Advancements and Innovations in Sterile Drug Product Manufacturing
Sterile drug product manufacturing is complex and plays a crucial role in the pharmaceutical industry, ensuring the production of safe and effective medications for patient use. Over the years, the advancements and innovations in this field have transformed the manufacturing processes, enhancing product quality, efficiency, and safety. This article explores the key developments in sterile drug product manufacturing, from traditional methods to cutting-edge robotic technologies, addressing regulatory challenges, ensuring patient safety and highlighting the industry’s commitment to continuous improvement.
Traditional Sterile Drug Product Manufacturing
Aseptic processing involves the sterilisation of components, equipment, and the control of the environment to prevent microbial contamination during drug product formulation and filling. Historically, sterile drug manufacturing relied on aseptic processing techniques such as filtration and terminal sterilisation to eliminate or control potential microbial contamination.
a. Sterile Filtration: Sterile manufacturing of monoclonal antibodies (mAbs) and other biologic modalities relies on effective and efficient filtration processes to remove micro-organisms and particles that compromise drug product purity. Sterilising-grade filters with extremely small pores, typically ranging from 0.1 to 0.2 micrometres in size are used in the manufacturing of sterile drug products and play a pivotal role in assuring final product sterility.
b. Terminal Sterilisation: Terminal sterilisation refers to the process of sterilising a drug product, typically in its final container, to eliminate any microorganisms that may be present and ensure its safety, efficacy and stability. This process is typically performed using methods such as steam, radiation, or chemical sterilisation. The method used depends on the drug product’s sensitivity, for example, gamma radiation may be used for drug products that cannot withstand heat. It is important to highlight that if a product can be terminally sterilised, it should not be filled aseptically alone. It can be processed aseptically if it is terminally sterilised after. Buffers, placebos and some small molecules would be representative of such products that require terminal sterilisation.
Novel Aseptic Techniques
From isolator technology to restricted access barrier systems (RABS), these innovations contribute to maintaining product integrity, safety and compliance with global regulatory standards. Inline monitoring and control systems further improve the aseptic processing environment, by separating operators from the product at all times.
- Single-Use Technologies
One of the significant innovations in sterile drug manufacturing has been the adoption of single-use technologies (SUTs) to replace conventional reusable stainless-steel vessels and processing lines. Single-use systems, including disposable bags, filters, tubing, and connectors, have also gained popularity due to:
Little or no cleaning required – replacing at the end of each batch, saves time and money involved with cleaning and validation requirements.
• Flexible and adaptable – single-use products can be quickly and easily modified to fit each process and scale requirements. They also allow for a safe and quick transition of changes, minimising validation costs.
• Time saving – Removing cleaning and validation or verification periods, helps reduce time to market and improves batch turnaround times.
• Reduced risk of product cross-contamination – single-use products are replaced after each batch, which eliminates the risk of cross-contamination between products.
• Creates a sealed barrier that separates the product from the operators, de-risking the process and enhancing sterility
