Bringing Legacy Pharma Manufacturing Facilities Into The Modern Age

By Ken Congdon

Whether you’re producing drugs using small molecule or biotechnology, keeping your manufacturing facilities current is of utmost importance. First, the FDA requires companies to use technologies and systems that are up-to-date in order to comply with cGMP (Current Good Manufacturing Practices) regulations. Second, leveraging the latest manufacturing technologies and processes can provide the added flexibility, throughput, and efficiency to give you a competitive edge.

Legacy Facilities Provide Challenges And Opportunities

Adhering to cGMP should be a goal for all pharmaceutical companies. However, this can often present a huge challenge, particularly when it comes to updating legacy manufacturing facilities. These are existing manufacturing sites that have developed over an extended period of time and have undergone incremental and continuous changes from their original configuration.

Managers of legacy facilities must constantly address problems associated with aging infrastructure, outdated equipment, and antiquated processes. In a recent presentation at the ISPE Quality Manufacturing Conference, David Marks, P.E., President and Principal Consultant at DME Engineering outlined a host of additional challenges associated with legacy facilities including:

• Facility unknowns
• Inadequate documentation
• GMP and technology gaps
• Complex process systems
• Facility segmentation and interrupted workflows
• Construction activities

Finally, legacy facilities may also have difficulty accommodating new products and technology. However, despite these drawbacks, established facilities possess many attributes that often make them worth updating and maintaining as opposed to shutting down and building anew. For example, legacy facilities represent a significant capital investment that has already been made. Better to refit and repurpose this infrastructure for the future rather than scrapping it. Moreover, legacy facilities already employ an experienced staff and have an established logistical infrastructure (i.e. location, set systems for support services, supply chain, shipping and distribution)

Use A Master Plan To Upgrade Existing Manufacturing Sites

A combination of risk factors (e.g. compliance, product quality, obsolescence, safety, reliability) and opportunity considerations (e.g. flexibility, throughput, sustainability, ROI) will ultimately drive manufacturing modernization. However, once the determination has been made to update a legacy facility, what best practices should be followed to ensure the effort is a success? Many experts champion the use of a master plan to analyze the strengths and weaknesses of your existing facility, identify improvement areas, and outline necessary process and workflow changes.

Authors Eric Bohn and Magdalena Nogalski Kraph outline the key components of master plan nicely in a 2014 ISPE blog. According to the authors, a master plan includes the following — an analysis of the existing building, a review of cGMP principles, programming, and plan development.

In order to gain a complete understanding of your current infrastructure and processes, it is necessary to gather data that will help you visualize existing conditions. This data should include flow diagrams for materials, personnel, and waste; hygiene zoning diagrams identifying areas of open product, air classifications, and cross contamination risks; and diagrams documenting gowning locations and procedures. Once you have a clear picture of your existing facility, the next step is to identify the current good manufacturing practices that will dictate facility operations.

A programming effort is then necessary to determine space and functional requirements, equipment needs, and necessary process and operational changes. The goal of this effort should be not only to make your legacy facility current, but position the site to accommodate future changes and growth.

With this information at hand, a final facility master plan can be developed. This plan should explore various layout and construction options, implementation logistics, and the associated project costs. The resulting master plan can be detailed down to the individual room level or can be more visionary and address larger functional areas. In essence, the master plan should serve as your roadmap to get you from where you are to where you want to be.

Building A Next-Generation Biopharm Facility

During his presentation at the Quality Manufacturing Conference, Marks focused on the building blocks necessary to transform an existing biopharm manufacturing site into a “next-generation” facility. According to Marks, next-generation biopharm facilities possess the following attributes:

• Smaller process scale
• More closed processing
• Expanded use of disposables and single use technology
• More “scale-out” versus “scale-up” architecture
• Increased continuous processing
• Emphasis on flexibility
• Consolidation of manufacturing space

Marks believes the move to next-generation facilities will be a growing trend in the industry as many biopharm companies tend to be laggards in this area. According to a 2014 DME Engineering survey of 30 manufacturing professionals, 28 percent of respondents said they didn’t have a cGMP facility that it would consider to be next-generation and had no immediate plans to build one. Another 19 percent said they didn’t have a next-generation manufacturing facility, but planned to build one in the next 5 years. And, 17 percent of respondents said they didn’t currently have a next-generation manufacturing facility, but were in the process of building one.

Marks also shared many of the facility and process changes that would likely be necessary when transitioning from an existing to next-generation biopharm facility. For example, increased use of single-use technology would lead to several design and equipment changes (e.g. different tube routing, spill and containment design), modified utility requirements (e.g. CIP [clean-in-place]/clean steam systems, compendial water, HVAC), and altered logistical plans (e.g. receiving and storage, disposal of single-use waste). All of the necessary modifications would ultimately be revealed and detailed during master plan development.