Quality by Design for ANDA

GOOD MANUFACTURING PRACTICE (cGMP) WHITE PAPERS
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CERTAIN KEY ASPECTS OF QbD, INCLUDE:
• The quality target product profile (QTPP) and critical quality attributes (CQAs)
• Drug substance and excipient properties
• Formulation design and development
• Manufacturing process design and development
• Identification of critical process parameters (CPPs) and critical material attributes (CMAs)
• Risk assessment and design space
• Scale-up and control strategy.

White Paper Attached [attach]260[/attach]

Quality-By-Design-for-Generic-Drugs.doc (47.0 KB)

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QbD is very hot and essential topic.
Today exactly at 1.00pm PST there is almost 2 hours Webminar about Qbd and its applications on Statistical Process control and validation.
I shall certainly post some important points here.
This topic is relatively new to me too.

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The EMA and the US FDA will conduct parallel assessment of QbD development and manufacturing data for new drug submissions under a new pilot scheme announced this week.
The voluntary scheme will see reviewers at each agency assess chemistry, manufacturing and control (CMC) data separately and communicate their findings to counterparts on the other side of the Atlantic.

Speaking at the launch of the new project Janet Woodcock, director of the US Food and Drug Administration (FDA) Center for Drug Evaluation and Research, explained that the aim of the pilot is to streamline the review process.

"As the number of applications that follow the QbD approach steadily increases, collaborative assessments will enhance understanding of QbD concepts. The tools used by FDA and EU reviewers will increase information sharing and reduce redundancy.

“To fully implement QbD, we need to further harmonize the implementation of the guidelines, work collaboratively, and provide scientific, risk-based regulatory decisions in a timely manner.”

This was echoed by Murray Lumpkin of the FDA’s office of international programmes, who said: “This is another concrete example of the very collaborative working relationship we have with our European regulatory colleagues and how we can leverage the scientific resources we both have for the benefit of our agencies and our citizens,”

This pilot program applies to NDAs and MAAs, as well as some nutritional supplements, and CMC meeting requests that include QbD elements submitted to both agencies at about the same time.

The pilot, which will only cover chemical entities and not biologically-derived products, will end in March 2014.

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FDA, EMA announce pilot for parallel assessment of Quality by Design applications

For Immediate Release: March 16, 2011
Media Inquiries: Morgan Liscinsky, 301-796-0397, morgan.liscinsky@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA

The U.S. Food and Drug Administration and the European Medicines Agency (EMA) have launched a new pilot program that will allow parallel evaluation of relevant development and manufacturing data components, known as Quality by Design (QbD), of new drug marketing applications that are submitted to both agencies.

The parallel evaluation within this voluntary pilot program means that reviewers from both agencies will separately assess the quality/chemistry, manufacturing and control (CMC) section of the new drug applications (NDAs) submitted to the FDA and marketing authorization applications (MAAs) submitted to the EMA. However, there will be regular communication and consultation between European regulators and their U.S. colleagues throughout the review process relevant to QbD aspects of the applications.

QbD in pharmaceuticals involves designing and developing pharmaceutical formulations and manufacturing processes to help ensure product manufacturing quality. Several guidelines have been developed by the International Conference on Harmonisation (ICH) to harmonize and facilitate the implementation of QbD. This pilot program began out of concern that certain ICH guidelines were being interpreted differently in Europe and the United States. Goals of the pilot program include:

Helping to ensuring consistent implementation of ICH guidelines for manufacturing quality in the application evaluation process
Increasing awareness of these regulatory concepts by staff that review marketing applications and inspect manufacturing facilities as part of the approval process
Defining the reviewer and inspector interaction for QbD applications
Creating a further way for EMA and FDA assessors/reviewers to share full knowledge about these applications
Developing and harmonizing regulatory decisions to the greatest extent possible.
“As the number of applications that follow the QbD approach steadily increases, collaborative assessments will enhance understanding of QbD concepts. The tools used by FDA and EU reviewers will increase information sharing and reduce redundancy,” said Janet Woodcock, M.D., director of FDA’s Center for Drug Evaluation and Research. “To fully implement QbD, we need to further harmonize the implementation of the guidelines, work collaboratively, and provide scientific, risk-based regulatory decisions in a timely manner.”

“This is another concrete example of the very collaborative working relationship we have with our European regulatory colleagues and how we can leverage the scientific resources we both have for the benefit of our agencies and our citizens,” said Murray M. Lumpkin, M.D., Deputy Commissioner of FDA’s Office of International Programs.

This pilot program applies to NDAs and MAAs, some supplements, and CMC meeting requests that include QbD elements submitted to both agencies at about the same time. The pilot will only include chemical entities and not biologically-derived products. Review of QbD applications does not change statutory deadlines. The pilot will end on March 31, 2014.

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Today’s new regulatory environment highlights innovative ideas regarding process development and manufacturing and forces us to think about the practicalities of implementing them. To achieve QbD, manufacturers need to carefully consider the role of five important areas: process understanding, design-space development, design for manufacturing, process improvements, and process upsets.

Process Understanding: Successful approaches to real-time quality assurance (RTQA) require that critical process parameters (CPP) driving variability in the critical quality attributes (CQA) be identified and understood during process development. They can then be measured and controlled in real time while each batch is being manufactured. This is what the FDA means by “process understanding.” It requires

• a culture of continuous improvement that produces sufficient process understanding so that regulatory approval is not needed for process changes
• close collaboration between process development and manufacturing teams
• deployment of appropriate enabling technologies.
Collaboration can drive QbD. Advantages include adoption of better practices and sustaining business benefits such as higher levels of process predictability and quality compliance across a global manufacturing network.

Design Space Development: Process development ultimately defines and gains approval of a manufacturing control space within the universe of possibilities about a process called a knowledge space. An approved manufacturing process can be operated within its control space to produce material that meets the required specifications regarding identity, potency, quality, and so on.

As a product moves through its life cycle, scale-up, economic, and other factors can require changes in the control scheme for that process, necessitating an updated control space. The scientific basis for a new control space is usually developed to cope with process shortcomings that arise long after the original process development work was done. Creating one can be a costly and inefficient process because it can trigger the need for new clinical studies.

With the publication of ICH Topic Q8, manufacturers can now develop an approvable design space in advance of commercial launch that anticipates and accommodates more than one control space.

Design for Manufacturing: Developing and gaining approval for a control space and/or design space depends on making full use of prior knowledge and experience of the process development and manufacturing teams. Data concerning how previous processes behaved when subjected to the constraints of full-scale commercial operations provides a vital source of guidance for designing later processes to operate successfully within similar constraints.

The FDA uses the phrase design for manufacturability to describe the use in process development of information from prior manufacturing to consistently achieve an acceptable standard of predictability and quality. This type of information comes from accessing and analyzing actual data from prior manufacturing processes operating under the same or similar conditions as a process currently in development. This work identifies, correlates, and monitors the relationships between CPPs and CQAs under the well controlled, full-scale operating conditions used for commercial manufacturing.

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Embedding QbD elements into drug development could make approval timelines and inspection success more predictable, say a Genentech team.

Quality-by-Design (QbD) takes effort but, say researchers, a science- and risk-based approach consistent with its philosophy can be adopted without excessively increasing workloads. In fact, companies, regulatory agencies and patients can all benefit from the approach.

“Overall, we believe [our QbD system] will have a favourable impact on drug product quality for patients and associated cost for companies and regulatory agencies”.

The proposed risk-based biopharm drug development model uses prior knowledge of processes, risk assessments and experimental design. Using prior knowledge unnecessary experiments can be eliminated, keeping extra work to a minimum while creating a stronger development plan.

A new roadmap for biopharmaceutical drug product development: Integrating development, validation, and quality by design

Journal of Pharmaceutical Sciences
Article first published online: 18 MAR 2011

Regulatory relief

Following the proposed model will create more standardised regulatory submissions. The logic of these filings will be easier to follow, say the team, and will give more confidence in the process and product control strategy.

“QbD submissions may be longer but stronger submissions, and there may be less need for supplemental submissions during the lifecycle of a product”, say the Genentech team.

Compliance may also benefit from defining acceptable deviations. For example, studying the impact of a temperature change on quality during design space work, defined on page 9 of Q8(R2) document , could minimise the effort required if this event actually happens.

Overall the team sees a number of benefits for those adopting QbD in biologics development. “An enhanced rigorous and standardised process…may result in greater opportunities for flexibility and post-approval process optimisation as well”, says the paper.

Q8(r2).pdf (401.8 KB)