Premarket Approval - PMA The route to market for Class III devices - PowerPoint PPT Presentation

FDA Medical Device Industry Coalition Premarket Approval - PMA The “route to market” for Class III devices –Fees required

PM A □ “515(c)” of the Medical Device Amendments of 1976 (but no one calls it a “515(c)”) □ 21 CFR 814 (Humanitarian) □ Required primarily for Class III devices □ All “new” devices, that are not substantially equivalent to a Class I or Class II device are automatically class III –until otherwise acted on

21 CFR 814 Subpart A--General § 814.1 - Scope § 814.2 - Purpose § 814.3 - Definitions § 814.9 - Confidentiality of data and information in a premarket approval application (PMA) file § 814.15 - Research conducted outside the United States § 814.17 - Service of orders § 814.19 - Product development protocol (PDP) Subpart B--Premarket Approval Application (PMA) § 814.20 - Application § 814.37 - PMA amendments and resubmitted PMA's § 814.39 - PMA supplements http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=814

21 CFR 814 Subpart C--FDA Action on a PMA § 814.40 - Time frames for reviewing a PMA § 814.42 - Filing a PMA § 814.44 - Procedures for review of a PMA § 814.45 - Denial of approval of a PMA § 814.46 - Withdrawal of approval of a PMA § 814.47 - Temporary suspension of approval of a PMA Subpart D--Administrative Review [Reserved] Subpart E--Postapproval Requirements § 814.80 - General § 814.82 - Postapproval requirements § 814.84 - Reports

Premarket Approval (PMA) https://www.fda.gov/medical-devices/premarket-submissions/premarket-approval-pma

PMA Device Advice Topics □ Definitions □ Postapproval requirements □ Review Process □ Supplements and □ Fees Amendments □ Application Methods □ Special Considerations □ Application Contents □ Import/Export □ Quality System □ FAQ’s □ Labeling □ Regulations □ Clinical Studies

PM A □ The PMA is required to prove safety and efficacy □ It requires substantial information, study, data, time and money. □ It receives the “most stringent” review □ Often requires bench and animal testing, and human clinical trials

PM A □ There are (primarily): > Original PMAs for new submissions > Modular PMAs > PMA Supplements for changes Real-Time Supplements for “minor” changes > Streamlined PMAs (clinical lab) □ Presubmission meetings are encouraged

Original PMA - Content Name and address of the applicant □ Table of contents specifying volume and □ page number Summary section (10-15 pages) including □  Indications for use  Device description  Alternative practices and procedures  Marketing history(foreign and US)  Summary of studies  Conclusions drawn from the studies

Original PMA - Content □ Acomplete description of the device □ Reference to any performance standard or voluntary standard. □ Technical sections containing data and information in sufficient detail to permit FDA to determine whether to approve or deny the application. □ Results of nonclinical laboratory studies □ Results of clinical investigations involving human □ Justification of a single investigator if applicable

Original PMA - Content □ Bibliography □ One or more samples of the device and its components, if requested by FDA □ Draft copies of labeling □ Environmental assessment if applicable □ Financial certification or disclosure statement or both □ Such other information as FDA may request

And – □ A draft of the FDA releasable Summary of Safety and Effectiveness See PMA database for examples: https://www.accessdata.fda.gov/scripts/cdrh /cfdocs/cfPMA/pma.cfm Pre-approval inspection generally required

PMA database https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm

Original PMA □ Six copies each bound in one or more numbered volumes of reasonable size □ Trade secret or confidential commercial or financial information must be included and identified

PMA –Primary Review Steps □ Administrative review by FDA to determine completeness (filing review) □ In-depth scientific, regulatory, and Quality System review by appropriate FDA personnel □ Review and recommendation by the appropriate advisory committee (panel review) □ Final deliberations, documentation, and notification of the FDAdecision.

The Approval Letter! □ Approved for marketing □ Post approval requirements may include > Restricted sale > Continuing evaluation –Post market Surveillance > Device tracking > Annual reports > QSR requirements (e.g. CAPA)

Device Approvals, Denials and Clearances https://www.fda.gov/medical-devices/products-and-medical- procedures/device-approvals-denials-and-clearances

Approval order (letter) example you have agreed report clinical outcomes conditions of approval collect information required training

Approval letter example expiration dating final labeling http://www.accessdata.fda.gov/cdrh_docs/pdf7/P070014a.pdf

Post-Approval Studies □ When ordered, or “agreed to” □ Tracked on line The CDRH Post-Approval Studies Program encompasses □ design, tracking, oversight, and review responsibilities for studies mandated as a condition of approval of a premarket approval (PMA) application… The program helps ensure that well-designed post- □ approval studies (PAS) are conducted effectively and efficiently and in the least burdensome manner Guidance Document: Procedures for Handling Post-Approval Studies Imposed by PMA Order https://www.fda.gov/regulatory-information/search-fda-guidance- documents/procedures-handling-post-approval-studies-imposed-pma-order

Generic Conditions of Approval □ Requirements for PMAsupplements □ Post approval reports □ Adverse reaction and device defect reporting □ M D R reporting

Also on line □ Summary of Safety and Effectiveness □ Labeling Professional □ Patient (when applicable) □ □ Consumer Information

PMA FEESFOR FY 2020 □ Premarket Application - $341K □ Small Business - $85K □ 180-Day PMA Supplement - $51K □ Small Business - $13K □ Real-time PMA Supplement - $24K □ Small Business - $6K □ 30-Day Notice - $5K □ Small Business - $3K

PMA Web Listing

Questions?

FDA Medical Device Industry Coalition IDE HDE Investigational Device Exemption Humanitarian Device Exemption

IDE –Investigational Device Exemption □ Required for all clinical trials or testing of devices on humans, whether or not for marketing submission data □ “Exemption” is a bit of a misnomer—you are exempt from certain provisions having to do with legally marketed devices…but you have another set of regulations to deal with instead

IDE –21 CFR 812 Subpart A--General Provisions § 812.1 - Scope. § 812.2 - Applicability. § 812.3 - Definitions. § 812.5 - Labeling of investigational devices. § 812.7 - Prohibition of promotion and other practices. § 812.10 - Waivers. § 812.18 - Import and export requirements. § 812.19 - Address for IDE correspondence. Subpart B--Application and Administrative Action § 812.20 - Application. § 812.25 - Investigational plan. § 812.27 - Report of prior investigations. § 812.30 - FDA action on applications. § 812.35 - Supplemental applications. § 812.36 - Treatment use of an investigational device. § 812.38 - Confidentiality of data and information.

IDE –21 CFR 812 Subpart C--Responsibilities of Sponsors § 812.40 - General responsibilities of sponsors. § 812.42 - FDA and IRB approval. § 812.43 - Selecting investigators and monitors. § 812.45 - Informing investigators. § 812.46 - Monitoring investigations. § 812.47 - Emergency research under 50.24 of this chapter. Subpart D--IRB Review and Approval § 812.60 - IRB composition, duties, and functions. § 812.62 - IRB approval. § 812.64 - IRB's continuing review. § 812.65 - [Reserved] § 812.66 - Significant risk device determinations.

IDE –21 CFR 812 Subpart E--Responsibilities of Investigators § 812.100 - General responsibilities of investigators. § 812.110 - Specific responsibilities of investigators. § 812.119 - Disqualification of a clinical investigator. Subpart F [Reserved] Subpart G--Records and Reports § 812.140 - Records. § 812.145 - Inspections. § 812.150 - Reports.

IDE Also □ 21 CFR 50, Protection of Human Subjects □ 21 CFR 56, Institutional Review Boards, □ 21 CFR 54, Financial Disclosure by Clinical Investigators

IDE https://www.fda.gov/medical-devices/premarket-submissions/premarket-notification-510k

IDE □ Pre-IDE discussions are encouraged □ Process depends on degree of risk Significant or Nonsignificant risk > Significant: IRB FDA > Nonsignificant: IRB only Note: In some Guidance Documents the degree of risk is defined, e.g. all spinal implants are significant risk

IDE –Contents –Significant □ Name and address of sponsor □ Complete report of prior investigations □ Investigational plan □ Design and manufacturing information □ Sample agreement and investigator certification □ Registered clinical trial and…

IDE –Contents –Significant □ All IRBapprovals □ Device charges if any □ Labeling □ Informed consent □ Other