In the past half-century, the name of the game in manufacturing industries worldwide has been continued improvement of product quality. It has not been an easy road, nor has it been one without blind alleys, but almost universally across the world two key figures have stood out in the drive to progressively improve the quality of the things we make: William Edwards Deming (1900-1993) and Joseph Moses Juran (1904-2008).
While adopting rather different approaches to achieving quality—Deming was a low-level, “nuts-and-bolts” man while Juran preferred a systems approach—both were widely recognized as having crucial roles in the most dramatic quality transformation of the 20th century—the transition of post-war Japan from a “me-too” manufacturer of third-rate products into an economic and quality powerhouse whose ideas and approaches were subsequently widely adopted in the West in an attempt to simply stay competitive.
The impact of the approaches fathered by these two giants has been immense. There are now entire industries (electronics manufacturing, for example) where a generational change in manufacturing technologies is expected every five years or so. It costs about the same to build a new semi-conductor wafer-fabrication plant as it does to build a state-of-the-art pharma manufacturing facility, yet the semiconductor plant will typically be replaced (or sold off) after five years because it is no longer capable of meeting the newer state-of-the-art manufacturing requirements.
There are industries where manufacturing is so flexible that products are made for individual customers (look at the latest plants from Toyota, Nissan, and Honda, where cars can, within reasonable bounds, be made to order), and where small continuous improvements in product and process are implemented at the rate of tens or even hundreds a year. There are industries in which the same technologies that pharmaceuticals use for solid-dosage manufacture are used to control material texture, uniformity, and content to much higher levels of accuracy than pharma routinely achieves. The list goes on.
A Lonely Furrow
The current relevance of Deming and Juran to the pharmaceutical industry is more a result of the absence of the approaches they developed than in their direct impact, because the industry, almost alone within the manufacturing world, has by-and-large ploughed a lonely furrow, ignoring much of what the two taught other industries. Why? There are many answers, but one of the most significant is that the drug industry (and its regulatory mirror) has progressively spiralled down into a deep “Not Invented Here” (NIH) mindset over the last 50 years.
Deming had a particular gift for a turn of phrase (what we today would call a “sound-bite”), and one of his frequently quoted comments was, “You cannot inspect quality into a product. It is already there.” These are words which should be ringing down the corridors of many pharmaceutical companies given the widespread quality failures over the last 12 months. The message was quite clear 50 years ago:
- The quality of a product is determined by its design and the processes used to make it.
- To change the quality of a product, it is necessary to either change the design of the product or change the process used to make it.
- The bigger the change desired in the product quality, the more significant the change in the design or the process.
Strangely, this is a message to which pharmaceutical manufacturers and regulators have been strongly resistant for many years, cocooned in the belief that eventually more and more inspection will deliver the product quality for which all are striving.
It is interesting, therefore, that in the midst of ploughing their own, lonely furrow, the pharmaceutical industry and its regulators have chosen to lift a phrase from one of these giants and use it in an attempt to transform the industry: Quality by Design, taken straight from the title of a book by Joseph Juran.
This phrase was brought into usage in a pharmaceutical context by Ajaz Hussain (then of FDA CDER) at the height of attempts by the Agency to change how the pharmaceutical industry viewed its manufacturing process. Hussain had already launched the process that would lead to the PAT (Process Analytical Technologies) Guidance, a revolution in pharmaceutical manufacturing approaches which the industry is still struggling to adopt. It is clear from his presentations from nearly a decade ago that his use of QbD was a direct reference to the work of Juran, and by implication a direct attempt to persuade the pharmaceutical industry to adopt precisely the approaches catalogued in Juran’s book.
Back to the Book
What is Quality by Design? What does it actually require in practical terms? It is the process of delivering the highest practical quality of product, and to achieve this, the delivery of that quality must be explicitly considered for, and planned into, every phase of development, design, manufacturing and marketing operations. These processes must effectively become an integrated whole, the primary focus of which is quality.
Juran’s approach was, as ever, built upon looking at the systems within the manufacturing process which give rise to quality characteristics. For convenience, he broke them down into 11 areas, but this is really just a means to allow users to identify particular starting points. In fact, his approach was built on the premise that it was the system as a whole which had to be working correctly to produce a quality product.
Juran’s 11 areas can be simplistically put into three clusters. The first is associated with the design process and includes:
- Identifying Customers
- Determining Customer Needs
- Developing Required Product Features
The second is associated with the quality process within all the operating sections of the facility: