Strategic Approaches to Process Optimization and Scale-up - Pharmaceutical Technology

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Strategic Approaches to Process Optimization and Scale-up
The authors present three approaches that a contract development and manufacturing organization can consider when designing development and process-optimization studies that will provide useful data for scaling up a project.


Pharmaceutical Technology
Volume 34, Issue 9

Approach 3: Hybrid method combining elements of approaches 1 and 2.

The use of a full design of experiments approach can result in a significant amount of batches being manufactured to cover the design space. As the number of batches required to describe the design space increases, the development time and cost increases. A third method combining elements from approaches 1 and 2 optimizes the balance between development time and cost and maintains a good understanding of the manufacturing process. This hybrid approach can be achieved by breaking the manufacturing process into defined sections. The initial blending step can be performed using Approach 1. The blend could be manufactured to specification, and end-product testing will show the quality (e.g. blend uniformity/assay). Parameters such as blending time and blending speed can be determined by intensive blend uniformity and bulk-assay analysis allowing blending windows to be established. A second confirmatory batch could be manufactured using the parameters obtained from the initial batch that could provide additional confidence in the manufacturing process.

The blend will have been shown to meet specification and can then be progressed to the next processing steps. An experimental design approach can then be performed. For example, the next steps could involve dry granulation followed by compression into tablets. As described in approach 2, following completion of a full risk assessment and subsequent cause and effect diagram detailing the potential process parameters, a structured design of experiments plan can be devised. Rather than completing each experiment at the full scale, the experiment can be performed using a suitably sized aliquot of the blend manufactured already. As both dry granulation and compression are a continuous throughput process, the parameters investigated are mainly independent of batch size used. Using this approach, a 60-kg blend could be divided into 3-kg sublots, allowing up to 20 experiments to be run.

Following completion of the experiments and analysis of the data, a confirmatory batch could be manufactured using the optimized parameters determined from statistical analysis and preparation of a design space. The resulting batch or tablet cores could be progressed to coating if required. Again, the coating process can be investigated using method 1 or 2.

Conclusion

Strategies for product development can vary from company to company and from product to product, and as such, a contract development and manufacturing organization (CDMO) must be able to provide a service that can suit the requirements of any customer. For a variety of reasons, a company might choose either an empirical approach or a more systematic approach to product development. The approaches described can aid in the provision of a high-quality development offering from the outset while striving to control timelines and costs, which are commonly seen as opposing forces in the pharmaceutical industry.

Conor P. Long* is a senior formulation development scientist and John Mc Quaid is a technical development manager, both at Almac Pharma Services, 22 Seagoe Industrial Estate, Craigavon, BT63 5QD, UK, tel: +44 (0) 2838 363363, fax +44 (0) 2838 363300,
.

*To whom all correspondence should be addressed.

References

1. ICH, Q1A (R2) Stability Testing of New Drug Substances and Products, (ICH, Geneva, Feb. 2003).

2. EMA, Note for guidance, Process Validation, CPMP/QWP/848/96, (EMA, London, Sept. 2001).

3. ICH, Q8 (R2) Pharmaceutical Development, (ICH, Geneva, Aug, 2009).


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