Real-Time Pathogen Monitoring: Revolutionizing Pharmaceutical Bioprocessing
Pharmaceutical bioreactors are highly susceptible to bacterial contamination, creating a need for real-time pathogen detection to prevent massive product loss and manufacturing delays.
What is Pharmaceutical Bioprocessing?
Pharmaceutical bioprocessing refers to the production of medications using biological sources, such as microorganisms, enzymes, or living cells. Bioprocessing harnesses the capabilities of biological systems carry out specific processes or transformations to produce products like vaccines, monoclonal antibodies, recombinant proteins, and gene therapies.
The journey begins with the cultivation of cells, which serve as the factories for producing the desired therapeutic molecules. Once cells are cultured, they are fermented in large-scale bioreactors or fermentation vessels. Fermentation requires precise control of various parameters, including pH, dissolved oxygen levels, and temperature to maximize cell growth and optimize the production of target compounds.
After fermentation, the mixture obtained from the bioreactor contains a combination of cells, desired therapeutic molecules, and various impurities. The mixture must then be purified to isolate and concentrate the target therapeutic molecules while removing contaminants and impurities. Finally, the target product is transformed into its final dosage form through the addition of additives and stabilizers, ensuring that the medication retains its efficacy and stability throughout its shelf life.
Threat of Bacterial Contamination
Since the manufacturing environment is designed to be conducive to microbial growth, with favorable temperature, humidity, and pH conditions, fermentations are highly susceptible to bacterial contamination. While these conditions are necessary to support the growth of the target cells or microorganisms, they can also inadvertently create a favorable environment for bacterial growth. If bacteria are accidentally introduced to the bioreactor during the inoculation or sampling process, even a small number of bacteria can multiply rapidly under favorable growth conditions, leading to mass contamination.
Often, contamination isn’t detected until after the medium has entered the bioreactor, requiring the whole batch to be discarded and the bioreactor to be disinfected. Since bacteria can produce metabolites, enzymes, or toxins that can alter the composition, functionality, or stability of the product, contaminated batches often cannot be recovered.
Furthermore, if the source of contamination is not identified and treated immediately, contamination may spread throughout the facility, causing substantial loss of product and significant disruptions to the production and supply chain. The entire manufacturing process may need to be halted to investigate and address the contamination issue, further exacerbating the impact on production timelines and overall business operations.
Sources of Contamination
Contamination in pharmaceutical bioreactors can occur through various pathways and sources.
Airborne Contamination: Airborne particles, including microorganisms, can enter the bioreactor through openings such as vents, filters, or improperly sealed connections. Contaminants from the surrounding environment, such as bacteria, fungi, or viruses, can be introduced if the air handling system is not adequately filtered or if there are breaches in the containment system.
Contaminated Raw Materials: Raw materials used in bioprocessing, such as cell culture media, growth factors, or additives, can serve as potential sources of contamination. If these materials are contaminated with microorganisms or other impurities, they can introduce contaminants into the bioreactor.
Equipment and Facility Contamination: Contamination can arise from improperly cleaned or maintained equipment, such as bioreactors, pumps, valves, or tubing. Residual substances or biofilms that harbor microorganisms can contaminate the product during subsequent runs. Poor facility hygiene, including inadequate cleaning and disinfection practices, can also contribute to contamination.
Operator Contamination: Human operators involved in the bioprocessing activities can inadvertently introduce contaminants. For example, improper aseptic techniques, inadequate hand hygiene, or wearing contaminated clothing can lead to microbial contamination. Operators should follow strict hygiene practices and wear appropriate personal protective equipment (PPE) to minimize the risk of contamination.
Cross-Contamination: Cross-contamination can occur when different batches or products come into contact with each other. If adequate separation measures are not in place, such as dedicated equipment or stringent cleaning procedures, contaminants from one batch can transfer to subsequent batches, leading to cross-contamination.
Water Contamination: Water is an essential component in bioprocessing, and contaminated water can introduce microorganisms or impurities into the bioreactor. The water used for preparing media, cleaning equipment, or operating the bioreactor should meet stringent quality standards to prevent contamination.
Controlling bacterial contamination in bioreactors is a critical aspect of bioprocessing. Strict adherence to aseptic techniques, proper facility design, and robust sterilization processes are implemented to minimize the risk of bacterial contamination. Routine monitoring of the bioreactor environment, including sampling and testing for bacterial presence, is also essential to detect and address any contamination issues promptly. By maintaining strict control over the manufacturing environment and implementing appropriate preventive measures, the risk of bacterial contamination can be minimized, ensuring the production of safe and high-quality biopharmaceutical products.
Real-Time Pathogen Monitoring: A Game-Changer
Real-time pathogen monitoring in pharmaceutical bioprocessing is revolutionizing the way pathogens are detected and managed throughout the manufacturing process. By continuously monitoring the bioprocessing environment, companies can take proactive measures to mitigate risks, minimize production losses, and ensure the production of safe and high-quality drugs.
One of the key benefits of real-time pathogen monitoring is early detection and response. Biopharmaceutical manufacturers can rapidly detect the presence of pathogens and initiate immediate corrective actions, such as isolating contaminated batches to prevent further spread and minimize the impact on the production line.
Real-time pathogen monitoring also plays a crucial role in process optimization. Continuous monitoring provides valuable data on contamination trends, allowing manufacturers to identify critical control points and potential sources of contamination. By analyzing these patterns, companies can optimize their processes, refine hygiene protocols, and implement targeted interventions to improve overall process efficiency and a reduce the risk of future contaminations.
From a cost perspective, timely identification of pathogen contamination reduces costs associated with production losses, batch rejection, and product recalls. By swiftly detecting and addressing contamination events, companies can avoid extensive testing, retrospective investigations, and the potential need for recalling large quantities of products. This not only saves resources but also minimizes the impact on the company's reputation and customer trust.
Finally, real-time pathogen monitoring strengthens quality assurance and compliance efforts. By demonstrating an active and robust monitoring system, pharmaceutical companies enhance their adherence to regulatory guidelines and industry standards. This, in turn, bolsters their quality control programs, ensures compliance with regulatory requirements, and helps establish a strong reputation for producing safe and high-quality drugs.
Conclusion
Real-time pathogen monitoring has emerged as a game-changer in pharmaceutical bioprocessing. Its ability to provide immediate insights into pathogen presence and its applications in early detection, process optimization, quality assurance, and cost reduction make it an indispensable tool for the biopharmaceutical industry. As technology continues to advance, real-time pathogen monitoring may transform pharmaceutical bioprocessing and contribute to improved patient outcomes for years to come.
About Kraken Sense
Kraken Sense develops all-in-one pathogen detection solutions to accelerate time to results by replacing lab testing with a single field-deployable device. Our proprietary device, the KRAKEN, has the ability to detect bacteria and viruses down to 1 copy/mL. It has already been applied for epidemiology detection in wastewater and microbial contamination testing in food processing, among many other applications. Our team of highly-skilled Microbiologists and Engineers tailor the system to fit individual project needs. To stay updated with our latest articles and product launches, follow us on LinkedIn, Twitter, and Instagram, or sign up for our email newsletter. Discover the potential of continuous, autonomous pathogen testing by speaking to our team.