By Scott Mangiacotti, Automation Solutions Leader, GE Healthcare Life Sciences and Trevor Marshall, Director of Global Engineering, Zenith Technologies

 

Over the last decade, the pharmaceutical industry has seen a dramatic evolution of its traditional business model. Rather than relying on blockbuster drugs that offer a substantial payoff, today’s companies are intensifying their efforts to generate targeted drug candidates to support personalized medicine and combinatorial therapies. Not only does this evolution call for new and innovative approaches to drug pipeline development, but it also increases the need for operational efficiency. Now, greater speed, productivity, and accuracy have gone from being just advantages in a complex manufacturing environment to requirements, leading to more investments in technology and automation.

However, integrating automation in a biomanufacturing environment successfully can become a daunting task without the right preparation and a clear implementation strategy. Through proper planning, you can eliminate costly errors and missteps and focus on developing efficient, future-proof automation strategies.

It is never too early to think about automation

Automation systems have the ability to provide you with streamlined, centralized control and improved transparency of your manufacturing processes. They can also collect and analyze valuable data that could potentially help accelerate the regulatory review process. This is possible only if your system is appropriately designed and considerations for its functionality and stakeholder deliverables begin as early in the project as possible. This should start in the early phases of project development, as part of the concept study phase, where it is important that automation needs and expectations are documented as well as defined.

What should the concept study and basic design include?

The main purpose of a concept study typically relates to the process requirements and process equipment needed to bring a new drug to market at a facility or to perform a transfer of production from one facility to another. The information in the concept study can be at a high level or as detailed as necessary, depending on the type of facility being developed.

The automation strategy serves as a key document as project execution evolves from concept design, to basic design, and then to detailed design and execution. Including the automation strategy for the project in the concept study will anchor a project to decisions that underpin the level and complexity of automation and manufacturing systems agreed upon for a project. It also keeps everyone on track by providing the rationale for the key pillars of the project. When different stakeholders or new hires enter throughout the lifecycle of the project, the potential for new strategies or ideas regarding the automation strategy can surface. This causes diversions from the original basis for the project, potentially leading to confusion and frustration.

For an existing facility where new equipment is being added, such as new bioreactors, the document can simply state to follow the same approach used in previous projects if no additional enhancements or integration is necessary or required. This statement creates a clear path forward for the project. For new greenfield facilities, with new manufacturing systems being deployed, it is important to spend an appropriate amount of time during the concept and basic design phase defining the complete scope of the automation project. This includes the level of integration of manufacturing systems across the shop floor up to the enterprise resource planning systems (ERP).

Verify that all automation software deliverables are clearly defined so that, as the project progresses, it can be measured accurately and reported on throughout detailed design and project execution. This involves identifying the software element required and putting the lifecycle of each one in the plan, i.e., design, code, and test. The more granular and detailed the plan, the greater the level of accuracy during project execution.

Align expectations now to avoid issues later

It is critical the overall project stakeholders are aligned on the automation scope and delivery from the beginning, to avoid late changes to key design principles, which can add cost and create delays. Both your team and the suppliers must also be aware of the end goal, including schedule and technical and commercial agreements. Identifying what is most important, and making compromises where necessary, creates a plan that satisfies all stakeholders. This means understanding your needs from a technical, schedule, budgetary, and compliance perspective. Do not overdo or underdo any of those expectations as it will inevitably lead to dissatisfaction. When providing new equipment to an existing facility, take time to understand how it will work with existing equipment as well as the interface techniques, so the integration is seamless.

Establish mutual understanding of validation and testing procedures

To ensure a system is going to function as intended once it is up and running and will meet the validation requirements, use good automation manufacturing practices (GAMP) to align validation and testing expectations. Using GAMP also establishes a mutual understanding between you and your suppliers in terms of the computer system validation process and what is expected from each side for it to be successful. When purchasing specialized equipment or software from a vendor, it is important to include their expertise in relation to the level of testing required at each stage of the project, be it at the vendor’s location or on site. Creating trusted relationships with key suppliers builds trust in the supplier’s validation and testing processes while also enabling the supplier to become familiar with a particular customer’s expectations or nuances related to corporate ways of working.

In cases where the automation software project to be supplied by a dedicated automation system integration supplier covers multiple equipment vendors, it is particularly important that an integrated project delivery schedule is planned. The inclusion of a risk-based approach to validation, where customers are looking to leverage testing from equipment vendor locations to the overall validation lifecycle, can present schedule challenges when supplying automation software components to the equipment vendor location. Equipment vendors that have strong automation software integration capabilities can often provide a lever that alleviates these challenges. This upfront planning helps set out what can be achieved within the team, based on the different constraints and requirements for the overall project program.

Staff appropriately to meet key deadlines

For an automation supplier to deliver on its commitments, the process inputs for the system must arrive in a timely manner. Often, though, there is a pull on key resources during the design phase of a project. Specifically, the team members with the most process knowledge are also involved in the equipment specification, equipment design review, and equipment testing. These activities run parallel with the automation project. If the automation supplier does not get the necessary information in time, challenges exist to provide the software to the equipment supplier for testing. Overall, incomplete requirements or assumptions on the supplier’s or customer’s part are always key gaps to close when engaging in project deliveries of any kind, and that is no different for automation.

Create clear expectations when working with multiple vendors

When trying to integrate unit operations from multiple vendors into one central automation platform, there must be clear, unambiguous lines or boundaries in the scope of supply between each vendor. Create software interface agreements that include a communication protocol with detailed requirements or parameters, so each vendor knows what it is expected to provide the other vendor. For example, if vendor A wants to put a supervisory control and data acquisition (SCADA) system on top of vendor B’s programmable logic controllers (PLCs), vendor A must know where any data blocks are and how the data is arranged. If vendor A does not have this information and has to wait until the PLC project is finished before it can do its SCADA screens, it will likely miss the project deadline.

It is possible to streamline this process by partnering with an equipment vendor that can also supply and integrate the software. This helps eliminate silos that can exist in a multi-vendor approach, increasing communication and speed and reducing potential confusion and errors. A partner with knowledge in both automation and process development not only understands what they are trying to automate but also has the foresight to recognize issues that could become major, and costly, roadblocks later.

Automation considerations during capacity expansion

New facilities are often designed based on the expected demand for a product. If that demand increases beyond the capacity of the facility, it is more than likely there will be a need for additional equipment. This creates one of the biggest challenges of automation integration, which is to connect new equipment without interrupting current production. With capacity expansion for stainless steel, this can lead to restrictions in the ability to clean-in-place (CIP) or sterilization-in-place (SIP) enough equipment with the current utility infrastructure. It can also lead to shortages from a water for injection (WFI) perspective, steam header pressure, or other utilities.

These issues and others related to stainless-steel equipment are in some cases being resolved by the use of single use mobile equipment. While offering the ability to move equipment to different locations dependent on the production process flow requirements it also provides the ability to increase capacity by scaling out production and adding more equipment units to the facility. By using disposable bags, single use equipment removes the need to cater for CIP and SIP of these units. With a growing need for production flexibility, this concept has made a steady trend in biomanufacturing and offers sizable benefits when employed across multiple facilities with automation. In addition, advances in inline conditioning for chromatography skids are giving way to using buffer on demand, reducing the need for a large number of buffer vessels or buffer totes. Advances in continuous chromatography are also helping to achieve greater throughput in downstream processing.

Plan for the future

When building for flexible production, do not forget about the small but important details of your facility design, such as locations for wiring and proper placement of communication and electrical outlets. Planning these details in advance allows you to reconfigure your facility later as needs change, which is critical in mobile single use production facility. In addition, as you expand and want to connect more than one facility, make sure to use consistent data models, so you can gather insight into what is going on across facilities. The more similar each automation product is or has the same type of batch context and taxonomy used within the software structure, the easier it is to collect and disseminate the information.

Finally, planning cannot stop with only establishing the details of how to successfully execute your current capacity expansion and automation integration. You must also think ahead and consider how you will maintain system performance, such as software upgrades and/or technical support after installation is complete, as well as future automation needs, such as add-ins. Do so by choosing a vendor that offers more than just a transactional relationship; your partner should be one that intends to play an active role in your long-term strategy by adding value throughout the expansion and beyond.