The LEAN manufacturing and management model, developed from the Toyota Production System (TPS), has triggered major transformations in various manufacturing industries. Implementation in the field of biopharmaceuticals, however, has been limited to date. We believe that properly implementing LEAN in biopharmaceutical manufacturing can bring huge benefits, despite the complexity of biotechnology and the stringent regulatory requirements. In this article, we provide practical examples to highlight the areas where such benefits can be achieved. We also describe our qualification concept and the implementation of a new flat and crossfunctional process-oriented organization in manufacturing sites, in line with TPS principles, to ensure the development of a "LEAN" culture—a culture of continuous improvement.
In the first part of this article, we present two case studies in which LEAN principles have been applied successfully to large-scale biopharmaceutical manufacturing, using our radical methodology. In the second part, we describe our qualification strategy and the implementation of a new flat, process-oriented organization in manufacturing sites, to ensure optimal support of LEAN and the development of a culture of continuous improvement, as described by the TPS. We conclude with some additional opportunities for how LEAN can be applied more broadly in (bio)pharmaceutical companies, with great benefits.
OUR LEAN METHODOLOGY
There are many different ways of implementing LEAN across an organization. Our methodology has been shaped over several years of application in the field of chemical, fill–finish, and now recently biomanufacturing operations. Our approach combines LEAN and the Six Sigma tools into a unique framework. The benefits of such a combination have been recognized by others.4
1. The first step in our LEAN methodology is a two-day assessment workshop, starting with a simulation game to create a strong awareness of what can be achieved with LEAN.
2. After defining the exact scope of the project, we assess the efficiency of the corresponding process—typically the manufacturing step including quality control (QC) and batch release activities—by drawing a high level "value stream map." We use only three measurements: throughput time, i.e., the overall cycle time for the production and release of a single batch; the throughput rate, i.e., the number of batches that can be produced per unit of time; and the failure rate, or "right first time" level.
4. In the second day of the workshop, the LEAN implementation plan is developed, systematically including the following key milestones:
a. selection and implementation of sensitive performance indicators
b. determination of a "drumbeat" for batch production (typically on an hourly basis)
c. overall equipment effectiveness (OEE) improvement at the identified bottleneck (usually the production bioreactor)
d. synchronization of quality assurance (QA) and QC activities with production (thus minimizing waiting time for samples and accelerating batch record reviews)
e. optimum sequencing of manufacturing activities
f. throughput time reduction through the elimination of non-added value tasks
g. implementation of a new process-oriented organization (see below).
Several different technical tools are used to support LEAN, not only during the assessment workshop, but also during the execution phase of the project, such as a process walk, value stream mapping, spaghetti diagrams, rhythm wheels, failure mode and effects analysis (FMEA), and Six Sigma. (A description of these tools is beyond the scope of this article.)
5. A multi-year implementation plan is then built from the above milestones, which typically are translated into specific sub-projects. Progress during the execution phase is monitored by a steering committee. Short and regular communication to all the stakeholders and personnel is also very important to support the LEAN transformation of the plant. Visualization of the LEAN key performance indicators (KPIs) through on-line display on various screens or information boards in the plant is also usually implemented, so that employees can quickly see and understand the improvements, as suggested by the TPS.