Product Quality Complaints versus Adverse Event Reports

Product Quality Complaints versus Adverse Event Reports

The United States Food and Drug Administration (FDA) places a significant amount of emphasis on the need for pharmaceutical companies to develop an effective approach to complaint management, including the establishment of well-written procedures. In fact, the Agency believes that complaint management is such a salient element for drug manufacturers that 21 CFR 211 has a dedicated section for the management and retention of complaint files, 21 CFR 211.198. Additionally, 21 CFR 314 expands on the post- market surveillance process under 21 CFR 314.80. Equally important is the reporting of adverse events through the use of the FDA Adverse Event Reporting System (FAERS). Although the management of complaint files and subsequent investigative process is distinctly different from the voluntary and in some cases mandatory reporting of adverse events through the use of FAERS, the two processes are linked.

Although FDA citation for failure to comply with 211.198 in a warning letter is a rare event, the Agency does occasionally cite such violations. More common is the citing of a failure to complete and/or document investigations pursued as a result of a complaint.

IMPORTANCE OF 21 CFR 314.80 AND 21 CFR 314.81

As part of the drug application process, FDA wants to reinforce the need for review and reporting of adverse drug experiences (that is, adverse drug event), post-marketing studies, periodic reporting requirements, annual reporting requirements, and the importance of record keeping. Similarly to medical devices, drug manufacturers are required to report adverse drug experiences through the use of form FDA 3500A. Once a drug manufacturer becomes aware of an adverse drug experience, the company is required to perform a thorough investigation followed by the completion and submission of form 3500A; however, an exemption is noted for post-marketing studies. A 15- calendar-day window must be adhered to when reporting an adverse drug experience. Within 15 calendar days of initial receipt of information, the drug applicant is required to report every serious adverse drug experience and every unexpected adverse drug experience. The best practice is to notify FDA has soon as possible when such adverse drug experiences occur. Additionally, drug manufacturers are required to script procedures that delineate their processes for managing surveillance, receipt, evaluation and reporting of post-marketing adverse drug experiences to FDA, including record keeping (10 years).

Additional reporting requirements delineated within 21 CFR 314 include periodic adverse drug experience reports and annual reports. Periodic adverse drug experience reports are required to be filed quarterly with FDA for a period of three years from the date the initial drug application was approved. These quarterly reports are due within

30 days after close of the quarter. At the discretion of the Agency, the quarterly reporting requirement can be extended. Annual reports are due to the Agency within 60 days of the anniversary date of the application approval.


The building of an effective complaint management system compliant with 21 CFR

211.198 commences with the establishment of written procedures. From a compliance perspective, FDA requires specific steps to be included in written procedures needed to support an effective complaint management system. When scripting procedures, a single well-written procedure delineating an organization’s approach to complaint management should be the goal. That being said, as a minimum, the following components of complaint management should be included in the procedure:

An applicability statement for oral and written complaints.

A mandatory review of all complaints by the quality function.

A discussion on the complaint investigation process; all decisions made in regard to not performing an investigation need to be documented and supported by written rationale.

A provision for reporting a complaint as an adverse event when deemed necessary (recommend creating a decision tree to support the reporting process).

The need to create and retain a complaint file for each complaint.

Complaint files (record) retention time periods (one year after the expiration of the drug product or one year after the complaint was received, whichever is longer).

Additionally, the complaint record must include the name and strength of the drug product, the lot number in question, the name of the individual and/or organization filing the complaint, the nature of the complaint, and the pharmaceutical company’s response to the complainant. Furthermore, if an investigation is performed, it is imperative that the result of the investigation be included in the complaint file. As previously stated, if the organization determines that a complaint investigation is not warranted, the decision not to investigate, including supporting rationale and the responsible person making the decision will need to be documented and retained in the complaint file. Finally, ensure that personnel  tasked  with complaint management duties  are  trained  on the  procedure and the training is documented.

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