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MedTech RA/QS Affinity Group Regulatory Update for Q1 2016

HIGHLIGHTS

Enforcement

Drugs

OPDP enforcement reaches record low in 2015 as drugmakers face uncertainty in digital marketing . . . . . . . . . . . . . . . . 2

First OPDP untitled letter of 2016 criticizes Pfizer subsidiary's YouTube video for misbranding Precedex . . . . . . . . . . . . . . 3

FTC FY2014 statistics highlight impact of FTC v. Actavis dispute as number of potential pay-for-delays falls . . . . . . . . . . . . 3

FDA concedes to Amarin in First Amendment off-label marketing row . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Devices

FDA enforcement statistics for FY2015 point to more enforcement by CDRH than by CDER . . . . . . . . . . . . . . . . . . . . 5

Laws, Regulations and Guidance

Drugs

FDA publishes updated guidance on selective safety data collection for late-stage premarket, postapproval clinical studies . . . 7

Dr. Robert Califf to lead FDA following confirmation as commissioner . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

FDA establishes Office of Regulatory Affairs ombudsman . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

Senators introduce bill to shed tax deduction for DTC pharma advertising . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

FDA revises guidance on pediatric study plans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

Devices

FDA publishes guidance on human factors review for devices, combination products . . . . . . . . . . . . . . . . . . . . . . . . 10

FDA publishes draft guidance on clinical trials for devices targeting neurological disease . . . . . . . . . . . . . . . . . . . . . . 11

FDA, industry hammer out details of $500M MDUFA IV deal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

FDA asks coverage organizations to participate in device pre-submission meetings . . . . . . . . . . . . . . . . . . . . . . . . . 12

FDA seeking input on refurbished medical devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Draft guidance calls on medical device manufacturers to establish processes to monitor, respond to cybersecurity vulnerabilities 12

Other

Revised FDA guidance allows term 'dietary supplement' to be used as entire statement of identity . . . . . . . . . . . . . . . . 13

FDA asks manufacturers of human cell, tissue-based products to report adverse events within 15 days . . . . . . . . . . . . . . 13

This publication may constitute "Attorney Advertising" under the New York Rules of Professional Conduct and under the law of other jurisdictions.

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ENFORCEMENT

Drugs

OPDP enforcement reaches record low in 2015 as drugmakers face uncertainty in digital marketing

Enforcement by the OPDP has fallen notably since 2010. The decline has been attributed, in part, to the agency's slow adoption of digital marketing guidance, even as drugmakers embrace the new marketing formats afforded them. Expected guidance on Internet, social media and promotional labeling could have an impact on enforcement levels.

In 2015, the FDA's Office of Prescription Drug Promotion (OPDP) issued markedly fewer warning and untitled letters than in previous years, continuing a downward trend .

After hitting a high of 196 in 1999, the number of letters issued by the Division of Drug Manufacturing, Advertising and Communications (DDMAC) began to plummet, dropping to 23 in 2003. There was a slight uptick in 2005 (29), but warning letters continued to fall overall until 2008. In 2008, the number of letters began to climb gradually, reaching 52 in 2010. During an FDA reorganization that year, DDMAC became OPDP, and since then the number of letters has continued to slide, reaching a record low of nine in 2015 . Only two of the nine letters issued in 2015 were warning letters; the rest were untitled letters. Five of the letters related to issues with risk information, while four related to unsubstantiated claims. Letters also addressed superiority claims (one), overstated efficacy (one), promotion of an unapproved drug (one) and other claims (six).

Graphic Source: ShiftCentral with FTC data

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Communication methods targeted in the letters were primarily digital (four) and traditional media. Three of the letters regarding digital media involved websites, while one related to a post on Instagram and Facebook that included risk information only via a link. To date, the FDA has issued little guidance on digital media, but the Center for Drug Evaluation and Research is planning to publish guidance on Internet, social media and promotional labeling this year. The lack of guidance to date could play a role in the declining enforcement levels, as the guidance needed to signal which violations could warrant letters has been missing. Significantly, the first letter sent in 2016 involved a YouTube video.

Notably, these letters were primarily sent to smaller, lesser-known pharmaceutical companies. In contrast, the first letter sent in 2016 was to one of the best-known pharmaceutical companies in the world — Pfizer — with regard to an online video for a sedative.

First OPDP untitled letter of 2016 criticizes Pfizer subsidiary's YouTube video for misbranding Precedex

The untitled letter sent to Hospira takes issue with a video advertisement for Precedex for failing to present risk information and representing the drug in ways that don't align with FDA-approved product labeling and indication. It is the first letter issued by the office in 2016.

The FDA's Office of Prescription Drug Promotion sent an untitled letter to Hospira, a subsidiary of Pfizer, over what it calls a "misleading" YouTube video on the sedative Precedex. The office reviewed that video as part of its monitoring and surveillance program and found that it omitted risk information, misbranding the drug based on the Federal Food, Drug, and Cosmetic Act.

The drug's approved product labeling includes warnings and precautions on its administration and adverse events. The video included multiple claims

of efficacy for the drug but failed to include this risk information; what’s more, it suggested arousability is a benefit instead of treating that as a warning and precaution. Because of these omissions, the FDA found that the video presents a misleading impression of the drug's safety.

The agency also cites the video's representations about the drug's use for sedation in the intensive care setting, finding that the video fails to include material information about the FDA-approved indication for Precedex. Specifically, Precedex is indicated for sedation of initially intubated and mechanically ventilated patients during treatment in an ICU.

The regulatory authority also criticized Hospira for failing to submit a copy of the video to the OPDP, as required at the time of initial publication of an advertisement for a prescription drug. The drugmaker should have submitted a transmittal Form FDA-2253 (Transmittal of Advertisements and Promotional Labeling for Drugs for Human Use).

The letter is the first to be issued by the OPDP in 2016 and comes in advance of expected guidance on Internet, social media and promotional labeling.

FTC FY2014 statistics highlight impact of FTC v. Actavis dispute as number of potential pay-for-delays falls

The Federal Trade Commission found that pharmaceutical companies filed a total of 160 agreements to resolve patent disputes in fiscal year 2014 — the first full year since the Supreme Court ruled in FTC v. Actavis that brand makers' reverse payments to generic competitors may violate antitrust laws .

In FY2014, the FTC found that the number of overall settlements was consistent with previous years, but the number of potential pay-for-delay deals dropped markedly. The overall number of deals increased slightly from 140 in the previous year, while the

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number of potential pay-for-delay deals slid from 29 in FY2013 to 21, continuing a fall from the record high of 40 such deals in FY2012.

During the year, 21 settlements constituted potential pay-for-delays because they contained clear compensation from a branded drugmaker to a generic drugmaker, along with a restriction on the latter's ability to produce its competitor product. These deals involved 20 branded products with combined annual sales of nearly $6.2 billion, the FTC said. Nearly half (10) involved a cash payment, which ranged from $35,000 to $5 million, while six included compensation in the form of a side business deal between the parties. The remaining deals involved compensation in the form of a branded maker's promise not to market an authorized generic in

competition with the generic maker's product for an established period of time.

Fifty-three of the 160 deals in FY2014 involved first-filer generics — producers who were the first to file abbreviated new drug applications. Of these, 11 contained compensations — the lowest number since 2007. In FY2013, 13 potential pay-for-delay deals involved first filers, down from 23 in FY2012.

The FTC identified another eight deals that contained "possible compensation" because it was not obvious whether provisions in the deals served as compensation. A majority of the overall deals (111) restricted the generic maker's ability to market its product, but did not include compensation. Twenty contained no restrictions on generic entry .

Graphic Source: ShiftCentral with FTC data

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The FTC also found that approximately 81 percent of the patent disputes were resolved without compensation — a trend that's been on the rise in recent years .

FDA concedes to Amarin in First Amendment off-label marketing row

The FDA and Amarin proposed settlement terms in a First Amendment battle over the off-label promotion of the triglyceride-lowering drug Vascepa. The settlement comes following a yearlong fight over Amarin sending promotional materials to doctors on an unapproved indication. The District Court for the Southern District of New York favored Amarin and ruled that the drugmaker is allowed to make statements about the drug for unapproved uses as long as it's truthful and non-misleading. As part of the settlement, the FDA and U.S. government agreed to allow Amarin to engage in truthful and non-misleading speech related to off-label uses. The agency also agreed to give Amarin an optional preclearance provision through 2020 for new off-label claims. Both sides also conceded to a dispute resolution to avoid future litigation. The terms of the agreement allow Amarin to submit up to two proposed communications per year to the FDA before promoting them to doctors in order to determine whether the FDA has concerns, after which the agency has 60 days to respond. Talking with STAT, former FDA associate chief counsel Patti Zeller said she thinks the settlement, though interesting, is unlikely to change how companies market their drugs. However, it may give them more fodder to negotiate with the FDA.

Source: Regulatory Affairs Professionals Society

Devices

FDA enforcement statistics for FY2015 point to more enforcement by CDRH than by CDER

The FDA's annual enforcement statistics show an overall spike in warning letters, but only a small

proportion of these letters were issued by the Center for Devices and Radiological Health (CDRH) and the Center for Drug Evaluation and Research (CDER). The statistics also point to a decline in seizures, a bump in injunctions and an uptick in recalls, particularly by CDRH.

In fiscal year 2015, the FDA issued more than 17,000 warning letters, seized one drug product, served 21 injunctions, recalled more than 9,000 products and delivered 14 drug debarments. The agency's annual enforcement statistics point to both lulls and rises in the regulatory body's enforcement activity.

A marked 17,232 warning letters were sent in 2015, notably higher than the 8,690 issued in 2014 and significantly higher than the mere 673 issued in 2010. However, these were issued primarily by the Center for Tobacco Products, which accounted for 16,629. The Center for Food Safety and Applied Nutrition (CFSAN) issued the second-highest number of letters (236), followed by the CDRH, with 168; the Center for Veterinary Medicine (CVM), with 119; and CDER, with 76.

The figures point to an ongoing decline in FDA seizures, from 15 in 2011 to just one in 2015. The CDER was the only division to seize a product during the year. Injunctions, on the other hand, climbed from 10 in 2014 to 21 in 2015 — the highest number in recent years (2010: 17; 2011: 16; 2012: 17; 2013: 19) . Of these, CDRH was responsible for four, and CDER was responsible for three. The CFSAN issued the most injunctions, 12, while the remaining two were issued by the CVM.

CDRH led the pack for recalls, with a total of 1,175 recall events affecting 2,850 products. Most of these recalls were class II (1,068), while class III recalls accounted for a small portion (69). CDER accounted for 303 recall events affecting 1,822 products, while CFSAN saw 621 recall events affecting 3,265 products and the Center for Biologics Evaluation

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Source: FDA Enforcement Statistics Summary Fiscal Year 2015 – FDA

Source: FDA Enforcement Statistics Summary Fiscal Year 2015 – FDA

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and Research (CBER) saw 651 recalls affecting 973 products. Recalls by the CVM and CTP were not as frequent and affected far fewer products.

LAWS, REGULATIONS, GUIDANCE

Drugs

FDA publishes updated guidance on selective safety data collection for late-stage premarket, postapproval clinical studies

The FDA revised and finalized guidance initially published in 2012 to help clarify safety data requirements during late-stage trials. The guidance is designed to help drugmakers strike a balance between collecting data that isn't pertinent and collecting sufficient data to characterize a drug's safety profile.

The FDA altered and finalized guidance initially published in 2012 on safety data requirements for late-stage premarket and postapproval clinical trials. The guidance, called Determining the Extent of Safety Data Collection Needed in Late-Stage Premarket and Postapproval Clinical Investigations, discusses when selective safety data collection should be considered.

In modifying the original guidance, the FDA took into consideration public comments requesting more detail and examples. The authority says it modified the document to provide further clarification on the specific types of safety data and circumstances that may be appropriate for selective collection, as well as to offer more information on safety data reporting issues. The FDA suggests sponsors discuss their plans for selective safety data with FDA review divisions at appropriate times, such as end-of-phase II meetings. The agency notes that the guidance is not

Source: FDA Enforcement Statistics Summary Fiscal Year 2015 – FDA

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meant to affect reporting of postmarketing adverse events pertinent to an approved drug.

Although the agency concedes that the recommendations may not align with safety data expectations in other countries, and that this may lead to implementation difficulties for some trials, it contends the guidance provides sponsors with the flexibility to design and implement trial protocols with selected safety data collections, where suitable.

The guidance states that selective data collection may be fitting during late-stage trials if the following conditions are met:

n The number of patients and their characteristics, as well as the duration of exposure and dose range, used in previous trials are adequate to characterize the safety profile and nonserious adverse events of a drug.

n The occurrence of common, nonserious adverse events has been relatively alike across multiple trials.

n The compound's safety profile is established enough that it's reasonable to conclude the occurrence of common, nonserious adverse events in the study population will be comparable to rates seen in previous trials.

The FDA outlines several types of clinical trials that may be considered for selective data collection, such as investigations of new indications, postapproval trials conducted as part of postmarketing commitments or requirements, and outcome clinical trials. The agency notes that some premarket clinical investigations for original applications may be considered for selective data collection, if adequate comprehensive safety data becomes available prior to completion of clinical development. Selective data collection may also be permitted in certain circumstances for postapproval investigations in a different population or with a different dose or

condition of use. Specifically, it may be appropriate to collect some adverse event data in only a subset of the overall study population, or selective data collection may be permitted in cases where a lower or shorter dose is being studied.

The guidance also outlines what data collection may be stopped or limited in cases of selective data collection. This includes nonserious adverse events not linked to dose modification, drug discontinuation or trial withdrawal; routine laboratory monitoring; and information on concomitant medications, as well as patient history and physical exams. Means of selective safety data collection include reducing collection to a pre-identified subset of the study population or decreasing the frequency of collection.

Dr. Robert Califf to lead FDA following confirmation as commissioner

A majority of the Senate voted to approve Califf's nomination as head of the FDA, although four continued to oppose his leadership. Califf, who joined the FDA last year as deputy commissioner, hopes to boost the FDA's workforce and improve safety surveillance systems.

Former Duke University researcher and cardiologist Dr. Robert Califf was confirmed as the new head of the FDA as a Senate majority voted in favor of his nomination. Four senators continued to oppose Califf's nomination — Edward Market, D-Mass.; Joe Manchin, D-W.Va.; Kelly Ayotte, R-N.H.; and Richard Blumenthal, D-Conn. Presidential candidate Bernie Sanders, D-Vt., was among those who opposed Califf's nomination, but he did not vote. Califf was serving as deputy commissioner and replaces interim commissioner Dr. Stephen Ostroff, who was filling the vacancy left by Dr. Margaret Hamburg.

Califf outlined several priorities for the agency going forward, with a particular focus on bolstering its workforce. He plans to fortify the regulatory body's workforce by working with academic and

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other centers to attract new talent. He also plans to establish what he calls professional "homes" for FDA researchers. For example, Califf said the agency is working toward "a coordinated effort to have all [the FDA's] statisticians have an identity and support services that they need." He hopes this move will reduce researchers' administrative burdens, such as maintaining medical licenses .

A second priority Califf identified is to enhance safety surveillance systems. He conceded that the agency's current system "is not enough." However, he said the agency isn't proposing to shed the current system. In particular, he pointed to the need to modernize the existing tools to monitor the safety of medical devices and the need for medical professionals to "step up" to be part of that process.

Califf takes over the agency amid lawmakers' mounting pressure for change. The 21st Century Cures Act, which would require the agency to consider more flexible clinical trials, recently passed the House of Representatives. The Senate is mulling similar legislation. For his part, Califf, who has worked on high-profile clinical studies in the past, said he's keen to make the clinical trial process more efficient.

FDA establishes Office of Regulatory Affairs ombudsman

In an effort to make the FDA's Office of Regulatory Affairs' (ORA) processes more transparent, the agency hired an ORA ombudsman — Jessica Zeller. In the newly established role, Zeller will work to address unresolved concerns in an unbiased manner and improve communication between the ORA and stakeholders. Zeller will report directly to FDA Associate Commissioner of Regulatory Affairs Melinda Plaisier, but will serve as a third party to consider and work on concerns . Zeller has held positions at the FDA in the Office of the Chief Counsel and the Office of Compliance and Enforcement in the

Center for Tobacco Products. She also served as in-house counsel for Procter & Gamble.

Source: FDA

Senators introduce bill to shed tax deduction for DTC pharma advertising

A group of senators proposed a bill calling for an end to the tax deduction for direct-to-consumer pharma advertising. Sens. Al Franken (D-Minn.), Sheldon Whitehouse (D-R.I.), Sherrod Brown (D-Ohio) and Tom Udall (D-N.M.) introduced the Protecting Americans from Drug Marketing Act, which defines DTC as advertising "primarily targeted to the general public" in mediums such as print, radio, TV, telephone communication and social media. However, the bill was criticized by John Kamp, executive director of the Coalition for Healthcare Communication, as a violation of First Amendment rights. Sen. Franken introduced similar legislation in 2009, which stalled after being referred to the Senate Finance Committee.

Source: Medical Marketing & Media

FDA revises guidance on pediatric study plans

The FDA published updated draft guidance on pediatric study plans to address comments from the public. The revised guidance clarifies aspects of the original guidance released in 2013, information on what constitutes an incomplete initial pediatric study plan (iPSP), and addresses the contents and timing of requested amendments to an iPSP. The guidance also discusses how to reach an agreement on a nonagreed iPSP and provides an updated iPSP template. The FDA addresses failed attempts to embolden sponsors to submit pediatric study plans to adequately inform pediatric drug use. Following the 2013 introduction of the Pediatric Research Equity Act (PREA), sponsors are required to submit an iPSP for drugs subject to PREA early on in the development

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process. The revised guidance applies to applications for drugs with a new active ingredient, a new dosage form or regimen, a new indication, or a new route of administration .

Source: Regulatory Affairs Professionals Society

Devices

FDA publishes guidance on human factors review for devices, combination products

The FDA published two draft guidance documents and one final guidance document to address the incorporation of human factors studies in the development of medical products and combination products. The guidance documents add to two existing documents on human factors: one on human device factors in medical device design and one on safety considerations to minimize medication errors.

The first draft guidance, called List of Highest Priority Devices for Human Factors Review, addresses what

devices require human factors data to be included in premarket submissions. The medical devices the FDA says require human factors data are those that it believes have the potential to cause serious harm if used improperly, such as anesthesia machines, duodenoscopes, automated external defibrillators, infusion pumps, robotic surgery devices and ventilators, among others. Premarket submissions for devices listed in the draft guidance should include a human factors test report and data, or a detailed rationale for not including such information .

The second draft guidance document addresses the incorporation of human factors studies in the development of combination products, which include any combination of a drug and a device; a device and a biological product; a biological product and a drug; or a drug, a device and a biological product. The draft guidance, called Human Factors Studies and Related Clinical Study Considerations in Combination Product Design and Development, provides recommendations on what human factors information should be

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included in investigational or marketing applications for combination products, and outlines the different types of human factors studies and how they may add to safety and efficacy evaluations. The FDA provides illustrations of how human factors assessments can be used in different types of combination products and in different clinical settings .

A final guidance called Applying Human Factors and Usability Engineering to Medical Devices, addresses implementation of human factors and usability design in medical device development. It seeks to ensure device user interfaces are designed to eliminate or reduce, to the greatest extent possible, use errors that may cause harm. It encourages medical device makers to incorporate human factors or usability engineering processes in the development process, particularly for the user interface, and calls on device makers to provide a report charting what human factors or usability engineering processes have been followed, as well as any initial assessments and human factors validation testing, results and findings. The new guidance supersedes guidance issued in 2000 on incorporating human factors engineering into medical device risk management, and it incorporates feedback suggested to make it more readable and understandable. The guidance explains the three major components of the device-user system in which human factors and usability engineering should be considered — device users, device use environments and device user interfaces.

FDA publishes draft guidance on clinical trials for devices targeting neurological disease

The FDA published draft guidance on investigational device exemptions (IDEs) for clinical trials on medical devices to treat neurological disease progression. The guidance stipulates that study designs for trials investigating medical devices that target neurological diseases should seek to make a distinction between symptomatic and disease-altering benefits, while

quantifying the extent of the benefits by evaluating biomarkers and clinical outcomes. The FDA states that clinical outcome assessments, including patient-, clinician- and observer-reported outcomes, should quantitatively measure the impact a treatment has on disease progression and the patient. The agency further states that sponsors should submit studies to validate biomarker tests used and to demonstrate that the biomarker reflects a characteristic important to the disease process and is associated with a clinically meaningful outcome. The guidance also outlines what informed consent documents for these devices should describe, such as the possibly of the treatment not having an impact or increasing the rest of progression, options for discontinuing participation in the study, and the potential necessity for long-term follow-up.

Source: Regulatory Affairs Professionals Society

FDA, industry hammer out details of $500M MDUFA IV deal

The FDA met with industry stakeholders to discuss what will be contained within the fourth reauthorization of the Medical Device User Fee Act (MDUFA). The agency laid out an integrated plan bringing together components of both the industry's and the FDA's proposals and said the additional resources needed to implement such proposals over five years would reach $500 million, in addition to the minimum user fees required to maintain activities supported by the current level of user fees. Among the FDA's proposals are:

n The addition of 20 full-time employees to establish a quality management team and to implement a Corrective and Preventive Action system.

n Transitioning some compliance and surveillance activities to the Office of Device Evaluation.

n Establishing a system to link and improve the

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regulatory quality of data sources so real-world evidence can be incorporated into premarket decision-making.

n Forming a new model for streamlining device-specific guidance documents."

Source: Regulatory Affairs Professionals Society

FDA asks coverage organizations to participate in device pre-submission meetings

The FDA is asking coverage organizations that use clinical data in their coverage decision-making to take part in medical device pre-submission meetings to enable timelier access to new devices. In a request for expressions of interest, the agency discusses the "sequential" manner in which medical device development takes place, under which plan sponsors design and conduct trials. Generally input is provided by the FDA, but the evidence to support approval doesn't always align with what payer's need to make coverage decisions. The FDA is requesting that coverage organizations interested in providing input on trial design and evidence gathering come forward. It said it plans to release a list of coverage organizations that have expressed willingness to participate in order to allow device makers to reach out for their participation in pre-submission meetings. Participation in the meetings will be voluntary.

Source: Regulatory Affairs Professionals Society

FDA seeking input on refurbished medical devices

The FDA is asking for input on refurbished medical devices in order to assess possible safety issues. The request for information on refurbished, reconditioned, rebuilt, remarketed, remanufactured, serviced or repaired medical devices comes amid appeals by manufacturers for elucidation on their duties when devices have been altered. The agency said manufacturers have raised concerns about third

parties that modify the devices, and possible public health issues that may arise as a result, such as ineffective recalls, disabled device safety features and incorrect device use. Additionally, the regulatory authority is asking for help in defining and revising the definitions of terms such as recondition, service, repair, refurbish, remarket and remanufacture. A meeting will be held later in the year to solicit input from the device industry and health care community.

Source: Regulatory Affairs Professionals Society

Draft guidance calls on medical device manufacturers to establish processes to monitor, respond to cybersecurity vulnerabilities

The FDA's draft guidance on cybersecurity risks associated with medical devices encourages medical device manufacturers to actively monitor potential issues, and outlines when they must report such issues. It aligns with the agency's efforts to establish a medical device evaluation system.

The FDA published draft guidance with recommendations for addressing medical device cybersecurity issues. The guidance, titled "Postmarket Management of Cybersecurity in Medical Devices," is meant to address the uptick in medical devices designed to be networked, which may make them vulnerable to cybersecurity risks.

The goal of the guidance is to encourage medical device manufacturers to take a proactive approach to dealing with cybersecurity risks. The guidance supplements guidance on premarket submissions for the management of medical device cybersecurity, which provides recommendations to address cybersecurity during the development of devices. The guidance follows the FDA's efforts to use more real-world evidence to monitor the safety of medical devices and its goal of establishing a medical device evaluation system.

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It outlines postmarket recommendations, urging medical device makers to incorporate cybersecurity risk monitoring into their postmarket management strategies. It applies to medical devices that contain software or programmable logic, as well as to software that is designated as a medical device. Risk management programs and documentation should be in line with the Quality System Regulation, and should focus on addressing vulnerabilities that may allow unauthorized access, modification, misuse or denial of use, and the unpermitted use of information shared between medical devices and external sources.

These programs should include methods to evaluate vulnerabilities, coupled with methods to investigate threat sources. The FDA recommends that these programs follow the NIST Framework for Improving Critical Infrastructure Cybersecurity, which defines the steps to an effective program as identify, protect, detect, respond and recover.

For most cases, the FDA defines actions to address cybersecurity issues as "routine updates or patches," which do not require advance notification or reporting. However, there are a small portion of cybersecurity issues that may alter the clinical performance of a device. For these issues, the FDA would require that a manufacturer provide notification. When certain conditions are met and issues are addressed sufficiently in a quick manner, the agency would not enforce urgent reporting.

Other

Revised FDA guidance allows term 'dietary supplement' to be used as entire statement of identity

The FDA published revised guidance on supplement labeling to address whether the term dietary supplement may be considered a statement of identity. In the original guidance on supplement labeling published in 2005, the FDA stated that

the term could not be considered a statement of identity. However, that response has been found to be inconsistent with the Federal Food, Drug, and Cosmetic Act and the good guidance practices regulation. The revised guidance makes clear that the term may be used as the entire statement of identity, noting that the term is "appropriately descriptive." The word dietary may still be removed in favor of another appropriately descriptive term identifying the contents of the product.

Source: Federal Registry

FDA asks manufacturers of human cell, tissue-based products to report adverse events within 15 days

The FDA's Center for Biologics Evaluation and Research published guidance to help facilities that manufacture human cells, tissues, and cellular and tissue-based products (HCT/Ps) comply with requirements for assessing and reporting adverse reactions involving communicable diseases. The guidance calls on HCT/P manufacturers to notify the FDA within 15 days about adverse events that may be fatal or life threatening, may cause permanent damage, or that require medical or surgical response. Additionally, they need to submit follow-up reports within 15 days of receiving new information or as requested by the FDA. To investigate adverse events, the guidance suggests manufacturers assess relevant information that may be related to possible etiologies of the adverse reactions, such as time course, symptoms and outcome of the reaction, as well as the recipient’s medical and social/behavior history, including history of transfusions, transplants, implants and transfers that may have been a source for disease transmissions. Additionally, the guidance suggests the assessment examine processing records to see whether any deviations from established procedures may have caused contamination or cross-contamination of the HCT/P. The guidance, which the agency says should

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be implemented within six months, also requires that manufacturers include information on what environmental control and monitoring information was reviewed in evaluating the adverse reaction, in addition to information related to storage and distribution, and tracking and labeling.

Source: Regulatory Affairs Professionals Society

For more information on any of these FDA regulatory and compliance updates, please contact Scott S. Liebman at sliebman@loeb.com .

Loeb & Loeb LLP’s FDA Regulatory and Compliance Practice

Loeb & Loeb’s FDA Regulatory and Compliance Practice comprises an interdisciplinary team of regulatory, corporate, capital markets, patent and litigation attorneys who advise clients on the full spectrum of legal and business issues related to the distribution and commercialization, including marketing and promotion, of FDA-regulated products. Focusing on the health and life sciences industries, including pharmaceuticals, biologics, medical devices, wellness products, dietary supplements and organics, the practice counsels clients on regulatory issues, compliance-related matters and risk management strategies; advises on laws and regulations related to product advertising and labeling; counsels on FDA exclusivity policies and related Hatch-Waxman issues; and provides representation in licensing transactions and regulatory enforcement actions .

This report is a publication of Loeb & Loeb LLP and is intended to provide information on recent legal developments. This report does not create or continue an attorney client relationship nor should it be construed as legal advice or an opinion on specific situations.

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