TreatiseTreatise

   

Medical Devices Law and Regulation Answer Book (2019 Edition)

 by Suzan Onel, Jacqueline J. Chan
 
 Copyright: 2018

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  • ISBN Number: 9781402431364
  • Page Count:
  • Number of Volumes:
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Medical Devices Law and Regulation Answer Book 2019 walks you through the current regulatory requirements governing medical devices and describes every aspect from pre-market requirements for specific types of devices to post-market regulation and ongoing government enforcement and investigation. The organization of this text broadly follows the typical life cycle of a device and covers a broad range of topics, including many that are not commonly included in surveys of this field.

  • Overview of the legal framework of FDA regulation of medical devices
  • Pre-market considerations, including clinical trials, IDEs, 510(k) and PMA submissions, 3D printed devices, devices used with regenerative therapies, combination products, restricted devices, custom devices, and radiological products
  • Manufacturing compliance, FDA inspections, and in vitro diagnostics
  • The Quality System Regulation, post-market issues, including device promotion, adverse event reporting, and international considerations
  • Interacting with FDA and government enforcement and device commercialization and related issues, including industry-supported scientific activities, intellectual property, licensing, reimbursement, privacy, product liability, preemption, criminal enforcement, and oversight by other federal agencies

With contributions from more than two dozen of the world’s leading experts in medical device regulation, this comprehensive work distills the complexities of FDA medical device regulation into a single practical guide that will be of value to virtually everyone doing business in the medical device sector — including lawyers, consultants, companies operating in the medical device sector, and individual or entity contemplating entry into this field.

  Foreword
  Introduction
  Table of Contents
  Table of Abbreviations
Chapter 1: Overview of the Legal Framework for Medical Device Regulation in the United States
  • : Regulatory Basics1-2
  • : Statutory Framework1-2
  • Q 1.1 : What law regulates medical devices?1-2
  • Q 1.2 : How did medical device regulation develop?1-3
  • Q 1.3 : What kinds of regulatory requirements apply to medical devices?1-4
  • : Definitions and Classifications1-4
  • Q 1.4 : What is a medical device?1-4
  • Q 1.5 : How do I know whether my product is regulated as a “medical device”?1-5
  • Q 1.6 : How are devices regulated under the statutory framework?1-6
  • Q 1.7 : What are the premarket requirements for medical devices?1-6
  • Q 1.8 : What are the key differences between 510(k) premarket notification, de novo classification requests, and premarket approval procedures?1-8
  • : Establishment Registration and Device Listing1-8
  • Q 1.9 : How does FDA know what devices are being marketed in the United States?1-8
  • Q 1.10 : What are the establishment registration requirements?1-9
  • Q 1.11 : What are the device listing requirements?1-9
  • Q 1.12 : Who is required to register and list?1-9
  • Q 1.13 : What device listing requirements apply to importers of a device?1-10
  • Q 1.14 : What information is required under the device listing regulations?1-10
  • Q 1.15 : Do the device establishment registration and device listing requirements apply to foreign manufacturers?1-11
  • : Premarket Requirements for Lawful Marketing of a Medical Device in the United States1-12
  • Q 1.16 : How can a manufacturer ensure that a medical device meets regulatory requirements to be marketed in the United States?1-12
  • : 510(k) Notification1-12
  • Q 1.17 : What is a 510(k) notification?1-12
    • Q 1.17.1 : What does “substantially equivalent” mean?1-13
    • Q 1.17.2 : What information must be included in a 510(k) notification?1-13
    • Q 1.17.3 : How long does it take to receive marketing clearance of a device under the 510(k) notification pathway?1-14
    • Q 1.17.4 : Can review of a 510(k) notification be expedited?1-14
    • Q 1.17.5 : What happens if FDA determines that the device is “not substantially equivalent”?1-14
    • Q 1.17.6 : What happens after FDA determines a device to be “substantially equivalent”?1-15
    • Q 1.17.7 : How does FDA determine the “intended use” of a device?1-15
    • Q 1.17.8 : Why are some Class III devices marketed under a 510(k) notification?1-16
    • Q 1.17.9 : Can a manufacturer make changes to its device after receiving 510(k) clearance?1-16
    • Q 1.17.10 : Are there other types of 510(k) notifications?1-17
  • : Premarket Approval Application (PMA)1-17
  • Q 1.18 : When is a PMA required?1-17
    • Q 1.18.1 : What if a manufacturer is uncertain whether a 510(k) or a PMA is required for its device?1-18
    • Q 1.18.2 : What information is required in a PMA?1-18
    • Q 1.18.3 : What if the PMA does not include all the required information?1-19
    • Q 1.18.4 : What is a “modular PMA”?1-19
    • Q 1.18.5 : How long does it take to get approval of a PMA?1-19
    • Q 1.18.6 : How does the PMA review proceed?1-20
    • Q 1.18.7 : Can review of a PMA be expedited?1-20
    • Q 1.18.8 : Can another company show that its device is substantially equivalent to a PMA device and receive a 510(k) notification?1-21
    • Q 1.18.9 : What if a manufacturer wants to modify a PMA device?1-21
  • : Investigational Use of a Device1-22
  • Q 1.19 : What requirements apply to clinical studies of a device in human subjects?1-22
  • Q 1.20 : What do the IDE regulations require?1-22
  • Q 1.21 : Can a sponsor modify an investigational device, or change the study protocol, in the middle of an IDE clinical study?1-23
  • Q 1.22 : How does a sponsor find out from FDA what clinical data are required for a PMA or 510(k) notification?1-23
  • Q 1.23 : Can a sponsor charge for an investigational device?1-24
  • : Humanitarian Device Exemption1-24
  • Q 1.24 : What options are available to device manufacturers who want to develop a device for a disease or condition affecting a small number of people?1-24
  • Q 1.25 : What are the requirements for obtaining a humanitarian device exemption?1-25
  • Q 1.26 : What requirements apply to use of a humanitarian device?1-25
  • Q 1.27 : Can a sponsor charge for a humanitarian use device?1-25
  • Q 1.28 : Are there other limitations on the humanitarian device exemption?1-26
  • : Reporting Requirements and Postmarket Surveillance1-26
  • : Medical Device Reporting Requirements1-26
  • Q 1.29 : Are device manufacturers required to submit reports to FDA after obtaining marketing clearance or approval of a medical device?1-26
  • Q 1.30 : What MDR requirements apply to a device manufacturer?1-27
  • Q 1.31 : When must a manufacturer’s MDR report be submitted?1-27
  • Q 1.32 : What MDR requirements apply to importers of a device?1-28
  • Q 1.33 : What MDR requirements apply to a device user facility?1-28
  • Q 1.34 : What MDR requirements apply to distributors of a device?1-28
  • : Notice of Correction and Removal1-28
  • Q 1.35 : Are other kinds of reports required to be submitted to FDA?1-28
  • Q 1.36 : When is a notice of correction and removal required?1-29
  • : Postmarket Surveillance1-29
  • Q 1.37 : Does FDA monitor postmarket experience with devices in other ways?1-29
  • Q 1.38 : What happens if a manufacturer receives a postmarket surveillance order?1-29
  • Q 1.39 : How long must postmarket surveillance be conducted?1-30
  • : Device Tracking1-30
  • Q 1.40 : Does FDA have any special recordkeeping or reporting requirements for high-risk devices?1-30
  • Q 1.41 : What kinds of devices might be subject to device tracking requirements?1-30
  • Q 1.42 : What is the purpose of the device tracking requirements?1-31
  • : Unique Device Identification1-31
  • Q 1.43 : Are manufacturers required to have a method of tracking every device they market?1-31
  • : Restricted Devices1-31
  • Q 1.44 : Does FDA have authority to restrict the distribution of medical devices?1-31
  • Q 1.45 : What kinds of restrictions can FDA impose?1-32
  • : Quality and Performance Requirements1-32
  • : Quality System Regulations and Good Manufacturing Practice Requirements1-32
  • Q 1.46 : Does FDA regulate the manufacturing of medical devices?1-32
  • Q 1.47 : How does FDA enforce the QSR requirements?1-32
  • : Performance Standards1-33
  • Q 1.48 : Are manufacturers required to conform to standards in designing or manufacturing a medical device?1-33
  • Q 1.49 : What is a “Declaration of Conformity”?1-34
  • Q 1.50 : What happens if a device fails to conform to an applicable standard?1-34
  • : Dispute Resolution1-34
  • Q 1.51 : What can a manufacturer do if it does not agree with a decision that has been made by an FDA employee during IDE, 510(k), or PMA review?1-34
  • Q 1.52 : What can a manufacturer do if there is a scientific dispute with FDA that does not seem to be resolvable within the Agency?1-35
  • : Statutory Penalties and Enforcement1-35
  • Q 1.53 : What if a device does not comply with a requirement of the FDCA?1-35
  • Q 1.54 : What are the enforcement actions that can result from a prohibited act?1-36
  • Q 1.55 : Can FDA require a product recall?1-36
  • Q 1.56 : Can FDA withdraw marketing authorization for a device?1-36
  • Q 1.57 : Do other agencies or entities regulate medical devices?1-37
Chapter 2: Clinical Studies of Investigational Devices
  • : General Categories of Data Used to Establish Safety, Effectiveness, and Substantial Equivalence of a Medical Device2-3
  • Q 2.1 : What information is necessary to establish the safety and effectiveness of a medical device, or the substantial equivalence of a medical device to a predicate device?2-3
  • Q 2.2 : What are the differences between bench testing, nonclinical laboratory studies, human factors testing, and clinical trials?2-4
  • : Regulation of Bench Testing and Nonclinical Laboratory Studies2-5
  • : Bench Testing2-5
  • Q 2.3 : What requirements apply to bench testing?2-5
  • : Nonclinical Laboratory Studies2-5
  • Q 2.4 : Do I need permission from the U.S. Food and Drug Administration before beginning a nonclinical laboratory study of a medical device?2-5
  • Q 2.5 : What requirements apply to the conduct of nonclinical laboratory studies?2-6
  • Q 2.6 : If the sponsor conducts a nonclinical laboratory study in-house, is the sponsor required to comply with the GLP Regulation?2-6
  • Q 2.7 : What is a sponsor required to do if it contracts for the conduct of any portion of a nonclinical laboratory study with a consulting laboratory or contractor, whether through a grant or otherwise?2-7
  • Q 2.8 : How long must a sponsor of a nonclinical laboratory study maintain records of the study?2-7
  • Q 2.9 : Will FDA consider nonclinical laboratory studies that are not conducted in compliance with the GLP Regulation?2-8
  • : Regulation of Clinical Studies2-8
  • Q 2.10 : What types of medical device studies are regulated by the U.S. Food and Drug Administration?2-8
  • Q 2.11 : Do I need permission from the U.S. Food and Drug Administration or other regulatory authority before beginning a clinical study of a medical device?2-9
    • Q 2.11.1 : Are there any exemptions from FDA approval?2-9
  • Q 2.12 : How does one determine whether a device is significant risk (SR) or nonsignificant risk (NSR)?2-10
  • Q 2.13 : What is an IDE?2-11
  • Q 2.14 : What is required to obtain FDA approval for a clinical study?2-11
    • Q 2.14.1 : Does my study have to provide relevant clinical data for a premarket submission in order to be approvable?2-12
  • Q 2.15 : What is the timing of the review of an IDE and what is FDA’s standard for the review of an IDE?2-13
  • Q 2.16 : What is the sponsor’s obligation to monitor a study?2-14
  • Q 2.17 : What is required of a sponsor in monitoring investigators involved in a study?2-15
  • Q 2.18 : What is required to make a change to an IDE after it has been approved?2-15
  • Q 2.19 : May an investigational device be used to treat patients outside of a clinical trial prior to the clearance or approval of the device?2-16
  • Q 2.20 : May a sponsor charge institutions, investigators or subjects/patients for the use of an investigational device?2-16
  • Q 2.21 : What confidentiality applies to an IDE application and a clinical study?2-17
  • Q 2.22 : How long must a sponsor keep records of a clinical study?2-17
  • Q 2.23 : Do any user fees apply to an IDE application?2-18
  • Q 2.24 : What are the reporting requirements to FDA? To the IRB? To investigators?2-18
  • : Table 2-1: Sponsor Reports to FDA2-18
  • : Informed Consent2-20
  • Q 2.25 : What must be disclosed to patients or subjects participating in a clinical trial?2-20
  • Q 2.26 : Is documented informed consent required for every patient or subject participating in a clinical trial?2-22
    • Q 2.26.1 : Are there exceptions to the requirement of documented informed consent?2-22
  • Q 2.27 : May the documentation of informed consent also serve as a waiver for liability?2-24
  • : Handling of Patient Records2-24
  • Q 2.28 : What protections apply to patient records?2-24
  • : Foreign Clinical Studies2-26
  • Q 2.29 : If a foreign clinical trial will be used to obtain clearance or approval of a medical device, must the foreign clinical trial be conducted under an IDE?2-26
  • Q 2.30 : What is required for FDA to accept a foreign clinical trial of a medical device as evidence of its safety and/or efficacy?2-27
  • Q 2.31 : Can a foreign medical device company sponsor a U.S. clinical trial?2-28
  • : Requirements for Investigators2-28
  • Q 2.32 : What must sponsors of a clinical study disclose to FDA about the financial interests of a clinical investigator?2-28
  • Q 2.33 : What records are investigators required to maintain during and after a clinical study?2-29
  • Q 2.34 : What are the reporting requirements for investigators?2-30
  • : Registering Clinical Studies on ClinicalTrials.gov, Reimbursement and Promotion of Clinical Studies2-30
  • : ClinicalTrials.gov2-30
  • Q 2.35 : What is ClinicalTrials.gov?2-30
  • Q 2.36 : What device clinical studies must be registered on ClinicalTrials.gov?2-31
  • Q 2.37 : Must foreign clinical trials be registered on ClinicalTrials.gov?2-31
  • Q 2.38 : Who is responsible for registering the clinical trials on ClinicalTrials.gov?2-32
  • Q 2.39 : What information about a clinical study must be provided on ClinicalTrials.gov?2-32
  • : Reimbursement2-33
  • Q 2.40 : Is it possible to obtain reimbursement for a clinical study?2-33
  • : Promoting Clinical Trials2-35
  • Q 2.41 : Is it permissible to promote a clinical study to encourage enrollment?2-35
  • Q 2.42 : Is it permissible to pay study subjects to participate in a clinical study?2-35
  • Q 2.43 : Is it permissible to discuss the results of clinical studies before the investigational device is cleared or approved?2-36
  • : Early Collaboration on the Design of Clinical Studies2-37
  • Q 2.44 : Is it possible to discuss the design of a clinical trial protocol with FDA before submitting an IDE?2-37
  • Q 2.45 : What is the Pre-Sub program?2-37
  • Q 2.46 : What is involved with a formal Early Collaboration meeting?2-39
Chapter 3: Device Premarket Submissions
  • : Introduction3-2
  • Q 3.1 : What are the different device classifications and what kinds of premarket submissions are available?3-2
  • : Determining Device Classification3-3
  • Q 3.2 : What are the potential device classifications?3-3
  • Q 3.3 : Are all devices covered by the current classification regulations?3-4
  • Q 3.4 : If a device has not been classified, how can I request FDA information regarding the classification of a device?3-4
  • Q 3.5 : What are the consequences of the classification determination?3-4
  • : Reclassification3-5
  • Q 3.6 : What is device reclassification?3-5
  • Q 3.7 : What is the procedure for device reclassification?3-5
  • : Exemptions from Premarket Review3-6
  • Q 3.8 : What medical devices are exempt from premarket review?3-6
  • Q 3.9 : What could cause a device to lose its exempt status?3-6
  • : Types of Premarket Review (510(k), De Novo Classification, PMA, HDE, Pediatric, PDP)3-7
  • Q 3.10 : What are the pathways to market for medical devices?3-7
  • : 510(k)3-7
  • Q 3.11 : What is 510(k) clearance?3-7
  • Q 3.12 : What is the difference between 510(k) approval and 510(k) clearance?3-8
  • Q 3.13 : What is the basis for finding “substantial equivalence”?3-8
  • : FIGURE 3-1 510(k) Chart3-10
  • Q 3.14 : How many predicate devices are needed?3-11
  • Q 3.15 : What is the procedure for obtaining 510(k) clearance?3-11
  • Q 3.16 : What are the essential elements of a 510(k) submission?3-11
  • Q 3.17 : Does FDA offer presubmission assistance with 510(k) submissions?3-13
    • Q 3.17.1 : How can FDA be contacted for presubmission assistance?3-14
    • Q 3.17.2 : What is FDA’s Pre-Submission Program?3-14
    • Q 3.17.3 : What if FDA refuses to accept my submission for filing?3-15
  • Q 3.18 : Once a submission is under FDA review, what interaction with FDA is likely?3-16
  • Q 3.19 : What may “stop” the review clock?3-17
  • Q 3.20 : How long does it typically take to obtain clearance?3-17
  • Q 3.21 : What are the next steps if your submission is found NSE?3-17
  • Q 3.22 : What user fees are charged?3-18
  • Q 3.23 : What is the third-party review program?3-18
  • Q 3.24 : When might it be a good idea to use the third-party review program?3-19
  • Q 3.25 : When is a new 510(k) clearance required for device modifications?3-19
  • Q 3.26 : Can a cleared 510(k) be supplemented?3-20
  • Q 3.27 : What is a Special 510(k)?3-20
  • Q 3.28 : What is an Abbreviated 510(k)?3-21
  • Q 3.29 : Can FDA rescind a 510(k) clearance?3-22
  • : De Novo Classification3-23
  • Q 3.30 : What is de novo classification?3-23
  • Q 3.31 : What is the procedure for obtaining de novo classification?3-23
  • Q 3.32 : What is the legal effect of de novo classification?3-24
  • : PMA3-24
  • Q 3.33 : What are the requirements for PMA application approval?3-24
  • Q 3.34 : What is the procedure for obtaining PMA application approval?3-25
  • Q 3.35 : What is the regulatory standard for PMA application approval?3-26
  • Q 3.36 : What are the essential elements of a PMA application?3-26
  • Q 3.37 : What are modular PMA applications?3-27
  • Q 3.38 : Does FDA offer presubmission assistance with PMA applications?3-27
  • Q 3.39 : Once a PMA application is under FDA review, what are the key milestones?3-27
  • Q 3.40 : Once a PMA application is under FDA review, what interaction with FDA is likely?3-28
  • Q 3.41 : What may “stop” the review clock?3-29
  • Q 3.42 : What is the likelihood of an advisory panel review?3-29
  • Q 3.43 : How do I prepare for an advisory panel meeting?3-29
  • Q 3.44 : What is a PMA amendment?3-30
  • Q 3.45 : How long does it typically take to obtain approval?3-30
  • Q 3.46 : What are the next steps if my PMA is not approved?3-30
  • Q 3.47 : When are PMA supplements required?3-31
  • Q 3.48 : What user fees are charged?3-32
  • Q 3.49 : Can FDA withdraw approval of a PMA application?3-32
  • : Humanitarian Use Device (HUD)/Humanitarian Device Exemption (HDE)3-33
  • Q 3.50 : What is HUD/HDE approval?3-33
  • Q 3.51 : What is the procedure for obtaining HUD/HDE approval?3-33
  • Q 3.52 : What are the essential elements of an HDE application?3-35
  • Q 3.53 : When are HDE supplements required?3-36
  • Q 3.54 : What user fees are charged?3-36
  • Q 3.55 : What is the legal standard for approval?3-36
  • Q 3.56 : Are these similar to orphan drugs?3-36
  • : Pediatric Devices3-37
  • Q 3.57 : What is a pediatric medical device?3-37
  • Q 3.58 : Is there a special pathway to market?3-37
  • Q 3.59 : What special considerations are involved in getting to market?3-38
  • : Product Development Protocol (PDP)3-38
  • Q 3.60 : What is a PDP?3-38
  • Q 3.61 : How practical is it to seek a PDP?3-38
  • : Breakthrough Devices Program3-39
  • Q 3.62 : What is the Breakthrough Devices Program?3-39
  • Q 3.63 : If my device may qualify, is the Breakthrough Devices Program worthwhile?3-39
  • : Least Burdensome3-40
  • Q 3.64 : What are the “least burdensome” provisions?3-40
  • : Confidentiality/Freedom of Information Act3-41
  • Q 3.65 : What information may FDA release about a pending submission?3-41
  • Q 3.66 : What information may FDA release about a submission denied clearance or approval, or that has been withdrawn?3-42
  • Q 3.67 : What information may FDA release about a submission after clearance or approval?3-43
  • Q 3.68 : Can a company prevent disclosure by labeling information as confidential?3-43
  • Q 3.69 : How can a company request information on a competitor’s product submission?3-44
Chapter 4: Other Device Categories: Radiological Devices, Restricted Devices, Custom Devices, 3D Printed Devices, Device Accessories, and Devices Used with Regenerative Therapies
  • : Radiation-Emitting Electronic Products and Radiological Devices4-2
  • : Overview4-2
  • Q 4.1 : What electronic products are regulated by FDA?4-2
  • Q 4.2 : How are radiation-emitting electronic products regulated?4-2
  • Q 4.3 : Are there any exemptions from performance standards?4-4
  • Q 4.4 : When can a manufacturer begin marketing an electronic product that emits radiation?4-4
  • : Marketing and Sale4-4
  • Q 4.5 : Can a manufacturer begin importing a radiation-emitting electronic product before receipt of an acknowledgment letter?4-4
  • Q 4.6 : What is a certification?4-5
  • Q 4.7 : What requirements are applicable to components of electronic products?4-5
  • Q 4.8 : What specific requirements apply to imports?4-5
  • : Regulation and Enforcement4-6
  • Q 4.9 : What enforcement powers does CDRH have over noncompliant electronic products that emit radiation?4-6
  • Q 4.10 : Are radiation-emitting medical devices regulated differently?4-6
  • Q 4.11 : What is the MQSA?4-7
  • : Restricted Devices4-8
  • Q 4.12 : What are restricted devices?4-8
  • Q 4.13 : What are typical restrictions?4-8
  • Q 4.14 : Are restricted devices the same as “prescription devices”?4-9
  • Q 4.15 : What are some examples of devices restricted by regulation?4-9
  • Q 4.16 : Does FDA require prior approval of advertising for restricted devices?4-9
  • : Custom Devices4-10
  • Q 4.17 : What are custom devices?4-10
  • Q 4.18 : What are the legal/regulatory requirements for a “custom” device?4-10
  • Q 4.19 : Are all devices that are created for specific patients custom devices?4-11
  • Q 4.20 : What are the legal/regulatory risks of selling a device as a custom device?4-11
  • : Devices Manufactured by 3D Printing4-12
  • Q 4.21 : What is a device manufactured by 3D printing?4-12
  • Q 4.22 : How does FDA regulate devices manufactured by 3D printing?4-12
  • : Device Accessories4-13
  • Q 4.23 : What is a device accessory?4-13
  • Q 4.24 : How does FDA regulate device accessories?4-14
  • Q 4.25 : How can an accessory classification be requested?4-15
  • : Devices Used with Regenerative Medicine Therapies4-16
  • Q 4.26 : What is regenerative medicine therapy?4-16
  • Q 4.27 : How does FDA regulate devices used in the recovery, isolation, or delivery of regenerative medicine advanced therapies?4-16
  • Q 4.28 : Are there devices that are excepted from FDA’s regulation of devices used in the recovery, isolation, or delivery of regenerative medicine advanced therapies?4-17
  • Q 4.29 : How is a device intended for use with a specific regenerative medicine advanced therapy regulated?4-18
  • Q 4.30 : What additional factors should be considered when preparing premarket submissions related to devices used with regenerative medicine advanced therapies?4-19
Chapter 5: Combination Products That Include Medical Devices
  • : Overview5-2
  • Q 5.1 : What are combination products?5-2
  • : Product Designation5-3
  • Q 5.2 : Which FDA Center will lead the premarket review?5-3
    • Q 5.2.1 : What is “primary jurisdiction” and “primary mode of action” (PMOA)?5-3
    • Q 5.2.2 : Are there any publicly available documents to help a company anticipate the most likely Center with primary jurisdiction?5-4
    • Q 5.2.3 : What is the role of the Office of Combination Products (OCP)?5-5
    • Q 5.2.4 : When should a company submit a formal “Request for Designation” (RFD)?5-6
    • Q 5.2.5 : What information needs to be provided in a RFD?5-7
    • Q 5.2.6 : Can a company obtain a preliminary product classification assessment prior to submitting a formal RFD?5-8
    • Q 5.2.7 : Can a company appeal a product designation issued by OCP?5-8
  • : Premarket Review5-9
  • Q 5.3 : How can a company obtain information regarding requirements for premarket clearance or approval of the combination product?5-9
    • Q 5.3.1 : Can a company rely on constituent product data and information to establish safety and effectiveness and what other data may be needed?5-10
    • Q 5.3.2 : Will two premarket applications need to be submitted?5-11
    • Q 5.3.3 : Is the lead Center solely responsible for reviewing the premarket applications?5-12
  • Q : Are there other elements that need to appear in a premarket submission to FDA for a combination product?5-13
    • Q 5.3.5 : How are user fees assessed?5-13
  • : Postmarket Requirements5-14
  • Q 5.4 : Which quality control regulations apply?5-14
  • Q 5.5 : How should companies report postmarket safety information?5-16
    • Q 5.5.1 : Who is subject to the final postmarket safety reporting rule?5-17
  • Q 5.6 : How should post-approval modifications or changes to constituent parts be assessed?5-18
Chapter 6: Regulation of Software, Digital Health, and Medical Information Technologies
  • : Overview6-3
  • Q 6.1 : Is software regulated by FDA?6-3
  • : Types of Software: Stand-Alone (Software as a Medical Device); Component, Part, or Accessory6-4
  • Q 6.2 : What is stand-alone software (or Software as a Medical Device)?6-4
  • Q 6.3 : How is Software as a Medical Device regulated?6-5
    • Q 6.3.1 : What does it mean to be exempt from FDA regulation?6-5
  • Q 6.4 : How is software regulated when it is integrated with a medical device or intended to be used with a medical device?6-6
    • Q 6.4.1 : How is software as a component or part regulated?6-7
    • Q 6.4.2 : How is software as an accessory regulated?6-7
  • : Device Premarket Submissions6-8
  • Q 6.5 : Are there unique issues that need to be addressed in premarket submissions?6-8
  • Q 6.6 : Do manufacturers using off-the-shelf (OTS) software with their medical devices need to obtain clearance to use the OTS software?6-9
  • Q 6.7 : What if device software is changed after a product is marketed?6-10
  • Q 6.8 : Is FDA adapting its traditional approach to device regulation to address the faster rate of development and innovation of software devices?6-12
  • : Software, Digital Health Products, and Medical Information Technologies That Are Not Regulated as Medical Devices6-13
  • Q 6.9 : What software, digital health products, and medical information technologies are excluded from the definition of “device” and thus not regulated by FDA?6-13
  • Q 6.10 : What qualifies as a software function intended for administrative support of a health care facility?6-15
  • Q 6.11 : What qualifies as a software function intended for maintaining or encouraging a healthy lifestyle?6-15
  • Q 6.12 : What qualifies as a software function intended to serve as electronic patient records?6-17
  • Q 6.13 : What qualifies as a software function intended for transferring, storing, converting formats, and displaying data and results?6-18
  • : Clinical Decision Support Software and Patient Decision Support Software6-20
  • Q 6.14 : What is clinical decision support software?6-20
  • Q 6.15 : Is clinical decision support software regulated by FDA?6-20
  • Q 6.16 : What are some examples of clinical decision support software that are not devices?6-21
  • Q 6.17 : What are some examples of clinical decision support software that are devices?6-22
  • Q 6.18 : What is patient decision support software?6-23
  • Q 6.19 : Does FDA regulate patient decision support software?6-23
  • Q 6.20 : What are some examples of patient decision support software functions for which FDA is exercising its enforcement discretion?6-24
  • Q 6.21 : In what circumstances may FDA regulate software excluded from the device definition?6-24
  • : Software, Digital Health Products, and Medical Information Technologies Subject to FDA Regulation6-25
  • Q 6.22 : What are other examples of software, digital health products, and medical information technologies that remain actively regulated by FDA?6-25
  • : Cybersecurity6-29
  • Q 6.23 : How does FDA address cybersecurity issues?6-29
Chapter 7: In Vitro Diagnostic (IVD) Devices
  • : In Vitro Diagnostic Products Defined7-2
  • Q 7.1 : What is an in vitro diagnostic product?7-2
  • : The Basic Regulatory Scheme7-3
  • Q 7.2 : How is an IVD regulated?7-3
  • Q 7.3 : How are IVDs classified within the medical device classification scheme?7-3
  • Q 7.4 : How does FDA look at Quality Control for IVDs?7-5
  • : The Regulators7-6
  • Q 7.5 : Who at FDA leads regulation of IVDs?7-6
  • Q 7.6 : Who else regulates IVDs at FDA?7-7
  • : Development of IVDs7-8
  • : Overview7-8
  • Q 7.7 : How is research conducted on IVDs?7-8
  • Q 7.8 : How are clinical investigations conducted on IVDs?7-9
  • : IDE Requirements7-9
  • Q 7.9 : What is an Investigational Device Exemption (IDE)?7-9
  • Q 7.10 : What is the “pre-IDE” process for IVDs?7-9
  • Q 7.11 : Is FDA willing to review and discuss a study protocol even if the study is exempt from most IDE requirements?7-9
  • Q 7.12 : Can I obtain a more formal evaluation of my study design or investigational plan?7-10
  • Q 7.13 : When are IVD clinical studies exempt from the IDE requirements?7-10
  • Q 7.14 : What requirements apply to IDE-exempt studies of IVDs?7-10
  • Q 7.15 : How do I determine if the study is a significant or non-significant risk study?7-11
  • Q 7.16 : How do I determine if an invasive sampling technique presents a significant risk?7-12
  • Q 7.17 : What does noninvasive mean for IVD devices or procedures?7-12
  • Q 7.18 : What does it mean to have “confirmation of the diagnosis by another, medically established diagnostic product or procedure”?7-13
  • Q 7.19 : What if no medically established means for diagnosing the disease or condition exists?7-13
  • Q 7.20 : Is it appropriate to use a quality systems approach in the conduct of IVD studies?7-13
  • Q 7.21 : If a sponsor’s own “in-house” laboratory (for example, Research and Development department) participates as a study site in an IVD study, should it conduct the study as an external or independent study site?7-14
  • : Human Subjects7-14
  • Q 7.22 : When does an IVD study involve human subjects?7-14
  • Q 7.23 : When does the “Good Laboratory Practice for Nonclinical Studies” apply to an IVD study?7-14
  • Q 7.24 : What regulations apply regarding human subject protection in investigational IVD studies?7-15
  • : Special Circumstances7-16
  • Q 7.25 : Can investigational IVD studies receive expedited review by an IRB?7-16
  • Q 7.26 : Can leftover specimens be used in IVD studies without informed consent?7-16
  • Q 7.27 : Can those who routinely do studies with IVDs (for example, research hospitals) use a general informed consent to address future studies using samples collected in their own facility?7-16
  • Q 7.28 : Can a human specimen that was initially collected in an IVD study with the informed consent of the subject be used in a later IVD study without a new consent process?7-17
  • Q 7.29 : Can an investigational IVD device be used outside of the study protocol in an emergency situation?7-17
  • Q 7.30 : Can an unapproved or uncleared investigational IVD device ever be used for non-emergency treatment of patients who do not meet the inclusion criteria of an investigational study?7-19
  • Q 7.31 : Are treatment IDEs and continued access available for investigational IVDs under an IDE?7-19
  • Q 7.32 : Can an IVD device be considered a humanitarian use device (HUD) and does the humanitarian device exemption (HDE) apply for marketing approval?7-20
  • Q 7.33 : Can an IVD device qualify for HUD designation if the affected patient population is fewer than 4,000 per year but each patient may need to be tested multiple times?7-20
  • : Obtaining Clearance or Approval7-20
  • Q 7.34 : When is an IVD exempt from the premarket notification requirement?7-20
  • Q 7.35 : What review criteria does FDA use for an IVD 510(k) submission?7-21
  • Q 7.36 : What questions does FDA ask in the review of an IVD 510(k)?7-22
  • Q 7.37 : What types of studies does FDA require to demonstrate substantial equivalence for an IVD?7-22
  • Q 7.38 : What other information must be in an IVD premarket notification?7-23
    • Q 7.38.1 : Specifically, what name should be included?7-25
    • Q 7.38.2 : What information and data supportive of a substantial equivalency claim should be included?7-25
    • Q 7.38.3 : Is an “indications for use” statement required?7-26
    • Q 7.38.4 : Should the 510(k) state conformance to voluntary standards and standards identified in guidance documents?7-26
  • Q 7.39 : Is there a way to seek expedited review of a 510(k) submission?7-26
  • Q 7.40 : What is the Replacement Reagent and Instrument Family Policy (RR-IFP)?7-26
  • Q 7.41 : What is the Assay Migration Guidance?7-27
  • Q 7.42 : What benefit-risk criteria does FDA use for an IVD premarket approval or de novo submission?7-27
  • Q 7.43 : What are FDA’s requirements on cybersecurity testing in regulatory submissions?7-30
  • : Home-Use IVDs7-30
  • Q 7.44 : Are IVDs intended for home use reviewed differently?7-30
  • Q 7.45 : What key factors does CDRH consider?7-31
  • Q 7.46 : What studies need to be conducted to support a home-use 510(k)?7-33
  • : Premarket Approval7-35
  • Q 7.47 : What studies are required to demonstrate safety and effectiveness?7-35
  • : De Novo Classification7-36
  • Q 7.48 : What is de novo classification for IVDs?7-36
  • : Evidence Required for Clearance or Approval7-37
  • Q 7.49 : Where can we find the specific rules for conducting IVD clinical studies?7-37
  • Q 7.50 : Can published literature be used to support an IVD premarket submission?7-37
  • Q 7.51 : Can data from studies performed outside the United States be used to support an IVD premarket submission?7-37
    • Q 7.51.1 : Can foreign/international data be used as the sole support of a marketing application?7-38
  • Q 7.52 : What information should the protocol include to ensure that the investigational IVD study will be scientifically sound?7-38
  • Q 7.53 : What guidance is available for sponsors to determine how to estimate IVD performance in terms of sensitivity and specificity, how to handle discrepant results, and what to do when a study is performed without a truth standard?7-39
  • Q 7.54 : How much leeway is there in deciding on the populations from which human specimens are collected and under what conditions are data on simulated specimens acceptable?7-39
  • Q 7.55 : Is it acceptable to eliminate data that appear to be out of line with the main body of the dataset (that is, “outliers”)?7-39
  • Q 7.56 : Is it acceptable to add additional readings on the same subject to the dataset, particularly when it is hard to find study subjects?7-40
  • Q 7.57 : How much precision is needed for measurement data (for example, in terms of decimal places)?7-40
  • Q 7.58 : What records should help to ensure scientific soundness of an IVD investigational study?7-40
  • Q 7.59 : What does FDA recommend to include in the final report of the investigation from the sponsor to all reviewing IRBs (and to FDA for significant risk studies)?7-41
  • : Labeling and Promotion Requirements for IVDs7-42
  • : Overview7-42
  • Q 7.60 : What are the requirements for IVD labeling?7-42
  • Q 7.61 : What are the label requirements for the immediate container?7-42
  • Q 7.62 : What are the labeling requirements for inserts and outer packaging?7-44
  • : Exemptions7-46
  • Q 7.63 : Are there exemptions from the labeling requirements?7-46
  • : Special Labeling Rules7-47
  • Q 7.64 : Are there special labeling rules for general purpose reagents and equipment?7-47
  • Q 7.65 : Are there special rules for labeling IVDs for home use?7-48
  • Q 7.66 : Can I use symbols in IVD labeling instead of words?7-52
  • : IVDs for Research or Investigational Use Only7-52
  • : Overview7-52
  • Q 7.67 : Are RUO and IUO IVDs exempt from FDA regulation?7-52
  • Q 7.68 : Are non-U.S. manufacturers of RUOs exempt from registration and listing requirements?7-52
  • Q 7.69 : What types of products does FDA generally consider to be appropriately labeled “Research Use Only” IVD products?7-53
  • Q 7.70 : What types of IVD products should not be labeled RUO?7-54
  • Q 7.71 : What types of products does FDA generally consider to be appropriately labeled “Investigational Use Only” IVD products?7-54
  • Q 7.72 : What types of IVD products should not be labeled IUO?7-54
  • Q 7.73 : Are RUO and IUO IVD products required to be manufactured in compliance with the Quality System regulation?7-55
  • : Marketing Practices of Manufacturers7-55
  • Q 7.74 : How may IVD products labeled RUO or IUO be marketed?7-55
  • Q 7.75 : What marketing practices would FDA consider to be generally inappropriate for IVD products labeled RUO or IUO?7-55
  • Q 7.76 : Can a manufacturer obtain clearance or approval for an IVD product that includes or is required to be used with one or more IUO- and/or RUO-labeled reagents or instruments?7-57
  • Q 7.77 : Should a manufacturer or distributor promote IVD components, instruments, or reagents labeled RUO or IUO for use in a Laboratory Developed Test (LDT) that the manufacturer knows is used in clinical diagnosis?7-57
  • Q 7.78 : Should the manufacturer include instructions for use with an IVD product labeled RUO or IUO?7-57
  • Q 7.79 : Is it appropriate for a manufacturer or distributor to market software labeled RUO or IUO?7-58
  • Q 7.80 : Can RUO/IUO manufacturers provide general technical support for use of its RUO/IUO product?7-58
  • Q 7.81 : Should the manufacturer of an IVD product labeled RUO or IUO help with the validation and verification of performance specifications of an LDT or other test that the manufacturer knows is used in clinical diagnosis that utilizes its product?7-58
  • Q 7.82 : What is FDA’s Policy on Products with Combined RUO/IUO and Cleared/Approved Diagnostic Functionality?7-59
  • : Alternatives to Ready-Made IVDs7-60
  • : Overview7-60
  • Q 7.83 : What are Analyte Specific Reagents (ASRs)?7-60
  • Q 7.84 : What is a General Purpose Reagent?7-62
  • Q 7.85 : What is an LDT?7-62
  • Q 7.86 : What is an LDT In Vitro Diagnostic Multivariate Index Assay?7-62
  • : FDA Regulation7-63
  • Q 7.87 : Does FDA have a proposal for regulating LDTs generally?7-63
  • Q 7.88 : Would all LDTs be regulated under the LDT framework described in FDA’s January 2017 Discussion Paper?7-63
  • Q 7.89 : What kinds of LDTs would still be under enforcement discretion under the January 2017 Discussion Paper framework?7-64
  • Q 7.90 : Does FDA enforcement discretion extend to direct-to-consumer LDTs?7-65
  • Q 7.91 : Why did FDA create the ASR category?7-66
  • Q 7.92 : How are ASRs regulated?7-67
  • Q 7.93 : What labeling restrictions apply to ASRs?7-68
  • Q 7.94 : What other restrictions apply?7-68
  • Q 7.95 : How are ASRs classified?7-69
  • Q 7.96 : If an ASR is in Class I, does that mean it is exempt?7-70
  • Q 7.97 : How does the classification of ASRs compare to the classification of ready-made IVDs used for the same purposes?7-71
  • Q 7.98 : Are there other limits on the promotion of ASRs?7-72
  • : In Vitro Companion Diagnostic Devices7-74
  • Q 7.99 : What was the reaction to the FDA’s draft guidance proposing regulation of IVD companion diagnostic devices?7-74
  • Q 7.100 : What is an IVD companion diagnostic device?7-74
  • Q 7.101 : What is the review and approval process of an IVD companion diagnostic device?7-75
  • Q 7.102 : When would FDA approve a therapeutic product without the cleared or approved IVD companion diagnostic device for which it is labeled?7-76
  • Q 7.103 : What labeling considerations apply to a therapeutic product and its IVD companion diagnostic device?7-77
  • Q 7.104 : Can an IVD companion diagnostic device be used for investigational use?7-79
  • : Clinical Laboratory Improvement Amendments of 1988 (CLIA)7-80
  • Q 7.105 : What are the Clinical Laboratory Improvement Amendments of 1988 (CLIA)?7-80
  • Q 7.106 : What laboratories does CLIA regulate?7-81
  • Q 7.107 : Which agency administers CLIA?7-81
  • Q 7.108 : What criteria are used under CLIA to categorize tests?7-81
  • Q 7.109 : When and how are CLIA categorization determinations made?7-82
  • Q 7.110 : How else are tests put in the waived category?7-83
  • Q 7.111 : What is the CLIA waiver process?7-84
  • : Next Generation Sequencing (NGS)-Based IVDs7-85
  • Q 7.112 : What is an NGS-Based IVD?7-85
  • Q 7.113 : How are NGS-based IVDs for germline conditions classified?7-86
  • Q 7.114 : What factors does FDA consider when evaluating the safety and effectiveness of an NGS-based IVD?7-86
Chapter 8: The Quality System Regulation
  • : Overview8-3
  • Q 8.1 : Where can I find the Quality System Regulation requirements?8-3
  • Q 8.2 : What is the scope of the QSR requirements?8-3
  • Q 8.3 : What entities are subject to the QSR requirements?8-4
  • Q 8.4 : How does FDA define “finished device manufacturer”?8-4
  • Q 8.5 : Do the QSR requirements apply to component and subassembly manufacturers?8-5
  • Q 8.6 : Are the QSR requirements identical to the ISO requirements?8-6
  • Q 8.7 : Do finished device manufacturers need two separate systems, one for ISO compliance and one for QSR compliance?8-7
  • Q 8.8 : If a manufacturer is ISO-certified, is it also compliant with the QSR requirements?8-8
  • Q 8.9 : What areas are covered under the QSR?8-8
  • : Finished Device Manufacturers8-8
  • Q 8.10 : Are finished device manufacturers required to comply with every element of the QSR?8-8
    • Q 8.10.1 : What if a finished device manufacturer by the nature of its business does not conduct every activity that is described in the QSR?8-9
    • Q 8.10.2 : What should a manufacturer do if it believes that it is not subject to certain provisions of the QSR?8-9
  • : Contract Manufacturers8-9
  • Q 8.11 : Are contract manufacturers subject to the QSR requirements?8-9
  • : Foreign Manufacturers8-10
  • Q 8.12 : Are foreign manufacturers subject to the QSR requirements?8-10
  • Q 8.13 : What are the QSR obligations of an initial importer/distributor?8-10
  • : Additional Resources8-11
  • Q 8.14 : Are any resources available to me to better understand FDA QSR requirements?8-11
  • : Management Responsibility Provisions8-12
  • Q 8.15 : What is the scope of the management responsibility provisions of the QSR?8-12
  • Q 8.16 : What are the management responsibilities for Quality Policy?8-12
    • Q 8.16.1 : What are the management responsibilities for ensuring an adequate organizational structure is in place to assure compliance with the QSR?8-13
    • Q 8.16.2 : What are the responsibilities of a management representative?8-14
    • Q 8.16.3 : What are the responsibilities of the company for quality planning and quality procedures?8-14
    • Q 8.16.4 : What are Management Reviews and what requirements must they meet?8-15
    • Q 8.16.5 : Does FDA have a right to review the results of Management Reviews?8-16
    • Q 8.16.6 : Does FDA have a right to review corrective and preventive actions that arise from Management Reviews?8-16
  • Q 8.17 : Who does FDA hold accountable for noncompliance with the QSR requirements?8-17
  • : Quality Audits8-18
  • Q 8.18 : What are the QSR requirements for Quality Audits?8-18
  • Q 8.19 : Who should perform Quality Audits?8-18
  • Q 8.20 : What quality functions should be assessed in a Quality Audit Plan/Schedule?8-18
  • Q 8.21 : How often should Quality Audits be conducted?8-19
  • Q 8.22 : What is the appropriate goal of a Quality Audit?8-19
  • Q 8.23 : How should information from a Quality Audit be used?8-19
  • Q 8.24 : Does FDA have a right to review Quality Audit reports?8-20
  • Q 8.25 : Does FDA have a right to review corrective and preventive actions that arise from Quality Audits?8-20
  • : QSR Requirements for Training8-21
  • Q 8.26 : Who should be trained?8-21
  • Q 8.27 : Who should conduct training?8-21
  • Q 8.28 : How are training needs identified?8-21
  • Q 8.29 : What procedures should a company utilize to ensure compliance with training requirements?8-22
  • Q 8.30 : Are there any special training requirements applicable to certain personnel?8-22
  • Q 8.31 : How and where should training be documented?8-22
  • : Design Controls8-23
  • Q 8.32 : What are the QSR requirements for design controls?8-23
  • Q 8.33 : Who is subject to design controls?8-23
  • Q 8.34 : What procedures should the company develop for design planning?8-23
  • Q 8.35 : What are the requirements for design inputs?8-24
  • Q 8.36 : What are the requirements for design outputs?8-24
  • Q 8.37 : What are the requirements for conducting design verification and validation activities?8-24
  • Q 8.38 : What is the process required for design review?8-25
  • Q 8.39 : How should design transfer be addressed?8-25
  • Q 8.40 : What requirements apply when design changes are transferred to manufacturing?8-26
  • Q 8.41 : What are the recordkeeping requirements for design and development?8-26
  • Q 8.42 : How is the company’s risk management plan associated with design activities?8-26
  • : Purchasing Controls8-27
  • Q 8.43 : What are the QSR requirements for purchasing controls?8-27
  • Q 8.44 : What entities should finished device manufacturers evaluate under the purchasing control provisions of the QSR?8-27
  • Q 8.45 : What are the finished device manufacturer’s requirements for identifying and qualifying suppliers?8-27
  • Q 8.46 : How do finished device manufacturers identify the type and extent of control to exercise over its suppliers?8-28
  • Q 8.47 : Should suppliers to the finished device manufacturer qualify their suppliers?8-28
  • Q 8.48 : Are finished device manufacturers required to conduct an on-site audit of all of its suppliers?8-29
  • Q 8.49 : If a finished device manufacturer conducts on-site audits, is FDA allowed to review the supplier audit reports?8-29
  • Q 8.50 : What recordkeeping requirements exist for finished device manufacturers with regard to suppliers?8-30
  • Q 8.51 : How should finished device manufacturers balance purchasing controls and acceptance activities over products and services provided by suppliers?8-30
  • Q 8.52 : How does FDA define “purchasing data”?8-31
  • : Product and Process Controls8-31
  • Q 8.53 : What are the QSR requirements for production and process controls?8-31
  • Q 8.54 : What issues should be addressed in the process control procedures?8-32
  • Q 8.55 : How should companies address changes in production and processes?8-32
  • Q 8.56 : How should companies address environmental control procedures?8-33
  • Q 8.57 : How should companies ensure personnel are adequately protected when engaged in production activities?8-33
  • Q 8.58 : What procedures should companies adopt to protect product and equipment from contamination?8-33
  • Q 8.59 : How should companies assure facilities and equipment are adequately designed to allow appropriate and safe production of products?8-34
  • Q 8.60 : How should companies ensure automated processes are properly designed?8-34
  • Q 8.61 : What are the requirements applicable to the maintenance and calibration of production, measuring, and testing equipment?8-34
  • : Process Validation8-35
  • Q 8.62 : What are the QSR requirements for process validation?8-35
  • Q 8.63 : When are process validation activities required?8-35
    • Q 8.63.1 : What procedures should govern process validation activities?8-36
    • Q 8.63.2 : How should companies monitor and control process parameters?8-36
  • Q 8.64 : What are the QSR requirements for receiving, in-process, and finished device acceptance?8-36
    • Q 8.64.1 : How should requirements for incoming acceptance activities be addressed?8-37
    • Q 8.64.2 : How should the company ensure activities are controlled and acceptable while in-process?8-37
    • Q 8.64.3 : What procedures should companies adopt for final acceptance?8-37
    • Q 8.64.4 : What recordkeeping requirements should be adopted for final acceptance and release activities?8-38
  • : Nonconforming Materials8-38
  • Q 8.65 : What disposition methods can be utilized to address nonconforming materials?8-38
  • Q 8.66 : What are the QSR requirements for nonconforming products?8-38
  • Q 8.67 : How should companies identify nonconforming products?8-39
  • Q 8.68 : How should nonconforming products be segregated and handled?8-39
  • : Corrective and Preventive Action8-40
  • Q 8.69 : What are the QSR requirements for corrective and preventive action?8-40
  • Q 8.70 : What is the difference between a “corrective” and “preventive” action?8-40
  • Q 8.71 : What quality system inputs should be included in the Corrective and Preventive Actions (CAPA) system?8-40
  • Q 8.72 : What processes should manufacturers adopt for initiating, implementing, and verifying the effectiveness of corrective and preventive action?8-41
  • : Device Recordkeeping and the Device Master Record8-41
  • Q 8.73 : What types of records should companies maintain and how long should these records be maintained?8-41
  • Q 8.74 : What documents related to the QSR are available to the public?8-42
  • Q 8.75 : What information should be contained in a Device Master Record?8-42
  • Q 8.76 : What information should be contained in a Device History Record?8-43
  • : Handling Complaints8-43
  • : Complaint Handling System8-43
  • Q 8.77 : How does FDA define “complaint”?8-43
  • Q 8.78 : What information should be included in complaint handling procedures?8-44
  • Q 8.79 : What are the inputs to the complaint handling system?8-44
  • : Complaint Handling and the Medical Device Reporting Regulations8-45
  • Q 8.80 : How and when should reportability of the complaint under the Medical Device Reporting (MDR) regulations be determined?8-45
  • Q 8.81 : When should MDR events be reported to FDA?8-46
  • : Investigation of Complaints8-47
  • Q 8.82 : What are the requirements regarding whether a complaint investigation should be performed?8-47
  • : Trending of Complaint Data8-47
  • Q 8.83 : How should complaint information tie into other quality system functions?8-47
  • : Recordkeeping Requirements8-48
  • Q 8.84 : What recordkeeping requirements apply to the complaint handling process?8-48
  • : Device Servicing8-48
  • Q 8.85 : What are the QSR requirements for device servicing?8-48
  • Q 8.86 : How should servicing information correlate with complaint handling?8-49
  • : Statistical Technique Requirements8-49
  • Q 8.87 : What are the QSR requirements for statistical techniques?8-49
  • : Enforcement8-50
  • Q 8.88 : How does an entity that is covered by the QSR demonstrate compliance with the QSR?8-50
  • Q 8.89 : What is FDA’s authority to conduct inspections of medical device manufacturers?8-50
  • Q 8.90 : How does FDA determine if an entity that is covered by the QSR is compliant with the regulations?8-51
  • Q 8.91 : What is the Quality System Inspection Technique?8-52
  • Q 8.92 : Does QSIT impose additional or different requirements on manufacturers?8-52
  • Q 8.93 : Are FDA investigators required to use this approach when conducting inspections?8-52
  • Q 8.94 : What are some common FDA inspectional observations?8-53
  • : Penalties8-54
  • Q 8.95 : What are the penalties for not complying with the QSR requirements?8-54
  • Q 8.96 : What can a company do to stay abreast of FDA policies that identify the Agency’s current positions with respect to the QSR?8-55
Chapter 9: Device Facility Inspections
  • : Overview9-2
  • : Definitions9-2
  • Q 9.1 : What is an inspection and where is it defined?9-2
  • Q 9.2 : How are types of inspections defined?9-3
  • Q 9.3 : How are the scope and depth of inspection determined?9-3
  • : FDA Authority, Scope, and Conduct of Inspections9-4
  • Q 9.4 : Where can I find FDA’s authority to conduct inspections?9-4
  • Q 9.5 : How frequently do inspections occur and why?9-4
  • Q 9.6 : Are FDA inspections announced?9-5
  • Q 9.7 : What are FDA’s responsibilities for conducting an inspection?9-5
  • : FORM 9-1 Inspectional Observations9-7
  • : Credentials and Notice of Inspection9-9
  • Q 9.8 : What are the credentials and Notice of Inspection?9-9
  • : FORM 9-2 Notice of Inspection9-11
  • : What May Be Inspected9-14
  • Q 9.9 : What areas of a facility may the FDA Investigator enter and inspect?9-14
  • Q 9.10 : Does FDA have the authority to review and collect records?9-14
  • Q 9.11 : Will FDA take original records?9-15
  • Q 9.12 : Are there records or data that the FDA Investigator is not authorized to review?9-16
  • Q 9.13 : What should I do if FDA asks for a sample?9-16
  • : FORM 9-3 Receipt for Samples9-17
  • Q 9.14 : If the appropriate management is not on-site for the inspection, should I ask FDA to return at a different time?9-20
  • Q 9.15 : Should I allow the FDA Investigator to take photographs?9-21
  • Q 9.16 : Am I required to sign forms or affidavits presented by the FDA Investigator?9-22
  • : FORM 9-4: Affidavit9-24
  • : Search and Inspection Warrants9-25
  • Q 9.17 : Does FDA use search warrants when conducting inspections?9-25
  • Q 9.18 : Are inspection warrants the same as search warrants?9-26
  • : Scope of Device Inspections and QSIT Approach9-27
  • Q 9.19 : What are the scope and depth of FDA medical device inspections?9-27
  • : TABLE 9-1 Level and Type of Inspection Summary9-28
  • Q 9.20 : What is the “Systems Approach” to inspections, or QSIT?9-29
  • : FIGURE 9-1 QSIT Subsystems and Satellites Pictorial9-30
  • : Concluding the Inspection9-31
  • Q 9.21 : How do you know when an inspection has ended?9-31
  • : Form FDA 4839-32
  • Q 9.22 : What is Form FDA 483, Inspectional Observations?9-32
  • Q 9.23 : Are Form FDA 483 observations violations of the FDCA?9-33
  • Q 9.24 : Should a company respond to a Form FDA 483?9-33
  • Q 9.25 : What is the discussion with management?9-34
  • Q 9.26 : What is “annotation” of the Form FDA 483?9-35
  • : Enforcement9-36
  • Q 9.27 : How does FDA determine if an inspection should result in an enforcement action?9-36
  • Q 9.28 : Who determines whether to issue a Warning Letter?9-37
  • Q 9.29 : What are inspection “close out letters”?9-37
  • Q 9.30 : What is the Establishment Inspection Report (EIR)?9-38
    • Q 9.30.1 : How do I receive a copy of my EIR?9-39
    • Q 9.30.2 : How do I obtain a copy of my competitor’s EIR?9-39
  • : Domestic and International Jurisdiction of FDA9-40
  • Q 9.31 : Are companies located outside the United States subject to FDA inspection?9-40
  • Q 9.32 : Are there differences between domestic (U.S.) and international (OUS) inspections?9-40
  • : Other Initiatives9-41
  • Q 9.33 : What is the FDA Program Alignment?9-41
  • Q 9.34 : What is the Medical Device Single Audit Program (MDSAP)?9-42
  • : Accredited Third-Party Inspections9-43
  • Q 9.35 : What are accredited third-party inspections?9-43
Chapter 10: Postmarket Considerations
  • : Postmarket Adverse Event Reporting10-2
  • Q 10.1 : What are the basic provisions which require the submission of adverse event information to FDA?10-2
  • Q 10.2 : Who must report required adverse event information to FDA?10-3
  • Q 10.3 : What is MedSun?10-3
  • Q 10.4 : Must all adverse event information be reported to FDA?10-4
  • Q 10.5 : What is a serious injury?10-4
  • Q 10.6 : When must MDRs be submitted to FDA?10-4
  • Q 10.7 : How do I submit MDRs?10-5
  • : FORM 10-1 Mandatory Reporting Form 3500A10-6
  • : FORM 10-2 Voluntary Reporting Form 350010-9
  • Q 10.8 : Does the submission of an MDR constitute an admission that the device at issue caused or contributed to the reportable event?10-12
  • Q 10.9 : Will the information in the MDR report be subject to public disclosure?10-12
  • Q 10.10 : Are there record-keeping requirements associated with MDRs?10-12
  • Q 10.11 : What are the consequences of not timely filing a required MDR?10-12
  • : Recalls, Notifications, and Reports of Removals and Corrections10-13
  • Q 10.12 : What are the basic provisions relating to recalls, notifications, and reports of removals and corrections?10-13
  • Q 10.13 : Are all removals or field corrections subject to the section 519(g) reporting requirements?10-14
  • Q 10.14 : What constitutes a risk to health which would trigger a reporting obligation under section 519(g)?10-15
  • Q 10.15 : When must the report of removal or correction be submitted?10-15
  • Q 10.16 : Will information in a 519(g) report be subject to public disclosure?10-15
  • Q 10.17 : Are there record-keeping requirements associated with a 519(g) report?10-15
  • Q 10.18 : When there is a recall, how does one determine the nature and scope of the recall?10-16
  • : Reprocessing of Single-Use Devices10-17
  • Q 10.19 : What regulatory requirements apply to the reprocessing of single-use devices?10-17
  • Q 10.20 : What are the obligations of an original equipment manufacturer that reprocesses SUDs?10-17
  • Q 10.21 : How does a manufacturer know if its device requires additional data?10-18
  • : Labeling and Advertising10-18
  • Q 10.22 : What are the basic provisions which govern the labeling and advertising for medical devices?10-18
  • Q 10.23 : What is a restricted device?10-19
  • Q 10.24 : Are all prescription devices also restricted devices?10-20
  • Q 10.25 : What is the significance of being subject to restricted device status?10-20
  • Q 10.26 : Does this mean that FDA has no jurisdiction over the content of advertisements for devices that are not restricted devices?10-20
  • Q 10.27 : Do all labeling for devices and all advertisements for restricted devices have to contain relevant information relating to intended uses, warnings, precautions, side effects, and contraindications?10-21
  • Q 10.28 : Are there different requirements for different types of promotional advertising with respect to “fair balance” and “brief statement” requirements?10-22
  • : Off-Label Uses10-23
  • Q 10.29 : What is an off-label use?10-23
  • Q 10.30 : Is a health care practitioner precluded from using a device for an off-label use?10-24
  • Q 10.31 : Are all communications by a company or its representatives relating to off-label uses prohibited?10-24
  • Q 10.32 : What are the consequences of off-label promotion?10-25
  • : Changes Relating to Previously Cleared/Approved Devices10-25
  • : PMA-Approved Medical Devices10-25
  • Q 10.33 : What types of changes to a PMA-approved medical device require FDA prior review and approval?10-25
  • Q 10.34 : What types of changes to a PMA-approved medical device do not require prior review and approval by FDA?10-26
  • Q 10.35 : What is “real-time review”?10-27
  • : 510(k)-Cleared Medical Devices10-28
  • Q 10.36 : What types of changes to a 510(k)-cleared medical device require FDA prior review and clearance?10-28
  • : Postmarket Studies/Surveillance10-28
  • Q 10.37 : When are postmarket studies required for an approved or cleared medical device?10-28
  • Q 10.38 : What is postmarket surveillance?10-29
  • Q 10.39 : What is device “tracking”?10-30
  • Q 10.40 : What is Unique Device Identification (UDI)?10-30
  • Q 10.41 : Can a patient refuse tracking of his device?10-31
  • : Clinical Trial Registries and Results Databases10-32
  • : Overview10-32
  • Q 10.42 : Are medical device manufacturers subject to requirements for registering clinical trials on a publicly accessible, government database?10-32
  • Q 10.43 : What is the clinical trial registry database?10-32
  • Q 10.44 : What is the clinical trial results database?10-32
  • Q 10.45 : Who is responsible for submitting clinical trial information to CT.gov in accordance with the FDAAA requirements?10-33
  • Q 10.46 : Do the federal reporting requirements for clinical trial registries and results databases apply to all clinical trials involving a medical device?10-33
  • : Foreign Clinical Studies10-34
  • Q 10.47 : If a device trial is being conducted in a foreign country, is the sponsor required to submit information about it to CT.gov?10-34
  • : Applicable Device Clinical Trials10-35
  • Q 10.48 : Do observational studies need to be submitted to CT.gov?10-35
  • Q 10.49 : If FDAAA requirements apply, when must a sponsor submit information about a device trial to the clinical trial registry database?10-35
  • Q 10.50 : What type of information must be submitted to the clinical trial registry for each “applicable device clinical trial”?10-35
  • : Public Availability of Registry and Results Information10-36
  • Q 10.51 : Does NIH make registry information publicly available at or near the time it is submitted to CT.gov?10-36
  • Q 10.52 : Does the FDAAA require a sponsor to submit results information for each device study for which registry information has been submitted to CT.gov?10-37
  • : Timing of Submissions10-37
  • Q 10.53 : If results information is required, when must it be submitted to CT.gov and by whom?10-37
  • Q 10.54 : Are there any mechanisms to delay the deadline for submission of results information?10-38
  • : Results Information and Reporting Requirements10-39
  • Q 10.55 : If required, what type of results information must be submitted to CT.gov for each applicable device clinical trial?10-39
  • Q 10.56 : Are sponsors required to update their submissions to CT.gov?10-40
  • : Compliance and Enforcement10-40
  • Q 10.57 : What are the consequences for failure to comply with the clinical trial reporting requirements under the FDAAA?10-40
  • Q 10.58 : How does the government monitor compliance?10-41
  • : FORM 10-3 Certification of Compliance with Requirements of ClinicalTrials.gov Data Bank10-42
  • : Registration and Listing10-44
  • Q 10.59 : What are the general registration and listing requirements?10-44
  • Q 10.60 : What types of establishments are subject to registration?10-44
  • Q 10.61 : If registration is required, when must registration information be submitted?10-45
  • Q 10.62 : How is registration information submitted?10-45
  • Q 10.63 : Is there a fee required for establishment registration?10-46
  • Q 10.64 : Are there any special requirements for foreign establishments?10-46
  • Q 10.65 : What types of establishments are subject to device listing?10-46
  • Q 10.66 : How and when is device listing required to be submitted?10-46
  • Q 10.67 : What type of information must be submitted for device listing?10-47
  • : Medical Device User Fees10-47
  • Q 10.68 : Do any user fees apply to medical devices?10-47
  • Q 10.69 : How much are the user fees?10-47
  • Q 10.70 : Are there reductions or waivers available for small businesses?10-48
  • : FORM 10-4 Small Business Qualification Certification10-49
  • : FORM 10-5 Small Business Qualification Certification for Foreign Firms10-55
  • Q 10.71 : Can several devices be bundled into one application to avoid paying multiple user fees?10-61
Chapter 11: International Considerations
  • : Imports11-3
  • Q 11.1 : Are FDA requirements the same for U.S.-produced and imported medical devices?11-3
  • Q 11.2 : What types of activities does FDA pursue to ensure that imports are in compliance with industry laws?11-3
  • Q 11.3 : What are the major risks FDA faces in regulation of imports?11-4
  • : Registration and Listing11-4
  • Q 11.4 : What requirements apply to foreign manufacturers of medical devices wishing to market their products in the United States?11-4
  • : Point-of-Entry Controls: Import Procedures11-6
  • Q 11.5 : Under what types of conditions would imported products not be permitted to be admitted?11-6
  • : Point-of-Entry Controls11-7
  • Q 11.6 : How does the import process work?11-7
  • Q 11.7 : What is an “Import Alert” and how is it implemented?11-8
  • : Foreign Inspections, Third Parties, and Technical Assistance11-9
  • Q 11.8 : What other FDA initiatives assure that imports meet requirements?11-9
  • : Exportation of Products11-11
  • : Products That Are Legally Marketed in the United States11-11
  • Q 11.9 : What are the requirements for exporting products that are legally marketed in the United States?11-11
  • Q 11.10 : What are the requirements for exporting products that are not legally marketed in the United States?11-11
  • : Exportation Under Section 801(e)(1) of the FDCA11-12
  • Q 11.11 : Can a company export an unapproved device that it reasonably believes could be cleared in the United States under the premarket notification process?11-12
  • : Exportation Under Section 801(e)(2) of the FDCA11-12
  • Q 11.12 : Can a company export an unapproved Class III device to a non-listed country?11-12
  • : Exportation Under Section 802 of the FDCA11-14
  • Q 11.13 : How can a company export unapproved Class III devices to listed countries?11-14
  • Q 11.14 : When is the provision of a simple notification necessary?11-16
  • Q 11.15 : How are devices exported for investigational use?11-17
  • : Import for Export Under Section 801(d)(3) of the FDCA11-18
  • Q 11.16 : What requirements apply to the importation, for later export, of components of medical devices?11-18
  • Q 11.17 : What are Certificates to Foreign Governments (CFG) and how does an exporting company obtain them?11-19
  • Q 11.18 : When adverse events occur overseas, are they reportable to FDA?11-20
  • : FDA’s International Activities11-21
  • Q 11.19 : Which trends have affected FDA’s international strategy?11-21
  • : Harmonization and Standards11-23
  • Q 11.20 : How and why are standards identified for recognition by FDA?11-23
  • : Sharing Information with Regulatory Counterparts11-24
  • Q 11.21 : How does FDA increase its ability to share with foreign counterparts?11-24
  • : Arrangements with Regulatory Counterparts in Other Countries11-24
  • Q 11.22 : How do arrangements affect the establishment of a joint implementation work strategy?11-24
  • : FDA-EU Activities11-26
  • Q 11.23 : What are mutual recognition agreements?11-26
  • Q 11.24 : What is the International Medical Device Regulators Forum (IMDRF)?11-27
  • : National Systems for Regulating Medical Devices11-29
  • Q 11.25 : What are features of a medical device regulatory system?11-29
  • : Medical Device Clinical Trials: International Aspects11-30
  • Q 11.26 : How are clinical trials outside the United States conducted?11-30
  • : European Union Regulation of Medical Devices11-31
  • Q 11.27 : What are the three main directives concerning medical devices in the European Union?11-31
  • Q 11.28 : How is a medical device defined?11-32
  • : Notified Bodies11-33
  • Q 11.29 : What is a notified body and how is it selected as having technical qualifications?11-33
  • : EEA “Presence” Requirement for European Authorized Representatives11-34
  • Q 11.30 : What do EU Directives require of a European Authorized Representative?11-34
  • : Classification11-35
  • Q 11.31 : What will classification of its product allow a manufacturer to do?11-35
  • : Standards11-36
  • Q 11.32 : Are standards voluntary?11-36
  • : Conformity Assessment Procedures11-37
  • Q 11.33 : When may medical devices be placed on the EU market?11-37
  • : Manufacturer’s Role in CE Marking11-40
  • Q 11.34 : What does the CE represent?11-40
  • Q 11.35 : What is the relevance of a CE Mark to FDA’s premarket review process?11-40
  • : EU Member State Authorities’ Roles11-40
  • Q 11.36 : Which key regulatory documents govern clinical trials?11-40
  • Q 11.37 : What did the Directive 2007/47/EC amendment address?11-42
  • : Recent Legislation11-44
  • Q 11.38 : What is the new regulatory framework?11-44
  • : Borderline and Combination Products11-63
  • Q 11.39 : What do the EU Demarcation Guidelines explain?11-63
  • Q 11.40 : What is a drug-delivery device?11-64
  • Q 11.41 : How is a medical device incorporating, as an integral part, an ancillary medicinal substance CE marked?11-65
  • Q 11.42 : How can I decide whether my product is a medical device or a medicinal product?11-66
Chapter 12: Interacting with FDA
  • : Informal Interactions with FDA12-3
  • Q 12.1 : How should one address general questions about the regulation of medical devices with FDA?12-3
  • Q 12.2 : Are there any precautions to take before directing a question to FDA?12-3
  • Q 12.3 : Is it appropriate to communicate directly with a reviewer or division director?12-4
  • Q 12.4 : Are anonymous calls to FDA permitted?12-4
  • Q 12.5 : Can one request an informal conference or meeting?12-4
  • : Formal Interactions with FDA12-5
  • : Submissions12-5
  • Q 12.6 : If a company is trying to resolve an issue or address a question related to a 510(k) or Premarket Approval Application (PMA), who is the best person to contact?12-5
  • Q 12.7 : What is the best way to contact the division reviewer?12-6
  • Q 12.8 : What if the reviewer is unresponsive or unable to resolve the issues?12-6
  • Q 12.9 : How long does it take to schedule a meeting with the division?12-6
  • Q 12.10 : What will take place at a meeting with the division and what preparation is necessary?12-7
  • Q 12.11 : If the issues are not resolved after meetings with the division, does the company have any recourse?12-7
  • Q 12.12 : Does FDA have a duty to document its rationale for significant regulatory decisions and actions taken by CDRH?12-8
  • Q 12.13 : Who may request documentation of CDRH’s significant decisions and how does this provision relate to requests under the Freedom of Information Act (FOIA)?12-9
  • : Meetings with the Office of Orphan Products Development12-10
  • Q 12.14 : Does FDA offer assistance with humanitarian use device (HUD) designation requests and funding opportunities through the Orphan Products Grants Program and the Pediatric Device Consortia Grants Program?12-10
  • Q 12.15 : What type meetings can occur with the OOPD?12-10
  • : Correspondence Related to Enforcement Actions, Adverse Events, and Corrective Actions12-11
  • Q 12.16 : Must an individual sign an affidavit if presented one by an FDA investigator?12-11
  • Q 12.17 : If one does not allow an FDA investigator to review requested materials, can FDA take enforcement action?12-11
  • Q 12.18 : Must a company allow an FDA investigator to take photographs of records or the manufacturing site?12-12
  • Q 12.19 : Should one go to the District Director or FDA headquarters if the FDA investigator is asking burdensome questions?12-13
  • Q 12.20 : Is correspondence related to enforcement actions, corrective action, or adverse event reporting made public?12-13
  • : Correspondence Related to User Fees12-14
  • Q 12.21 : How does one request a refund of a User Fee?12-14
  • : Citizen Petitions12-14
  • Q 12.22 : What is a petition?12-14
  • Q 12.23 : What must a Citizen Petition include?12-14
  • Q 12.24 : When must FDA respond to a Citizen Petition?12-15
  • Q 12.25 : Are there other avenues for reconsideration of FDA action?12-15
  • : Rulemaking12-16
  • Q 12.26 : How can one comment on a proposed rule?12-16
  • : Public Meetings12-16
  • Q 12.27 : When will FDA convene a Public Advisory Committee meeting?12-16
  • Q 12.28 : Are there particular procedures for meetings of the Medical Devices Advisory Committee?12-17
  • Q 12.29 : Can anyone participate in a public meeting?12-17
  • Q 12.30 : Where does FDA announce an advisory committee meeting?12-17
  • Q 12.31 : How can an interested person participate in the public hearing?12-17
  • Q 12.32 : What happens if the person does not register to speak in advance?12-18
  • Q 12.33 : How long is the Public Hearing portion of each advisory committee meeting?12-18
  • Q 12.34 : Can FDA close to the public portions of an advisory committee meeting?12-18
  • Q 12.35 : What are some examples of portions of FDA advisory committee meetings that ordinarily should not be closed to the public?12-18
  • Q 12.36 : What is a Public Board of Inquiry?12-18
  • : Company-Requested Meetings12-19
  • Q 12.37 : When may a company request a meeting with FDA?12-19
  • Q 12.38 : Are company-requested meetings considered public?12-19
  • Q 12.39 : When may a company contact FDA about an IDE application?12-20
  • Q 12.40 : What is an informal guidance meeting?12-20
  • Q 12.41 : What is a determination meeting request?12-20
  • Q 12.42 : What is an Agreement Meeting?12-20
  • : Hearings12-21
  • Q 12.43 : When are hearings available?12-21
  • Q 12.44 : What types of hearings are available?12-21
  • Q 12.45 : When are Formal Evidentiary Public Hearings available?12-22
  • Q 12.46 : What procedures apply in Formal Hearings?12-22
  • Q 12.47 : What types of evidence may be presented at Formal Hearings?12-23
  • Q 12.48 : When are other hearing types available?12-24
  • Q 12.49 : What are the advantages and disadvantages of the various hearing types?12-24
  • : Appeal Process for Formal Hearings12-25
  • Q 12.50 : May a participant appeal an initial decision issued in a Formal Hearing before that decision becomes final?12-25
  • Q 12.51 : What must be included in the appeal of the initial decision?12-25
  • Q 12.52 : Is oral argument available on appeal of an initial decision?12-25
  • Q 12.53 : What is the scope of review when an initial decision is appealed to the Commissioner?12-26
  • Q 12.54 : What are potential outcomes upon appeal to the Commissioner?12-26
  • Q 12.55 : What further appeal options are available once the Commissioner issues a final decision?12-26
  • Q 12.56 : When can a party seek judicial review of an FDA action?12-27
  • : Ombudsman12-27
  • Q 12.57 : Who is the Ombudsman and what is the role of an Ombudsman?12-27
  • Q 12.58 : What types of matters does the Ombudsman handle?12-28
  • Q 12.59 : What else does the Ombudsman do?12-28
  • : Litigation12-29
  • Q 12.60 : When a U.S. Marshal is in a company to initiate a product seizure, is there an opportunity to prevent the seizure?12-29
  • Q 12.61 : If FDA has issued a Notice of Violation, Warning Letter, or some other enforcement correspondence, including litigation, can a company request a meeting to discuss the issues?12-29
  • Q 12.62 : If FDA permits a meeting or telephone request, who at FDA might be present?12-29
  • Q 12.63 : Are phone calls or emails considered formal communication in responding to FDA in enforcement or litigation matters?12-29
  • Q 12.64 : Can FDA deny a request for a meeting in a litigation or enforcement matter?12-30
  • Q 12.65 : Must a company respond to a product seizure, injunction, or other court enforcement initiative?12-30
  • Q 12.66 : Is a Consent Decree negotiable?12-30
  • Q 12.67 : Can one seek arbitration or a third-party intermediary, other than a court, in an enforcement action?12-30
  • Q 12.68 : Can a third party sue FDA to take enforcement action, such as initiating a court action, against another company?12-30
  • Q 12.69 : In a court action, to whom does a company communicate to negotiate?12-31
  • : Persuading FDA to Your Position12-31
  • Q 12.70 : How should one approach advocating a particular position to FDA?12-31
  • Q 12.71 : How can one gather the intelligence that will advance this type of planning?12-31
  • Q 12.72 : Whom should one contact to advocate a position?12-32
  • Q 12.73 : Are there particular advocacy strategies that are most effective?12-32
  • Q 12.74 : Any final suggestions?12-33
  • : Chain of Command Considerations12-33
  • Q 12.75 : What are acceptable protocols if an issue needs to be escalated within FDA?12-33
  • Q 12.76 : Are there any other factors to consider concerning the chain of command?12-34
  • : Information Disclosure Considerations12-34
  • Q 12.77 : What is the Freedom of Information Act?12-34
  • Q 12.78 : Who can request FDA-related information from the Agency under FOIA?12-34
  • Q 12.79 : How is a FOIA request processed?12-35
  • Q 12.80 : Will FDA redact confidential information from records before releasing them under FOIA?12-35
  • Q 12.81 : Are there exemptions to FOIA disclosure?12-35
  • Q 12.82 : Will FDA disclose data provided to support a marketing application?12-36
  • Q 12.83 : Are there fees associated with the processing of a FOIA request?12-36
  • Q 12.84 : Does FDA make information available online?12-36
Chapter 13: Enforcement and Government Investigations Relating to Medical Devices
  • : FDA Enforcement—Generally13-2
  • Q 13.1 : What violations of the Federal Food, Drug, and Cosmetic Act can prompt FDA enforcement?13-2
  • Q 13.2 : What are the sources of FDA enforcement powers relating to medical devices?13-4
  • Q 13.3 : What is FDA’s enforcement strategy?13-5
  • Q 13.4 : What factors influence FDA’s decision to bring an enforcement action?13-8
  • Q 13.5 : What is the extent of FDA jurisdiction over devices in enforcement matters?13-8
  • Q 13.6 : Does FDA have subpoena powers?13-9
  • Q 13.7 : Do other government agencies enforce the FDCA?13-9
  • Q 13.8 : How does FDA involve state authorities in enforcement actions?13-14
  • : Inspections13-14
  • Q 13.9 : Under what authority does FDA conduct inspections?13-14
  • Q 13.10 : What is the purpose of FDA inspections?13-15
  • Q 13.11 : Are inspections announced beforehand?13-15
  • Q 13.12 : What constitutes refusal of an inspection?13-15
  • Q 13.13 : What facilities and records may FDA inspect?13-16
  • Q 13.14 : What is the Quality Systems Inspection Technique (QSIT)?13-16
  • Q 13.15 : How should a company prepare for an inspection?13-17
  • Q 13.16 : Can information obtained in an investigation be used in criminal proceedings?13-18
  • Q 13.17 : Can FDA investigators take samples or photographs during an inspection?13-18
  • : FORM 13-1: FDA Collection Receipt (Example)13-19
  • : Form FDA 48313-21
  • Q 13.18 : Can inspectors interview personnel?13-21
  • Q 13.19 : What is Form FDA 483?13-21
  • : FORM 13-2: List of Observations Following Inspection (Example)13-22
  • Q 13.20 : How should a company handle requests outside the scope of FDA authority?13-24
  • Q 13.21 : Must company personnel sign affidavits prepared by FDA during an inspection?13-24
  • : Establishment Inspection Report13-24
  • Q 13.22 : What is an Establishment Inspection Report (EIR)?13-24
  • Q 13.23 : What policies and manuals govern FDA investigations?13-25
  • : Warning Letters13-25
  • Q 13.24 : What is the purpose of a Warning Letter?13-25
  • Q 13.25 : Are Warning Letters subject to judicial review?13-25
  • Q 13.26 : Are Warning Letters made public?13-25
  • Q 13.27 : What is a Warning Letter “close-out”?13-26
  • Q 13.28 : Are there other forms of FDA enforcement correspondence?13-26
  • : Adverse Publicity13-27
  • Q 13.29 : Can FDA issue public enforcement statements?13-27
  • Q 13.30 : How should companies respond to such publicity?13-27
  • : Recalls and Notifications13-27
  • Q 13.31 : May FDA order medical device recalls?13-27
  • Q 13.32 : Must a company notify FDA of a recall?13-28
  • Q 13.33 : What is the difference between a recall, market withdrawal, removal, and stock recovery?13-28
  • Q 13.34 : What kind of information is required when notifying FDA?13-29
  • Q 13.35 : What are the different classes of recalls?13-30
  • Q 13.36 : How is FDA involved in a recall?13-30
  • Q 13.37 : What is FDA’s authority to require notification to physicians and the public of device problems?13-30
  • : Imports and Exports13-31
  • Q 13.38 : What is an import detention?13-31
  • Q 13.39 : What is an import alert?13-31
  • Q 13.40 : How should a company respond to an import detention?13-31
  • Q 13.41 : Under what conditions can a refused product be permitted to enter?13-32
  • Q 13.42 : Can uncleared/unapproved products be exported?13-32
  • : Seizures13-32
  • Q 13.43 : When is a device subject to seizure?13-32
    • Q 13.43.1 : Who actually conducts FDA seizures?13-32
    • Q 13.43.2 : Against whom is a seizure action taken?13-32
  • Q 13.44 : What is FDA’s process for obtaining a seizure?13-33
  • Q 13.45 : When does FDA choose to initiate seizure actions?13-33
  • Q 13.46 : What is the difference between a seizure action and an injunction?13-33
  • : Injunctions13-34
  • Q 13.47 : Why does FDA seek injunctive relief against a company?13-34
  • Q 13.48 : What types of injunctions may FDA seek?13-34
  • Q 13.49 : When may a company be held in contempt of court for violating the terms of an injunction?13-34
  • Q 13.50 : What can a company do to avoid an injunction?13-34
  • Q 13.51 : Who may be enjoined?13-35
  • : Civil Money Penalties13-35
  • Q 13.52 : What is a civil money penalty (CMP)?13-35
  • Q 13.53 : What statute authorizes FDA to impose CMPs for violations of FDA requirements applicable to medical devices?13-35
  • Q 13.54 : What rules and regulations apply to small entities regarding CMPs?13-36
  • Q 13.55 : What are the standards for imposing a CMP?13-36
  • Q 13.56 : For what medical device violations may FDA not impose CMPs?13-37
  • Q 13.57 : What is a “significant departure” from FDA requirements that incurs a CMP?13-37
  • Q 13.58 : What is a “knowing departure” from FDA requirements that incurs a CMP?13-37
  • Q 13.59 : What is a “minor violation”?13-37
  • Q 13.60 : What are the limits on CMPs?13-37
  • Q 13.61 : What factors does FDA consider in deciding the amount of a CMP?13-38
  • Q 13.62 : What statutory authority does FDA have to impose CMPs regarding device clinical trials?13-38
  • Q 13.63 : What are the penalties for violation of clinical trials requirements?13-39
  • Q 13.64 : How are CMP proceedings resolved?13-39
  • Q 13.65 : What is the relationship between CMPs and criminal penalties?13-39
  • : Criminal Liability13-40
  • Q 13.66 : What information is sought in a criminal investigation?13-40
  • Q 13.67 : What is the role of FDA’s Office of Criminal Investigations (OCI)?13-40
  • Q 13.68 : When may the government bring a criminal action?13-41
  • Q 13.69 : Who files charges?13-42
  • Q 13.70 : What is vicarious corporate liability?13-44
  • Q 13.71 : What are the defenses to criminal liability?13-44
  • Q 13.72 : What factors will FDA consider in deciding whether to recommend prosecution?13-45
  • Q 13.73 : What factors will DOJ consider in deciding whether to proceed with FDA’s recommendation to prosecute?13-45
  • Q 13.74 : When will FDA offer a company the opportunity to “present views” arguing against prosecution?13-48
  • Q 13.75 : What happens in a plea bargain?13-48
  • Q 13.76 : What is enforcement discretion?13-49
  • Q 13.77 : What types of penalties are available to FDA in a criminal enforcement matter?13-50
  • : Compliance Programs13-51
  • Q 13.78 : What must an organization do to have an effective compliance and ethics program?13-51
Chapter 14: Continuing Medical Education (CME) and Industry-Supported Scientific Activities
  • : Overview14-2
  • Q 14.1 : Does FDA regulate all scientific and educational industry-supported activities?14-2
    • Q 14.1.1 : How do these activities differ from advertising and labeling?14-2
  • Q 14.2 : What are promotional activities versus nonpromotional or independent activities?14-3
    • Q 14.2.1 : What factors help demonstrate independence from the substantive influence of a company?14-4
    • Q 14.2.2 : What types of disclosure of potential conflicts of interest should be made?14-4
  • : Off-Label Promotion14-5
  • Q 14.3 : What is off-label promotion and how does it differ from the practice of medicine and the promotion of approved labeling indications?14-5
    • Q 14.3.1 : What role does education, scientific exchange, and commercial free speech play?14-6
  • : Allowable Industry-Supported Activities14-7
  • Q 14.4 : What types of industry-supported scientific and educational activities are allowable?14-7
  • : Conferences and Symposia14-8
  • Q 14.5 : When is a conference, symposium, or other program an allowable industry-supported activity?14-8
    • Q 14.5.1 : What “red flags” typically lead FDA to conclude that an industry-supported activity is promotional in nature?14-11
  • Q 14.6 : Can sales or promotional meetings occur as an adjunct to a scientific or educational meeting?14-13
  • : Disease Awareness and Help-Seeking Communications14-14
  • Q 14.7 : Has FDA issued and/or withdrawn guidance on “help-seeking” and other disease awareness communications?14-14
  • Q 14.8 : Where do specific types of educational or scientific communications by industry fit?14-14
    • Q 14.8.1 : What are the required elements in “disease awareness” and “help-seeking” communications?14-14
    • Q 14.8.2 : What are the rules regarding combination help-seeking/disease awareness ads with reminder ads or product claim promotions?14-16
    • Q 14.8.3 : What types of references to company name/information may be included in a help-seeking ad?14-17
  • : Live-Case Demonstrations14-17
  • Q 14.9 : What about live-case demonstrations conducted at medical and educational meetings?14-17
    • Q 14.9.1 : What are FDA’s principal concerns?14-17
    • Q 14.9.2 : Must there be “balance” in demonstrations, such as single method or product versus multiple methods or products?14-18
  • Q 14.10 : Can off-label indications be discussed for cleared/approved devices during product training?14-19
  • : Statements Concerning Investigational Devices14-20
  • Q 14.11 : Are there limits on speeches or exhibits discussing devices in development or under investigation?14-20
  • : Trade Shows and Exhibits14-21
  • Q 14.12 : What are acceptable promotional activities during trade shows for products not yet cleared or approved?14-21
  • Q 14.13 : Are there disclosures that can “cure” the display or advertisement of a device that has not received clearance or approval from FDA?14-22
  • : Reprints of Scientific Publications14-22
  • Q 14.14 : What constitutes appropriate dissemination of scientific publications and reprints?14-22
  • Q 14.15 : How is the analysis different if the scientific publication discusses an off-label use of the company’s product?14-24
  • Q 14.16 : What type of information should accompany distribution of journal articles, reference text excerpts, and CPG excerpts?14-25
  • Q 14.17 : How should entire scientific or medical reference texts and entire CPGs be distributed?14-27
  • : Voluntary Guidelines14-28
  • Q 14.18 : What are some examples of voluntary guidelines that have been developed and current trends in this area?14-28
  • Q 14.19 : What are the considerations for incorporation of voluntary codes of conduct into company procedures?14-29
  • : State Laws14-30
  • Q 14.20 : Are there additional considerations at the state level?14-30
  • : Donations for Educational Purposes14-31
  • Q 14.21 : Can industry provide educational grants or other charitable donations to support the development of an educational conference or program?14-31
Chapter 15: Intellectual Property Considerations for Medical Device Companies
  • : Overview15-2
  • Q 15.1 : What are intellectual property rights?15-2
  • Q 15.2 : What general considerations should a medical device company have with respect to the protection of its intellectual property rights?15-2
  • Q 15.3 : What concerns should a medical device company have about intellectual property rights of others?15-3
  • Q 15.4 : When FDA regulations conflict with intellectual property rights, which prevails?15-3
  • : Patents15-4
  • Q 15.5 : What is a patent?15-4
  • Q 15.6 : What is the source of law for patents in the United States?15-4
  • Q 15.7 : What types of patents are available in the United States?15-5
  • Q 15.8 : What protection is available for inventions outside the United States?15-6
  • Q 15.9 : What subject matter cannot be patented?15-7
  • Q 15.10 : What rights does a patent confer on a patent holder’s patented invention?15-7
  • Q 15.11 : What is required to obtain a patent?15-8
  • Q 15.12 : What is the “utility” or usefulness requirement for an invention to be patented?15-9
  • Q 15.13 : What is the novelty requirement for an invention to be patented?15-9
  • Q 15.14 : What does the non-obvious requirement for patentability mean?15-10
  • Q 15.15 : Who owns a patent?15-11
  • Q 15.16 : How does a medical device company obtain title to patents in a medical device?15-12
  • Q 15.17 : If two individuals acting independently each invent the same invention, which inventor is entitled to receive the patent?15-13
  • Q 15.18 : When must a patent application be made?15-13
  • Q 15.19 : What is the term of a patent?15-14
  • Q 15.20 : How should a medical device covered by a patent be marked?15-15
  • Q 15.21 : When should “patent pending” be used on a medical device?15-16
  • Q 15.22 : What is patent infringement?15-17
  • Q 15.23 : What steps can the medical device company take during the development of a new product or process to avoid infringing a third-party patent?15-17
  • Q 15.24 : What can the medical device company do to minimize the risk of infringing third-party patents?15-18
  • Q 15.25 : How can a U.S. patent be challenged in court?15-18
  • Q 15.26 : How can a U.S. patent be challenged at the U.S. Patent Office?15-19
  • Q 15.27 : What is a “patentability search”?15-20
  • Q 15.28 : What is a “freedom-to-operate” opinion?15-21
  • Q 15.29 : What limitations are inherent in patent searches and patent opinions?15-22
  • Q 15.30 : Can a company “design around” an issued patent and avoid infringement?15-22
  • Q 15.31 : What is the duty of candor and good faith before the PTO?15-23
  • Q 15.32 : After the patent issues, what must a patent holder do to maintain a patent in force?15-24
  • : Copyrights15-24
  • Q 15.33 : What is a copyright?15-24
  • Q 15.34 : What is the source of law for copyrights?15-25
  • Q 15.35 : What subject matter is not covered by copyright?15-25
  • Q 15.36 : How can copyright law be used to protect medical devices?15-26
  • Q 15.37 : Who owns a copyright?15-26
  • Q 15.38 : What rights does a copyright confer on the copyright owner?15-27
  • Q 15.39 : Is any filing required to obtain a copyright?15-27
  • Q 15.40 : Why should copyrights be registered in the United States?15-28
  • Q 15.41 : How is a copyright registered?15-28
  • Q 15.42 : What is the term of copyright protection?15-29
  • Q 15.43 : What should a copyright notice contain?15-29
  • Q 15.44 : What constitutes copyright infringement?15-30
  • Q 15.45 : What circumvention of a technological measure is prohibited by the Copyright Act?15-30
  • Q 15.46 : What circumvention of a technological measure is allowed by the U.S. Copyright Office?15-31
  • Q 15.47 : What is “fair use”?15-31
  • Q 15.48 : What can a medical device company do to minimize the risk of infringing copyrights of others?15-32
  • Q 15.49 : What are the remedies for copyright infringement or circumvention?15-33
  • : Trade Secrets15-33
  • Q 15.50 : What is a trade secret?15-33
  • Q 15.51 : What is the source of law for trade secrets?15-34
  • Q 15.52 : To what extent can a medical device company rely on trade secret protection outside the United States?15-35
  • Q 15.53 : How can a medical device company maintain trade secrets with respect to confidential information it provides to the FDA?15-36
  • Q 15.54 : What constitutes misappropriation of trade secrets?15-37
  • Q 15.55 : Can a competitor reverse engineer a medical device and replicate it without violating trade secrets?15-38
  • Q 15.56 : How should a medical device company protect its trade secrets?15-38
  • Q 15.57 : Can a medical device company prohibit employees from disclosing the company’s trade secrets to government officials in connection with reporting or investigating a suspected legal violation?15-39
  • Q 15.58 : What is the term of protection for trade secrets?15-40
  • Q 15.59 : What notice or marking should be used to protect trade secrets?15-40
  • Q 15.60 : How is a trade secret different than a patent?15-40
  • : Trademarks15-41
  • Q 15.61 : What is a trademark?15-41
  • Q 15.62 : What is the source of law for trademark protection?15-41
  • Q 15.63 : What are the advantages of registering a trademark in the United States?15-42
  • Q 15.64 : How are trademarks registered?15-42
  • Q 15.65 : How should a medical device company choose a trademark?15-43
  • Q 15.66 : Can a generic term be a trademark?15-45
  • Q 15.67 : What should a medical device company do to avoid adopting a mark that might infringe another company’s rights?15-45
  • Q 15.68 : What is the term of protection for trademarks?15-45
  • Q 15.69 : What notice and marking should be used with trademarks?15-46
  • Q 15.70 : After a trademark is registered, what must a trademark owner do to maintain a trademark registration in force in the United States?15-46
  • Q 15.71 : What is trademark infringement?15-47
  • Q 15.72 : How do the false advertising provisions of the Lanham Act apply to medical devices?15-47
  • : Managing and Enforcing Intellectual Property15-47
  • Q 15.73 : How should a medical device company manage intellectual property?15-47
  • Q 15.74 : What steps can a medical device company take to avoid intellectual property losses?15-50
  • Q 15.75 : How can a medical device company enforce their intellectual property rights?15-52
Chapter 16: Licensing, Product Development, and Commercialization
  • : Contracts in Strategic Alliances16-2
  • Q 16.1 : What contracts are involved in the life cycle of a medical device?16-2
  • Q 16.2 : What laws may apply to contracts relating to medical devices?16-4
  • Q 16.3 : What intellectual property rights are involved in various contracts affecting medical devices?16-4
  • : Licensing Arrangements16-6
  • Q 16.4 : When should a company use a licensing arrangement?16-6
  • Q 16.5 : When is a licensing agreement required?16-7
  • Q 16.6 : How is the scope of a license grant determined?16-8
  • Q 16.7 : What are some specialized types of licenses?16-12
  • Q 16.8 : When can licenses be sublicensed or assigned?16-13
  • Q 16.9 : What are typical licensing fee arrangements?16-14
  • : Legal Considerations16-20
  • Q 16.10 : What are other common provisions in a license pertaining to medical devices?16-20
  • Q 16.11 : What special provisions do patent licenses contain?16-23
  • Q 16.12 : What specific terms are needed for licenses involving mobile device technologies?16-24
  • Q 16.13 : What is the effect of bankruptcy on intellectual property licenses?16-27
  • : Maintaining Confidentiality16-28
  • Q 16.14 : When should I use non-disclosure agreements?16-28
  • Q 16.15 : What are the critical components of a non-disclosure agreement?16-29
  • : Ownership of Newly Created Assets16-30
  • Q 16.16 : Who owns employee-developed inventions?16-30
  • Q 16.17 : How should parties allocate ownership of jointly developed intellectual property?16-31
  • Q 16.18 : Are there alternatives to joint ownership of jointly developed intellectual property?16-33
  • : Licensing from Universities16-34
  • Q 16.19 : Why would I want to license technology from a university?16-34
  • Q 16.20 : How can I obtain rights to intellectual property owned by a university?16-34
  • Q 16.21 : What is the Bayh-Dole Act and how does it affect university licensing activities?16-36
  • Q 16.22 : How are potential conflicts of interest for university faculty managed?16-37
  • Q 16.23 : What liability provisions are typical in intellectual property licenses from universities?16-38
  • Q 16.24 : Do licenses from universities typically include due diligence milestones?16-39
  • Q 16.25 : Who owns the intellectual property developed as a result of university research sponsored by a private entity and how is it licensed or commercialized?16-40
  • Q 16.26 : Who owns future improvements on inventions licensed from universities?16-41
  • Q 16.27 : What about publication of research results?16-41
  • Q 16.28 : How do universities treat confidential information?16-41
Chapter 17: Fraudulent and Abusive Practices in the Reimbursement for Medical Devices
  • : Overview17-2
  • : Federal Reimbursement for Medical Devices in General17-2
  • Q 17.1 : What is “reimbursement”?17-2
  • Q 17.2 : Who are the “payors”?17-2
  • : Reasonable and Necessary Devices17-3
  • Q 17.3 : How does CMS make reimbursement decisions regarding medical devices?17-3
  • Q 17.4 : How does CMS determine whether a medical device is reasonable and necessary?17-3
  • : Devices in Development17-4
  • Q 17.5 : Will CMS reimburse for devices that are still in development?17-4
    • Q 17.5.1 : What are Category B devices?17-5
    • Q 17.5.2 : What are Category A devices?17-5
  • : Table 17-1: Investigational Device Agency Decisions17-6
  • Q 17.6 : Will CMS reimburse for the use of investigational devices?17-6
  • Q 17.7 : Are FDA decisions definitive for CMS reimbursement purposes?17-6
  • : Coding17-7
  • Q 17.8 : How are claims for medical devices processed to ensure consistency and efficiency?17-7
  • : Understanding the Nature of Fraud in Reimbursement17-7
  • : Defining Fraud17-7
  • Q 17.9 : What is fraud?17-7
  • : Fraud in Reimbursement17-8
  • Q 17.10 : What does reimbursement have to do with fraud and abuse?17-8
  • Q 17.11 : How do federal laws governing reimbursement affect medical device manufacturers?17-9
  • Q 17.12 : How do a medical device manufacturer’s promotional practices implicate fraud and abuse laws?17-9
  • Q 17.13 : How can a medical device manufacturer’s financial relationships with health care providers implicate fraud and abuse laws?17-9
  • Q 17.14 : How can medical device manufacturers be implicated in laws designed to curb fraudulent and abusive reimbursement practices if the reimbursement flows to the health care provider?17-10
  • : Potential Fraud and Abuse in the Medical Device Manufacturing Industry17-11
  • Q 17.15 : What laws are most likely to affect medical device manufacturers in the context of reimbursement from Medicare and other federal health care programs?17-11
  • : The False Claims Act17-11
  • Q 17.16 : What is the FCA?17-11
  • Q 17.17 : What does “knowingly” mean?17-11
  • Q 17.18 : What is a “claim” in the context of the FCA?17-12
  • Q 17.19 : What statements are “material” to a false or fraudulent claim?17-12
  • Q 17.20 : What are the penalties for violating the FCA?17-12
  • Q 17.21 : Who brings an action under the FCA?17-12
  • Q 17.22 : How does a private individual bring a FCA action?17-12
  • Q 17.23 : Has the government been successful in prosecuting under the FCA?17-13
  • Q 17.24 : What FCA claims have been brought against medical device manufacturers?17-13
  • : The Anti-Kickback Statute17-15
  • Q 17.25 : What is the federal Anti-Kickback Statute?17-15
  • Q 17.26 : What are the penalties for violating the AKS?17-15
  • Q 17.27 : How does the AKS impact the activities of a medical device manufacturer?17-15
  • Q 17.28 : What AKS claims have been brought against medical device manufacturers?17-16
  • Q 17.29 : Are all financial relationships between medical device manufacturers and physicians (or other health care providers) illegal?17-17
  • Q 17.30 : How can you distinguish between acceptable and unacceptable financial relationships between health care providers and medical device manufacturers under the AKS?17-17
  • : Table 17-2: Payment Practices Eligible for Safe Harbor Protection17-18
  • Q 17.31 : How can you obtain safe harbor protection?17-19
  • Q 17.32 : Which safe harbors are likely to apply in the context of financial arrangements between medical device manufacturers and health care providers?17-19
    • Q 17.32.1 : What are the requirements for the personal services safe harbor?17-19
    • Q 17.32.2 : What are the requirements for the investment interests safe harbor?17-20
  • Q 17.33 : How can a medical device manufacturer or health care professional assure that safe harbor protection applies?17-21
  • : The Civil Money Penalty Law17-21
  • Q 17.34 : What is the Civil Money Penalty law?17-21
  • Q 17.35 : What constitutes a violation of the CMP law?17-22
    • Q 17.35.1 : What is an “item or service”?17-22
  • Q 17.36 : When should a person know that a claim is false or fraudulent?17-23
  • Q 17.37 : What are the penalties under the CMP law?17-23
  • Q 17.38 : Who enforces the CMP law?17-24
  • Q 17.39 : How could a medical device manufacturer be found to have violated the CMP law?17-24
  • Q 17.40 : Have CMP claims been brought against medical device manufacturers?17-24
  • : State Laws17-25
  • Q 17.41 : What state laws might apply to the same circumstances?17-25
  • Q 17.42 : What are state false claims acts?17-25
  • Q 17.43 : What are insurance fraud laws?17-26
  • Q 17.44 : How can state professional licensure laws apply?17-26
  • Q 17.45 : What other types of repercussions are there if a medical device manufacturer is found to have violated one of the federal or state laws discussed?17-26
  • : Avoiding Violations17-27
  • Q 17.46 : What best practices can a medical device manufacturer employ in avoiding violation of the fraud and abuse laws?17-27
  • Q 17.47 : What are some examples of best practices?17-28
Chapter 18: HIPAA’s Impact on the Medical Device Manufacturing Community
  • : Overview18-2
  • Q 18.1 : What are the major challenges HIPAA presents to a medical device manufacturer?18-2
  • : Compliance Challenges18-3
  • Q 18.2 : When does HIPAA apply to a medical device manufacturer?18-3
  • : Entities Subject to HIPAA18-3
  • Q 18.3 : What entities are subject to HIPAA?18-3
  • Q 18.4 : Why is it important to know if you are a covered entity or a business associate?18-3
  • Q 18.5 : What are “covered entities”?18-3
    • Q 18.5.1 : When is a medical device manufacturer likely to be a covered entity?18-4
    • Q 18.5.2 : What if only a small segment of a medical device manufacturer’s business provides health care services?18-4
  • Q 18.6 : What is a “business associate”?18-4
    • Q 18.6.1 : Are employees of a covered entity business associates?18-5
    • Q 18.6.2 : When is a medical device manufacturer a business associate?18-5
    • Q 18.6.3 : How does a covered entity appoint a business associate?18-6
    • Q 18.6.4 : What is a business associate agreement?18-6
    • Q 18.6.5 : Is there a standard business associate agreement?18-6
  • : Information Subject to HIPAA18-7
  • Q 18.7 : What health information does HIPAA protect?18-7
    • Q 18.7.1 : What does “individually identifiable health information” mean?18-7
    • Q 18.7.2 : How does HIPAA define “health care”?18-7
  • Q 18.8 : What does protected health information include?18-7
  • : Penalties for Noncompliance18-8
  • Q 18.9 : What are the penalties for noncompliance?18-8
    • Q 18.9.1 : What are the civil penalties?18-8
    • : Table 18-1: Tiered Civil Penalties18-9
    • Q 18.9.2 : What other repercussions might a violator face?18-9
    • Q 18.9.3 : When do criminal penalties apply?18-10
    • Q 18.9.4 : What are the criminal penalties?18-10
  • : Safeguards18-10
  • Q 18.10 : What are the rules for safeguarding protected health information?18-10
  • Q 18.11 : What is the Privacy Rule?18-11
    • Q 18.11.1 : When does the Privacy Rule allow using or disclosing protected health information?18-11
    • Q 18.11.2 : When does the Privacy Rule require the use or disclosure of protected health information?18-11
    • Q 18.11.3 : When are covered entities permitted to disclose protected health information?18-11
    • : Table 18-2: Permitted Uses and Disclosures18-12
    • Q 18.11.4 : What are the limits on the amount of protected health information the Privacy Rule allows to be used or disclosed?18-12
    • Q 18.11.5 : What does “minimum necessary” mean?18-13
    • Q 18.11.6 : What are “limited data sets”?18-13
    • : Table 18-3: Identifiers Removed to Create Limited Data Set18-14
    • Q 18.11.7 : What if a limited data set does not provide enough information for the intended use or disclosure?18-14
    • Q 18.11.8 : Are there any exceptions to the “minimum necessary” requirement?18-15
    • Q 18.11.9 : What rights does HIPAA give individuals regarding their protected health information?18-15
    • Q 18.11.10 : What responsibility does a covered entity have to inform individuals of these rights?18-15
    • Q 18.11.11 : What information must the Notice of Privacy Practices include?18-16
    • Q 18.11.12 : What obligation does a medical device manufacturer have for producing a Notice of Privacy Practices?18-16
    • Q 18.11.13 : What policies and procedures does the Privacy Rule require?18-16
    • Q 18.11.14 : Who is responsible for overseeing a covered entity’s compliance with the Privacy Rule?18-17
  • Q 18.12 : What is the Security Rule?18-17
    • Q 18.12.1 : What is the difference between the Privacy Rule and the Security Rule?18-18
    • Q 18.12.2 : How does the Security Rule apply to a medical device manufacturer?18-18
    • Q 18.12.3 : How does a medical device manufacturer know what safeguards it must adopt?18-18
    • Q 18.12.4 : What are “addressable” safeguards?18-19
    • Q 18.12.5 : What are “required” safeguards?18-19
    • Q 18.12.6 : What are the three categories of required and addressable safeguards in the Security Rule?18-19
    • Q 18.12.7 : What are “administrative safeguards”?18-19
    • : Table 18-4: Administrative Safeguards18-20
    • Q 18.12.8 : What are “physical safeguards”?18-22
    • : Table 18-5: Physical Safeguards18-22
    • Q 18.12.9 : What are “technical safeguards”?18-24
    • : Table 18-6: Technical Safeguards18-24
    • Q 18.12.10 : Who has overall responsibility for complying with the Security Rule?18-25
  • : Research Challenges18-25
  • Q 18.13 : What challenges does HIPAA present to a medical device manufacturer conducting research?18-25
  • Q 18.14 : What are the methods by which a medical device manufacturer can obtain protected health information from covered entities?18-25
  • : Authorizations18-26
  • Q 18.15 : What are “authorizations”?18-26
    • Q 18.15.1 : What information must be included in an authorization?18-26
    • Q 18.15.2 : What are the core elements of an authorization?18-26
    • Q 18.15.3 : What are the required statements?18-27
    • Q 18.15.4 : How do authorizations compare to “consents” that may otherwise be required in order to conduct research?18-27
    • Q 18.15.5 : Whose responsibility is it to get the authorization?18-28
    • Q 18.15.6 : Can a medical device manufacturer share the information with the sponsor of a clinical trial or others?18-28
  • : Exceptions to the Authorization Requirement18-28
  • Q 18.16 : Are authorizations always required?18-28
  • Q 18.17 : How do researchers get waivers of the authorization requirement from an IRB or a privacy board?18-29
    • Q 18.17.1 : Who has to be on the IRB or privacy board?18-29
    • Q 18.17.2 : What are the criteria for getting a waiver of the authorization requirement from the IRB or privacy board?18-30
    • Q 18.17.3 : What constitutes “minimal risk”?18-30
    • Q 18.17.4 : How much protected health information would be available if a waiver of the authorization requirement is satisfied?18-31
    • Q 18.17.5 : What documentation must exist regarding the waiver of the authorization requirement?18-31
  • Q 18.18 : What are the requirements for reviewing protected health information that is preparatory to research?18-31
  • Q 18.19 : What are the requirements for getting a waiver of the authorization requirement when the information relates to decedents?18-32
  • : Determining Scope of Information18-32
  • Q 18.20 : What if the researcher only needs aggregated data?18-32
    • Q 18.20.1 : What is “de-identified information”?18-32
    • Q 18.20.2 : How do you get de-identified information?18-32
    • Q 18.20.3 : What information must be removed?18-33
    • : Table 18-7: Identifiers Removed to Create De-Identified Information18-33
    • Q 18.20.4 : Why is de-identified information not protected by HIPAA?18-34
  • Q 18.21 : What is the difference between a limited data set and de-identified information?18-35
    • Q 18.21.1 : When can a researcher use a limited data set?18-35
    • Q 18.21.2 : What is a “data use agreement”?18-35
    • Q 18.21.3 : What terms must a data use agreement include?18-35
  • : Addressing Breaches of Protected Health Information18-36
  • Q 18.22 : What is a “breach” of protected health information?18-36
    • Q 18.22.1 : Are there situations where the unauthorized acquisition, access, use or disclosure of unsecured protected health information is not a breach?18-36
    • Q 18.22.2 : Other than these three exceptions, is any acquisition, access, use, or disclosure of protected health information contrary to the Privacy Rule deemed a compromise of the privacy or security of such information?18-38
    • Q 18.22.3 : What if the information is in the form of a limited data set?18-39
  • Q 18.23 : How do you know when a breach occurs?18-39
  • Q 18.24 : What should a medical device manufacturer do if a breach occurs?18-39
    • Q 18.24.1 : What mitigation steps are required?18-40
    • Q 18.24.2 : When is notification required?18-40
    • Q 18.24.3 : What is “unsecured” protected health information?18-40
    • Q 18.24.4 : What technologies and methodologies has HHS specified?18-41
    • Q 18.24.5 : Does adopting HHS standards and methodologies allow a medical device manufacturer subject to HIPAA to avoid other laws or regulations that otherwise require notification?18-42
    • Q 18.24.6 : What are a medical device manufacturer’s obligations regarding notification?18-42
    • Q 18.24.7 : What should the notification say?18-43
    • Q 18.24.8 : Where do you send the notice?18-43
    • Q 18.24.9 : What if current contact information for the affected individuals is not available?18-43
    • Q 18.24.10 : How is substitute notice provided?18-44
    • Q 18.24.11 : When must notice be provided?18-44
    • Q 18.24.12 : What if the breach occurred at the business associate?18-45
  • : Coordinating HIPAA with Other Laws18-46
  • Q 18.25 : How does HIPAA work with state laws that also protect health information?18-46
    • Q 18.25.1 : What is preemption?18-46
    • Q 18.25.2 : How does HIPAA address preemption?18-46
    • Q 18.25.3 : What are “contrary” laws?18-46
    • Q 18.25.4 : What are the exceptions?18-46
    • Q 18.25.5 : What if the state law touches on the same subject but is not contrary to the federal law?18-47
  • Q 18.26 : What are examples of state laws that may preempt HIPAA?18-48
    • Q 18.26.1 : How would the state laws preempt?18-48
  • Q 18.27 : Are state laws the only ones at issue?18-48
  • Q 18.28 : How do you know whether you are compliant with the right laws?18-48
  • Q 18.29 : Does preemption apply to breach notification requirements?18-49
  • Q 18.30 : Are medical device manufacturers likely to experience breaches of unsecured protected health information?18-49
Chapter 19: Litigation, Products Liability, and Preemption
  • : Litigation Theories and Defenses19-3
  • : Overview19-3
  • Q 19.1 : What are typical products liability claims brought against the makers of medical devices?19-3
  • Q 19.2 : What claims have emerged in recent years?19-5
  • Q 19.3 : What litigation issues arise regarding the training of medical personnel to use medical devices?19-8
  • Q 19.4 : What potential issues arise out of company personnel being present during medical device procedures?19-9
  • : The Learned Intermediary Defense19-11
  • Q 19.5 : What is the learned intermediary defense?19-11
  • Q 19.6 : What is off-label use of medical devices?19-12
  • : Communications About Medical Devices19-13
  • Q 19.7 : What is off-label promotion of medical devices and are there safe harbors for certain off-label communications?19-13
  • Q 19.8 : What litigation issues arise concerning scholarly articles about medical devices?19-17
  • : Admissibility in Products Liability Actions19-18
  • Q 19.9 : What standards govern testimony about whether a medical device caused an injury?19-18
  • Q 19.10 : What is the role of “human factors” experts in medical device litigation?19-19
  • Q 19.11 : What is the role of foreign regulatory actions in U.S. litigation?19-20
  • : Spoliation19-21
  • Q 19.12 : What is spoliation?19-21
  • : Preemption19-22
  • Q 19.13 : What is preemption?19-22
  • Q 19.14 : What is the express preemption provision of the Medical Device Amendments?19-23
  • : Express Preemption for Premarket Approved (PMA) Medical Devices and Investigational Device Exemptions (IDEs)19-23
  • Q 19.15 : Are claims involving premarket approved (PMA) medical devices and investigational device exemptions (IDEs) preempted?19-23
  • Q 19.16 : What types of claims involving PMA devices can survive under Riegel?19-25
  • : Express Preemption for 510(k) Medical Devices19-27
  • Q 19.17 : Are claims involving 510(k) medical devices preempted?19-27
  • : Implied Conflict Preemption19-28
  • Q 19.18 : What is Buckman preemption?19-28
  • Q 19.19 : Beyond preemption, what state law safe harbors are available to medical device manufacturers that comply with federal standards?19-30
  • : FDA Considerations Potentially Affecting a Preemption Defense19-31
  • Q 19.20 : What has FDA said about the scope of preemption under the FDCA provisions applicable to medical devices?19-31
  • Q 19.21 : What factors in FDA review of a product can affect the availability of a preemption defense?19-34
Chapter 20: FDA Criminal Enforcement
  • : Overview20-4
  • Q 20.1 : What are the criminal provisions of the Federal Food, Drug, and Cosmetic Act?20-4
  • Q 20.2 : Does liability for an individual require participation in the “prohibited act”?20-4
  • Q 20.3 : Does the government prosecute individuals under the strict liability approach?20-5
  • Q 20.4 : Can a “prohibited act” result in felony liability?20-7
  • Q 20.5 : Is the government restricted to only charging individuals and companies using the FDCA?20-8
  • Q 20.6 : Who is subject to prosecution?20-9
  • : Commencing the Investigation20-11
  • Q 20.7 : What causes the government to commence a criminal investigation?20-11
  • Q 20.8 : How important are whistleblower complaints?20-12
  • : Conducting the Investigation20-13
  • : Generally20-13
  • Q 20.9 : Who conducts the investigation?20-13
  • Q 20.10 : Will FDA agents be involved in the investigation?20-14
  • Q 20.11 : How will the investigation be conducted?20-14
  • Q 20.12 : Will the government contact executives and employees directly?20-15
  • Q 20.13 : What should an executive be advised to say and do when approached by the government?20-17
  • Q 20.14 : Can government agents simply seize documents and information from a company?20-17
  • : Search Warrants20-18
  • Q 20.15 : How much evidence is needed to support a search warrant?20-18
  • Q 20.16 : Can a company prepare for the execution of a search warrant?20-19
  • : Grand Jury Investigations20-21
  • Q 20.17 : Will the government conduct a grand jury investigation?20-21
  • Q 20.18 : Will the grand jury investigation involve testimony from individuals?20-22
  • : Refusing to Testify and Penalties20-22
  • Q 20.19 : Can an individual refuse to testify?20-22
  • Q 20.20 : What penalties can be imposed against a company?20-23
  • Q 20.21 : What sentence can be imposed on an individual?20-24
  • : Prosecution and Future Compliance20-26
  • Q 20.22 : What conduct leads to a criminal prosecution?20-26
    • Q 20.22.1 : Have recent court decisions addressed the off-label-promotion theory?20-27
    • Q 20.22.2 : Will the government pursue other potential violations in the regulated industries?20-29
  • Q 20.23 : Can a corporation negotiate successfully once the government has decided to prosecute?20-31
  • Q 20.24 : Can the government insist on an agreement that controls the company’s future conduct?20-32
Chapter 21: Overlapping Jurisdiction with Other Agencies and Law Enforcement Entities
  • : The Centers for Medicare and Medicaid Services21-2
  • Q 21.1 : How is coverage and reimbursement determined for medical devices?21-2
    • Q 21.1.1 : Does FDA approval or clearance guarantee CMS coverage and reimbursement?21-3
    • Q 21.1.2 : What criteria will CMS use in making coverage determinations?21-3
    • Q 21.1.3 : How does CMS review medical devices?21-3
    • Q 21.1.4 : What does CMS require for a device to be covered?21-4
    • Q 21.1.5 : How does CMS code medical devices?21-4
    • Q 21.1.6 : How does CMS determine reimbursement for medical devices?21-4
    • Q 21.1.7 : How long does it take for CMS to make decisions about new medical devices?21-5
  • : Medical Devices Covered by CMS21-5
  • Q 21.2 : What types of medical devices are eligible for coverage and reimbursement determinations?21-5
    • Q 21.2.1 : Does CMS provide reimbursement for IDEs?21-5
    • Q 21.2.2 : What is a Category A Device?21-6
    • Q 21.2.3 : What is a Category B Device?21-7
    • Q 21.2.4 : Does CMS cover Hospital Institutional Review Board–approved IDE devices?21-7
    • Q 21.2.5 : Does CMS cover off-label use of medical devices?21-8
  • : Federal Trade Commission (FTC) Regulation of Medical Device Advertising21-8
  • Q 21.3 : How does FTC regulation of medical devices overlap with FDA regulation?21-8
    • Q 21.3.1 : How is medical device labeling regulated?21-9
    • Q 21.3.2 : How does FDA enforce its labeling requirements?21-9
    • Q 21.3.3 : How does FDA determine whether a device has been misbranded?21-10
    • Q 21.3.4 : Is FTC responsible for regulation of all device advertising?21-10
    • Q 21.3.5 : How are off-label use and promotion regulated?21-11
    • Q 21.3.6 : How does the FTC regulate medical device advertisement?21-13
    • Q 21.3.7 : How does the FTC determine compliance with the FTCA?21-13
    • Q 21.3.8 : How does the FTC enforce the FTCA?21-14
  • : The Federal Communications Commission (FCC)21-14
  • Q 21.4 : How does FCC and FDA regulation overlap?21-14
    • Q 21.4.1 : How does FCC regulation of radio frequencies affect medical telemetry devices?21-15
    • Q 21.4.2 : What is the National Broadband Plan and how are FDA and the FCC addressing the increased use of wireless medical devices?21-16
  • : The Environmental Protection Agency (EPA)21-17
  • Q 21.5 : How does EPA’s regulation of medical devices overlap with FDA’s?21-17
    • Q 21.5.1 : What devices are covered by EPA regulations?21-18
    • Q 21.5.2 : Is EPA approval required to market a pesticidal device?21-18
    • Q 21.5.3 : How does the EPA regulate medical devices containing or manufactured with chlorofluorocarbons and other Class I ozone depleting substances?21-19
  • : The Occupational Safety and Health Administration (OSHA)21-19
  • Q 21.6 : How does OSHA regulation of medical devices overlap with FDA regulation?21-19
    • Q 21.6.1 : How does OSHA regulate PPE?21-19
    • Q 21.6.2 : How does OSHA regulate the use and cleaning of medical devices?21-20
    • Q 21.6.3 : How do OSHA and FDA regulate industrial prescription safety lenses?21-20
  • : The Nuclear Regulatory Commission (NRC)21-21
  • Q 21.7 : How does the Nuclear Regulatory Commission’s regulation of medical devices overlap with FDA’s?21-21
    • Q 21.7.1 : How does FDA regulate radiation-emitting products?21-21
    • Q 21.7.2 : How does the NRC regulate radioactive materials?21-22
  • : The Department of Homeland Security (DHS) and the Department of Defense (DOD)21-23
  • Q 21.8 : How does DHS’s regulation overlap with FDA’s?21-23
    • Q 21.8.1 : What is FDA’s emergency use authorization for medical devices?21-23
    • Q 21.8.2 : What is FDA’s obligation to undertake expedited development and review of medical products upon request by DOD?21-24
    • Q 21.8.3 : How do FDA and the DOD regulate lasers?21-25
  • : The Department of Homeland Security (DHS) and the Bureau of Customs and Border Protection (CBP)21-25
  • Q 21.9 : How does FDA work with CBP?21-25
    • Q 21.9.1 : How does FDA regulate imported medical devices?21-25
    • Q 21.9.2 : How does CBP enforce trade laws on imported medical devices?21-27
    • Q 21.9.3 : Who ensures that medical devices entering the United States are in compliance with FDA requirements?21-27
  • : The Department of Justice (DOJ) and the Office of Inspector General (OIG)21-28
  • Q 21.10 : How are medical devices regulated under health care fraud and abuse laws?21-28
    • Q 21.10.1 : How do the OIG and the DOJ enforce the Anti-Kickback Statute?21-28
    • Q 21.10.2 : How do the OIG and the DOJ enforce the False Claims Act?21-28
    • Q 21.10.3 : Has there been recent enforcement activity by the DOJ and the OIG related to medical devices?21-29
  • : The Securities and Exchange Commission (SEC) and the Department of Justice (DOJ)21-31
  • Q 21.11 : How do SEC regulations overlap with FDA regulations?21-31
    • Q 21.11.1 : Does FDA review public filings and share information with the SEC?21-32
    • Q 21.11.2 : How do the DOJ and the SEC enforce the Foreign Corrupt Practices Act with respect to medical devices?21-32
    • Q 21.11.3 : Are there recent examples of FCPA enforcement against medical device manufacturers?21-33
  • : State Authorities, State Attorneys General, and Other State Agencies21-36
  • Q 21.12 : Does FDA jurisdiction overlap with state laws?21-36
    • Q 21.12.1 : Does FDA coordinate with state attorneys general?21-37
    • Q 21.12.2 : Does FDA receive assistance from state authorities?21-37
  • : Other Players (Consumer Protection Agencies)21-38
  • Q 21.13 : Does FDA jurisdiction overlap with the U.S. Consumer Product Safety Commission?21-38
  • Q 21.14 : What does the National Advertising Review Council do?21-39
  Index
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