FDA test

cost of de novo submission

$145k

510(k) cost

$21k

original PMA cost

$483k

30-day notice for manufacturing changes

$7k' risk of conversion by FDA to 135 day supplement

general controls

- electronic establishment registration (annual Oct - Dec) - Electronic device listing - quality systems regulations - labeling regulations - medical device reporting (MDR) - premarket notification

1937

100 people died after ingesting a liquid version of a sulfa drug prepared using diethylene glycol, resulted in the Federal Food, Drug and Cosmetic Act of 1938

panel track supplement

180 day review; $386k

traditional 180-day supplement

180 day review; $72k

special 510(k)

30 day fda review; use of design controls to assure substantial equivalence for device modifications

premarket notification

510(k); marketing clearance process; majority of class I are exempt but majority of class II must do this

abbreviated 510(k)

90 day fda review (average review is less); claim conformance with recognized standards

traditional 510(k)

90 day fda review; demonstration of substantial equivalence to legally marketed device in U.S

form FDA 3514

CDRH premarket review submission cover sheet

CDRH

Center for Devices and Radiological Health; purpose is to protect and promote the public health

warning letters / nonconformances

FDA 483; observations of non-compliance or violation during inspection

investigational device exemption

FDA application that allows the sponsor to conduct a human clinical trial to gather safety and efficacy data to support a PMA or 510k submission; sponsor submits all in vitro and in vivo animal study data to show that the device is safe to test in humans

1906

Pure Food and Drug Act passed in response to Upton Sinclair's The Jungle

q-sub/presubmission

a formal submission to fda requesting feedback to guide product development, clarify submission requirements, review of study protocols, application preparation; voluntary with no fees; fda provides written feedback and a meeting can be requested

pma post approval studies

additional clinical studies or longer follow-up; section 522 post-market surveillance studies; additional laboratory studies

1848-1902

adulterated malaria drugs from Mexico for US troops resulted in the Drug Important Act, Bureau of Chemistry, and Poison Squad

Tamper Resistant Packaging Regulations

any attempt to corrupt packaging must be 'visibly evident'

medical device

any healthcare product that does not achieve its principal intended purpose by chemical action or by being metabolized

1962

birth defects in EU due to a sedative containing thalidomide; resulted in the Drug Efficacy Amendment of 1962

Medical Device Amendments of 1976

categorized medical devices based on risk; required medical devices to meet certain performance standards; mandated adverse event reporting

when to use q-sub

clarification on regulatory pathway, predicate device; animal study protocol review; amount of pre-market or post-market clinical data required; clinical study plan review

device classes

class I, II, III

q-sub submission elements

cover letter, detailed device description, proposed intended use/indications for use; overview of product development; summary of previous discussions or submissions regarding the same device; specific questions for fda feedback (or they won't give feedback)

real time supplement

decided on a case by case basis; review time 60-90 days; $33k

formal early collaboration meetings

determination or agreement meetings

submission issue meetings

discuss deficiencies identified during the review of a pma, 21 day time frame

day 100 meetings

discuss review status of pma application; request in original pma application or within 70 days of pma filing

efs

early feasibility study

Pure Food and Drug Act

established minimum level of purity in food and food preparation practices, prohibited interstate commerce of misbranded and adulterated food and drugs; forbade false label statements about identity or ingredients of drugs

study risk determinations

fda helps sponsors, clinical investigators, or IRB make study risk determination, official letter

510k required forms

form FDA 3514, form FDA 3654, FDA CDRH acceptance checklist for 510k

Drug Efficacy Amendment of 1962

governed the reporting of adverse events and contraindications

special controls

guidelines/guidance for specific devices; mandatory performance standards; special labeling

product rejection

health authority scrutiny over future submissions and refuse to grant approval

class III

high risk; subject to general controls and premarket approval; devices are approved

suspension of license or registration

inability to sell existing products

cover letter

include preferred method to receive FDA feedback; propose meeting dates/times; list of attendees

additional types of q-subs

informational meetings, study risk determinations, formal early collaboration meetings, submission issue meetings, day 100 meetings

510k labeling requirements

instructions for use; labels affixed to device and its packaging; promotional material; training material; patient labelling; predicate device labelling

510k executive summary/device description requirements

intended use; device classification; principles of operation; new features/summary of change; predicate device; list of disposables and accessories; configurations/variants/identification of a device; technical and electrical description; materials in contact with dialysate, concentrates, and water

IDE

investigational device exemption

fda post approval/clearance activities

labeling promotion; change controls; complaints; field actions/recalls; additional submissions

litigation

lawsuits against entities or specific individuals; criminal prosecution, possible prison time

predicate device

legally marketed device in the US that a new device can be shown as substantially equivalent to or just as safe and effective as

class I

low risk; subject to general controls

510k required design and manufacturing information

manufacturing flow chart

when 510(k) is required

marketing class I or II non-exempt device for first time or significant change to existing device that can effect safety and efficacy

class II

medium risk; subject to general controls and special controls; devices are cleared

q-sub timeframe

minimum of 75 days; written feedback received approximately 5 days prior to scheduled meeting

1840 to post civil war

no regulations on food or drugs

when de novo classification request is required

novel medical devices classified into class I or class II; no legally marketed predicate device; general and special controls provide reasonable assurance of safety and effectiveness for the intended use; devices maybe used as predicates for future premarket notifications

pma supplements

panel track supplement; traditional 180-day supplement; real time supplement; 30-day notice for manufacturing changes; special supplement - changes being effected

510k

primary mechanism by which FDA reviews medical devices for safety and effectiveness; manufacturer demonstrates substantially equivalence to a device cleared prior to 1976; results in a cleared device

FDA authority over medical devices

proviced by the Medical Device Amendments of the Federal Food Drug and Cosmetic Act and Title 21 Code of Federal Regulations Parts 800-1299

when not to use a q-sub

request for general information or questions; FDA will not design protocols or clinical trial designs; interactive review of an active submission; an appeal of a premarket submission decision

Federal Food Drug and Cosmetic Act of 1938

required drugs to be cleared for safety prior to market introduction

510k other requirements

risk management, risk analysis, substantial equivalence discussion

S&E

safety and efficacy

informational meetings

share information with fda, no fda feedback/listening only, 90 day timeframe

early feasibility study

small clinical study that assesses technical feasibility of a device design or procedure but does not assess device safety or efficacy

debarment

specific person(s) prohibited from working in the medical field; the list is public

form FDA 3654

standards data report form

pma post approval standard requirements

submission of final labeling and annual reporting requirements

SE

substantial equivalence

510k device specification requirements

technical specification, previous generations of the device

types of 510(k) applications

traditional 510(k), abbreviated 510(k), special 510(k)

510k required statements

truthful and accuracy statement, class III summary and certification, financial certification or disclosure statement, declaration of conformity and summary reports

1982

tylenol cyanide scare resulting in tamper resistant packaging regulations

pivotal study

under IDE; large clinical study to prove the device is safe and effective in humans; primary clinical study for regulatory submissions; statistically drive study

special case supplement changes being effected

used for limited additions to quality steps and labeling to increase safety; no fee

manufacturer consequences

warning letters (FDA 483)/nonconformances; suspension of license or registration; debarment; product rejection; litigation; customer perception