Pharmaceutical companies today must produce an increasing variety of products while continuing to meet regulatory demands. In addition, competition within the industry has become more acute. Dave Drew, group pharmaceutical director of Matcon (Moreton-in-Marsh, UK), says that lean production is essential for drugmakers to survive in the current environment.
In his presentation at INTERPHEX (Mar. 26–28), titled “Efficient Material Handling Is the Key to Lean Manufacturing,” Drew recognized that the pharmaceutical industry has unique requirements. He emphasized, however, that its manufacturing challenges can be addressed by lessons that the food, cosmetic, and automotive industries have already learned.
Drew explained that the lean manufacturing philosophy is based on the principles of eliminating waste, reducing inventory, and producing high-quality products efficiently and economically. To achieve lean manufacturing, companies should adopt a “pull” production model, according to Drew. The pull model is based on performing continuous production to meet customer demand, rather than to increase inventory in storage. Pull production requires short lead times and facilitates continuous improvement.
One of the challenges a pharmaceutical company faces, Drew noted, is that a new drug application “locks in manufacturing operations” with regulators before the company can find the optimum manufacturing process. Fortunately, regulators are emphasizing process analytical technology (PAT), which helps producers improve, monitor, and control the process in real time. This constant improvement maintains high quality and facilitates lean manufacturing. Controlling the process is critical, Drew observed, because “Quality cannot be inspected into the product.”
One important attribute of lean manufacturing is continuous production. Continuous processes proceed without interruption and use automation to reduce human error. In the pharmaceutical industry, compression and packaging are already continuous operations.
Drew turned to the automotive industry for an example of a lean manufacturing process. Toyota manufactures a “batch” of components in parallel and assembles them “in a continuous, timely manner,” he said. The production line only retrieves parts that have been used up, and only parts that have been retrieved are produced and replenished. This organization minimizes waste by producing based on customer demand.
Drug companies can take a parallel approach to batch mixing to achieve continuous, multiproduct production. This approach uses intermediate bulk containers (IBCs) and IBC mixers when production increases, thereby providing flexibility to the process.
A continuous process, Drew explained, requires a buffer hopper that stores enough product to keep the process in operation and allow sufficient time for manual or automated changing of IBCs. These IBCs can be used on a batch basis with processes such as dispensing and blending, provided the production rate does not starve any of the continuous processes. Operators can use a mixture of batch and continuous methods to monitor product quality.
To achieve lean blending of single products, Drew recommended continuous mixing in a Y- or double-cone blender. These blenders are also appropriate for long campaigns, he remarked. An IBC blender, however, is the best choice for multiproduct production. Y-cone and IBC blenders provide great flexibility, Drew added, but IBC blenders require no cleaning and present less segregation risk.
Drew assessed the relative merits of wet and dry granulation. He noted that wet granulation is expensive and time consuming, making it “the weakest link” in the process. Yet wet granulation is highly effective and presents minimal solids-handling risk. Dry granulation requires only one-quarter of the capital and operating cost of wet granulation, but it presents the risk of bridging and packing at process interfaces. A controlled feed to the dry-granulation process from the IBC is critical in overcoming this risk, Drew said.
Typical pharmaceutical solids-handling problems that affect lean manufacturing include bridging in IBCs, chutes, and infeed hoppers. In addition, flow control in mills, sieves, and roller compactors is sometimes difficult, Drew observed.
One solution is for IBCs to be fitted with active cone valves that rise into the product and break bridges. Operators can achieve an adjustable flow rate by continuously moving the cone valve up and down. “This method of operation provides a controlled feed to the process and prevents blockage of interconnecting chutes and processes,” Drew explained.
The segregation of blended solids in the discharge from blenders, tablet-press infeed, and capsule fillers can be solved by using IBCs for mass flow and venting displaced air correctly. PAT will not solve these problems, Drew warned.