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Inside Medical Devices

Updates on Developments for Medical Devices from Covington & Burling LLP

FDA Holds Public Meeting on When a 510(k) Should be Submitted for a Modification to a Cleared Device

By Afia Asamoah on Posted in FDA Device Regulation

Last week, FDA held a public meeting to solicit stakeholder input to inform FDA’s development of both a report to Congress and, ultimately, a new policy on when a 510(k) should be submitted for a modification to a cleared device.  We described the purpose and goals of FDA’s public meeting in an earlier post.

At the June 13 public meeting, industry and consumer groups expressed differing views about the appropriate role for manufacturers in deciding when to submit a new 510(k) for a modified device.  For example, AdvaMed reiterated the position set forth in its white paper (released the day before the public meeting) that the manufacturer is best qualified to determine whether a change “could significantly affect the safety or effectiveness of a device,” thereby meeting the regulatory standard for submission of a new 510(k).  Industry groups, such as AdvaMed and the Medical Device Manufacturers Association, argued that a new regulatory approach was not needed.  Instead, AdvaMed recommended that FDA make only modest changes to address concerns with the 1997 memorandum, “Deciding When to Submit a 510(k) for a Change to an Existing Device,” by making the following modifications:

  • require manufacturers to evaluate device changes in accordance with an established procedure and retain records detailing how they evaluated whether a premarket submission was needed for a device change;
  • establish a procedure within their quality systems to ensure design changes before and after production of the device are reviewed, validated (or verified where appropriate) and approved; and
  • indicate that manufacturers should document how the decision was made based on validation or verification testing (if applicable) in compliance with the QSR requirements.

In contrast, some consumer groups, such as the National Research Center for Women and Families, argued that FDA, not device manufacturers, should determine whether a new 510(k) is required for a device modification.  Such groups did not support keeping the 1997 memorandum, and instead advocated for FDA to issue a new guidance.

At the meeting, FDA indicated that changes to the 1997 memorandum were necessary, for example, to keep up with new technologies, such as wireless or Bluetooth.  But the agency noted that change might not happen quickly because some proposals might require regulatory or legislative action to implement.  FDA noted that it will continue to seek stakeholder input on this issue.

The webcast of the public meeting is available on the FDA website and the agency is accepting written comments until July 13, 2013.

Florida Adopts Daubert Standard for Expert Testimony

By Brianne Bharkhda on Posted in Products Liability

On June 4, 2013, Florida’s Governor signed into law a bill amending Florida’s evidence code,  replacing the Frye standard, which had previously governed the admissibility of expert testimony in Florida, with the Daubert standard.  Florida’s new rules closely track Federal Rules of Evidence 702 and 703.  One major implication of the new evidence rules is that they will require judges in the state to perform a much more prominent gatekeeping function than they did under the previously used Frye standard.  However, how the new rules will be interpreted and applied remains to be seen.

Under Florida’s new standard, as with Federal Rule of Evidence 702, if scientific, technical, or other specialized knowledge will assist the trier of fact, a witness qualified as an expert by knowledge, skill, experience, training, or education may provide opinion testimony if:

  1. the testimony is based upon sufficient facts or data;
  2. the testimony is the product of reliable principles and methods; and
  3. the witness has applied the principles and methods reliably to the facts of the case.

Fla. Evid. Code § 90.702.  Additionally, similar to Federal Rule of Evidence 703, the Florida statute also specifies that facts or data that are otherwise inadmissible may not be disclosed to the jury unless the court determines that their probative value substantially outweighs their prejudicial effect.  Fla. Evid. Code § 90.704.  The new rules of evidence take effect July 1, 2013.

Interestingly, the statute itself provides courts with specific guidance on how the legislature meant it to be interpreted and applied.  Indeed, the preamble to the statute expressly states that Florida’s new Daubert standard should be interpreted consistent with Daubert v. Merrell Dow Pharmaceuticals, 509 U.S. 579 (1993), General Electric Co. v. Joiner, 522 U.S. 136 (1997), Kumho Tire Co. v. Carmichael, 526 U.S. 137 (1999).  The statute also specifies that Florida courts are no longer to allow the admission of “pure opinion testimony” as was permitted in Marsh v. Valyou, 977 So.2d 543 (2007), under the Frye standard.  In Marsh, the Florida Supreme Court held that a causation expert’s proffered expert testimony that trauma can cause fibromyalgia was “pure opinion testimony” which was not subject to the requirements of the Frye standard and was therefore admissible regardless of whether the hypothesis had not gained general acceptance in the scientific community.  According to the court, the expert’s causation opinion was “pure opinion testimony” because it was based on his experience and training.  The changes to Florida’s evidence rules are intended to prohibit the admission of such testimony.

Congress Continues to Press Medical Device Tax Repeal

By Dena Feldman on Posted in Federal Taxation

Congress continues to consider repeal of the medical device tax passed as part of the Affordable Care Act (ACA).  We have previously discussed the requirements of the final IRS rule implementing tax and well as accompanying interim guidance.

In February 2013, two bills to repeal the medical device tax were introduced in the House and the Senate.  Since then, efforts have continued in both houses of Congress.

At the end of March, the Senate overwhelmingly voted, in a non-binding resolution, to repeal the 2.3 percent tax on medical devices that went into effect in January.  The amendment to the budget resolution was offered by Senator Orrin Hatch of Utah, and garnered a vote of  79-20.  All Republican Members of the Senate voted in favor, as did over half of the Democratic Senators.  However, because the vote was part of the budget resolution, it has no legislative effect on the existence of the tax.

Meanwhile, repeal of the tax also continues to receive strong, bipartisan support in the House of Representatives.  The Protect Medical Innovation Act of 2013 (H.R. 523), introduced by Reps. Erik Paulsen (R-MN) and Ron Kind (D-WI) has gathered  247 co-sponsors, over half of the House.  And advocates of repeal are continuing to put pressure on lawmakers in Capitol Hill press.

Nevertheless, the Administration opposes the repeal efforts.  In a hearing last week before the House Education and Workforce Committee, Secretary of Health and Human Services (HHS) Kathleen Sebelius said that many of the millions of Americans who will receive coverage under ACA will gain access to medical devices, thereby increasing the industry’s number of customers.

Still, given the broad support of repeal in both Houses of Congress, it is possible that Congress would have the votes to override any presidential veto.

Supreme Court Issues Decision on Gene Patenting in Myriad Case

By Natalie Derzko on Posted in Intellectual Property

Kurt Calia and Allison Kerndt also contributed to this post.

The Supreme Court released its decision in Association for Molecular Pathology et al. v. Myriad Genetics, Inc. et al. (Appeal No. 12-398) earlier today.  The question presented was whether human genes are patent eligible.  In a unanimous decision, the Supreme Court held that naturally occurring DNA sequences are products of nature and not patent eligible merely because they have been isolated.  However, complementary DNA sequences (cDNA) are patent eligible because they are not naturally occurring.

In its decision, the Court acknowledged that patent protection attempts to balance the need to create incentives for research and innovation against the danger of impeding the flow of information that permits discovery.   The Court indicated that products of nature are not patent eligibile because they are “basic tools of scientific and technological work” and “there would be considerable danger that the grant of patents would ‘tie up’ the use of such tools and ‘inhibit future innovation premised upon them.’”  The Court acknowledged that the rule against patents on naturally occurring things has its own limits, because all inventions, at some level of abstraction, rely upon laws of nature and natural phenomenon and, if interpreted too broadly, could “eviscerate” patent law.

The Court concluded that although Myriad found the location of BRCA 1 and BRCA 2 genes, neither this discovery nor the separation of the genes from their surrounding genetic material rendered the genes new compositions of matter that are patent eligible.  The Court also rejected the notion that isolating the sequence from the rest of the genome by severing chemical bonds creates a non-naturally occurring molecule, stating that the claims are not expressed in terms of their chemical composition but rather in terms of the order of bases — i.e., the genetic information.

In contrast, the Court determined that cDNA sequences are not products of nature because their creation removes the non-coding regions from the sequence, resulting in something new that is the product of human intervention.  Per the Court:  “cDNA retains the naturally occurring exons of DNA, but it is distinct from the DNA from which it was derived” and, as such, it “is not a ‘product of nature’ and is patent eligible . . . except insofar as very short series of DNA may have no intervening introns to remove when creating cDNA,” in which case “a short strand of cDNA may be indistinguishable from natural DNA.”

At the end of its opinion, the Court made clear “what is not implicated by [its] decision.”  The opinion does not consider the patent eligibility of Myriad’s method claims, patents on new applications of knowledge about the BRCA 1/BRCA 2 genes, or the patentability of DNA in which the order of nucleotides has been altered.  Specifically, the Court wrote that an innovative method of manipulating genes while searching for BRCA 1/ BRCA 2 genes could potentially be the subject of a method patent, that many of Myriad’s unchallenged claims were directed to applications of the knowledge gleaned from its isolation of BRCA 1/2 genes, and that the Court has no opinion on the patent-eligibility implications of alterations to the genetic code.

In a short concurrence, Justice Scalia declined to join portions of the opinion “going into fine details of molecular biology,” stating “I am unable to affirm those details on my own knowledge or even my own belief.”

FDA Issues Draft Guidance Document on Cybersecurity in Medical Devices

By Chris Pruitt on Posted in FDA Device Regulation, Medical Information Technology

The issue of cybersecurity has been on FDA’s radar in the last year, due in part to a Government Accountability Office report issued last August that urged FDA to consider the risk of intentional threats to device information security.  Although the GAO report noted that FDA was not aware of any actual incident of device hacking, researchers have demonstrated the ability to remotely exploit devices such as implanted defibrillators and insulin pumps.

Addressing such threats, FDA has issued a draft guidance document entitled “Content of Premarket Submissions for Management of Cybersecurity in Medical Devices.”  The draft guidance is intended to make “recommendations to consider and document in FDA medical  device premarket submissions to provide effective cybersecurity management and to reduce the risk that device functionality is intentionally or unintentionally compromised.”

FDA outlines three general principles of cybersecurity that manufacturers should consider:

  • Confidentiality of data, information, and systems;
  • Integrity of data and information; and
  • Availability of data, information, and information systems when needed.

According to the draft guidance, devices that connect with other devices, with the Internet, or with portable media could be more vulnerable to cybersecurity threats.  Manufacturers will be expected to perform a hazard analysis for their particular devices.

The draft guidance makes specific recommendations of security features to consider and document in premarket submissions, including measures to limit access to trusted users, ensuring trusted content, and using fail safe and recovery features.  The draft guidance also specifies the type of documentation that should be included in submissions to address cybersecurity issues, such as a traceability matrix that links cybersecurity controls to risks that were considered.

Although the guidance is geared toward premarket submissions, it may be useful for manufacturers of class I devices as well.  Class I devices that are automated with computer software are subject to the design controls of the Quality System Regulation (QSR).  FDA recommends several specific cybersecurity activities that manufacturers should consider as part of a risk assessment under the QSR.

FDA Releases Final Guidance on Priority Review of Premarket Submissions for Devices

By Mingham Ji on Posted in FDA Device Regulation

On May 17, 2013, FDA issued a guidance document regarding priority review of premarket submissions for devices.  This newly released guidance supersedes the document “Expedited Review of Premarket Submissions for Devices,” which the agency issued in 2008, and incorporates changes from the Medical Device User Fee Amendments of 2012 (MDUFA III).  As part of its goals under MDUFA III, FDA committed to process and timing improvements.  For more information on MDUFA III, which was enacted in the Food and Drug Administration Safety and Innovation Act of 2012 (FDASIA), please see our client alert.

Priority review allows designated applications to be “placed at the beginning of the appropriate review queue” and to receive additional review resources from the FDA on an “as needed” basis.  In order to be considered appropriate for priority review, the device (or combination product where CDRH is the lead Center) must be intended to treat or diagnose a life-threatening or irreversibly debilitating disease or condition, and also satisfy one of the following:

  • The device represents a breakthrough technology that provides a clinically meaningful advantage over existing technology;
  • No approved alternative treatment or means of diagnosis exists;
  • The device offers significant, clinically meaningful advantages over existing approved alternatives; or
  • The availability of the device is in the best interest of patients.

FDA has applied this priority review criteria to all premarket submissions, rather than only to premarket approval applications (PMAs).  The agency’s timeframe goals for reaching a decision on whether to grant priority review status depend on whether it is a pre-submission communication (2 weeks), 510(k) or de novo classification action (2 weeks), a PMA (within the 45-day filing review, or within 30 days of filing a 180-day supplement), or biologics license application or supplement (at the IND stage, or within 60 days of the submission).  The agency warns in its guidance document, however, that a grant of priority review status does not guarantee that the device submission will enjoy a more accelerated approval than submissions that are not granted priority review status.

The guidance document specifically emphasizes that industry and FDA share the responsibility of identifying devices that may be appropriate for priority review.  The agency encourages sponsors to consider a device’s eligibility for priority review status throughout the development process and suggests that sponsors consider submitting a Pre-Submission if they develop a device that may qualify.

FDA’s new guidance document also includes a discussion of the agency’s own administrative procedure, including a “Priority Review Checklist,” for determining whether priority review is appropriate for a particular device.

Advocate General Opinion on Reclassification of Medical Devices

By Sarah Cowlishaw on Posted in Device Regulation in Europe

On May 30, 2013, Advocate General Sharpston delivered an opinion on a request for a preliminary ruling from the Finnish national courts concerning the laws governing reclassification of medical devices (Advocate General: Opinion, Case C-109/12).  The Advocate General’s opinion does not bind the Court of Justice of the European Union (CJEU).  However, in the majority of cases the Court follows the Advocate General.

National courts use the preliminary ruling procedure if they are in doubt about the interpretation or validity of an EU law. In such cases, they may ask the CJEU for advice. The Advocate Generals, who are part of the composition of the CJEU but distinct from the CJEU judge, provide the CJEU with public and impartial opinions to assist the Court in its decision making. The Advocate Generals’ opinions are advisory and non-binding, but they are nonetheless very influential.

The Finnish Supreme Administrative Court sought a preliminary ruling on three questions.  In brief:

  1. Can one Member State classify a product as a medicinal product while another Member State classifies it as a medical device?
  2. What is the process for reclassifying a medical device as a medicine?  Is it sufficient to follow the procedures set out in Directive 2001/83/EC (the Medicinal Products Directive)?  Or is it necessary, prior to initiating procedures under the Medicinal Products Directive, for the competent authorities to follow the applicable provisions of Directive 93/42/EEC (the Medical Devices Directive), particularly Articles 8 and 18?
  3. Can a product with the same active substance and mode of action be on the market in one Member State as both a medicine and a medical device?

Background

Laboratories Lyocentre manufactures a vaginal capsule used for correcting bacterial imbalances.  The product’s composition consists of a particular bacterium of the lactobacillus genus, together with lactose and magnesium stearate.  Gelatine is used for the capsule’s protective shell.  Until 2006, the product was marketed in Finland as a natural medicine under the name Gynophilus.  Since 2006, the same product has been marketed in Finland under the name Gynocaps as a medical device with a CE marking.  It is also sold and marketed in the same manner in Austria, Spain, Italy and France.

In 2008, the Finnish National Agency for Medicines considered the composition and mechanism of action of the product and decided that Gynocaps could no longer be marketed as a medical device within the meaning of the Finnish Law on medical devices and accessories.  It considered the product to be a medicine that required a marketing authorization.  Laboratories Lyocentre appealed the decision, and the Finnish Supreme Administrative Court subsequently sought a preliminary ruling on Questions 1 – 3.

Opinion

The Advocate General’s Opinion does not consider the actual classification of the product at issue.  It takes no position on the merits of the National Agency for Medicines’ decision to reclassify the product as a medicine.  However, it address the three Questions 1 – 3 referred by the Finnish court.  In summary, the Advocate General expressed the following opinions:

Question 1

The Medical Devices Directive and the Medicinal Products Directive do not exclude the possibility that a product can be classified as a medicine in one Member State and as a medical device in another.  The Advocate General states: “In my opinion, as long as there is no complete harmonisation with respect to these types of product, it is possible for one Member State to conclude with confidence that a given product is a medical device whereas another takes the position that the same product is a medicinal product.” (para. 55).  Although he goes on to recognize that different classifications in different Member States may result in legal uncertainty and create some impediment to the smooth functioning of the single market, he states that “those consequences are the corollary of incomplete harmonisation.” (para. 67).

Question 2

The Advocate General discusses the overlap of Article 18 of the Medical Devices Directive, which concerns “wrongly affixed CE marking,” and Article 8, the “safeguard clause” allowing Member States to take action to remove unlawful or unsafe products from their markets.  He also considers these provisions in the context of the Medicinal Products Directive.  In brief, the Advocate General opined that “where a product which has previously been classified as a medical device ought in fact to be classified as a medicinal product only immediate removal from the market can achieve compliance with both sets of rules [the Medical Devices Directive and the Medicinal Products Directive].” (para. 95).  Further, “a product that is reclassified as a medicinal product cannot remain or be placed on the market until a marketing authorisation has been obtained and the other conditions set out in the Medicinal Products Directive have been met.” (para. 98).

Question 3

If two products are identical in all respects, a Member State cannot classify the products differently and allow one product to be marketed as a medicine and the other as a medical device.  In cases of doubt, the Medicinal Products Directive must apply.  However, EU law does not preclude Member States from classifying two similar products differently, even if they contain the same active substance and have the same mode of action.  The Advocate General concludes that “the mere fact that two products contain the same substance and have the same modes of action is insufficient to conclude that they must be classified and put on the market in the same manner...” (para. 74)

Concluding remarks

The Advocate General’s opinion confirms that Member States must make classification decisions on a case-by-case basis.  It recognized that there is incomplete harmonization in the EU.  As such, there is a risk that Member States may adopt different views leading to inconsistent positions in each jurisdiction.  It will be interesting to see whether the CJEU follows the Advocate General’s opinion in its final judgment on the case.

Lessons from FDA’s First Public Mobile Medical Apps Enforcement Letter

By Chris Pruitt on Posted in FDA Device Regulation, Medical Information Technology

As we discussed in a previous post, FDA took its first publicly announced enforcement action against a mobile app developer on May 22, issuing an “It Has Come to Our Attention Letter” to India-based app developer, Biosense Technologies.  The letter received extensive media coverage, and the mHealth sector was immediately abuzz with interest (and concern) about its implications.

Commentators observed that the letter appeared to be intended, in large part, as an educational tool for industry.  As such, it’s appropriate to ask:  what lessons should industry draw?  Although single enforcement actions do not always serve as reliable predictors of future actions, the letter offers a handful of key takeaways:

  • Public and political pressure can spur FDA action.  Biosense’s app hardly was flying under the radar.  The app received media coverage after being featured at a TED conference, and it was called out in trade press and in testimony to the House Energy and Commerce Committee.  These factors likely helped push FDA to finally take a public enforcement action.
  • Lack of a final guidance document doesn’t preclude enforcement.  Although FDA’s draft guidance document on mobile medical apps was “distributed for comment purposes only,” the principles FDA proposed were on display in the Biosense enforcement letter.  The uCheck app had the effect of transforming “the mobile platform into a medical device”—causing FDA to conclude that “the phone and device as a whole functions as an automated strip reader.”  It thus fell into one of the categories of apps that FDA stated that it would regulate.
  • FDA will second-guess how an app is listed.  Though not mentioned in the enforcement letter, the uCheck app is listed in FDA’s establishment registration and device listing database as a class I “[a]utomated urinalysis system” under 21 C.F.R. § 862.2900, defined as a “device intended to measure certain of the physical properties and chemical constituents of urine by procedures that duplicate manual urinalysis systems.”  Though not an inaccurate description of the device’s overall function, FDA’s letter observed that the app is intended to work with certain reagent strips that were cleared as part of class II test systems, and FDA offered an example 510(k) for a similar strip-reading device.  Thus, when determining the proper classification for an app, developers should thoroughly research how similar devices are regulated—as classification regulations that appear applicable on first blush may not capture all of a device’s functionalities.  Developers also should be aware of the “.9 regulations” contained in each device classification Part, which state that devices used for certain purposes (including “diabetes management”) are not exempt from the requirement of 510(k) premarket notification.

Lab Association Petition Challenges FDA’s Authority To Regulate LDTs Under the FDCA

By Ellen Flannery on Posted in FDA Device Regulation

The American Clinical Laboratory Association (ACLA) filed a citizen petition on June 4 challenging Food and Drug Administration (FDA) authority to regulate laboratory developed tests (LDTs) as “devices” under the Federal Food, Drug, and Cosmetic Act (FDCA).  ACLA’s petition requests that FDA refrain from promulgating any draft or final guidance or rule purporting to regulate LDTs as “devices” under the FDCA, and to confirm that LDTs are not “devices” under the FDCA.   The full citizen petition can be found on ACLA’s website: www.acla.com.

ACLA’s petition argues that the text and legislative history of both the FDCA and the Clinical Laboratories Improvement Act of 1967 (CLIA) and its 1988 amendments (CLIA ’88) demonstrate that FDA lacks statutory authority to regulate LDTs as “devices.”  Instead, Congress intended to regulate clinical laboratory testing under a single statute — the comprehensive statutory framework of CLIA ’88.  ACLA also states that FDA regulation of LDTs would be contrary to the public health and would result in numerous unintended consequences with significant economic impact on the laboratory industry.  ACLA points out that amending CLIA would be the most logical and appropriate approach if stakeholders have concerns about possible regulatory gaps under CLIA.

FDA Commissioner Margaret Hamburg presented remarks at the American Society of Clinical Oncology meeting on June 2 that addressed both companion diagnostics and laboratory-developed tests.  She said that FDA has a “risk-based framework” under development to “ensure that diagnostics used in cancer treatment will provide medical professionals with a critical baseline for confidence in the tests they order for their patients.”  She also said:  “Our intent in considering what to do about LDTs is to provide for safe and effective diagnostics while promoting innovation and patient access.”  ACLA’s press release indicates that the petition was filed in response to statements that FDA intends to regulate LDTs as devices.

 

Summary of FDA Advertising and Promotion Enforcement Activities in April 2013

By Saurabh Anand on Posted in FDA Device Regulation

Covington & Burling LLP issues monthly e-alerts summarizing publicly-available FDA enforcement letters (i.e., warning letters and untitled letters) relating to the advertising and promotion of drugs, medical devices, and biologics.  In April 2013, FDA’s Office of Prescription Drug Promotion (OPDP), Center for Devices and Radiological Health (CDRH), and Office of Compliance and Biologics Quality (OCBQ) in FDA’s Center for Biologics Evaluation and Research (CBER) each posted one enforcement letter on their respective websites relating to advertising and promotion.  A summary of these enforcement letters can be found here.  You can also sign up for our e-alerts here.