Burkholderia cepacia Complex (Bcc) Contamination in Nonsterile Pharmaceuticals

The resilient nature of Bcc species

The Bcc is a group of over 20 closely related Burkholderia species widely distributed in soil and aquatic environments. Originally identified as plant pathogens, many Bcc strains are now recognized for their beneficial roles in plant growth promotion, biocontrol, and bioremediation.^2,3 However, despite their environmental versatility and potential utility in agriculture, Bcc species pose a significant threat to humans as opportunistic pathogens capable of causing serious infections, particularly in individuals with compromised immune systems.²

Bcc strains are incredibly adaptable due to their high genetic diversity, rapid mutation rates, and versatile metabolic capabilities.^2,4,5 These traits, coupled with the bacteria’s ability to form biofilms and their intrinsic resistance to preservatives and antimicrobials commonly used in pharmaceutical product formulations, enable Bcc strains to persist in a wide range of low-nutrient environments like nonsterile, water-based pharmaceutical products (e.g., nasal sprays, topical antiseptics).⁵ This resilience has led to repeated product recalls and prompted U.S. Food and Drug Administration (FDA) warnings about the contamination risks they pose in pharmaceutical manufacturing.¹

The consequences of Bcc contamination

Outbreaks linked to Bcc contamination have resulted in serious public health and regulatory consequences. For patients, exposure to contaminated products has resulted in hospitalizations, invasive infections, and, in some cases, death. For example, a January-October 2016 outbreak of healthcare-associated Bcc strains linked to contaminated liquid docusate sodium resulted in 108 reported infections (63 confirmed) across 12 states. Among those infected, 43 patients had Bcc cultured from multiple sites throughout their body and 21 patients died.⁶ Another notable example is the May-September 2021 outbreak of Burkholderia stabilis infections linked to contaminated nonsterile ultrasound gel. This incident resulted in 119 reported infections across 10 states; of these, 106 were bloodstream infections and 14 resulted in death.⁷

Manufacturers involved in Bcc-related outbreaks have also faced significant repercussions. In addition to regulatory investigations, legal action, and reputational damage, companies have incurred substantial financial losses through product recalls, halted production, and costly litigation.¹ These outcomes underscore the importance of microbial testing methods throughout the pharmaceutical manufacturing process.

Microbiological examination of nonsterile products

Contamination with Bcc strains can occur at multiple points during the manufacture of nonsterile aqueous pharmaceutical products. The most common culprit is the water system. If the design, maintenance, or monitoring of the water system is inadequate, it can allow Bcc strains to grow and multiply in water needed for drug development.^1,5 Once present, Bcc can contaminate raw materials, equipment, or finished products. Because of the bacteria’s resistance to disinfectants and their ability to form resilient biofilms, they can be difficult to eliminate from a water system once present.

In response to the serious risks posed by Bcc contamination—particularly to vulnerable patient populations—the United States Pharmacopeia (USP) introduced Chapter <60>: Microbiological Examination of Nonsterile Products—Tests for Burkholderia cepacia Complex.⁸ This chapter outlines standardized methods for detecting Bcc in raw materials, in-process samples, and finished products and is intended to complement USP <61>, <62>, and <1111> in the microbial quality control testing of nonsterile products. Recognizing the public health implications of Bcc contamination, the FDA recommends that manufacturers use the method described in USP <60> to test drug products for the presence of Bcc organisms—provided the method is appropriately verified for its intended use.¹

How ATCC can support your Bcc quality control testing

Ensuring compliance with USP <60> requires reliable reference materials, and that's where ATCC steps in. ATCC offers highly authenticated Bcc strains specified as control materials in USP <60>: B. cepacia (ATCC® 25416™), B. cenocepacia (ATCC® BAA-245™), and B. multivorans (ATCC® BAA-247™). These strains are now available in our precisely quantitated, ready-to-use MicroQuant™ format to help streamline microbial quality control testing. Our new Bcc MicroQuant™ products include both high and low CFU formulations. The low-titer (CFU) strains are specifically calibrated (100-1,000 CFU per vial; 10-100 CFU per 100 µL once rehydrated) to fall within USP <60> acceptance ranges, simplifying test setup and ensuring reliable results. With ATCC’s trusted quality and batch-to-batch consistency, you can accelerate your workflows while maintaining compliance with microbiological standards.

MicroQuant™ Burkholderia cepacia complex strains for USP <60> testing

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ATCC’s MicroQuant™ portfolio enables streamlined microbial quality control testing supporting USP <51>, <60>, and <61> with plans to include strains covering USP <62> and <71> this fall.

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References

1. US Food and Drug Administration. FDA advises drug manufacturers that Burkholderia cepacia complex poses a contamination risk in nonsterile, water-based drug products. Published 2021. Accessed June 17, 2025. https://www.fda.gov/drugs/drug-safety-and-availability/fda-advises-drug-manufacturers-burkholderia-cepacia-complex-poses-contamination-risk-nonsterile 
2. Vial L, et al. The various lifestyles of the Burkholderia cepacia complex species: a tribute to adaptation. Environ Microbiol 13(1): 1-12, 2011. PubMed: 20880095
3. Burkholder W. Sour skin, a bacterial rot of onion bulbs. Phytopathol 64: 468–475, 1950.
4. Sousa SA, et al. Burkholderia cepacia Complex: Emerging Multihost Pathogens Equipped with a Wide Range of Virulence Factors and Determinants. Int J Microbiol 2011: 607575, 2010. PubMed: 20811541
5. Tavares M, et al. Burkholderia cepacia Complex Bacteria: A Feared Contamination Risk in Water-Based Pharmaceutical Products. Clin Microbiol Rev 33(3): e00139-19, 2020. PubMed: 32295766
6. Glowicz J, et al. A multistate investigation of healthcare-associated Burkholderia cepacia complex infections related to liquid docusate sodium contamination, January - October 2016. Am J Infect Control 46(6): 649-655, 2018. PubMed: 29329922
7. Hudson MJ, et al. Outbreak of Burkholderia stabilis infections associated with contaminated nonsterile, multiuse ultrasound gel—10 states, May–September 2021. MMWR Morb Mortal Wkly Rep 71(48): 1517–1521, 2022. PubMed: 6454695
8. United States Pharmacopeial Convention. Microbiological Examination of Nonsterile Products—Tests for Burkholderia cepacia complex <60>. In: United States Pharmacopeia and National Formulary (USP 47–NF 42). United States Pharmacopeial Convention; 2024.

The United States Pharmacopeia and USP are registered trademarks of The United States Pharmacopeial Convention.