By David B. Clissold –

Last week, House Democrats and a consortium of public health organizations turned up the heat on FDA to issue “deeming” regulations that would bring electronic cigarettes and other types of tobacco products under the Agency’s jurisdiction. The Family Smoking Prevention and Tobacco Control Act (“Tobacco Control Act”), Pub. L. No. 111-31, 123 Stat. 1776 (2009), broadly defined the term “tobacco product” to include “any product made or derived from tobacco that is intended for human consumption, including any component, part, or accessory of a tobacco product.”  However, the Tobacco Control Act only provided FDA the immediate authority to regulate cigarettes, cigarette tobacco, roll-your-own tobacco, and smokeless tobacco.  All other “tobacco products” could only be regulated if FDA first issued regulations “deeming” such other tobacco products to be subject to the Federal Food, Drug, and Cosmetic Act (“FDC Act”). 

In a letter dated September 16, 2013, Representatives Waxman (D, CA), DeGette (D, CO), Pallone (D, NJ), and Dingell (D, MI) urged Dr. Margaret Hamburg, Commissioner of FDA, to issue deeming regulations that would assert jurisdiction over electronic cigarettes.  On the same day, these representatives sent a letter to the Chairmen of the House Committee on Energy and Commerce, Subcommittee on Oversight and Investigations, and Subcommittee on Health urging a Congressional hearing on e-cigarettes and other tobacco products.  Among other topics, the authors recommended that the hearing examine trends in the use of e-cigarettes, cigars, and pipe tobacco and statutory changes needed to bolster FDA’s ability to regulate these products.

Finally, the Tobacco Control Legal Consortium filed a Citizen Petition urging FDA to assert jurisdiction over additional tobacco products, including waterpipes (“hookahs”) and electronic cigarettes.

As noted in the letter to Dr. Hamburg, FDA has been “working on these ‘deeming’ regulations for years.”  It remains to be seen whether these additional efforts will encourage the Agency to propose deeming regulations, or whether the Agency believes that additional statutory authority or clarity may be needed first.

By Kurt R. Karst –   

The titles – and sometimes even the content – of some of our posts are inspired by the things we experience (or have experienced) in our regular, non-attorney lives.  For years now we’ve weaved together with food and drug law topics such seemingly disparate things as movies (A Few Good Men and Fletch – see our posts here and here), television (Star Trek and Monty Python and the Holy Grail – see here and here), and even Frau Rommelfanger’s seventh grade German class (see here).  We hope these (clever) mash-ups grab readers’ attention and keep you interested in things that can, at times, seem boring or hypertechnical, or that may not be in your bailiwick, but that matter nevertheless. 

Although one of our posts from way back in 2007 shortly after we started this blog was inspired by the Bard of Avon, William Shakespeare, and the famous line he penned in Hamlet – “To be, or not to be” (see here) –  we’ve never dragged the Bard’s Romeo and Juliet into food and drug law.  As you can see, now we have.  And it’s a nice fit with a Citizen Petition (Docket No. FDA-2013-P-1153) the Generic Pharmaceutical Association (“GPhA”) recently submitted to FDA on biosimilar naming.  If Act I of what will likely be a long-running and many-act play on biosimilars concluded with the March 23, 2010 enactment of the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”), then Act II has been all about topics related to, but that are not specifically covered by, the BPCIA.  Act II, Scene I is about the continuing state-by-state battle over biosimilar substitution laws (see our scorecard here).  Act II, Scene II is about the battle over whether biosimilar versions of their brand-name reference product counterparts should each be assigned a distinct nonproprietary name specific to the manufacturer.  (Act III, which is only in early development, may be based on the April 2012 Citizen Petition – Docket No. FDA-2012-P-0317 – submitted by Abbott Laboratories requesting that FDA not accept for filing, file, approve, or even discuss with any company any application or any investigational new drug application for any biosimilar that cites as its reference product any product for which the BLA was submitted to FDA prior to the date on which the BPCIA was enacted (see our previous post here)). 

In Act II, Scene II of Romeo and Juliet – the famous balcony scene – Juliet argues that the names of things don't matter, and all that matters is what things are:

'Tis but thy name that is my enemy;
Thou art thyself, though not a Montague.
What's Montague? it is nor hand, nor foot,
Nor arm, nor face, nor any other part
Belonging to a man. O, be some other name!
What's in a name? that which we call a rose
By any other name would smell as sweet;
So Romeo would, were he not Romeo call'd,
Retain that dear perfection which he owes
Without that title. Romeo, doff thy name,
And for that name which is no part of thee
Take all myself. 

While it might be true that names don’t matter when it comes to matters of love, names do matter in other contexts, like in food and drug law.  As such, GPhA respectfully disagrees with the Bard and says that names do matter when it comes to biosimilars! 

In its September 17, 2013 Citizen Petition, GPhA requests that FDA implement its International Nonproprietary Name (“INN”) naming policy equally to all biologics, whether that biological product is approved as a biosimilar under Section 351(k) of the Public Health Service Act (“PHS Act”) as added by the BPCIA, or as a brand-name reference product under PHS Act § 351(a).  More specifically, GPhA says that “because all biologics approved under the Section 351(k) pathway are ‘highly similar’; and thus, have no clinically meaningful differences from the reference protein product (RPP) [they should] share the same INN name as the RPP, just as comparable originator products produced by a change in a manufacturing process or facility (post-change product) share the same INN as the original RPP (pre-change product).” (Emphasis in original)

The BPCIA, as enacted, does not specifically address biosimilar product naming.  Although previous biosimilar legislation did address the issue, such as Representative Henry Waxman’s (D-CA) Access to Life-Saving Medicine Act (H.R. 1038) and Senator Judd Gregg’s (R-NH) Affordable Biologics for Consumers Act (S. 1505) (both from 2007), it was ultimately decided that naming provisions should not be included in the final biosimilars bill.  Given this history, GPhA says that “[w]ithout new statutory authority, FDA lacks specific authority to require separate INNs for biosimilars, and existing conventions for biologics should be expected to prevail.” 

Referencing a 2006 policy paper FDA sent to the World Health Organization (“WHO”) in support of WHO naming conventions, GPhA says:

FDA clearly supports the original purpose of the INN (to identify the active ingredient of a product), rejects the use of nonproprietary names to communicate interchangeability, and states that concerns about pharmacovigilance “transcend a naming convention,” explaining that “[i]t would be the FDA's preference that INNs continue to be granted based only on molecular characteristics and pharmacological class of the active ingredient(s). ”  In this paper FDA agrees that there should be no change in global policy and rejects distinctive INN designations for biosimilars. . . .  While [the] BPCIA was enacted subsequent to this policy position being presented to WHO, nothing in the new statute is incompatible with the 2006 FDA position on biosimilar naming.

Moreover, says GPhA, FDA is obligated to apply its standards equally to all applicants and products:

Requiring unique INNs for biosimilars while allowing sharing of INNs for other biologics in comparable situations would run contrary to this tenet.  FDA routinely allows originator biologic products in the same class approved under separate 351(a) or 505(b) applications and using different manufacturing methods implemented by different sponsors to share the same INN.  For example, a number of Anti-hemophilic Factor (Recombinant) products, some of the most complex biologics licensed in the US, share the same INN.  [(Appendix A to the Petition is an extensive list of products that share INNs.)]  Further, FDA has for many years without question authorized originator manufacturers to modify biologics' manufacturing processes and develop biologics that have minor changes and differences that are not clinically meaningful without requiring a change in non-proprietary name.  This authorization is contingent on a sponsor submitting data that the post-change product is “comparable” to the pre-change product.  If the sponsor demonstrates such comparability FDA deems the (pre- and post-change) products interchangeable for all indications irrespective of the mechanism of action being understood.  The standard for both comparability and biosimilarity is “highly similar” quality attributes.

And what about concerns raised by some that distinct biosimilar names are necessary to facilitate accurate attribution of adverse events?  GPhA addresses that issue as well and says:

GPhA concurs that any concerns with pharmacovigilance call for tailored solutions capable of fixing the actual problem without creating additional confusion.  Unsupported pronouncements of inadequate tracking capabilities for biosimilars with the same INN as their RPPs represents, at best, a hypothetical problem given that no biosimilars have yet been approved in the US and Europe has been successful at tracking biosimilars which share INNs with their RPPs. . . .  Currently, a well-established process exists to track product quality problems that does not rely prirnarily on INNs, but instead uses a product's brand name, manufacturer, lot number and NDC to track quality and safety events.  GPhA does not believe requiring unique I NNs for biosimilars could remedy the poorly defined concerns and, instead would cause confusion and potential harm to patients by interfering with the present system.  In contrast, we fully support vigorous enhancement of track and trace and education of physicians and pharmacists to include NDCs, manufacturer names and other relevant identifiers on all safety reports.  This applies equally to all biologics, and must not be used as a wedge to create an anticompetitive barrier to biosimilar development and commercialization.

On the other side of the debate are organizations like the Alliance for Safe Biologic Medicines (“ASBM”).  As we previously reported, ASBM has urged FDA to adopt unique non-proprietary names for all biological products licensed under the PHS Act, and in particular biosimilar versions of reference products (even those that are interchangeable).

Other than FDA’s 2006 policy paper, the Agency has remained pretty silent on the biosimilars naming issue.  Over the summer, there was a rumor circulating that FDA was in the process of drafting a guidance document on biosimilar naming issues; however, nothing has been confirmed.

In a typical three-act play, the main character encounters a complication in Act II – an obstacle that prevents that character from achieving his or her dramatic need – and reaches his or her lowest point.  In Act II of the biosimilars play at hand, we’re not sure yet who – the brand or generic side of the debate – is playing the role of the main character.  But whoever that is is sure to be disappointed with the outcome.   

Update:

• GPha Press Release: Generic Industry Calls on FDA to Uphold Consistent, Proven International Standard for Biosimilar Naming; Citizen Petition Urges Identical, Non-proprietary Names to Promote Patient Access to More Affordable Biosimilars

By Wes Siegner & Paul M. Hyman – 

The term “medical food” was first defined by statute in the Orphan Drug Act Amendments of 1988.   The medical food category is closely related to the already existing category of “foods for special dietary use,” authorized by the Federal Food, Drug, and Cosmetic Act (FDC Act), section 403(j).  In very simplified terms, medical foods and foods for special dietary use are foods that are formulated to meet the needs of individuals with diseases or conditions that may benefit from ingestion and/or clinical management by specialized foods.  Unlike most other foods, the labeling for foods that fall in these categories may legally mention the disease or condition for which they are intended.  As our understanding of nutrition and its role in both normal and disease processes of the human body advances, many diseases and conditions that could only be addressed through drug therapies are now being improved by combination drug/food therapies.  Access to and development of medical foods is, therefore, of enormous potential importance to public health, both because of the potential for improved health as well as the opportunity to reduce healthcare costs. 

Within the last month, FDA has issued a draft medical food Q&A guidance and a final guidance on INDs that will dramatically impact the availability and development of medical foods.  Previous blogposts on these guidance documents can be viewed here and here.  These guidances also further illustrate the FDA trend of issuing important and controversial policy decisions through legally “non-binding” guidance (see our previous post here), which short-cuts the notice and comment rulemaking process, deprives stakeholders of a meaningful opportunity to change FDA policy, and makes legal challenge to these new policies problematic at best.

Regardless, it is essential for patient groups, physicians, academic researchers, and the industries that these guidances will negatively impact to make their voices heard.

FDA’s Draft Medical Food Q&A

Medical foods help to manage a disease or condition by meeting the “distinctive nutritional requirements” that the disease or condition creates.  As FDA points out in its medical food draft guidance, certain rare inborn errors of metabolism (“IEMs”) such as phenylketonuria (“PKU”) require careful manipulation of the diet to avoid certain nutrients (phenylalanine in the case of PKU).  Failure to do so can lead to serious medical consequences, including death.  It is difficult, but not impossible, for individuals with these diseases to accomplish the necessary dietary manipulation without medical foods that are specially formulated to help manage the disease.  In FDA’s view, “[m]edical foods become indispensable for individuals with these IEMs in order to meet the daily requirements of essential nutrients and to limit the metabolic disturbances associated with the particular IEM.”  Q&A 17. 

However, there is a growing recognition that medical foods can also play important disease management roles in a much broader array of diseases where distinctive nutritional requirements have been established, including cancer, AIDS, arthritis, heart disease, osteoporosis, and gastrointestinal diseases, among others.  As new research into disease, nutrition, and health shows better ways to manage disease through nutrition, medical foods, which are inherently safe and do not therefore require years of costly product safety and efficacy testing and FDA premarket approval, are increasingly becoming a cost-effective component of disease management. 

FDA’s new draft Q&A, as well as a number of recent warning letters to medical food marketers, indicate that FDA is determined to narrowly interpret the definition of “medical food” and prohibit the marketing of many novel products that might fit into this category and benefit patient health.  One of FDA’s primary tools in restricting access to the medical food market is a criterion that FDA promulgated in a medical food labeling regulation, 21 C.F.R. §101.9(j)(8), but that does not exist in the statutory definition.  This regulation requires that, to qualify for an exemption for medical foods from otherwise applicable food labeling requirements, the food must supply “medically determined nutrient requirements, the dietary management of which cannot be achieved by the modification of the normal diet alone.”  This concept is nowhere implied in the statutory definition, and it makes no sense from a medical perspective in the context of addressing the management of a patient’s disease or condition.

FDA’s draft medical food Q&A guidance relies particularly on that restriction in an attempt to eliminate what is likely the largest potential patient base for medical food products, patients with diabetes.  FDA recognizes that there are distinctive nutritional requirements that are critical to the health of all individuals with diabetes mellitus (“DM”), but nonetheless answers “No” to the following question – “Does FDA consider type 1 or type 2 DM to be conditions for which a medical food could be labeled and marketed?”  Draft medical food guidance, Q&A 22 and 23.  What is FDA’s explanation?  “Diet therapy is the mainstay of diabetes management.  A regular diet can be modified to meet the needs of an individual affected by either type of DM.”

This new policy position ignores the essential role that food convenience plays in compliance with the often difficult dietary manipulations that are needed in a variety of diseases and conditions, including diabetes.  Why should FDA want to make it difficult for patients to comply with diets that are essential to the management of serious, life-threatening diseases?  The new policy position is also arbitrary, as FDA recognizes that medical foods are essential to the management of certain genetic diseases, such as PKU, where dietary manipulation is also difficult but still possible, but not others, such as diabetes.  FDA’s draft guidance is internally inconsistent on this point (see Q&A 17) and raises the question, just how difficult does dietary manipulation have to be for FDA to permit a medical food to be marketed?  As medical foods are inherently safe, it would appear that the question of whether dietary compliance, and therefore patient health, will benefit from a medical food should be left to the medical community, not to FDA. 

Indeed, this approach amounts to FDA’s dictating the therapeutic regimen for these patients, substituting the agency’s judgment for that of the clinician.  No one would stand for FDA’s allowing only one drug or course of therapy to be used for a patient, despite the availability of other effective measures.  Yet FDA here essentially would do just that – prohibit the use of available, safe and effective agents of dietary management of the patient’s disease if, in FDA’s view, management might be accomplished by modification of the diet, regardless of how impractical that might be.

FDA’s draft guidance also leaves open the question of whether there might be medical foods appropriate for pregnant women, as well as the question of whether medical foods intended to manage the wide variety of diseases and conditions that are not “inborn errors of metabolism” would qualify for medical food status.  However, FDA’s draft Q&A combined with a recent increase in FDA warning letters suggests that the entire medical food category is under increased scrutiny and risk of FDA enforcement.  The impact, if the guidance is not revised, will be to stifle creative and cost-effective use of nutrition to improve patient health through use of medical foods. 

FDA’s Final IND Guidance

FDA’s final IND guidance potentially will require FDA approval of an investigational new drug application (“IND”) for most, if not all, clinical studies intended to support the benefits of any medical food.  The “non-binding” medical food IND requirement was inserted into the final guidance in a new section D.2., titled “Conventional Food,” even though there was no such provision in the draft guidance FDA issued in 2010, thereby making any comment on this new policy impossible before FDA issued the final guidance. 

The new requirement poses significant challenges to clinical studies into disease management:

• The final IND guidance attempts to distinguish between medical food studies that do not require an IND – safety studies and studies of the taste, aroma, or nutritive value of a medical food – and those that do require an IND – studies into how the medical food might affect the structure or function of the body in ways that do not derive from “nutritive value,” however FDA might interpret that term.  As set forth by FDA, this distinction is difficult if not impossible to comprehend. The guidance is intended to affect the behavior of institutional review boards ("IRBs") that are not usually willing to second-guess FDA policy.  Therefore, IRBs are likely to require INDs unless FDA is willing to agree that an IND is not needed, which FDA is unlikely to do. 
• The need to conduct studies under an IND will put many novel medical foods in a quandary, as FDC Act §301(ll) potentially prohibits the marketing of a food where the food is first studied under an IND, even if the study is ultimately intended to support food rather than drug use.  Medical food companies might attempt to avoid the prohibition by marketing products as foods or dietary supplements prior to conducting medical food studies, or by using only ingredients already widely consumed as food, but this strategy increases the risk that FDA will challenge the medical food on the basis that the nutritional requirement can be met by modification of the normal diet.  Whether this conundrum is deliberate or is a result of FDA’s failure to think through its new policy, first announced in FDA’s final guidance, is unclear.  Regardless, because IRBs will take FDA’s guidance and gospel, the final guidance will restrict medical food development and research into the understanding of nutrition and disease generally.

In order to create the requirement for an IND for medical food studies, FDA’s IND guidance reverts to a legal theory for regulating structure/function claims for foods that we believed (or hoped) the agency had long ago abandoned. 

Consistent with case law interpreting the “other than food” exception as applying to articles consumed primarily for taste, aroma, or nutritive value, FDA regulates conventional foods (including infant formula) that are intended to affect the structure or function of the body as foods, not drugs, as long as the intended structure or function effect derives from the product’s character as a food — its taste, aroma, or nutritive value.   

IND Guidance at 13 (citing Nutrilab v. Schweiker, 713 F.2d 335 (7th Cir. 1983)).  FDA then goes on to narrowly construe the term “nutritive value” by stating, as an example of a food study that would require an IND, that “a study of the effect of soy isoflavones on bone metabolism would [require an IND].”  Id. 

Contrary to FDA’s assertion that its interpretation is “consistent with case law,” FDA’s reliance on Nutrilab for the agency’s narrow interpretation of the “other than food” provision of the FDC Act is in direct conflict with the opinion of the Seventh Circuit as well as subsequent case law that relied on Nutrilab.  That case law establishes that, in the view of the courts, a “food” may properly make any claim in labeling that is truthful and nonmisleading about a “physiological effect” of the food, including a physiological effect of a component of the food, on the structure or function of the human body, provided that the claim does not represent that the product is intended to cure, treat, mitigate, or prevent disease (which would create “drug” status for the product), and does not “characterize the relationship” between a “substance” and “disease,” “damage,” or “dysfunction” of the body (which would meet the definition of a “health claim” and create separate requirements.  713 F.2d at 338 (“To hold as did the district court that articles used as food are articles used solely for taste, aroma or nutritive value is unduly restrictive since some products such as coffee or prune juice are undoubtedly food but may be consumed on occasion for reasons other than taste, aroma, or nutritive value.”); American Health Products Co., Inc. v. Hayes, 574 F. Supp. 1498, 1507 (S.D.N.Y. 1983), aff’d, 744 F.2d 912 (2d Cir. 1984) (“[I]f an article affects bodily structure or function by way of its consumption as a food, the parenthetical [i.e., the ‘(other than food)’provision in 21 U.S.C. §321(g)(1)(C)] precludes its regulation as a drug notwithstanding a manufacturer's representations as to physiological effect . . . .  The presence of the parenthetical in [21 U.S.C. §321(g)(1)(C)] suggests that Congress did not want to inhibit the dissemination of useful information concerning a food’s physiological properties by subjecting foods to drug regulation on the basis of representations in this regard.”) 

FDA’s IND guidance is yet another example of the agency, contrary to law, “subjecting foods to drug regulation” by requiring any study of the physiological effect of a food that does not derive from “nutritive value” to first be approved as a drug study through FDA’s IND approval process.  As FDA’s isoflavone example illustrates, perhaps intentionally, FDA has so muddled the picture as to what effects of food derive from “nutritive value” and which do not, that even experts will find it difficult to advise clients or, more important, IRBs, when an IND is required.  This will predictably lead IRBs to either require INDs for virtually all clinical studies that examine structure/function effects or any beneficial effects of foods, or to require that FDA’s drug center be consulted before conducting such studies, which will likely yield the same result.

Oddly, according to FDA’s IND guidance, it appears that if the same isoflavone study on bone metabolism were conducted as a dietary supplement study rather than a conventional food study, no IND would be required, since “a dietary supplement is not considered a drug and is not subject to the premarket approval requirements for drugs if the intended use for which it is marketed is only to affect the structure or any function of the body (i.e., not intended to be used for a therapeutic purpose).”  IND Guidance at 12. 

What Should Be Done?

The question for patients, physicians, academic researchers and industry is “now what?”  Some short term measures may bring temporary results, including:

• File comments – FDA has withdrawn and/or rewritten controversial draft and final guidance in the past in response to negative comments.  Given the important medical, research, and patient health implications of FDA’s recent guidances, comment from patients, researchers, and medical specialty associations will be important to a change of FDA’s course. 
• Enlist the help of Congress – congressional representatives can effectively influence FDA’s course through letters, hearings, and other measures.
• Some companies in the medical food arena may qualify as small businesses, which may make it possible to engage the Small Business Administration (“SBA”).  SBA has been an effective advocate for small business in other flawed FDA initiatives.
• Carefully design study protocols to avoid IND implications, or if that is not possible, conduct studies that IRBs and FDA will not permit in the U.S. without an IND in Canada or Europe.

A longer-term industry strategy is also needed.  It is clear that FDA is determined to severely restrict both access to and research on medical foods in the U.S., regardless of the potential importance of such products to public health and the effect on the cost of medical treatment.  Currently, there is no trade association devoted to protecting the interests of the medical food industry, but it appears that the time has arrived for one to be created.  A trade association could help the industry interact more consistently with FDA, would help develop long-term allies in Congress, and provide industry with the necessary resources to litigate critical issues if necessary. 

By Riëtte van Laack –

As previously reported here, in July, the American Meat Institute and several international meat industry organizations filed a lawsuit in an effort to stop the Agricultural Marketing Service ("AMS") of the USDA from implementing the Country of Origin Labeling ("COOL") rule, which requires packages of beef, pork and poultry products to say where animals were raised, slaughtered, and processed.  In August, four agricultural and consumer groups, the National Farmers Union, U.S. Cattlemen's Association, Sheep Industry Association and the Consumer Federation of America, filed to intervene in the case in support of the new COOL regulation. 

On September 11, 2013, Judge Ketanji Jackson of the U.S. District Court for the District of Columbia issued an 80-page ruling holding that USDA can continue implementing its regulations for mandatory country-of-origin labeling.

Plaintiffs argued that the amended rule constituted unduly compelled speech in violation of the First Amendment of the Constitution.  However, the Judge disagreed.  She held that the amended Final Rule mandates ‘“purely factual and uncontroversial disclosures about where an animal was born, raised and slaughtered”’ and constitutes compelled commercial speech.  This type of speech is not subject to the strict scrutiny standard.  In fact, “when the compelled speech is commercial and purely factual in nature, the speaker’s First Amendment rights are not unduly burdened “‘as long as [the] disclosure requirements are reasonably related to the [government’s] interest in preventing deception of consumers.’”  The judge determined that there is “clearly a reasonable relationship between the government’s interest in preventing consumer confusion about the origins of muscle cut meat, on the one hand, and the required disclosure of specific production step information, on the other.”  Thus, Plaintiffs’ First Amendment challenge is unlikely to be successful. 

Plaintiffs’ loss does not mean that the battle is over.  On September 12, 2013, they appealed the denial of the preliminary injunction (D.C. Circuit Case No. 13-5281).  Moreover, in August, Canada and Mexico filed a complaint with the World Trade Organization, and a ruling is expected later this year.  Thus, the future of the COOL regulation remains uncertain.

By Etan J. Yeshua –

Three months after announcing a strategic research plan to support its regulatory agenda, FDA's Center for Food Safety and Applied Nutrition ("CFSAN") this week announced its regulatory priorities for 2013 and 2014, giving those in the food, dietary supplement, and cosmetic industries an indication of what to expect from FDA in the near future.  The priorities include publishing and finalizing rules to enforce the Food Safety Modernization Act’s ("FSMA’s") food safety requirements and the Affordable Care Act’s menu labeling provisions, revising food labeling regulations, finalizing the Agency’s controversial New Dietary Ingredient ("NDI") guidance, developing a strategy to regulate energy drinks, and issuing various guidance documents regarding cosmetics.

The six “program goals,” most of which correspond to a dozen or so specific objectives are to:

1. Reduce foodborne illness rates and cosmetic injury rates each year;
2. Establish regulations, policies, guidances, and inspection and compliance strategies based on best science, prevention, and public health risk;
3. Increase compliance with newly created preventive control standards across the farm-to-table continuum;
4. Improve public health indicators through better nutrition and dietary choices;
5. Develop and swiftly deploy the fastest most effective methods for identifying, containing, and eliminating food and cosmetic hazards; and
6. Achieve optimal use of staff and resources.

The full list of over 80 specific objectives is available on FDA’s website divided by program goal, but we’ve identified a few that we think may be of particular interest to our readers and organized them by subject area.  Check the FDA Law Blog for regular updates as FDA moves forward with the rules, guidance documents, and policies that the Agency forecasted this week.

Food

Continuing its effort to implement FSMA, CFSAN plans to issue new regulations regarding food safety, and will develop approaches to several topics about which the Agency has yet to finalize its position.  By the end of 2014, FDA plans to publish proposed rules for preventive controls in food transportation and for recordkeeping requirements for high-risk foods.  By 2015, FDA plans to finalize rules regarding intentional food contamination, third party auditor accreditation, and preventive controls for food processing facilities and produce safety.  Although we do not know whether to expect a proposed rule, draft guidance, or something else, FDA also plans to “address [an] approach to determine” the most significant foodborne contaminants (for FSMA § 104(a)) and an approach to determine high risk foods (for FSMA § 204(d)(2)).

To promote better dietary choices, FDA plans to roll out a number of new food labeling regulations.  In the coming year, CFSAN plans to propose rules to update the nutrition facts label and serving size information and, before 2015, intends to propose rules about dietary guidance statements in food labeling (“to improve consumer understanding of the usefulness of a food or a category of foods in maintaining healthy dietary practices”); CFSAN also plans to issue final guidance about labeling foods made without bioengineered ingredients (e.g., “GMO-free”).  In 2014, FDA intends to finalize rules that are required by the Affordable Care Act (and were delayed earlier this year) to require nutrition information on menus and on vending machines.  To supplement these efforts, CFSAN also plans to complete a review of “nutrition and related activities to identify, with respect to nutrition in America, what problems we have now, in the near future, and in the next 10–15 years, and how CFSAN might best address them.”  Together with this review, and for implementation in 2015, FDA will “complete a plan . . . to promote broad, gradual reduction of added sodium in the food supply.”

Other goals of note include determining whether to issue guidance or otherwise weigh in on arsenic levels in foods other than apple juice and rice, and publishing draft guidance on conflicts of interest for experts participating in GRAS panels—an issue spurred in part by the PEW Charitable Trust’s Food Additives Project.

Dietary Supplements

In the supplement area, FDA may be making big waves in the coming years.  The Agency intends to finalize its draft guidance on new dietary ingredients (NDIs) in 2014.  The draft guidance has been a source of much recent debate between FDA and the supplement industry. 

FDA also plans to “modernize [the] postmarket surveillance system for regulating dietary supplements.”  Earlier this year, the National Institute of Health launched a database of supplement labels—a resource that the Agency may very well use in this effort.

Weighing in on a topic that may attract as much attention from Congress and the media as it will from industry, FDA intends to develop a regulatory approach in 2013 for energy drinks.  This effort will include publication of a “final guidance to help dietary supplement and beverage manufacturers and distributors determine whether a liquid food product (such as energy drinks) may be labeled and marketed as a dietary supplement.” 

Cosmetics

Finally, this year, FDA plans to finalize its 2012 guidance regarding the safety of nanomaterials in cosmetic products and, in 2014, intends to develop draft guidance on lead in lipstick.

By Delia A. Stubbs –

As previously reported, the Physicians for Responsible Opioid Prescribing (“PROP”) filed a Citizen Petition in March requesting that FDA limit the labeling of “controlled release” opioids to severe-only pain in non-cancer patients.  The petition also requested that FDA impose certain quantity and day limits on those medications.

After over 1900 comments on the petition were posted, including a rare endorsement by DEA, FDA issued its response last week (“PROP Petition Response”).  (FDA also responded to another similar petition, here).  Therein, FDA granted and rejected in part PROP’s requests.  FDA agreed to propose changes to the approved labeling of all Extended-Release/Long-Acting (“ER/LA”) opioid analgesics, but rejected PROP’s request for quantity and day limits.  It also rejected PROP’s request that the labeling changes be limited to “non-cancer” pain.

In sum, FDA’s proposal, which it issued pursuant to its authority under Section 505(o) of the Federal Food, Drug, and Cosmetic Act (“FDCA”), requests that all ER/LA opioid application holders, including NDA, BLA, and ANDA holders, modify those products’ labels as follows:

• Change the indication to “the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.”  This change deletes the reference to moderate pain and adds the requirement to rule out other treatment options.  FDA explained that the change is intended to encourage prescribing decisions based on an individualized assessment.  PROP Petition Response at 8.
• Add to the Limitations of Use section:  “Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve [the product] for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.”  Id.
• Change the boxed warning to include the risk of neonatal opioid withdrawal syndrome (NOWS) and to urge providers to asses and monitor the patient’s risk of abuse/misuse of the drug.

FDA’s full changes are captured in its letter to affected application holders (“FDA Letter”).

FDA explained its reasoning for imposing these changes on ER/LA opioid analgesics only.  FDA’s decision is based on data demonstrating that the risk associated with these medications is greater than it is for their immediate-release counterparts.  See PROP Petition Response at 7.

FDA rejected, however, PROP’s requests to impose quantity and day limits on these medications.  FDA stressed that it could not grant those requests based on the data submitted by PROP, noting, among other reasons, that “creating a maximum dose of 100 mg MED, or another dose ceiling, could imply a superior opioid safety profile under that set threshold, when there are no data to support such a conclusion.”  PROP Petition Response at 12. 

Likewise, pursuant to its authority under Section 505(o), FDA is requiring ER/LA opioid analgesic application holders to conduct post-marketing studies to evaluate, among other things, the impact of long-term use of these medications on misuse, abuse, hyperalgesia, addiction, overdose, and death.  Interestingly, the scope of the data requested by FDA extends beyond the mere physiological effects of these drugs to behavioral and social phenomena associated with their misuse and abuse.  For example, FDA is requesting that holders conduct “a study to define and validate ‘doctor/pharmacy shopping’ as outcomes suggestive of misuse, abuse and/or addiction” that will then be used to inform the design and analysis of a study providing “quantitative estimates” of their “serious risks.”  See FDA Letter at 3-4.  Currently, concerns regarding doctor/pharmacy shopping are addressed on a federal level through enforcement actions by DEA.  FDA stated it expects application holders to “work together” to complete the post-approval studies.  It set milestones for completion which range from 2014 to 2018. 

So, what impact will these changes have on industry?  From a law enforcement perspective, likely little-to-none.  DEA’s enforcement actions against physicians, pharmacists, and other registrants, are predicated on proof that controlled substances were prescribed for “illegitimate medical purposes,” and that determination is based on an interpretation of state law, which permits physicians to prescribe drugs for “off-label” purposes.  However, physician and pharmacy boards may more carefully scrutinize the prescribing and dispensing of medications for off-label purposes, and may consider the treatment recommendations provided in these products’ labeling, if revised as FDA intends, as instructive of the standard of care. 

The results of the post-marketing studies could also inform FDA’s decision-making regarding scheduling recommendations for these and other drugs with potential risks of abuse.  One potential outcome would be the obtainment of an acceptable measure of a substance’s abuse potential, which is a required finding for determining whether, and in which category, to schedule a drug (or other substance) for control by DEA.  In a recent advisory committee meeting regarding the up-scheduling of hydrocodone combination products, clear concerns arose regarding the lack of such an agreed upon standard.  See our previous post, here. 

Douglas Throckmorton, M.D., Deputy Director of Regulatory Programs in FDA’s Center for Drug Evaluation and Research, stated “[t]he new labeling requirements and other actions are intended to help prescribers and patients make better decisions about who benefits from the use of these medications.”  Some might welcome these changes as a substitute for enforcement actions targeted at removing that discretion.  See Larry Houck, AMA Tells Pharmacists: “Don’t Call Us We’ll Call You.”

In response to FDA’s action, all ER/LA opioid analgesic application holders must submit a prior-approval supplement with revised labeling consistent with FDA’s proposal, or a declination and a statement of reasons for the declination, by October 10, 2013.  FDA stated that it may, after discussions with stakeholders, issue an order directing these (or other) labeling changes. 

By Kurt R. Karst –     

In the 1992 movie A Few Good Men, military lawyer Lt. Daniel Kaffee (played by Tom Cruise) handles the court martial of two U.S. Marines charged with the murder of a fellow Marine.  The Marines contend they were acting under orders – a “code red” that came down from Col. Nathan R. Jessup (played by Jack Nicholson), Commanding Officer Marine Ground Forces Guantanamo Bay, Cuba – when they disciplined their fellow Marine who died.  During the court martial, Lt. Kaffee faces off against prosecuting attorney Capt. Jack Ross (played by Kevin Bacon).  Though there are several memorable scenes from the movie, one scene in particular came to mind when we read a recent decision from the U.S. District Court for the District of New Jersey stemming from a Complaint Endo Pharmaceuticals, Inc. (“Endo”) filed last year against Actavis. Inc. and Actavis South Altantic LLC (collectively “Actavis”) alleging that Actavis violated the federal Lanham Act and the New Jersey Fair Trade and Consumer Fraud Acts by marketing its Oxymorphone HCl Extended-release Tablets drug products (approved under ANDA No. 079046) as “AB-rated” to Endo’s OPANA ER (oxymorphone HCl extended-release) Tablets drug products.  No, it’s not Col. Jessup’s famous “you can‘t handle the truth! ” scene that came to mind, though we did work that into the headline of this post.  It’s the scene where Capt. Ross questions Cpl. Jeffrey Barnes (played by Noah Wyle) about where the extrajudicial punishment “code red” is authorized in various Marine handbooks, and Lt. Kaffee’s cross-exam of Cpl. Barnes.  Here’s the script (you can view the video clip here):

Capt. Ross: Corporal Barnes, I hold here the Marine Outline for Recruit Training. You're familiar with this book?
Cpl. Barnes: Yes, sir.
Capt. Ross: Have you read it?
Cpl. Barnes: Yes, sir.
Capt. Ross: Good. Would you turn to the chapter that deals with code reds, please?
Cpl. Barnes: Sir?
Capt. Ross: Just flip to the page of the book that discusses code reds.
Cpl. Barnes: Well, well, you see, sir code red is a term that we use, I mean, just down at Gitmo, I don't know if it’s actually…
Capt. Ross: Ah, we're in luck then. Standard Operating Procedures, Rifle Security Company, Guantanamo Bay Cuba.  Now I assume we'll find the term code red and its definition in that book.  Am I correct?
Cpl. Barnes: No sir.
Capt. Ross: No?  Corporal Barnes, I'm a Marine.  Is there no book.  No manual or pamphlet, no set of orders or regulations that lets me know that, as a Marine, one of my duties is to perform code reds?
Cpl. Barnes: No sir.  No book, sir.
Capt. Ross: No further questions. [As Ross walks back to his table Lt. Kaffee takes the book out of his hand]
Lt. Kaffee: Corporal, would you turn to the page in this book that says where the mess hall is, please.
Cpl. Barnes: Well, Lt. Kaffee, that's not in the book, sir.
Lt. Kaffee: You mean to say in all your time at Gitmo you’ve never had a meal?
Cpl. Barnes: No, sir. Lt. Three squares a day, sir.
Lt. Kaffee: I don’t understand.  How did you know where the mess hall was if it’s not in this book?
Cpl. Barnes: Well, I guess I just followed the crowd at chow time, sir.
Lt. Kaffee: No more questions.

By way of background, the term “therapeutic equivalence” is not defined in the FDC Act or in FDA’s ANDA regulations.  The Orange Book Preface, however, states that “[d]rug products are considered to be therapeutic equivalents only if they are pharmaceutical equivalents and if they can be expected to have the same clinical effect and safety profile when administered to patients under the conditions specified in the labeling” (i.e., bioequivalent), and that “FDA believes that products classified as therapeutically equivalent can be substituted with the full expectation that the substituted product will produce the same clinical effect and safety profile as the prescribed product.” 

Pharmaceutically equivalent prescription drug products (i.e., multi-source drug products approved under FDC Act § 505) are identified in the Orange Book with either an “A” or “B” therapeutic equivalence code designation, generally, which is further defined by a one-character sub-code.  “A-rated” drug products are considered to be to therapeutically equivalent to other pharmaceutically equivalent products, because there are no known or suspected bioequivalence problems, or such problems have been resolved with adequate evidence supporting bioequivalence.  Drug products assigned an “A” rating fall under one of two categories: (1) those active ingredients or dosage forms for which no in vivo bioequivalence issue is known or suspected, and for which bioequivalence to the Reference Listed Drug (“RLD”) is presumed and considered self-evident based on other data in an application or by a showing that an acceptable in vitro dissolution standard is met; or (2) those active ingredients or dosage forms presenting a potential bioequivalence problem, but the applicant’s approved application contains adequate scientific evidence establishing (through in vivo and/or in vitro studies) the bioequivalence of the product to a selected RLD.  Drug products that fall under the first category are assigned a therapeutic equivalence code depending on the dosage form (e.g., “AA,” “AN,” “AO,” “AP,” or “AT”).   Drug products that fall under the second category are coded “AB.” 

OPANA ER is approved under two NDAs.  NDA No. 021610 covers an old formulation of OPANA ER and is no longer marketed.  It is listed in the “Discontinued Drug Product List” section of FDA’s Orange Book without a therapeutic equivalence rating, and is the NDA referenced in Actavis’s approved ANDA No. 079046.  Endo currently markets a crush-resistant version of OPANA ER approved under NDA No. 201655, for which there are currently no approved therapeutic equivalents, though ANDAs are pending.  As such, there is no therapeutic equivalence rating for the drug product in the Orange Book.  (For additional background on these products, see our previous posts here and here.)  

According to Endo’s Complaint:

Despite the fact that its Generic Oxymorphone ER Tablets are not crush-resistant and were not approved based on the current Opana® ER [NDA], Actavis is falsely marketing its Generic Oxymorphone ER Tablets as “AB Rated to Opana® ER” . . . .  Actavis’s Generic Oxymorphone ER Tablets are not and never have been AB rated to the only Opana® ER tablets sold by Endo since May 2012, i.e., the crush-resistant tablets, and those Generic Oxymorphone ER Tablets are not designed to be crush-resistant like Opana®ER.

Endo goes further in a Cross-Motion for Partial Summary Judgment, saying:

[T]he [Orange Book] listings for both the currently available Opana® ER CRF formulation and the discontinued original Opana® ER formulation state that “There are no Therapeutic Equivalents” . . . .  FDA removed the Actavis AB rating to the Discontinued Formulation of Opana® ER from the Orange Book when it moved that version of Opana® ER to the discontinued drug products list, such that Actavis’s Tablets have not been listed by FDA as AB rated to any version of Opana® ER since June 2012. . . .  Accordingly, Actavis’s implication that its oxymorphone ER Tablets are currently listed in the Orange Book as AB rated to the Discontinued Formulation of Opana® ER is incorrect. . . . [and] Actavis’s advertising is literally false. [Emphasis in original]

As such, says Endo, “Actavis’s misrepresentations concerning the nature, characteristics and qualities of the Generic Oxymorphone ER Tablets in connection with its commercial advertising and promotion of such Tablets constitutes a violation of Section 43(a) of the Lanham Act, 15 U.S.C. § 1125(a),” and the court should order Actavis to immediately cease making such representations.

Actavis filed a Motion to Dismiss the case, arguing that the federal Lanham Act cannot be used as a tool to privately enforce the FDC Act:

The courts of appeal (including the Third Circuit [in Sandoz Pharmaceuticals Corp. v. Richardson-Vicks, Inc., 902 F.2d 222 (3d Cir. 1990)]) have uniformly held that matters pertaining to the identity or bioequivalence of generic drugs are vested in FDA’s regulatory authority under the FD&C Act.  Accordingly, the courts have uniformly held that the Lanham Act cannot be used by companies like Endo as an end-run around the lack of a private right of action under the FD&C Act.

We’ve previously tackled that topic here.

After the completion of briefing in the case (see additional briefs here, here, and here), Judge Dennis M. Cavanaugh of the New Jersey District Court issued his ruling granting Actavis’s Motion to Dismiss.  Applying the doctrine of primary jurisdiction, Judge Cavanaugh said that the issue of AB-rating is one for FDA to decide.  “This Court defers to the FDA to determine whether the new formulation of Opana ER is no longer AB equivalent to the generic Actavis product. . . . [I]t would be improper for the Court to make a determination on this matter before the FDA has had an opportunity to do so,” says the opinion. 

Judge Cavanaugh did not delve into the issue raised by Endo as to whether or not “Actavis’s implication that its oxymorphone ER Tablets are currently listed in the Orange Book as AB rated to the Discontinued Formulation of Opana® ER” is literally false and violates the Lanham Act.  It’s an interesting question: Is a generic version of an RLD that is discontinued A-rated to that RLD?  As noted above, the Orange Book does not list therapeutic equialence ratings for discontinued drug products.  But is such a rating implicit?  Some might say so; thus, we come full circle to A Few Good Men and Lt. Kaffee’s cross-exam of Cpl. Barnes:

Lt. Kaffee:  How did you know where the mess hall was if it’s not in this book?
Cpl. Barnes:  Well, I guess I just followed the crowd at chow time, sir.
Lt. Kaffee:  No more questions.

By Allyson B. Mullen –

Earlier this summer, CDRH issued a new Draft Guidance for the Content of Premarket Submissions for Management of Cybersecurity in Medical Devices (the “Draft Guidance”).  We have previously posted on the Draft Guidance here.  As noted in our earlier post, we considered the Washington Post’s assertion that the Draft Guidance imposed new “tightened standards” which would “allow the FDA to block approval of devices if manufacturers don’t provide adequate plans for protecting them” to be a bit dramatic.  However, it appears as though the Post may have been right. 

We have learned through industry contacts that even before the comment period has even closed on the Draft Guidance (closed on September 12, 2013), FDA has already invoked it as a basis for rejecting at least one 510(k) submission under its relatively new “Refuse to Accept Policy for 510(k)s.”  FDA, Guidance for Industry and FDA Staff, Refuse to Accept Policy for 510(k)s (December 2012).  The particular 510(k) refuse to accept notification that we learned of came less than two months after CDRH issued the Draft Guidance.  As anyone in industry knows, at that point the applicant is usually putting the final touches on the submission, not completely overhauling the software design to address a draft guidance document.  Therefore, it seems unreasonable (let alone unlawful) for FDA to impose compliance with a draft guidance document as part of its Refuse to Accept Policy.

As discussed in our previous post regarding FDA’s Refuse to Accept Policy (here), we raised the concern that in order to assess the “completeness” of a 510(k) submission, the reviewer may perform a substantive review.  The checklist in the Refuse to Accept Policy for a Traditional 510(k) (the “RTA Checklist”) includes three specific questions with respect to software: 1 – does the submission contain a statement that the device contains software or not; 2 – does the “[s]ubmission include[] a statement of software level of concern and rationale for the software level of concern;” and 3 – is “[a]ll applicable software documentation provided based on level of concern identified by the submitter, as described in Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices, or the submission includes information to establish that the submitter has otherwise met the applicable statutory or regulatory criteria through an alternative approach (i.e., the submitter has identified an alternate approach with a rationale).”  Refuse to Accept Policy at 35. The RTA Checklist never mentions the Draft Guidance.  Thus, during the acceptance review of this particular submission, it appears as the reviewer must have performed at least a cursory substantive review to determine that the 510(k) was not sufficiently complete due to its failure to address the Draft Guidance. 

It is important not to forget that the standard for 510(k) clearance is whether the device is substantially equivalent to a predicate device, not does the device comply with FDA’s new Draft Guidance.  However, as FDA issues more and more policies and guidance documents, the standard for 510(k) clearance seems to move further from being equivalent to a device currently on the market to meeting FDA’s new heightened standards, including those communicated through draft guidance documents.

In sum, it seems as though devices which contain or use software will not just have a more difficult time getting cleared based on the Draft Guidance, but applicants may have difficulty just getting their 510(k) submissions accepted for review.  Equally, if not more, concerning though is FDA’s expansion of the Refuse to Accept Policy to require compliance with draft guidance documents not even specifically referenced in the RTA Checklists.

By Kurt R. Karst –       

Earlier this week, the Pharmaceutical Research and Manufacturers of America (“PhRMA”), along with several other trade groups – the Maine Pharmacy Association, Maine Society of Health-System Pharmacists, and Retail Association of Maine – and two pharmacists, filed a Complaint and Motion for Preliminary Injunction in the U.S. District Court for the District of Maine against Maine’s Attorney General and Commissioner of Administrative & Financial Services in an effort to bar the state from implementing a state law that would permit the importation of drug products into the U.S. from licensed retail pharmacies located in certain foreign countries.  The state law, enacted on June 27, 2013 (after Governor Paul LePage declined to sign the bill) and titled “An Act To Facilitate the Personal Importation of Prescription Drugs from International Mail Order Prescription Pharmacies,” is scheduled to go into effect on October 9, 2013.

The law is pretty short.  Section one amends 32 MRSA §13731, sub-§1 to state:

1. Applicability. It is unlawful for any person to engage in the practice of pharmacy unless licensed to practice under this Act, except that:

A. Physicians, dentists, veterinarians or other practitioners of the healing arts who are licensed under the laws of this State may dispense and administer prescription drugs to their patients in the practice of their respective professions where specifically authorized to do so by law;

B. A licensed retail pharmacy that is located in Canada, the United Kingdom of Great Britain and Northern Ireland, the Commonwealth of Australia or New Zealand that meets its country's statutory and regulatory requirements may export prescription drugs by mail or carrier to a resident of this State for that resident’s personal use. A licensed retail pharmacy described in this paragraph is exempt from licensure under this Act; and

C. An entity that contracts to provide or facilitate the exportation of prescription drugs from a licensed retail pharmacy described in paragraph B may provide or facilitate the provision of prescription drugs from that pharmacy by mail or carrier to a resident of this State for that resident's personal use. An entity that provides or facilitates the provision of prescription drugs pursuant to this paragraph is exempt from licensure under this Act.

Section two adds 32 MRSA §13799:

§ 13799. Consumer choice preserved

Nothing in this chapter may be construed to prohibit:

1. Ordering or receiving prescription drugs. An individual who is a resident of the State from ordering or receiving prescription drugs for that individual’s personal use from outside the United States by mail or carrier from a licensed retail pharmacy described in section 13731, subsection 1, paragraph B or an entity described in section 13731, subsection 1, paragraph C; or

2. Dispensing or providing prescription drugs. A licensed retail pharmacy described in section 13731, subsection 1, paragraph B or an entity described in section 13731, subsection 1, paragraph C from dispensing, providing or facilitating the provision of prescription drugs from outside the United States by mail or carrier to a resident of the State for that resident's personal use.

Controversy over the importation of drugs into the U.S. is not new.  As we previously discussed, the FDC Act generally prohibits importation of drugs by individuals.  For example, the 1988 Prescription Drug Marketing Act amended the FDC Act to explicitly prohibit the reimportation of drugs manufactured in the U.S by individuals or entities other than manufacturers.  In addition, the 2003 Medicare Prescription Drug, Improvement, and Modernization Act (“MMA”) amended the FDC Act to include provisions authorizing the creation of a system for importation of prescription drugs from Canada, upon certification of safety and cost savings.  The provisions are only effective if the Secretary of Health and Human Services (who has authority over FDA) certifies safety, but that has not yet happened.  In the years since, there have been numerous legislative attempts to permit importation, but each attempt has failed (see, e.g., here).

For its part, FDA has long opposed permitting individual imports of prescription drugs except under very limited conditions.  The Agency has said on many occasions (here, here, and here, for example) that drugs imported for personal use “violate the FDCA because they are either unapproved new drugs[,] labeled incorrectly[,] or dispensed without a valid prescription” and can post safety risks.  FDA has found support for its position on importation in court.  In one case – Vermont v. Leavitt, 405 F. Supp. 2d 466 (D. Vt. 2005) – a federal court concluded that a state plan for importing drugs from Canada violated the FDC Act (see here).

According to PhRMA, et al., Maine’s drug importation law – dubbed an “unauthorized experiment” – “was enacted with the specific goal of encouraging and enabling state health insurers in Maine to direct their customers toward less expensive foreign mail-order pharmaceutical brokers, even though such foreign brokers and the products they supply are not subject to the exacting standards mandated by federal law and so pose serious health risks.”  The state law, say Plaintiffs, violates federal law, and implementation of it would mean that Maine is aiding and abetting violations of federal laws prohibiting unauthorized importation of drug products. 

The alleged violations are numerous.  For example, Plaintiffs say that the state law “violates the Foreign Commerce Clause (U.S. Const. Art I, § 8 cl. 3) because it purports to regulate in an area where the federal government possesses exclusive and plenary power,” and that it is also preempted under the Supremacy Clause (U.S. Const. Art. VI, cl. 2) because federal statutes, like the FDC Act Act and the MMA “occupy the field and the Maine law conflicts with and obstructs compliance with those statutes.”  More directly, the Plaintiffs state that the Maine law “rips a hole in the ‘closed’ pharmaceutical delivery system and thus clearly constitutes an obstacle to full and effective implementation of federal goals.  Most obviously, ‘[b]ecause the [Maine] Act authorizes [foreign pharmaceutical vendors] to engage in conduct that the federal Act forbids, it stands as an obstacle to the accomplishment and execution of the full purposes and objectives of Congress.’”

A hearing date on the Plaintiff’s Motion for Preliminary Injunction has not yet been set.  We’ll keep an eye on the court docket and keep you posted.

By Jeffrey N. Wasserstein and Alexander J. Varond –

On September 11, 2013, Adheris, Inc. (“Adheris”) and the Department of Health and Human Services (“HHS”) filed a joint motion requesting the suspension of Adheris’s motion for a preliminary injunction seeking to prohibit HHS from enforcing its final rule restricting certain paid marketing communications.  We posted on that case earlier this week (see here). 

HHS informed the court that that it intends to issue guidance pertaining “to the final remuneration that would be considered ‘reasonable’ for providing refill reminders or other communications about a drug or biologic currently being prescribed to an individual.”  HHS stated that it expects to issue such guidance by September 23, 2013.  In addition, HHS announced that it decided “not to enforce the restrictions on remuneration refill reminders and other communications about drugs and biologics (as set forth in 45 C.F.R. § 164.501) for a period of 45 days . . . or until November 7, 2013.” 

We will keep you posted on this developing issue.

By Jennifer D. Newberger –

The Food and Drug Administration Safety and Innovation Act (“FDASIA”), signed into law in July 2012, requires the Secretary of Health and Human Services (“HHS”) to “post a report—within 18 months (or by January 2014)—that contains a proposed strategy and recommendations on a risk-based regulatory framework pertaining to health IT, including mobile applications, that promotes innovation, protects patient safety, and avoids regulatory duplication.”  FDASIA § 618.  The three entities tasked with developing this report are the Food and Drug Administration (“FDA”), Office of the National Coordinator for Health Information Technology (“ONC”), and the Federal Communications Commission (“FCC”).  As required by FDASIA, a workgroup was formed to assist those entities in making recommendations with respect to the risk-based regulatory framework.

At the workgroup’s most recent meeting on September 4, 2013, its draft recommendations were accepted by the Health IT Policy Committee, which will pass on the information to FDA, ONC, and FCC for further action.  The report of the workgroup recognizes that while there are risks associated with the failure to adequately regulate certain types of health IT, there would also be negative impacts to regulating it too extensively.  The task of the workgroup, and FDA, ONC, and FCC, is to find a way to strike an appropriate balance.

The workgroup has stated that health IT must be assigned to one of two categories:  “subject to risk-based regulatory framework” or “not subject to risk-based regulatory framework.”  The methods for determining how to assign products to one group or another are not clear.  While the workgroup has made progress in this area, there are still no bright-line rules for determining whether a health IT product should or should not be regulated.

The workgroup recommendations are clear that functionality of the product is a key feature in helping to determine whether a product should be subject to regulation.  One note with respect to regulation:  while ONC and FCC can and do impose certain regulatory requirements on varying types of health IT products, when discussing a “risk-based regulatory framework” we assume that the primary regulator is FDA, since the burdens associated with FDA regulation undoubtedly outweigh those of the other two entities combined.

The workgroup describes a number of factors to consider in determining the appropriate level of regulation, including the complexity of the software; intended users; purpose of the software; severity of potential injury from either appropriate or inappropriate use; likelihood of a risky situation arising; transparency of the software operation, data, and knowledge content sources; and the ability to mitigate a harmful condition.  These factors seem to present a reasonable basis for assessing the level of regulation appropriate to a particular health IT product, and indicate that each product or narrow class of product must be assessed individually to determine the appropriate regulatory framework.  These considerations show that even all products that fit into an overarching product type (e.g., clinical decision support software) should not be regulated the same way. 

Perhaps most helpful, the workgroup includes specific recommendations for FDA, ONC, and FCC to consider in developing its risk-based approach.  Of particular interest is the recommendation that health IT should generally not be subject to FDA premarket requirements, with a few exceptions:  medical device accessories, high-risk clinical decision support, and higher risk software use cases.  The recommendations ask that FDA clearly define accessories and high-risk clinical decision support, a task that, while important, may not be accomplished in a reasonable timeframe, given the difficulty of defining those categories of products.  The recommendations also include a suggestion to develop post-market surveillance of health IT, which is consistent with FDA’s stated intent to improve its post-market device surveillance generally.

The workgroup recommendations appear to present a reasonable framework for FDA in assessing whether and which health IT products should be subject to what level of regulation.  The question is now whether and how the agency will adopt those suggestions, and in what period of time.  Even though a report is due to Congress by January of 2014, it will certainly take longer for FDA to develop and implement a workable approach to health IT regulation.

By Jeffrey N. Wasserstein & Alexander J. Varond –

Several months ago, when HHS released the final HITECH rule, we noted that several of the provisions represented a sea change from prior practice (see our previous post here).  Well, the seas have gotten rougher and one company feels that federal court is the safest port in this storm.  (Have we pushed the metaphor too far?)   On September 5, 2013, Adheris, Inc., a company that provides refill reminder and adherence messaging services, filed a complaint (and accompanying memorandum) seeking injunctive and declaratory relief to prohibit the Department of Health and Human Services from enforcing its final rule restricting certain paid marketing communications.  The final rule is scheduled to go into effect on September 23. 

Adheris’s refill reminder and adherence services

Adheris’s core business model involves sending reminders to customers of participating pharmacies to refill their existing prescriptions before their refills are due, and also preparing and sending letters that encourage customers to adhere to their prescribed treatment regimens.  The letters the company sends include “educational information about the medication, safety information, positive reinforcement to stay on therapy, and a direction to follow the treating physician’s advice.”  Adheris’s complaint states its services have a “verifiably significant impact on the percentage of patients still complying with their prescribed regimens at the end of a program period,” and, therefore, improve patient health.  Although pharmaceutical companies are the sponsors of these refill reminders and adherence messages, Adheris does not disclose protected health information to pharmaceutical manufacturers.  According to the complaint, Adheris derived total revenues of $49 million from these services in 2012. 

HHS’s final rule

Before the Health Information Technology for Economic and Clinical Health Act (HITECH Act), which became law on February 17, 2009, pharmaceutical companies could hire pharmacies and pharmacy chains to remind patients to refill their prescriptions, or recommend switching to alternative therapies.  These types of communications were considered treatment communications and did not require a written authorization from the patient to comply with HIPAA.  As we discussed in our prior blogposts (here and here), Congress muddied the water by calling these communications “health care operations” (a separate category under HIPAA) without addressing treatment communications.  The final rule, issued by HHS’s Office for Civil Rights on January 25, 2013, seeks to implement the HITECH Act and requires patient authorization before using protected health information to direct any paid communication recommending a product or service to the patient, regardless of whether the purpose of the communication is treatment or health care operations. 

One exception provided for in the final rule is that refill reminders, adherence communications, and other communications to patients with current prescriptions for that drug do not require authorization if the payment received by the covered entity is “reasonably related to the covered entity’s cost of making the communication.”  As we noted in our prior post, HHS explained that this means that a covered entity cannot profit from the communication.  If the covered entity receives a financial incentive beyond its cost, it must obtain the patient’s authorization.  Because, as the complaint states, Adheris’s service-related expenses far exceed its permissible remuneration, Adheris’s business is threatened by the rule.

It is unlikely, despite repeated requests from industry, that HHS will issue guidance before its final rule goes into effect.  Without guidance from HHS indicating that refill reminders and adherence communications are permitted even where the payments to a covered entity or its business associate may include a profit component, Adheris stands to lose the lion’s share of its business – the complaint states that “substantially all” of the companies that use Adheris’s services have cancelled or are re-evaluating their programs.  Pharmaceutical companies fear that, under HHS’s final rule, using Adheris’s service may expose them to sanctions and other harm for the use of protected health information for marketing purposes.
                                                                                                                           
The complaint

In its complaint, Adheris states that the final rule (referred to as the “Omnibus Final Rule”) violates the First Amendment.  The following paragraph from the complaint nicely summarizes Adheris’s First Amendment position: 

The Omnibus Final Rule places content- and speaker-based burdens on Adheris’s protected speech.  The Omnibus Final Rule is content-based because its restrictions on refill reminders and adherence communications apply only to communications that “encourage individuals to purchase or use a third party’s product or service.” 78 Fed. Reg. at 5596.  The Omnibus Final Rule is speaker-based because it discriminates against speakers who communicate in exchange for payment from “a third party whose product or service is being described.”  45 C.F.R. § 164.501.  HHS itself has explained that the restrictions of the Omnibus Final Rule are triggered only where financial remuneration is provided in exchange for making the communication from or on behalf of the entity whose product or service is being described, and that identical speech funded by anyone other than the manufacturer of a product or provider of a service is permissible without individual authorization. Id. at 5593.  These content- and speaker-based restrictions have already had a serious chilling effect on Adheris’s refill reminders and adherence communications.

Adheris thus asserts that the rule is subject to heightened scrutiny and violates the First Amendment “because its restrictions on refill reminders and adherence communications do not directly advance a substantial government interest in a proportional manner.”

A decision in this case would shed light on the scope of the Supreme Court’s 2011 decision in Sorrell v. IMS Healthcare Inc., which declared that certain restrictions on the use of prescriber-identifying information were unconstitutional.  We blogged on that decision here.  In Sorrell, the Supreme Court held that Vermont’s Prescription Confidentiality Law, which provided that “absent the prescriber’s consent, prescriber-identifying information may not be sold by pharmacies and similar entities, disclosed by those entities for marketing purposes, or used for marketing by pharmaceutical manufacturers,” violated the First Amendment.  The Court further held that the law imposed a content- and speaker-based restriction on the sale, disclosure, and use of prescriber-identifying information and that, when subjected to heightened scrutiny, Vermont’s justifications were insufficient.

Adheris also advanced an administrative law position and argued that:

The HITECH Act, properly construed, does not limit the pre-existing ability of health care providers to make “treatment” communications that are funded by pharmaceutical manufacturers.  Instead, it only limits their ability to make “health care operations” communications when funded by pharmaceutical manufacturers.  42 U.S.C. § 17936(a)(1).  As HHS has previously recognized, refill reminders and adherence communications are “treatment” communications, not “health care operations” communications, when made by health care providers such as pharmacies, and their business associates, such as Adheris.  67 Fed. Reg. 53187.  The HITECH Act does not change the pre-existing definition of “treatment” [and, therefore, those aspects of the Omnibus Final Rule] restricting refill reminders and adherence communications are not in accordance with law.

This is an interesting next issue in the pharmaceutical industry’s struggle with free speech, and we will keep you posted as the case progresses. 

By Jeffrey K. Shapiro –

In 2012, the U.S. Supreme Court held that agency regulations and enforcement policy violate due process if they do not provide fair notice of what is prohibited or required, or are so standardless that they permit seriously discriminatory enforcement.  FCC v. Fox Television, Inc., 132 S.Ct. 2307 (2012) (“Fox”).  (We previously posted about the case here.)  

There are two ways an agency may fail to provide fair notice.  One is to change its policy and apply it without adequate notice to the regulated community.  Fox, 132 S.Ct. at 2319.  Another is to impose requirements based upon subjective judgment without definitions, narrowing context, or settled legal meanings, thereby forcing the regulated community to guess at what is expected of them.  See id. at 2817; U.S. v. Williams, 128 S.Ct. 1830, 1846 (2008). 

If fair notice is not provided, even a warning letter can violate due process if the public rebuke could cause reputational harm and/or could be considered in determining punishment of a subsequent violation.  Fox, 132 S.Ct. at 2318.

As an example of an apparent FDA violation of due process under Fox, consider the 2011 warning letter to the Animas Corporation.  (We previously blogged about the warning letter here.)

As background, under FDA’s Medical Device Reporting (“MDR”) regulation (21 C.F.R. Part 803), a malfunction must be reported to FDA if is “likely” to cause serious injury or death upon recurrence.  21 C.F.R. § 803.50.  In the preamble to this regulation, FDA explains its interpretation of “likely” as meaning a “not remote” probability of serious injury or death.  60 Fed. Reg. 63,577, 63,585 (Dec. 11, 1995). In 1997 guidance, FDA states that once a malfunction has caused a serious injury or death, the agency will presume it is likely to do so again unless two years pass with no additional serious injuries or deaths.

The Animas Corporation incorporated this two year presumption in its MDR procedure.  FDA’s warning letter acknowledged the 1997 guidance, but indicated that the two year expiration of the presumption was no longer acceptable.  This abrupt departure from written guidance, announced in a warning letter, constitutes a failure to provide fair notice very similar to the agency’s conduct in Fox.  As in that case, the lack of fair notice should be considered a due process violation. 

As another example, consider FDA’s general malfunction reporting requirement.  As noted, a malfunction MDR is reportable if its recurrence is “likely” to cause serious injury or death, which FDA interprets as a “not remote” probability.  In this context, the terms “remote” or “not remote” are probability estimates that, unless applied correctly, can mean the difference between not being required to report and committing a civil and criminal violation by failing to report.

Unfortunately, nowhere in the statute, regulation or FDA guidance is “remote” or “not remote” defined or explained.  Nor does either term have a settled legal meaning.  Certainly, FDA has never pointed the regulatory community toward any such settled meaning. 

A dictionary definition of “remote” is “small in degree” or “slight,” as in slight possibility.  This definition does not indicate what the probability cutoff is, nor does it provide adequate qualitative guidance as to how this term should be applied in the context of MDR reporting.

The fact is, the regulated community has been left to guess what the probability cutoff is that makes a malfunction reportable versus not reportable.  What is “not remote”?  Is it 1 in 100?  1 in 1,000?  1 in 10 thousand?  1 in 10 million?  No one knows for sure.  This uncertainty as to what is required, as the Court held in Fox, is a violation of due process.

One last point – although not necessarily a due process concern: FDA’s two year presumption stretches the statutory term “likely” to the breaking point, resting on the premise that a malfunction is “likely” to cause serious injury or death if even a single serious injury or death has occurred, without regard for the denominator.  A device might be used 100 times annually or 100 million times annually and a single serious injury trips the presumption in both cases.  This result effectively equates “likely” with any probability of occurrence above zero, no matter how vanishingly small, and “remote” with a nullity.  As subjective as these terms are, there are limits, and a court could well find that this interpretation of “likely” exceeds FDA’s statutory authority.

By Allyson B. Mullen –

On August 28, 2013, FDA’s Center for Devices and Radiological Health issued a draft guidance, “The Applicability of Good Laboratory Practice in Premarket Device Submissions: Questions & Answers.”  This new, short guidance restates the requirements of the Good Laboratory Practices (“GLP”), set forth in 21 C.F.R. Part 58, and provides some additional clarification.

By regulation, GLPs must be followed when “conducting nonclinical laboratory studies that support or are intended to support applications for research or marketing permits for products regulated by the Food and Drug Administration, including food and color additives, animal food additives, human and animal drugs, medical devices for human use, biological products, and electronic products.”  21 C.F.R. Part 58.  The guidance clarifies that nonclinical laboratory studies are in vivo and in vitro experiments which prospectively evaluate a test article under laboratory conditions to determine safety.  Draft Guidance at 4.  In addition, for purposes of the draft guidance, a test article is a medical device for human use.  Id. However, the draft guidance acknowledges that in vitro diagnostic device studies typically do not require compliance with GLPs because they generally use human subjects or specimens derived from human subjects; thus, the testing samples are outside the scope of GLPs.  Id. at 7.

In addition, the draft guidance requires companies submitting medical device marketing and research applications, including, without limitation, 510(k)s, PMAs, and IDEs, to indicate whether the applicable studies being submitted have complied with GLPs.  Id. at 5.  In addition, applicants are now required to include a statement within their submissions indicating that the nonclinical laboratory studies in the submission comply with GLPs.  Id. at 5-6.  This requirement applies to all studies regardless of whether they were conducted in the United States or abroad.  Id. at 7.  To some, it may appear as though this statement is a new requirement for medical device submissions.  For example, 21 C.F.R. § 807.87 does not require applicants to address GLP compliance as part of necessary information in a premarket notification.  However, FDA has been requiring such a statement as part of its “Refuse to Accept Policy for 510(k)s” issued at the end of 2012.  FDA, Guidance for Industry and FDA Staff, Refuse to Accept Policy for 510(k)s, 39 (December 2012). (This indicates how a seemingly innocuous checklist can effectuate changes in practice.)

The draft guidance goes on to explain that if the studies have not complied with GLPs, the applicant should indicate such non-compliance and include an explanation.  Draft Guidance at 6.  The draft guidance also suggests information to provide when a study has not complied with GLPs, including, for example, a detailed list of deviations from the regulations, an explanation of how the sponsor limited study bias, and an explanation of how the sponsor ensured the validity and integrity of the data.  Id. at 6. 

Lastly, FDA concludes the draft guidance with questions regarding testing facilities.  The draft guidance indicates that companies performing nonclinical laboratory testing to support device safety are required to allow FDA to inspect the applicable facilities.  Id. at 7.  Further, if a testing establishment does not permit FDA to conduct such an inspection, FDA will not consider study data generated by such facility in support of a device application.  Id. Therefore, applicants should be advised to choose their testing facilities wisely and ensure that such companies are able and willing to endure an FDA inspection.  Overall, this document will mean more companies will need to pay more attention to GLPs than has been the case.

By Kurt R. Karst –      

We present to you the Biosimilars State Legislation Scorecard.  Links are provided to each piece of legislation.  We also give you a word or two on status.  In most cases, a summary of each bill is provided at the linked-to website.  In general, legislation introduced follows the principles advocated for by organizations such as the Biotechnology Industry Organization – specifically: (1) substitution should occur only when the FDA has designated a biologic product as interchangeable; (2) the prescribing physician should be able to prevent substitution; (3) the prescribing physician should be notified of the substitution; (4) the patient, or the patient’s authorized representative, should, at a minimum, be notified of the substitution; and (5) the pharmacist and the physician should keep records of the substitution.

Biosimilars State Legislation Scorecard

 View State Map

Overview

• Five states (Florida, North Dakota, Oregon, Utah, and Virginia) have enacted laws specifying the circumstances under which pharmacists could substitute biosimilars for reference products.  Three of the laws (Oregon, Utah, and Virginia) include a sunset date.
• Legislation has failed to pass in eleven states (Arizona, Arkansas, California, Colorado, Delaware, Illinois, Indiana, Maryland, Mississippi, Texas, and Washington).
• Two states (Arkansas and Indiana) have referred biosimilar legislation to a study committee for further review.
• Legislation is pending in two states (Massachusetts and Pennsylvania)

Alabama (None)  

Alaska (None)    

Arizona

• S.B. 1438 (2013) – Died on Adjournment

Arkansas

• S.B. 149 (2013) – Died on Adjournment (Recommended for study in the Interim Committee on Senate Committee on Public Health, Welfare and Labor)
• S.B. 386 (2013) – Died on Adjournment

California

• S.B. 598 (2013-2014) – Passed Senate and Assembly; Vetoed by Governor (see here)
• A.B. 1139 (2013-2014) – In Committee

Colorado

• H.B. 1121 (2013) – Senate Committee on Health & Human Services Postpone Indefinitely (effectively dead)

Connecticut  (None)

Delaware

• S.B. 118 (2013) – Died on Adjournment

Florida

• H.B. 365 (2013) – Enacted; Chapter No. 2013-102
• S.B. 732 (2013) – Laid on Table; Companion bill passed (H.B. 365)

Georgia (None)  

Hawaii (None)  

Idaho  (None)  

Illinois

• S.B. 1934 (2013) – Referred to Assignments (effectively dead)

Indiana

• S.B. 272 (2013) – Died on Adjournment
• H.B. 1315 (2013) – Enacted without biosimilar provisions
• Senate Resolution 112 (2013) – Adopted voice vote

Iowa (None)  

Kansas (None)  

Kentucky (None)  

Louisiana (None)  

Maine (None)  

Maryland

• S.B. 781 (2013) – Died on Adjournment

Massachusetts

• H.B. 1927 (2013) – Pending; Joint Public Health Committee (Related Bills: H.B. 3734 and H.B. 3667)

Michigan (None)  

Minnesota (None)  

Mississippi

• S.B. 2085 (2013) – Died on Adjournment
• H.B. 1387 (2013) – Died on Adjournment

Missouri (None)  

Montana (None)  

Nebraska (None)  

Nevada (None)

• The Generic Pharmaceutical Association has identified Nevada as a state in which legislation was “killed”; however, we are not aware of any legislation introduced.

New Hampshire (None)  

New Jersey (None)  

New Mexico (None)  

New York (None)  

North Carolina (None)  

North Dakota

• S.B. 2190 (2013) – Enacted; Chapter 19-02.1

Ohio (None)  

Oklahoma (None)  

Oregon

• S.B. 460 (2013) – Enacted; Chapter 342, 2013 Laws
• H.B. 2705 (2013) – Died on Adjournment

Pennsylvania

• S.B. 405 (2013-2014) – Pending; Senate Public Health & Welfare Committee
• H.B. 746 (2013-2014) – Pending; House Health Committee

Rhode Island (None)  

South Carolina (None)

South Dakota (None)  

Tennessee (None)  

Texas 

• S.B. 190 (2013-2014) – Died on Adjournment
• H.B. 542 (2013-2014) – Died on Adjournment

Utah

• S.B. 78 (2013) – Enacted

Vermont (None)  

Virginia

• S.B. 1285 (2013) – Enacted; Chapter 544
• H.B. 1422 (2013) – Enacted; Chapter 412

Washington

• S.B. 5469 (2013-2014) – Pending (1/2014: by resolution, reintroduced and retained in present status) 
• H.B. 1528 (2013-2014) – Pending (1/2014: by resolution, reintroduced and retained in present status)

West Virginia (None)  

Wisconsin (None)  

Wyoming (None)  

This post, originally posted to the FDA Law Blog on September 4, 2013, opened as follows:

With the news last week that the Assembly in the bellwether state of California passed a bill – S.B. 598 – concerning the substitution of biosimilar and interchangeable biosimilar products for their brand-name reference product counterparts, and with bills currently passed, failed or pending in other states (and the likelihood that legislation will continue to be pushed in several states for some time to come), we thought it was high time to put together a new scorecard – the Biosimilars State Legislation Scorecard – to keep tabs on such legislation.  Once we get a chance, we’ll add a direct link to this new scorecard, along with any others we have created (such as our popular Generic Drug Labeling Carve-Out Citizen Petition Scorecard) to the FDA Law Blog website where our various trackers (Citizen Petition Tracker, Legislation Tracker, 180-Day Exclusivity Tracker, and REMS Tracker) are linked to as well.  We’ll update the scorecards periodically and post separately on items that are particularly newsworthy.

(UPDATE: On September 4th, the California Senate voted to pass S.B. 598 – see here.  The Generic Pharmaceutical Association subsequently issued a press release – as well as a bunch of additional materials – urging Governor Jerry Brown to veto S.B. 598.)

State legislation addressing biosimilar substitution issues has been particularly controversial (see our previous post here).  Indeed, after the California Assembly’s passage of S.B. 598, an FDA spokesperson reiterated concerns previously expressed by FDA Commissioner Margaret Hamburg that “[e]fforts to undermine trust in these products are worrisome and represent a disservice to patients who could benefit from these lower-cost treatments.” 

Others might say that state legislative efforts to address substitution are premature.  After all, FDA has not yet even approved (let alone filed) a Section 351(k) biosimilar application submitted pursuant to the procedures established by the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”) and discussed in draft FDA guidance (see our previous post here).  Then there’s that April 2012 citizen petition (Docket No. FDA-2012-P-0317) submitted by Abbott Laboratories requesting that FDA not accept for filing, file, approve, or even discuss with any company any application or any investigational new drug application for any biosimilar that cites as its reference product any product for which the BLA was submitted to FDA prior to the date on which the BPCIA was enacted (see our previous post here).  FDA has not yet substantively responded to the petition; however, query whether FDA’s meetings with biosimilar sponsors (see the next paragraph), if they concern pre-BPCIA products, is a constructive denial of the petition (at least in part).  (And, as an aside, there’s ongoing debate about including a 12-year period of exclusivity for biological products in the Trans-Pacific Partnership agreement chapter on intellectual property rights – see our previous posts here, here, here and here, and a recent letter and paper from the Biotechnology Industry Organization here and here.) 

Despite efforts that some have alleged are intended to stymie the nascent biosimilars industry, interest in developing biosimilars remains high.  According to one report, FDA “continues to meet with sponsors interested in developing biosimilar products,” and as of the last week of August 2013, the Agency “had received 57 meeting requests for an initial meeting to discuss biosimilar development programs for 13 different reference products and held 47 initial meetings with sponsors.”