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The Elephant in the Room: Modernizing Non-Compliant Sterile Facilities

The Elephant in the Room: Modernizing Non-Compliant Sterile Facilities

by Hite Baker

According to DME Facility Focus, an industry-wide survey of the life sciences industry conducted by DME in partnership with INTERPHEX, we asked cGMP manufacturers to weigh in on facility modernization coupled with the challenge of achieving closed processing in legacy facilities.

Our results show that 27% of the respondents plan to modernize proactively. The troubling news is that almost half the respondents (44%) do not plan to pull the trigger on modernization unless driven by FDA scrutiny or product quality problems—in other words, a crisis situation. Surprisingly, another 17% do not plan to modernize at all.

For those manufacturers who are planning to upgrade a legacy facility, the majority stated it would occur sometime in the next 5 years (66%). The remaining owners who were planning to upgrade stated they would be undertaking it within 5-10 years (12%).

Some History
Approximately 15 years ago, the FDA began stating candidly that risk-based inspections would place more scrutiny on legacy facilities than on modern isolator/RABS-based facilities, basically those that incorporate automation and closed-system processing. This “FDA-speak” was commonly understood to mean: “You get a pass from FDA if you modernize, but you will be sorry if you don’t…eventually.”

What do owners of aging noncompliant facilities with fundamental design deficiencies need to know? The complex interplay of challenges, risks, and drivers affecting the design (or re-design in the case of legacy facilities) of sterile manufacturing facilities is staggering. Issues that range from contamination to inadequate process control and testing capabilities to evolving regulations and increased inspection scrutiny to escalating costs can seriously hinder the best-intentioned owner.

Advantages of Facility Modernization Planning
The ideal situation is to get a plan in place to modernize before there is a crisis, so as to avoid regulatory action (483’s or warning letter) or quality issues. Planning ahead for modernization begins with a feasibility study, whether achieved through a facility renovation or a new facility.

Performing a modernization feasibility study prior to a crisis allows for a paced and phased approach, where there is plenty of time for risk analysis and risk mitigation, ensuring efficient design and implementation. If there is a crisis; however, a phased approach can be compromised; an owner’s control is diminished; some options disappear; and risks and costs frequently escalate. Furthermore, if a legacy owner fixes a problem pro-actively it costs 1X vs. up to 10X if a remediation.

Moving Into the Future of Sterile Manufacturing
Historically, our industry has evolved slowly and deliberately. Up until the 2000’s, there were inevitable gaps and weak links in the aseptic “chain-of-custody” for sterile manufacturing facilities. We believe we are entering an era where a spate of legacy facilities will be forced to modernize.

From DME’s perspective, the future looks very bright. Today, those gaps can be bridged with reliable solutions, including:

  • Advanced aseptic filling/packaging systems – i.e., barrier systems, isolators, and closed RABS, BFS (blow-fill-seal), FFS (form-fill-seal), automation and robotics, closed vial filling
  • More effective statistical process capability and control metrics
  • Quality risk management and assessment techniques
  • Process Analytic Technology (PAT)
  • Risk-based, scientific lifecycle approaches to process and system validation
  • Innovative sterilization techniques – e.g., E-beam surface sterilization
  • Single-use drug manufacturing and filling systems with 100% weight checks
  • Highly-flexible, small-batch combination filling machines for vials, syringes, cartridges
  • Ready-to-use primary containers, components, stoppers, over-seal/caps
  • Real-time and rapid microbiological monitoring and testing
  • Post-Aseptic Lethal Treatment

About the Author

An industry innovator in cGMP manufacturing, Hite Baker, Principal Process Engineer, DME focuses on equipment and facility design for parenteral fill-finish operations. He has extensive experience in the regulated life sciences industry, including biopharmaceuticals, vaccine products, cleanroom facility design, and technology transfers. He is an active member of ISPE and a frequent speaker on sterile manufacturing technology.


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