Client

A combination product manufacturer received an FDA 483 warning letter for a facility that produces a branded prefilled syringe (PFS) drug delivery system with manual needle guard, vial and vial adapter, and auto injector.

 

Project Timeline

Gap Assessment – 2 weeks

Remediation – 3 months per DHF technical file

 

Client Challenge

RCA’s client unsuspectingly received a warning letter for violating regulatory standards (e.g. 21 CFR 3, 21 CFR 820) after a bi-annual FDA inspection revealed new 483 observations had occurred. Specifically, FDA regulators cited the medical device portion of the combination product was no longer following current good manufacturing practices (cGMP). Further, technical documentation required for regulatory compliance was noted as either missing or mislabeled by the Quality Assurance (QA) team in charge of the quality management system (QMS).

 

Regulatory Compliance Associates Approach

RCA’s combination product consulting team laid out a detailed strategy for bringing the client’s operation back into compliance. A gap analysis discovered multiple manufacturing departments with a younger team needed refresher training to review QA best practices. Additionally, the data revealed a growing decline of compliance resources for supporting the internal team – which began a planning discussion about optimizing the manufacturing team headcount. 

 

Design Controls

RCA consultants began the process of reviewing existing technical documentation in the QMS folders and found multiple gaps for remediation. Additionally, the team knew implementing updated and compliant procedures for design validation was critical to address early in the project. One of the 483 observations listed in the warning letter was a failure to show how proposed actions will be incorporated into the consumer complaint process due to design validation problems.

 

Design Control Process

First, an updated design control process was developed to improve all existing design procedures as a whole. The goal of the process improvement strategy was to define user needs more clearly so regulators could validate the accuracy of production testing methods for components. Additionally, new technical documentation was needed to show the results of testing current production units under both actual conditions and simulated conditions.  

 

Remediation Services

During the gap assessment, RCA’s consulting services team established the need to streamline information in the client’s design history file. The RCA manufacturing consulting team developed an updated annual requirement for design changes and SOP review. This included updating the SOP procedures for product design (e.g. identification, documentation, and validation) for approval and before implementation (per 21 CFR 820). Finally, a corrective action and preventative action (CAPA) program was launched to ensure the client operations team would have the necessary technical documentation in place to confirm these SOP improvements could be measured in real time. 

 

Quality Assurance

RCA’s quality assurance services team simultaneously supported the project by conducting validation studies to help define the actual use conditions of the combination product. These were critical to executing since the 483 observations noted “minimal information in the design history file” to help identify prescribed user needs or the product’s intended use.

 

Results

The client’s regulatory response improved the internal expectations needed by employees on the manufacturing operations team. The CAPA program was formally approved by the FDA and helped establish a standards process with both leadership accountability and team visibility. Finally, the client’s facility returned to full compliance approximately fifteen months after the project began.

 

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