Quality by Design: A Contract Organization's Perspective - Pharmaceutical Technology

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Quality by Design: A Contract Organization's Perspective
The author discusses how a CDMO helps in gaining process understanding and in developing robust, high-quality products and processes. This article is part of a special issue on outsourcing.

Pharmaceutical Technology
Volume 36, Issue 8, pp. s20-s26

Current state of QbD: a CDMO view

A CDMO develops products for virtual companies, biotech, specialty, mid-size, large pharma, and generic drug companies, and sees different philosophies and strategies adopted by sponsors in applying QbD to product development. As key players in industry, CDMOs need to move the QbD initiative forward by helping sponsors and clients see potential benefits, so they will give QbD a higher priority and understand the risks of not using the QbD toolbox.

Figure 1: When is it too late to adopt a quality-by-design approach to your product at a CDMO? (Ref. 4).
The benefits of using QbD at various stages of development have been well documented. In a live poll conducted during a QbD conference, the majority of representatives from the industry felt that it is "never too late" to adopt QbD and generate data to get an in-depth process understanding (see Figure 1) (4).

Figure 2: At what stage are quality-by-design initiatives in your organization? (Ref. 6).
In a 2008 survey, 58% of the respondents said that their QbD initiatives were only in the ideas and vision stage (5). In 2010, at another QbD conference represented by the small, medium, large pharmaceutical, and generic drug sectors, results of a live poll, shown in Figure 2, indicated that more had moved on from this stage (6).

Figure 3: What is the biggest obstacle to pursuing quality by design in your organization? (Ref. 6).
Organizations have been slow in thinking about the best way to implement the principles of QbD in their development programs as a part of their corporate strategy. When asked about the biggest obstacles, poll respondents' answers, shown in Figure 3, indicated that pursuing QbD did not fit into the priorities of many organizations (6).

Based on various discussions, Patheon has compiled comments from the sponsors' perspective as to reasons for not adopting QbD in their programs:

  • "Our process is well developed and scalable. There may not be any need for additional process development to set appropriate design space."
  • "We need to meet aggressive timelines to ensure continued funding. For virtual to small organizations, proof of concept and moving quickly to the next phase of the clinical program are of top priority."
  • "Our goal is to have a product that will be successful in clinical trials. We can always optimize the process after the clinical phase is done."
  • "This product will be partnered or sold post Phase 2b; why invest in QbD now?"
  • "There are regulatory risks associated with conducting QbD experimentation and the risk of delays due to large experimentation and possible reformulation in the late stages of development. This could also lead to an additional bioequivalence study, which is costly and time-consuming."
  • "We are reluctant to share development or proprietary information (e.g., filing or historical data)."

On the other hand, comments from CDMOs, compiled by Patheon from various discussions, offer a different perspective on why QbD is worthwhile:

  • "Many transferred processes are not well defined. Selection of excipients and their levels are not scientifically justified. Processes are scaled up to provide larger quantities of clinical trial supplies without sufficient data."
  • "The failure rate in clinical trials is high. Using sound judgment and a calculated risk-based approach, however, will help move the clinical program forward by balancing the scientific approach with capital investment."
  • "Often there is no time to optimize products in later phases, which has impact on the cost of goods and security of supply."
  • "Failed batches and additional regulatory scrutiny will cause more delay than doing a systematic study correctly now."
  • "A well-understood, stable product developed using sound QbD principles adds value to robust development, and the product is more attractive to potential partners for out-licensing."

Figure 4: What is the biggest concern you have in conducting a quality-by-design approach using a CDMO? (Ref. 4).
The live-poll results in Figure 4 show that, when considering conducting QbD with a CDMO, respondents are concerned about project delays, cost, information sharing, and the expertise of the contractor (4). As more and more product development is outsourced to a CDMO, however, sponsors will have to partner with CDMOs in pursuing the QbD strategy.

In recent years, Patheon has seen an increase in the number of sponsors/clients asking for QbD. Sponsors would like to know what strategy a CDMO would propose to proceed with this exercise and the experience level of the CDMO in designing a QbD work plan. More organizations are now conducting statistical design-of-experiment (DOE) studies to understand the design space for critical process steps in solid oral and sterile dosage manufacturing operations.


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