TBM Case Study - Roche: Lean Labs at Roche Carolina Define Good Manufacturing Practices
Case study | Pharmaceutical Manufacturing: Progressive 5S
Lean Labs at Roche Carolina Define Good Manufacturing Practices
By applying lean tools, such as 5S and visual management, Roche Carolina laboratories set the standard for quality control and help the company respond to market demand for critical drugs like Tamiflu®.
Client: The Roche Carolina campus (www.rochecarolina.com) develops production processes for and makes active pharmaceutical ingredients (APIs) and intermediate drug compounds. It is a division of the global pharmaceutical company, Roche, headquartered in Basel, Switzerland.
Challenge: Rather than follow the minimum guidelines for pharmaceutical production enforced by the U.S. Food and Drug Administration, the managers at Roche Carolina have chosen to set the standard for best manufacturing practices. This case study looks at what they have done in the QC labs using 5S and process standardization to both meet regulatory requirements and release product as quickly as possible.
Solution: Lab associates implement 5S principles, sorting material and equipment into what’s needed and what’s not, setting everything in order by storing it in common and highly visible locations, standardizing labels, and driving sustainability with daily, weekly and monthly checklists. Combined with frequent communication between departments, the improvements in the QC labs contribute to the successful production ramp up for the unexpectedly high demand for Tamilfu®.
Results: The QC labs achieved zero observations following their most recent FDA audit. The inspectors even used the laboratorie's 5S processes to train their staff in best manufacturing practices. From a customer point of view, testing lead times remain constant at industry-leading levels of less than five days, despite a five-fold increase in output for critical drugs.
When it comes to pharmaceutical manufacturing, the U.S. Food and Drug Administration (FDA) inspects facilities on a two- to three-year cycle for conformance to “good manufacturing practices.” Intentionally vague, the regulations recognize the fact that the best manufacturing and quality control practices are constantly evolving (see box below). Rather than follow the FDA’s minimum guidelines, the quality team at Roche Carolina (www.rochecarolina.com) have chosen to lead the way.
“Being regulated, that first impression is absolutely enduring,” says Tracy Taylor, Manager of Quality Control at Roche Carolina. “When the FDA walks in, I literally have 10 minutes notice. They arrive at the front gate, security calls, and we bring them in. If they come into a place that’s a mess, their impression will be that this is not a well-managed lab. On the other hand, if it looks stellar, if it’s clean and organized, that’s another story.”
This case study explores how Roche Carolina has applied 5S, one of lean manufacturing’s core tools, to a laboratory environment. By emphasizing workplace organization, order and cleanliness, 5S helps employees do their job more efficiently and effectively. How Roche went about implementing 5S in a laboratory setting offers some valuable lessons to others implementing visual process improvement methods beyond the factory floor.
5S Supports a Culture of Excellence
Roche Carolina has a comprehensive operational improvement program with green belt and black belt-certified employees who’ve been formally trained in a variety of lean and Six Sigma tools. Following the example set in the laboratories, they have rolled out 5S in manufacturing, in the pilot plant where new production processes are tested and perfected, and in its laboratories. The area where they perform drug stability tests, for example, have been cleaned out and outfitted with only the liners and containers required to perform the designated tests.
Roche also conducts regular Kaizen events. These are typically one-week improvement projects that target a particular process, drawing on team members from a cross-section of departments to analyze and make immediate process changes. A recent event reduced the number of handoffs and thereby improved the efficiency of providing all of the documentation required for each shipment. One of the key metrics here is the amount of time between when product is produced and the time when it’s released for shipment.
Compared to a two- to three-week lead time in the past, today the lab consistently tests products for release in just over six days.
“This contributes to lower inventory requirements, higher throughput and the fast shipment of high-demand drugs,” says Doug Bonner, TBM senior consultant who has worked with Roche Carolina on a number of projects. One of these was the logistics processes for Tamiflu®, demand for which spiked with the onset of the H1N1 flu virus. “We helped them establish key metrics, set up visual boards and an online tracking system for reporting batch status,” he reports.
At the beginning of the year, before the flu pandemic was declared, the company hadn’t planned for extraordinary production volumes for Tamiflu because they had a sufficient quantity in stock to meet the typical demand caused by seasonal flu, according to Taylor. Ramping up production required a lot of coordination and communication between suppliers, manufacturing and logistics. Taylor’s labs did their part by maintaining consistent release times despite the significant volume increase.
When visitors tour Roche Carolina, they invariably visit the quality control labs. The typical comment, Taylor reports, is that it doesn’t look like anyone works there. There aren’t a lot of vials and flasks and papers lying about. It looks sterile, as it should. By comparison, the labs, now 15 years old, look just as good as another lab on the site that went through a major renovation last year.
Eye of the Beholder
Taylor’s team of nine analysts works in five labs where they test incoming raw material and final products. They follow a well-defined test protocol for each active pharmaceutical ingredient (API) and intermediate compound, which after release are shipped to other Roche facilities for final formulation. Taylor has worked with the QC labs to implement 5S and update standard operating procedures. Their efforts have paid off in a variety of ways. Achieving zero observations on its most recent FDA audit, the head investigator even used the laboratory’s practices and processes as an example for junior investigators of what to look for in a well-managed QC lab.
The analytical laboratories are outfitted just as you would expect, with benches and a variety of instrumentation, and tons of storage in cabinets and drawers. Analytical test capabilities include high-performance liquid chromatography, gas chromatography, XRF spectroscopy, infrared spectroscopy, mass spectrometry, particle size analysis, wet methods, titrations, and more. Applying the 5S principles in this setting proved to be no more difficult, and just as beneficial, as it is in manufacturing areas.
Sort – During the initial 5S implementation, the defining question is, “Do we need it, or not?” The question is asked of equipment, materials or consumables. If the answer is no, it’s disposed of. “We freed up so much space because everything was all over the place,” recalls Taylor. “We discarded a bunch of stuff, and found stuff we didn’t know we had.” This included many high performance liquid chromatography (HPLC) columns that are used to separate drugs from impurities, which cost upward of $600 each.
Set in order – During the sort process, if the answer is, “Yes, we need it,” the equipment and materials are moved to a logical place and labeled or otherwise identified. This is where taped lines on the floor and shadow boards for frequently used tools often come in. In the labs they moved gloves, which people had been hoarding in various cabinets and drawers, to a standard location in each of the five labs, and they mounted the HPLC columns on wall racks.
Shine – Roche implemented the cleaning and housekeeping aspect of 5S through daily, weekly and monthly audits in each laboratory. Detailed checklists included dusting shelves and cleaning floors, as well as maintenance items such as requesting repairs to lights and fans that aren’t working. Guest inspectors from elsewhere on the Roche campus brought a fresh set of eyes and offered their comments and feedback.
Standardize – Instrument status log books record equipment qualification, maintenance, repairs, and operational data. When they started to implement 5S in the labs these log books were incomplete, they were stored in different locations, and some needed data has stored elsewhere. As part of the standardization process, they bought new log books and put them in a defined place in each lab so everyone would know where to find them and what instrument they went to.
“The key when we first started was that management was involved,” says Taylor. “It wasn’t just the analysts. My director came on audits, made comments and was very involved to show how important it was.”
Roche also standardized how they labeled containers of chemical mixtures. Previously everyone had been doing it their own way. They had easily removable, custom labels printed and required that each label be filled out completely by whoever had mixed the containers’ contents. The labels were then checked as part of the daily audits.
Sustainability – “Anyone can go in and do 5S, but if they don’t have the sustainability part of it, they’ll be doing it again and again. It’s a continuous process; you don’t just do it and forget about it,” says Taylor. After six months, Roche cut out the weekly audits and rolled those activities into the daily and monthly checklists. Making a 5S project part of every analyst’s annual objectives has been another key to sustainability. “One of the important parts of 5S is accountability,” he adds. “If you’re working in a laboratory that’s clean, you will have more ownership. You will be more accountable for keeping it clean. I don’t have to go in the lab and tell people to pick up their stuff. It has become self policing.”
“Even though the workload went up five-fold, the testing time stayed the same or was slightly less. That was driven by 5S and other efficiency improvements. ”
Roche Carolina and TBM Consulting Group
Located in Florence, S.C., Roche Carolina (www.rochecarolina.com) makes and develops manufacturing processes for active pharmaceutical ingredients (APIs) and intermediate compounds. A division of Roche, with global headquarters in Basel, Switzerland, the site makes the active ingredients for Xeloda® for breast/colorectal cancer, Xenical® for obesity, Tamiflu® for the flu virus, and Pegasys® for hepatitis C. The South Carolina campus includes one of the company’s Pharma Tech Centers, a research and process development center that includes a pilot-scale production plant.
TBM Consulting Group has worked with Roche Carolina, which won the Shingo Silver Medallion for Operational Excellence in 2008, on a number of process improvement projects and kaizen events. These include: Manufacturing process changes. The change request process was taking too long, was too complicated and involved too many people.
By mapping it out and documenting issues, the team consolidated three separate databases into one database, and cut out a number of unnecessary steps. Including all of the follow-up work, the new processes eliminated unnecessary handoffs and reduced delay time, total processing time, and overall lead times.
Quality control release time. Release time for a high-demand API ranged from 1 to 12 days and was very unpredictable. Mapping the process and documenting issues identified inbound and outbound constraints, TBM helped Roche Carolina develop an optimum flow for inbound processing, quality control and outbound logistics. The team eliminated redundant checks, excessive material movement, and developed standard work and the testing schedule. The end result of this project and related work was a smooth workflow and a 4.9-day average release time (7-day maximum) from the drying stage to product shipment.
Production scale up. The process of scaling up production of an API from the laboratory to production was not well defined. This initiative included developing a standardized project plan, visual tracking of project milestones, removal of non-value-added tasks, reducing documentation redundancy, elimination of loop backs, and earlier approval of raw material purchases. These efforts collectively reduced and stabilized the time from request for a production campaign to actual production in the pilot plant.
Technician hiring process. The lead time for hiring technicians sometimes took more than six months, including 50 steps, 30 handoffs and 14 different types of delays. Mapping and streamlining the process, including voice-of-the-customer input from applicants and managers, identified a variety of improvement opportunities. New processes designed by the kaizen improvement team reduced the collective identification-of-need to job posting time, ad posting to interview time, and hiring conference/ application to communication time, from 25 weeks to 7 weeks.
Current Good Manufacturing Practices: A Regulatory Scheme that Requires Continuous Improvement
The U.S. Food and Drug Administration (FDA, www.fda.gov) regulates pharmaceutical manufacturing operations under the authority of the Federal Food, Drug, and Cosmetic
Act. It ensures the quality of drug products by monitoring drug manufacturers' compliance with Current Good Manufacturing Practices (cGMPs) regulations. As noted by the FDA, “adherence to the cGMP regulations assures the identity, strength, quality, and purity of drug products by requiring that manufacturers of medications adequately control manufacturing operations. This includes establishing strong quality management systems, obtaining appropriate quality raw materials, establishing robust operating procedures, detecting and investigating product quality deviations, and maintaining reliable testing laboratories.”
Departing from more prescriptive regulatory models, the FDA maintains cGMP guidelines but the requirements are intended to be flexible, allowing companies to use the latest technology and management approaches to achieve superior levels of quality control through continual improvement. The agency essentially leaves it up to manufacturers to determine and define what these good manufacturing processes are, and expects them to continue to push the envelope. Increasingly, in the lab and in the factory, these practices are incorporating lean manufacturing principles, methods and tools to protect the nation and the world’s drug supply.
About the TBM Pharmaceutical Practice
TBM Consulting Group is the worldwide leader in lean innovation and rapid sustainable business improvement for manufacturing and service industries. We have helped pharmaceutical companies improve quality, eliminate order backlogs, remove capacity constraints, increase productivity and asset utilization, rapidly integrate new acquisitions, streamline research and development processes, and improve customer responsiveness. Learn more at www.tbmcg.com or contact Bill Schwartz at 800-438-5535.
