Reasons for FDA violations….

Reasons for FDA violations….

Most FDA violations involve one of the following:

• Not having procedures in a regulated area that conform to FDA regulations;
• Having procedures that conform to FDA regulations, but not following them; or
• Having procedures that conform to FDA regulations and following them, but not having adequate documentation to show that you’re following them.

Most commonly receive FDA-483 Observations and Warning Letter citations.

1. Complaint Handling Procedures are Inadequate

Manufacturer must maintain complaint files, as well as procedures for receiving, reviewing, and evaluating complaints. Such procedures must ensure that:

• All complaints are processed in a uniform and timely manner;
• Verbal complaints are documented upon receipt; and
• Complaints are evaluated to determine whether the complaint represents an event that must be reported to the FDA.

The regulation further requires that complaint files and procedures be contained “within a formally designated unit.”

2. Corrective and Preventive Action (CAPA) Procedures are Inadequate

Manufacturers must establish and maintain procedures for corrective and preventive actions, including procedures for:

• Analyzing processes, work operations, concessions, quality audit reports, quality records, service records, complaints, returned product, and other sources of quality data to identify existing and potential causes of nonconforming product, or other quality problems. Appropriate statistical methodology must be employed where necessary to detect recurring quality problems.
• Investigating the cause of nonconformities relating to products, processes, and the quality system.
• Identifying the action(s) needed to correct and prevent recurrence of nonconforming products or other quality issues.

Verifying or validating a corrective and preventive action to ensure that it is effective and does not adversely affect the finished product.

• Implementing and recording changes in methods and procedures needed to correct and prevent identified quality problems.
• Ensuring that information related to quality problems or a nonconforming product is disseminated to those directly responsible for assuring the quality of the product or preventing problems.
• Submitting relevant information on identified quality problems, as well as corrective and preventive actions, for management review.

3. Written Procedures are Inadequate

Manufacturers, user facilities, and importers of medical devices must develop, maintain, and implement written procedures for internal systems. The procedures must provide:

• Timely and effective identification, communication, and evaluation of events that may be subject to requirements;
• A standardized review process or procedure for determining when an event meets the criteria for reporting; and
• Timely transmission of complete medical device reports to manufacturers or the FDA (or both, if required).

In addition, FDA regulation requires manufacturers, user facilities, and importers of to establish documentation and recordkeeping requirements for:

• The information that was evaluated to determine whether an event was reportable;
• All medical device reports and information submitted to manufacturers and/or the FDA;
• Any information that was evaluated for the purpose of preparing the submission of annual reports; and
• Systems that ensure access to information for facilitating timely follow-up and inspection by the FDA.

4. Corrective and Preventive Actions are Inadequately Documented

Manufacturers must document all activities and results of activities related to corrective/ preventive action procedures. In other words, the FDA wants solid proof of a fully functional CAPA system that includes:

• A documented analysis of the sources of quality data (for example, incoming raw materials, manufacturing processes, inventory management, etc.);
• Documentation of investigations of the causes of nonconformities;
• Documentation of the actions needed to correct and prevent the recurrence of nonconforming products or other quality problems;
• Documentation of the procedures used to verify or validate corrective actions;
• Documentation of the procedures used in the implementation of corrective and preventative actions;
• Documentation that demonstrates that information about nonconforming products or quality problems is being properly disseminated to the responsible parties; and
• Documentation that demonstrates that information about nonconforming products (or quality problems) is being properly disseminated for management review.

5. Process Validation Procedures are Inadequate

The results of a process cannot be fully verified by subsequent inspection and testing, the process must be validated with a high degree of assurance and approved according to established procedures. The validation activities and results, including the date and signature of the individual(s) approving the validation and, where appropriate, the major equipment validated, must be documented.

6. Quality Audits were not Adequately Conducted

Quality audits must be conducted by individuals who do not have direct responsibility for the matters being audited, and corrective action(s), including a re-audit of deficient matters, must be taken when necessary. A report of the results of each quality audit, and re-audit(s) where taken, must be made and such reports must be reviewed by management having responsibility for the matters audited. The dates and results of quality audits and re-audits must be documented.

Hence, the sixth most common reason for getting an Obs. 483 or Warning Letter is because the FDA believes that a quality audit may not have been conducted properly, for one (or more) of the following reasons:

• The quality audit was not conducted by the proper individuals;
• Necessary corrective actions (including re-audits) were not taken;
• A report of the results of the quality audit (and any necessary re-audits) were not made according to FDA specifications; and/or
• The quality audit (or re-audit) report was not reviewed by management having responsibility for the matters audited.

7. Executive Management Failed to Ensure Quality at all Organizational Levels

Management with executive responsibility must ensure an adequate and effective quality system at all levels of the organization.

• Quality Policy: Management with executive responsibility must establish its policy and objectives for, and commitment to, quality. Management with executive responsibility must also ensure that the quality policy is understood, implemented, and maintained at all levels of the organization.
• Organization: Each manufacturer must establish and maintain an adequate organizational structure to ensure that devices are designed and produced in accordance with the requirements listed below:
• Responsibility and authority: Each manufacturer must establish the appropriate responsibility, authority, and interrelation of all personnel who manage, perform, and assess work affecting quality; in addition, each manufacturer must provide the independence and authority necessary to perform these tasks.
• Resources: Each manufacturer must provide adequate resources, including the assignment of trained personnel, for the management and performance of work, and for assessment activities, including internal quality audits.
• Management representative: Management with executive responsibility must appoint and document the appointment of a member of management who, irrespective of other responsibilities, must have established authority over and responsibility for (i) ensuring that quality system requirements are effectively established and effectively maintained in accordance with the stipulations defined in this section, and (ii) reporting on the performance of the quality system to management with executive responsibility for review.
• Management review: Management with executive responsibility must review the suitability and effectiveness of the quality system at defined intervals and with sufficient frequency according to established procedures to ensure that the quality system satisfies the requirements of this part and the manufacturer’s established quality policy and objectives. The dates and results of quality system reviews must be documented.
• Quality planning: Each manufacturer must establish a quality plan which defines the quality practices, resources, and activities relevant to devices that are designed and manufactured. The manufacturer must establish how the requirements for quality will be met.
• Quality system procedures: Each manufacturer must establish quality system procedures and instructions. An outline of the structure of the documentation used in the quality system must be established where appropriate.

8. Procedures for Conducting Quality Audits are Inadequate

Manufacturers must establish procedures for quality audits and conduct such audits to assure that their quality system is in compliance with their established quality system requirements, and to determine the effectiveness of their established quality system.

Hence, the eighth most common reason for getting an Obs. 483 or Warning Letter has to do with the manufacturer’s procedures for conducting a quality audit. If the FDA believes that the procedures are inadequate, the reason may be because:

• The manufacturer doesn’t have procedures for conducting quality audits;
• The manufacturer has procedures for conducting quality audits, but the procedures are not in compliance with the manufacturer’s established quality system requirements; or
• The manufacturer has procedures that are in compliance with the manufacturer’s established quality system requirements, but the system requirements are not adequate for determining the effectiveness of the established quality system.

9. Procedures for Controlling the Design Process are Inadequate

Each manufacturer must establish and maintain procedures for controlling the design of the device in order to ensure that specified design requirements are met.