IVD Enthusiast

I am a regulatory affairs and quality assurance professional in the in vitro diagnostic space. I have a Masters in Biomedical Regulatory Affairs from the University of Washington, and am RAC-device certified. I host this website in my free time, and provide all content free-of-cost. Please note that the content on this website is for informational and educational purposes only, and does not constitute legal or professional advice. All content and opinions shared are solely my own, and not affiliated with any company or organization.
I am a regulatory affairs and quality assurance professional in the in vitro diagnostic space. I have a Masters in Biomedical Regulatory Affairs from the University of Washington, and am RAC-device certified. I host this website in my free time, and provide all content free-of-cost. Please note that the content on this website is for informational and educational purposes only, and does not constitute legal or professional advice. All content and opinions shared are solely my own, and not affiliated with any company or organization.
27
Jan
2024
21 CFR Part 861: Procedures for Performance Standards Development

21 CFR Part 861: Procedures for Performance Standards Development

One of the ways that the FDA ensures the safety and effectiveness of medical devices is by establishing performance standards, which are rules that specify the minimum requirements for certain aspects of device design, construction, performance, or testing.

This regulation describes the procedures for developing, publishing, and revising performance standards, and the role of standards advisory committees in advising the FDA on technical matters related to performance standards. These procedures ensure that performance standards are based on sound scientific, technical, or clinical data, and that they provide reasonable assurance of the safety and effectiveness of medical devices.

Content of Standards

Performance standards established by the FDA include the following elements:

  • The purpose and scope of the standard, including the device or devices to which it applies, the risk or risks that it addresses, and the intended benefit to public health.
  • A description of the performance characteristics or requirements that the device or devices must meet, such as specifications, test methods, limits, or tolerances.
  • The effective date of the standard, and any transitional or compliance periods for manufacturers, importers, or distributors of the device or devices.
  • As applicable, any labeling, recordkeeping, reporting, or postmarket surveillance requirements.

Development and Publication

To develop and publish a performance standard, the FDA…

  • identifies a need for a performance standard for a device or devices, based on scientific, technical, or clinical data, or on recommendations from standards advisory committees, other federal agencies, or external stakeholders.
  • publishes a notice of proposed rulemaking (NPRM) in the Federal Register, which announces the FDA’s intention to establish a performance standard, and invites public comments on the proposed standard.
  • reviews and analyzes the public comments, and consults with standards advisory committees, other federal agencies, or external stakeholders, as appropriate.
  • publishes a final rule in the Federal Register, which establishes the performance standard, and responds to the public comments on the proposed standard.
  • publishes a notice of availability in the Federal Register, which announces the availability of any guidance documents, test methods, or other supporting materials related to the performance standard.

Use of Existing Standards

In some cases, the FDA may adopt an existing standard, such as a national or international consensus standard, as a proposed or final performance standard for a device or devices, if the FDA determines that the existing standard is appropriate and adequate to provide reasonable assurance of the safety and effectiveness of the device or devices. For instance, the FDA is considering adoption of ISO 13485, an international standard for quality systems for medical devices. In such cases, the FDA will follow the same procedures for development and publication as described above, but will also include a reference to the existing standard, and an explanation of any differences or modifications that the FDA made to the existing standard.

Changes to Standards and Effective Dates

The FDA may amend or revoke a performance standard for a device or devices, if the FDA determines that the standard is no longer appropriate or adequate to provide reasonable assurance of the safety and effectiveness of the device or devices, or if the FDA finds new scientific, technical, or clinical data that warrant a change to the standard. The FDA will follow the same procedures for development and publication as described above, but will also include a statement of the reasons for the amendment or revocation, and the effective date of the change.

The effective date of a performance standard is the date on which the standard becomes legally binding for the device or devices to which it applies. The FDA may specify different effective dates for different provisions of the standard, or for different types or classes of devices. The FDA may also provide transitional or compliance periods for manufacturers, importers, or distributors of the device or devices, to allow them time to meet the requirements of the standard.

Standards Advisory Committees

Standards advisory committees are groups of experts that advise the FDA on technical matters related to performance standards for medical devices. The FDA may establish one or more standards advisory committees for a specific device or devices, or for a general area of device regulation. The members of the standards advisory committees are appointed by the FDA, and may include representatives of scientific, professional, industry, or consumer organizations, as well as federal employees or consultants.

The role of the standards advisory committees is to provide the FDA with scientific, technical, or clinical advice, recommendations, or information on the development, amendment, or revocation of performance standards, or on the use of existing standards. The FDA may consult with the standards advisory committees at any stage of the performance standards development process, and may request them to review and comment on proposed or final standards, or on any supporting materials related to the standards.

The standards advisory committees operate in accordance with the Federal Advisory Committee Act, which requires that their meetings be open to the public, and that their records and reports be available for public inspection.

Posted by IVD Enthusiast in IVDs
20
Jan
2024
21 CFR Part 860: Medical Device Classification

21 CFR Part 860: Medical Device Classification

Three Classes of Regulatory Control

The FDA classifies devices into one of three classes based on their risk and regulatory oversight.

Class Risk Level Controls Examples
I Low General Bandages, tongue depressors, dental floss
II Moderate Special + General, premarket notification and clearance Pregnancy tests, blood glucose meters, infusion pumps
III High General, premarket approval Implants, pacemakers, artificial heart valves, companion diagnostics
  • general controls include registration, listing, labeling, good manufacturing practices, and adverse event reporting.
  • special controls include performance standards, postmarket surveillance, patient registries, special labeling, or guidance documents.

Classification Panel

A classification panel is an advisory committee of experts that makes recommendations to the FDA on the classification and reclassification of devices. The FDA has 16 classification panels, each covering a major medical specialty or device type such as Anesthesiology, Cardiovascular, and Pathology.

To simplify regulations for special controls, devices are grouped into generic types of devices, which have similar features and require similar regulatory controls to ensure their safety and effectiveness. Classification panels help the FDA develop a classification regulation for each type of device (see 21 CFR parts 862 through 892). A panel may also recommend whether a class I or II device should be exempt from some or all general or special controls.

Factors that Determine Classification

The FDA classifies a device based on the following factors:

  • Intended users: The persons who will use the device
  • Indications and conditions of use: How, when, and where the device will be used, including labeling and advertising
  • Technological characteristics: The design, material, and performance of the device
  • Benefit-risk profile: The potential benefits and harms of using the device
  • Regulatory necessity: The level of regulation needed to ensure safety and effectiveness
  • Regulatory alternatives: The existing options for regulating the device
  • Reliability: The consistency and accuracy of the device
  • Novelty: The degree of innovation and uniqueness of the device
  • Availability of alternatives: The presence or absence of other devices that serve the same or similar purposes
  • Public health need: The importance and urgency of addressing the medical problem that the device aims to solve
  • Health care system impact: The effect of the device on the cost, quality, and accessibility of health care

Evidence for Classification

For devices that require premarket approval or clearance, the FDA requires valid scientific evidence of safety and effectiveness to classify the device. This includes:

  • Well-controlled investigations: Studies that follow rigorous scientific principles and use appropriate control groups and methods
    • Objectives and methods: The study plan and report should clearly state the goals, the selection and assignment of subjects, the observation and measurement methods, and the comparison and analysis of results.
    • Control groups: The study should use a suitable control group that minimizes bias and allows quantitative evaluation. The study should explain the type and methods of the control group and the degree and methods of blinding, if any.
    • Test device standardization: The study should use a test device that is consistent in its composition, design, and performance to ensure the reliability of the results.
  • Partially controlled studies: Studies that use some but not all elements of well-controlled investigations
  • Uncontrolled studies: Studies and trials that do not use control groups but have other means of ensuring validity and reliability
  • Qualified case histories: Well-documented reports of clinical experience by experts
  • Significant human experience: Reports of widespread and consistent use of a marketed device
  • Nonclinical methods: Laboratory tests, animal studies, or analytical studies for in vitro diagnostic devices, when required, to assess the safety of the device

Note that isolated case reports, random experience, reports lacking details, and unsubstantiated opinions are NOT valid scientific evidence.

How the FDA Evaluates Evidence

The FDA evaluates the quality, quantity, relevance, and applicability of the evidence to the device and its intended use. The evidence must:

  • Demonstrate safety: Show that the device does not pose unreasonable risk of illness or injury for its intended uses and conditions of use, based on valid scientific evidence
  • Demonstrate effectiveness: A device is effective if it produces clinically significant results for most of the target population, under the intended uses and conditions of use, with proper instructions and warnings.
  • Provide directions and warnings: Include adequate instructions and cautions to prevent unsafe use of the device

When submitting evidence, the sponsor must:

  • Comply with any reports or information requests related to the classification of the device and its safety and effectiveness, including the reason, description, time, form, and manner of the report or information.
  • Incorporate by reference any required information that has been previously submitted to the relevant Center.

De Novo Classification

The de novo classification process is for novel devices that are not similar to any existing device or are automatically classified as Class III. The FDA can classify such devices as Class I or II based on their risk and regulation level.

The process begins with a De Novo request from the device sponsor, which includes the device description, proposed classification, benefits and risks summary, scientific evidence summary, and bibliography. The FDA will make a decision within 150 days, and may ask for more information, consult experts or panels, or inspect the device.

The sponsor can withdraw the request before the FDA issues an order, but will not get a refund of the de novo fee. The FDA will grant or decline the request based on the evidence and risk, and will issue an order, publish it in the Federal Register, and update the database. De Novo submissions are confidential until granted.

Reclassification

Reclassification is changing the class of a device. A reclassification petition from an interested person or a device manufacturer or importer contains the type, action, basis, reasons, and data for reclassification. The classification panel will recommend the appropriate class before the FDA or the Commissioner issues an order to reclassify the device. There are five types of reclassification processes, depending on the situation and the law. They are:

  • Based on new or existing information on its safety and effectiveness.
  • Based on new performance standard or information, requiring premarket approval for a Class I or II device.
  • Requiring premarket approval for a Class III device subject to premarket notification.
  • Reclassifying a device without a predicate device (De Novo request).
  • Reclassifying a product that was a drug or biological product before 1976. Each process starts with a petition or notification from the FDA, with panel consultation and public comment.
Posted by IVD Enthusiast in IVDs
13
Jan
2024
21 CFR Part 830: Unique Device Identification

21 CFR Part 830: Unique Device Identification

The FDA requires certain medical devices to have a unique device identifier (UDI) that can be used to identify and track them throughout their distribution and use. A UDI is a code that consists of two parts: a device identifier (DI) and a production identifier (PI). The DI identifies the specific version or model of a device, and the PI identifies the unit of device production, such as the lot or batch number, the serial number, the expiration date, or the date of manufacture. The UDI must be displayed on the device label and package, and in some cases, on the device itself. The purpose is to improve patient safety by making device recalls and postmarket surveillance easier.

UDI Applies to Only a Subset of Devices

The UDI system applies to a subset of devices that are classified by the FDA according to their risk level (see 21 CFR Part 821 for the list of devices and compliance dates).

Issuing UDIs

The UDI must be issued by an FDA-accredited issuing agency, such as GS1, and conform to international standards for data structure and character set. The UDI must use only one DI per version or model of a device, and must not reuse a DI that has been previously assigned to another device.

Global Unique Device Identification Database (GUDID)

The FDA also maintains a Global Unique Device Identification Database (GUDID) that stores the UDI and other information about each device. The GUDID allows the public and health care professionals to access information about medical devices. The labeler of a device, which is usually the manufacturer, is responsible for electronically submitting the UDI and other information to the GUDID no later than the date the label is placed on the device, or the date the device is released for commercial distribution. The labeler must also update the GUDID if any information changes, or if a new DI is required for a device.

The information that must be submitted to the GUDID for each version or model of a device includes:

  • The labeler’s name and contact information, and the name of the issuing agency
  • The DI, and any previous DI that was assigned to the device
  • The device name, and the version or model number
  • Any applicable statements that indicate if the device is sterile, has a permanent marking of the DI, contains natural rubber latex, has safety issues if exposed to magnetic resonance, or has multiple sizes
  • The type of PI that is displayed on the device label
  • The premarket submission number, if any, that was assigned by the FDA
  • The FDA listing number that identifies the device
  • The Global Medical Device Nomenclature (GMDN) term or code that describes the device
  • The number of devices contained in each package

The FDA may grant a waiver or an exception from the UDI requirements for certain devices, or allow voluntary submission of UDI information for devices that are not subject to the requirements.

Significant Changes to Devices Require a New UDI

A new DI is required for a device if there is a change in the device’s specifications, performance, size, or composition that could affect its safety or effectiveness, or if there is a change in the device’s package or labeling. The labeler must notify the FDA of any changes that require a new DI, and update the GUDID accordingly.

Corrections to UDI Data

The FDA may review the GUDID data and request corrections or explanations from the labeler if the data is incorrect or misleading. The FDA may also delete or modify the data if necessary.

Records

The labeler must keep records of all UDIs and the relationship of prior and current DIs for each device, and retain the records for three years after the device is no longer marketed. The FDA may inspect the records and request copies as part of its regulatory oversight.

Posted by IVD Enthusiast in IVDs
06
Jan
2024
21 CFR Part 822: Postmarket Surveillance

21 CFR Part 822: Postmarket Surveillance

Postmarket surveillance (PMS) is the process of monitoring the safety and effectiveness of medical devices after they have been approved or cleared for marketing by the FDA. PMS can help identify unforeseen adverse events, the actual rate of anticipated adverse events, or other information necessary to protect the public health when using a medical device.

Applicability

Not all medical devices require PMS. If PMS is needed, the FDA will let you know by issuing an order that specifies the reason for the surveillance, the type of surveillance, and the timeframe for submitting and completing the surveillance plan. The FDA may order PMS for any device that meets one or more of the following criteria.

  • The failure of the device would be reasonably likely to have serious adverse health consequences.
  • The device is intended to be implanted in the human body for more than one year.
  • The device is intended to be a life-sustaining or life-supporting device used outside a device user facility.
  • The device is new or modified and raises new or increased safety or effectiveness concerns.

PMS orders are mostly for Class III devices.  The FDA has a database that shows all active and completed PMS orders here:  https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pss.cfm

Postmarket Surveillance Plan

The manufacturer must submit a postmarket surveillance plan to the FDA within 30 days of receiving the order, unless otherwise specified. The plan must be scientifically sound and include the following elements:

  • A statement of the postmarket surveillance question or issue and an explanation of how the data or other information to be collected will address it.
  • A description of the device, including the indications for use, the marketing history, and any relevant information from premarket testing or postmarket studies.
  • A description of the population to be studied, including the number of patients, the selection criteria, the enrollment procedure, and the follow-up schedule.
  • A description of the data or other information to be collected, including the sources, the methods, the variables, the endpoints, and the analysis plan.
  • A description of the surveillance methods, including the study design, the data collection procedure, the quality control measures, and the data management system.
  • A description of the organizational structure, including the roles and responsibilities of the manufacturer, the investigators, the contractors, and the institutional review boards (IRBs).
  • A timetable for conducting the surveillance, including the milestones, the interim reports, and the final report.

IRB Approval

Because a PMS study is also a human study, the plan must be reviewed and approved by an IRB that meets the requirements of 21 CFR Part 56. The manufacturer must also obtain informed consent from the patients who participate in the surveillance, unless the FDA or the IRB waives this requirement.

FDA Review and Actions

The FDA will review the postmarket surveillance plan and (typically) within 60 days either approve, disapprove, or request modifications to the plan.

  • If approved, the plan must be followed and you must submit periodic reports to the FDA.  You must also notify the FDA of any changes to the plan and obtain the FDA’s approval before making the changes.
  • If disapproved, you typically must submit a new plan within 15 days of receiving the notice of disapproval. The FDA may take regulatory actions, such as administrative detention, seizure, injunction, or civil money penalties, if you don’t submit a new plan or submit an inadequate plan.
  • If the FDA requests modifications to the plan, you must typically revise and submit a changed plan within 15 days.  Again, the FDA will give a decision within 60 days.

You can request a meeting with the FDA to discuss the plan or the FDA’s decision. There is also the option for an informal review or a formal appeal of the decision.

The FDA may terminate the postmarket surveillance order if they determine it is no longer needed to protect the public health.

Posted by IVD Enthusiast
30
Dec
2023
21 CFR Part 821 Medical Device Tracking Requirements

21 CFR Part 821 Medical Device Tracking Requirements

The point medical device tracking regulation is make sure the FDA, manufacturers, distributors, and patients can track certain devices from the manufacturing to the patient. The main reasons to do this are:

  • to ensure we can locate, remove, or notify patients of dangerous or defective devices or serious risks to health.
  • to help the FDA and manufacturers to monitor the performance and safety of the devices and to identify and address any potential problems or issues.
  • to protects the rights and interests of the patients who have received the devices and ensures that they receive timely and accurate information and assistance.

Which devices are subject to tracking?

The tracking requirements apply to Class II or Class III devices that meet the following criteria:

  • The device failure is likely to have serious adverse health consequences. This means that the device failure could cause death, life-threatening injury, permanent impairment, or require medical or surgical intervention to prevent permanent harm.
  • The device is intended to be implanted in the human body for more than one year.
  • The device is life-supporting or life-sustaining and is used outside a device user facility. This includes devices such as ventilators, infusion pumps, and oxygen concentrators.

The FDA maintains a list of devices that require tracking on its website.

What are the responsibilities of manufacturers?

Manufacturers of tracked devices must comply with the following requirements:

  • Establish a procedure for tracking the device throughout its distribution. There must be a way to collect and record the following information:
    • The name and address of the distributor, the date of shipment, the lot number, the serial number, and the expiration date of the device.
    • The name and address of the device user facility, the licensed practitioner who implanted the device, or the patient who received the device.
    • The date of implantation, if applicable, or the date of receipt by the patient.
    • The status of the device, such as whether it is in use, explanted, returned, or disposed of.
  • Establish a quality assurance program that includes auditing to verify the accuracy and completeness of the tracking information. The audits must be conducted at least once a year and must include a representative sample of the tracked devices.
  • Provide the FDA with the tracking information upon request. The FDA may request the tracking information for any reason, such as to conduct a recall, to investigate a safety issue, or to monitor compliance. The manufacturer must provide the tracking information within 10 working days of the request, unless otherwise specified by the FDA.
  • Update the tracking information at least every six months for the useful life of the device. The useful life of the device is the expected duration of the device’s functionality, as determined by the manufacturer. The update must include any changes in the status or location of the device, as well as any corrections or additions to the tracking information.

What are the responsibilities of distributors?

Distributors of tracked devices must cooperate with the manufacturers and the FDA. They must:

  • Maintain records of the tracking information provided by the manufacturer. The records must include the information listed above, as well as the date of receipt and the date of shipment of the device, and records of individual patients the device was sold to.
  • Provide the manufacturer or the FDA with the tracking information upon request. The distributor must provide the tracking information within 10 working days of the request, unless otherwise specified by the manufacturer or the FDA.
  • Provide the patient or the implanting physician with the tracking information upon request. The distributor must provide the tracking information within 10 working days of the request, unless otherwise specified by the patient or the physician.
Posted by IVD Enthusiast in IVDs
23
Dec
2023
21 CFR Part 820: Quality System Regulation

21 CFR Part 820: Quality System Regulation

This article provides an overview of the key parts of 21 CFR Part 820, also called the Quality System Regulation, or just QSR, so called because it tells medical device manufacturers, importers, and distributors how to establish a quality system.

Key Terms before we go on:

  • The word ‘establish’ is used 80 times in the regulation, and means to define, document, and implement.
  • A quality system means the organizational structure, responsibilities, procedures, processes, and resources to ensure the safety and effectiveness of medical devices.

Management Responsibility

Management must establish a quality policy, assign quality roles and responsibilities, provide adequate resources, conduct management reviews, and ensure effective communication within the organization and with customers and regulators.

Design Controls

Establish a way to control the design and development of medical devices, from the initial planning to the final transfer to production. Define design inputs (what a device needs to do) and outputs (how you make sure it does that), conduct design reviews and verification and validation activities, manage design changes, and maintain design history records.

Customer Needs / Satisfaction

Identify and meet the needs and expectations of its customers, including the end users of the medical devices.

Establish a way to determine customer requirements, communicate with customers, handle customer complaints, and measure customer satisfaction.

Process Controls

Establish a way to control the processes that affect the quality of the medical devices, from the receipt of raw materials to the delivery of finished products. The process controls include the following:

Materials

Ensure the materials that end up in the medical devices are suitable, safe, and conform to specifications. Control the purchase, receipt, inspection, storage, handling, and distribution of those materials.

Mother Nature

Ensure that manufacturing environmental conditions, such as temperature, humidity, lighting, and cleanliness, are appropriate for the medical device processes and do not negatively affect the quality of the products.

Methods

Ensure that the methods used in the medical device processes are documented, validated, and followed. The methods include the procedures, instructions, standards, and techniques for performing the processes.

Measurements

Ensure the measurements used in the medical device processes are accurate, reliable, and traceable. The measurements include the inspection, testing, calibration, and monitoring of the processes and products.

Man

Ensure the personnel involved in the medical device making processes are qualified, trained, and competent. Provide a safe and healthy work environment for personnel.

Machines

Ensure the equipment and software used in the medical device processes are suitable, maintained, and controlled. The equipment and software include the tools, instruments, devices, and programs that perform the manufacturing and testing processes.

Corrective and Preventive Actions

Establish a way to identify, analyze, correct, and prevent the causes of nonconformities (failures to meet requirements) in the medical device processes and products. Investigating the root causes of nonconformities, implement corrective and preventive measures, verify the effectiveness of actions taken, and document the results.

Posted by IVD Enthusiast in IVDs
16
Dec
2023
21 CFR Part 814: Premarket Approval (i.e. PMA)

21 CFR Part 814: Premarket Approval (i.e. PMA)

The FDA needs to agree a medical device is reasonably safe and effective before you can sell it in the US. For Class III (high risk devices), this agreement is called ‘approval’. To get ‘approval’, you’ll need to submit evidence your device is safe and effective (a process called a ‘premarket approval’). In this article, we will explain what a PMA submission is, when it is required, how to prepare it, and what to expect from the FDA review process.

What is a PMA submission?

A PMA submission is a document provides evidence to the FDA of reasonable assurance of safety and effectiveness of a device when used as intended. A PMA submission must include all information about the device, such as its design, manufacturing, labeling, performance testing, clinical data, and risk analysis. A PMA submission may also include a request for an advisory panel meeting, where a group of experts will review and discuss your device and make recommendations to the FDA. A PMA submission is the most rigorous and costly type of premarket submission for medical devices.

When is a PMA submission required?

You need to submit a PMA to the FDA if:

  • Your device is high-risk, or does not qualify for a 510K or de novo.  See my article on 21 CFR Part 807-E which covers pre-market notification (510Ks) for moderate-risk devices, which is a less rigorous and costly type of submission for devices that are substantially equivalent to an existing device.

You do not need to submit a PMA if:

  • Your device is exempt by regulation or order (see FDA’s list of exempt devices)
  • Your device is for export only
  • Your device is for investigational use only (see 21 CFR Part 812).

What information is required in a PMA submission?

A PMA submission must include the following information:

What Does Device Do? What is it for?

  • Device description: A description that provides the name, the classification, the product code, the regulatory status, the marketing history, and the physical and technical characteristics of the device
  • Indications for use statement: A statement that describes the intended use of the device, including the patient population, the disease or condition, and the mode of application
  • Proposed labeling: A copy of the proposed labeling for the device, including the instructions for use, the indications, the contraindications, the warnings, the precautions, and the adverse effects

Answer Most Important Question: Is it Safe and Effective?

  • Performance testing: A description of the performance testing (bench, animal, and/or clinical) and results for the device, to demonstrate its safety and effectiveness for its intended use.
  • Animal and clinical testing: A description of any animal and clinical testing and results for the device, including the study design, the study population, the study endpoints, the statistical analysis, and the ethical considerations. Clinical studies are typically required for a PMA.
  • Sterilization and shelf life: A description of the sterilization method, the sterility assurance level, the packaging, the storage conditions, and the shelf life of the device, if applicable
  • Biocompatibility: A description of the biocompatibility testing and results for the device, if it contacts human tissues or fluids
  • Software: A description of the software design, development, verification, validation, and hazard analysis for the device, if it contains software
  • Electromagnetic compatibility and electrical safety: A description of the electromagnetic compatibility and electrical safety testing and results for the device, if it emits or is affected by electromagnetic radiation.
  • Additional information: Any other information that may be relevant or requested by the FDA, such as risk analysis, literature review, reference standards, etc.

Honesty Stuff

  • Truthful and accuracy statement: A statement that certifies that all information in the submission is truthful and accurate, and that no material fact has been omitted
  • Financial certification or disclosure statement: A certification or a disclosure that are required for clinical investigators who conducted or participated in clinical studies that support the PMA (see 21 CFR Part 54)
  • Environmental impact statement, or a claim for categorical exclusion

Administrative Stuff

  • User fee cover sheet: A form that identifies the submitter and the type of submission, and confirms the payment of the FDA’s fee.
  • PMA cover letter: A letter that summarizes the purpose and content of the submission, and provides the contact information of the official correspondent.
  • PMA summary or statement: A summary that provides an overview of the device, the predicate device, and the substantial equivalence comparison, or a statement that agrees to make the complete PMA available upon request.

How to format a PMA submission?

A PMA submission are now required to be electronic and submitted using the FDA’s Electronic Submissions Gateway (ESG) and eCopy Program. A PMA submission can also be formatted in different ways depending on the type and number of devices. For example:

  • Multiple devices: A PMA can include more than one device, if they have the same intended use, the same technological characteristics, and the same performance specifications. The submission should clearly identify and distinguish each device and its corresponding information.
  • Modular PMA: A PMA can be submitted in sections or modules, such as device description, preclinical data, clinical data, etc. These can be submitted over time, rather than all at once.  THe DA will review each module separately and provide feedback before the next moduleis submitted.  The submission should follow the FDA’s Modular PMA Program Guidance and include a table of contents for each module.
  • Expedited PMA: A PMA can be eligible for expedited review, if the device is intended to treat or diagnose a life-threatening or irreversibly debilitating disease or condition, and meets certain criteria. The submission should follow the FDA’s Expedited Access Pathway Program Guidance and include a data development plan.

What is a PMA summary?

A PMA summary sometimes called a ‘technical summary’, is a document that provides an overview of the device, the predicate device, and the substantial equivalence comparison. It is intended to be a concise and accurate summary of the PMA submission, and it is made available to the public by the FDA. A PMA summary must include the following information:

  • Applicant’s and Correspondent’s name and address: The name and address of the person or entity who submitted the PMA and who is authorized to communicate with the FDA about the PMA
  • Device name: The trade or proprietary name, the common or usual name, and the classification name and product code of the device
  • Device description: A brief description of the device, including its function, principle of operation, and technological characteristics
  • Intended use: A statement of the intended use of the device, including the patient population, the disease or condition, and the mode of application
  • Summary of technological characteristics: A summary of the technological characteristics of the device and the predicate device, and a comparison of their similarities and differences
  • Summary of performance data: A summary of the performance data (bench, animal, and/or clinical) that support the safety and effectiveness of the device for its intended use
  • Conclusions: A statement of the conclusions drawn from the comparison of the device and the predicate device, and the demonstration of substantial equivalence

What is a PMA statement?

A PMA statement is a document that agrees to make the complete PMA submission available to any person within 30 days of a written request. It is an alternative to a PMA summary, available under certain conditions, and it is not made available to the public by the FDA. A PMA statement must include the following information:

  • Statement that all information in the submission is truthful and accurate, and that no material fact has been omitted.
  • Statement that the submitter will make the complete PMA available to any person within 30 days of request and specifies the address where such requests should be sent
  • Name, title, address, telephone number, and signature of the official correspondent with the FDA

What to expect from the FDA review process

  • Submission acceptance: The FDA will check if the submission is complete and meets the minimum requirements for review. This usually takes 15 days once received. The FDA will issue an acceptance or a refusal letter to the submitter.
  • Substantive review: The FDA will conduct a detailed review of the submission to determine if the device is safe and effective for its intended use, and that it provides a reasonable assurance of safety and effectiveness. This usually takes 180-320 days from the date of acceptance. The FDA will communicate with the submitter during the review to request additional information, clarify issues, or resolve problems.
  • Advisory Panel: The FDA may also convene an advisory panel meeting to obtain expert opinions and recommendations on the device. The FDA will issue an approval or a denial order to the submitter.
  • Marketing approval: If the FDA approves the device, the submitter can market the device in the U.S. subject to the general and special controls applicable to the device. The FDA will list the device on its PMA database and publish the PMA summary or statement on its website.
Posted by IVD Enthusiast in IVDs
09
Dec
2023
21 CFR Part 807-E: Premarket Notifications (i.e. 510K)

21 CFR Part 807-E: Premarket Notifications (i.e. 510K)

The FDA needs to agree a medical device is reasonably safe and effective before you can sell it in the US.  For Class II (moderate risk devices), this agreement is called ‘clearance’.  To get ‘clearance’, you’ll need to submit evidence your device is safe and effective (a process called a ‘premarket notification’). In this article, we will explain what a 510(k) submission is, when it is required, how to prepare it, and what to expect from the FDA review process.

What is a 510(k) submission?

A 510(k) submission is a document that shows the FDA your device is safe and effective for its intended use, and that it is substantially equivalent to a legally marketed device (also known as a predicate device).  In case you were wondering, its known as a 510(k) submission, because the regulation is based on section 510K of the Federal Food, Drug, and Cosmetic Act (FD&C). Substantial equivalence means that your device has the same intended use, technological characteristics, and performance as the predicate device, or that any differences do not raise new questions of safety and effectiveness.

When is a 510(k) submission required?

You need to submit a 510(k) to the FDA if:
  • Your device is new or not substantially equivalent to an existing device (this process is called a ‘de novo’ and it allows the FDA to create a new category of device). You selling a device and the registered manufacturer, importer, or repackager has changed.
  • You significantly change or modify the devices design, components, manufacture, or intended use.
You do not need to submit a 510(k) if:
  • Your device is exempt by regulation or order (see FDA’s list of exempt devices)
  • Your device is for export only
  • Your device is for investigational use only (see 21 CFR Part 812).
Class III certification is a special rule regarding 510Ks that may apply to devices that were on the market before May 28, 1976, and have not been reclassified by the FDA.  It is not relevant to most device manufacturers.

What information is required in a 510(k) submission?

A 510(k) submission must include the following information:

What Does Device Do? What is it for?

  • Device description: A description that provides the name, the classification, the product code, the regulatory status, the marketing history, and the physical and technical characteristics of the device
  • Indications for use statement: A statement that describes the intended use of the device, including the patient population, the disease or condition, and the mode of application
  • Proposed labeling: A copy of the proposed labeling for the device, including the instructions for use, the indications, the contraindications, the warnings, the precautions, and the adverse effects

Comparison to Predicate(s)

  • Substantial equivalence discussion: A discussion that compares the device with the predicate device(s) already on the market in terms of intended use, technological characteristics, and performance, and explains how any differences do not raise new questions of safety and effectiveness.

Answer Most Important Question: Is it Safe and Effective?

  • Performance testing: A description of the performance testing (bench, animal, and/or clinical) and results for the device, to demonstrate its safety and effectiveness for its intended use.
  • Animal and clinical testing: If applicable, a description of any animal and clinical testing and results for the device, if applicable, including the study design, the study population, the study endpoints, the statistical analysis, and the ethical considerations.  NOTE: Class II devices generally do not require animal or clinical testing.
  • Sterilization and shelf life: A description of the sterilization method, the sterility assurance level, the packaging, the storage conditions, and the shelf life of the device, if applicable
  • Biocompatibility: A description of the biocompatibility testing and results for the device, if it contacts human tissues or fluids
  • Software: A description of the software design, development, verification, validation, and hazard analysis for the device, if it contains software
  • Electromagnetic compatibility and electrical safety: A description of the electromagnetic compatibility and electrical safety testing and results for the device, if it emits or is affected by electromagnetic radiation.
  • Additional information: Any other information that may be relevant or requested by the FDA, such as risk analysis, literature review, reference standards, etc.

Honesty Stuff

  • Truthful and accuracy statement: A statement that certifies that all information in the submission is truthful and accurate, and that no material fact has been omitted
  • Financial certification or disclosure statement: A certification or a disclosure that are required for clinical investigators who conducted or participated in clinical studies that support the 510(k) (see 21 CFR Part 54)

Administrative Stuff

  • User fee cover sheet: A form that identifies the submitter and the type of submission, and confirms the payment of the FDA’s fee.
  • 510(k) cover letter: A letter that summarizes the purpose and content of the submission, and provides the contact information of the official correspondent.
  • 510(k) summary or statement: A summary that provides an overview of the device, the predicate device, and the substantial equivalence comparison, or a statement that agrees to make the complete 510(k) available upon request.

How to format a 510(k) submission?

A 510(k) submission are now required to be electronic and submitted using the FDA’s [Electronic Submissions Gateway (ESG)] and eCopy Program. A 510(k) submission can also be formatted in different ways depending on the type and number of devices. For example:
  • Multiple devices: A 510(k) can include more than one device, if they have the same intended use, the same technological characteristics, and the same performance specifications. The submission should clearly identify and distinguish each device and its corresponding information.
  • Abbreviated 510(k): A 510(k) can follow an abbreviated format, if it relies on the use of FDA-recognized standards to demonstrate substantial equivalence. The submission should include a summary report that describes how the device conforms to the standards or guidance.
  • Special 510(k): A 510(k) submission can follow a special format, if it is submitted by the manufacturer of a legally marketed device, and it requests a modification to the device’s design, labeling, or indications. The submission should include a declaration of conformity to design control requirements.

What is a 510(k) summary?

A 510(k) summary sometimes called a ‘technical summary’, is a document that provides an overview of the device, the predicate device, and the substantial equivalence comparison. It is intended to be a concise and accurate summary of the 510(k) submission, and it is made available to the public by the FDA. A 510(k) summary must include the following information:
  • Applicant’s name and address: The name and address of the person or entity who submitted the 510(k)
  • Correspondent’s name and address: The name and address of the person who is authorized to communicate with the FDA about the 510(k)
  • Device name: The trade or proprietary name, the common or usual name, and the classification name and product code of the device
  • Predicate device name and 510(k) number: The name and the 510(k) number of the legally marketed device that is claimed as the predicate device
  • Device description: A brief description of the device, including its function, principle of operation, and technological characteristics
  • Intended use: A statement of the intended use of the device, including the patient population, the disease or condition, and the mode of application
  • Summary of technological characteristics: A summary of the technological characteristics of the device and the predicate device, and a comparison of their similarities and differences
  • Summary of performance data: A summary of the performance data (bench, animal, and/or clinical) that support the safety and effectiveness of the device for its intended use
  • Conclusions: A statement of the conclusions drawn from the comparison of the device and the predicate device, and the demonstration of substantial equivalence

What is a 510(k) statement?

A 510(k) statement is a document that agrees to make the complete 510(k) submission available to any person within 30 days of a written request. It is an alternative to a 510(k) summary, and it is not made available to the public by the FDA. A 510(k) statement must include the following information:
  • Statement that all information in the submission is truthful and accurate, and that no material fact has been omitted
  • Statement that the submitter will make the complete 510(k) available to any person within 30 days of request and specifies the address where such requests should be sent
  • Name, title, address, telephone number, and signature of the official correspondent with the FDA

What to expect from the FDA review process

  • pre-submissions:  These are technically optional, but before you submit pre-market notification, you should have at least one pre-submission with the FDA to get feedback on the key aspects of your submission.  It will save you time and hassle.  I’ll cover pre-submissions in a later article.
  • online Registration process on CDRH Portal assigns a number to each 510 (k) submission.  There is a monitoring tool and contact information for the FDA lead reviewer. The fact that you are submitting is confidential.
  • acceptance review: The FDA will check if the submission is complete, the fee is paid, and meets the minimum requirements for review. This usually takes 15 days once received. The FDA will issue an acceptance or a refusal letter to the submitter.
  • substantive review: The FDA will conduct a detailed review of the submission to determine if the device is substantially equivalent to the predicate device, safe, and effective. This usually takes 60 days. Communication is typically either:
    • an email stating that FDA will proceed to resolve any outstanding deficiencies using Interactive Review (back and forth emails); or
    • an Additional Information (AI) request which places the submission on hold for up to 180 days.
    • Note that the FDA has a goal of 90 FDA days to issue a decision letter with the findings of substantial equivalence or not, but this does not could the time waiting for the submitter to respond.
  • marketing clearance: If the FDA finds the device substantially equivalent, the submitter can market the device in the U.S. subject to the general and special controls applicable to the device. The FDA will list the device on its 510(k) database and publish the 510(k) summary or statement on its website.
Posted by IVD Enthusiast in IVDs
02
Dec
2023
21 CFR Part 812: Investigational Devices

21 CFR Part 812: Investigational Devices

Investigating A Medical Device

Consider this Catch-22:

  • You can’t distribute a medical device before getting FDA approval.
  • You can’t get FDA approval without evidence the medical device works.
  • You can’t get evidence a device works without using the medical device.

The FDA solved this problem with 21 CFR Part 812, which allows an exemption to distribute a device for a clinical trial to investigate it (i.e. ‘investigational device exemption’ or ‘IDE’).

21 CFR Part 812 takes a risk-based approach to IDEs, as well as the procedures for obtaining IRB and FDA approval, and the responsibilities of sponsors and investigators who conduct device studies.  It also addresses how investigational devices must be labeled.

Risk-Categories of Investigational Devices

The FDA classifies investigational devices into three categories based on the level of risk they pose to human subjects:

  • exempt,
  • non-significant risk (NSR), and
  • significant risk (SR).

The risk category determines the type and extent of regulatory oversight required for the device study.

Exempt devices are those that do not require an IDE from the FDA, because they meet one of the following criteria:

  • They are legally marketed devices that are used in accordance with their approved labeling
  • They are diagnostic devices with little or no risk to subjects (see 21 CFR 809.10(c))
  • Testing is not to determine safety or effectiveness of device, and does not put subjects at risk
  • They are custom devices not intended for general distribution.

Significant Risk (SR) devices are those that:

  • Are implants
  • Support or sustain human life
  • Are of substantial importance to diagnose, cure, mitigate, or treat disease, or otherwise prevent impairment of human health
  • Present a potential for serious risk to the health, safety, or welfare of a subject

Non-Significant Risk (NSR) devices are everything else.

Actions Required Based on Risk

Exempt devices

The sponsor does not need to submit an IDE application to the FDA, but must:

  • Obtain approval from an IRB before initiating the study
  • Label the device as investigational
  • Obtain informed consent from subjects

NSR devices

The sponsor does not need to submit an IDE application to the FDA, but must. The sponsor must do everything required for an exempt device AND also comply with the abbreviated requirements in 21 CFR 812.2(b), which include:

  • Conduct the study per the approved protocol
  • Monitor the study and ensure that any unanticipated adverse device effects are reported to the FDA and the IRB
  • Maintain certain records and reports (see 21 CFR 812.140(b)(4) and (5))

SR devices

The sponsor must submit an IDE application to the FDA and obtain approval from both the FDA and an IRB before initiating the study. The sponsor must also comply with the full requirements in 21 CFR Part 812, which include everything for exempt and NSR devices AND:

  • Conduct the study in per any conditions of approval imposed by the FDA or the IRB
  • Maintaining all records and reports as required by 21 CFR Part 812.  NOTE: There are considerably more records and reports needed for SR devices.

IRB approval process for device studies

The Institutional Review Board (IRB) is an ethics committee responsible for reviewing and approving human studies to ensure that they are ethically sound and protect the rights and welfare of human subjects. The IRB must follow the general requirements in 21 CFR Part 56 (IRB), as well as the specific requirements in 21 CFR Part 812 for device studies.

The IRB must review and approve:

  • The research protocol
  • The informed consent document
  • The investigational device brochure (if any)
  • The investigator’s qualifications
  • The site where the study will be conducted
  • Any other relevant information

The IRB must also determine whether the device is NSR or SR based on the information provided by the sponsor. If the IRB disagrees with the sponsor’s initial NSR determination, it must notify the sponsor and the FDA within five working days.

FDA approval process for device studies

The FDA is responsible for reviewing and approving IDE applications for SR devices to ensure that they are scientifically valid and protect public health. The FDA will follow the general requirements in 21 CFR Part 50 (Protection of Human Subjects), as well as the specific requirements in 21 CFR Part 812 for IDE applications.

The FDA will review and approve:

  • The research protocol
  • The risk analysis
  • The device description
  • The manufacturing information
  • The preclinical and clinical data (if any)
  • The investigator’s qualifications
  • The informed consent document
  • The investigational device brochure (if any)
  • Any other relevant information

The FDA will also determine whether the device is SR or NSR based on the information provided by the sponsor. If the FDA disagrees with the sponsor’s initial SR determination, it must notify the sponsor and the IRB within 30 days.

Sponsor Responsibilities

The sponsor is the person or entity who initiates a device study, or who assumes responsibility for a study initiated by another person or entity. The sponsor is typically the manufacturer of the device, a clinical investigator, an academic institution, or a contract research organization.

The sponsor must:

  • Obtain an IDE from the FDA (if required) and an approval from an IRB before initiating a device study
  • Select qualified investigators and provide them with the necessary information and training to conduct the study
  • Provide the investigators with the investigational devices and ensure that they are properly labeled, stored, distributed, and accounted for
  • Obtain agreements from the investigators to comply with the protocol, the IDE regulations, and any other applicable regulations
  • Monitor the progress and conduct of the study and ensure that any problems or deviations are corrected or reported
  • Report any unanticipated adverse device effects, withdrawals of IRB or FDA approval, progress reports, final reports, and any other information as required by 21 CFR Part 812
  • Maintain records and reports as required by 21 CFR Part 812

Investigator responsibilities

The investigator is the person who actually conducts a device study, or who supervises the conduct of a device study by other persons under his or her direction. The investigator may be a physician, a nurse, a technician, or any other person qualified by training and experience to conduct the study.

The investigator must:

  • Obtain approval from an IRB before initiating a device study
  • Obtain informed consent from each subject before enrolling them in the study
  • Conduct the study per the approved protocol and any conditions of approval imposed by the IRB or the FDA
  • Use the investigational device only for the purposes and in the manner specified in the protocol
  • Control the investigational device and ensuring that it is not used for any other purpose or by any other person
  • Report any unanticipated adverse device effects, deviations from the protocol, changes in the study status, and any other information as required by 21 CFR Part 812
  • Maintain records and reports as required by 21 CFR Part 812

Device labeling requirements for investigational devices

The labeling of investigational devices is regulated by 21 CFR Part 812 to ensure that they are clearly identified as such and that they provide adequate information for their safe and effective use.

The labeling of investigational devices must:

  • Bear the statement “CAUTION — Investigational device. Limited by Federal (or United States) law to investigational use.”
  • Identify the device, the name and address of the manufacturer or sponsor, and any relevant information such as expiration date, lot number, serial number, etc.
  • Provide directions for use, warnings, precautions, potential adverse effects, contraindications, and any other information necessary for the protection of subjects
  • Not contain any false or misleading statements or claims about the safety or effectiveness of the device.
Posted by IVD Enthusiast in IVDs, LDTs
25
Nov
2023
21 CFR Part 810: Medical Device Recall Authority

21 CFR Part 810: Medical Device Recall Authority

Recalls are ‘Voluntary’… …Until They Are Not

21 CFR Part 810 is one of the more serious and impactful regulations for most medical device manufacturers to understand, as it can impact a company’s reputation and bottom line. But for Laboratories worried about the impact of Laboratory Developed Tests (LDTs) becoming IVDs, it’s unlikely to cause concern, because the IVD is ‘distributed’ to only one customer (who is also the manufacturer), which majorly simplifies the actions needed to comply.

In my article about 21 CFR Part 806 Corrections and Removals: The Recall Regulation, I discussed what a recall is, that you must report it to the FDA, and how. Here’s a quick summary.

A recall is a voluntary action taken by a manufacturer, importer, or distributor to correct or remove a device that is in violation of the FD&C Act or that may present a risk to health. It may include if you:

  • Repair, modify, adjust, relabel, or destroy the device
  • Inspect the device even if you don’t physically remove it from the customer.
  • Monitor patients due to suspected device issues.
  • Notify the device users of the problem and provide instructions on how to handle or dispose of the device

Recalls occur when:

  • the FDA determines there is a reasonable probability that a device intended for human use would cause serious adverse health consequences or death and requests a recall.
  • you start a correction or removal of a device to reduce a risk to health.

Voluntary, in this context is a relative term.  The regulation doesn’t mean recalls are optional.  It just means that are voluntary relative to other options, for instance if the FDA decides to enforce its medical device recall authority under the powerful Federal Food, Drug, and Cosmetic Act (FD&C Act), as we will describe in this article.

Cease Distribution and Notification Order

The word ‘order‘ sounds serious, doesn’t it? It’s worth remembering at this point that Federal Agencies like the FDA have actually legal power, that was passed to them by the US Congress. They can, and do, issues ‘orders’ much in the way a police officer can.  And like a police officer, they have the very real ability to physically walk into a company and shut down activities they find illegal.

A cease distribution and notification order (CDANO) is the equivalent of a police officer give a lawful order to stop doing something.  It must be obeyed, or a company risks more serious consequences. This type of order issued by the FDA requires a manufacturer or importer to immediately:

  • Stop distributing a device
  • Notify all persons who received, purchased, or used the device of the order and the reason for it
  • Instruct them to stop using the device and to take appropriate action to prevent further use

Just as a police officer issues an order when they have just cause, a cease distribution and notification order may be issued when:

  • The FDA has credible evidence that the device presents an unreasonable risk of substantial harm to the public health
  • The FDA has consulted with the manufacturer or importer regarding the evidence and the need for an order
  • The FDA has provided an opportunity for an informal regulatory hearing on whether the order should be issued

The FDA will share the reason with you when they issue the order.

Complying With a CDANO

I remember this as “Can’t Distribute Any New Orders” because to comply with a cease distribution and notification order, the manufacturer or importer must Immediately stop distributing the device and with 24 hours confirm in writing to the FDA that distribution has ceased.

A single-site IVD would have few logistical issues notifying their single customer, though this is not to say you wouldn’t potentially still have issues in maintaining testing as the lab runs out of IVD reagent inventory.  But that’s little ins relation to a large-scale manufacturer.  As you can imagine, depending on the number devices out there and a large distribution chain, this can be quite the scramble.  And it gets worse, you also need to provide proof of what you did.

Within 10 working days of receiving the order, you have to submit a written report to the FDA that includes:

  • The name, address, telephone number, and email address of each person who received, purchased, or used the device
  • The date on which each person received, purchased, or used the device
  • A copy of each notification sent to each person
  • A description of any actions taken by each person in response to the notification
  • A description of any problems encountered in complying with the order

Recall Strategy

This is where recall strategies come into play.

A recall strategy is a planned, specific course of action to be taken by the manufacturer or importer in response to a cease distribution and notification order or a mandatory recall order. A recall strategy addresses:

  • The depth of the recall (i.e., how far down the distribution chain the recall will extend)
  • The need for public warnings (i.e., whether any announcements or notices should be issued to inform the public of the recall)
  • The effectiveness checks (i.e., how to verify that all persons who received, purchased, or used the device have been notified and have taken appropriate action)

To develop and implement a recall strategy, the manufacturer or importer must:

  • Consult with the FDA on the elements of the strategy
  • Submit a written proposal of the strategy to the FDA within 15 working days of receiving a cease distribution and notification order or a mandatory recall order
  • Obtain approval from the FDA before implementing the strategy
  • Follow up with periodic status reports on the progress and results of the strategy

Mandatory Recall Orders – It’s Serious Now

Some people just don’t obey Officers.  But then what?  At this point, the manufacturer had an option to ‘voluntarily’ recall, and has been issued a cease distribution and notification order. They’ve had the chance to discuss a recall strategy with the FDA to comply. At this point most manufacturers choose to comply.

If not, a mandatory recall order can be issued by the FDA and requires a manufacturer or importer to recall a device. It may be issued when the FDA determines that the device presents an unreasonable risk of substantial harm to the public health and that the manufacturer or importer has not taken sufficient action to recall the device.

A mandatory recall order is public in nature and has serious consequences for the manufacturer or importer. The FDA will:

  • Publish a notice of the order in the Federal Register and on its website
  • Notify all persons who received, purchased, or used the device of the order and the reason for it
  • Instruct them to stop using the device and to take appropriate action to prevent further use
  • Monitor and enforce compliance with the order
  • Impose civil penalties for violations of the order

It’s the last two items that make this option the most serious. The FDA is not toothless.  They can revoke a manufacturer’s registration, effectively shutting down production.  Still not complying?  They can call in the local police and show up at your facility.  They can take the product away physically, lock up the product in a room, or lock up the entire facility and send your staff home.  For foreign manufacturers, they can hold the product in customs.  F-around and find out.

What if You and the FDA Don’t Agree or the Situation Changes?

There is recourse if you end up at odds with the FDA.  Say you don’t agree with their CDANO, or can’t agree on a recall strategy?

A regulatory hearing is an informal proceeding conducted by an FDA official who is independent of the CDANO or a mandatory recall order. It provides an opportunity for:

  • The manufacturer or importer to present information and views on whether there is credible evidence that supports issuing or continuing an order
  • The FDA to explain its rationale for issuing or continuing an order

A modification request is a written request submitted to the FDA to modify or terminate a cease distribution and notification order or a mandatory recall order. A modification request may be based on:

  • New information or evidence that shows that the order is not warranted or is no longer necessary
  • Changes in the circumstances or conditions that led to the issuance of the order
  • Compliance with the terms and requirements of the order

To request a regulatory hearing or a modification request, the manufacturer or importer must:

  • Submit a written request to the FDA within 10 working days of receiving a cease distribution and notification order or a mandatory recall order
  • Include a statement of the factual and legal basis for the request and any supporting information or evidence
  • Specify whether the request is for a regulatory hearing, a modification, or both
Posted by IVD Enthusiast