The Federal Trade Commission (“FTC”) and the Antitrust Division of the Department of Justice (“Antitrust Division”) released their respective year-end reviews highlighted by aggressive enforcement in the health care industry. The FTC, in particular, indicated that 47% of its enforcement actions during calendar year 2016 took place in the health care industry (including pharmaceuticals and medical devices). Of note were successful challenges to hospital mergers in Pennsylvania (Penn State Hershey Medical Center and Pinnacle Health System), and Illinois (Advocate Health Care Network and North Shore University Health System). In both actions, the FTC was able to convince the court that the merger would likely substantially lessen competition for the provision of general acute-care hospital services in relevant areas in violation of section 7 of the Clayton Act. See FTC v. Penn State Hershey Med. Center, 838 F. 3d 327 (3d Cir. 2016); and FTC v. Advocate Health Care Network et al No. 1:15-cv-11473, 2017 U. S. Dist. LEXIS 37707 (N.D. Ill.Mar. 16, 2017)

The Antitrust Division, in similar fashion, touted its actions to block the mergers of Aetna and Humana, and Anthem and Cigna. Complaints against both mergers were filed simultaneously in July of 2016, and tried before different judges in the Federal District Court for the District of Columbia. After extensive trials, Judge Bates blocked the Aetna/Humana deal, and Judge Amy Berman Jackson blocked the Anthem/Cigna transaction. United States v. Aetna Inc., No. 1:16-cv-1494, 2017 U.S. Dist. LEXIS 8490 (D.D.C. Jan 23, 2017) and United States v. Anthem Inc., No. 1:16-cv-01493, 2017 U.S. Dist. LEXIS 23614 (D.D.C. Feb8, 2017).

In addition to their enforcement activities, the agencies promoted jointly issued policy guidelines, including their “Antitrust Guidance for Human Resources Professionals.” Although not specific to any industry, this guidance has particular relevance to the health care industry. Among other things, this guidance makes clear that naked wage-fixing (such as the wave of wage fixing claims relating to nurses) and no-poaching agreements (that would include agreements not to hire competing physicians) are not only per se illegal, but also subject to criminal prosecution.

While a marginal enforcement shift may be in store as a result of the change in administration, most signs point to a continued focus on the health care industry. Maureen K. Ohlhausen, appointed by President Trump as acting Chair of the FTC, reiterated in a speech recently delivered at the spring meeting of the American Bar Association’s antitrust section, that “[i]t’s extremely important we continue our enforcement in the health care space.” Likewise the Acting Director of the FTC’s Bureau of Competition – Abbott (Tad) Lipsky, appointed by Chairman Ohlhausen, applauded the FTC’s success in challenging the Advocate/Northshore Hospital merger noting, in a related FTC press release, that the “merger would likely have reduced the quality, and increased the cost, of health care for residents of the North Shore area of Chicago.”

Makan Delrahim, President Trump’s selection (awaiting confirmation) to head the Antitrust Division, recently lobbied on behalf of Anthem and its efforts to acquire Cigna, and has openly stated with respect to certain announced mergers, that size alone does not create an antitrust problem. Nevertheless, given the political climate and overall impact the health care industry has on the U.S. economy, the Antitrust Division’s efforts to open markets in the health care sector, particularly to generics and new medical technologies by challenging pay for delay deals and scrutinizing unnecessarily restrictive agreements among medical device manufacturers is likely to continue.

A wild card affecting future antitrust enforcement is increasing possibility of passage of the Standard Merger and Acquisitions Review Through Equal Rights Act of 2017 (H.R. 659 a/k/a the “SMARTER ACT”). This bill, recently approved by the House Judiciary Committee, would eliminate the FTC’s administrative adjudication process as it relates to merger enforcement, forcing the FTC to bring all such actions in court. In addition, it would align current preliminary injunction standards such that both the FTC and DOJ would face the same thresholds required of the Clayton Act rather than the more lenient standard under the FTC Act. A similar bill passed the House in 2016, but was not taken up by the Senate.

Our colleagues Joshua A. Stein and Frank C. Morris, Jr., at Epstein Becker Green have a post on the Health Employment And Labor blog that will be of interest to many of our readers: “The U.S. Access-Board Releases Long-Awaited Final Accessible Medical Diagnostic Equipment Standards.”

Following is an excerpt:

As part of a flurry of activity in the final days of the Obama Administration, the U.S. the Architectural and Transportation Barriers Compliance Board (the “Access Board”) has finally announced the release of its Accessibility Standards for Medical Diagnostic Equipment (the “MDE Standards”).  Published in the Federal Register on Monday, January 9, 2017, the MDE Standards are a set of design criteria intended to provide individuals with disabilities access to medical diagnostic equipment such as examination tables and chairs (including those used for dental or optical exams), weight scales, radiological equipment, mammography equipment and other equipment used by health professionals for diagnostic purposes. …

Read the full post here.

Early January has seen the release by FDA of a flurry of information on drug and device manufacturer communications, largely reaffirming FDA’s long-held approach to restricting manufacturer communications regarding off-label uses of approved drugs and medical devices. The most significant positive development arising from these documents is the Agency’s concession on proactive pre-approval communications with payors about investigational drugs and devices, allowing certain information to be provided to payors prior to a product’s approval. FDA’s guidance documents issued this week also clarify some grey areas surrounding the circumstances under which manufacturers may communicate about information that is consistent with or related to an approved indication, but is not included in approved product labeling.

While these pronouncements provide drug and device manufacturers with some additional leeway in their communications regarding investigational products and certain information about the approved uses of their products that is not included in the approved labeling, they do not address long-standing questions regarding the circumstances under which manufacturers may communicate about unapproved uses of their products in light of recent First Amendment case law. Instead, these last words of the Agency under the outgoing administration signal that, at least under the direction of current administration, FDA is not inclined to significantly expand manufacturers’ ability to communicate regarding unapproved uses of their products without the risk of enforcement. The eventual impact of the new administration on FDA’s approach to off-label communications remains a significant unknown.

In draft guidance on Drug and Device Manufacturer Communications with Payors, Formulary Committees and Similar Entities – Questions and Answers released on January 18, FDA signifies its acceptance of the position long held by industry and payors alike that payors need access to information regarding investigational drugs and devices to help them plan and budget for coverage of these products once they are approved. In the draft guidance, FDA states that it will not object to manufacturers providing payors with “unbiased, factual, accurate and non-misleading” information regarding investigational drugs and medical devices, provided that those communications include a clear statement of the investigational status of the product and that its safety and effectiveness have not been established, along with information regarding the stage of product development of the product.

Information that may be provided by manufacturers in accordance with FDA’s recommendations in the draft guidance includes information about the product such as its drug class or design, the indication sought and the patient population under investigation, a factual presentation of the results of clinical and pre-clinical studies without any conclusions regarding the product’s safety and effectiveness, the anticipated timeline for FDA approval, product pricing information, and anticipated marketing strategies and product-related programs and services, such as patient assistance programs. FDA also recommends that manufacturers update payors with any significant new information about the investigational product that differs from information previously communicated to them.

As suggested by its title, the primary focus of the draft guidance is on the communication of health care economic information (“HCEI”) regarding prescription drugs to payors, interpreting the changes to FDAMA Section 114 included in the 21st Century Cures Act that was signed into law in December. Notably, unlike FDA’s recommendations regarding pre-approval product communications with payors, this portion of the draft guidance does not apply to HCEI regarding medical devices. The draft guidance also makes it clear that the expanded HCEI communications permitted by FDAMA 114, as amended, are limited to payors, and similar flexibility in the levels of evidence required to support HCEI communications to payors do not apply to communications with health care providers or consumers. Additionally, consistent with the statute, the draft guidance limits the HCEI that may be provided to information that “relates to” an approved indication, confirming that FDA does not currently intend to permit the proactive dissemination to payors of HCEI related to off-label use.

In a series of questions and answers, FDA provides recommendations regarding the types of HCEI that may be provided, the scope of the payor audience to which this information may be provided, the types of competent and reliable scientific evidence that may be relied upon, the information that must be disclosed along with HCEI provided to payors, and perhaps mostly usefully, examples of the circumstances under which FDA will determine HCEI to relate, and not to relate, to an approved indication. FDA describes the categories of information that will be deemed to relate to an approved indication, even if they do not appear within, or vary in some respects from, the approved labeling; provided that the information is not inconsistent with the approved labeling. These include, among others, information on duration of treatment, burden of illness, length of hospital stay, information including actual patient use of an approved drug that varies from the approved dosing regimen, and information derived from clinical data demonstrating an effect on a validated surrogate endpoint or a comparison of safety and effectiveness with another drug or intervention.

FDA’s approach to “related” information in the draft guidance is similar to that taken in another draft guidance it released on January 17 on Medical Product Communications that are Consistent with the FDA-Required Labeling – Questions and Answers. In the Medical Product Communications draft guidance, FDA provides recommendations for manufacturers of drugs and medical devices on communications, including communications with health care providers, consumers and payors and in promotional materials, regarding information that is not included within the FDA-approved package labeling, but is consistent with that labeling.

In determining whether information provided by manufacturers is consistent with the product’s approved labeling, FDA will consider three factors. First, FDA will compare the information to the conditions of use in the approved labeling. To comply with the recommendations in the guidance, the information must relate to an indication, patient population, and dosing and administration instructions within the scope of those set forth in approved label, and it must not be inconsistent with any use limitation or directions for handling or using the product in the approved labeling. Second, the suggestions regarding the use of the product in the HCEI information must not increase the potential for patient harm relative to information in the approved labeling or otherwise adversely impact the risk-benefit profile of the product. Finally, the directions for use in the approved labeling must allow the product to be used safely and effectively under the conditions of use suggested in the HCEI information distributed by the manufacturer. If all three of these factors are met, FDA will not view that information, alone, as evidence that the manufacturer intends to promote the drug or device for a new intended use.

To assist manufacturers in applying these factors, the guidance includes examples of the types of communications that are, and are not, consistent with a product’s approved labeling. In describing the types of evidence required to support the disclosure of information that is not included in, but is consistent with, the approved labeling, FDA states that the data must be scientifically and statistically sound to support the representations made by the manufacturer to avoid being false or misleading, but because the safety and effectiveness of the product for the approved indication has already been established, the evidence need not meet the applicable approval or clearance standard for the product. For drug products, this means that two adequate and well-controlled clinical trials will not be required. The evidence must, however, be accurately characterized and any material limitations on the evidence must be clearly and prominently disclosed in language appropriate for the intended audience.

FDA also has, within a ten day period, released two other pieces of information relating to drug and device manufacturers’ communications regarding their products. On January 9, FDA issued a Final Rule on Clarification of When Products Made or Derived From Tobacco Are Regulated as Drugs, Devices, or Combination Products; Amendments to Regulations Regarding “Intended Uses”, clarifying the Agency’s position that a determination of a regulated product’s intended use may be determined based upon the totality of the evidence of the manufacturer’s objective intended use of the product, including the manufacturer’s knowledge of the product’s actual use for an off-label indication in practice.[1]  FDA states in the preamble to the Final Rule, however, that it will not bring an enforcement action based solely on a manufacturer’s knowledge that an approved or cleared product is being prescribed or used for an unapproved use.

The Proposed Rule released in September 2015 deleted from the drug and device intended use regulations at 21 CFR §§ 201.128 and 801.4 a reference to a manufacturer’s knowledge of off-label uses, specifically the statement that “[Intended use] may be shown by the circumstances that the article is, with the knowledge of such persons or their representatives, offered and used for a purpose for which it is neither labeled nor advertised.” Many commenters on the Proposed Rule had interpreted that deletion as excluding a manufacturer’s knowledge of off-label use from the evidence that may be relied upon to establish a manufacturer’s intent to promote a drug or device for an off-label use. The preamble to the Final Rule expresses FDA’s disagreement, and clarifies that FDA proposed deleting that language merely to avoid a potential misinterpretation that a manufacturer’s knowledge of an unapproved use of an approved or cleared medical product, without more, automatically triggers a requirement for that manufacturer to provide additional labeling for the unapproved use. FDA asserts that its intent was not to change the scope of information that could be relied upon as evidence of a manufacturer’s intended use of the product.  The amended language set forth in the Final Rule provides that “”intended use may be shown, for example, by circumstances in which the article is, with the knowledge of such person or their representatives, offered and used for a purpose for which it is neither labeled nor advertised.”

In the preamble to the Final Rule, in response to comments that existing First Amendment jurisprudence restricts FDA from bringing enforcement actions based on truthful and non-misleading speech regarding a product’s off-label use, FDA states that it is separately examining its rules and policies relating to firm communications regarding unapproved uses of approved and cleared medical products, and while those broader policy considerations are being addressed separately from the Final Rule, “[n]evertheless, it is important to note here that we do not agree with the assertion that the current case law allows FDA to consider speech as evidence of intended use only when it is false or misleading.” FDA cites recent Second Circuit precedent[2] to support its view that the Second Circuit’s 2014 Caronia decision does not foreclose the government’s ability to prove misbranding using promotional speech as evidence that a drug is intended for an off-label use. FDA goes on to describe the significant public health considerations that the Agency believes support its approach to limiting manufacturer communications regarding off-label uses of their approved or cleared products.

FDA makes similar assertions in a document posted to the docket for the November public hearing on Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products entitled, “Memorandum: Public Health Interests and First Amendment Considerations Regarding Unapproved Uses of Approved or Cleared Medical Products.” In a notice published in the Federal Register on January 19, 2017, FDA announces that it has reopened the comment period that was opened in connection with the public hearing on off-label communications that took place November 9 and 10, 2016 to allow interested parties an opportunity for additional comment based on the content of the memorandum and the two draft guidances discussed above. In this memorandum, FDA describes in detail the public policy considerations guiding its assessment of its restrictions on off-label communications, and the legal authority it believes supports its restriction of these communications and their use as evidence of intended use to support misbranding actions. FDA also describes its views on several alternative approaches to addressing the public health interests at issue.  FDA seeks additional comments on its views expressed in the memorandum and potential alternative approaches to regulating manufacturer communications regarding off-label indications of their approved products.  The docket will remain open until April 19, 2017.

[1] In addition to its provisions specific to determinations of when a tobacco product will be regulated as a drug or device, the Final Rule also amended intended use regulations at 21 CFR §§ 201.128 and 801.4.

[2] United States ex rel. Polansky v. Pfizer, Inc., 822 F.3d 613 n.2 (2d Cir.2016).

On August 31, 2016, FDA issued a notification of public hearing and request for comments on manufacturer communications regarding unapproved uses of approved or cleared medical products. The hearing will be held on November 9-10, 2016, and individuals wishing to present information at the hearing must register by October 19, 2016. The deadline for written comments is January 9, 2017.

In the notice, FDA posed a series of questions on which it is seeking input from a broad group of stakeholders, including manufacturers, health care providers, patient advocates, payors, academics and public interest groups. The topics on which FDA is seeking feedback are broad, but generally include:

  • The impact of off-label communications on public health,
  • The impact of changes in the health care system on the development of high-quality data on new uses of cleared or approved products,
  • Preserving incentives for manufacturers to seek approval for new uses, standards for truthful and non-misleading information,
  • Factors FDA should consider in monitoring and bringing enforcement actions based on off-label communications by manufacturers,
  • The extent to which data on which off-label communications are based should be publicly available, and
  • The changes FDA should consider to existing regulations governing manufacturers’ communications regarding their products.

This announcement comes in the wake of increased pressure from lawmakers, public interest groups, and regulated industry for FDA to issue guidance or propose regulatory changes to address recent litigation clarifying commercial speech protections for pharmaceutical and medical devices manufacturers under the First Amendment. On May 26, 2016, the House Committee on Energy and Commerce sent a letter to HHS Secretary Sylvia Burwell expressing concern that FDA had failed to clarify its current thinking on permissible manufacturer communications about uses of cleared and approved drugs and devices beyond the scope of their approved labeling. In the letter, the committee noted that FDA had neither issued guidance, including guidance on the permissible scope of “scientific exchange” that has been on FDA’s Guidance Agenda since 2014, nor conducted the public hearing it announced in May 2015 in connection with negotiations on the proposed 21st Century Cures bill.  The committee expressed concern that HHS was preventing FDA from issuing guidance or proposing new regulations to address a string of recent court victories for companies and individuals prosecuted for off-label communications about drug and medical devices.

In light of the current state of First Amendment commercial speech protections, which makes it clear that manufacturers’ truthful and non-misleading speech regarding their products is not unlawful even if that speech includes uses of their products that have not been approved or cleared by FDA, other stakeholders have actively encouraged FDA to issue guidance or modify its regulations to conform its regulatory oversight and enforcement activities to this reality. While stakeholder groups have been actively engaged on these issues for several years, recent examples include the February 2016 white paper issued by the Duke-Margolis Center for Health Policy outlining policy options for off-label communications, and the joint release by BIO and PhRMA of the Principles on Responsible Sharing of Truthful and Non-Misleading Information about Medicines with Health Care Professionals and Payers on July 27, 2016.

Despite pressure from interested stakeholders, FDA has yet to propose changes to its regulations or issue long-awaited guidance on a number of topics related to manufacturers’ communications regarding off-label uses of their cleared or approved products. While FDA’s 2016 Guidance Agenda, updated most recently on August 6, 2016, continues to promise guidance on manufacturer communications regarding unapproved, unlicensed, or uncleared uses of approved, licensed, or cleared human drugs, biologics, animal drugs and medical devices and the inclusion of health care economic information in promotional labeling and advertising for prescription drugs, among others, the post-election timeline for the public hearing and FDA’s ongoing collection of feedback announced in the August 31st notice may suggest that FDA is going back to the drawing board. In particular, the focus in the notice’s background discussion and in FDA’s questions on the public health impact of off-label communications may suggest that FDA is re-evaluating its position in response to the HHS concerns about broader dissemination of off-label by manufacturers that were highlighted in the Energy and Commerce committee letter.  While FDA’s notice and request for comments is a step in the right direction, it likely signals a further delay in the issuance of guidance that is needed to bring greater clarity to the currently unsettled regulatory framework for FDA’s oversight of manufacturers’ off-label communications, and a punting of these important decisions to the next administration.

On May 17, 2016, FDA issued Draft Guidance for Industry on Use of Electronic Health Record Data in Clinical Investigations (“Draft Guidance”).  This Draft Guidance builds on prior FDA guidance on Computerized Systems Used in Clinical Investigations and Electronic Source Data in Clinical Investigations, and provides information on FDA’s expectations for the use of Electronic Health Record (“EHR”) data to clinical investigators, research institutions and sponsors of clinical research on drugs, biologics, medical devices and combination products conducted under an Investigational New Drug Application or Investigational Device Exemption.

While the recommendations set forth in the Draft Guidance do not represent a significant departure from existing guidance, research sponsors, institutions and investigators should consider the extent to which their existing policies and procedures, template agreements, protocols and informed consent documents should be updated to incorporate FDA’s recommendations.

Specifically, the draft guidance provides additional detail on FDA’s expectations for the due diligence to be performed by sponsors prior to determining the adequacy of any EHR system used by a clinical investigator to capture source data for use in a clinical investigation. FDA expects sponsors to assess whether systems have adequate controls in place to ensure the confidentiality, integrity, and reliability of the data. FDA encourages the use of EHR systems certified through the ONC Health IT Certification Program, and will presume that source data collected in Health IT certified EHR systems is reliable and that the technical and software components of privacy and security protection requirements have been met. Sponsors should consider requesting additional detail in site pre-qualification questionnaires or pre-study visits regarding any EHR system utilized by clinical investigators to record source data, including whether such systems are Health IT certified. Sponsors may also consider the extent to which their existing site qualification policies and clinical trial agreements templates adequately reflect the technical requirements for sites utilizing EHR systems to record source data, the need to ensure that any updates to those systems do not impact the reliability of the security of the data, and the extent to which the data, including all required audit trails, are backed up and retained by the site to ensure necessary access by FDA.

The Draft Guidance also includes recommendations regarding the information it expects to be included in study protocols and informed consent documents. When the use of EHR systems is contemplated, FDA recommends that study protocols include a description or diagram of the electronic data flow between the EHR and the sponsor’s EDC system, along with information regarding the manner in which the data are extracted and imported from the EHR and monitored for consistency and completeness. FDA also recommends incorporation into informed consent forms of information regarding the extent of access to EHRs granted to sponsors, contract research organizations, and study monitors, as well as a description of any reasonably foreseeable risks with the use of EHRs, such as those involving an increased risk of data breaches. While information related to third party access to health information is typically addressed in informed consent documents, specific details related to access to EHRs and their associated risks are less common. Sponsors and research institutions should consider the extent to which their template informed consent documents should be updated to incorporate the best practice recommendation in the Draft Guidance.

In addition, in the Draft Guidance, FDA encourages the development and use of interoperable EDC and EHR systems to permit electronic transfer of EHR data into the eCRFs being utilized for a clinical trial, including the adoption of data standards and standardization requirements of the ONC Health Information Technology (Health IT) Certification Program. While interoperability of EHR and EDC systems offers the promise of increasing efficiency of clinical trial data collection and reducing the transcription errors that commonly result from the maintenance of this information in separate repositories, FDA acknowledges challenges related to the diverse ownership of the data and EHR systems used to capture them, and the confidentiality of clinical trial information, that will need to be overcome in order to realize the benefits offered by interoperability.

Telemental/telebehavioral Health SurveyEpstein Becker Green has just released the 50-State Survey of Telemental/Telebehavioral Health (2016), a groundbreaking, comprehensive survey on the laws, regulations, and regulatory policies impacting telemental health in all 50 states and the District of Columbia.

While other telehealth studies exist, this survey focuses solely on the remote delivery of behavioral health care.

Compiled by attorneys in Epstein Becker Green’s Telehealth practice, the survey details the rapid growth of telemental health—mental health care delivered via interactive audio or video, computer programs, or mobile applications—and the increasingly complex legal issues associated with this trend. Additionally, the survey provides one source for state-by-state coverage of legal issues related to telemental health, such as:

  • Definitions of “telehealth” or “telemedicine”
  • Licensure requirements
  • Governing bodies
  • Reimbursement and coverage issues
  • The establishment of the provider-patient relationship
  • Provider prescribing authority
  • Accepted modalities for delivery (e.g., telephone, video) to meet standards of care

Read the firm’s full announcement and click here to download the complimentary survey.

While FDA made a push last fall to explore the technical challenges associated with 3-D printed devices (holding a public workshop in October 2014), the Agency’s planned guidance on the topic fell to the “B-list” in FDA’s 2015 medical device guidance agenda. According to the agenda, the Agency will issue a draft guidance document on 3-D printing as “guidance-development resources permit.” In light of the regulatory uncertainty facing 3-D printing stakeholders, this may seem like unwelcome news – but is it?

Recent comments from Agency officials suggest that immediate guidance is unnecessary because 3-D printing, despite prior comments, is “business as usual” regulatory review work for FDA that might not need extensive specialized guidance.  At a conference last month, the director of FDA’s Office of Science and Engineering Laboratories, Steven Pollack, explained that the Agency generally sees 3-D printing as a manufacturing technology, “not something that exotic from what [its] seen before.” Pollack also expressed that the Agency does not feel particularly unprepared to review 3-D printed devices under its current regulatory paradigm.

Still, during a January interview, Pollack did acknowledge that there are some unique challenges that 3-D printing may present for FDA and device manufacturers. For example, he expects that 3-D printed devices may require additional or different testing than is usually done. To minimize regulatory challenges, Pollack recommends that manufacturers looking to market 3-D printed devices participate in pre-submission meetings with FDA review teams. Such meetings can help FDA reviewers get a better understanding of the technology involved in manufacturing the device, which is critical.  However, pre-submissions are, essentially, case-by-case and fact-specific negotiations.  The process, though invaluable, also has some inherent inefficiencies and potential for inconsistencies that Agency-wider guidance can ameliorate.

3-D printing regulatory challenges may also be compounded by difficulties faced by manufacturers earlier in the design and development process.  Dr. Scott Hollister, University of Michigan biomedical engineering professor and developer of a 3-D printed tracheal splint, has identified specific material-related challenges. In an article for PlasticsToday, Hollister cited the following as key issues related to 3-D printing materials: particle size (impacts the laser sintering process), the availability of materials, heat resistance, strength, and degradation rate.

So for now, FDA seems intent to function without specific regulatory guidance.  While this may be a way to bring some advances to market, it seems like there are still regulatory challenges and uncertainties to address, which will likely only multiply as 3-D printed devices are  developed for a greater variety of (and more complicated) uses.  Therefore, the more guidance and transparency FDA can provide to stakeholders, the better. Considering FDA’s 2015 guidance priorities, however, manufacturers hoping for specific regulatory clarity in this space likely will have a while to wait.

When FDA published its draft guidance Internet/Social Media Platforms with Character Space Limitations— Presenting Risk and Benefit Information for Prescription Drugs and Medical Devices in June 2014, I, like many others with an interest in pharmaceutical and medical device promotion, believed that the issue of social media promotion of drugs and medical devices was largely settled. Even with the limited concessions offered by FDA to reduce the traditional risk disclosure requirements, absent a substantial shift in FDA’s position, Twitter was not going to be a medium that drug and device companies could use to effectively promote their products. Sure, companies could use Twitter for corporate communications, disease awareness messaging and reminder ads that didn’t mention products’ indications, but promotional claims for products appeared to be off limits. Only the simplest and lowest risk drugs and medical devices could possibly meet the standards for disclosure of risk and indication information recommended by FDA in the guidance within the 140-character limit, and once the required disclosures were included, there was little room remaining for effective product messaging. But that was before Twitter rolled out promoted video last August.

Imagine my surprise when late one night, while scanning my Twitter feed to catch up on the day’s news, I came across this video:

In it, Biogen Idec provides a detailed overview of the manufacturing process for the recombinant hemophilia treatment intended for a direct to consumer audience.  In a therapeutic area in which traditional blood derived clotting factors may give rise to infection risk, the manufacturing process for this recombinant alternative may be a key differentiator for patients.  While the video is educational in tone and does not make claims about the efficacy or relative safety of the product, the four and a half minute video includes robust disclosures of the product’s indication and risks. It is a terrific example of the creative ways in which manufacturers may be able to use Twitter’s video capabilities to escape the strict 140-character limit, allowing them to produce compliant promotional communications for use in this medium. Up next from Elocatate’s Twitter account as the company continues to test the waters – patient testimonial videos.

 


Will the promoted video format be right for every company or every product?  No, but it does add another alternative that companies may consider when determining how best to promote their products where they are – and these days, that’s increasingly on Twitter and other social media platforms.  The freedom from Twitter’s character space limitations offered by the video format presents an intriguing opportunity for drug and medical device manufacturers to use Twitter in a new and complaint way.

As we move into 2015, stories about the use of 3-D printing (also called additive manufacturing) in the health care industry continue to hit headlines. Some 3-D printed products are already available to U.S. patients, including knee and cranial implants, while others, including a graft device to treat aneurysms, are coming down the pipeline.

In touch with this trend, FDA has formed an Additive Manufacturing Working Group, and in October 2014, the Agency engaged industry stakeholders to discuss technical considerations surrounding 3-D printed products. However, according to workshop remarks from Dr. Matthew Di Prima, head of the FDA Additive Manufacturing Working Group, the workshop was strictly focused on technical issues related to 3-D printing and “regulatory policy” was “going to be a whole separate discussion.”

Indeed 3-D printing presents many regulatory questions that currently translate to regulatory uncertainty.   However, leading innovators seem to be moving full steam ahead in the development of various 3-D printed technologies because of the value they offer patients.  With the right kind of regulation, the “personalized medicine” these 3-D printers can provide, and the speed with which custom devices can be produced relative to conventionally manufactured products, could greatly advance the public health.  Accordingly, many are hoping that FDA will soon move past technical discussions and work with stakeholders to develop the best possible regulatory framework to expand access to safe and effective 3-D printed devices.

Below is a roundup of some of the latest news stories in the 3-D printing field. The buzz that these stories are creating further demonstrates the need for FDA to take a more definitive stance on how it plans to regulate an increasingly complex array of 3-D printed products.

New 3-D Printed Devices in the Works

The Washington-based Aortica Corporation announced in November of 2014 that it had raised $7 million to complete a pivotal FDA study on its groundbreaking 3-D device intended to treat abdominal aortic aneurysms (AAA).  An AAA is an enlarged bulge in the aorta that gradually gets bigger over time and can eventually burst, causing severe internal bleeding and death without immediate specialized treatment. Over 150,000 U.S. patients are diagnosed with AAA each year.

Open heart surgery can be used to treat AAA, but the gold standard (and less invasive) treatment option is endovascular therapy, which involves the insertion of a graft through the femoral artery.  Despite the advantages of endovascular therapy, Aortica co-founder, Dr. Starnes, explains, “Approximately 30-40% of patients diagnosed annually in the U.S. with moderate to severe AAA disease are ineligible for less invasive endovascular therapy due to anatomical limitations.” To address this, Aortica is working to develop a patient-specific 3-D printed endograft to make more candidates eligible for this gold standard treatment option.

Researchers in Washington, D.C. are also making waves in the development of 3-D printed products. For example, George Washington University assistant professor, Lijie Grace Zhang, recently received a $2.2 million NIH grant to study the use of 3-D printing to build human tissue.  While Zhang admits that the tissue engineering field has a long way to go, she ultimately hopes to build 3-D printed organs in her lifetime. One obstacle she and her team will have to overcome, however, is the task of printing vascular tissue, such as veins and arteries, which was cited by Zhang as the biggest challenge in tissue organ regeneration (the specific difficulty is replicating the density of vascular tissue such that blood is able to circulate through the entire structure).

What about Cost?

Because 3-D printed products are so cutting edge, patients might assume that the ones currently available are incredibly expensive. But, according to Maryland surgeon, Chris Cannova, this is not necessarily the case. Cannova, who performs knee replacements with 3-D printed knee implants, explained that insurance companies see a knee replacement as a knee replacement regardless of whether a traditional or 3-D printed implant is used. He noted that both insured and Medicaid patients receiving 3-D printed implants only face a minor cost increase compared to traditional implants as most insurance companies will cover the CT scan needed to size the patient’s knee to create the 3-D printed implant (and such scans only cost a few hundred dollars).

Texas surgeon, Bruce Bollinger, confirmed Cannova’s insight on cost. He stated that his office usually charges between $4,000 and $7,000 for a knee implant, and that the cost of a 3-D printed implant (of the same brand used by Cannova) is $5,000.

Cost considerations surrounding 3-D printed products are also a topic of discussion among device manufacturers. One commentator has noted the benefits of 3-D printing for device manufacturers, particularly in the prototype phase, explaining that “3-D printing gives you the freedom to redesign while in production.” Whereas a design change for a traditional mold would typically set a manufacturer back at least a few thousand dollars and create a timing delay, a 3-D printing company could immediately implement the change and start printing the revised products.

3-D printed products will undoubtedly continue to be a hot topic in 2015. And, hopefully, FDA will respond by offering some definitive insight into its regulatory intentions with respect to these products. While it’s hard to predict what this guidance might look like, back in 2013, Jeffrey Shuren, director of FDA’s Center for Devices and Radiological Health, provided some thoughts on this topic. Shuren explained that the manufacturing component (i.e., how 3-D printing actually occurs and the materials used) would likely be the focus of the guidance. This seems to align with the “technical” focus of the recent public workshop.  Shuren also shared that FDA is not aiming to get in the way of 3-D printing innovators in carrying out its regulatory efforts, and that the Agency views 3-D printing as an important piece of the personalized medicine movement.

In early October, FDA held a public workshop to discuss the challenges of regulating medical devices made through additive manufacturing (also known as 3-D printing). Additive manufacturing gives designers the ability to build devices directly from 3-D images, like patient CT or MRI scans. As the push toward personalized medicine continues, 3-D printed devices hold incredible potential for advancing the ball. While additive manufacturing isn’t completely mainstream yet, FDA and industry stakeholders expect to see major growth in this field in coming years. Experts project that the global market for healthcare 3-D printing will reach $1.13 billion by 2020.

With industry innovators moving forward, FDA’s goal for last month’s workshop was to get a handle on the technical challenges and patient safety concerns that come with 3-D devices.

What’s Already Out There?

3-D-Printed-Hand-640x480FDA has already begun receiving (and clearing) submissions for 3-D printed devices. For example, additive manufacturing company, Oxford Performance Materials (OPM), has received 510(k) clearances for two 3-D printed devices over the past two years (the OsteoFab Patient-Specific Cranial Device (cleared in February 2013) and the OsteoFab Patient-Specific Facial Device (cleared in July 2014).

Following the clearance of its 3-D printed facial device, OPM’s CEO, Scott DeFelice, noted, “Until now, a technology did not exist that could treat the highly complex anatomy of these demanding [facial reconstruction] cases. With the clearance of our 3D printed facial device, we now have the ability to treat these extremely complex cases in a highly effective and economical way, printing patient-specific maxillofacial implants from individualized MRI or CT digital image files from the surgeon.” OPM plans to continue innovating in the additive manufacturing space. In fact, the company recently announced a partnership with Yale University to pursue new 3-D printed biomedical technologies.

Other types of 3-D printed devices have also recently hit headlines, including 3-D printed tracheal splints and vertebrae.

FDA Evaluation of 3-D Printed Devices 

As mentioned earlier, OPM’s two implant devices were cleared through FDA’s 510(k) process. To obtain FDA clearance through this process, a manufacturer must show that its device is “substantially equivalent” to another device that is legally marketed in the U.S. (a “predicate device”). In each of its 510(k) applications, OPM compared its proposed 3-D printed device to predicate devices that had similar intended uses (i.e., replacing bony voids in the cranial skeleton (for its 3-D printed cranial device) and correcting trauma/defects in facial bone (for its 3-D printed facial device) and similar technical specifications (i.e., customized for each patient). The fact that the suggested predicate devices had not been manufactured using 3-D printing did not prevent FDA from determining that the new proposed devices were “substantially equivalent” to the predicates.

However, in light of the highly individualized nature of many 3-D printed devices, some commentators have questioned whether the 510(k) process (or any of the typical premarket pathways for that matter, i.e., PMA, de novo, etc.) are appropriate for these devices. Part of the argument is that the traditional tools manufacturers have used to support a proposed device’s safety and effectiveness (e.g., clinical trials) hardly apply for many 3-D printed devices.  For example, how do you create a clinical trial where the intended user of a device is just one patient?

Yet, at this point, FDA is not evaluating 3-D printed devices in a way that is vastly different than how it evaluates any other medical device. FDA has stated that depending on its use, “[a]dditive manufacturing may or may not present new questions.” Still, FDA acknowledges that additive manufacturing is a complex process (that will likely become increasingly more complex) and is actively seeking input from stakeholders in industry and academia to help shape its regulatory approach (including future guidance documents). Going forward, it appears that a key Agency focus in reviewing 3-D printed product submissions will be on process verification and validation, which according to FDA, “are especially important when devices are produced individually or in very small batches.”

3-D printed devices have clear promise for providing treatment solutions that are both patient-specific and cost-efficient. Guided by stakeholder discussion and feedback, FDA will hopefully be able to come up with a regulatory approach that appropriately addresses the risks posed by 3-D printed devices without significantly impeding patient and clinician access to these valuable innovations.