The authors, Ikhlas Khan, PhD and Troy Smillie, PhD, both of the University of Mississippi, argue in their paper in the Journal of Natural Products, published by the American Chemical Society, that using the approach could ensure that what’s on the label in a herbal product is what ends up in the bottle.
"It is clear that only a systematic designed approach can provide the required solution for complete botanical characterization, authentication and safety evaluation," they wrote.
QbD applied first to automobiles
The QbD philosophy was originated by Joseph M. Juran in 1992 and has been applied to the manufacture of many products with good results, automobiles being a prime example. More recently, FDA has adopted the idea as the process validation procedure in the pharmaceutical industry and has seen quality improvements in companies following this approach.
A key tenet of the approach is a systematic evaluation of quality and procedures at every step of the process, with an eye toward quick identification and rectification of shortfalls.
But some aspects of herbal products are more complicated than pharmaceuticals, and more complicated than automobiles. The components of drugs must be precisely characterized at their inception, and as for cars, well, you don’t poke around in forests to find fan belts.
Quality throughout development cycle
“QbD is nothing new,” Khan said. What’s significant is the concept of applying this approach throughout the cycle of herbal product development from inception to final marketing, so that a system is in place to characterize the raw materials and control for quality at several stages of the cycle. “A company can use several tools, as long as they are following some quality built into the process,” Khan said.
The paper details advances in the many different analytical methods available to an herbal product manufacturer, including classical botanical and organoleptic techniques, genetic fingerprinting, microscopic methods and the phalanx of modern analytical chemistry techniques.
One of the key difficulties when discussing herbal products lies in their vast diversity. “Some people are making teas, other are making extracts, some are making powders,” Khan said. It means there can be no is no one-size-fits-all approach to verifying the indenity of their constitutents. The paper acknowledges this. “Establishing a QbD model to evaluate as many of the key aspects that identify each botanical is imperative since there is no single method that can authenticate every plant sample or characterize each dietary supplement. For each botanical, there needs to be a full understanding of the constituents being considered and the capabilities of the techniques specifically suited for authentication purposes,” the paper states.
QbD vs GMPs
So let’s say a company incorporates these QbD ideas and carefully considers its source materials, designs a testing suite to adequately characterize them and ensure they consistently meet quality standards, and then manufactures them with adequate process controls to make sure that quality is maintained throughout. How is that different than making sure your company complies with GMP requirements?
It isn’t, really, Khan said. The difference lies in the application of a systematic approach to product development right at the outset, so that quality procedures are woven into the DNA of the product, so to speak. GMP compliance, by contrast, can manifest as a patchwork system of retrofitting procedures when they are shown to be lacking either in an audit or an FDA inspection.
“If you are following GMPs you are already doing it,” Khan said. “But applying Quality by Design is going to make you think before you (develop a product). It’s going to give you peace of mind,” he said.