USFDA Warning Letter to Akron Formulations Flags BCC Contamination Risks and Use of APIs Under Import Alert

The USFDA has issued a Warning Letter to Hyderabad-based OTC manufacturer Akron Formulations for critical deviations in the manufacture of drug products. The Warning Letter, issued in December 2024 following a review of records submitted by Akron to FDA in March 2024, highlighted significant lapses in Current Good Manufacturing Practice (cGMP) compliance. Akron was found to be using Active Pharmaceutical Ingredients (APIs) suppliers under USFDA Import Alerts. The suppliers were under Import Alerts (99-32), (66-79) and (66-40) for refusing FDA inspection of the sites and not meeting drug GMPs. Akorn sourced API Docusate Sodium from a supplier under Import Alert 66-40 for GMP deviations for inadequate control of water.

Akron did not test drug products for Burkholderia cepacia complex (BCC) organisms prior to release though BCC is a known organism of concern in drugs containing docusate sodium. Akron also failed to conduct Antimicrobial Effectiveness Testing (AET) across various drug products and did not study the drug products to evaluate the ability to inhibit growth of certain objectionable organisms

Burkholderia Cepacia Complex (BCC) Organisms

The FDA has long been concerned about the risk of contamination of water-based non-sterile liquid formulations with BCC strains. BCC is a group of gram-negative bacteria that can thrive in aqueous environments and is resistant to many common preservatives and antimicrobial agents. Even if a formulation contains preservatives or the API itself has intrinsic antimicrobial properties, the growth and multiplication of BCC cannot be ruled out, even if the product passes initial release testing. The FDA advises drug product manufacturers to implement robust contamination control systems based on comprehensive risk assessments and ensuring appropriate material quality, equipments and facilities, process design and monitoring of environmental conditions. The water system should be designed, controlled, and maintained to prevent microbial contamination. Drug manufacturers should establish appropriate specifications and test procedures for microbial quality including BCC testing, for drug release. The FDA issued a statement on the control of BCC in non-sterile drug formulations in 2017 and also issued a draft guidance in 2021 titled “Microbiological Quality Considerations in Non-Sterile Drug Manufacturing.” It is imperative for drug product and drug substance manufacturers to critically assess the risk of microbial contamination and establish appropriate controls.

Risk of Non-Compliant Supply Chain Partners

The FDA takes official regulatory actions, such as issuing Warning Letters and Import Alerts, when serious cGMP lapses are observed at drug product or drug substance manufacturing facilities. It is crucial for drug manufacturers to continuously monitor their supply chain partners for any regulatory actions from the FDA (and other regulatory agencies). Upon noticing regulatory actions, manufacturers should conduct a thorough risk assessment to evaluate potential risks. Based on the assessment, remediation actions, including recalls if necessary, may need to be taken. Pharmaceutical manufacturers should incorporate these practices into their Standard Operating Procedures (SOPs) for Supplier Qualification and Supply Chain Monitoring.

References:

• USFDA Warning letter to Akron (December 2024)
• FDA advises drug manufacturers that Burkholderia cepacia complex poses a contamination risk in non-sterile, water-based drug products – FDA Statement
• USFDA Guidance – Microbiological Quality Considerations in Non-Sterile Drug Manufacturing