FDA Issues Draft Guidance on Microbial Contamination for Non-Sterile Drugs

By Miranda Greenberg -

September 30, 2021

The US Food and Drug Administration (FDA) has issued a draft guidance to assist manufacturers in assuring the control of microbiological quality of their non-sterile drugs (NSDs).

The draft guidance, Microbiological Quality Considerations in Non-sterile Drug Manufacturing Guidance for Industry, discusses product development considerations, risk assessments, and certain current good manufacturing practices (cGMPs) that are particularly relevant to microbiological control in a manufacturing operation for a NSD.

The recommendations in the draft guidance apply to solid non-sterile dosage forms, as well as semi-solid, and liquid non-sterile dosage forms (e.g., topically applied creams, lotions and swabs, and oral solutions and suspensions). It also applies to prescription or non-prescription drugs and covers approved new drug applications, abbreviated new drug applications as well as over-the-counter monograph drugs.

This guidance was developed, in part, as a result of the agency’s review of FDA Adverse Event Reports (FAERs) and recalls involving contamination of non-sterile dosage forms. A review of FAERs that occurred between 2014 and 2017 revealed 197 FAERs associated with intrinsic microbiological or fungal contamination, and of those, 32 reported serious adverse events. Because spontaneous reports in FAERs are voluntary by definition, the agency anticipates a degree of underreporting. The FDA says the actual number of incidents associated with microbiological contamination is likely significantly higher than the number of events reported.

The review of voluntary recall actions during the same time period revealed over 50 events associated with objectionable microbiologically contaminated NSDs. The recalls showed that a wide range of objectionable microorganisms were found in both aqueous and non-aqueous NSDs.

The draft guidance discusses incidents of Burkholderia cepacia complex (BCC) and other microorganism contamination in non-sterile dosage forms that resulted in adverse events and recalls of the drug products. The guidance describes proper prevention of and testing for BCC in aqueous-dosage forms of NSDs.

The FDA says it is also aware of specific concerns regarding BCC and its association with contamination of aqueous-based NSDs that resulted in a number of serious adverse events, i.e., infections and deaths. In May 2017, FDA released a statement alerting drug manufacturers of the recent product recalls associated with the presence of BCC in NSDs. The statement also reminded drug manufacturers of their responsibilities to prevent objectionable microorganisms from adversely impacting their NSD manufacturing processes, as well as the products themselves.

Source: US Food and Drug Administration