Quality by Design (QbD) with JMP® – A reliable partner

QbD was born out of a cultural shift within the pharma sector, promoting a scientific and risk-based approach to pharma product development and manufacture. Prior to QbD, pharma development and manufacture placed a higher premium on checklist procedures than on scientific knowledge. The high attrition rate of drug candidates during development, the high value of pharma products, and the extremely high regulatory load, resulted in risk-averse corporate practices that limited process improvements and changes, and the introduction of new technology.

Historically, pharma process and product development relied on unstructured experimentation, usually with one factor at a time. In production, processes were operated under fixed conditions and monitored via offline analytical testing (involving a lengthy delay) and end-product testing. Additionally, it was customary to disclose minimum process and scientific information to regulatory bodies, and for these agencies to respond to this with a barrage of specific inquiries.

Recognising that more testing will almost certainly not improve the quality of a drug, the US Food and Drug Administration (FDA) started this paradigm shift through its imitative “Pharmaceutical Quality for the 21st Century: A Risk-Based Approach.” Regulators are now placing process understanding centre stage, encouraging pharma companies to develop the ability to assess the dependability and robustness of their manufacturing systems, and rewarding them for doing so.

These initiatives, coupled with a general realisation that the pharma sector had low levels of productivity, efficiency and quality compared with other industries that have long embraced QbD-like approaches, have led to the rapid and widespread adaptation of QbD by pharma and bioscience companies.

Transition to QbD
Science has always been important in the development of pharmaceuticals, and its commercial application has been a key to the industry’s many life-saving and life-enhancing drugs. Biotechnology-based drugs are more difficult to understand, make and analyse than small molecules; but specialised therapies such as advanced therapeutic medicinal products and gene therapies are beginning to emerge. At the same time, developments in IT and data acquisition mean that it’s now easier than ever to take a holistic and data-driven approach. For example, although used by other industries for many years, Process Analytical Technology (PAT) is relatively new for the pharma industry and is now being used to gather more information, more quickly, than offline and end-product tests produce. And now that data is more available and is easier to process, new possibilities such as Design of experiments (DOE) and multivariate analysis (MVA), arise.

The pharma supply chain has become more fragmented and diverse, with more parties involved, including CROs, CMOs and external suppliers, leading to the rise of “virtual” companies. In a world where many countries are involved in the supply chain, maintaining quality across national borders and cultures has become essential.

At the same time, the public insists on safeguarding patient safety and on a ‘right first time’ approach, and the industry is making structural changes to try to reduce production costs and make supply chains more lean and agile. So, from development to manufacturing and supply, the management of knowledge is crucial. Knowledge includes an understanding of science, as well as its applications in technology, manufacturing, engineering, material science and other fields. Regulators now have a vigorous emphasis on data integrity, lifecycle management, process validation, quality metrics and knowledge management.

QbD eases pharma product development
QbD is applicable to any pharma dosage form or manufacturing process, from small chemical molecules to large biopharmaceuticals and biological products. When QbD is used in the development of a new product, the following stages are followed:
◆ Establish the Quality Target Product Profiles (QTPPs) and Critical Quality Attributes (CQAs) for the intended product profile
◆ Review options for formulation and manufacturing process design
◆ Decide formulation and manufacturing process design
◆Design review by development team
◆ Develop and optimise formulation and manufacturing process design

JMP’s strengths supporting QbD: Design of Experiments (DOE)

DOE is a logical and practical method for investigating multi-factor opportunity spaces, and JMP provides world-class design and analytical tools in a user-friendly application. Structured
experimentation may be used in a variety of ways for generating new process understanding efficiently and reliably. The best way to reveal and model connections between an input, or factor and an output, or response, is to modify the former and observe if the latter changes as well. And, with multiple factors, the best approach to get relevant, new information is to actively manipulate these together according to a pre-specified plan.

JMP offers a state-of-the-art custom design capability that tailors your design to answer specific scientific or technological questions without wasting valuable resources. Furthermore, JMP simplifies data collection, analysis and the development of the associated statistical models so you can quickly understand the pattern of response, identify active factors, and optimise responses.

JMP in process and product development
JMP allows you to keep track of project deadlines and dependencies. Missed milestones increase workload and stress, resulting in late product releases and increased costs – leading to being late to market, poor profitability and unpredictability of supply.

JMP helps to improve the efficacy and safety profile of your product by supporting data-driven methods that are effective and repeatable. You can also increase R&D efficiency by codifying and reusing process understanding and automating regular, manual operations to improve analytical speed and quality.

JMP’s advantage when enabling QbD processes

When JMP is used to enable QbD, it helps manage quality conformance and regulatory compliance while considering trade-offs in speed and cost. With JMP, you can monitor processes to make sure they stay the same, find and fix problems with batches more quickly, continuously improve processes and products to get more value, and cut down on waste. Effective analysis plans can help you get rid of parts of a process that don’t work well or cost too much. You can save time by accessing and processing production data on a single self-service application that is intuitive and easy to use.

Implementation of a control strategy with JMP

At each step along the way, there are many tests to see how well the product and process are working. In the lab, scientists and technicians use high-tech instruments that produce a lot of data, and PAT initiatives bring these on-line in real time.

Using JMP, you can quickly access any data and check its quality to see if there’s anything that needs to be done before you can analyse it successfully. You save a lot of time by supporting the whole process of data analysis in one self-service application. JMP also allows you to communicate more effectively, promoting a collaborative data-driven approach that shows when a product or process needs to be fixed and, more importantly, what needs to be done to fix it.

Resources
White Paper – Optimizing Pharmaceutical Production Processes Using Quality by Design Methods
https://www.jmp.com/en_in/whitepapers/jmp/pharmaceutical-qualityby-design-methods.html

Webinar – QbD QbD: Using DOE to Increase Knowledge of the Process and Design Space
In this on-demand webinar, you will learn about JMP’s select the best DOE approach for your experimental needs, weighing options like custom designs, mixture designs and definitive screening designs. By adopting the right, tailor-made approach to experimentation, you’ll be able to identify the design space and get your processes back into control faster and at lower cost to your organization and deriving the JMP’s QbD advantage.

https://www.jmp.com/en_in/events/ondemand/technicallyspeaking/qbd-using-doe-to-increase-knowledge-of-the-process-and-design-space.html

Download your free trial of JMP®
Used by hundreds of thousands of data explorers worldwide, JMP data analysis software reveals insights that raw tables of numbers or static graphs tend to hide. Get more out of your data by downloading a free, fully functional 30-day trial now.

https://www.jmp.com/en_us/download-jmp-free-trial.html