ADCs Manufacturing and High Containment Aseptic Isolators

FPS Pharma engineers Occupational Exposure Band (OEB) isolators—from OEB 4 up to the latest OEB 7—equipped with advanced safety and monitoring systems tailored to your specific process and OEL requirements, ensuring safe and compliant ADC operations.

ADC production phases and related risks

The production of antibody drug conjugates involves many critical phases starting from cell culture (such as CHO cells for example) to produce the antibody. It then progresses thought the synthesis of the anti-cancer drug(s) and of the linker(s), followed by conjugation, purification, formulation, final filling, and packaging of the finished therapeutic dose. Each phase presents inherent different risks and requires specific containment strategies.

Monoclonal antibodies (mAbs) are proteins synthesized in the laboratory to mimic the function of antibodies found in the human immune system. They are usually made by animal/mammalian cells (such as CHO, (Chinese Hamster Ovary)) which are cultivated under strictly controlled conditions. The next step involves the clarification of the solution and the antibody purification. This phase poses minimal health risks, as mAbs are not inherently toxic. However, depending on the production method, there may be potential exposure to biological agents (e.g., bacteria, viruses), so containment strategies must be evaluated on a case-by-case basis. cGMP cleanrooms and closed systems as well as BSCs or aseptic containment isolators are therefore necessary to preserve the sterility of this process and prevent contamination. While mAb production poses relatively low risk to operators, the same cannot be said for the synthesis of the cytotoxic payload.This is unquestionably the most hazardous phase in ADC production. Payloads are often rated OEB 5 up to OEB 7, they can be lethal in infinitesimal quantities, and may pose a risk of DNA damage. Due to their extreme toxicity, this phase requires the use of aseptic high-containment isolators to simultaneously protect operators, the environment, and the cytotoxic compound from contamination. These isolators typically operate under negative pressure to protect the operators while grade A airflow to protect the product. Those isolators are equipped with glove ports, HEPA filters, closed transfer systems, and integrated cleaning and decontamination systems. In contrast, linker toxicity depends on its chemical structure, and its synthesis poses safety risks because it implies the handling of active chemicals and solvents. Therefore, aseptic containment isolators are also used in this phase, with containment depending on OELs.

Next, we move into the conjugation, purification, and quality testing phases, all of which share similar safety risks for operators due to the presence of cytotoxic payloads—while also requiring strict process sterility. For these reasons Aseptic high-containment custom isolators (from OEB5 up to OEB 7) play a critical role in ensuring safe and sterile operations. The final phase is formulation and fill-finish, where the ADC is prepared in its final buffer and filled into vials or syringes. Fill-finish operations are conducted in Grade A isolators, which provide a sterile environment and high containment. FPS Pharma custom fill-finish isolators can be easily integrated with automated filling lines and equipped with CIP and SIP systems to ensure the utmost safety and efficiency. As we’ve seen, ADC is a multi-phase process that demands strict aseptic conditions, high-potency API containment, and full compliance with regulatory guidelines to ensure both operator safety and product quality. Each phase presents distinct challenges and risks, requiring a comprehensive approach to risk management, along with the right containment strategies and safety protocols. FPS Pharma is globally renowned as a trusted partner in the engineering and manufacturing of innovative, custom high-containment isolators used for handling and producing highly potent and sterile pharmaceutical ingredients—such as ADCs, a class of HPAPIs. Given that every ADC manufacturing process presents unique requirements, only custom aseptic containment isolators designed for toxic applications can ensure full regulatory compliance and meet all necessary safety and quality standards. FPS Pharma recognizes how critical Occupational Exposure Limits (OELs) are in the production of Antibody Drug Conjugates (ADCs) due to the unique and ultra-potent nature of these compounds. For this reason FPS Pharma engineers Occupational Exposure Band (OEB) isolators—from OEB 4 up to the latest OEB 7—equipped with advanced safety and monitoring systems tailored to your specific process and OEL requirements, ensuring safe and compliant ADC operations.