FDA Submissions

BioReg experts provide full FDA Submission support, including writing a 510(K), De novo, or PMA submission; Identifying a predicate device; providing support during FDA audits; Responding to FDA warning letters, and others.
See our blog about Common FDA Form 483 Observations.
If you need help defining your roadmap for a successful FDA submission, do not hesitate to contact our experts and request a preliminary meeting.

A company that wants to market a medical device in the US, for which a Premarket Approval (PMA) is not required, must submit a 510(k) to FDA unless the device is exempt from 510(k) requirements. Before marketing a device, each submitter must receive an order from FDA which finds the device to be substantially equivalent (SE) and states that the device can be marketed in the US. This order “clears” the device for commercial distribution. A 510(k) is a premarket submission made to FDA to demonstrate that the device to be marketed is at least as safe and effective, that is, substantially equivalent, to a legally marketed device (predicate device) that is not subject to PMA.

PMA is the most stringent type of device marketing application required by FDA. The applicant must receive FDA approval of its PMA application prior to marketing the device. PMA approval is based on a determination by FDA that the PMA contains sufficient valid scientific evidence to assure that the device is safe and effective for its intended use(s).
The De Novo request provides a marketing pathway to classify novel medical devices for which general controls, or general and special controls, provide reasonable assurance of safety and effectiveness for the intended use but for which there is no legally marketed predicate device. De Novo classification is a risk-based classification process. Devices that are classified into class I or class II through a De Novo classification request (De Novo request) may be marketed and used as predicates for future premarket notification [510(k)] submissions, when applicable.

FDA Form 483 Observations

An FDA Form 483 is issued to the company after an inspection. This FDA Form 483 document includes the inspector’s observations and judgment regarding the conditions that may constitute violations of the Food Drug and Cosmetic (FD&C) Act and related acts. At the end of the audit, the FDA inspector presents the Form 483 findings to the company management. Each observation is discussed with the management to understand what the observations are and what they mean. The companies should respond to the FDA Form 483 in writing with their corrective action plan within 15 days and then expeditiously implement it.

FDA Form 483 is not an all-inclusive list and does not include every deviation from the law. Therefore the companies are encouraged to take corrective action to address not just the cited objectionable conditions but also any related non-cited objectionable conditions that might exist.

In investigation pre-announcement, the FDA investigators usually inform the firm regarding the planned timeframe and duration of the inspection. The investigations usually last from 3-6 days. To the extent possible, the FDA also provides advance notice of the records requested during the inspection (e.g., specific procedures and any associated records).

Common FDA Form 483 Observations

We’ve reviewed and selected 33 common FDA Form 483 observations issued lately by the FDA inspectors during their audits at medical device facilities. We hope you will find these 33 common FDA form 483 observations for medical device manufacturers helpful for your FDA audit preparation.

MDR (Medical Device Reporting)

1. Written MDR procedures have not been developed and implemented.
2. Complaints representing MDR reportable events were not promptly reviewed, evaluated, and investigated by a designated individual.
3. The results of the evaluation of each MDR event are not documented and maintained in the manufacturer’s MDR event file.

Design Validation & Documentation

1. The design validation results, including method(s), were not adequately documented in the design history file.
2. The device history record does not demonstrate that the device was manufactured following the device master record.
3. A device history record has not been maintained.
4. A device master record has not been maintained.
5. Process validation results have not been adequately documented.
6. Procedures for design change have not been adequately established.
7. Design validation did not ensure the device conforms to defined user needs and intended uses.
8. A process that cannot be fully verified by subsequent inspection and test has not been adequately validated according to established procedures.
9. Process validation activities and results have not been documented and approved.

Acceptance Criteria

1. Procedures for finished device acceptance have not been adequately established.
2. Procedures for acceptance of incoming products have not been adequately established.
3. Procedures to ensure that all purchased or otherwise received products and services conform to specified requirements have not been adequately established.
4. Acceptance activities were not documented and maintained as part of the device history record.
5. The acceptance status of the product was not identified to indicate conforming or nonconformance with acceptance criteria.
6. Procedures have not been adequately established to control product that does not conform to specified requirements.

Corrective & Preventive Actions

1. Procedures for corrective and preventive action have not been adequately established.
2. Corrective and preventive action activities and/or results have not been adequately documented.

Complaints

1. Procedures for receiving, reviewing, and evaluating complaints by a formally designated unit have not been established.
2. Records of complaint investigations do not include the required information.
3. Complaint files are not maintained.
4. Records of complaint investigations do not include the required information.

Other Observations

1. Procedures to prevent contamination of equipment or product by substances that may have an adverse effect on product quality have not been adequately established.
2. Labeling and packaging operations were not controlled to prevent labeling mix-ups.
3. The responsibilities and procedures applicable to the quality control unit are not thoroughly followed.
4. Document control procedures have not been adequately established.
5. Rework and reevaluation activities have not been fully documented in the device history record.
6. Schedules for the adjustment, cleaning and other equipment maintenance have not been established.
7. Risk analysis is inadequate.
8. Equipment calibrations have not been documented.
9. Requirements that suppliers must meet have not been adequately established.

For more information, please get in touch with the BioReg team.