FDA Warning Letter highlights critical Failures in Supplier and Quality Oversight

A Florida-based pharmaceutical distributor primarily engaged in the wholesale distribution of active pharmaceutical ingredients (APIs) received an FDA Warning Letter. The FDA identified serious weaknesses in the company's system for evaluating and qualifying API suppliers. Specifically, the Quality Unit (QU) failed to adequately verify supplier information, investigate inconsistencies, and ensure that contractual quality requirements were met before approving and re-qualifying a supplier.

What Happened?

Deficiencies in Supplier Qualification

The firm received APIs from a supplier that had been "approved" and subsequently "re-qualified". As part of the supplier qualification process, the supplier completed vendor surveys regarding its regulatory inspection history. However, the surveys contained conflicting information. In one survey, the supplier stated that it had been inspected by the FDA with a "satisfactory" outcome, although FDA records indicate that no such inspection had occurred. In a later survey, the supplier stated that it had not undergone any regulatory inspections. The firm did not investigate or resolve this discrepancy prior to re-qualifying the supplier.

In addition, the Quality Agreement with this supplier required the provision of ongoing and annual stability data generated in accordance with an approved stability protocol. However, during a subsequent FDA inspection of the supplier, investigators observed that the facility had no stability chambers and no stability or reserve samples. Despite these deficiencies, the firm continued to qualify the supplier and imported and distributed APIs obtained under the quality agreement.

The firm's response to the Form FDA 483 was later considered inadequate because it failed to acknowledge these deficiencies as systemic failures of the supplier qualification process. The FDA also noted that similar compliance concerns existed with other API suppliers previously used by the firm, increasing regulatory concern regarding the overall effectiveness of the supplier oversight program.

Deficiencies in Quality and Supplier Oversight

The inspection further found that the firm's Quality Unit (QU) did not adequately oversee the investigation of customer complaints or assess their impact on supplier qualification and ongoing supplier oversight.
The QU failed to ensure that product quality complaints were investigated beyond the initially reported lot and customers. For example, the firm received complaints from two customers regarding the presence of black particles in an API lot. This lot had been distributed multiple times to several customers. Although the firm returned the remaining inventory of the affected lot to the manufacturer, the QU did not:

• Contact all customers who received the affected lot,
• Determine whether similar complaints had occurred at other customer sites, or
• Evaluate whether the issue could affect other lots manufactured by the same supplier.

In its response, the firm stated that the supplier attributed the particles to equipment shedding during manufacturing and classified them as "technically unavoidable particles" that did not affect product quality. This explanation was accepted by the firm without critical evaluation.

The QU relied on the supplier's assessment and informed the two complaining customers that the particles could be removed manually. However, manual removal of visible particles by customers is not an acceptable control under CGMP and does not ensure that the API meets required quality and purity standards.

Notably, despite accepting the supplier's conclusion, the QU chose to return the remaining inventory of the affected lot to the manufacturer, indicating internal recognition that the issue had not been adequately resolved.

Failure to Reassess Supplier Qualification and Supply Continuity

There is no evidence that the QU evaluated whether the supplier's response reflected a lack of understanding of CGMP requirements or whether continued sourcing from this supplier was appropriate. The firm continued to distribute another lot of the same API, manufactured by the same supplier, which had been received prior to the second complaint and before the supplier could have implemented corrective actions to address the equipment-related issue.

This demonstrates a failure to link complaint management with supplier re-qualification and ongoing supplier performance monitoring.

Deficiencies in Supplier Recall Management and Communication

In addition, the firm's recall procedure did not clearly define responsibilities for managing supplier-initiated recalls and notifying downstream customers. After receiving notice of the supplier's voluntary recall following FDA-identified violations, the firm quarantined and returned all remaining stock to the supplier. However, there is no documented evidence that the QU notified all customers who had received APIs manufactured by this supplier.

The absence of documentation indicates inadequate quality oversight of recall communications and recall effectiveness.