the pharmacy’s current DEA registration to dispense via the Internet. (It is unclear whether the Act would require Internet pharmacies to first register and then obtain a modification to their registration or if “online pharmacy” will be a separate category of registrant on the registration application.);

3.  The pharmacy reports to DEA the quantity dispensed over the Internet if it dispenses 100 prescriptions or 500 or more dosage units in a month;

4.  The pharmacy notifies DEA 30 days prior to offering to sell, deliver, distribute or dispense controlled substances over the Internet; and

5.  The pharmacy certifies that it complies with the Act and posts its name, address, telephone number and pharmacist in charge on its homepage.

The Act would also enhance penalties for the illegal distribution of schedule III-V controlled substances and provide state Attorneys General with the ability to bring civil action in federal district court to enjoin Internet pharmacies.

The Act prohibits controlled substances from being “delivered, distributed or dispensed by means of the Internet without a valid prescription.”  The Act defines “valid prescription” as “a prescription that is issued for a legitimate medical purpose in the usual course of professional practice by . . . a practitioner who has conducted at least 1 in-person medical evaluation of the patient . . . or a covering practitioner.”  An “in-person medical evaluation” is a “medical evaluation that is conducted with the patient in the physical presence of the practitioner, without regard to whether portions of the evaluation are conducted by other health professionals.”  A “covering practitioner” is “a practitioner who conducts a medical evaluation (other than an in-person medical evaluation) at the request of a practitioner who . . . has conducted at least 1 in-person medical evaluation of the patient or an evaluation through the practice of telemedicine, within the previous 24 months . . . and is temporarily unavailable to conduct the evaluation of the patient.”

To “deliver, distribute, or dispense by means of the Internet refers, respectively, to any delivery, distribution, or dispensing of a controlled substance that is caused or facilitated by means of the Internet.”

An “on-line” pharmacy is an entity or Internet site that “knowingly or intentionally delivers, distributes, or dispenses, or offers or attempts to deliver, distribute, or dispense, a controlled substance by means of the Internet” but does not include registered manufacturers or distributors who do not dispense to unregistered individuals or entities; registered nonpharmacy practitioners; hospitals or medical facilities operated by U.S. agencies; “mere advertisements that do not attempt to facilitate an actual transaction involving a controlled substance;” or a registered pharmacy “whose dispensing controlled substances via the Internet consists solely of” filling or refilling schedule III-V prescriptions.

The Act contains a lengthy section discussing the new requirements for telemedicine and provides the U.S. Attorney General with the authority to issue registrations to practitioners who practice telemedicine.       

There are several aspects of the Act that will need to be clarified.  For example, pharmacies do not “distribute” controlled substances pursuant to a prescription so it is unclear why the Act prohibits distributing, along with delivery and dispensing, without a valid prescription.  “Distribute” means “to deliver (other than by administering or dispensing) a controlled substance or listed chemical.”  21 U.S.C. § 802(11).  Controlled substances are “dispensed,” not “distributed,” pursuant to a prescription.  “Dispensing” is the delivery of “a controlled substance to an ultimate user or research subject by, or pursuant to the lawful order of, a practitioner.”  21 U.S.C. § 802(10).  By prohibiting distribution without a valid prescription the Act prohibits something that should not occur.

Also, the Act would define a “valid prescription,” although historically DEA has deferred to local medical standards on these issues.  Including this definition raises a number of issues.  A “valid prescription” is defined as one “issued for a legitimate medical purpose in the usual course of professional practice by . . .a practitioner who has conducted at least 1 in-person medical evaluation of the patient . . . or a covering practitioner.”  The regulations have long required that for controlled substance prescriptions “to be effective,” they must be issued for a legitimate medical purpose by an individual practitioner acting in the usual course of professional practice.  21 C.F.R. § 1306.04(a).  DEA has addressed the issue of Internet pharmacies and opined that a bona fide physician/patient relationship must exist for a doctor to issue a prescriptions in the usual course of professional practice and that the doctor must have conducted a physical examination to establish such a relationship.  The Act requires an “in-person  medical evaluation.”  Is “an in-person medical evaluation” the same as a “physical examination?”  We surmise that an “in-person medical evaluation” appears close to a “physical examination.”  But conducting an “in-person medical evaluation” may involve diagnosing a patient without physically examining them, while a physical examination seems to include, at the very least, looking at the patient, listening to their heartbeat and taking their blood pressure.  DEA needs to further clarify what qualifies as “in-person medical evaluation.” Secondly, the definition of  “covering practitioner” appears to indicate that “an evaluation of the patient through the practice of  telemedicine” is an adequate substitute for an “in person medical evaluation.”   

Interestingly, a valid prescription has no time constraints during which a prescribing practitioner had to have conducted at least one in-person medical evaluation, but requires a practitioner for whom a prescriber is covering, to have conducted an evaluation within the past 24 months. 

There is also no information on the type of endorsement or registration DEA will provide to pharmacies so they can dispense via the Internet.  And while endorsement requests will assist DEA in determining the legitimate pharmacies, how will DEA keep those lacking endorsements from dispensing over the Internet, especially if they lack a permanent physical address?  The endorsement and notification requirements will help ensure a pharmacy’s legitimacy by providing DEA with a physical address, but in order for the Act to be effective, DEA must prevent patients from ordering from pharmacies that have not met the Act’s requirements.

By John A. Gilbert and Larry K. Houck

A citizen petition has been submitted to FDA asking the agency to take regulatory action under § 301(ll) against any foods to which sweetening compounds present in the botanical Stevia rebaudiana have been added, on the ground that those compounds (known as steviol glycosides) are drugs.  The petition asks FDA to seize foods to which steviol glycosides have been added, enjoin the distribution of such foods, and refuse importation of such foods.  The petition further asks FDA to “abstain from issuing a letter of no objection to any pending GRAS notification that addresses any use of a steviol glycoside in food.”  A GRAS notification is a voluntary submission that informs FDA of the notifier’s conclusion that the proposed use of a substance in food is generally recognized as safe (GRAS).  If the use of a substance is GRAS, then it is not subject to premarket approval as a food additive.

Two GRAS notifications for steviol glycosides currently are pending at FDA, and there was some expectation within the food industry that the agency might respond to those notifications as early as November.  Issuance of a letter of no objection by FDA is not required prior to marketing a substance for a GRAS use, but FDA had previously raised a number of questions about the safety of the use of steviol glycosides as sweeteners.  In light of those safety concerns, major food companies have deferred market entry until such time as FDA issues letters of no objection to the pending GRAS notifications.  The petition asserts that issuance of those letters “would effectively sanction a violation of law.”

As we have discussed in a number of previous blog posts, § 301(ll) prohibits the marketing of any food to which has been added an approved drug, a licensed biologic, or a drug or biologic for which substantial clinical investigations have been instituted and their existence made public.  The petition contends that the § 301(ll) prohibition applies to steviol glycosides because they are drugs for which substantial clinical investigations have been instituted and made public: clinical investigations focusing on the effect of steviol glycosides on hypertension have been published in peer-reviewed journals.  Although § 301(ll) provides a number of exceptions, most notably a first-to-market exception for drugs that are first marketed in food, the petition argues that none of those exceptions apply to steviol glycosides.

By Diane B. McColl & Ricardo Carvajal

FDA recently published a final rule to expand and streamline authorized health claims related to osteoporosis risk reduction. Effective January 1, 2010, companies may use the newly simplified health claims for calcium and vitamin D products, and calcium products in relation to osteoporosis risk reduction. In addition to adding a “calcium and vitamin D” health claim to FDA’s regulations, the Agency shortened and simplified the language of approved claims in an effort to promote wider use of the claims on product labeling.

The final rule:

• Adds a claim for calcium and vitamin D combination products to reduce osteoporosis risk;
• Eliminates current mandated references to age, sex and race as specific risk factors  and makes optional mention of the prevalence of osteoporosis in U.S. population (and/or subpopulations);
• Eliminates the requirement that the claim include a statement that total dietary intake greater than 200 percent of the recommended daily intake has no further benefit to bone health;
• Makes optional the currently required explanation of the mechanism through which calcium (and calcium and vitamin D) reduces osteoporosis risk; and
• Makes optional a reference to the need for physical activity in reducing risk.

FDA's examination of calcium and vitamin D health claims for osteoporosis originated in response to a 2004 citizen petition submitted by the Beverage Institute for Health and Wellness, a Coca Cola research company. Relying heavily on the 2000 National Institutes of Health “Consensus Statement on Osteoporosis, Prevention and Therapy” and the 2004 Surgeon General’s report, “Bone Health and Osteoporosis,” FDA proposed these changes to the previously allowable health claims to increase the use of osteoporosis risk health claims for calcium and vitamin D in an effort to “improve the U.S. population’s consumption of these nutrients.”

In its final rule, FDA acknowledges that the cumbersome nature of the old format for these claims and their limited scope is the likely reason that so few eligible products use the claim on their labels. These claims were long and difficult to include on labels where space already is precious. A 2001 Food Label and Package Survey report showed the health claims being used in only one of 87 shelf-stable juices and none of the ten milk products in the survey.

The current revisions make the osteoporosis health claim language shorter and more flexible and thus more appealing to put on labels. FDA hopes the simplification of calcium claims and the addition of vitamin D claims will increase their use.

Some model claims under the new regulations include:

• Adequate calcium throughout life, as part of a well-balanced diet, may reduce the risk of osteoporosis.
• Adequate calcium and vitamin D throughout life, as part of a well-balanced diet, may reduce the risk of osteoporosis.
• Adequate calcium as part of a healthful diet, along with physical activity, may reduce the risk of osteoporosis later in life.
• Adequate calcium and vitamin D as part of a healthful diet, along with physical activity, may reduce the risk of osteoporosis later in life.

FDA presents some sobering numbers in support of its effort. According to the final rule osteoporosis “affects more than 10 million individuals and causes approximately 1.5 million fractures annually. Every year, these lead to more than 2.6 million physician office visits, over 800,000 emergency room visits, and more than 500,000 hospitalizations. . . .  The direct care expenditures for osteoporotic fractures along range from 12 to 18 billion dollars each year (measured in 2002 dollars).”

By Ricardo Carvajal & Colleen M. Brown

UPDATE:

• On October 13, 2008, the American Academy of Pediatrics issued a report recommending a doubling of vitamin D for children.

Inside Health Policy recently reported on the writings of several professors who opined on courts’ deference to the FDA.  The writings discussed in the Inside Health Policy piece were from the July 2008 Cornell Law Review, which devoted an entire issue to “Symposium: U.S. Food and Drug Regulation in its First Century and Beyond.” 

Regardless of whether you agree with the arguments the authors make, this isn’t a bad resource.  Need a good quote for a brief challenging FDA’s decision-making?  Try n. 29 to Lars Noah’s The Little Agency that Could (Act with Indifference to Constitutional and Statutory Strictures).  Want to argue in favor of deference to FDA?  Pages 943-952 of James T. O’Reilly’s Losing Deference in the FDA's Second Century: Judicial Review, Politics, and a Diminished Legacy of Expertise discusses six important Supreme Court cases involving deference to FDA. 

If you have a products liability case, several articles are worth a skim, including David C. Vladeck’s The FDA and Deference Lost: A Self-Inflicted Wound or the Product of a Wounded Agency? and Carl Tobias’ FDA Regulatory Compliance Reconsidered.

With all due respect to the learned authors, there isn’t an overwhelming amount of useful information for the FDA practitioner.  There are two exceptions, however.  Catherine Struve’s article Greater and Lesser Powers of Tort Reform: The Primary Jurisdiction Doctrine and State-Law Claims Concerning FDA-Approved Products, makes a clever – if untested – argument that the Seventh Amendment right to jury trial limits the effect of the primary jurisdiction doctrine in cases where there is such a right to trial by jury.  In addition, Gary Lawson’s Dirty Dancing – The FDA Stumbles with the Chevron Two-Step, makes the argument that FDA has incorrectly internalized the second step of a court’s analysis under Chevron U.S.A., Inc. v. NRDC, and has given itself license to make a permissible interpretation rather than the “best interpretation possible.” 

In sum, this issue of the Cornell Law Review may be worth skimming the next time you find yourself litigating with FDA or even just a litigating case involving the FDC Act.

By James P. Ellison 

On October 2, 2008, the Consumer Product Safety Commission (“CPSC”) held a public meeting on the testing and certification requirements imposed by the recently enacted Consumer Product Safety Improvement Act (“CPSIA”).  A similar meeting was held on September 4, 2008 and several others are planned for the near future.  The meeting included sessions on general conformity certification, laboratory accreditation, and mandatory third-party testing for children’s products, followed by a question and answer period.  Of particular interest was the statement by Gib Mullan, the CPSC Director of Compliance and Field Operations, that the CPSIA’s general conformity certification under section 102 applies to any drug product that is also regulated by the Commission through other laws, such as through the Poison Prevention Packaging Act.  This is true, according to Mr. Mullan, even if the drug is not indicated for use in a pediatric population.  In fact, if the drug is indicated for pediatric use, there may be additional requirements imposed by the CPSIA, such as mandatory third-party testing.  A video of the meeting is available on CPSC’s website. 

Section 102(a)(1) of CPSIA amends section 14(a)(1) of the Consumer Product Safety Act (“CPSA”) to require each manufacturer (including an importer) of any consumer product to issue a certificate that the product complies with CPSC rules under the CPSIA or similar requirements under any of the other Acts administered by the CPSC.  According to the Commission, “the certificate must be based on a test of each product or on a reasonable testing program.  This requirement is effective beginning on November 12, 2008.  There are additional third party testing requirements for children’s products.”

Preceding the October 2 sessions was a welcome by Nancy Nord, Acting Chairman of the CPSC, who emphasized that the CPSIA has ambitious time deadlines and that in an effort to meet these deadlines the CPSC will be publishing regulations via a new process not normally used by CPSC.  Ms. Nord stated that interested parties should pay attention to the Federal Register and the CPSC Website and provide comments quickly so that they receive full consideration by the Commission.  The CPSC recently posted a Request for Comment and Information regarding CPSIA’s Section 102 requirements for certificates for conformity testing and third-party testing.  The post indicates that the CPSC is particularly interested in comments on the use of electronic certificates as well as the issue of multiple certifications for the same product.  The CPSC is accepting comments regarding certification for conformity testing and third-party testing through October 29, 2008.

By John R. Fleder and Serafina E. Lobsenz

BNA, a leading provider of expert information and analysis, is holding a one-day, information-packed conference, titled “Pharmaceutical Patent Laws: A prescription for Success in Challenging Times.” Hyman, Phelps & McNamara, P.C.’s Kurt R. Karst will be on a panel discussion of Non-Patent Marketing Exclusivity with Brian McCormick (Hogan & Hartson), Stephen Albainy-Jenei (Frost Brown Todd LLC; Patent Baristas Blog), and Shashank Upadhye (Apotex).

Billed as a conference to “get a prescription for success as legislative, judicial, administrative, and ‘marketplace’ developments continue to advance at breakneck speed,” the conference is intended to help participants:

• Get maximum value from your patents;
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• Avoid antitrust consequences when settling cases; and
• Look for trends – where does case law go from here?

The conference will be held at the Ritz-Carlton, Pentagon City, 1250 South Hayes Street, Arlington, VA, on November 12, 2008. A copy of the conference brochure is available here. Additional conference information is available here.

Special FDA Law Blog Discount – BNA is offering FDA Law Blog readers a 40% discount off of the registration fee. Further, if you sign up two people at the discounted rate, the third person is free. To register for the conference, go to the BNA website and enter the following code – [CONF40NE]. FDA Law Blog is a conference media sponsor.