By Kurt R. Karst –      

2008 was a banner year for orphan drug designations.  FDA’s Office of Orphan Products Development (“OOPD”), which, since September 2007, has been under the leadership of Timothy Coté, M.D., M.P.H., designated a record 165 products for orphan (i.e., rare)  diseases and conditions.  FDA also approved 15 orphan products in 2008.  The 2008 orphan drug designation figure continues a recent trend in an uptick in designations.  From 2004 to 2007, OOPD granted 130, 122, 141, and 119 designations, respectively.  From 1983 to 2003, the greatest number of orphan drug designations in a single year was 95.  The table below illustrates OOPD’s designation and FDA’s orphan drug approval track record since the enactment of the Orphan Drug Act of 1983 (“ODA”).

It is unclear whether the recent increase in orphan drug designations reflects a shift in OOPD policy, or whether the Office is receiving more designation requests.  Our experience is that the depth and thoroughness of OOPD review has certainly not decreased.  In fact, OOPD seems to be placing a greater emphasis on the scientific rationale and medical plausibility components of an orphan drug designation request than it has in the past.  Thus, we believe the increase in orphan drug designations is largely a function of the quantity of requests OOPD is receiving.    

Orphan drug designation qualifies a company for several benefits under the ODA, as amended.  These benefits include a 7-year period of orphan drug exclusivity upon product approval (which generally prevents FDA from approving another firm’s version of the “same drug” for the same disease or condition for 7 years), a tax credit for certain clinical testing expenses for the orphan drug, written guidance on the non-clinical and clinical studies needed to obtain marketing approval of an orphan drug, and orphan drug grants.  In addition, there are certain user fee, pediatric assessment (i.e., FDC Act § 505B(k)), and “extra-statutory” benefits for orphan drugs (e.g., the quantity and quality of evidence needed to support the approval of an orphan product seems to reflect the understanding that there is a limited subject population in which to study the product – see ICH/FDA, Guideline for Industry: The Extent of Population Exposure to Assess Clinical Safety: For Drugs Intended for Long-term Treatment of Non-Life-Threatening Conditions, at 4 (Mar. 1995)).  

By John A. Gilbert & Larry K. Houck –      

WMSN-TV Fox 47 of Madison, Wisconsin, recently reported that pharmacies are experiencing difficulty obtaining oxycodone to fill their patients prescriptions.  Oxycodone, a schedule II opioid painkiller, is indicated for patients suffering from moderate to severe pain.  The report stated that “[a] DEA spokesperson in Chicago says this is not a nationwide shortage, and if pharmacies can’t get supply, it’s likely their manufacturer has reached its quota.”

While there may not be a nationwide oxycodone shortage, pharmacies and hospitals outside Wisconsin have also been unable to obtain the drug.  Oxycodone has been reported in short supply in Oregon and Washington, as well as in parts of California, Colorado and Maine.

The shortages have been attributed to several factors.  Some have blamed DEA for delaying the annual quota, giving manufacturers a late start.  Others have said that manufacturers have already hit their quota and were forced to cease production.  A recall by manufacturer Mallinckrodt and cutbacks by Ethex have also purportedly contributed to the problem.  One pharmacy expert observed that a few years ago five companies manufactured extended-release oxycodone and that four of the companies no longer manufacture the drug.

Other than the statement by the DEA spokesperson in Chicago, there has been no mention of the shortage by the agency.  The Controlled Substances Act (“CSA”) requires DEA to establish quotas that control the quantity of schedule I and II controlled substances that may be manufactured in the United States in a calendar year.  21 U.S.C. § 826.  DEA establishes an annual aggregate quota for each schedule I or II substance.  21 U.S.C. § 826(a).  The agency assigns individual manufacturing quotas to manufacturers of controlled substances such as oxycodone in bulk.  21 U.S.C. § 826(b).  DEA issues procurement quotas that authorize manufacturers to procure a basic class of schedule I or II substances to make dosage forms.  Manufacturers can only manufacture quantities within their assigned manufacturing quota and they may only procure source materials or manufacture dosage forms within their procurement quota.  Manufacturers apply for quotas in April of the year prior to the year of the quota request.

DEA regulations require the agency to publish aggregate production quotas on or before May 1 of each year, and individual procurement quotas and individual manufacturing quotas on or before July 1, 21 C.F.R. §§ 1303.11(c), 1303.12(c), 1303.21(a).  The CSA requires DEA to establish individual manufacturing quantities on or before October 1.  21 U.S.C. § 826(c).  DEA published the proposed aggregate production quotas for 2009 on November 7, 2008 and “established initial aggregate production quotas” for 2009 on December 29, 2008.

By J.P. Ellison –

Twenty-Seven Attorneys General have given FDA prior approval authority over Bayer’s Direct-to-Consumer (“DTC”) television and print advertising for its prescription oral contraceptive Yaz, and also required to company to run a $20 million corrective advertising campaign as part of a settlement agreements with the states (see press releases here and here).

The AGs were able to achieve this result even though the FDC Act is clear that the enforcement of the FDC Act can only be brought in the name of the FDA (the provision in FDC Act § 310 which allows States to bring actions relating to food did not apply here).  Though FDA “collaborated” with the state AGs and thus was a seemingly willing third party beneficiary of the settlement agreements, it was not a party to the litigation.

This is somewhat curious because, while the AG’s apparent leverage for the 2009 settlements came from earlier 2007 settlements with Bayer concerning its drug Baycol (see here and here), the AG press releases plainly state that the impetus for their actions was  an October 2008 FDA Warning Letter to Bayer concerning two Yaz TV spots.

The FDA Warning Letter alleges violations of the FDC Act, which one would think the FDA would enforce through agency action.  It’s equally clear that FDA’s position is that Warning Letters, like the one that Bayer received, are not final agency action.  FDA’s Regulatory Procedures Manual states that “[a]Warning Letter is informal and advisory . . . . [T]he agency does not consider Warning Letters to be final agency action on which FDA can be sued.”  So while FDA never took final agency action, the states did, and FDA has prior approval authority as a result.

While this settlement was announced shortly after President Obama took office and could be seen as a rollback on the Bush era FDA preemption doctrine, it seems likely that this settlement was agreed to in principle prior to the Administration change.  Thus, given the expectations for this administration, one can only expect increased state AG and FDA collaboration in the coming months.

By Bill T. Koustas –

On February 9, 2009, FDA (or “the Agency”) announced it has invited the sponsors of opioid drug products to a private meeting in March in order to begin the process of developing Risk Evaluation and Mitigation Strategies (“REMS”) that will impact 24 opioid products from 16 different sponsors.  This will be the first class-wide REMS program instituted by FDA.  While sponsors of investigational opioids are not immediately affected, the meeting outcome and eventual REMS will undoubtedly affect their products as well.      

According to FDA, the risks that the REMS is intended to mitigate are: (1) the use of certain opioid products in patients who are not opioid tolerant; (2) abuse; and (3) accidental and intentional overdose.  The Food and Drug Administration Amendments Act of 2007 (“FDAAA”) gives FDA the authority to require REMS for approved products when it becomes aware of new safety information and determines that a REMS is necessary to “ensure the benefits of the drug outweigh the risks of the drug,” but has no express provisions authorizing class-wide REMS. FDC Act § 355-1(2).  The Agency, however, has broad discretion in determining what constitutes “new safety information” and would likely defeat a challenge that it failed to make the requisite finding for each individual drug.  While FDA’s public statement regarding this issue notes that the Agency “recognizes the need to achieve balance between appropriate access and risk mitigation,” it is unclear what REMS elements will be required for this class of products.  In a call with the media, Dr. John Jenkins, Director of the Office of New Drugs, indicated that the REMS may include added labeling and patient monitoring among other elements to assure safe use.

According to FDA’s announcement, the opioid drugs affected by this announcement include both brand name and generic products that contain fentanyl, hydromorphone, methadone, morphine, oxycodone and oxymorphone.  The meeting described in the letter signed by Dr. Bob Rappaport, Director of the Division of Anesthesia, Analgesia and Rheumatology Products, is scheduled to take place on March 3, 2009 at 3:30pm on FDA’s White Oak campus.  Implicitly acknowledging that developing class-wide REMS for these drug products is complicated and potentially controversial, the Agency noted in the announcement that it is also planning to hold several meetings with other federal agencies, non-government organizations, patient and consumer advocates, pain and addiction treatment advocates and other health care professionals and stakeholders.  Additionally, the Agency is planning a public meeting on this issue in late spring or early summer to permit more public participation.  FDA expects to inform the sponsors of the affected opioid products regarding the required REMS after the public meeting. 

FDA will likely consult with the Drug Enforcement Administration ("DEA") on the class-wide REMS.  The Controlled Substances Act and DEA regulations require that manufacturers and registrants of controlled substances maintain effective controls against diversion and compliance with REMS could arguably be viewed as a part of this duty.  Manufacturers will need to consider that DEA will evaluate compliance with REMS as a factor in determining ongoing compliance with DEA requirements.

By Ricardo Carvajal –      

Disagreeing with an earlier New Jersey district court decision, a California district court has ruled that there is no federal preemption of an unfair competition claim against the manufacturer of a food that contains high fructose corn syrup ("HFCS") and is labeled as “all natural.”  According to the decision, the claim is not expressly preempted by FDC Act section 403A, nor is the claim impliedly preempted under the doctrines of field or conflict preemption.  On the question of implied preemption, the California court rejects as unpersuasive the reasoning relied on by a New Jersey district court to reach the opposite conclusion (Holk v. Snapple Beverage Corp., 574 F.Supp.2d 447 (D.N.J. 2008)).  This latest decision is likely to add to the existing confusion over the precise contours and reach of the doctrine of implied preemption in food liability cases.  Notably, FDA has indicated that products that contain HFCS can be labeled as "natural," depending on how the HFCS is made.

By Jamie K. Wolszon –    

On January 21, 2009, the California Supreme Court decided that it would not review a remarkable California appeals court decision that a brand-name drug manufacturer could be liable for an adverse event the plaintiff suffered as a result of taking a generic version of the drug, if the physician foreseeably relied upon the brand-name drug company’s labeling.  We previously reported on the First Appellate District in the Court of Appeal in the State of California decision.

Wyeth submitted a petition in Conte v. Wyeth, Inc., et. al. requesting that the California Supreme Court review the appeals court decision. The California Supreme Court does not automatically review appeals court decisions in civil cases:  Parties seeking review file petitions for review with the court.  The California Supreme Court did not provide any explanation of its decision to deny the petition, although it did note that Justice Marvin Baxter wanted to grant the petition.

The Washington Legal Foundation (“WLF”), a group well known in food and drug law circles for challenging FDA’s policies regarding the dissemination of information pertaining to off-label information, filed an amicus brief urging the California Supreme Court to hear the case.  WLF argued in its brief that the appeals court holding represented a radical departure from the long-standing legal principle that a manufacturer only can be liable under products liability law if it makes the drug that injured the plaintiff.

WLF also argued in its brief that allowing the appeals court ruling to stand would discourage generic drug makers’ from ensuring that their labeling contain sufficient safety information.  FDA regulations call on generic drug manufacturers, as well as innovator drug makers, to ask FDA to change the label if new information comes to light. 
 
WLF stated in a litigation update about the case that it expects other plaintiff attorneys will try to use a similar theory in future cases.  The group added that it will look for opportunities to defeat the theory as it arises in other cases. 

The controversial appellate court ruling that was the subject of the petition for review held: “that the common law duty to use due care owed by a name-brand prescription drug manufacturer when providing product warnings extends not only to consumers of its own product, but also to those whose doctors foreseeably rely on the name-brand manufacturer’s product information when prescribing a medication, even if the prescription is filled with the generic version of the prescribed drug.” 
 
The appellate court also found that the plaintiff created a sufficient factual dispute as to whether the plaintiff’s physician relied on the information submitted by Wyeth to the Physician’s Desk Reference (“PDR”) for its drug REGLAN (metoclopramide) to defeat a motion for summary judgment.  The plaintiff claimed that the information Wyeth submitted to the PDR did not adequately warn about the adverse effects that could occur from taking the drug for more than 12 weeks at a time, that the physician relied on that information, and as a result, the plaintiff suffered injury. 

The trial court, reversed by the appellate court, had granted Wyeth’s motion for summary judgment on the grounds that a brand-name drug manufacturer does not owe a duty of care to the plaintiff who only took the generic version of the drug, and that the plaintiff could not show that she or her physician relied upon warnings or product labeling disseminated by Wyeth. 

Now that the California Supreme Court has refused to hear the case, the case will return to the trial court.

By Michelle L. Butler –

With the effective date for a number of requirements imposed by the Consumer Product Safety Improvement Act (“CPSIA”) quickly approaching (February 10, 2009), the Consumer Product Safety Commission engaged in a flurry of activities.  We recently reported on the Commission’s decision to stay enforcement of the testing and certification requirements in the CPSIA as to the majority of products, including products subject to the child resistant packaging standards of the Poison Prevention Packaging Act.  Late last week, the Commission took a number of actions related to the underlying requirements pertaining to phthalates and lead content in children’s products.

Phthalates:  On February 5, 2009, a judge in the United States District Court for the Southern District of New York set aside an advisory opinion letter issued by the General Counsel of the Commission that the prohibitions on phthalates in children’s products (children’s toys and child care articles) did not apply to existing inventory.  See National Resources Defense Council, Inc. v. U.S. Consumer Product Safety Commission, No. 08-10507 (PGG), Memorandum Opinion and Order (S.D.N.Y. Feb. 5, 2009).  On February 6, 2009, the Commission stated in a press release that it would abide by the Court’s decision.  This position, along with the fact that the Commission chose not to avail itself of certain procedural arguments that might have delayed a ruling, indicates that the Commission wanted a ruling from the Court, even if the decision was contrary to the position originally taken by the General Counsel.  The press release also stated that the Commission would be issuing further guidance this week. 

Lead Content:  On January 28, 2009, a coalition of manufacturers requested emergency relief from the Commission to stay the effective date of February 10, 2009 for the lead content limit in section 101(a)(2) of the CPSIA, which requires that consumer products intended for children 12 and under not have more than 600 parts per million (“ppm”) of lead in any accessible part.   On February 6, 2009, the Commission denied this request.  Notwithstanding this decision, the Commission voted on February 6, 2009 to adopt a draft “Statement of Commission Enforcement Policy on Section 101 Lead Limits.”   The Commission’s Office of Compliance and Field Operations drafted this enforcement policy because the rulemaking process to grant certain relief from the lead limits could not be completed before February 10, 2009, when the lead content limits are to go into effect.  Among other things, this enforcement policy provides that the Commission will not impose penalties against anyone for making, importing, distributing, or selling

• a children’s product that is made of certain natural materials, such as wood, cotton, wool, or certain metals and alloys that the Commission has recognized as rarely, if ever, containing lead;
• an ordinary children’s book printed after 1985; and
• dyed or undyed textiles (not including leather, vinyl, or PVC) and non-metallic thread and trim used in children’s apparel and other fabric products, such as baby blankets – this class does not include such products if (1) they have undergone further treatment that may impart lead, (2) they are ornamented with metal, rhinestones, or other objects, or (3) they have plastic or metal fasteners with possible lead content (such as snaps, grommets, zippers, or buttons).

The enforcement policy states that the Commission generally will not prosecute someone for making, selling, or distributing an item in these categories even if it turns out that such an item actually contains greater than 600 ppm lead.  The policy states, however, that a seller could face prosecution if the Commission’s Office of Compliance finds that the seller had actual knowledge that one of these children’s products contained greater than 600 ppm lead or continued to make, import, distribute, or sell such a product after being put on notice of the lead content by the Commission staff.  The Commission intends to issue further guidance addressing these categories of products in greater detail.

Though this enforcement policy will provide relief to certain manufacturers, sellers, distributors, and importers of children’s products while the Commission’s rulemaking is underway, it does not affect the ability of interested persons, including State Attorneys General, to bring an action for violation of the lead content limits contained in the CPSIA.

On February 6, 2009, the Commission also decided to withdraw a proposed rule relating to exemptions for electronic products for which it is not technologically feasible to meet the lead content limits.  At the same time, the Commission issued an interim final rule that provided exemptions for such products. 

Proposed Legislation:  On February 4, 2009, Senator Jim DeMint introduced legislation to amend the Consumer Product Safety Act.  (This bill is not yet available from the Government Printing Office.)  According to a press release issued by Senator DeMint, the bill is intended to reform the CPSIA to protect the needs of small businesses and has six major components:

• Delays implementation of certain regulations for six months to balance the needs of small business and public safety.
• Allows small manufacturers to use testing and certification from component suppliers to certify that the components do not contain impermissible amounts of lead.
• Exempts thrift stores, yard sales, consignment shops, and other re-sellers from the prohibitions in the CPSIA.
• Prevents retroactive enforcement of the CPSIA.
• Provides a one-time, good faith exemption for small businesses from the requirements of the CPSIA.
• Requires the Commission to provide small business with a compliance guide.

By Ricardo Carvajal –      

FDA has approved the biological product ATryn, an anticoagulant derived from the milk of genetically engineered ("GE") goats.  The approval follows on the heels of the agency’s issuance of long-awaited guidance on its regulatory approach to GE animals, which we discussed in a prior posting.  Responses to the agency’s approval of ATryn are already raising concerns about animal welfare, environmental effects, and food safety.  FDA’s press release attempts to address all of these concerns. 

With respect to food and feed safety, the approval of ATryn is conditioned on exclusion of the goats from  the food and feed supply.  A Freedom of Information summary of the NADA lists the following as control measures supporting a conclusion that there exists a “reasonable certainty” that the GE goats won’t enter the food supply:

• Secure locked fencing around the entire facility, with double fencing around animal paddocks;
• Well maintained secure barns leading to fenced paddock and exercise yards;
• Round-the-clock staffing of the facility;
• Active on-site security with personnel supplemented with video surveillance;
• SOPs for animal identification and disposal that include procedures to ensure that all GE animals are identified by ear tag, tattoo, and implanted identification chip;
• all animals are incinerated at termination use.

Hyman, Phelps & McNamara, P.C.’s Anne Marie Murphy will present at the International Consumer Product Health and Safety Organization’s (“ICPHSO’s”) 16th Annual Meeting and Training Symposium, which is scheduled to take place from February 24-27, 2009 at the Florida Hotel and Conference Center in Orlando, Florida.  A copy of the conference agenda is available here.  Ms. Murphy, along with other panel members, will discuss questions arising from the potential effects of the Consumer Product Safety Improvement Act of 2008 ("CPSIA”) on FDA-regulated products, such as:

• Jurisdictional overlaps between the FDA and the Consumer Product Safety Commission on safety of products regulated by both agencies;
• How to prepare properly qualified General Conformity Certifications for products regulated by both agencies;
• How third-party testing for dual-regulated children's products may affect product development and manufacture; and
• How new enforcement authorities in the CPSIA potentially may affect dual-regulated products.

To register for the conference, visit ICPHSO’s website.

By Ricardo Carvajal & Susan J. Matthees –      

The FDA Globalization Act (“FDAGA”) of 2008 was “meant to stimulate discussion about how to provide adequate funding and authority for FDA to ensure safety” of products over which the agency has jurisdiction.  When we commented on that proposed legislation, we couldn’t help but make special mention of the many fees that were included.  FDAGA 2009 brings back the fees, and adds a number of new authorities – and responsibilities – for FDA and for industry.  Below we summarize some of the principal changes that are not fee-related.

FDAGA 2008 proposed several new requirements and authorities applicable to foods, including establishment of a food safety plan, safety standards for fresh produce, periodic inspections, certification of facilities and accreditation of laboratories, and mandatory notification and recall, among others.  FDAGA 2009 retains these and adds others, including:

• All facilities would be required to develop and implement a HACCP plan (conduct a hazard analysis, implement preventive controls, monitor effectiveness of those controls, and keep records).
• FDA’s access to records would be significantly strengthened, perhaps finally putting to rest the decades-long debate over the extent of FDA’s authority to access records during a food inspection. In addition, farms and restaurants would be subject to recordkeeping requirements.
• FDA’s administrative detention authority would be significantly strengthened.
• Some of the violations that were previously categorized as “prohibited acts” (e.g., failure to register or pay fees) would now render a food misbranded.
• Making false statements to a facility or laboratory certifying agent would be a prohibited act.
 
Many of these provisions (as well as those carried over from FDAGA 2008) would require FDA to issue implementing regulations or guidance, for which tight timeframes are provided.  It is not clear whether the costs of doing so would be covered by the fees that would be raised under FDAGA.  In addition, the Department of Health and Human Services (“HHS”) is tasked with taking numerous additional measures to improve surveillance and understanding of food borne illness.  If those efforts meet with success, they could result in greater capabilities to link outbreaks to specific foods, thereby helping to overcome one of the historic obstacles to successful product liability actions in the food arena – that of establishing causation.  Finally, we couldn’t help but notice that FDAGA 2009 requires HHS to conduct research to “develop methods to reduce or destroy pathogens before, during, and after processing.”  Unfortunately, getting those methods approved by FDA is another matter, as illustrated by the ongoing difficulties in getting irradiation technologies to market.
 
The sections of FDAGA 2008 that pertained to drugs included provisions for FDA inspections of manufacturing facilities, requirements for risk management plans, detailed supply chain requirements, greater recall authority for FDA, country of origin labeling, and requirements for testing of purity and identity for drug products.  The drug section of FDAGA 2009 retains many of these same provisions and includes others, such as: 
 
• Failure to pay registration fees would render a drug misbranded, but FDAGA 2009 exempts orphan drugs and certain not-for-profit medical centers from paying registration fees and allows for a waiver or reduction of fees for drugs that are necessary for public health or where the fee would be a financial hardship for the company. 
• New inspection requirements call for drug facilities to be inspected every 2 years unless the Secretary determines that once every 4 years would be sufficient. 
• No personal use exemption from the requirement that imported drugs have information demonstrating compliance with FDA requirements. 
• A drug is misbranded if the manufacturer’s Website does not list the country of origin of the active pharmaceutical ingredients and finished dosage form of the drug. 
• New “voluntary” procedures for manufacturers to follow for a recall.
 
As with the food section of FDAGA, many of the provisions in the drug section would require FDA to issue regulations or guidance.
 
FDAGA 2008 proposed several new requirements for cosmetic products, including good manufacturing practice and adverse event reporting requirements.  FDAGA 2009 retains these, expands some of them, and adds a few new ones.  Of particular interest:
 
• FDAGA 2009 retains the requirement that cosmetic manufacturers register and adds more detailed registration requirements, including annual registration of both foreign and domestic facilities and  the requirement that the Secretary keep a list of registered establishments.
• Cosmetic companies will be required to submit an ingredient list for every cosmetic manufactured. 
• More comprehensive requirements for adverse event reporting

Finally, for those of you who have been following the bouncing ball on preemption, section 2 of FDAGA 2009 makes clear that no preemption of state law is intended.

FDAGA 2008 proposed several new requirements for cosmetic products, including good manufacturing practice and adverse event reporting requirements.  FDAGA 2009 retains these, expands some of them, and adds a few new ones.  Of particular interest:

• FDAGA 2009 retains the requirement that cosmetic manufacturers register and adds more detailed registration requirements, including a requirement for annual registration of both foreign and domestic facilities and a requirement that the Secretary keep a list of registered establishments.
• Cosmetic companies will be required to submit an ingredient list for every cosmetic manufactured. 
• More comprehensive requirements for adverse event reporting

Finally, for those of you who have been following the bouncing ball on preemption, section 2 of FDAGA 2009 makes clear that no preemption of state law is intended.

By Ricardo Carvajal –      

USDA has suspended, and proposes to debar, Peanut Corporation of America ("PCA") from “participating in government contracts or subcontracts, as well as federal non procurement programs,” among other activities.  The suspension is for one year and is effective immediately.  The proposed debarment would be effective for three years.  PCA has 30 days to object to USDA’s actions. In its press release announcing the actions, USDA had harsh words for PCA, alleging that the firm “lacks business integrity and business honesty.”

Meanwhile, in a written statement submitted by FDA/CFSAN Director Stephen Sundlof to the Senate Committee on Agriculture, Nutrition and Forestry, FDA reiterated its confidence that the PCA facility in Georgia is the source of the current Salmonella outbreak, and confirmed that FDA’s Office of Criminal Investigations is investigating.  FDA has taken the somewhat unusual step of posting the Form 483 issued at the conclusion of its recent inspection of the Georgia facility on the internet.  The inspectional observations listed in the Form 483 detail numerous apparent failures to adhere to good manufacturing practice requirements.

The Center for Business Intelligence (“CBI”) will hold its 2nd Annual Summit on Biosimilars and Follow-On Biologics on March 10-11, 2009.  The Conference will be held at the Marriott Baltimore Inner Harbor at Camden Yards in Baltimore, Maryland.  A copy of the conference brochure is available here.  Hyman, Phelps & McNamara’s Kurt R. Karst will present at the conference on the patent and non-patent market exclusivity provisions of follow-on biologic legislation that has been introduced. 

The CBI conference is intended to provide participants with the opportunity to evaluate follow-on biologic legislation while also investigating the guidelines being used in other countries – and most importantly, how these guidelines have affected company strategies, profits and the economic landscape.  Key topics to be addressed at the conference include:

• WHO Guidance, expectations and implications for globally accepted biosimilar standards
• The similarities, differences and potential impact of Canadian biosimilar legislation
• Naming concerns for biosimilar products and post-launch tracking
• The FTC’s perspective on biologic fair competition
• The exclusivity issues in proposed legislation
• Lessons learned from pharmaceutical patent litigation
• How the criteria for comparability is being/should be established
• The economic implications of the EU approval pathway
• The testing, distribution and pricing of biosimilars in India, China and Brazil

Special FDA Law Blog Discount – CBI is offering FDA Law Blog readers a $400 discount off of the registration fee.  To register for the conference, go to the CBI website and enter the following code – KZG958.

By Kurt R. Karst –      

The American Intellectual Property Law Association (“AIPLA”) recently submitted a letter to FDA concerning § 4 of the recently enacted “QI Program Supplemental Funding Act of 2008” (the “QI Act”).  (The "QI" stands for Qualifying Individual).  As we previously reported, the QI Act was enacted on October 8, 2008 and amended the FDC Act to add new § 505(v) – “Antibiotic Drugs Submitted Before November 21, 1997” – to create Hatch-Waxman benefits for so-called “old” antibiotics. 

In November 2008, FDA issued a draft guidance document describing the Agency’s current thinking on the implementation of § 4(b)(1), which includes three transition provisions on Orange Book patent listing, certification, and 180-day exclusivity for each ANDA applicant that not later than 120 dates after enactment of the QI Act (i.e., February 5, 2009) amends a pending application to contain a Paragraph IV certification to a newly listed antibiotic drug patent.  FDA’s latest Paragraph IV Certification List shows two entries with a “PIV received prior to 2/5/2009” notation: (1) DORYX (doxycycline hyclate) Delayed-Release Tablets; and (2)  SOLODYN (minocycline HCl) Extended Release Tablets.  Patent infringement lawsuits have been initiated with respect to the Orange Book patent listings for each drug product – see the compalints here (DORYX), here (DORYX), and here (SOLODYN).  (Also, as a point of interest, earlier this week, FDA responded to a citizen petition concerning generic SOLODYN.)

AIPLA’s letter to FDA requests that the Agency establish a docket requesting public comment on QI Act implementation, similar to the docket FDA established after the enactment of the 2003 Medicare Modernization Act (“MMA”).  In addition, AIPLA raises three issues for FDA to consider as the Agency works to implement the QI Act: (1) the availability of 30-month stays with respect to patents submitted to FDA for Orange Book listing under the QI Act transition provisions; (2) the availability of additional exclusivity given the limitations described in FDC Act § 505(v)(3)(A); and (3) the availability of exclusivity for old antibiotics covered under FDC Act § 505(v)(2)(A).  With respect to the availability of a 30-month stay, AIPLA comments that:

If FDA interprets the law such that the amendments made to the FDC Act by the MMA apply, then presumably no 30-month stay would apply to an ANDA applicant with a pending ANDA that amends such application to add a Paragraph IV certification to a newly-listed Orange Book patent.  It is unclear, however, whether FDA intends to interpret the law in such manner, or whether FDA believes that the law could be interpreted to permit a 30-month stay under such circumstances, similar to pre-MMA version of the FDC Act. 

FDA’s February 3, 2008 approval of an ANDA for generic SOLODYN (with 180-day exclusivity) does not address the availability of a 30-month stay, because a patent infringement lawsuit was not brought within the statutory 45-day period. 

FDC Act § 505(v)(3)(A) – “Limitations — Exclusivities And Extensions” – states that FDC Act §§ 505(v)(1)(A) and (2)(A) “shall not be construed to entitle a drug that is the subject of an approved application described in [FDC Act §§ 505(v)(1)(B)(i) or (2)(B)(i)], as applicable, to any market exclusivities or patent extensions other than those exclusivities or extensions described in [FDC Act §§ 505(v)(1)(A) and (2)(A)].”  AIPLA comments that “[w]hile FDC Act § 505(v)(3)(A) clearly places limits on how the new law can be interpreted, it is unclear whether it is also intended to limit the availability of” pediatric and orphan drug exclusivity under FDC Act § 505A and § 527, respectively. 

Finally, FDC Act § 505(v)(2)(A) states that an application for an antibiotic drug submitted to FDA after October 8, 2008, and which antibiotic drug was the subject of an application submitted under FDC Act § 507 but not approved by FDA before the enactment of the 1997 FDA Modernization Act “may elect to be eligible for, with respect to the drug,” a period of 3-year exclusivity “and” a period of 5-year NCE exclusivity, or a PTE under 35 U.S.C. § 156, subject to the requirements for obtaining such patent or non-patent exclusivity.  AIPLA’s letter notes that:

The use of the conjunctive “and” in FDC Act § 505(v)(2)(A) is curious.  It is unclear how a drug can simultaneously qualify for both 3-year “new use” exclusivity and 5-year [New Chemical Entity] exclusivity. . . . Congress’ use of the word “and” might have been intentional, such that an old antibiotic drug covered under FDC Act § 505(v)(2) can qualify for 3-year exclusivity for a new condition of use after an initial NDA approval that would qualify for 5-year exclusivity or a [Patent Term Extension] – as an old antibiotic drug covered under FDC Act § 505(v)(2) does not appear to convert to an old antibiotic drug covered under FDC Act § 505(v)(1) once it is initially approved. Under this interpretation, 3-year and 5-year exclusivity are not granted simultaneously, but rather sequentially, provided the requirements for granting such exclusivity are met.

Given the interest we have seen in QI Act implementation issues, FDA will likely receive substantial comment from interested parties if the Agency decides to open a public docket.   

LATE-BREAKING NEWS:

• FDA has received a citizen petition requesting that the Agency address whether the 30-month stay provisions of the Hatch-Waxman Amendments apply to a pending ANDA for a generic version of an old antibiotic drug (i.e., DORYX), which ANDA contains a Paragraph IV certification to a patent listed in the Orange Book in accordance with the QI Act.  The petition argues that the plain language of the QI Act requires application of the 30-month stay provisions of the original Hatch-Waxman Amendments, instead of the version of the statute amended by the MMA.

By Ricardo Carvajal –      

In January 2008, FDA received a citizen petition asking it to “issue a formal determination that when applied to foods and dietary supplements, California's Proposition 65 causes consumer confusion, ‘misbrands’ safe and wholesome products, and frustrates FDA's ability to carry out its statutory mandates.”  California’s recent Proposition 65 action against lead in dietary supplements appears to be reinvigorating that effort.  FDA has received a supplemental submission to the docket established for the petition noting that California’s action is founded on an FDA survey showing that the products at issue posed no safety concerns.  The supplemental submission also highlights the cooperation between California’s Attorney General (AG) and private plaintiffs in the case, and attacks the AG’s inclusion of claims under the state’s unfair competition law, which would give rise to additional penalties and extend the statute of limitations.  If the recent news about the potential presence of mercury in high fructose corn syrup begets another Proposition 65 action, we’re betting that this citizen petition will find a few more friends.

By Kurt R. Karst –      
 
On February 2, 2009, the Federal Trade Commission (“FTC”) announced that the Commission filed a complaint in federal district court challenging agreements in which Solvay Pharmaceuticals, Inc. allegedly paid two generic drug companies to delay generic competition to Solvay’s drug product ANDROGEL (testosterone gel) 1%.  Specifically, the FTC’s complaint alleges that in 2006, Solvay agreed to share its profits with certain  generic competitors – one of whom already has ANDA approval and is eligible for 180-day exclusivity – provided they would not launch their generic versions until 2015.  Under FDC Act § 505(j)(5)(D)(i)(V), which the Medicare Modernization Act (“MMA”) made retroactive to pre-MMA cases, if there is a final court decision that an agreement violates antitrust laws, then 180-day exclusivity is forfeited.

On the heels of the FTC’s announcement, Senators Herb Kohl (D-WI) and Chuck Grassley (R-IA) introduced S. 369, “The Preserve Access to Affordable Generics Act.”  According to a press release issued by Sen. Kohl, “[t]he legislation would make illegal anti-competitive, anti-consumer patent payoffs in which brand name drug companies pay generic manufacturers millions of dollars to keep generic competition off the market.”  (Check out our new “FDA Legislation Tracker” for a copy of the bill and other FDA legislation.)  Sen. Kohl introduced similar legislation in the 110th Congress – S. 316.  Rep. Henry Waxman (D-CA) introduced the House version of the bill – H.R. 1902.  Similar to previous versions, the latest iteration of the bill (S. 369) would:  

• Amend the Clayton Act to add new § 29 (Unlawful Interference With Generic Marketing) making it unlawful for a person, in connection with the sale of a drug product, to be a party to any agreement resolving or settling a patent infringement claim in which: (1) an ANDA applicant receives anything of value; and (2) such generic applicant agrees not to research, develop, manufacture, market, or sell the generic product for any period of time;

• Amend MMA § 1112 to set forth additional filing requirements related to agreements between brand name and generic drug companies; and

• Amend the 180-day exclusivity forfeiture provision at FDC Act § 505(j)(5)(D)(i)(V) to provide that an ANDA applicant that is a “first applicant” forfeits exclusivity if an agreement violates new § 29 of the Clayton Act.