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p. 32 / OVERVIEW ON PEPTIDES
The use of QbD for peptide manufacturing processes
ANDERS TSIRK1*, JON H. RASMUSSEN2
*Corresponding author
1. Global Development Manager,  PolyPeptide Group (PPL)
2. Global Development Director,  PolyPeptide Group (PPL)

KEYWORDS: Quality by Design, Active Pharmaceutical Ingredients.

INTRODUCTION
The introduction of QbD in the pharmaceutical industry (1-6) has been a key driver for creating the foundation for a new approach. The acceptance of a more science and risk-based approach has created the opportunity to employ techniques long existing in other industries, for instance, design for six sigma (DFSS) (7).
Peptide APIs are very different for several reasons: Sequence and difficulty, API volume requirements, indication, potency, OEL. However, for the majority of peptide APIs manufactured today some common denominators are:

  • More process steps (as compared to small molecules);
  • More process parameters;
  • High degree of repetition of similar process steps.


The use of QbD for peptide manufacturing processes

This combination lends itself very well to a platform technology thinking where both in-silico analyses and empirical knowledge will guide and drive the development of processes for new APIs. New learning and discoveries will be fed back into the platform, and will increase further the predictability capabilities of it.

Within PPL, the QbD/ DFSS concepts have been embraced and the methodologies have been adapted into an approach suitable for the specific business aspects of PPL. The key elements in this adapted approach are: accurate target setting, efficient knowledge management and process evaluation and target-focused and risk-based assessments and planning of actions. The overall development approach is depicted in the figure above. There is still a degree of flexibility among the possibilities harnessed in the development program(s), and the new approach displays clearly what consequences there may be by performing, or not, specific development tasks.
As an example, within PPL the improvement of the throughput and cost reduction for the production of a specific drug substance became an important objective. The process development strategy was outlined according to the QbD policy/mindset.
And the specific objectives were to:

  • Fulfill the  API specification;
  • Reduce costs by >30%;
  • Increase annual capacity without new investments;
  • Obtain regulatory approval.

Through the systematic approach laid out, all objectives were met. The Chart below shows the overall yield (relative values) before and after the process improvements. Following submission of the changes to the regulatory bodies, approval was successfully achieved.

CONCLUSION

In conclusion, the employment of QbD throughout the development and lifecycle management of the API manufacturing processes offers many advantages both internally, i.e. better and more efficient knowledge management, and externally, i.e. obtaining smoother regulatory approval on the basis of the data generated.




Figure 1.Synchronizationbetweenclinicalprogram,cGMPmanufactureand...In order to continue reading this article please register to our website – registration is for free and no fees will be applied afterwards to download contents.

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