Building a Quality by Quality by Design (QbD) and Quality Culture

The quality of a product does not occur on its own. People throughout an organization do not always carry out instructions or perform their role correctly. It is the continuing task of quality management to deal with this situation and ensure that all members of the industrial team are aware of their quality responsibilities and are accountable for their actions. Quality must be designed into products– discipline, attitude and inventiveness must be encouraged to create easy to make and easy to use fool proof products. Quality must then be planned into manufacture – methods must be devised so that the easiest way to do the job is the right one; so that, where appropriate, worker interest is created; and elsewhere complete control is built into the process. Finally, quality must be built into the product– the people concerned with the cutting, fitting and assembling must be well trained and enthusiastically led to achieve “right first time” production. This is the simple overall formula, but it is by no means simple to put into practice.

Quality cannot however be achieved solely by the Quality people; it depends on everyone being actively involved. The Quality People’s contribution is essentially one of coordinating the efforts of others to ensure the achievement of quality by communicating information on the many aspects affecting quality to all concerned and exercising control over quality monitoring throughout the organization. It must be the task/goal of all managers to ensure that the quality function of their own departments is fulfilled. This places a heavy responsibility on all senior managers.

Managers should be aware that the quality of their products is a vital factor in the continuing competitiveness and profitability of their company. Not only should they be concerned with producing products at the right price and at the right time, but they should also ensure that they are marketing the right product and that it will fully meet the customer’s and regulatory compliance requirements.

An example is enough to understand why quality and regulatory is needed:

In 1982,12-year-old Mary Kellerman died after taking an extra-strength Tylenol acetaminophen capsule, six other people died after taking the same drug. Johnson & Johnson announced a nationwide recall of 31 million bottles of Tylenol. The investigation revealed that a criminal tamperer had opened and laced some capsules with cyanide. The company destroyed all 31 million bottles of the largest-selling over- the counter (OTC) medicine in the country. FDA issued tamper-resistant packaging regulations for all OTC human drug products and incorporated them into the GMPs.

Above example shows that a single mistake can affect many lives so quality is needed with respect to regulatory.

I have mainly focussed on two points: Quality by Design (QbD) and Quality Culture which are necessary weapons to produce consistent quality products.

Quality by Design (QbD):

The Quality of the pharmaceutical product can be evaluated by in vivo or in vitro performance tests. Quality by design assures in vitro product performance and In vitro product performance provides assurance of in vivo product performance. “Hence Quality by design relate to Product Performance”.

Quality by Design (QbD) is one of the most important initiative by US FDA. “Pharmaceutical Quality for the 21st Century: A Risk-Based Approach in 2002 by FDA was the first step towards this goal of QbD compliance. Same period FDA issued another guideline on “Process Analytical Technology” (PAT) to guide the Generic Industry about the advantages of PAT in Real Time Release. This was the beginning of the journey towards implementing QbD. The concept is based on enhancement of Process & Product understanding with the help of Risk assessments, identifying Critical Quality Attributes & Critical Process Parameters to be monitored through right control strategy. Customers are benefitted through consistency in commercial manufacturing. FDA strongly recommends to include QbD elements in ANDA submissions since January 2013. It can be implemented for Biopharmaceuticals products too.

QbD facilitates design of products and processes that enhances the product’s Quality, Efficacy and Safety in the interest of Patients. 

The US Food and Drug Administration (FDA) recognised that increased testing does not necessarily improve product quality and thus quality must be built into the Product following the QbD concept. Consequently, pharmaceutical QbD has now evolved guided by standardised documents associated with Pharmaceutical Development, Quality Risk Management, Pharmaceutical Quality System and Development and Manufacture of Drug Substances. Quality by design (QbD) finally matured and evolved into quality by control (QbC) which describes the design and operation of a robust manufacturing system. This is normally achieved by an integrated and comprehensive process control underpinned by automation principles and it is based on a clear understanding of the process. Overall, therefore, Quality by Control enables a continuous monitoring and control of process operations and systematic release of the correct specification. 

Above figure shows a plot of drug quality in development stages vs. Product and Process knowledge. It demonstrates the evolutionary process of batch manufacturing through to continuous manufacturing and then smart manufacturing and the corresponding quality assurance checks in place. As drug quality development progresses from the batch to continuous and then smart manufacturing, quality assurance changes from quality by testing to quality by design and then consolidating to quality by control based on standards and requirements. 

Advantages of Quality by Design (QbD): 

• Better understanding of the process and the products.
• Less chance of batch failure.
• To achieve consistency in Quality
• More efficient and effective control of change.
• Return on investment / cost savings.
• Innovative Process Validation approaches.
• Improved yields, lower cost, less investigations, reduced testing, etc.
• Right first time & every time concept.
• More efficient technology transfer.

   

An enhance QbD approach to pharmaceutical development provides opportunities for more flexible regulatory approaches for example: Manufacturing changes within the approved design space can be without regulatory review or approval. 

Quality Culture: 

A successful quality culture cannot be built in a day, but it takes time with a commitment to the quality from top management to shop floor employee. After a short period, everyone gets the benefit of the quality commitment when a culture of quality is built in the firm. 

• A company having a quality culture will never face any problem in any regulatory audit and the company will not require preparing for any quality audit.
• Employees will not get frustrated and have satisfaction for their work hence they will feel engaged and attached to the company and they will perform better.
• Employees will also get the benefit of the quality culture in terms of their promotions, salary hikes and better opportunities.
• When pharmaceuticals company creates a quality culture, it will improve the reputations of its brands and regulatory market.
• Commitment to quality: Including establishing effective pharmaceutical quality systems & maintaining, modernizing as needed, equipment and facilities.
• Adopt a “Quality Culture”: Stress importance of product quality from the top down. Decision making with end-user / patient in mind.
• Proactively monitoring products and processes: Using risk- based approaches and modern analytical methods.
• Invest in quality and continual improvement: Quality can pay for itself!

Quality Culture is a demand to survive in today’s competitive regulatory market. A company without quality culture cannot run for long and will have a dark future. 

Quality Metrics: 

Quality is everything when it comes to the pharmaceutical company. Compromise on the quality of pharmaceutical products would mean a compromise on the overall health of the patients and other clients. To achieve the desired quality standard means that organization and management’s thinking must be well structured to ensure that quality and reliability figure appropriately in corporate planning. It is essential for any manager not only to have a good appreciation of the fundamentals of quality and reliability, but also fully understand his/ her own responsibility for the management. 

Since the introduction of Quality-by-Design (QbD) concepts, it has been accepted that quality of pharmaceutical products should be designed and built during the manufacturing process. Most of quality problems are related to the way in which a pharmaceutical product was designed. A poor-designed pharmaceutical product will show poor safety and efficacy, no matter how many tests or analyses have been done to verify its quality. Thus, QbD begins with the recognition that quality will not be improved by merely increasing testing of pharmaceutical products. In other words, quality must be built into the product. The Quality-by-Design (QbD) guidance issued by the USFDA. This advance has since been evolving into the concept of Quality-by-Control (QbC). 

A quality culture can easily overcome the non – compliance in the pharmaceutical company therefore, as a pharmaceutical employee you must take this initiative today.

Managers should be aware that the quality of their product is a vital factor in the continuing competitiveness and profitability of their company. Not only they should be concerned with producing products at the right price and at the right time, but they should also ensure that they are marketing the right product and it will fully meet the regulatory and customer’s compliance requirements.

Query: 

Ask if you have any Query visit  http://pharmasolution1.blogspot.com, I will revert back to you with a solution. To learn more always visit and connect with Pharma solutions by Dr. Ajay. 

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About the Author:

Dr. Ajay Kumar Singh, M.Sc. (Gold Medalist), Ph.D. is the author and founder of “Pharma Solutions by Dr. Ajay”.

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