China Drugmaker Drops Paper-Based Documentation

April 26, 2017
Drugmaker Zhejiang Medicine uses PharmaSuite MES to produce antibiotics on FDA’s drug-shortage list more efficiently and cost-effectively

Zhejiang Medicine Company (ZMC) is a large-scale pharmaceutical producer with roots in China dating back to the 1950s. It operates six subsidiary units that produce a diverse drug portfolio, including natural and synthetic vitamins, antibiotics, anti-viral drugs and food additives. ZMC recently created a new subsidiary, Novus Pharmaceuticals Pvt. Ltd., to serve regulated markets, primarily the U.S. and Europe. ZMC funded the construction of a new powder-for-injection production facility at one of its manufacturing sites -- a 350-acre campus located about two hours outside of Shanghai. 

One of the key drugs that ZMC will produce in this greenfield facility is vancomycin, an antibiotic used to treat bacterial infections. The drug has appeared in recent years on the U.S. Food and Drug Administration’s (FDA) drug-shortage list, due in part to the inefficient production cycle time.   

ZMC, however, developed a new technique for producing vancomycin that replaces the traditional freeze-drying process with a spray-drying process. The new approach is expected to reduce batch times from as many as seven days to half a day, making production significantly more efficient and increasing throughput. 

A key element of this new approach is the manufacturing execution system (MES). By completely eliminating the paper-documentation burden from production operations, MES helps increase efficiencies, reduce costs and enforce compliance in real-time.

Laws and regulations worldwide require extensive documentation of pharmaceutical production. The requirements vary by country or region, but they share the same goals: making sure drugs are safely produced, and reducing the threats of counterfeiting or tampering.

However, these requirements can create a mountain of paperwork that makes getting new and highly regulated products to market challenging. During production, valuable time and labor is spent on recording virtually every process-related data in batch records. Even more time and labor is needed to review those records in quality assurance (QA). 

Paper-based documentation methods also can be prone to errors, from incorrectly entering information to misreading data, which can create quality and compliance issues. 

“Our goal was to eliminate the presence of paper 100 percent in the powder-for-injection facility,” said Choon Teo, manufacturing systems architect for ZMC. “That meant eliminating not only our standard operating procedure paperwork, but also our handwritten equipment and material labels, and our auxiliary and training records.”

The challenge for ZMC was twofold. First, the company needed an MES with electronic batch recording (EBR) capabilities that could completely digitize the facility’s documentation requirements in accordance with U.S. and European regulations. Second, the company needed an MES supplier with a presence in China to provide localized integration support.

After conducting an extensive vendor-selection process, Teo and his team ultimately chose Rockwell Automation and its Rockwell Software PharmaSuite MES.

“PharmaSuite MES gave us everything we wanted,” Teo said. “Rockwell Automation also had an excellent integration team in China. We looked at other major vendors, but they lacked either the local presence or the local experience that Rockwell Automation could provide.”

PharmaSuite MES is fully integrated into ZMC’s network architecture, with connectivity up to the enterprise resource planning (ERP) layer and down to the facility’s programmable logic controllers (PLCs). It also communicates with the facility’s warehouse management system (WMS) and laboratory information management system (LIMS). 

From a process standpoint, the solution pulls production orders from ZMC’s ERP business systems and identifies the materials that need to be retrieved from the staging room. It then guides operators through production – including weighing and dispensing, sterile filtration, aseptic spray drying, filling, and inspection and packaging – to help verify tasks are completed according to the recipe. 

Integration with the process automation systems enables MES software to manage the status of production equipment and bulk containers used to transport product material. MES also captures key parameters throughout the entire process. 

Real-time alarm monitoring and exception handling can alert operators of abnormal situations and help confirm issues are immediately addressed, rather than after a batch is complete. Any collected exceptions also can serve as the starting point for QA reviews, enabling quality personnel to more efficiently address documented deviations and more quickly close out reviews.

“Using common smartphone devices, operators can scan labels with a mobile application developed by Rockwell Automation to monitor processes and confirm the correct equipment is being used,” Teo said. “It’s a more efficient alternative to using handwritten labels. And it eliminates the risk of the labels falling off or being altered.”

MES software has helped ZMC achieve its goal to make its new powder-for-injection facility 100 percent paperless. 

The facility is expected to come online later this year, at which point it will undergo an FDA preapproval inspection before commencing production. Until then, ZMC has conducted a cost analysis and undergone two phases of user-acceptance testing to confirm that the user experience matches the user requirements specifications.

“We’re saving 5 to 10 percent on our labor costs using PharmaSuite MES by eliminating manual data recording,” Teo said. “More importantly, going paperless will help prevent potential operator mistakes, such as incorrect data transcription.”

With automated data management and a far more efficient batch-review process, the company also calculates MES will help reduce supervisory and QA batch product review by 46 to 75 percent, and cut management-review cycle time by 50 percent. 

All of these savings have helped pave the way for ZMC to produce vancomycin in a more efficient and compliant facility. 

“Our unique approach to producing this drug combined with PharmaSuite MES will help us meet compliance requirements, and combined with our innovative process cut our operation costs by almost 80 percent compared to the traditional approach,” Teo said. “It’s created an opportunity for us to deliver a drug that people need while meeting our business goals.”

The results mentioned above are specific to Zhejiang Medicine Company’s use of Rockwell Automation products and services in conjunction with other products. Specific results may vary for other customers.