Device Exam Questions
What are the requirements for promotion and advertising?
" 21CFR801 is the main labeling regulation for devices. Promotional materials are considered other labeling. There is no specific regulation governing advertising of devices drugs. All devices require directions for use unless specifically exempted. All device labeling claims and implied claims require substantiation. FTC generally regulates device advertising, except for restricted devices: most class III devices are restricted devices by PMA order. Section 502® of the act has specific labeling requirements for restricted devices analogous to the brief summary required for drugs. No requirement to pre-submit promotion and advertising materials at the time of initial release. Within labeling requirements, recommended that instructions be clear, concise and understandable. No requirement to submit promotion and advertising materials at the time of initial dissemination as for drugs. "
What is the 1991 FDA Intercenter agreement between CBER and CDRH?
"Describes product characteristics or medical indications that require a collaborative review effort by the two centers and regulatory jurisdiction for biologic product and medical devices is clearly stated. CBER has the responsibility for regulating all in vitro tests. http://www.fda.gov/CombinationProducts/JurisdictionalInformation/ucm121175.htm"
What are design history files?
(For each type of device): contains or reference the records necessary to demonstrate that the design was developed in accordance with the approved design plan and the general requirements of design control. All approved changes to a cleared device needs to be chronicled in the DHF.
What is the purpose of Medical Product Safety Network?
(MedSun): an enhanced surveillance network comprised of approx 280 hospitals nationwide that work interactively with FDA to better understand and report on device use and adverse outcomes in the real-world clinical environment.
What are they different types of premarket approval applications?
(there are several types of PMA: traditional, Product development process, modular PMA, streamlined PMA, HDE)for class III devices, in depth scientific review of the safety and effectiveness of a device in its own right, review standard: reasonable assurance of safety and effectiveness, FDA holds an advisory panel meeting for many, but not all PMAs. (Key PMA Contents: administrative information, device description, manufacturing information (FDA generally conducts pre-approval GMP inspection), bench, animal, clinical data, labeling, summary of safety & effectiveness data.
FDA is authorized to regulate advertising for what types of medical devices? 1)Restricted devices, 2) Non-restricted devices, 3) all medical devices, 4) None- the FTC oversees advertising
1) Restricted devices
A physician reports to a manufacturer that a patient was hospitalized with acute sepsis after treatment with an approved device. This side effect is not listed in the package insert. This event must be reported by the manufacturer to FDA no later than: 1) 5 calendar days, 2) 15 calendar days, 3) 30 calendar days, 4) the next quarterly report
1)5 calendar days (review)
How are the DMR, DHF related?
1. The finished design output is the basis for the DMR (Device master record). The results from the design review with be documented in the Design History File. Design verification will be documented in the Design History File. The design history file forms the Device Master Record.
What are the different types of PMAs?
1. The product development protocol: PDP, for class III devices subject to premarket approval, the successful completion of a PDP results in market clearance and essentially is a PMA approval.2. Modular PMA: must meet with FDA (pre-ide meeting) to develop the PMA shell. Then each module is submitted to FDA as it is completed. The target review period is 90 days for fda for each module and amendment submitted. Upon receipt of final module a PMA # is assigned and 180 review day clock will start. Entire PMA user fee is due at first module submission. 3. Streamlined PMA: designed for devices using well-known technologies for well known disease processes. To qualify: device has a guidance, two of more previous PMAs have been approved for the same type of device or the device has a study protocol jointly developed by the manufacturer and FDA. Manufacturing facility inspection may be deferred if FDA completed a GMP inspection in the past 2 years. Same review time as traditional pma. 4. HDE
A medical manufacturer is preparing a submission that requires a Declaration of Conformity with design control requirements. What type of submission is the manufacturer preparing to submit to FDA? 1) A PMA 2) A special 510k, 3) an individual device exemption (IDE), 4) an annual report for a PMA
2) special 510k
When design validation activities are being performed by a manufacturer, which element is NOT included as a requirement under the device design validation section of QSR? 1)Conformance to defined user needs and intended uses, 2) testing of production units under actual or simulated use conditions, 3) software validation and risk analysis where appropriate, 4) translation of device design into production specifications
2) testing of production units under actual or simulated use conditions
Where are the GMPS located for devices?
21 CFR 800
An important distinction of a Humanitarian Device Exemption (HDE) is that: 1) The HDE application must contain the same information as a PMA 2) An HDE application is not required to contain the results of scientifically valid analytical safety studies 3) An HDE application is not required to contain the results of scientifically valid clinical investigations demonstrating effectiveness for its intended purpose. 4) An HDE application must be submitted within 30 days after marketing begins.
3) An HDE application is not required to contain the results of scientifically valid clinical investigations demonstrating effectiveness for its intended purpose
While reviewing complaint files for a drug-eluting stent, a single entity combination product, it was noticed that an adverse event had occurred and a patient was hospitalized for two additional days. Such an adverse event was a foreseeable event and the mechanical features of the stent contributed to the occurrence. As a regulatory professional, your decision regarding the adverse event reporting would be: 1) Report to FDA in a 15 day alert report, 2) No action is needed as ADE reporting is only required for serious and unexpected adverse events; this ADE is expected so no reporting is needed. 3) report to FDA in form 3500A(MDR) within 30 days of becoming aware of the event. 4) Report to FDA within seven calendar days of becoming aware of the event.
3) Report in 30 days on Form 3500A
According to the Quality System Regulation, when an investigation of a complaint is conducted, all of the following are requirements for inclusion in the record of the investigation except: 1) the dates and results of the investigation, 2) the nature and details of the complaint, 3) changes in procedures correcting quality problems, 4) any reply to the complainant
3) changes in procedures correcting quality problems
Advertising and promotional materials are required to be submitted to FDA at the time of initial dissemination or publication for all prodcuts EXCEPT: 1) prescription drugs, 2) biologics, 3)non-restricted devices and OTC drugs, 4) none, all products require submission of advertising and promotional material.
3) non-restricted devices and OTC drugs
How many days does the FDA have to review a special 510k, abbreviated 510k and traditional 510k?
30 (special), 90 (abbreviated), 90 (traditional)
A company intends to add an indication for use to a 510k device that is currently being marketed, but which has not yet been distributed. Which type of submission is most appropriate? 1) A PMA, 2) An investigational device exemption, 3) a special 510k 4) a traditional or abbreviated 510k
4) traditional or abbreviated 510k
What does it mean to submit a modular PMA?
50% of PMAs use this approach. Increases efficiency and effectiveness. Sponsor can submit modules as the sections become complete ( review sections) FDA assigns a review team that should remain stable throughout the process. Requirements for each module will be determined by agreement between FDA and sponsor. 90 review process.
What is a real time supplement?
90 FDA days. Standard 180-day supplement: 180 FDA days. a supplement to an approved premarket application or premarket report under section 515 that requests a minor change to the device, such as a minor change to the design of the device, software, sterilization, or labeling, and for which the applicant [PMA holder] has requested and the agency has granted a meeting or similar forum to jointly review and determine the status of the supplement
What does the IDE contain?
: investigational plan: clinical protocol, risk analysis, device description, monitoring procedures, labeling, informed consent document, investigator information, institutional review board (ethics committee) information. Report of prior investigations: bench, animal, prior clinical studies, manufacturing information, administrative sections. This can be several volumes,
What is QSIT?
A quality systems inspections technique: 1. Corrective and Preventative Action 2, Design Controls, 3. Production and Process controls, 4. Management Controls, 5. Records/Documents/Change Controls, 6. Material Controls, 7. Facility and Equipment Controls
When would you schedule a determination meeting?
A sponsor or applicant anticipating the submission of a PMA may submit a written request to discuss the type of valid scientific evidence that will be necessary to demonstrate that the device is effective for its intended use. This meeting is to focus on the broad outline of clinical trial design. The request and summary information for a meeting should be submitted as a pre-IDE submission and identified as a determination meeting request. FDA's determination is provided to the applicant in writing within 30 days following the meeting.
When would you schdeule an agreement meeting?
A sponsor or applicant may submit a written request for a meeting to reach an agreement with FDA regarding FDA's review of an investigational plan (including a clinical protocol). The request and summary information should be submitted as a pre-IDE submission and identified as an agreement meeting request. This meeting should take place no later than 30 days after receipt of the request. The written request should include a detailed description of the device, a detailed description of the proposed conditions of use of the device, a proposed plan (including a clinical protocol) for determining whether there is a reasonable assurance of effectiveness, and, if available, information regarding the expected performance of the device. If an agreement is reached between FDA and the sponsor or applicant regarding the parameters of an investigational plan (including a clinical protocol), the terms of the agreement are put in writing and made part of the administrative record by FDA.
A medical device company has received a warning letter because mold has been found in two batches of its product. The letter cites that the product is: Quarantined, Adulterated, Misbranded, Fraudulent
Adulterated
How do manufacturers of devices demonstrate performance specifications and standards?
By Non-clinical safety and effectiveness data. May include: animal studies, bench testing, biocompatibility, software verification/validation, electromagnetic compatibility/interface, and other tests appropriate to the device. Test protocols and results, interpretation of results, explanation of how results demonstrate safety and effectiveness. Drawings/prints, proposed labeling, instructions for use, marketing materials.
What type of change would require a new PMA?
Certain changes may require the submission of a complete new PMA. If any of the following changes occur, the applicant should consult the appropriate reviewing branch in the Office of Device Evaluation if: the design change causes a different intended use, mode of operation, and technological basis of operation, there will be a change in the patient population that will be treated with the device, or the design change is so significant that a new generation of the device will be developed.
Describe the difference types of recalls
Class I recall: a situation presenting a reasonable probability that the use of or exposure to a violative product will cause serious adverse health consequences or death. Class II: a situation in which use of or exposure to a violative product may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote. Class III: a situation in which use of or exposure to a violative product is not likely to cause adverse health consequences. Don't need to be reported to FDA (but FDA does want them reported).
What are the requirements for reporting recalls?
Class III recalls do not need to be reported, however FDA prefers that you do. All recalls must be reported within 10 working days.
When would you schedule a pre-investigational device exemption (Pre-IDE)?
Considered a "type B" meeting, typically 60 day review process, opportunity for sponsors to obtain FDA guidance, originally started for IDE related clinical protocols, but now used more widely (animal, bench, regulatory pathway) even if IDE is not necessary. FDA provides feedback by meeting, telephone or email.
What is the humanitarian deice exemption to the CDRH?
Contents in 21 CFR 814.104. Approval Standard: Safety and Probably Benefit. Nominally a 75 day review process.
A Special 510k requires _________ along with the submission with the design control requirements
Declaration of conformity
What is a formal guidance meeting and what are the two types?
Determination Meeting: a sponsor anticipating the submission of a PMA submits a written request to discuss the types of valid scientific evidence necessary to demonstrate the device is effective for its intended use. The request and summary information should be submitted as a Pre-IDE submission and identified as a determination meeting request. FDA's determination will be provided in writing 30 days. Agreement meeting: Sponsor submits a written meeting request to reach an agreement with FDA regarding the agency's review of an investigational plan (including a clinical protocol). The request and summary information should be submitted as a Pre-IDE submission and identified as an agreement meeting request. This meeting should take place no later than 30 days after receipt of request. Written request includes a detailed description of the device, proposed conditions of use of the device, a proposed plan (clinical protocol) for determining whether there is a reasonable assurance of effectiveness, and if available , information regarding the device's expected performance. If sponsor and FDA are in agreement regarding the investigational plan including clinical protocol the terms of the agreement are put into writing and made part of the administrative record by FDA.
The document required by the Quality System Regulation (QSR) that tracks each device's manufacture by unit, lot and batch is the:
Devices History Record
What is the FDA review process for a 510k?
FDA focus: scientific soundness of study, protection of subjects' rights, safety, welfare; 30 review period- study "deemed approved" if FDA does not act in 30 days (rare), FDA actions on an IDE: approve (may include staged approval), approve with conditions (may begin study after correcting certain deficiencies in application), disapprove.
What is an annual report change or 30 day supplement?
FDA may allow certain changes to be reported in an annual report or 30-day supplement an instead of a PMA supplement submission. (If this method is utilized, FDA will typically request that the information be reported in the annual report and not as a 30-day supplement.) FDA will notify applicants of this alternative through an advisory opinion to the affected industry or in correspondence with the applicant. FDA will identify a change to a device for which the applicant has an approved PMA and for which a PMA supplement is not required under 814.39(a). FDA will identify such a change in an advisory opinion under §10.85, if the change applies to a generic type of device. Such changes will be identified in written correspondence to each PMA holder who may be affected by FDA's decision. FDA will require that a change, for which a PMA supplement under §814.39(a) is not required, to be reported to FDA in a periodic (annual) report or a 30-day PMA supplement. In written correspondence, FDA will identify the type of information that is to be included in the report or 30-day PMA supplement. If FDA requires that the change be reported in a periodic report, the change may be made before it is reported to FDA. If FDA requires that the change be reported in a 30-day PMA supplement, the change may be made 30 days after FDA files the 30-day supplement, unless FDA informs the PMA holder that additional information is required, the supplement is not approvable, or the supplement is denied. The 30-day PMA supplement must follow the instructions in the correspondence or advisory opinion. Any 30-day PMA supplement that does not meet the requirements of the correspondence or advisory opinion will not be filed and, therefore, will not be deemed approved 30 days after receipt. The applicant is encouraged to contact the PMA staff to assist in determining if the change meets the requirements of §814.39(e).
What is the requirement for postmarket surveillance studies?
FDA may order a manufacturer of certain class II or class III devices to conduct postmarket surveillance studies "522 studies". Nonclinical device testing, analysis of existing clinical databases, observational studies, randomized controlled trials.
What is the requirement for post approval studies?
FDA may order post approval studies as a condition under PMA approval. Used to address device safety, effectiveness, and/or reliability.
What does it mean when FDA says "use of consensus standards"?
FDA recognizes specific national and international consensus standards during the premarket submission review process. Companies may provide declaration of conformity to these standards, including any ways standard adapted/modified. (Need to consider extent of FDA's recognition (may be only some aspects); often need to provide data demonstrating compliance with the standard). Standards address many aspects of safety and effectiveness for affected devices, but often not all aspects.
What does the least burdensome mean?
FDAMA (1997) requires FDA to eliminate unnecessary burdens in regulatory process. The statutory requirements for clearance and approval remain unchanged. FDA must consider the least burdensome means of: evaluating device effectiveness that would have a reasonable likelihood of resulting in approval; demonstrating substantial equivalence and request information accordingly
What does third party review mean?
FDAMA established Accredited Persons Program. Can be companies or individuals that are authorized to perform 510k review for certain class II devices. The product classification database includes if any are authorized to perform third party review for the device classification. Not subject to FDA user fee. Shorter review times, responsiveness to questions, expertise in testing, standards and international requirements. Local service, depending on location of the third party reviewer.
What is a PMA manufacturing site change supplement?
For moving the manufacturing site if certain conditions apply. Manufacturing site must have received a Quality System/GMP inspection within the last two years. If requirements are not met, 180-day PMA Supplement must be submitted.
What are the quality management system subsystems?
Management, Corrective and Preventive Actions, Production and Process Controls, Equipment and Facility Controls, Records, Documents, Change Controls, Material Controls, Design Controls.
What are the enforcement process?
Notices of Violations/Untitled letters: for least violative practices that in the agency's opinion do not greatly jeopardize the public health. Company must stop using material that the agency found violative. Warning Letters: addressed to CEO, cease use of violative materials and may require corrective actions. Judicial Action: injunctions, seizures, or criminal prosecutions. Company can also enter in a "consent decree" where there are severe restrictions on the company operations until the company is in compliance.
What is the review process for PMA?
PMA review has 4 broad stages, initial screening review (15 calendar days/administrative completeness), filing review (45 days, focus: company did what it set out to do; sufficient information to conduct in depth review. In-depth scientific and regulatory review ("substantive interaction" within 90 calendar days), review and recommendation by an FDA advisory committee ("panel") not necessary for all PMA's, FDA premarket quality system inspection. Additional submissions during course of review are called "PMA amendments"; 180-day review process by law and regulation: review clock may be stopped or reset if additional information is necessary or submitted, depending on the scope/extent; current performance goals: for submissions that do not require Advisory Committee input, FDA will issue a MDUFA decision within 180 FDA days for 70% of PMAs received in 2013 (ramping up to 90% in FY 2017).
What is humanitarian use designation?
Request for HUD designation from OOPD. Contents described in 21 CFR 814.102. Precisely define indication for use- any medically plausible subset must be justified. Documentation <4,000 patients/year. 45 days to approve, disapprove, request AI.
For Medical Devices what is the requirement for establishment registration and product listing?
US establishment owner or operator that initiates or develops medical device specifications; manufactures, assembles, processes, repackages, or relabels medical devices For domestic human use; or is the initial importer of medical devices must register the establishment annually and submit medical device listing information. Registration must happen 30 days prior to starting any operations at the establishment for production or commercialization of finished devices. FURLS is the device registration and listing electronically.
what is a 30 day notice/ 135 day PMA supplement?
Used for modifications to manufacturing procedures or methods of manufacture that affect the safety and effectiveness of the device. Changes in a manufacturing/sterilization site or to design or performance specifications do not qualify. If the change qualifies as a 30day Notice, the change may be made 30 days after FDA receives the 30day notice unless FDA informs the PMA holder that the 30-day Notice is not adequate and describes the additional information or action required. If the 30-day Notice was not adequate, but contained data meeting appropriate content requirements for a PMA supplement, then the 30-day Notice will become a 135-day PMA Supplement.
What are device history records?
a copy of the DMR that has been completed (values entered, process steps checked off, initials/signatures applied) during the manufacturer of a batch, lot or unit quantity of medical device product to document the production. (individual batch record for drugs). Has completed forms and reports for each manufactured batch/lot/unit and demonstrates that devices were manufactured in accordance with the DMR. Include: dates manufactured, quantity manufactured, quantity released for distribution, acceptance records that demonstrate that the device is manufactured in accordance with the DMR, primary identification label and labeling used for each production unit, device identification(s) and control number(s) used.
What is a significant risk Device?
a device that is intended as implant and poses a serious risk to patient health, a device whose purpose is to support or sustain life and presents a serious risk to the patient health, a device that is of substantial importance in diagnosing, curing, mitigating or treating disease or in preventing impairment of health and poses a serious risk to patient health, a device that otherwise poses a serious risk to patient health (both FDA and IRB ethics committee approval required).
What does section 801(e) refer to?
a. Ensure that the identified risks have been appropriately flagged and monitored.b. Initiate process to obtain non proprietary (USAN) and proprietary names.
What is the overview big picture review process from FDA standards?
a. Ensure that the project is in compliance regarding submission format (CTD/eCTD, etc.). b. Review application for completeness according to "refuse-to-file" guidelines.c. Negotiate/interact as appropriate with Agency during development/submission process (Pre-IDE/IND, End of Phase 2, Meetings, Respond to Agency comments, etc.).d. Monitor and maintain ongoing IDE/IND applications (e.g., amendments, annual reports, updates).e. Determine requirements for export/import of investigational products (customs, USDA, etc.).
What does approvable mean (in regards to PMA)?
additional information is necessary before PMA can be approved.
What are the contents of a 510k?
administrative information, executive summary(not in regs but in guidance) , 510k summary or 510k statement, indications for use statement, truthful and accuracy statement, class III summary and certification, financial certification/disclosure statement, device description, substantial equivalence, labeling, sterilization, test data (bench, biocompatibility, animal, clinical).
What is required once you have PMA?
approval: all PMAs are subject to certain conditions of approval (annual reports); these requirements often tailored to the individual products (postapproval studies: new study for a particular group of patients, continued long term follow up, special reporting requests.
When can a traditional 510k be used?
can be used for any new type of device or modification. Used for most new devices and significant modifications in intended use or technology. 90 day review process. ~80% of all 510ks.
what is Special PMA supplement?
changes being effected: generally labeling changes to add/strengthen instructions, warnings, contraindication. for any change that enhances the safety of the device or the safety in the use of the device; may be placed into effect by the applicant prior to the receipt of a written FDA order approving the PMA supplement. After FDA approves a PMA, any change described below that enhances the safety of the device or the safety in the use of the device [§814.39(d)(2)] may be placed into effect by the applicant prior to the receipt of a written FDA order approving the PMA supplement, but after the applicant receives specific acknowledgment that the application qualifies for review under §814.39(d)(2) provided that: the PMA supplement and its mailing cover are plainly marked "Special PMA Supplement -- Changes Being Effected;"; the PMA supplement provides a full explanation of the basis for the changes; the applicant has received acknowledgment that the application qualifies as a "Special PMA Supplement -- Changes Being Effected" from FDA for the supplement; the PMA supplement specifically identifies the date that such changes are being effected; and the change is made according to the good manufacturing practices regulation. The following changes are permitted [§814.39(d)(1)]: labeling changes that add or strengthen a contraindication, warning, precaution, or information about an adverse reaction; labeling changes that add or strengthen an instruction that is intended to enhance the safe use of the device; labeling changes that delete misleading, false, or unsupported indications; and changes in quality controls or the manufacturing process that add a new specification or test method, or otherwise provide additional assurance of purity, identity, strength, or reliability of the device. The applicant is encouraged to contact the PMA Staff to assist in determining if the change meets the requirements of §814.39(b).
When would you schedule a Pre-PMA meeting?
considered a "type B" meeting, opportunity for sponsors to obtain FDA guidance prior to application submission-especially clinical data, opportunity to discuss need for panel meeting and eligibly of device for expedited review.
What is the quality procedures?
describe how specific quality system operating processes and controls are implemented. The strength of a set of quality procedures lies in cross functional and interdepartmental linages among associated processes and controls.
What are design controls?
design control requirements are not intended to apply to development of concepts and feasibility studies. FDA will evaluate the process, the methods, and the procedures that a manufacturer has established to implement the requirement for design controls. FDA has amended the IDE regulation, reaffirming that an IDE device is exempted from complying with GMP's... with the exception of Sec. 820.30 "Design controls". FDA will not inspect design controls during bioresearch monitoring inspections. They are applicable to all class II and class III and the following class I devices (devices automated with computer software, tracheobronchial suction catheters, surgeon's gloves, protective restraints, system radionuclide applicator manual, source radionuclide teletherapy.
What is a humanitarian device process?
designation process: designation program administered by FDA's Office of Orphan Product Development (OOPD). Must be for treatment/diagnosis of condition affecting fewer than 4,000 US patients per year. Note: orphan drug is <200,000 total persons in US at any time, not per year. No comparable FDA approved therapy exists. Applicant could not otherwise bring device to market. Less than 10 HDEs/year.
What is a preamemdment device?
device from before 1976, can be used but sponsor should really find a predicate device.
What agency approval is required for abbreviated IDEs?
do not require FDA approval but require IRB approvals. Informed (consent, record keeping and reporting.
What is the quality manual?
document that demonstrates corporate quality policy, describes quality system components and how the system is implemented and assigned authority and responsibilities.
what are some modifications to a 510k that would require a new 510k?
examples that require a new 510k submission: sterilization method, structural material, manufacturing method, operating parameters or conditions for use, patient or user safety features, sterile barrier packaging material, stability or expiration claims, design. When a new 510k is not submitted sponsors should document and file a rationale as to the reasoning.
When would you use a document to file?
for changes that do not affect the safety or effectiveness of the device. very limited or no FDA involvement prior to implementation of the change. Minor manufacturing changes and minor quality control changes can be documented to file. Examples of changes that can be documented to file include editorial changes to a Standard Operating Procedure (SOP) to make instructions clearer and combining two SOPs into one.
What is a180 day PMA supplement?
for significant changes that affect the safety and effectiveness of the device; in-depth review and approval by FDA is required before implementation of the change; A full PMA review including a review by an outside advisory panel may be required. The criteria for a full PMA review includes changes in the device that may raise different types of safety and effectiveness questions or changes in which there may be no accepted test methods for evaluating the issues of safety or effectiveness; Some 180-day PMA supplements may be reviewed using the Real-Time Review process. In this process the supplement is reviewed during a meeting or conference call with the applicant. FDA will fax its decision to the applicant within five working days after the meeting or call. The change must meet certain criteria to be eligible for this type of review. Supplements with detailed clinical data are generally not considered for this program. The criteria and process for the Real Time Review program are outlined in Real-Time Premarket Approval Application (PMA) Supplements.
What does "ne-novo" device mean?
formally called "evaluation of automatic class III designation", for "low risk" devices with no predicate device, traditional approach: FDA issues NSE decision, company has 30 days to respond, new approach: prior 510k/NSE decision not required, the device becomes a new predicate that others can use to claim substantial equivalence. This allows the sponsor to petition FDA to reclassify as Class I/II.
What do GMP and QSR have in common?
good manufacturing practice (GMP) requirements set forth in QSR are promulgated under section 520 of the FD&C act. cGMP: "c" = current (changing), control & management of manufacturing and quality control of pharmaceuticals, medical devices and foods. Fundamental GMP concepts: documentation, quality should be built into the product, and testing alone cannot be relied on to ensure product quality. A drug or device is deemed adulterated unless it is manufactured in accordance with cGMP.
What is the definition of device?
intended to affect the structure of any function of the body of man or other animals, and which does not achieve its primary intended purposed through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes. Devices are short lived and always changing.
What constitutes a misbranded device?
is false or misleading in any way and does not contain adequate directions for use. Prescribed medical devices approved via PMA must include FDA-approved labeling in or within the packaging from which the device is dispensed (failure to do so constitutes misbranding).
What are device master records?
just like the master batch record. Includes approved component and finished device specifications and drawings, and complete printout of approved device software code; production equipment, process and environment specifications, methods and procedures; quality assurance procedures and specifications including acceptance criteria and quality assurance equipment tools and fixtures; packaging and labeling specifications; installation maintenance and servicing procedures.
What is a predicate device?
legally marketed device that was cleared by 510k.
What is the requirement for dissemination of information on unapproved/new uses for maketed drugs, biologics and devices?
manufacturers must submit information at least 60 days prior to dissemination and eventually submit a supplemental application for the new use.
When would a special 510k be used?
may be used for device modifications that do not affect intended use or fundamental scientific technology. Company must certify compliance in the 510k. 30 day review process. ~18% of all 510ks
When would an abbreviated 510k be used?
may be used when device complies with: guidance document, special control, FDA recognizes consensus standard. 90 day review process, ~3% of all 510ks- not widely used.
What is substantial equivalence?
means the new/modified device has the: same intended use as predicate device and same technological characteristics as the predicate device or different technological that don't raise new types of safety or effectiveness questions. Performance data may be necessary to demonstrate equivalence (technological differences will require performance data) (at least as safe and as effective ~10%-15% have clinical data). Must have the same intended for use.
What are the requirements for MDRs?
medical device reporting first came into effect in 1984. MDR regulations were amended by medical device amendments (1992) to establish a single reporting standard for device manufacturers, initial importers, domestic distributors and user facilities. When FDAMA became effective in 1988, four changes affected MDR: manufacturers and distributors/importers did not need to submit annual certification. Domestic distributors were no longer required to file MDR reports, but were required to maintain complaint files. Importers continue to be subject to the remaining requirements of MDR regulation 21 CFR 803. User facilities must now file an annual report instead of semiannual reports to summarize their adverse event reports. Form FDA 3500A
What are device QSR milestones?
medical devices included in 1976 under the amended FD&C act. GMPs for devices added in 1978; codified under 21CFR820. SMDA: addition of design control and harmonized of cGMP and QSR with international standards - ISO 9001:1994 and ISO 13485; QSR went into effect in 1997. QSR applies to all finished devices (includes accessories to the device per 21 CFR 820.3(l)) intended to be commercially distributed for human use unless the device is exempt. Device requirements can be found under 21 CFR 820.
What does not approvable mean (in regardint PMA)?
more serious deficiencies, but PMA can still be approved after the issues are resolved. Denial: rarely are PMAs issued "denial" orders, not approvable more frequent.
Devices that are exempt from premarket notification are:
most Class I and some Class II
What are modifications that would require a new 510k?
new indications for use, modifications to device's "fundamental scientific technology", modification that could impact safety or effectiveness.
What are pre-submissions used for?
opportunity for sponsors to obtain FDA guidance. Originally start for clinical protocols/IDE related but now used more widely even if no IDE is necessary. 75-90 day review process, FDA provides feedback by meeting, telephone, or email
What is an IDE?
permits shipment of devices in interstate commerce for clinical investigation that otherwise adulterated or misbranded because they are unapproved. Provides exemption from complying with the requirement to have a 510(k) or PMA, establishment registration, device listing, MDR, and QSR (except for the design control provisions). 21 CFR 812.
What is a presubmission program?
pre-IDE program for when working on the formal IDE if any questions arise (i.e. clinical protocol design, preclinical testing proposal, preclinical test results, protocols for foreign studies when the studies will be used to support future marketing applications to be submitted to FDA. Response from FDA within 60 days of receipt. Can be used for PMA applications, 510k submissions,
What is a non-significant risk device?
proposed research may be considered non-significant risk study if certain safeguards, fail-safe mechanism, backups, and redundancies in procedure or treatment are included in the study, a non-significant risk device study may be conducted after obtaining the IRB approval, the sponsor makes the initial significant/non-significant risk study determination, sponsor required to provide rationale to IRB of why the study is non-significant risk. If IRB agrees and approves = approved IDE, If IRB disagrees and designates significant risk = Must submit IDE application to FDA & notify IRBs (only IRB ethics committee approval required).
What does the QSR contain?
quality management and organization, device design, buildings, equipment, purchase and handling of components, production and process controls, packaging and labeling control, device evaluation, distribution, installation, complaint handling, servicing, records.
When is a 510k required?
required for most class II and some class I devices. Some class III devices are still subject to 510(k). Required for both new devices and some modified devices. Must demonstrate that the device is substantially equivalent to a predicate device. Predicate device is a legally marketed device that is not subject to a premarket approval (PMA).
What is the QSR?
requires procedures that allow identification and traceability for each unit, lot or batch of finished devices. This is all documented in the device history record (DHR). Differs from medical device tracking: where the manufacturer must be capable of tracking certain devices from manufacturing to distributor to patient.
What is the quality management system?
risk presented by the device, complexity of device and manufacturing processes, size and complexity of organization.
What are detailed work instructions?
specify the individual, intradepartmental steps necessary to consistently and reliably perform specific activities such as those involved in component procurement, inspections, fabrication, assembly, testing, labeling and final acceptance, packaging, shipping, installation, maintenance and servicing of device.
What is an informal guidance meeting?
supporting preclinical data or investigational plan (telephone conference calls, video conference calls or face to face). Sponsor contacts reviewing division directly or may contact IDE staff for assistance
What does device NSE mean?
there is no predicate device, device has a new intended use, device has different technological characteristics compared to the predicate device and raise a new type of question of safety and effectiveness, performance data do not demonstrate that device is at least as safe and effective as the predicate. 2%-3% of 510k are found not substantially equivalent, but this has been rising.
What is a special PMA supplement?
this is used when the change enhances or increases the devices safety.
What is an Pre-IDE meeting?
to obtain guidance prior to submission of IDE application, can also be used to obtain guidance for 510ks. Can also be a Pre-IDE submission.
What did FDASIA implement for devices?
tracking device risk and analyzing public health trends. FDA also has the ability to require postmarketing studies at any time in the product's marketed lifecycle.
What are the MDR timeframes?
user facility: within 10 working days after 1st becoming aware of the event. Importers: not more than 30 calendar days after 1st becoming aware of the event. Manufacturers: two timeframes: within 5 working days after 1st becoming aware of an event requiring remedial action to prevent unreasonable risk of substantial harm to public health. Within 30 calendar days after 1st becoming aware of a report of death, serious injury but could if it were recur. Within 30 days of becoming aware of information that was not provided because it was unknown or unavailable when the initial report was submitted- also known as supplemental or follow-up report.
What is a panel track supplement?
usually for major indication requiring advisory panel review.
What does cGMP require?
various specifications and controls shall be established for devices. Devices shall be designed under a quality system to meet these specifications. Devices shall be designed under a quality system to meet these specifications. Devices shall be manufactured under a quality system. Finished devices shall meet the established specifications. Devices shall be correctly installed, checked, and serviced (where applicable). Quality data shall be analyzed to identify and correct quality problems. Complaints shall be processed.
What is the refuse to accept policy for 510k?
whether the application meetings minimum threshold for acceptability and should be accepted for substantial review. Once submitted FDA has 15 days to complete this review and let the sponsor know whether the 510k is administratively complete. If not complete, FDA will send back and checklist of the missing items which is the basis for the RTA (refuse to accept).
