Risks related to Burkholderia Cepacia Complex (BCC)
A necessary evil in the manufacture of pharmaceutical formulations is the need to make use of differing grades and sources of water particularly in production of non sterile products where the controls are not as stringent a those seen in the manufacture and use of water for injection (WFI). While simply deciding to use WFI for everything would eliminate some of these risks it is typically prohibitively expensive to do so.
Even in the most controlled environments, there are microbial contaminants that can compromise product quality. One of particular concern and focus is the Burkholderia cepacia complex (BCC), a group of bacteria known to resist several common disinfectants and present a threat to certain vulnerable patient populations. Bacteria within the complex including:
B. cepacia, B. multivorans, B. cenocepacia, B. vietnamiensis, B. stabilis, B. ambifaria, B. dolosa, B. anthina, B. pyrrocinia and B. ubonensis
They can be found in soil and water and are catalase-producing, lactose-nonfermenting, gram-negative bacteria.
Why is BCC a problem?
Risk to Vulnerable Patients: Medicines are consumed by diverse populations, including those with weakened immune systems or underlying health conditions. For these patients, a contamination with BCC can be serious, if not deadly.
Resistance to Disinfectants: BCC species are known for their innate resistance to many disinfectants commonly used in the pharmaceutical industry. This resistance can be attributed to their robust outer membrane and the ability to form biofilms on various surfaces.
Resistance to Preservatives: In several cases BCC persisted and even multiplied in drug products (even with antimicrobial preservatives present) where significant growth emerged later in the product’s shelf-life (post testing).
While BCC is often harmless to healthy individuals, it can cause life-threatening lung infections in people with underlying health conditions, such as cystic fibrosis.
The resilience and adaptability of this complex make it a significant challenge in pharmaceutical environments while the ability to act as an opportunistic pathogen poses a direct risk to patients.
BCC Outbreaks in the Past
Historically, there have been instances where products were found contaminated with BCC.
Medicines and Healthcare products Regulatory Agency (filecamp.com)
Mitigating the Risk of BCC
Control of BCC and associated risks should be part of your overall contamination control strategy. Example approaches to adopt include:
Enhanced Environmental and Water Monitoring: Regular monitoring of the manufacturing environment for microbial contamination is vital. This helps in early detection and mitigation. Ensuring your system can recover BCC is critical.
Reviewing Disinfection Protocols: Given the resistance of BCC to common disinfectants, it's crucial for manufacturers to review and possibly update their disinfection protocols.
Quality Control: Rigorous testing of end products to ensure they are free from contaminants is essential. This might include more frequent batch testing or introducing new methods that are more sensitive to BCC detection.
Equipment Maintenance and Disinfection: Regular maintenance and cleaning of equipment can prevent the buildup of biofilms and potential BCC contamination.
Vendor Screening and Approval/Maintenance: Raw materials can be a source of contamination. Hence, thorough screening and validation of vendors can reduce the risk of introducing BCC into the manufacturing process.
Conclusion
While the risk of Burkholderia cepacia complex poses a significant challenge in pharmaceutical manufacturing, understanding its nature and potential impact can lead to better preventive measures. By investing in rigorous monitoring, training, and quality control, manufacturers can minimize the risk and ensure the safety of their products. As with many challenges in the pharmaceutical industry, a combination of fit for purpose equipment, validated processes, and continuous vigilance offers the best defence against BCC and its potential patient impact.