By Kurt R. Karst –      

Last Friday, 32 State Attorneys General filed an amicus brief with the U.S. Supreme Court asking the Court to grant the Petition for Writ of Certiorari filed last month by a group of drug purchasers in Louisiana Wholesale Drug Co., Inc., et al., v. Bayer AG, et al. (Case No. 10-762).  As we previously reported, the case centers around whether a patent settlement agreement (what opponents call “pay-for-delay” agreements or “reverse payments”) involving manufacturers of Ciprofloxacin HCl (CIPRO) is per se lawful under the Sherman Act. 

In September 2010, the U.S. Court of Appeals for the Second Circuit denied a Petition for Rehearing and Rehearing En Banc filed on behalf of certain drug purchasers in In Re Ciprofloxacin Hydrochloride Antitrust Litig., 604 F.3d 98 (2d Cir. 2010), that a panel of judges on the Court invited in their April 2010 decision affirming a 2005 decision by the U.S. District Court for the Eastern District of New York granting summary judgment for defendants (i.e., Ciprofloxacin HCl manufacturers).  The Second Circuit panel affirmed the district court decision because the Court believed its 2005 decision in In re Tamoxifen Citrate Antitrust Litig., 466 F.3d 187 (2d Cir. 2005), compelled it to do so.  According to the Court, “[s]ince Tamoxifen rejected antitrust challenges to reverse payments as a matter of law, we are bound to review the Cipro court’s rulings under the standard adopted in Tamoxifen.”  The drug purchasers, in their petition to the Supreme Court, say that the Court’s decision is necessary to resolve a 3-way circuit split over the proper standard for determining whether an exclusion payment violates the antitrust laws.

California Attorney General Kamala D. Harris, the lead on the amicus brief in support of the direct purchasers’ Petition, announced the submission of the brief late last Friday.  According to the State Attorneys General, “[a] surge in reverse payment agreements is threatening the existence of generic competition and the availability of affordable drugs to the states and their citizens.” 

Overturning [the] Tamoxifen and Cipro [decisions], and permitting broader antitrust scrutiny of reverse payments would reinforce Congressional intent underlying the Hatch-Waxman Act.  Doing so also would not undermine the courts’ general policy of promoting settlement. Without reverse payments, patent litigants can settle, as they did in the pre-Tamoxifen years, with licensed entry, in which the license terms are based on the strength of the patent rather than sharing of monopoly profits.  Reverse payments are not necessary to settle patent cases, and the payments “serve no obvious redeeming social purpose.”  State antitrust enforcers have a keen interest in ensuring that generic exclusion results from the strength of the patent rather than rivals’ common interest in eliminating competition and sharing the spoils at the consumers’ expense. [(Internal citation omitted)]

Joining California Attorney General Harris on the amicus brief are the Attorneys General from Arizona, Arkansas, Delaware, Florida, Hawaii, Idaho, Illinois, Iowa, Maine, Maryland, Massachusetts, Minnesota, Mississippi, Missouri, Montana, Nebraska, Nevada, New Hampshire, New Mexico, North Carolina, Oklahoma, Ohio, Oregon, South Carolina, Tennessee, Texas, Utah, Vermont, Washington, West Virginia, and Wyoming.

UPDATE:

• A second amicus brief submitted by several public interest groups (Consumer Federation of America, Prescription Access Litigation LLC, U.S. PIRG, and the National Legislative Association on Prescription Drug Prices) also urges the U.S. Supreme Court to grant the Petition for Writ of Certiorari.  "Few competition problems are as critical as pay-for-delay settlements such as the one involving Cipro," say the amici.  "Four arguments, slavishly followed by the courts, have introduced the gravest mistakes: (1) settlements are beneficial, (2) patents are presumed valid, (3) reverse payments fall within the scope of the patent, and (4) reverse-payment settlements are a natural by-product of the Act.  Strict adherence to these arguments flies in the face of the Hatch-Waxman Act and unnecessarily increases price and jeopardizes patients’ health."

By Susan J. Matthees –

Last week, FDA announced that the Agency has adopted final amended informed consent regulations.  As we noted last year, the Food and Drug Administration Amendments Act ("FDAAA") § 801(b)(3)(A) required that FDA amend the informed consent regulations set forth at 21 C.F.R. § 50.25 to include a statement to inform potential clinical trial participants that data from the trial has been or will be entered into a databank accessible to the public via www.clinicaltrials.gov.  FDA published the proposed rule implementing the FDAAA requirement in December 2009, and after considering comments, adopted the final rule, which will become effective on March 7, 2011.  However, FDA is providing a grace-period of 1 year, stating that the Agency intends to enforce the rule only for informed consent documents that are initiated on or after March 7, 2012. 

The statement that is required by amended 21 C.F.R. § 50.25 reads: “A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law.  This Website will not include information that can identify you.  At most, the Website will include a summary of the results.  You can search this Website at any time.”

Of note, FDAAA § 801(b)(3)(A) amends FDC Act § 505(i), which applies to drugs, so facially, it would appear that the new informed consent statement would only apply to drug trials.  However, FDA stated that because 21 C.F.R. Part 50 is one of the implementing regulations for FDC Act § 505(i), and 21 C.F.R. Part 50 applies to drugs and devices, FDA is applying the new informed consent language for drug and device trials.  FDA further explained that this will help maintain a uniform system for human subject protection and prevent confusion. 

Also interesting to note is that it is the investigator’s responsibility to obtain informed consent from research subjects.  21 C.F.R. § 50.20.  However, it is typically the responsibility of the sponsor of an applicable clinical trial to post the information to www.clinicaltrials.gov. 

By James R. Phelps –

California's SB 657, adopted in 2010, enlists manufacturers and retailers of goods with annual worldwide gross receipts over $100 million in the effort to eradicate “slavery and human trafficking.”  They are to provide information on their website to detail what they do to 1) verify that their chain of supply is not tainted with such practices, 2) conduct audits of suppliers to confirm lack of such involvement, 3) require direct suppliers to certify that materials used in products are complying with laws concerning slavery and human trafficking, 4) maintain accountability standards for employees and suppliers who fail to comply, and 5) provide employees involved in supply chain management with training about the slavery and human trafficking issues and how to mitigate their risks in the businesses.  Failure to comply, the law says, may subject the business to injunction actions brought by the state’s attorney general.  Presumably, this would apply to most manufacturers of food, drugs, and medical devices that purchase raw materials or components from overseas sources.

Some national governments that are U.S. trade partners are not so punctilious about the rights of workers.  In some of those jurisdictions people are told where they will work, without regard to the individuals’ wishes; how should those doing business in California react to these situations?  What would be the effect, should the businesses identify those jurisdictions in their websites?  How will they, in order to provide correct information on the website, police the compliance of suppliers from those jurisdictions?  There are other practical issues that need no elaboration.

It is admirable that the California legislature, with so many grave issues before it, is able to find the time and energy to address the international blight of slavery and human trafficking.  The wisdom of directing California businesses to take the lead in solving the problem is yet to be determined.

Thanks to lawyer/lobbyist Randy Pollack for alerting us to this new law = Randy@Pollacklaw.com, (916) 448-4848.

By Kurt R. Karst –      

In a notice slated for publication in the January 7th Federal Register, FDA is seeking to end the continued marketing of many unapproved oral prescription drugs for the relief of cough, cold, or allergy.  The action will likely affect hundreds of marketed unapproved drug products evaluated under the Drug Efficacy Study Implementation (“DESI”) program –  including any Identical, Related, or Similar (“IRS”) product – that have been marketed for decades on the basis that such products are somehow shielded from obtaining approval of a marketing application.  (For background on DESI see the article here.)

FDA’s notice is broken down into two categories: (1) DESI cough, cold, or allergy dockets for which hearing requests have been withdrawn; and (2) DESI cough, cold, or allergy dockets with outstanding hearing requests.  The first category includes specific drug products identified in certain DESI proceedings noted in Docket Nos. FDA-1981-N-0361 (formerly 1981N-0391), FDA-1982-N-0225 (formerly 1982N-0078), FDA-1982-N-0310 (formerly 1982N-0311), including products IRS to them, for which all outstanding requests in response to a notice of opportunity for hearing have been withdrawn.  “Shipment in interstate commerce of the products identified in those dockets, or any [IRS] product that is not the subject of an approved new drug application (other than an over-the-counter (OTC) product that complies with an applicable OTC monograph), is unlawful as of the effective date of this notice,” FDA states in the notice.  The second category includes drug products identified in certain DESI proceedings noted in Docket Nos. FDA-1981-N-0077 (formerly 1981N-0393), FDA-1981-N-0248 (formerly 1981N-0396), FDA-1982-N-0046 (formerly 1982N-0095), FDA-1982-N-0264 (formerly 1982N-0096), and FDA-1983-N-0137 (formerly 1983N-0095), including products IRS to them.  For the drug products identified in these dockets, FDA is offering an opportunity for firms to affirm outstanding hearing requests.  “FDA will assume that companies with outstanding hearing requests that do not respond to this notice are no longer interested in pursuing their requests, and will deem the requests withdrawn,” according to FDA. 

FDA also states in the notice the Agency plans to take swift enforcement action against companies that continue to market unapproved drug products subject to the Federal Register notice.  “Firms should be aware that, after the effective date of this notice, FDA intends to take enforcement action without further notice against any firm that manufactures or ships in interstate commerce any unapproved product covered by this notice that is not the subject of an ongoing DESI proceeding.”  Although some of the drug products identified by FDA and marketed with well-known brand names might be able to be reformulated to comply with an OTC drug monograph, FDA cautions against firms using the same brand name, or a new brand name that is substantially the same as the brand name.  “Reformulated products marketed under a name previously identified with a different active ingredient or combination of active ingredients have the potential to confuse health care practitioners and harm patients.”

By Riëtte van Laack –

More than 9 years after issuing a proposed rule, the Food Safety and Inspection Service (“FSIS”) published the final rule for nutrition labeling of single-ingredient meat and poultry products, as well as ground and chopped meat and poultry products.  Starting January 1, 2012 (FSIS’s uniform compliance date for new food labeling regulations issued between January 1, 2009, and December 31, 2010), major cuts of single-ingredient, raw meat and poultry products are required to carry nutritional information on labels or at point-of-purchase (“POP”).  All raw ground and chopped meat and poultry products, with or without seasoning, must carry nutrition labels. 

The new rule allows POP nutritional information for major cuts because the nutrient content of a major cut is relatively uniform and because consumers can generally estimate the fat content in major cuts.  Thus, consumers can easily find the applicable information for the cut.  Manufacturers need not perform any analyses to determine the nutrient content of the major cuts, but may use data from USDA’s National Nutrient Data Bank or the USDA’s National Nutrient Database for Standard Reference.  FSIS will use these same data to determine compliance with the regulations.  No nutritional information is required for non-major cuts of single-ingredient, raw meat and poultry products. However, if a manufacturer voluntarily provides nutritional information for these products, then they must comply with the regulation for the major cuts.
 
In contrast, raw ground and chopped products, such as hamburger, ground beef, ground beef patties, ground chicken, ground turkey, chicken, ground pork, and ground lamb must carry a nutritional label on the package.  Producers can precisely formulate these products to a specific fat content.  The fat is uniformly distributed throughout the ground product making it difficult for consumers to determine and compare the level of fat in these products.   POP nutritional information is not a viable alternative because there are numerous formulations of ground and chopped products; it would be difficult if not impossible for producers or retailers to develop POP materials that address all different formulations. Moreover, if POP nutritional information were provided, it would be difficult for consumers to find the correct information for a specific ground or chopped product. 

The nutritional information to be provided under the regulation is similar to that required by FDA for other foods.  However, unlike FDA, FSIS does not require labeling of trans fat content.  In addition, because raw meat products typically have random weights, the regulations do not require inclusion of the number of servings per container.

Numerous exemptions apply, including an exemption for ground or chopped products that qualify for the small business exemption, i.e., products produced by a facility that employs less than 500 people and produces no more than 100,000 lbs per year of a particular product. Note, however, that the small business exemption does not apply to nutritional labeling requirements for major cuts of single ingredient raw meat and poultry products because it is relatively easy to prepare point-of-purchase materials for these products. Moreover, FSIS will make POP materials available over the internet free of charge.

FSIS intends to conduct webinars on the final rule.

By Ricardo Carvajal –

The Food Safety Modernization Act ("FSMA") is now law.  We previously blogged on some provisions that take immediate effect (namely stronger records access authority under FDC Act § 414, mandatory recall authority, whistleblower protection, and authority to refuse admission of imported food from a facility that refuses inspection).  Other provisions that enhance FDA’s existing authorities but will take time to implement include suspension of registration, lower threshold for administrative detention, and import certification. Still other provisions will impose or authorize FDA to impose significant ongoing burdens on industry, most notably mandatory HACCP and associated recordkeeping requirements, additional recordkeeping requirements for high risk foods, compliance with performance standards and produce safety standards, implementation of measures to protect against intentional adulteration, verification of foreign suppliers’ compliance with U.S. law, and payment of reinspection fees.  We plan to spotlight these provisions as their effective date draws nearer. 

For now, it’s worth revisiting an issue we raised with respect to the FSMA’s companion bill, the Food Safety Enhancement Act – namely that of burdens imposed on FDA.  The FSMA directs FDA to substantially increase the number and frequency of domestic and foreign inspections.  Further, by our estimate, the FSMA directs FDA to engage in 10 rulemakings, issue no fewer than 10 guidance documents, prepare 13 reports (some on a recurring basis), and engage in numerous other resource-intensive implementation activities.  The burdens that these directives will impose on multiple components within FDA should not be underestimated.  In the absence of commensurate funding, it seems likely that the law will not be fully implemented and that numerous other food-related agency initiatives could once again find themselves on the back burner.  This type of discrepancy between increased agency responsibilities and the level of funding needed to fulfill those responsibilities has been identified as a cause of under-performance at FDA, such that a coalition of consumer and professional groups and trade associations (including a number of food trade associations) joined forces in the Alliance for a Stronger FDA to pressure Congress for additional agency funding.  The need for adequate funding to implement FSMA has already been acknowledged by the FDA Commissioner in her statement on the FSMA’s significance.  Whether FDA can buck the promised trend toward less government spending in 2011 and beyond will be one story to watch.

By Kurt R. Karst –    

In a letter recently submitted to FDA by the three principal authors of the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”) – Representatives Anna Eshoo (D-CA), Jay Inslee (D-WA), and Joe Barton (R-TX) – the legislators take issue with FDA’s characterization of the 12-year exclusivity period provided by the law and seek to clarify Congressional intent on granting new 12-year exclusivity periods for “next generation” products.

The BPCIA amended the Public Health Service Act (“PHS Act”) to, among other things, create an approval pathway for biosimilar and interchangeable versions of reference products (so-called § 351(k) applications) and establish a 12-year exclusivity period for reference products.  Specifically, PHS Act § 351(k)(7) provides for a 12-year period of exclusivity from the date of first licensure of the reference product, during which approval of a § 351(k) application cannot be made effective.  PHS Act § 351(k)(7)(C) includes certain limits on obtaining 12-year exclusivity.  That provision states that the date of first licensure, and therefore the 12-year exclusivity period, does not apply to a license for or approval of:

(i) a supplement for the biological product that is the reference product; or

(ii) a subsequent application filed by the same sponsor or manufacturer of the biological product that is the reference product (or a licensor, predecessor in interest, or other related entity) for –

(I) a change (not including a modification to the structure of the biological product) that results in a new indication, route of administration, dosing schedule, dosage form, delivery system, delivery device, or strength; or

(II) a modification to the structure of the biological product that does not result in a change in safety, purity, or potency.

In October 2010, FDA issued a Federal Register notice announcing a two-day public hearing to obtain input on specific issues and challenges associated with the implementation of the BPCIA.  Among the myriad issues for which FDA sought public comment were two questions on exclusivity:

1. In light of the potential transfer of BLAs from one corporate entity to another and the complexities of corporate and business relationships, what factors should the agency consider in determining the types of related entities that may be ineligible for a period of 12-year exclusivity for a subsequent BLA?

2. What factors should the agency consider in determining whether a modification to the structure of the licensed reference biological product results in a change in safety, purity, or potency, such that a subsequent BLA may be eligible for a second 12-year period of marketing exclusivity?

The BPCIA’s principal authors, in their December 21, 2010 letter, felt compelled to address FDA’s characterization of the 12-year exclusivity period as a period of “marketing exclusivity” in the Agency’s meeting notice.  The BPCIA “does not provide ‘market exclusivity’ for innovator products,” according to the letter.  “Rather, it provides data exclusivity for 12 years from the date of FDA approval . . . .”  The letter goes on to note the “significant and critical differences between the two types of exclusivity.”  “Data exclusivity only prohibits the FDA from allowing another manufacturer to rely on the data of an innovator to support approval of another product.  Importantly, it does not prohibit or prevent another manufacturer from developing its own data to justify FDA approval of a similar of competitive product.” 

The second issue raised in the letter concerns so-called “evergreening.”  Evergreening, which is the practice of obtaining additional periods of exclusivity for product modifications, was hotly debated during consideration of what ultimately became the BPCIA.  One legislative proposal even included an express prohibition on evergreening, and the Obama Administration’s 2009 10-year budget proposal raised concern about the practice.  PHS Act § 351(k)(7)(C) is intended to prevent evergreening by excluding most product changes from qualifying for a new 12-year exclusivity period.  

According to the December 21st letter, the BPCIA “is clear that no product, under any circumstances, can be granted ‘bonus’ years of data exclusivity for mere improvements on a product.”  Nevertheless, the legislators “want to be clear that if a ‘next generation’ product is approved by the FDA as a new product (significant changes in safety, purity, or potency) then that new biologic will receive its own 12-year period of data exclusivity.”  “Any proposal to limit the definition of a ‘new’ product, and thus one which is entitled to its own period of data exclusivity has the potential to stifle innovation and negatively impact patient care,” according to the letter. 

The scope the 12-year exclusivity period provided by the BPCIA is also discussed in lengthy comments (here and here) submitted to FDA by the Pharmaceutical Research and Manufacturers of America (“PhRMA”) and the Biotechnology Industry Organization (“BIO”).  Both PhRMA and BIO request that FDA apply the concept of “umbrella exclusivity” to new BLAs and BLA supplements that do not independently qualify for the 12-year exclusivity period. 

Under FDA’s “umbrella policy” for drug products, any remaining 5-year New Chemical Entity (“NCE”) exclusivity period granted under the Hatch-Waxman Amendments for the original NDA NCE approval applies to subsequent applications (both new NDAs and NDA supplements) for drug products containing that NCE until the NCE term expires.  According to BIO:

[I]it is important for FDA to clarify that BLA supplements and full BLAs that may not themselves be eligible for 12 years of exclusivity because they seek certain non-qualifying changes to already-approved products will nevertheless benefit from any remaining exclusivity for the underlying, previously-approved biologic.

PhRMA contends that any decision by FDA apply the Agency’s “umbrella policy” to BPCIA exclusivity would mean that: “(1) a supplement or subsequent application that was not entitled to its own 12-year period would be protected for any remaining period of exclusivity applicable to the first licensed product to which it is related, and (2) an affiliate or related entity’s product that was not entitled to its own 12-year period would be protected for any remaining period of exclusivity applicable to the initial applicant’s product.”  “Any other approach,” according to PhRMA, “would be inconsistent with [FDA’s] longstanding approach to data exclusivity [and] would seriously undermine the value of exclusivity and incentives to innovate.”

Hyman, Phelps & McNamara, P.C. (“HPM”) is pleased to announce that Anne K. Walsh has joined the firm as Of Counsel.  Prior to joining the firm in January 2011, Ms. Walsh served as an Associate Chief Counsel with the U.S. Food and Drug Administration’s Office of Chief Counsel from 2004 to 2010.  She worked closely with federal prosecutors and law enforcement agencies to investigate, negotiate, and litigate civil and criminal violations of the Federal Food, Drug, and Cosmetic Act.  Ms. Walsh has extensive knowledge of issues concerning health care fraud, off-label promotion, cGMP and reporting regulations, and clinical study fraud, as it relates to both corporate and individual liability.  She has won numerous awards for her work in groundbreaking prosecutions and settlements, including cases involving pharmaceutical, medical device, and in vitro diagnostics companies.  She also has experience advising on matters involving other FDA enforcement activities, including for-cause inspections, warning letters, and recalls. 

Ms. Walsh graduated from the College of William and Mary in 1994 with a B.A. in economics, and with a J.D. in 1997.  She is admitted to practice law in New York and the District of Columbia.  After graduating from law school, Ms. Walsh worked as an attorney in private practice representing major pharmaceutical and medical device clients. 

By Jeffrey K. Shapiro –

A group of nine U.S. Senators has sent a letter to FDA expressing concern over potential changes to the 510(k) medical device clearance program.  The letter is similar to a November 2010 letter from Minnesota lawmakers and an October 2010 letter from House lawmakers (see our previous posts here and here).  Each letter takes issue with FDA’s August 2010 report recommending changes to the 510(k) program, which we reported on last year. 

The Senatorial letter points to several “controversial” recommendations that “have the potential to disrupt the current regulatory balance under the 510(k) pathway, jeopardizing patients' timely access to new treatments and cures.”  In particular, the Senators “believe that the recommendations regarding rescission authority; split and multiple predicates; intended use and indications for use; splitting Class II; and the treatment of proprietary information, including trade secrets could have significant unintended adverse consequences on the existing regulatory process.”

By Diane B. McColl & Ricardo Carvajal –

On December 28th, FDA reopened the public comment period for its 1997 proposed rule that outlined the voluntary GRAS notification process intended to replace the voluntary GRAS affirmation petition process.   FDA stopped accepting GRAS affirmation petitions and implemented the ongoing GRAS notification process when the 1997 proposed rule published.  According to the agency, publication of the December 28th  notice is the first step in FDA’s effort to at long last finalize the proposed rule.

FDA seeks comments not only on the 1997 proposal, but also on numerous issues raised by CFSAN's 13-year experience with the GRAS notification process for human foods, as well as some of the recent GAO recommendations (for our take on the GAO report, see here and here).  Because the notice raises several issues that were not explicitly addressed in the 1997 proposed rule, it should be carefully reviewed by anyone with an interest in FDA’s voluntary GRAS notification process, including those with long-pending GRAS affirmation petitions.  Note also that the agency requests input on issues relating to the GRAS notification process for animal feed and pet food ingredients newly implemented by CVM. Among the issues on which FDA requests comments:

• FDA’s proposed revisions to the regulation that states the eligibility criteria for GRAS classification (21 C.F.R. § 170.30);
• incorporation by reference of previously submitted data in a GRAS notice;
• requests to cease evaluation of a GRAS notice;
• inclusion in a GRAS notice of information claimed to be confidential;
• submission of specific descriptive information such as biological source, known toxicants, and particle size (the latter recommended by GAO due to concerns about nanotechnology)
  submission of information about dietary exposure;
• submission of species-specific information in the case of animal feed ingredients;
  coordination of FDA’s evaluations with USDA/FSIS;
• potential issuance by FDA of guidance on conflicts of interest among GRAS expert panelists (as recommended by GAO);
• potential issuance by FDA of additional guidance on documentation of GRAS conclusions (as recommended by GAO); and
• FDA’s disposition of pending GRAS affirmation petitions.

Any public comments submitted previously to FDA in response to the 1997 proposed rule need not be resubmitted.  New public comments are due by March 28, 2011.

By Cassandra A. Soltis –

The Food and Drug Administration (“FDA”) posed that question in 2005, when it issued an advance notice of proposed rulemaking concerning the serving sizes of products that could reasonably be consumed at one eating occasion.  70 Fed. Reg. 17010 (Apr. 4, 2005).  The notice stemmed from recommendations made by FDA’s Obesity Working Group, which called for public comments on how to make calorie information more prominent on food labels.  In the notice, FDA explained that if data show that consumers are drinking larger amounts of beverages, and FDA increases the reference amount customarily consumed (“RACC”) for beverages accordingly, the serving sizes for beverages would likely increase, which might imply to consumers that larger serving sizes are being recommended.  70 Fed. Reg. at 17012. 

Although there has been no further action on this advance notice, FDA recently released a draft compliance policy guide (“CPG”) on serving size labeling for certain beverages.  Notice, Draft Compliance Policy Guide Sec. 510.800 Beverages – Serving Size Labeling; Availability, 75 Fed. Reg. 80828 (Dec. 23, 2010).  Through this draft CPG, FDA permits certain beverages to declare a larger serving size in labeling.  However, FDA sidesteps the question of whether larger serving sizes will be viewed as being recommended.       

The draft CPG, which is intended to provide guidance to FDA staff, provides that “FDA will typically consider not taking an enforcement action when a beverage container larger than 20 fluid ounces states the calories for 12 fluid ounces on the [front panel] and correspondingly provides the number of 12 fluid ounce servings in the container and the nutrition information is based on a 12 fluid ounce serving in the Nutrition Facts panel.”  Ordinarily, the labels of beverages must declare the number of servings in a product using 8 fluid ounces, which is the current RACC for beverages, and the nutrition information must also be based on that amount.  21 C.F.R. §§ 101.12, Table 2, 101.9(b). 

The policy described in the CPG is limited “to the following beverages in containers larger than 20 fluid ounces that display calorie information per 12 fluid ounce serving on the” front panel:  sports and energy drinks (neither of which are FDA-defined food categories); bottled water and water beverages; soft drinks and diet soft drinks; and ready-to-drink teas.  FDA does not intend the policy to apply to other beverages, “including 100% juices, diluted juice beverages, alcoholic beverages, or 100% milks.” 

A May 27, 2010, letter from the American Beverage Association ("ABA") to FDA requested the changes outlined in the draft CPG.  The ABA’s letter followed the beverage industry’s announcement of its “Clear on Calories” initiative, which is intended to make calorie information clear and consumer friendly. 
 
Comments on the draft CPG can be submitted to the Agency at any time, but FDA encourages comments to be submitted by February 22, 2011.  75 Fed. Reg. 80828.

By Kurt R. Karst –      

Amphastar Pharmaceuticals Inc. (“Amphastar”) has filed with the U.S. District Court for the District of Columbia an Amended Complaint for Declaratory and Injunctive Relief against FDA in Amphastar’s continuing battle to win approval of the company’s long-pending Abbreviated New Drug Application (“ANDA”) for a generic version of sanofi-aventis U.S. L.L.C.’s (“sanofi’s”) blockbuster anti-coagulant drug LOVENOX (enoxaparin sodium injection).  The December 22nd amended complaint follows, as we previously reported (here and here), Amphastar’s October 25th Complaint and November 5th Motion for Preliminary Injunction filed against FDA with regard to the Agency’s detention of two entries of semi-purified heparin, the starting material for Enoxaparin Sodium.  That issue was resolved after FDA released the raw material. 

Amphastar’s Amended Complaint, like the company’s original Complaint, alleges violations of the Administrative Procedure Act (“APA”).  The Amended Complaint accounts for the factual change arising from FDA’s release of the imported semi-purified heparin raw material and “expounds upon Amphastar’s broader claim of arbitrary and capricious actions by [FDA].”  Amphastar alleges a litany of APA violations, including that “FDA’s imposition of immunogenicity testing requirements on enoxaparin ANDAs is beyond the authority of the FDA,” and that “FDA has treated Amphastar disparately from Amphastar’s similarly situated competitors.”

Amphastar’s battle with FDA is not the only current case concerning Enoxaparin Sodium.  In a different case pending in the D.C. District Court, sanofi is challenging FDA’s approval of Sandoz Inc.’s ANDA No. 77-857 for generic LOVENOX, as well as FDA’s July 23rd response to a February 2003 citizen petition, in which the Agency outlined the five criteria (i.e., standards for identity) that an ANDA applicant needs to demonstrate sameness of its active ingredient as compared to LOVENOX.  As we recently reported, sanofi filed a Motion for Summary Judgment alleging that FDA’s approval of ANDA No. 77-857 is unlawful and should be set aside.  Among other things, sanofi alleges that FDA exceeded its authority under FDC Act § 505(j)(2)(A) by requiring Sandoz to submit studies beyond what is permitted for ANDAs – specifically, immunogenicity studies that, according to Sanofi, are studies intended “to demonstrate safety and effectiveness.”

In his latest article appearing in FDLI Update, Hyman, Phelps & McNamara, P.C. Director John R. Fleder explores whether the FDA should enforce the FDC Act by giving different treatment to similarly-situated competitors.  The article reaches the conclusion that the public is not well served if companies correctly conclude that they are being held to a harsher standard than their competitors.  Mr. Fleder explains why the best way to avoid this concern is for FDA to take a nationwide approach to enforcement decisions.  He argues that an FDA decision to take an enforcement action must be preceded by an analysis by the agency of whether it is unfairly singling out one competitor for an enforcement action while leaving competitors free from the public stigma of an FDA enforcement action.

By Kurt R. Karst –      

Another week, another Petition for Writ of Certiorari filed with the U.S. Supreme Court on an issue involving the drug industry.  The latest petition comes from Caraco Pharmaceutical Laboratories, Ltd. (“Caraco”) and Sun Pharmaceutical Laboratories, Ltd. (“Sun”) and requests the Court’s review of an April 14, 2010 decision from the Federal Circuit in Novo Nordisk A/S v. Caraco Pharmaceutical Laboratories, Ltd., 601 F.3d 1359 (Fed. Cir. 2010), which addressed whether the patent delisting counterclaim provisions at FDC Act §505(j)(5)(C)(ii)(I), as added by the Medicare Modernization Act, may be used to correct or delete an Orange Book-listed Patent Use Code (“PUC”).

FDC Act §505(j)(5)(C)(ii)(I) states:

If an owner of the patent or the holder of the approved application under [FDC Act § 505(b)] for the drug that is claimed by the patent or a use of which is claimed by the patent brings a patent infringement action against the applicant, the applicant may assert a counterclaim seeking an order requiring the holder to correct or delete the patent information submitted by the holder under [FDC Act § 505(b)] or (c) on the ground that the patent does not claim either – (aa) the drug for which the application was approved; or (bb) an approved method of using the drug.

As we previously reported (here, here, and here), in 2009, the U.S. District Court for the Eastern District of Michigan (Southern Division) ruled and issued an Order and Injunction requiring Novo Nordisk, Inc. (“Novo”) to change an Orange Book-listed PUC for a patent – U.S. Patent No. 6,677,358 (“the ’358 patent”) – on its drug product, PRANDIN (repaglinide) Tablets, as a result of Caraco’s FDC Act §505(j)(5)(C)(ii)(I) counterclaim.  Novo appealed and the Federal Circuit reversed and vacated the district court’s judgment in a 2-1 decision.  The Federal Circuit ruled that Caraco “does not have a statutory basis to assert a counterclaim requesting” a court to enter an order to replace Novo’s new PUC with the former PUC.  (See our previous posts for additional background on the case.)  First, the Federal Circuit ruled that “the Hatch-Waxman Act authorizes a counterclaim only if the listed patent does not claim any approved methods of using the listed drug.”  Second, “the terms of the counterclaim provision do not authorize an order compelling the patent holder to change its use code narrative,” just the patent number and expiration date of an Orange Book-listed patent.  Judge Dyk lodged a 28-page dissent arguing that “the majority’s crabbed view of the statute sanctions an unjustified manipulation of the Orange Book,” and that FDC Act §505(j)(5)(C)(ii)(I) should be available with respect to challenging PUCs, because “all Orange Book information is ‘patent information.’”

In May 2010, Caraco/Sun filed a Petition for Panel Rehearing and Rehearing en banc of the Federal Circuit’s panel decision.  The Federal Circuit denied that petition in a July 29, 2010 Order, but Judges Gajarsa and Dyk took the opportunity to lodge their complaints with the majority’s decision.  Among other things, Judges Gajarsa and Dyk believe that the majority’s opinion renders “section viii” labeling carve-out statements “a virtual nullity and leaves generic drug manufacturers without a remedy to challenge inaccurate Orange Book listings with respect to method of use patents.”

In their December 2010 Petition for Writ of Certiorari, Caraco/Sun “seek review of a splintered Federal Circuit decision raising issues of recurring importance under the Hatch-Waxman Act,” and ask the Court to address “[w]hether [FDC Act §505(j)(5)(C)(ii)(I)] applies where (1) there is ‘an approved method of using the drug’ that ‘the patent does not claim,’ and (2) the brand submits ‘patent information’ to the FDA that misstates the patent’s scope, requiring ‘correct[ion].’”  According to Caraco/Sun, the Federal Circuit’s decision is “[i]n conflict with this Court’s precedents and recent D.C. Circuit authority” (i.e., Teva Pharms. USA, Inc. v. Sebelius, 595 F.3d 1303 (D.C. Cir. 2010), which is also at the heart of another Petition for Writ of Certiorari) and “effectively nullifies both a critical provision of the [FDC] Act and related FDA regulations – which Congress ratified in 2003 – without calling for the FDA’s views.”  Moreover, Caraco/Sun argue that:

By the majority’s lights, no counterclaim is available because (1) Novo’s patent claims one approved use, even though it “does not claim” two other “approved method[s] of use”; and (2) the counterclaim is effectively limited to “delet[ing]” wrongly-listed patents, when Congress also authorized “correct[ing]” patent information.   The majority reached this result by announcing that the phrase “an approved method of us[e]” really means “any approved method of us[e].”  But that rewriting of the [FDC] Act violated this Court’s precedents – not least because the word “any” appears elsewhere in the same provision.  Moreover, the majority read the term “patent information” as limited to “an erroneous patent number or expiration date” – i.e., to exclude “use codes” – invalidating the FDA’s contrary interpretation, which Congress ratified. [(internal citations omitted)]

Interest in the Caraco/Sun petition will likely run high and may generate several amicus briefs.  GPhA, Mylan, Teva, Apotex, Impax, the National Legislative Association on Prescription Drug Prices, and the Consumers Federation of America filed briefs in the Federal Circuit in support of Caraco/Sun’s rehearing petition. 

By Ricardo Carvajal - 

Although many of the Food Safety Modernization Act's ("FSMA's") major provisions have a delayed effective date (including the requirement to develop and implement a HACCP plan), some significant provisions will take immediate effect, including:  

• Stronger records access authority (FSMA § 101).  FDA gains authority under amended FDC Act § 414(a) to access and copy “all records relating to the manufacture, processing, packing, distribution, receipt, holding, or importation” of a food if FDA believes that there is a reasonable probability that the use of or exposure to the food will cause serious adverse health consequences or death to humans or animals.  The provision extends to any other food that FDA reasonably believes is likely to be affected in a similar manner.  FDA can access records that the agency needs to determine whether there is “a reasonable probability that the use of or exposure to the food will cause serious adverse health consequences or death to humans or animals.”  FDA’s access to records is contingent on “presentation of appropriate credentials and written notice.”

• Mandatory recall authority (FSMA § 206).  The FDA Commissioner gains authority to order a mandatory recall when the agency determines that there is a reasonable probability that a food other than infant formula is adulterated under FDC Act § 402 or misbranded under § 403(w), and that the use of or exposure to the food will cause serious adverse health consequences or death to humans or animals.  FDA must first give the responsible party an opportunity to conduct a voluntary recall.  If the responsible party refuses to do so, and the Commissioner issues an order, FDA must give the responsible party an opportunity for an informal hearing within two days of the order’s issuance. 

• Whistleblower protection (FSMA § 402).  An employee is protected from retaliation by an employer when that employee (1) provides an employer, the U.S. government, or a state attorney general with information relating to any violation of the FDC Act, (2) testifies or is about to testify in a proceeding concerning such a violation, (3) assists, participates, or is about to assist or participate in such a proceeding, or (4) objects to or refuses to participate in any activity, policy, practice, or assigned task that the employee reasonably believes to be a violation.  An employer found to have engaged in retaliation is liable for relief needed to make the employee whole, as well as costs and expenses related to the complaint. 

• Foreign facilities and refusal of inspection (FSMA § 306).  An imported food will be refused admission if it is from a foreign establishment to which a U.S. inspector is refused entry for the purpose of conducting an inspection.  Entry is deemed refused if the inspector isn’t granted access within 24 hours of requesting entry. 

 Affected firms would do well to review these particular provisions, modify their SOP’s as needed, and train their personnel accordingly.