Despite these successes, not every batch manufacturer has figured out how to address these issues. Kam Yuen, Proficy product manager at GE Fanuc, says GE Fanuc is seeing more flexible batch management projects that include quality initiatives. However, sometimes they’re designed incorrectly, so the installed solution doesn’t deliver the expected or potential benefits.
Yuen’s observations are shared and expanded on by Paul Wlodarczyk, vice president at JustSystems. Wlodarczyk believes that for the biopharma industry—product-owner companies and contract manufacturers—to work together, they must use a standardized batch control and recipe development solution.
“Product development information is often recorded by scientists using flowcharts and spreadsheets. When it comes time to transfer product and process information from R&D to a pilot plant and, later, to production, extracting and interpreting this information requires a series of conversations and manual development of new documents. This is difficult and time-consuming when all parties work for the same company, but transferring this information between the product owner and a contract manufacturer to produce an executable recipe can be downright maddening. By leveraging the World Batch Forum’s BatchML implementation of the ANSI/ISA 88 family of standards, it’s possible, using the XML schema language, to develop upstream recipe development tools that can output BatchML-conformant recipes,” claims Wlodarczyk.
Changing the Picture
Since about 1990, the biopharma industry has invested heavily in information technologies (IT), and those investments have paid dividends. However, according to a number of surveys, these IT investments could be doing much more.
One such poll occurred during a recent batch management webinar about moving from paper to paperless manufacturing. During the presentation participants were asked, “How are you managing recipes and process definitions today?”
Participants selected from one of four pre-defined answers, and the tabulated results were as follows:
- 42.3% selected “Manual, ad hoc, spreadsheets, flow charts and other static documents;”
- 11.5% selected “Manufacturing operation adopted ISA88 standards, but in isolation (no coordination with R&D or enterprise ERP systems);”
- 30.7% selected “Process development hands off process specifications to contract manufacturer responsible for recipe development;”
- 23.0% selected “Standardized, authoritative, reusable process definitions and manufacturing actions.”
When you compare these poll results to how to address Lenich’s four goals, one solution keeps showing up—create a robust MES environment based on quality-by-design principles the FDA has been evangelizing for nearly a decade.
Kircher says MES solutions come in many flavors, but users should still expect out-of-the-box capabilities that address:
- Document control and archiving that provides controlled access and version control per FDA 21 CFR Part 11 requirements;
- Electronic batch records that conform to cGMP best practices, support multiple entry methods, manage execution of standard operating procedures and production batch protocols, while providing complete traceability, batch history, audit trails and consistent reporting;
- Equipment tracking that includes equipment properties, status states and events such as usage, cleaning and maintenance;
- Material management that supports material lifecycle workflow, including management of material purchasing, receiving, warehousing and shipping;
- Recipe authoring that uses object-oriented techniques, supports multiple languages and produces XML-based work instructions;
- Scheduling and tracking that meets requirements dictated by master recipes, manages conflicts and keeps ERP systems updated;
- Security and audit capabilities that rigorously conform to the FDA’s 21 CFR Part 11 regulation for electronic records and signatures;
- Statistical analysis of analog values and discrete events, with charting and trending tools that help with continuous improvement efforts;
- Training and development records management and tracking of cGMP courses, administration and personnel scheduling;
- Weighing and dispensing that guides operators through pre-defined and approved workflows, uses bar-code scanning, electronic weigh-scales, etc., and produces a complete record to facilitate product release and regulatory review.
We’ve taken a peek at a few biopharma companies that have successfully made the business-to-production connection. Abbott shared some impressive, quantified improvements resulting from their MES implementation. We know that volumes of stories exist that describe successful S88, S95, BatchXL, MES and production-to-ERP implementations. With so many tools and publicized successes, why would the FDA’s Woodcock say that pharmaceutical manufacturing is not “state-of-the-art?”
I’m going out on a limb, and say the problem Woodcock refers to isn’t so much about availability of advanced batch management technologies, but rather about the slow adoption rate of commercial off-the-shelf technologies caused by our reluctance to embrace change.
Logically, those who recognize, embrace and pioneer batch management improvements will be here in 2020 and beyond. Those who don’t, won’t.
Dave Harrold is co-founder of the AFAB Group.
ISA88 in Brief
ISA88 is designed to address four areas of batch control and automation:
Note: ANSI/ISA88 is known internationally as IEC 61512.
Abbott’s Quantified MES Success
After one year of operation, Abbott validated the benefits of its Baceloneta, Puerto Rico, facility’s MES implementation. According to Kircher, Abbott’s use of MES eliminated 40% of documented exceptions, with contributions coming from:
ISA95 in Brief
ISA95 addresses three areas of control-system-to-business-system integration:
BatchML in Brief
BatchML is a set of XML schemas written using the World Wide Web Consortium’s XML Schema language (XSD) for implementing batch, master recipe and equipment data in part or in whole per the ANSI/ISA88 family of standards. BatchML is available royalty-free provided credit is given to the World Batch Forum. Visit www.wbf.org for more information.