Critical aspects of applying QbD to pharmaceutical process and product

development for US Pharmaceutical Companies

Short Abstract
If the product is the process understanding both is critical for commercial
success, a QbD approach is essential for process and product knowledge
generation the foundations that are being used for your product
development will determine its success or failure which do you chose
knowledge or ignorance for the path forward

Over the recent decade it is clear that the expected critical output in terms
of regulatory agency expectations of product development is an in depth
understanding of both the process and product characteristics. This is a
foundational requirement upon which the complete product lifecycle is
based. This encompasses the principles of Quality by Design (QbD), the
heart of which is the idea that Quality, safety, and efficacy are designed or
built into the product and that Quality cannot be adequately assured merely
by in-process and finished-product inspection or testing. These are the
fundamental concepts and once understood and accepted the QbD
approach can become an integrated component of the overall process
development effort. The process is logical and the underling concepts
rational and yet adoption by industry is not without some resistance to
change. Often the long term benefits are not well understood and shorter to
mid-term business objectives become the key drivers, speed to market is
the critical path. Which is a valid objective given the cost of product
development and the need to return the investment? However consider the
better investment of staying the complete course of the product lifecycle
and not suffering a premature ending due to commercial manufacturing
failures or out of control costs.

Still QbD is often viewed as a means to an end perhaps facilitating a

speedier review by the regulatory agencies. Then the question might be is
this worth the effort is the potentially longer process development times and
higher cost offset by any strategic business and commercial benefit. Well
the answer really is what worth knowledge, knowledge of process and
product are invaluable in terms of firstly achieving approval to market the
product and then keeping the product supplied to the market. This is not just
a regulatory nice to have element it is the foundation upon which the whole
product commercialisation can be built.

http://www.biopractice.com/webinar/recorded/10/critical-aspects-ofapplying-qbd-to-pharmaceutical-process-and-product-development-for-uspharmaceutical-companies.html

Applying Quality by Design ideas to herbal products

The development of new of herbal products could be significantly improved
by applying a Quality by Design (QbD) approach to the characterization of
source materials, the authors of a recently published paper assert.
"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 dont poke around in forests to find fan belts.
Quality throughout development cycle
QbD is nothing new, Khan said. Whats 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-sizefits-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 lets 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 isnt, 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). Its going to give you peace of mind, he said.
Source: Journal of Natural Products
Volume 75, Number 9, doi: 10.1021/np300434j
Implementing a Quality by Design Approach to Assure the Safety and
Integrity of Botanical Dietary Supplements

Quality by Design Model for Safer Dietary Supplements

Till date dietary supplements are governed under the foods section of the
USFDA, thus making it the liability of the manufacturer to make good quality
and safe supplements.
Hence, they need not require approval from the FDA to market supplements
containing ingredients that are generally considered safe. However, this is
raising issues regarding safety of herbal dietary supplements and the
variation in the quality of the same product from different companies.
Quality by Design Model (QbD)
To solve this problem the scientists have published a paper describing the
various analytical techniques that one can use to ensure the use of high
quality raw materials and excipients in the production of a drug. These
include the classic techniques to the most modern ones that one can adopt
during the manufacture of a drug.
Further, the scientists suggest that these techniques be applied right at the
drug discovery and development stage. This will ensure that the
manufacture of the right drug happens in line with its development. The
final result would be a fine and safe product that would also be marketed
using the same quality by design rule.
QbD v. GMP
GMP is nothing but Good Manufacturing Procedures. This ensures that the
manufacture of the product happens using the best raw materials and
techniques possible. QbD however, ensures that these good procedures are
followed even in the development process. So the final product has quality
etched in every level of its production.
Hence, following QbD in herbal dietary supplement manufacture is
recommended to make the supplement market more reliable.
http://www.altmedicinezone.com/latest-news/quality-by-design-model-forsafer-dietary-supplements/

Ensuring high-quality dietary supplements with 'quality-by-design'

Implementing a Quality by Design Approach to Assure the Safety and
Integrity of Botanical Dietary Supplements
Journal of Natural Products
If applied to the $5-billion-per-year dietary supplement industry, quality by
design (QbD) a mindset that helped revolutionize the manufacture of
cars and hundreds of other products could ease concerns about the
safety and integrity of the herbal products used by 80 percent of the worlds
population. Thats the conclusion of an article in ACS Journal of Natural
Products.
Ikhlas Khan and Troy Smillie explain that the U.S. Food and Drug
Administration (FDA) regulates dietary supplements as a category of foods,
rather than drugs. Manufacturers are responsible for the safety of their
products. However, they need not obtain FDA approval to market
supplements that contain ingredients generally regarded as safe. While
manufacturers, packagers and distributors are required to follow good
manufacturing practices, variations in growing, processing and even naming
the plants used to make supplements opens the door to problems and
introduces challenges with reproducibility. As a result, the consumer must
take it on faith that the supplement they are ingesting is an accurate
representation of what is listed on the label, and that it contains the
purportedly active constituents they seek, Khan and Smillie note. The
authors looked for solutions in a review of more than 100 studies on the
topic.

They concluded that a QbD approach ensuring the quality of a product

from its very inception is the best strategy. One key step in applying QbD
to dietary supplements, for instance, would involve verifying the identities of
the raw materials the plants used to make supplements. It is clear
that only a systematic designed approach can provide the required solution
for complete botanical characterization, authentication and safety
evaluation, they say.

https://www.acs.org/content/acs/en/pressroom/presspacs/2012/acspresspac-october-3-2012/ensuring-high-quality-dietary-supplements-withquality-by-design.html