By G.K. Raju, CEO, Light Pharma, Inc.Pharmaceutical manufacturing is a capability — a capability that helps determine how effectively and efficiently its products — drugs — can serve their vital purpose of transforming patient’s lives. Any pharmaceutical manufacturing process has the potential to meet or exceed the expectation of the industry’s various stakeholders, be they patients, regulators, executives, or CEOs. How a process fulfills that capability is determined by how the process’s “voice,” or its inherent control limits, meets with the voice of its customers and stakeholders.The pharmaceutical industry’s stakeholders form an implicitly interdependent hierarchy: At the most fundamental level, patients expect product safety and efficacy. Regulators such as the U.S. Food and Drug Administration seek assurances that product is safe and effective, and that it will be available over sustained periods of time. Heads of manufacturing organizations seek not only to assure safety and efficacy but also to improve their operations continually, and go beyond initial levels of capability. CEOs of pharmaceutical companies, each with its own processes and product lifecycles, seek to enhance the overall effectiveness and efficiency of their organizations. Finally, although removed from the actual day-to-day manufacturing effort, academics and scientists seek to understand the underlying first principles behind phenomena observed with specific pharmaceutical processes, compounds or ingredients, so that behavior can be predicted across products and across lifecycles.
The voice of the underlying process indicates the variability inherent in its quality attributes — those most critical to the customer. Capable processes, whose critical attributes show low levels of underlying variability, provide a basis for pharmaceutical manufacturing to not only meet but exceed customer and stakeholder expectations. Capability can thus be viewed as a consequence of the extent of process understanding, or manufacturing science, and the extent to which quality is designed into the manufacturing system.The current system of pharmaceutical manufacturing is overly dependent on quality testing and procedural aspects of regulatory compliance to assure safety and efficacy. At the same time, many established pharmaceutical manufacturing processes show very low levels of capability.Both industry and regulators have realized that fundamental structural change is needed, and the transformation has begun. Like other manufacturing sectors before it — automobiles, semi-conductors and aerospace — pharmaceutical manufacturing is increasingly looking to process capability analysis, which provides a means and set of metrics to facilitate change. Regulators are taking note, and applying some of these principles as well.At an operational level, process capability is a comparison of the voice of the customer as defined by specification limits versus the voice of the process as defined by control limits. Simple metrics such as the Cpk assign an actual value to capability. Computing this capability is a process in itself, since a number of conditions must be in place before a metric such as a Cpk can truly become meaningful. Some of these prerequisites include:
- having a clear scientific rationale for setting specifications
- assuring that the measurement system is itself capable and
- ensuring that the process being analyzed is in statistical process control.