Data-Driven Manufacturing Operations

Summary

A biopharmaceutical, also known as a biological medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Biopharmaceuticals may be produced from microbial cells, mammalian cell lines, or plant cell cultures in bioreactors. In the final stage of the (sterile) manufacture of such large molecules, the active pharmaceutical ingredient (or drug substance), excipients, and water must be amalgamated and transferred into the designated containers (i.e., vials or syringes). Despite the automation of the actual production processes (e.g., filling or visual inspection), numerous other processes such as planning and troubleshooting are manual and time-consuming.

A plethora of data is generated in this setting, which can be utilized for decision-making or for sampling. This encompasses data from manufacturing instructions, deviation reports, electronic batch records, sensor and alarm data from the operational historian, or business data from the enterprise resource planning system.

The objective of this endeavour was to scrutinize and digitalize the (remaining) manual processes and to leverage the available data to cultivate a culture of data-driven pharmaceutical manufacturing. This culminated, for instance, in the establishment of a digital hub.

Examples

Artificial Intelligence

A large amount of documentation is typically generated during the commercialisation of pharmaceuticals. This documentation can include manufacturing instructions, regulatory documents, and guidelines for operational excellence, to name a few examples. Generative artificial intelligence has the potential to make this knowledge more accessible. Additionally, in certain cases, rough drafts of documents can be created.

Regulatory Bot

User: What are relevant principles applicable to sterile manufacturing?

Assistant: The relevant principles applied to sterile manufacturing can be summarized as follows:

1. Facility, Equipment, and Process Design
   • Must be optimized, qualified, and validated according to Good Manufacturing Practices (GMP) guidelines. Use of appropriate technology such as Restricted Access Barriers Systems (RABS), isolators, and rapid microbial testing systems to protect the product from potential contamination.¹
   • Should include measures to prevent contamination, such as cleanrooms, airlocks, RABS, and isolator.
2. Personnel
   • Personnel should possess adequate qualifications, experience, training, and attitude focused on protecting sterile products during manufacturing, packaging, and distribution.
   • Proper gowning and hygiene practices are crucial to minimizing contamination risks.
3. Quality Risk Management (QRM)
   • Processes, equipment, facilities, and activities should be managed in accordance with QRM principles to proactively identify, evaluate, and control potential risks to quality.
   • QRM should be integrated into all areas of the product life cycle, aiming to minimize microbial contamination and ensure product quality.
4. Quality Assurance and Quality Control (QA/QC)
   • Quality Assurance (QA) should involve established and validated methods of manufacturing and control, and a Contamination Control Strategy (CCS) covering all critical control points and assessing the effectiveness of contamination control measures must be implemented.
   • QC includes specific requirements for testing raw materials, components, products, and environmental monitoring, especially focusing on microbial quality and bioburden testing.
5. Premises and Cleanroom Standards
   • Sterile manufacturing must be carried out in appropriately designed cleanrooms maintained to specific cleanliness standards and fitted with efficient air filtration systems. There are defined grades (A, B, C, and D) for cleanroom environments based on the activity and contamination risk involved.
6. Production and Sterilization Technologies
   • Specific approaches and technologies for aseptic and terminal sterilization processes, including handling of materials, equipment sterilization, and microbial contamination detection must be employed. The process simulation and validation are important to ensure sterility throughout the production.
7. Contamination Control
   • Continuous and effective contamination control, including cleaning, disinfection, and depyrogenation (removal/inactivation of pyrogens) are critical. Proper environment monitoring, including viable and non-viable particle monitoring, is essential to ensure ongoing sterility compliance.
8. Documentation and Record Keeping
   • Thorough documentation and review of records related to aseptic processing, including process simulations, interventions, environmental monitoring data, and microbial testing results, are required to verify compliance and address any issues effectively.

Understanding and implementing these principles are key to maintaining the quality and sterility of manufactured products, ensuring their safety and efficacy for patients.

Data Science

There are several data sources that can be used for pattern recognition, including sensor data from production equipment and entries in electronic batch records.