Burkholderia cepacia complex: FDA Expectations for Drug and Personal Care Product Manufacturers

What is Burkholderia cepacia?

The Burkholderia cepacia complex (BCC) species are a group of Gram-negative, rod-shaped bacteria that are known to present a significant health risk to the immune system compromised patient populations, mechanically ventilated patients, and those suffering from underlying diseases (especially cystic fibrosis).

Burkholderia cepacia has been linked to illnesses and even the death of vulnerable patients including infants. This group of organisms are highly opportunistic and are capable of rapidly establishing a foothold in water systems, on manufacturing equipment surfaces and within non-sterile water-based products of any type.

Regulatory agencies in many jurisdictions including the US have issued numerous recalls of drugs and other product-types found to contain Burkholderia cepacia.

Among the recalled products within the US are oral liquid drugs, liquid dietary supplements, saline flush solutions and no-rinse hand cleaners/sanitizers.

On May 22, 2017 FDA issued a public notice, advising drug manufacturers of the health risk posed by Burkholderia cepacia contaminated products. FDA also indicated that the risk was especially high due to all of the following: BCC is resistant to certain preservatives and antimicrobial agents; the detection of Burkholderia cepacia poses a challenge; there currently is no “official” (compendial) testing procedure for detecting BCC.

Current FDA expectations for manufacturers of drug products include the following:

• Procedures must be established to prevent objectionable microorganism contamination of non-sterile products. This includes assuring adequate quality of incoming materials; sanitary design, maintenance and cleaning of processing equipment (including water systems); production and storage time limitations; and environmental monitoring.
• The use of scientifically sound and appropriate acceptance criteria (e.g., USP <1111> “Microbiological Examination of Non-sterile Products: Acceptance Criteria for Pharmaceutical Preparations and Substances” and procedures (e.g., USP <61/62> “Microbiological Examination of Non-sterile Products: Microbiological Enumeration Tests and Tests for Specified Microorganisms”) to assure that components (especially water) and finished products conform to appropriate quality standards.
• Ensure that methods used to test finished drug products prior to release for distribution are properly validated, accurate, sensitive, specific and reproducible.
• Test in-process materials during the production process using valid, in-process specifications to assure that the drug product will meet its final specifications, including the absence of microbial contamination, where appropriate.
• Investigate any failure to meet specifications, including other batches of the same drug product and other products that may be associated with the specific failure or discrepancy.
• Adverse events or quality problems associated with non-sterile water-based drug products reported by users should be reported to FDA’s MedWatch Adverse Event Reporting Program.

What about Personal Care and other Non-Drug Products?

Although personal care and other non-drug products are not regulated as tightly as drug products, the US Food, Drug and Cosmetic Act establishes that owners of such products are responsible for the safety of their products as they are introduced into interstate commerce.

For FDA, the “safety” of products includes being free of microbial contamination which could pose a risk to public health. This being the case, it is prudent for manufacturers of water-based non-drug products to also observe FDA’s current requirements for drug manufacturers, and to voluntarily apply those elements which may factor into the quality of their finished products.

The importance of this recommendation is underscored by the fact that US distributed water-based non-drug products are among those which have already been recalled due to confirmed or suspected Burkholderia cepacia contamination.

Testing for Burkholderia cepacia

FDA now expects manufacturers of water-based non-sterile drug products to test for the presence of BCC in their products. In the absence of an “official” (compendial) test procedure for Burkholderia cepacia, FDA requires that any procedure utilized for this purpose must be validated.

It is important to note that the United States Pharmacopeia (USP) has published an official procedure for the testing of Burkholderia cepacia. USP<60> Microbiological Examination of Nonsterile Products-Tests for Burkholderia cepacia Complex was published in December 2019 for non-sterile water-based drug products. It is expected that most if not all manufacturers will employ the USP procedure in their testing for Burkholderia cepacia. Additionally, this methodology can be used to test for the presence of B. cepacia in water systems. FDA has recently cited manufacturers for lack of testing for B. cepacia in water systems.

A Final Summary

Burkholderia cepacia complex (BCC) now poses a significant health risk to specific population groups within the US.

Non-sterile water-based drug and non-drug products have been shown to contain Burkholderia cepaciacontamination and have been included in product recalls within the US.

FDA now expects drug manufacturers to monitor their finished products for the presence of Burkholderia cepacia contamination. There is now an official USP testing method for Burkholderia cepacia: USP<60> Microbiological Examination of Nonsterile Products-Tests for Burkholderia cepacia Complex was published in December 2019 for non-sterile water-based drug products.

Since non-drug products are among those recalled for Burkholderia cepacia contamination, it is prudent for manufacturers of such products to implement suitable specifications and controls to prevent microbial contamination of their products, and to conduct monitoring for Burkholderia cepacia in their water-based products and water systems.

How Can CPT^SM Labs Assist with your Burkholderia cepacia testing?

CPT Labs Microbiological Division routinely tests for Burkholderia cepacia complex (BCC) in raw materials and non-sterile water-based products using USP <60>.

This method is ready to be applied to your raw materials, in-process samples and finished products. Feel free to contact us at any time to learn more about BCC contamination, how to control it within your manufacturing environment or to establish a testing program that is specifically designed to suit your needs.