Category: FDA

FDA Issues Final Guidance on Biosimilars

Shortly after approving the first biosimilar under the abbreviated approval pathway created by the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”), the FDA has recently issued 3 final guidances regarding biosimilars. Biological products, or “biologics,” are pharmaceutical products created from biological sources. Unlike chemically synthesized pharmaceuticals, biologics are isolated from natural sources, and are typically more complex than conventional pharmaceutical drugs.

The BPCIA provides abbreviated pathways for the FDA to approve two types of follow-on biologics: biosimilar and interchangeable biological products. Similar to the 1984 Hatch-Waxman Act’s abbreviated pathway for pharmaceuticals, the BPCIA allows a sponsor to seek approval of a “biosimilar” product under section 351(k) of the Public Health Service Act (“PHS Act”) by relying on certain existing scientific knowledge about the safety, purity, and potency of the reference product. The BPCIA defines “biosimilar” as (1) “highly similar to the reference product notwithstanding minor differences in clinically inactive components” and (2) having “no clinically meaningful differences between the biosimilar product and the reference biological product in terms of the safety, purity, and potency of the product.” To meet the higher standard of “interchangeability,” the application must further show (1) the biosimilar is expected to produce the same clinical result as the reference product and (2) a patient can switch back and forth between the biosimilar and the reference product with no adverse effects.

The BPCIA provides abbreviated pathways for the FDA to approve two types of follow-on biologics

The FDA has been slow to accept and approve biosimilar applications, which has left open questions about how to establish biosimilarity and interchangeability under the statutory definitions. On April 28, 2015, the FDA finalized three draft guidances originally published in 2012:

  • Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009

  • Scientific Considerations in Demonstrating Biosimilarity to a Reference Product

  • Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product

The new guidances provide insight into the FDA requirements for establishing biosimilarity.

Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009

This final guidance addresses three categories of commonly asked questions regarding FDA implementation of the BPCIA: (1) biosimilarity or interchangeability; (2) definitions relevant to the BPCIA; and (3) exclusivity. With regard to biosimilarity or interchangeability, the guidance states that a proposed biosimilar may have a different formulation, delivery device, or container closure than the reference product under certain circumstances. Additionally, the guidance discloses conditions permitting an applicant to obtain licensure for fewer than all routes of administration, presentations, and conditions of use for which the reference product is licensed. Further, the guidance describes conditions in which a sponsor may support biosimilarity using comparative data with a non-U.S.-licensed product or extrapolated clinical data designed to support a different condition of use. The guidance additionally instructs applicants how to describe the “strength” of a proposed injectable biosimilar. Finally, the guidance states that a biosimilar product that cites a reference product subject to the Pediatric Research Equity Act must include a pediatric assessment unless the applicant initially seeks approval as an interchangeable biological product.

With regard to the BPCIA’s definition of “biological product,” the guidance discloses the FDA’s regulatory definitions of “protein” and “chemically synthesized polypeptide.” Additionally, it defines when a proposed biological product is considered to be within the same “product class” as previously approved protein products.

With regard to exclusivity, the guidance instructs applicants and sponsor to search an online database to identify whether the reference product is subject to unexpired orphan exclusivity. The FDA will not approve a biosimilar during the 7-year exclusivity period.

Scientific Considerations in Demonstrating Biosimilarity to a Reference Product
This final guidance provides an overview of the FDA’s recommendations for establishing biosimilarity and discusses in detail relevant scientific principles for designing data and information to show biosimilarity. The FDA stresses that it will apply a totality-of-the-evidence approach in its assessment of biosimilarity and will use a risk-based approach to evaluate all data and information submitted. The FDA further emphasizes that the information sufficient to demonstrate biosimilarity will be determined on a product-specific basis.

The BPCIA requires an application to include analytical, animal, and clinical studies demonstrating that the biological product is “biosimilar” to a single reference product. As discussed above, the application must establish the product is “highly similar” to the reference product and has “no clinically meaningful differences.” Although the reference product must be U.S.-licensed, the application may rely on data from comparative studies with a non-U.S. licensed comparator product if the data is scientifically relevant. Because the FDA has discretion to determine what data is required to establish biosimilarity in a particular application, it encourages sponsors of the application to meet with the FDA early during product development to discuss adequate scientific justifications.

The FDA encourages sponsors to use a three step approach to develop evidence necessary to establish biosimilarity.

First, the sponsor should characterize the structural and functional aspects of both the proposed product and the reference product to identify potentially clinically relevant safety or efficacy risks. Structural analyses must use “state-of-the-art technology” to analyze multiple representative lots and show the proposed product will encode the same primary amino acid sequence as the reference product. Any minor modifications must be explained by the sponsor. The structural analyses for all relevant characteristics of the protein product (such as primary, secondary, tertiary, and quaternary structure; posttranslational modifications; and biological activities) must also be included. The FDA further recommends structural analysis of the finished dosage form to assess the effect of excipients or any other formulation effects. In vitro and/or in vivo functional assays must also be used to evaluate the pharmacologic activity of protein products.

Second, the sponsor should demonstrate safety and biosimilarity through animal studies. These studies generally do not establish safety, but are relevant to support the demonstration of biosimilarity through evidence of PK and PD measures. Nevertheless, animal toxicity and immunogenicity studies may be useful where uncertainty about safety remains after the initial structural and functional characterization.

Third, the sponsor should conduct comparative human PK and PD studies and a clinical immunogenicity assessment of the two products in an appropriate study population. The sponsor should discuss study proposals and overall clinical development plan with the FDA before initiating such studies. A sponsor should provide adequate scientific justification for choices in study design, population, endpoints, and other parameters. Human PK and PD measures comparing the proposed product to the reference product are typically fundamental to demonstrate biosimilarity. Even where relevant PD measures are not available, sensitive PD endpoints may be assessed. The FDA further expects at least one comparative clinical study regarding immunogenicity in order to assess the safety and effectiveness of the proposed product. The overall immunogenicity assessment should consider the nature of the immune response, the clinical relevance and severity of consequences, the incidence of immune responses, and the population being studied. Generally, the FDA expects studies to present statistical evidence that the proposed product is neither significantly inferior nor superior to the reference product. An applicant may provide sufficient scientific justification to extrapolate clinical data to support a determination of biosimilarity for various indications.

If there is uncertainty at each step, the sponsor should evaluate the uncertainty and consult with the FDA to adequately address it.

Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product

This guideline relates to the biosimilarity of therapeutic protein products and describes nine factors that are relevant in developing analytical studies to show a proposed product is “highly similar” to a reference product.

1. Expression System. The application should seek to minimize differences between the proposed and referenced expression systems. The FDA expects the expression construct for a proposed product encodes the same primary amino acid sequence as its reference product. However, minor modifications (such as N- or C- terminal truncations) that are not expected to change the product performance may be justified.

2. Manufacturing Process. The application should demonstrate its manufacturing process does not result in significant differences between the proposed product and its reference product.

3. Assessment of Physiochemical Properties. Physicochemical assessments are designed to maximize the potential for detecting differences between the proposed and reference products. The sponsor should consider all relevant characteristics of the protein product and design tests to account for the heterogeneity of the proposed product and the reference product as well as the ranges of variability for each.

4. Functional Activities. Functional assays are designed to complement physicochemical analyses and evaluate the function of the protein product. Sponsors should perform appropriate assays to evaluate the range of relevant functional activities for a product.

5. Receptor Binding and Immunochemical Properties. Sponsors should analyze specific binding or immunochemical properties when they are part of the activity attributed to the protein product.

6. Impurities. Sponsors should characterize, identify, and quantify impurities in the proposed product and reference product. Sponsors should further perform a risk-based assessment regarding any differences in process-related impurities between the proposed and reference products.

7. Reference Product and Reference Standards. Sponsors should provide a broad comparison of the proposed product to the reference product that is not strictly limited to analysis of each product in isolation. For example, the biosimilarity analysis may further consider applicable reference standards and relevant publicly available information.

8. Finished Drug Product. Product characterization studies should be performed on the most downstream intermediate best suited for each analytical procedure. Thus, sponsors should analyze the finished drug product if it is best suited for a particular analysis. If the analysis is performed on an earlier intermediate, sponsors should provide additional information. Additionally, sponsors should clearly identify excipients used in the proposed product that differ from those in the reference product.

9. Stability. Sponsors should include comparative studies conducted under multiple stress conditions to establish degradation profiles of the proposed and reference product.

Conclusion

The recently issued final guidances provide insight into how the FDA will evaluate biosimilarity and directions for sponsors throughout product development. However, many additional questions surrounding the BPCIA remain. For example, the currently issued guidances do not address how the FDA will determine “interchangeability.” Interchangeable drugs are likely to be more profitable than mere biosimilars because they can be sold in place of the reference drug without a prescribing doctor’s approval.

Upcoming draft guidances plan to provide additional information regarding the required scientific requirements for establishing biosimilarity and interchangeability as well as naming and labeling requirements for approved biosimilars. In January, the FDA’s Center for Drug Evaluation and Research (CDER) announced plans to publish five draft guidances on biosimilars in 2015:

  • Biosimilars: Additional Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009

  • Considerations in Demonstrating Interchangeability to a Reference Product

  • Labeling for Biosimilar Biological Products

  • Nonproprietary Naming for Biological Products

  • Statistical Approaches to Evaluation of Analytical Similarity Data to Support a Demonstration of Biosimilarity

ARTICLE BY Imron T. Aly, Sailesh K. Patel, John K. Hsu and Helen H. Ji of  Schiff Hardin LLP
© 2015 Schiff Hardin LLP

FDA Regulation of mHealth Updates

Covington & Burling LLP

At the Food Drug and Law Institute’s annual conference on April 21, 2015, Bakul Patel, Associate Director for Digital Health, Office of Center Director, Center for Devices and Radiological Health (CDRH), held a discussion of “FDA Regulation of Mobile Health/Medical Applications.”  There have already been several important developments in FDA regulation of mHealth products this year.  Patel stated that FDA recognizes the importance of digital health, and its potential to drive be

ARTICLE BY

Cassie Scherer
Covington & Burling LLP
Covington E-Health

tter health outcomes and promote patient engagement.  Patel discussed two recently released draft guidances that impact FDA regulation of mHealth, the draft General Wellness Guidance and the draft Accessories Guidance, and highlighted that FDA continues to work promote innovation while at the same time protecting patient safety.  The public comment period for these guidances ended on April 20th, and Patel noted that CDRH did not receive many comments.  Finally, Patel emphasized that industry can continue to reach out to FDA with questions about mobile health at mobilemedicalapps@fda.hhs.gov or digital health at digitalhealth@fda.hhs.gov.

The discussion draft of the 21st Century Cures Act includes sections that would exclude “health software” from regulation as a medical device, and would require FDA to promulgate regulations to establish standards and procedures for regulating “medical software.”  New 21st Century Cures language may be released by the end of this month.  We will be watching closely to see if there are any changes to the software language.

FDA Requests Comments on WHO Recommendation to Classify Two Common Industrial Solvents as Psychotropic Substances

Beveridge & Diamond PC environmental and energy law firm

On January 27, 2015, the Food and Drug Administration (“FDA”) requested comments on a recommendation by the World Health Organization (“WHO”) to classify two common industrial solvents – gamma-butyrolactone (“GBL”) and 1,4-butanediol (“BDO”) – as psychotropic substances under Schedule I of the 1971 Convention on Psychotropic Substances (“Psychotropic Convention”). See 80 Fed. Reg. 4283.  The comments will be used by the Secretary of Health and Human Services (“HHS”) to prepare a recommendation on the WHO proposal to the Secretary of State, which will be binding on the U.S. representative to the upcoming 58th Session of the UN Commission on Narcotic Drugs (“CND”) in Vienna, Austria, on March 9-17, 2015.  At the Vienna meeting, CND may accept the WHO recommendations, reject the recommendations, or decide to control the chemicals in another way (i.e., under a different Schedule of the Convention).

FDA notes that if either chemical – or any of the other chemicals that are also recommended for listing, but are not addressed here because they have few, if any, legitimate industrial uses – are added by CND to Schedule I of the Psychotropic Convention, the U.S. will have to impose additional controls on the chemical(s) under the Controlled Substances Act (“CSA”) administered by the Drug Enforcement Administration (“DEA”).  Although FDA does not elaborate on what those controls might consist of, they would likely include additional restrictions on manufacture, distribution, import, and export of the chemicals, as well as enhanced recordkeeping and reporting requirements. For example, Article 2(7)(a)(i) of the Psychotropic Convention states that parties shall require licenses for manufacture, trade, and distribution of Schedule I substances.  Moreover, Article 7(a) provides that parties must “[p]rohibit all use [of Schedule I substances] except for scientific and very limited medical purposes by duly authorized persons,” although Article 2(7)(a) allows individual parties to notify the UN that they cannot do so as a result of “exceptional circumstances,” in which case the party need only “take into account” the prohibition “as far as possible.”

It is worth noting that GBL is already regulated under the CSA as a precursor to gamma-hydroxybutyric acid (“GHB”), which is a commonly abused central nervous system depressant drug that is currently regulated under Schedule II of the Psychotropic Convention and Schedule I of the CSA.  In particular, GBL is classified under the CSA as a “List I” precursor (not to be confused with a CSA Schedule I or other controlled substance), and thus is already subject to significant DEA controls.  In addition, some U.S. states and authorities in some other countries already regulate GBL directly as a controlled substance or its equivalent.  Nevertheless, the addition of GBL to Schedule I of the Convention would likely require new and more stringent controls in most jurisdictions.  Additional information on the basis for the WHO recommendation for GBL (including the chemistry of the chemical, abuse potential, legitimate uses, and current regulation around the world) can be found in the 2014 GBL Critical Review Report of the WHO Expert Committee on Drug Dependence.

BDO is also a precursor to GHB, but is not currently regulated under the CSA.  It is regulated in several U.S. states and other countries as a precursor or controlled substance equivalent.  Once again, however, if it is added to Schedule I of the Psychotropic Convention, it will likely become subject to substantial additional restrictions.  Additional information on the basis for the WHO recommendation for BDO can be found in 2014 BDO Critical Review Report of the WHO Expert Committee on Drug Dependence.

FDA will accept written comments on the WHO recommendations until February 26, 2015.  Requests for a public meeting will be accepted until February 6, 2015.

ARTICLE BY

Aaron H. Goldberg
OF
Beveridge & Diamond PC

Filthy Pharma – Whistleblowers and Current Good Manufacturing Practices

Mahany Law Firm

Last year a federal appeals court in Richmond, Virginia upheld the dismissal of a whistleblower suit alleging violations of current good manufacturing practices, known in the industry as “cGMP.” Filed under the federal False Claims Act, the whistleblower claimed that his former employer, Omnicare, violated a series of cGMP safety regulations requiring that penicillin and non-penicillin drugs be manufactured in complete isolation from one another. The regulations are designed to prevent cross contamination.

Because Omnicare’s drugs were not manufactured in isolation, the whistleblower claimed that they were not eligible for reimbursement under Medicare and Medicaid programs. A judge in Baltimore dismissed the suit saying that this particular alleged cGMP was not one that could be prosecuted privately by a whistleblower.

The case was appealed and ultimately upheld by a three judge appeals panel last year. (United States ex. rel Barry Rostholder vs. Omnicare) Is this the end for “filthy pharma” cases under cGMP and the False Claims Act? No!

The Justice Department and Food and Drug Administration (FDA) support whistleblower filings for cGMP violations. In the aftermath of the Omnicare decision, however, it is prudent to have more than a mere allegation that products were not manufactured in properly segregated facilities.

In April 2013, the Justice Department announced that it would be taking “an especially hard look” at cGMP violations. Jeffrey Steger, deputy director of the Justice Department’s consumer protection unit, said the agency’s priority was to “identify and prosecute the most serious instances of food, drug and medical device violations… and in general [protect] consumers from adulterated or misbranded products…”

Notwithstanding the big loss for whistleblowers in Omnicare, the court did not slam shut the door on all cGMP violations. The court appears to have left the door open for cGMP violations that are significant and substantial and give rise to actual discrepancies in the functioning of the product.

What does this mean in practical terms? Merely claiming that a drug wasn’t manufactured properly may no longer be enough. To qualify for a whistleblower award, one should show both bad practices and that the product is tainted, adulterated, mislabeled, diluted or contaminated.

People with inside knowledge of adulterated drugs and cGMP violations may qualify for cash awards under state and federal False Claims Acts. Last year the federal government alone paid out $635 million to whistleblowers. Under the federal law, companies can be assessed triple damages and fined up to $11,000 per violation. Whistleblowers can receive up to 30% of whatever the government collects. (The average award is closer to 20%.)

ARTICLE BY

Brian Mahany
OF
Mahany Law

FDA Denies Citizen Petition’s Request to Ban Marketing of Non-Absorbable Surgical Mesh Products for Transvaginal Repair of Pelvic Organ Prolapse

Covington BUrling Law Firm

 

On July 14, 2014, FDA publicly posted its response denying Public Citizen’s August 2011 citizen petition concerning the marketing of non-absorbable surgical mesh products for transvaginal repair of pelvic organ prolapse (POP).  In its response, FDA took the position that a ban or recall of POP devices is not warranted at this time.

As background, in August 2011, Public Citizen filed a citizen petition asserting that POP devices “offer no clinically significant benefits in comparison to surgical repairs for POP performed without placement of surgical mesh” and “have high rates of serious complications.”  Public Citizen requested that the agency take the following actions: (1) ban the marketing of all available non-absorbable surgical mesh products for transvaginal repair of POP; (2) order all manufacturers to recall these products; and (3) classify all new non-absorbable surgical mesh products for transvaginal repair of POP as class III devices and approve the products only under a premarket approval application (PMA).

In its response, dated May 1, 2014, FDA denied the citizen petition.  While the agency rejected Public Citizen’s call for a ban or recall of POP devices, FDA noted that it shares some of the concerns outlined in the citizen petition and is taking actions to address these concerns.  In addition, the agency also determined that “a citizen petition is not the appropriate mechanism for requesting a reclassification of a device.”

FDA explained that in September 2011, the agency convened an advisory committee meeting of the Obstetrics and Gynecology Devices Panel to discuss the safety and efficacy of transvaginal surgical mesh products used for repair of POP.  The Panel determined that “a favorable benefit-risk profile” for these devices “had not been well-established” and that the devices should be reclassified from class II to class III.  The Panel also recommended that manufacturers conduct postmarket studies of currently marketed surgical mesh products for transvaginal repair of POP.  As of May 2014, FDA had issued 126 postmarket surveillance orders to 33 manufacturers of these devices.

FDA explained that it has evaluated information from the Panel’s recommendations and the published scientific literature and has tentatively determined that the device should be reclassified as a class III device.  On May 1, 2014, FDA published a proposed order in the Federal Register to reclassify surgical mesh for transvaginal repair of POP from class II to class III.  On the same day, FDA published another proposed order in the Federal Register to require the filing of a PMA following the reclassification of the device to class III.  Thus, although FDA did not grant Public Citizen’s third request, the agency “initiated the process that could ultimately result” in reclassification of the device and the requirement to submit a PMA for these devices.

Article By:

Colleen Kelly
Of:
Covington & Burling LLP

FDA Issues Guidance for Safety of Nanomaterials in Cosmetic Products (as well as in Food)

GT Law

For the last seven or so years, the U.S. federal government and some state governments have been collecting cradle-to-grave information regarding nanomaterials. The data collection call-ins were intended to create a collaborative, scientific dialogue with the goal of examining relevant information, and identifying information gaps and ways to address those gaps.

Last week, the FDA issued guidance documents for both cosmetic and food manufacturers. The guides are one more step intended to assist industry and other stakeholders in identifying the potential safety issues of nanomaterials in consumer products and in developing a framework for evaluating them. It also provides contact information for those who wish to discuss safety considerations regarding the use of specific nanomaterials in cosmetic products with the FDA.

If your company is considering the use of nanomaterials in its products, it is important to recognize that although nanotech cosmetics are still subject to the same legal requirements as other cosmetics, in that they do not require premarket approval, the products must be safe under customary usage conditions and properly labeled. Additionally, although the FDA has explained that the current safety framework used for conventional cosmetics is still appropriate for cosmetics using nanotech, companies should keep in mind the unique properties of nanomaterials when testing safety. Ultimately, as this guidance reminds, companies are legally liable for ensuring the safety of their products. As to food products, the FDA encourages manufacturers to contact the agency early in the development process to assist in assessing the safety and potential issues with using nanotechnology.

Read the complete press announcement from the FDA here.

Article By:

Angela Diesch
Of:
Greenberg Traurig, LLP

Making Use of Social Media: FDA Releases Two Draft Guidelines on the Use of Social Media Platforms by Drug and Device Manufacturers

MintzLogo2010_Black

The Food and Drug Administration (FDA) has released two long-awaited draft guidance documents for the drug and device industries revolving around the use of social media platforms by drug and device manufacturers — Internet/Social Media Platforms: Correcting Independent Third Party Misinformation About Prescription Drugs and Medical Devices (“Guidance on Correcting Third Party Misinterpretation”), and Internet/Social Media Platforms with Character Space Limitations – Presenting Risk and Benefit Information for Prescription Drugs and Medical Devices (“Guidance on Presenting Risk/Benefit Information”).

As the titles suggest, the purpose of the documents is to clarify how social media may be utilized by drug and medical device companies for the voluntary correction of misinformation provided by independent third parties, as well as for presenting promotional messaging regarding risk/benefit information of products. But while the guidelines provide helpful clarification regarding how such platforms may be utilized, they each also raise considerations that companies should take heed of before beginning to use these outlets, and should be factored into a company’s social media guidelines.

Internet/Social Media Platforms: Correcting Independent Third Party Misinformation About Prescription Drugs and Medical Devices

As an initial matter, the Guidance on Correcting Third Party Misinterpretation (“Draft Guidance #1”) establishes two points: first, Draft Guidance #1 only applies to misinformation posted to Internet-based platforms by an independent third party, therefore excluding content provided by the company itself, its employees and agents. Second, Draft Guidance #1 establishes that the exception to a company’s obligation to respond to or correct misinformation only applies to information that is “truly independent,” for example posted by an independent third party to an unaffiliated platform or a platform providing content that is not controlled by the company.

However, Draft Guidance #1 does not completely exclude company-operated sites. In stark contrast with the company’s obligation to correct content when that content is “owned, controlled, created …influenced or affirmatively adopted or endorsed by, or on behalf of, the firm,” where such corrections are obligatory and also carry advertising and labeling regulatory requirements, Draft Guidance #1 does not hold companies responsible for correcting misinformation where a company owns or operates an online platform that allows for user-generated content (chat room, etc.) over which a company does notexert control. However, Draft Guidance #1 cautions that such a site should contain an “overarching and conspicuous statement that the firm did not create or control the [user-generated content].”

If a company chooses to voluntarily respond to truly independent misinformation, Draft Guidance #1 sets parameters on the process for taking correction action, which should either be by (i) providing appropriate truthful corrective information or (ii) providing “a reputable source for correct information, such as the firm’s contact information. In either approach, in order to constitute “appropriate corrective information” a firm’s communication should denote the affiliation of the corrective post with the company, and be:

  • relevant and responsive to the misinformation;
  • limited and tailored to the misinformation;
  • non-promotional in nature, tone, and presentation;
  • accurate;
  • consistent with the FDA-required labeling for the product;
  • supported by sufficient evidence; and
  • posted either in conjunction with or reference the misinformation.

In acknowledgement of the vast nature of the Internet and certain forums and the reality that it may be impractical for a company to attempt to correct all misinformation about its products that may appear, Draft Guidance #1 stipulates that companies do not need to address all incorrect information that may be posted regarding a particular drug or device, even if a company elects to correct a selective portion. When addressing any misinformation, therefore, Draft Guidance #1 recommends that a company create a figurative box around the particular misinformation and portion of the forum it intends to correct, and then revise all the incorrect information within that defined boundary, which should include also correcting positive misinformation or exaggerations. Following corrective action, while Draft Guidance #1 does not hold companies responsible for monitoring the communication, it does recommend that companies keep records that include (i) the date, location, and content of the misinformation; (ii) when the wrongful information was discovered; and (iii) a description of the corrective information provided, including the date it was furnished.

Finally, Draft Guidance #1 suggests that the FDA does not intend to object if a firm voluntarily corrects misinformation and the voluntarily provided corrective information does not satisfy otherwise applicable regulatory labeling or advertising requirements, so long as the corrective information is not non-truthful, misleading, or in a manner other than recommended by Draft Guidance #1. However, companies should take heed that any corrective action that goes beyond merely providing accurate information that is specifically tailored to the misinformation it is addressing (i.e., including slogans or promotional information) must comply with applicable regulatory requirements related to labeling or advertising.

While helpful for establishing clearly both the parameters for correctly responding to misinformation as well as for clearly limiting a company’s obligation to respond to any or all misinformation posted by an independent third party, the Guidance on Correcting Third Party Misinterpretation also reminds companies to take caution when doing so to ensure that their responses are narrowly tailored enough to fall under the purview of the guidance and outside regulatory requirements. That caution includes carefully considering where misinformation clearly constitutes “truly independent” information. Companies should be mindful of the reality that “truly independent” is not a concept that is well defined, and should thus be cautious before asserting that certain misinformation may fall under the purview of Draft Guidance #1 as the FDA advances a broad interpretation of when a company is responsible for taking corrective action.

Internet/Social Media Platforms with Character Space Limitations — Presenting Risk and Benefit Information for Prescription Drugs and Medical Devices

Prepared by the Office of Prescription Drug Promotion, the second guidance issued by the FDA last week, the Guidance on Presenting Risk/Benefit Information (“Draft Guidance #2”), addresses the parameters around presenting benefits and risks information on Internet and social media platforms with character spacing limitations, such as microblogs (e.g., Twitter) and online paid search (e.g., “sponsored links” on search engines such as Google). Draft Guidance #2 clearly establishes that, as a threshold matter, the character restrictions do not eliminate the company’s responsibility to ensure its promotional messaging complies with all applicable regulations related to advertising and labeling, and cautions that such forms of media may not be appropriate for promotion of certain products, such as those with complex indications or risk profiles.

For companies that choose to make product benefit claims on character-space-limited communication sites, while each may reasonably use common abbreviations (including scientific and medical abbreviations), punctuation marks, and other symbols to comply with space constraints, Draft Guidance #2 presents a broad set of rules that must be satisfied by each communication relating to both risk and benefit information.

Benefit Information

  • Benefit information should be accurate, non-misleading, and reveal material facts within each individual message or tweet.
  • Benefit information should be included with risk information in the same message. Do not spread benefit and risk information across multiple messages or tweets.

Risk Information

  • Risk information should be included with benefit information in the same message. Do not spread risk and benefit information across multiple messages or tweets.
  • Risk information should be “comparable in scope” to the benefit information, and should, at minimum, include the most serious risks, e.g., those included in a boxed warning or known to be life-threatening, among others, associated with the product. To determine whether risk information is “comparable in scope” to the benefit information, the FDA weighs (i) whether the risk information “qualifies any representations made about the product,” and (ii) whether the risk information is presented with a “prominence and readability comparable to the benefit claims about the product.” While risk disclosures may be concise when paired with benefit information, a hyperlink to a complete, and exclusive, discussion of risks should be included and appropriately titled and not promotional in nature.
  • Both the proprietary and established (generic) name for the product should be included within the character-space limited communication and on each landing page associated with each hyperlink in that initial communication. Draft Guidance #2 recommends that the landing page be devoted exclusively to the communication of risk information about the product and not to the promotional home page. Such landing page should also prominently display quantitative ingredient and dosing information for prescription drugs.

In light of the restrictions set forth by Draft Guidance #2, while companies should feel comfortable taking advantage of current social media platforms including those with character restrictions, they should also ensure that the parties responsible for drafting any such posts are aware of the parameters placed on such communications. A hypothetical example provided by Draft Guidance #2 exemplifies some of the potential disadvantages of such messaging:

NoFocus (rememberine HCl) for mild to moderate memory loss-May cause seizures in patients with a seizure disorder www.nofocus.com/risk

While the message complies with each of Draft Guidance #2’s directives, the balancing of risk and benefit information in a space restricted communication may have the unintended result of highlighting risk over benefit. Additionally, from a practical standpoint, the space constraints may prevent the inclusion of all necessary information. If a company cannot conclude that “adequate” benefit and risk information (along with other required disclosure) may be communicated in the same message or tweet — particularly at 140 characters — Draft Guidance #2 recommends that the company reconsider whether the use of the particular platform is the appropriate forum for the dissemination of such messaging before making use of such forums, once again in particular for drugs with complex indications or high risk profiles.

As a general conclusion, while the Guidance on Presenting Risk/Benefit Information is self-admittedly limited in scope, and does not address “promotion via product websites, webpages on social networking platforms (e.g., [Facebook, Twitter, YouTube]), and online web banners,” it undeniably provides helpful direction for drug and device companies’ use of social media sites for promotional messaging where communications are restricted to a limited number of characters, as well as highlighting how the FDA may intend to regulate such use. Companies should pay careful attention to the restrictions while taking advantage of the opportunities these social media platforms offer, and should take care to ensure to instill clear policies that comply with Draft Guidance #2 that are available to, and understood by, individuals tasked with producing and monitoring social media content for the company.

The FDA will be accepting comments on both Draft Guidance #1 and Draft Guidance #2 until September 16, 2014.

Article By:

Cynthia J. Larose
Christine M. Wahr
Of:
Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.

New York Federal Court Rejects Preemption and Primary Jurisdiction Arguments in “All Natural” Case

GT Law

In our February 12, 2014 post, entitled “Consumer Class Actions Trending From Attacking ‘All Natural’ to ‘Raw,’” we addressed whether claims challenging consumer product advertising as “all natural” were preempted in the absence of specific guidance from the FDA and the mixed results the argument has produced.  In Ault v. J.M. Smucker Co. et al., 2014 WL 1998235 (S.D.N.Y. May 15, 2014), the Court denied a motion to dismiss based on preemption and primary jurisdiction where the plaintiff alleged that it was deceived into purchasing Smucker’s Crisco oil by “all natural” advertising where the product contained genetically modified organisms, or GMOs, because the FDA has not addressed the use of the term “all natural” in this context.

All Natural

Smuckers argued that FDA policies regarding the use of the term “natural” preempt state law false advertising claims based on this language, even if those policies are informal.  However, the Court found, “no federal specifications exist here.”  Id. at *3.  And “[e]ven if an informal FDA definition does exist, the term ‘natural’ ‘may be used in numerous contexts and may convey different meanings depending on that context[]” [citation,] [and] “that is one of the reasons the FDA has never adopted a formal definition.”  Id. (citing Pelayo v. Nestle USA, Inc.,<“> No. CV 13–5213, 2013 WL 5764644, at *5 (C.D.Cal. Oct. 25, 2013)).  In addition, “the FDA has declined to consider the specific issue here:  whether and under what circumstances food products containing ingredients produced using genetically engineered ingredients may or may not be labeled ‘natural.’”  Id. (citation and some internal quotation marks omitted).  “As a result,” the Court found, “any general, informal FDA guidance is not controlling.”  Id. (citing In re Frito–Lay N. Am., Inc. All Natural Litig., No. 12–md–2413,2013 WL 4647512, at *10 (E.D.N.Y. Aug. 29, 2013)).

The Court also rejected Smucker’s argument that the FDA’s decision not to impose a labeling requirement for foods with GMOs supports preemption, stating, “[i]n effect, Defendant interprets the FDA’s lack of action as approval for Defendant’s use of the phrase ‘All Natural’ to describe foods containing GMO [but] [i]n reality, the FDA has stayed silent because it ‘operates in a world of limited resources’ where it ‘must prioritize which issues to address.’”  Id. (citation omitted.)

In addition, the Court found Smucker’s primary jurisdiction argument unavailing:  “three federal district judges previously referred the question of whether foods containing GMOs may be labeled ‘natural’ to the FDA under the primary jurisdiction doctrine [and on] January 6, 2014, the FDA responded and explicitly declined to make such a determination.”  Id. at *4 (citing January 6, 2014 FDA Letter).  “The FDA’s refusal to consider the question demonstrates that ‘resort to the agency at this time would be unavailing,’ [citation] and therefore weighs against applying the primary jurisdiction doctrine.”  Id.

This case signals that, until the FDA acts, preemption and primary jurisdiction arguments against “all natural” advertising of products with GMOs may be more and more challenging.

Article By:

Jordan D. Grotzinger
Of:
Greenberg Traurig, LLP

California Proposes Enhanced Prop. 65 Warnings and Possible Online Disclosures – Dietary Supplements and Foods Specially Targeted

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The California Office of Environmental Health Hazard Assessment (OEHHA)announced on March 7, 2014, that it is considering implementation of the most significant changes to Prop. 65 regulations in more than two decades.  OEHHA has posted the draft regulation and Initial Statement of Reasons on its website.

Passed by voters in 1986, Prop. 65 requires warnings prior to exposures to chemicals listed by OEHHA as “known to the State” to cause cancer or reproductive harm.  The law, which carries the potential penalty of $2,500 for each violation, may be and routinely is enforced by entrepreneurial private plaintiffs who are permitted to bring legal actions against alleged violators with minimal evidence.  OEHHA’s proposed regulations will affect almost every industry subject to Prop. 65 and nearly every aspect of compliance.  In all but a few cases, OEHHA’s changes have the capacity to make compliance with Prop. 65 costlier, riskier, and more disruptive to companies doing business in California.

Four Important Provisions Affecting Food and Dietary Supplements

In its far-reaching proposal, OEHHA aims a number of significant changes directly at food and dietary supplement manufacturers, distributors, and retailers.  Four specific proposals stand out as impactful for the industry:

  1. Chemical Identification: Under OEHHA’s proposal, warning labels would have to specifically identify the chemical in question if it is on a proposed list of 12 “common” substances.  One substance on OEHHA’s list, lead, is sometimes naturally occurring in the ingredients used to produce dietary supplements and has been the source of considerable litigation and expense for the industry.  In OEHHA’s draft regulation, products requiring a warning for lead would have to “conspicuously” state its presence in the product.
  2. Display Requirements: For foods not already subject to a consent judgment, the “safe-harbor” warning language must also be enhanced with specific information about the chemical in question, specific text sizing, and the phrase “Cancer [and/or] Reproductive Hazard.” Even where a food supplier has data showing that the chemical poses no actual health threat, a private plaintiff may still litigate knowing that the costly burden of showing no significant risk is borne by defendants.  Unless modified or declared preempted by federal law, OEHHA’s regulation would virtually ensure that this language will be required for food and supplement packaging in California.
  3. Online Reporting: OEHHA would also mandate reporting of exposure data to the agency for its website if a new Prop. 65 warning does not contain 10 details specified by OEHHA.  The details include, among others, the name of the chemical at issue, anticipated exposure routes, exposure levels, and options for minimizing exposure.  Businesses that fail to provide the required detail, no matter how misleading it might be to the consumer, must disclose the additional information to OEHHA and will likely see such data published online.
  4. More Litigation: Despite statements from the agency to the contrary, OEHHA’s complex rules would encourage even more litigation from an already active community of plaintiffs.  OEHHA’s draft litigation reform, a “cure” or fix-it period for retailers with fewer than 25 employees, would do little to stem the current tide of lawsuits, the vast majority of which are ultimately directed at and defended by suppliers.  Additionally, by replacing the generic safe-harbor warning with specific requirements, a regulatory safe-harbor warning would no longer provide a safe harbor from liability or deter plaintiffs from alleging violations for exposures to unspecified or newly listed chemicals.

What You Can Do

Businesses which stand to be affected by OEHHA’s plans, including those operated out of state, have an opportunity to voice their concerns to the agency.

OEHHA will hold a public workshop on April 14, 2014 to discuss the proposed regulations.  In addition, OEHHA is accepting written comments from the public until May 14, 2014.  Unless OEHHA is convinced to delay or withdraw its plans, formal regulations will likely be proposed in the summer of 2014.

Because OEHHA’s proposals are currently in the preliminary stages, interested parties have a time critical opportunity to engage the agency and encourage it to address specific concerns.  Companies that manufacture distribute, or retail dietary supplements in California should consider retaining experienced counsel to analyze the impact of the proposals on their business and to participate in the public comment period on their behalf.   Given the potentially far-reaching consequences of the proposed changes on the individual companies and the industry at large, interested parties should be diligent in bringing their concerns to OEHHA as early and as persuasively as possible.

Article By:

James Mattesich
Justin J. Prochnow
Anthony J. Cortez
Greg Sperla
Of:
Greenberg Traurig, LLP

FDA (Food and Drug Adminsitration) Releases Final Electronic Medical Device Reporting (eMDR) Rule and Deadline for Compliance

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The Food and Drug Administration (FDA) announced and is promulgating today the Final Rule on Electronic Medical Device Reporting (eMDR). Originally proposed in 2009, the rule is now final and a deadline for compliance has been identified. The rule impacts device manufacturers and importers and mandates electronic submission of individual medical device adverse event reports. User facilities may continue to submit only written reports.

As of August 14, 2015, postmarket medical device adverse event reports by manufacturers and importers must be submitted only electronically to the FDA’s Center for Devices and Radiological Health via the Electronic Submissions Gateway (ESG). The ESG is used for all forms of electronic filing to the FDA; information specific to medical device submissions is available here. Guidance about the eMDR is available here.

It is recommended you review your current system for submitting reports, and if you are not already utilizing the ESG for all reporting, develop a plan now for integrating the electronic process into your operations.

Article by:

Of:

Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.