Judge Says FDA Can Stop Clinic from Selling Stem Cell Treatments

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The decision may facilitate the agency cracking down more effectively on the unproven interventions these companies sell.

By Emma Yasinski
June 7, 2019

 In 2015, a stem cell clinic in Florida conducted a procedure on three women to treat their macular degeneration. Instead, it left each of them with severe vision loss. The tragedy has been held up as an example of the lack of regulatory oversight the US government has had over such outfits that offer unproven stem cell treatments—and now, it’s an example of how that is changing.

On June 3, a federal judge ruled that the US Food and Drug Administration (FDA) is entitled to a permanent injunction against US Stem Cell, forcing the company to stop conducting procedures using a particular technique that involves isolating stem cells from clients’ fat.

The FDA also filed a suit against a California-based company Cell Surgical Network, which provides similar interventions, that is still pending in court.

“The lawsuit itself wasn’t surprising. The allegations weren’t surprising. And the judge’s conclusion wasn’t very surprising,” Andrew Ittleman, an attorney at Miami-based Fuerst, Ittleman, David & Joseph, a law firm that counts government compliance for stem cell and regenerative medicine companies as one of its key practice areas, tells The Scientist. “If anything, people were wondering why it took so long.”

Hundreds of stem cell clinics have popped up across the US and other countries in recent years, making promises with little evidence that their treatments can cure ailments that traditional medicine cannot. The clinics have often avoided FDA oversight by claiming that their procedures, which often use a patient’s own cells, are not subject to FDA regulations.

The agency has been cracking down on the industry, but it has only successfully obtained a judgment against a stem cell clinic once before. This latest ruling by Judge Ursula Ungaro of the United States District Court for the Southern District of Florida may represent a sea change in regulatory enforcement, and possibly open the door for the FDA to file suits against companies violating FDA guidelines for marketing stem cell treatments en masse, according to Ittleman.

“This is a landmark decision because this is only the second time the FDA has obtained a judgment against a stem cell clinic, and the first judgment since FDA announced in 2017 the agency’s risk-based enforcement priorities for regenerative medicine,” FDA spokesperson Stephanie Caccomo tells The Scientist in an email.

See “Texas Stem Cell Law Opens Door for Controversial Treatments”

 Research on stem cell therapies has ballooned in recent years, and some procedures for certain blood disorders have even been FDA-approved, but most remain unproven as far as the FDA is concerned. Extracting fat cells using liposuction, processing them to extract stem cells (known as stromal vascular fraction cells or SVF), and injecting them into other areas of the body— the strategy US Stem Cell uses—has been an FDA target before. Some clinics provide treatments with stem cells derived from bone marrow, cord blood, or birth tissue.

Ittleman, who has represented clients sued by the FDA, doesn’t believe the ruling will immediately affect clinics using other types of stem cells. “The fat [derived stem cell treatment] has been really the one place where the FDA has been very clear for very long about its position. We don’t necessarily have that clarity in other areas,” he says. The ruling may inspire the FDA to target other unapproved stem cell treatments with litigation, he adds.

The three patients who lost all or most of their sight were the first (and only) three participants in a discontinued clinical trial US Stem Cell was running on the procedure. Afterward, the patients saw university-based ophthalmologists for treatment, and those doctors published a report in March of 2017 in the New England Journal of Medicine detailing the adverse effects on each individual and raising concern about stem cell clinics.

US Stem Cell failed to follow best practice in ophthalmology of operating on one eye first, and returning later for a second surgery on the remaining eye. This way, if there is an adverse reaction, the patient can still see with the untreated eye. But the company conducted both procedures simultaneously.

Shortly after the failed procedures, two of the patients settled lawsuits with US Stem Cell, but the company faced few other penalties. While it stopped offering fat-derived stem cell treatments for macular degeneration, it continued to provide services using SVF that it claimed could treat myriad ailments, from Parkinson’s disease to chronic obstructive pulmonary disease (COPD).

The FDA sent a warning letter to US Stem Cell in August 2017 about marketing the unapproved products and violations to good manufacturing practices. But the company did not comply. Ittleman says they were “really sticking their fingers in the FDA’s eyes over the course of time saying, ‘You don’t regulate us.’”

In a written statement sent to The Scientist, US Stem Cell said, “While we believe there is substantial evidence to prove the efficacy of this protocol, we must immediately comply with the court as we review the decision.” A spokeswoman told The New York Times that the company plans to continue offering stem cell treatments derived from other tissue.

“Precedent from cases like this helps the FDA in future enforcement actions,” says Caccomo. “The FDA will continue to take steps—such as issuing warning letters or initiating court cases—against clinics that abuse the trust of patients and endanger their health with inadequate manufacturing conditions or by manufacturing and promoting products in ways that make them drugs under the law, but which have not been proven to be safe or effective for any use.”

Click here to read the full article.

Approval of Epidiolex, a Cannabis derived drug for the treatment of Seizures

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By Jane Clarke
April 16, 2019

Epidiolex became the first cannabis-derived medication to be approved by the FDA in June of this year. It is used to treat two types of serious childhood epilepsy from the British organization GW Pharmaceuticals. The Food and Drug Administration approved the drug for sale in the US on Monday. It will probably be available in pharmacies by prescription.

Epidiolex contains a chemical compound, cannabinoid otherwise called CBD. It is popular for its reported abilities to help relief from illnesses, for example, anxiety, joint pain, a sleeping disorder, and nausea.

Moreover, epidiolex is useful in treating an uncommon type of epilepsy called Lennox-Gastaut Syndrome (LGS) and a genetic brain dysfunction known as Dravet syndrome. According to CNN, the two disorders can cause seizures. In any case, Epidiolex, with its cannabis derivatives, has been found to reduce a particular kind of those seizures by as much as 25% to 28%.

FDA endorsed the medication back in April, but GW couldn’t sell it. The reason is the DEA has regarded cannabis a Schedule I drug alongside heroin, LSD, and cocaine. It means it is considered to have “no currently accepted restorative use and a high potential for abuse.” Now, Epidiolex specifically — however not CBD or cannabis — is Schedule V. “The DEA is stating, ‘if you’ve satisfied FDA, you’ve satisfied us,’” says Andrew Ittleman, a partner of the law firm FIDJ. It’s appearing “considerable amount of deference” to the FDA.

The Cooperation of DEA with Researchers:
The Department for Drug Enforcement (DEA) says it will work with the researchers to help them in their research. Marijuana and CBD got from cannabis stay unlawful in the United States except if they are in items endorsed by the FDA, for example, Epidiolex. Researchers are conducting more research into the medical benefits of cannabis.

“DEA will keep on supporting sound and logical research that advances legitimate therapeutic uses for FDA-approved components of cannabis, consistent with the federal law,” said Acting DEA Administrator Uttam Dhillon in a written proclamation. “DEA is focused on proceeding to work with our federal partners to look for approaches to make the procedure for research progressively proficient and effective.” The greatest unknown is how insurance agencies will choose to cover Epidiolex.

The double-blind, placebo-controlled trials required for FDA endorsement just covered two rare types of epilepsy—Dravet Syndrome and Lennox Gastaut Syndrome. Around 50,000 patients are suffered by these two diseases. However, there is evidence that Epidiolex could help with many distinctive kinds of seizures and epilepsy syndromes.

Without a doubt, 66% of the 1,756 patients who have attempted Epidiolex in the previous five years didn’t have Dravet or LGS. Epidiolex demand was so high among medication inert patients like Sam that GW permitted neurologists at almost four dozen hospitals that weren’t a part of the formal trials to direct their own so-called open-label trials. It helped GW to study more about how Epidiolex functioned in a more extensive population. It allowed many sick patients to gain access to medication that may help them.

That parallel research should make it simpler for specialists to suggest the medication for different diseases, a training known as “prescribing off label.”

To conclude, the expectation among CBD advocates is that the FDA’s endorsement could goad more investigation into medicinal cannabis items, however, weed itself stays illicit.

Although therapeutic or medical cannabis is accessible in about half of U.S. states. But federal regulations still characterize CBD as a Schedule 1 medicate, which implies it has no therapeutic value however it has a high potential for abuse since it is a chemical component of the cannabis plant.

Same Surgical Procedure Exception under 21 CFR 1271.15(b): FDA Raises More Questions Than it Answers Regarding the Scope of the Exception

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November 12th, 2014

The FDA has released a new draft guidance document for industry entitled “Same Surgical Procedure Exception under 21 CFR 1271.15(b): Questions and Answers Regarding the Scope of the Exception” (the Guidance Document), which can be read here. This Guidance Document is FDA’s attempt at clarifying the “same surgical procedure” exception set forth at 21 C.F.R. 1271.15. That exception allows for the use of autologous stem cell treatments without submitting to regulation under FDA’s drug or biologic regulations. As always, “FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities.”

As background, FDA regulates human cells and tissues intended for use in transplantations, implantation, or transfer into human recipients as human cells, tissues, or cellular or tissue-based products. FDA defines “human cells, tissues, or cellular or tissue-based products” (HCT/Ps) to mean:

[A]rticles containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient. Examples of HCT/Ps include, but are not limited to, bone, ligament, skin, dura mater, heart valve, cornea, hematopoietic stem/progenitor cells derived from peripheral and cord blood, manipulated autologous chondrocytes, epithelial cells on a synthetic matrix, and semen or other reproductive tissue. 21 CFR 1271.3(d).

FDA has set forth its regulations for HCT/Ps in 21 C.F.R. part 1271. In this part of the Code of Federal Regulations, FDA has divided HCT/Ps into two categories: (1) HCT/Ps regulated solely under part 1271 and section 361 of the Public Health Service Act (PHSA) (42 USC 264), and (2) HCT/Ps regulated under part 1271 and FDA’s regulations governing medical devices or drugs under the FDCA or biological products under section 351 of the PHSA (42 USC 262). However, practitioners can avoid regulation under Part 1271 if their treatment modalities fall within the “same surgical procedure” exception under 1271.15(b), which states “you are not required to comply with the requirements of this part if you are an establishment that removes HCT/Ps from an individual and implants such HCT/Ps into the same individual during the same surgical procedure.”

FDA’s new Guidance Document gives a brief overview of the history of the exception. In 1997, the FDA issued a document called “Proposed Approach to Regulation of Cellular and Tissue-Based Products” in which it stated “[t]he agency would not assert any regulatory control over cells or tissues that are removed form a patient and transplanted back into that patient during a single surgical procedure. The communicable disease risks, as well as the safety and effectiveness risks, would generally be no different than those typically associated with surgery.” After that, in 1998, FDA published a proposed rule in the Federal Register, 63 Fed Reg 26744, regulating the registration of HCT/P establishments followed by a final rule in 2001, 66 Fed Reg 5447. In the proposed rule, FDA stated that it received a comment assuming that a hospital retaining autologous tissue to be used in a subsequent application on the same patient, even if the use would occur in a future, not-yet-scheduled surgical procedure, would not be subject to registration and listing. In its final rule, FDA agreed that “so long as the hospital does not engage in any other activity encompassed with in [sic] the definition of “manufacture,” the hospital would not be required to register or comply with the other provisions to be codified in part 1271. For example, if the hospital expanded the cells or tissues, it would not meet the terms of the exception.”

After describing that historical background, FDA concludes in the new Guidance Document that “autologous cells or tissues that are removed from an individual and implanted into the same individual without intervening processing steps beyond rinsing, cleansing, or sizing, or certain manufacturing steps, raise no additional risks of contamination and communicable disease transmission beyond that typically associated with surgery.” FDA does not explain the leap from its 2001 explanation regarding hospital activities to its new decision that anyintervening steps outside of “rinsing, cleansing, or sizing” would bring a procedure outside of the “same surgical procedure” exception. What has happened between 2001 and now that has led FDA to determine that rinsing, cleansing, and sizing fit within the 1271.15 exception? This is only the first of many questions this new Guidance Document raises but does not answer. While attempting to provide some clarity to the regenerative medicine industry, FDA has, as it often does, raised additional questions and confusion as to how certain treatments and procedures will be regulated.

For instance, in addressing “[w]hen does the exception in 1271.15(b) apply?” (see Q4. of the Guidance Document), FDA states there are three criteria that must be met to fall under the exception. These criteria are that (1) the HCT/Ps must be removed and implanted into the same individual (autologous use), (2) the HCT/Ps must be implanted within the same surgical procedure, and (3) the HCT/Ps remain “‘such HCT/Ps;’ they are in their original form.” FDA has included a footnote to the third criterion stating:

Note that the criteria of “minimal manipulation” expressed in 21 CFR 1271.10 (a) is not the standard for establishing whether an HCT/P is “such HCT/P” under § 1271.15. Accordingly, even manufacturing steps considered minimal manipulation within § 1271.10(a), will typically cause the HCT/P to no longer be “such HCT/P” under §1271.15(b), unless the HCT/P is only rinsed, cleaned, sized, or shaped. (Emphasis added.)

This new narrower 1271.15 same surgical procedure exception leads to numerous other questions that our clients are asking in their medical practices. This footnote makes clear that the 1271 same surgical procedure exception is actually narrower than the “more than minimal manipulation” standard, which FDA has previously interpreted in guidance documents and regulatory preambles as being incredibly narrow. Would FDA consider centrifugation to be “rinsing, cleansing, sizing or shaping?” How does this Guidance Document affect the physicians in the United States who are utilizing centrifugation to work with stromal vascular fraction (SVF), many of whom using SVF in their practices under the auspices of the same surgical procedure exception? How does this interpretation affect cell separation procedures?

In attempting to clarify the types of procedures that fall within the same surgical procedure exception, FDA provides the following insights: “[P]rocedures that involve an incision or instrumentation (e.g., incision or surgical technique) during which an HCT/P is removed from and implanted into the same patient within a single operation performed at the same establishment, are considered to be the same surgical procedures. Examples include autologous skin grafting and coronary artery bypass surgery involving autologous vein or artery grafting.” (See Q3 of the Guidance Document.) As this statement seems to encompass a fairly broad range of procedures, it will be interesting to see exactly which procedures, other than those specifically mentioned, FDA will consider “surgical.”

FDA also attempts to address whether procedures that involve more than a single operation could fall under the same surgical procedure exception and whether autologous tissue can be shipped within the exception. In the Guidance Document, FDA writes that, in most situations, more than one procedure would not qualify under this exception. However, neither time nor the number of “procedures” involved is dispositive. Instead, there may be circumstances in which “removal and future implantation may be a number of days apart” and still fall within the exception (see A4 of the Guidance Document). HCT/Ps may only be rinsed, cleansed, and/or stored during the intervening time, according to FDA, and no other “manufacturing steps beyond labeling and storage may be performed.” Accordingly, it seems that procedures performed days apart can still be deemed to be the same surgical procedure. FDA also states that shipping of HCT/Ps cannot be done at any time during the procedure to fall under this exception, no matter what the purpose of the shipment (even for storage).

Despite the new questions raised, one of the few clear conclusions that can be drawn from this new draft Guidance Document is that FDA has decided to apply the same surgical procedure exception of part 1271 very narrowly. Practitioners and professionals in the regenerative medicine industry who believe that they are currently practicing within the same surgical procedure exception should closely scrutinize their practices in light of this Guidance Document to prepare and insulate themselves from potential enforcement action that may stem from violation of FDA’s newest interpretations. As this Guidance Document is a draft, FDA has chosen to accept comments, and comments must be submitted in writing by December 22, 2014. Fuerst, Ittleman, David, and Joseph, PL will continue to monitor this policy document and all other issues relating to FDA’s regulation of the regenerative medicine industry.

Food Labeling and Marketing after POM LLC v. Coca-Cola Co.: Why Compliance with FDA Regulations May Not Be Enough

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On June 12, 2014, the United States Supreme Court issued a unanimous decision in POM Wonderful LLC v. Coca-Cola Co., holding that competitors may bring Lanham Act claims challenging food and beverage labels regulated by the federal Food, Drug, and Cosmetics Act (“FDCA”). (For the full text of the Supreme Court’s decision, please click here.) In this landmark decision, the Supreme Court overturned the Court of Appeals for the Ninth Circuit’s decision as “incorrect,” holding that “[n]either the Lanham Act nor the FDCA, in express terms, forbids or limits Lanham Act claims challenging labels that are regulated by the FDCA.” As we discuss in greater detail below, this decision could play a significant role in changing the landscape of food labeling and marketing because it puts industry on notice that complying with FDA regulations and policies will not be enough to shield against lawsuits from competitors, and potentially even consumers.

Background

POM Wonderful LLC (“POM”) filed a Lanham Act claim against its competitor, Coca-Cola Co. (“Coca-Cola”), for the labeling of its “pomegranate blueberry” juice blend. POM alleged that the name, label, marketing, and advertising of Coca-Cola’s juice blend misled consumers into believing that it consisted predominantly of pomegranate and blueberry juice, when in reality it only contains 0.3% and 0.2% of each juice, respectively. In response, Coca-Cola argued that its label was perfectly compliant with FDA regulations governing juice labels and therefore POM’s Lanham Act claim was precluded.

The Lanham Act was passed by Congress to regulate commerce and, among other things, to create a cause of action for unfair competition through misleading advertising or labeling. Under this provision of the Lanham Act, competitors, and not consumers, are the intended beneficiaries of enforcement. See 15 U.S.C. §1125. The FDCA, on the other hand, is intended to protect the health and safety of the public and contains specific provisions prohibiting any food or beverages in commerce from being misbranded. Under the FDCA, a food or beverage may be deemed “misbranded” if, inter alia, “its labeling is false or misleading,” information required to appear on its label “is not prominently placed thereon,” or a label does not bear the “common or usual name of the food, if any there be.” See 21 U.S.C. §§343.

After POM sued Coca-Cola in the United States District Court for the Central District of California, the court ruled that the FDCA and its regulations preclude challenges to the name and label of Coca-Cola’s juice blend. (To read the full text of this opinion, please click here.) The District Court explained that “the FDA has directly spoken on the issue” through its regulations, where the regulations “ha[ve] not prohibited any, and indeed expressly ha[ve] permitted some” aspects of Coca-Cola’s labeling. On appeal, the Ninth Circuit affirmed the District Court’s decision, reasoning that Congress decided “to entrust matters of juice beverage labeling to the FDA.” (To read the full text of the Ninth Circuit’s decision, please click here.) In its decision, the Ninth Circuit barred POM’s Lanham Act claim “[o]ut of respect for the statutory and regulatory scheme,” and to avoid the “risk [of] undercutting the FDA’s expert judgments and authority.” The Supreme Court granted certiorari to consider whether a private party may bring a Lanham Act claim challenging a food label that is regulated by the FDCA. (For additional coverage of the Supreme Court’s decision, please click here, here, here, and here.)

United States Supreme Court Decision

At the outset of its opinion, the Supreme Court framed this case as “concern[ing] the intersection and complementarity” of the Lanham Act and the FDCA. In its decision, the Supreme Court relied on traditional rules of statutory interpretation and dedicated much of its opinion to a thorough analysis of Congressional intent. The Supreme Court held that nothing in the express terms of the text, history, or structure of the Lanham Act or the FDCA forbids or limits competitors from bringing Lanham Act claims to challenge labeling regulated by the FDCA. To emphasize that Congress did not intend for Lanham Act claims to be precluded, the Supreme Court gave significant weight to the fact that Congress amended the FDCA to include an express preemption provision with respect to state laws addressing food and beverage misbranding, but did not create a similar preclusion of other federal laws. In light of the 70-year co-coexistence of the FDCA and the Lanham Act, the Supreme Court viewed Congress’s inaction as “powerful evidence that Congress did not intend FDA oversight to be the exclusive means” of ensuring proper food and beverage labeling.

Furthermore, the Court recognized the limits on FDA’s regulatory oversight and competence on competitive practices in the marketplace. In reversing the Ninth Circuit, the Supreme Court reasoned that competitors “have detailed knowledge regarding how consumers rely upon certain sales and marketing strategies” and an “awareness of unfair completion practices [that] may be far more immediate and accurate than that of agency rulemakers and regulators.” The decision implied that competition in the marketplace and consumer safety are better preserved by allowing both Lanham Act claims and administrative regulation and enforcement under the FDCA.

The Court emphasized that “[i]t is unlikely that Congress intended the FDCA’s protection of health and safety to result in less policing of misleading food and beverage labels than in competitive markets for other products.” Therefore, to find that Lanham Act claims are precluded by the FDCA would, according to the Supreme Court, “not only ignore the distinct functional aspects of the FDCA and the Lanham Act but also would lead to a result that Congress likely did not intend.”

In addition, the Supreme Court rejected Coca-Cola’s argument that preclusion is proper because Congress intended national uniformity in food and beverage labeling. The Supreme Court explained that the centralization of FDCA enforcement authority in the Federal Government “does not indicate that Congress intended to foreclose private enforcement of other federal statutes.” Because the Lanham Act and FDCA can be implemented together, the Court concluded that the FDCA’s greater specificity with respect to food labeling does not create any more or different variability in food labeling than that of any other industry. Based on the Court’s interpretation of the two statutes, “neither the statutory structure nor the empirical evidence” presented any difficulty in fully enforcing each statute according to its terms.

What Does This Mean? What are the Implications of this Decision?

At first glance, the POM decision may appear narrow in its application to food labeling and advertising. However, the rationale used in the Supreme Court’s opinion could have a much more expansive impact on the way the courts construe the interplay of federal statutes that have overlapping applications. Furthermore, it seems possible that this opinion could be expanded to apply to other federal regulatory bodies, like the U.S. Department of Agriculture (“USDA”) and the Alcohol and Tobacco Tax and Trade Bureau (“TTB”), which require similar labeling requirements under their respective regulatory frameworks.

For example, in a blog entry we posted prior to the Supreme Court’s POM decision, we discussed how the FTC’s regulation of advertising and promotion of FDA-regulated products can create a complex and confusing regulatory framework for industry. Because both agencies have enforcement authority over product promotion but different standards and regulations, the blurred jurisdictional lines fail to provide industry with a clear directive as to which agency’s set of standards it should comply. Under this framework, for example, a product’s labeling claim may comply with the FDCA’s regulations and still run afoul of the FTC’s policies as misleading or lacking adequate substantiation. Therefore, in the absence of clear guidance, industry is forced to guess how its products will be regulated and which standards it must meet to be compliant with both sets of federal laws and regulations. (For more information on this topic, please also read the article “Need for Regulatory Harmonization: How FDA and FTC’s Shared Jurisdiction Poses Problems for Labeling& Advertising Compliance” here.)

The Supreme Court’s POM decision seems to lead industry down a similar rabbit hole. On the one hand, the Supreme Court’s decision emphasizes the importance of compliant labeling under the FDCA. However, the same opinion informs industry that the very same FDCA-compliant labeling can be brought before a court for misleading consumers in violation of the Lanham Act. In the absence of clear guidance, however, it is unclear what, if any, compliance measures may fully immunize manufacturers under all of the applicable laws.

For these reasons, this decision will likely have a significant impact on how manufacturers will choose to label and advertise their food products in the future. In order to minimize the risk of a possible enforcement or legal action, industry should not only ensure that their product labeling complies with the FDCA’s misbranding provisions, but should also be prepared to defend against any possible challenges to the truthfulness and accuracy of any labeling or advertising claims they make. In particular, industry should be prudent in analyzing their labeling and advertising to ensure that the overall context of their claims do not rise to the level of false or misleading claims under the Lanham Act, FTC Act, and state laws governing deceptive advertising.

While it remains to be seen how courts will rule on the merits of future Lanham Act claims like POM’s, it seems evident that industry will have to take more expansive precautions to insulate themselves from advertising and labeling lawsuits in the post-POM era. Fuerst Ittleman David & Joseph, PL will continue to monitor any developments in the regulation of food labeling and advertising. The attorneys in our Food, Drug, and Life Sciences practice group are experienced in assisting regulated industry to ensure that products are marketed and advertised in compliance with all applicable federal laws and regulations. For more information, please call us at (305) 350-5690 or email us at contact@fidjlaw.com.

FDA Regulatory Update: International Crack Down on Online Pharmacies Identifies Over 1,900 Websites Selling Unapproved or Potentially Counterfeit Drugs to U.S. Consumers

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By participating in the organized, global action known as Operation Pangea VII, the U.S. Food and Drug Administration (“FDA”) made good on its promise to continue working with the international community to investigate online pharmacies that sell potentially unapproved, counterfeit, or adulterated drugs and medical devices. (To read the full text of FDA’s press release, please click here.) Between May 13 and May 20, 2014, the FDA partnered with the U.S. Customs and Border Protection (“CBP”), the U.S. Department of Homeland Security, INTERPOL and over 111 law enforcement, customs, and regulatory authorities around the world in targeting websites that sell potentially dangerous, unapproved prescription drugs to consumers. (For additional media coverage of Operation Pangea VII, please click here, here, and here.) This world-wide collaborative effort brought together even more countries than in previous years and required participating countries to carry out “extensive examinations at U.S.-based international mail facilities.” (To read INTERPOL’s summary of Operation Pangea VII, please click here and here.)

Operation Pangea VII resulted in the detention or seizure of 19,618 packages containing over 9.4 million unapproved or suspected counterfeit drugs, including insulin, estrogen, bimatroprost, tramadol, and sildenafil citrate. A large number of these packages claimed to contain medicines from Australia, the United Kingdom, New Zealand, and Canada. Upon further investigation, however, many of those packages were found to contain unapproved or suspected counterfeit drugs from other countries, such as India, China, Singapore, Taiwan, Mexico, Laos, and Malaysia. The total value of these seized and detained products amounted to approximately $36 million.

Based on these findings, regulators and customs authorities across the globe ordered more than 10,000 websites to shut down their operations and remove over 19,000 advertisements for these medicines on social media. Through these efforts, the FDA identified over 1,975 websites as selling products in violation of U.S. law and notified related internet service providers and domain name registrars of the websites’ allegedly violative practices.

Together, the participating countries launched roughly 1,235 investigations and made 239 arrests in connection with online operations for the sale of potentially dangerous or unapproved prescription drugs. Furthermore, INTERPOL’s report explained that Operation Pangea VII “identifi[ed] and dismantle[d] three illicit laboratories in Colombia” and “targeted the main areas exploited by organized crime in the illegal online medicine trade: rogue doman name registrars, electronic payment system and delivery services.” (To read the full text of INTERPOL’s announcement, please click here.)

As we previously reported here, after 2012’s Operation Pangea V, which targeted over 4,100 internet pharmacies and required 18,000 pharmacy websites to shut down their operations, the FDA launched a new website, BeSafeRx: Know Your Online Pharmacy, to provide consumers with information about the dangers of purchasing medicine from online pharmacies. Last year, the FDA participated in Operation Pangea VI, which resulted in the shutdown of over 9,600 websites and seizure of more than $41 million worth of illegal medicines worldwide. (To read the FDA’s announcement regarding Operation Pangea VI, please click here.)  The FDA’s continued participation in Operation Pangea sends a strong signal to industry that the FDA does not plan to back down anytime soon. Rather, it seems clear that the FDA intends to closely monitor online pharmacies and will continue to actively enforce drug and medical device regulations.

Fuerst Ittleman David & Joseph, PL will continue to monitor the regulation of online pharmaceutical drug companies. The attorneys in the Food, Drug, and Life Sciences practice group are well-versed in the complex regulatory framework for prescription drugs and medical devices. If you have any questions or would like more information, please email us at contact@fidjlaw.com or call us at (305) 350-5690.

FDA Publishes New Draft Guidance on Biosimilars As Congress Raises Questions About FDA’s Use of Draft Guidance Documents

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As we previously reported here, here, and here, the U.S. Food and Drug Administration (“FDA”) has been drafting guidance regarding the regulation of biosimilars since as early as 2011. A biological product is biosimilar if it is “highly similar to the reference product notwithstanding minor differences in clinically inactive components” and if there are “no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product.” See section 351(i)(2) of the PHS Act here. The biosimilar approval process is an abbreviated pathway for FDA licensure of biological products that are demonstrated to be biosimilar to or interchangeable with an FDA-licensed reference product under the Biologics Price Competition and Innovation Act (“BPCIA”).

In 2012, the FDA released three guidance documents, which outlined its expectations for submitting applications for biosimilar products to FDA pursuant to the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”). Together, these three draft guidances provided industry with general questions and answers regarding the implementation of BPCIA, as well as scientific and quality considerations for demonstrating biosimilarity to a reference product. The following year, the FDA released a fourth draft guidance document outlining the procedures for formal meetings that occur between the FDA and sponsors or applicants during the development phase of a biosimilars. Since then, manufacturers of biological products have eagerly anticipated the FDA’s release of final guidance.

On May 14, 2014, instead of issuing final guidance on biosimilars, the FDA issued yet another draft guidance document, Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product. According to the FDA, this draft guidance is “intended to assist biological product sponsors with the design and use of clinical pharmacology studies to support a showing that a proposed therapeutic biological product is ‘biosimilar’ to its reference product under [BPCIA].” This draft guidance specifically applies to products for which pharmacokinetic (“PK”) and pharmacodynamic (“PD”) data are required to help demonstrate biosimilarity.

Summary of FDA’s Draft Guidance on Clinical Pharmacology Data to Support a Demonstration of Biosimilarity

Although the information set forth in the FDA’s newest draft guidance is extensive, much of the information covered here was previously addressed in the draft guidances issued in 2012 and 2013.  Unfortunately for industry, the FDA’s newest draft guidance does not offer much insight into the FDA’s regulation of biosimilars, the specific requirements for submitting a biosimilar application (“§351(k) application”), nor the likelihood of success of obtaining approval through this pathway. (For coverage of the FDA’s recent draft guidance, please click here, here, and here.)

Similar to the draft guidances issued by the FDA in 2012, FDA’s 2014 guidance explains the step-wise process for demonstrating biosimilarity. This draft guidance emphasizes the “critical” role of pharmacological studies in the demonstration of biosimilarity because they “support[] a demonstration that there are no clinically meaningful differences between the proposed biosimilar and the reference product.” Moreover, clinical pharmacology studies are important because they “add to the totality of the evidence, reduce residual uncertainty, and thus guide the need for and design of subsequent clinical testing” in the overall demonstration of biosimilarity. Id. When developing proposed biosimilar products, the FDA identified three key concepts that must be addressed in any §351(k) application: (1) exposure and response assessment, (2) evaluation of residual uncertainty, and (3) assumptions about analytical quality and similarity.

–          Exposure and Response Assessment: The FDA explains that exposure-response information is important for determining the “safety, purity, and potency of any biological product.” For the purposes of this guidance document, exposure refers to PK variables, including input of all active components of a biological product as measured by dose and drug concentrations in plasma and other biological fluids. Response, on the other hand, refers to PD variables, or the direct measures of the pharmacological or toxicological effects of a drug on the body.

–          Evaluation of Residual Uncertainty: The FDA intends to use a risk-based approach in evaluating the data provided in a sponsor’s § 351(k) application. Specifically, the FDA announced that it will consider the “totality of the data and information submitted,” including data from structural and functional characterization, nonclinical evaluations, human PK and PD studies, clinical immunogenicity testing, and investigation of clinical safety and clinical effectiveness.

–          Assumptions About Analytical Quality and Similarity: The FDA directs sponsors to conduct “extensive and robust comparative structural and functional studies (e.g. bioassays, binding assays, and studies of enzyme kinetics)” to evaluate whether the proposed biosimilar and the reference product are highly similar. The capabilities and limitations of these “state-of-the-art analytical assays” should be fully described in the § 351(k) application’s analytical assessment. Interestingly, the FDA encourages applicants to compare the quality attributes of the proposed biosimilar product with those of the reference product using a “meaningful fingerprint-like analysis algorithm” that “covers a large number of product attributes and their combinations with high sensitivity using orthogonal methods.” In using this “fingerprint-like analysis algorithm,” the FDA expects sponsors to reach one of four assessments about their product: not similar, similar, highly similar, and highly similar with fingerprint-like similarity. “Not similar” products are not recommended for the biosimilar pathway unless, for example, modifications are made to the manufacturing process that are likely to lead to a highly similar biological product. “Similar” products require additional data or studies to determine if the differences are acceptable to consider the proposed product as highly similar to the reference product. Proposed biosimilars that are “highly similar” and “highly similar with fingerprint-like similarity” permit high or very high confidence that the proposed product meets the statutory standard for biosimilarity and allow sponsors to “conduct targeted and selective animal and/or clinical studies to resolve residual uncertainty and support a demonstration of biosimilarity.”

Furthermore, the FDA explains that using “accurate, precise, specific, sensitive, and reproducible” bioanalytical methods of evaluating PK and PD properties of a proposed biosimilar and its reference product is “critical” to evaluating clinical pharmacology similarity. The draft guidance document goes on to detail the requirements for these data types, including specific information regarding ligand binding assays, concentration and activity assays, and pharmacodynamics assays that should be included in an application. In addition to these bioanalytical evaluations, the FDA recommends that applicants collect safety and immunogenicity data to supplement the overall assessment of biosimilarity.

Lastly, the guidance document encourages applicants to discuss crucial aspects of their clinical pharmacology development plan with the FDA. Specifically, the draft guidance outlines nine different study design areas that industry should consider in those discussions: crossover design, parallel design, the reference product, study population, dose selection, route of administration, pharmacokinetic measures, pharmacodynamic time profile, and the statistical comparison of PK and PD results.

The FDA is accepting comments on this draft guidance until the August 12, 2014. Comments can be submitted electronically to http://www.regulations.gov [Docket No. FDA-2014-D-0234].

FDA Under Scrutiny for Draft Guidances

In its 2014 biosimilars draft guidance, the FDA reiterates that, once finalized, this guidance will be a part of a series of guidance documents intended to implement the BPCIA. It will be interesting to observe how swiftly the FDA issues final guidance on biosimilars, especially in light of the recent scrutiny the FDA has faced regarding its policies on and use of draft guidances. One week before the most recent draft guidance was issued, the FDA received a letter from the U.S. Senate Committee on Health, Education, Labor and Pensions (the “Senate HELP Committee”), expressing “significant concern about the [FDA’s] use of draft guidances to make substantive policy changes.” (The full text of the Senate HELP Committee’s letter to FDA can be accessed here, courtesy of Hyman, Phelps, & McNamara, P.C.) In its letter to FDA, the Senate HELP Committee voiced its concern that “that these draft guidances are not being revised, finalized, or withdrawn in a timely manner.” As a result of the FDA’s failure to finalize guidances in a timely manner, FDA review staff, patients, clinicians, and FDA-regulated companies “feel compelled to follow draft guidances as if they were final” because these drafts are the only information available on the agency’s most current thinking on important issues.

Furthermore, the Senate HELP Committee expressed concern that the FDA “issues guidance that seemingly does not take into account, or may even conflict with, the scientific community.” In order to better understand the FDA’s use of guidance to effectively communicate with FDA-regulated entities seeking advice on how to bring life-saving medical products to patients, the Senate HELP Committee has requested FDA to provide additional information about all Level 1 Draft Guidances, including the date issued, and the timeline with which the FDA plans to withdraw, revise, or finalize each guidance. The Senate HELP Committee also requested the FDA to provide an update on FDA-wide activities to implement the “best practices” to make the finalization of guidance more efficient and expeditious. In addition, the letter asked the FDA to produce information on the average amount of time that FDA has taken to finalize draft guidances in the last five years, and to explain how it ensures that FDA staff does not follow the guidance in the absence of any other policy or final guidance.

Conclusion

Given that the FDA is operating under the Senate’s microscope, it is difficult to speculate exactly when industry should expect the FDA to publish final guidance on biosimilars. It remains to be seen whether issuing the recent draft guidance shortens FDA’s timeframe for releasing final guidance or tolls FDA action in asking for public comment. The attorneys at Fuerst Ittleman David & Joseph, PL will continue to monitor any developments in the FDA’s regulation of biosimilars. For more information, please feel free to contact us by email at contact@fidjlaw.com or by phone at (305) 350-5690.

“Prescription” v. “Recommendation”: How State Medical Marijuana Laws May Insulate Treating Physicians From Liability Under The Controlled Substances Act

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As of today, twenty states and the District of Columbia have legalized marijuana for medicinal purposes. (A complete list of the states which have legalized  marijuana use, including summaries of each state’s use laws can be found here.) While the nationwide debate has focused on how the patchwork of laws in the United States treats patient use and commercial dispensaries, physicians must also assess their potential liabilities when recommending or prescribing marijuana for their patients.

As we have previously reported, despite changing state legislation, federal law still lists marijuana as a Schedule I controlled substance under the Controlled Substances Act (“CSA”); 21 U.S.C § 801 et seq. Schedule I controlled substances are subject to the most strict regulation under the CSA because the federal government has determined that these substances have a “high potential for abuse,” “no currently accepted medical use in treatment in the United States, “ and a “lack of accepted safety” for “use under medical supervision.” See  21 U.S.C. § 812(b)(1). The CSA prohibits physicians from prescribing Schedule I drugs. Under the CSA, Schedule I drugs may only be dispensed in the United States through strictly-controlled, federally-approved research programs.

In order to prescribe a controlled substance, a physician must first register with the Attorney General of the United States. However, the CSA also confers authority on the Attorney General to revoke a physician’s registration for a variety of reasons, including if the physician “has committed such acts as would render his registration under section 823 of this title inconsistent with the public interest. . . .” See 21 U.S.C. § 824(a)(4). In determining whether a physician has acted “inconsistent with the public interest,” the Attorney General may consider a physician’s “compliance with applicable State, Federal, or local laws relating to controlled substances.” See 21 U.S.C. § 823(f). Thus, because marijuana is a Schedule I substance that the CSA makes unlawful to possess, use, or distribute, a physician prescribing medicinal marijuana pursuant to State law could subject himself to federal criminal penalties and revocation of his registration to dispense controlled substances. However, as explained below, physician liability under federal law may turn on whether doctors can be properly classified as “prescribing” marijuana for patient use.

Pursuant to the CSA and its implementing regulations, a “prescription” is defined as “an order for medication which is dispensed to or for an ultimate user but does not include an order for medication which is dispensed for immediate administration to the ultimate user.” See 21 C.F.R. § 1300.01. However, many states with medicinal marijuana laws, including California, Massachusetts, Michigan, Maine, Colorado, and Illinois do not authorize their physicians to “prescribe” marijuana as that term is defined under state law or the CSA. Instead, these states provide that a patient’s treating physician “recommend” or “certify” that the patient qualifies for participation in the state’s medicinal marijuana program. In addition, these recommendations or certifications are not designed to allow patients to directly obtain marijuana. Instead, patients gain access to medicinal marijuana solely through registration with the state and purchase the product through state licensed dispensaries. Put simply, the physician’s role is limited to evaluating whether, in the physician’s medical opinion, a patient qualifies for participating in the state sanctioned marijuana program.

In Conant v. Walters, 309 F.3d 629 (9th Cir. 2002), a case analyzing California’s Compassionate Use Act, the Ninth Circuit found that the recommendation of marijuana use by a treating physician to a patient cannot serve as the sole basis for revoking or suspending the physician’s registration to dispense controlled substances under the CSA. In Conant, the Ninth Circuit made clear that a doctor’s recommendation that a patient use a controlled substance is not the same as a prescription for a controlled substance, and without more, would fall outside of the scope of aiding and abetting or conspiracy to commit a violation of the CSA.

As explained in greater detail in the decision, a doctor’s recommendation of marijuana could lead to several lawful and legitimate responses, including lawful use of medicinal marijuana through a federally-approved experimental therapy program or travel to a country where marijuana is legally dispensed. Moreover, the Ninth Circuit found that the mere possibility that illegal conduct could occur was too attenuated to justify a restriction on the free speech rights of doctors and patients. Thus, the Ninth Circuit found that the First Amendment prohibited the government policy which threatened to punish physicians for recommending to a patient the medical use of marijuana on the ground that the recommendation might encourage illegal conduct by the patient. Therefore, at least as it stands in the Ninth Circuit, recommendation alone cannot serve as a basis for liability under the CSA. As medicinal marijuana statutes proliferate in states outside of the Ninth Circuit, it remains to be seen whether other Circuits will adopt the Ninth Circuit’s interpretation.

Fuerst Ittleman David & Joseph, PL will continue to watch for the latest developments in the regulation of the marijuana industry. The attorneys at Fuerst Ittleman David & Joseph, PL have extensive experience in the areas of administrative law, anti-money laundering, food & drug law, tax law and litigation, constitutional law, regulatory compliance, white collar criminal defense and litigating against the U.S. Department of Justice. If you are a physician or marijuana-related business, or if you seek further information regarding the steps which your business must take to become or remain compliant, you can reach an attorney by emailing us at contact@fidjlaw.com or by calling us at 305.350.5690.

False Claims Act Litigation Update: Bayer Decision Sheds Light on Pleading in False Claims Act Cases

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A recent win for a large company in a False Claims Act suit (a seeming rarity as of late) alleging illegal off-label promotion could provide some helpful insight to similarly situated manufacturers and support dismissals of similarly defective lawsuits. Laurie Simpson, the relator and an employee at Bayer Corporation for seven years, helped market and promote Trasylol, a prescription drug approved by the FDA for patients undergoing coronary artery bypass graft using a cardiopulmonary bypass pump to prevent excess bleeding. In Simpson’s 131-page complaint containing 30 causes of action, she alleged that Bayer violated the False Claims Act by “engaging in a campaign of concealment and disinformation concerning Trasylol’s safety and efficacy.” Specifically, Simpson’s complaint alleged that Bayer promoted Trasylol for other types of surgeries and failed to provide safety and efficacy information about those other uses. Simpson alleged that such omissions resulted in the misbranding of Trasylol under the Federal Food, Drug, and Cosmetic Act (“FDCA”).

Generally, the False Claims Act is a federal law that imposes liability on corporations who defraud governmental programs. Notably, the Act includes a “qui tam” provision, which allows individuals not affiliated with the government to file actions on behalf of the government. There are two categories of false claims upon which a relator can base a qui tam complaint: factually false claims and legally false claims. While factually false claims are false as to a matter of fact, legally false claims involve false certifications of compliance with laws or regulations that are prerequisites to payment.

The allegations Simpson presented were legally false claims because they were based on the alleged misbranding of Trayslol in violation of the FDCA. In response to Simpson’s allegations, Bayer filed a motion to dismiss Simpson’s complaint. In its motion, Bayer argued that Simpson failed to adequately plead a false claim for payment, a critical element of a False Claims Act violation. Under the False Claims Act, to adequately plead a legally false claim, Simpson had to establish that Bayer made an implied certification that Trasylol complied with the FDCA restriction against misbranding, and that such compliance with the FDCA was a “condition of payment” from the government.

The U.S. District Court for the District of New Jersey reviewed each of the government programs that Bayer allegedly defrauded (i.e., Medicare, DOD, Tricare) to determine whether the government conditioned its payments for Trasylol on the limited on-label use of the drug.  On April 11, 2014, the court granted Bayer’s motion to dismiss Simpson’s complaint concluding that Simpson’s “bare legal conclusions” did not adequately plead the existence of a condition of payment. In other words, even assuming that Bayer marketed Trasylol for purposes other than those included on Trasylol’s FDA approved label, the District Court ruled that Simpson needed to allege more to properly state a claim under the False Claims Act. The court noted that the purpose of the False Claims Act “was not designed for use as a blunt instrument to enforce compliance with all medical regulations, but rather only those regulations that are a precondition to payment.” The court’s decision can be read here. This statement by the court will surely support dismissals of other complaints with similarly defective allegations.

The attorneys at Fuerst Ittleman David & Joseph, PL will continue to monitor developments in this and similar cases. Our attorneys have extensive experience in the areas of food and drug, administrative law, qui tam, regulatory compliance, and white-collar criminal defense.  If you have any questions, an attorney can be reached by emailing us at contact@fidjlaw.com or by calling (305) 350-5690. Let FIDJ show you how we can help today.

FDA Regulatory Update: FDA to Recommend Reclassifying Hydrocodone Combination Drugs; Issue Highlights Cooperative Relationship Between FDA, DEA

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On October 24, 2013, Janet Woodcock, the U.S. Food and Drug Administration’s (“FDA”) Director for the Center for Drug Evaluation and Research (“CDER”),issued a statement explaining that the FDA will recommend that the U.S. Drug Enforcement Administration (“DEA”) reclassify hydrocodone combination products from Schedule III to Schedule II under the Controlled Substances Act (“CSA”). This statement comes ten years after the DEA first approached the U.S. Department of Health and Human Services (“HHS”) for a recommendation. The reclassification, however, will not go into effect unless the proposed change is approved and accepted by the DEA.

Regulatory Framework for Controlled Substances

Pursuant to the CSA, the DEA has regulatory authority over controlled substances, which are certain drugs that have potential for abuse and dependence. (For more information on the regulation of controlled substances, please read 21 U.S.C. § 801  et seq.  and the DEA’s Office of Diversion Control Controlled Substance Schedule, which can be accessed here.) Controlled substances are classified into five distinct categories, or schedules, depending on the drug’s acceptable medical use and potential for abuse or dependency.

Schedule I consists of the drugs with the highest potential for abuse and Schedule V represents the class of drugs with the lowest potential for abuse. Specifically, Schedule I drugs are defined as having “no currently accepted medical use,” lacking accepted safety for use under medical supervision, and carrying a high potential for abuse. Examples of Schedule I drugs are heroin, ecstasy, peyote, and marijuana. (To read our previous posts regarding the federal regulation of marijuana as a controlled substance, please click here, here, here and here.) Schedule II drugs are also considered dangerous but have a lower abuse potential than Schedule I drugs, with use potentially leading to severe psychological or physical abuse. Examples of current Schedule II drugs are methamphetamines and oxycodone. Schedule III drugs are defined as having a “moderate to low potential for physical and psychological dependence” and pose a higher abuse potential than Schedule IV drugs, which are defined as having a “low potential for abuse and low risk of dependence.” Carrying the lowest risk of drug abuse potential are Schedule V drugs, which usually consist of preparations containing limited quantities of certain narcotics, such as those used for antidiarrheal, antitussive, and analgesic purposes. (For more information about the scheduling of controlled substances, please visit the DEA’s website here.)

Proceedings to control, remove from control, or re-schedule a drug or substance may be initiated by the DEA, HHS, or by petition from any interested party, such as a drug manufacturer, medical society, public interest group, state agency, or individual. When a petition is received by the DEA, the agency begins its own investigation of the drug. Once the DEA has collected the necessary data, the DEA Administrator, by authority of the Attorney General, requests from HHS a thorough scientific and medical evaluation and recommendation “as to whether such drug or other substance should be so controlled or removed as a controlled substance.” See 21 U.S.C. § 811(b). Then, HHS solicits information from the FDA, the National Institute on Drug Abuse, and if it so chooses, the scientific and medical community. The scientific and medical matters contained in the recommendation “shall be binding on the Attorney General.” Id. Once the DEA has received the scientific and medical evaluation from HHS, the DEA will evaluate all available data and make a final decision. Section 811(c) of the Controlled Substances Act directs the DEA to consider the following factors:

  1. Its actual or relative potential for abuse;
  2. Scientific evidence of its pharmacologic effect, if known;
  3. The state of current scientific knowledge regarding the drug or other substance;
  4. Its history and current pattern of abuse;
  5. The scope, duration and significance of abuse;
  6. What, if any, risk there is to public health;
  7. Its psychic or physiological dependence liability; and
  8. Whether the substance is an immediate precursor of a substance already controlled under this subchapter.

Although the DEA works hand-in-hand with HHS with respect to controlled substances, the DEA has the ultimate decision-making authority to take

DEA Seeks Recommendation Regarding the Reclassification of Hydrocodone Combination Products

        FDA’s recent statement that it intends to formally recommend the reclassification of hydrocodone combination products comes after nearly ten years of debate. Back in 2004, the DEA asked the FDA to investigate and recommend whether to reclassify hydrocodone combination products from Schedule III to Schedule II. In response, the FDA concluded that hydrocodone combination products should remain a Schedule III drug because “hydrocodone combination products have a less potential for abuse than the drugs or other substances in Schedule II.” (For more information regarding the FDA’s scientific and medical investigation of hydrocodone, please click here.)

        As a result of continued pressure from the public and industry organizations, the DEA collected and re-analyzed new data regarding the abuse of hydrocodone combination products in 2008. The following year, DEA submitted another request to FDA to reconsider moving all hydrocodone combination products to Schedule II. On January 24 – 25, 2013, the FDA’s Drug Safety and Risk Management Advisory Committee convened to discuss the public health benefits and risks of drugs containing hydrocodone, as well as the potential for abuse or dependency. (For a comprehensive review of the FDA’s recommendation, please read the FDA Briefing Document, Drug Safety and Risk Management Advisory Committee (DSaRM) Meeting 1 here and here.) At the culmination of this meeting, the FDA Advisory Committee voted 19 to 10 in favor of rescheduling hydrocodone combination products from Schedule III to Schedule II. (To read FDA’s Memorandum summarizing the events of this meeting, please click here.) Nine months later, the FDA announced its intention to formally recommend reclassifying hydrocodone combination products to Schedule II.

In light of the Advisory Committee’s decision in January 2013, the FDA’s statement that it intends “to recommend to HHS that hydrocodone combination products should be reclassified to a different and more restrictive schedule” comes as no surprise. (To read the FDA’s statement, please click here. For additional news coverage, please click here, here, here, and here.) The FDA’s recommendation to reclassify hydrocodone combination products could have a significant impact on how physicians prescribe these products. For instance, Schedule II drugs require patients to present a written prescription to the pharmacy, as physicians cannot call in a prescription for Schedule II drugs. Most notably, if the DEA accepts the FDA’s recommendation, hydrocodone combination products will be subject to stricter security controls, including a restriction on the amount of medication that a patient can be prescribed. If reclassified as Schedule II drugs, a physician would only be permitted to prescribe refills of hydrocodone combination products for up to three months, which is half the amount allowed for Schedule III drugs.

The FDA has not submitted a final recommendation package to HHS, but expects to do so by early December 2013. If this recommendation is accepted by the DEA, new regulations could go into effect as early as 2014. (For more information, please read the New York Times’s coverage here.)

Fuerst Ittleman David & Joseph, PL will continue to monitor the developments in the classification of hydrocodone combination products. For more information, please feel free to contact us by email at contact@fidjlaw.com or by phone at (305) 350-5690.

FDA Medical Device Regulation Update: FDA Issues Final Rule for Unique Device Identification System

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On September 20, 2013, the U.S. Food and Drug Administration (“FDA”) announced the issuance of the final rule for the Unique Device Identification System (“UDI System”). The final rule sets forth the labeling and reporting criteria for medical devices, combination products that contain devices, and devices licensed under the Public Health Service (“PHS”) Act. In its press announcement, the FDA explained that the UDI System was developed to help “identify product problems more quickly, better target recalls, and improve patient safety.” (For additional coverage of the FDA’s final rule for the UDI System, please read Reuters’ article here and Bloomberg BNA’s article here.)

The medical device industry has anxiously awaited the FDA’s final rule for the UDI System since 2007, when President Bush signed the Food and Drug Administration Amendments Act (“FDAAA”). Despite pressure from industry and lawmakers, the FDA failed to release a final rule in a timely fashion. In 2012, President Obama signed the Food and Drug Administration Safety and Innovation Act (“FDASIA”), which imposed on the FDA mandatory publication deadlines. Thereafter, on July 10, 2012, the FDA issued a proposed rule for the UDI System.

UDI System Requirements

The UDI System requires certain medical devices to bear a UDI on the device’s package and label. The UDI System is comprised of two main parts: 1) the device identifier (“DI”) and 2) the production identifier (“PI”). The DI is a mandatory, fixed portion of the UDI that identifies the labeler and the specific version of a model of a device. The PI is a conditional or variable portion of the UDI that identifies one or more of the following when included on the label of a device: the lot or batch number of the device, the serial number of a device, the expiration date of a device, the device’s manufacturing date, and if the product is a human cell, tissue, or cellular and tissue-based product (“HCT/P”) regulated as a device, a distinct identification code.

The final rule articulates target dates by which medical devices are expected to comply with the applicable UDI regulations. These compliance dates come into effect as early as 2014 and as late as 2020. Within one year of the publication of the final rule for the UDI System, all class III medical devices and devices licensed under the PHS Act must bear a UDI. Class II medical devices are expected to bear a compliant UDI within three years of the publication of the final rule, and all class I, II, and III medical devices must bear a UDI within five years of the publication of the final rule. Within seven years of the publication of the final rule, all Class I devices and devices that have not been classified into any class are required to bear a UDI as a permanent marking on the device if the device is intended to be used more than once and intended to be reprocessed before each use. (For a more detailed explanation of the FDA’s compliance dates, please click here.)

Global Unique Device Identification Database

In addition to specific requirements for UDI labeling, the FDA will also require medical device manufacturers to submit information about the devices to the FDA. Together with the final rule for UDI labeling, the FDA released the Draft Guidance for the Global Unique Device Identification Database (“GUDID”). The GUDID is a new database that will serve as a “repository of key device identification information.” The draft guidance explains that manufacturers of medical devices are required to submit information about the labeler and the device model to the FDA, which will be entered into and publicly searchable through the GUDID. Production Identifier information, on the other hand, does not need to be submitted to or stored in the GUDID. The FDA is currently accepting public comments on the draft guidance and recommends submitting a comment for consideration before November 25, 2013.

The FDA’s staggered timeline for compliance with the new UDI System provides industry with considerable time to modify their device labeling and reporting operations in accordance with the new regulations. Consumers and advocates for the UDI requirements, however, seem dismayed by the lengthy implementation timeline. In addition to the six years it took the FDA to finalize the UDI regulations, consumers will have to wait another seven years for the UDI medical device tracking system to be fully functional and operational.

Fuerst Ittleman David & Joseph, PL will continue to monitor any new developments in the implementation of the UDI System and the GUDID. Our regulatory attorneys are experienced in working with medical device companies to ensure product labeling is compliant with all FDA laws and regulations. If you need assistance with your medical device or have further questions about these new changes to medical device labeling, please do not hesitate to contact us via email at contact@fidjlaw.com or by telephone at (305) 350-5690.