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) is currently working towards the development of an official procedure for the testing of Burkholderia cepacia in non-sterile water-based drug products. Once published, it is expected that most if not all manufacturers will employ the USP procedure in their testing for Burkholderia cepacia.
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 cepacia contamination 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 currently is no “official” testing method for Burkholderia cepacia, although the USP is working towards the development of such a procedure. Until the “official” method is published, FDA requires that testing methods used for this purpose must be validated.
- 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 CPTSM Labs Assist with your Burkholderia cepacia testing?
CPTSM Labs Microbiological Division scientists have developed, validated and now employ a procedure for testing Burkholderia cepacia complex (BCC) in raw materials and non-sterile water-based products. This procedure and its validation have previously been reviewed by FDA.
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 Bu contamination, how to control it within your manufacturing environment or to establish a testing program that is specifically designed to suit your needs.
Services Provided by CPTSM Labs
The Microbiology Department at CPTSM Labs performs all the Antimicrobial Preservative Effectiveness testing indicated above. Many more microbiological testing services are also provided, and a full list may be found at www.cptclabs.com.
In addition to Antimicrobial Preservative Effectiveness testing, other supporting departments are available at CPTSM to provide the ultimate in product support.
- Clinical. Conducting an HRIPT test, the Clinical Department will help to determine whether or not your product will be responsible for causing sensitization and/or irritation responses. Upon request, tests can be performed in order to support claims, such as “Dermatologist Tested”.
- In-Vitro Safety/Toxicology. Available to perform skin-irritation tests, ocular-irritation tests, skin-corrosion tests, etc.
- Photobiology. When a product is applied topically, it is important to understand how molecules will change when exposed to UV light. This is ideal when aiming to tests the phototoxic and photo-allergic reaction potential of a product.
- Analytical. From stability shelf-life testing to low-level impurities, detecting claims, before a product is launched, the Analytical department ensures that all requirements are met, based on industry and regulatory standards.
- Consulting. The staff at CPTSM can perform GMP and GLP audits of a client’s facilities and/or vendors’ operations We are also available to help create SOPs, develop Raw Material testing programs, as well as provide guidance as to which testing methodologies are best for developing meaningful claim support tests