Production optimisation

Mathematically the maximum productivity optimisation problem can be presented as ... 

Myers, R. H. and Montgomery, D. C. (2002). Response Surface Methodology Process and Product Optimisation Using Designed Experiments. John Wiley and Sons, New York. 

To develop a product from inception to market, the product and process have to be optimised and the process scaled up and transferred to commercial production. Definitions and descriptions of the requirements for all these stages of development are discussed in Chapter 8, although the major discussion is on the preformulation/formulation input to product optimisation. The many factors which a formulator should consider in the selection of pharmaceutical excipients and packaging are discussed. Useful sources of information and techniques for selection such as expert systems and experimental design tools are included. 

Whilst there are many traditional approaches to dosage form design, newer approaches based on expert systems are now becoming available. Expert systems are discussed further in Chapter 8 on Product Optimisation. 

The major objective of the product optimisation stage is to ensure that the product selected for further development (the intended commercial product) is fully optimised and complies with the design specification and critical quality parameters described in the Product Design Report (refer to Chapter 5). The key outputs from this stage of development will be... 

At the early stages of optimisation, preformulation studies are usually conducted to screen excipients or packaging materials and to select those compatible with the candidate drug, using accelerated stress testing procedures. More details about the preformulation techniques, which can be employed for compatibility studies, are discussed in Chapter 3. The importance of doing compatibility studies is for reducing the number of excipients and formulation options to test in further product optimisation studies. 

At the completion of product optimisation, when the best product variant has been selected, it is a good idea to summarise the work conducted in a Product Optimisation Report. The report should reference the primary data from preformulation, product optimisation and stability studies, cross-referencing other investigational reports where necessary. It should clearly justify the recommendations for the quantitative formula and the excipient, component and product specifications. Such a document can be very useful to aid smooth technology transfer into production and for writing regulatory submissions. 

In conclusion, during product optimisation, excipients will be selected based on a variety of acceptance criteria. The quantities included in the formulation will be finalised, based on the performance characteristics of the excipient in the final product. At this stage it is important to fix the specifications of the excipients to ensure that the materials used, and hence the product, will be consistent throughout development. Setting specifications is discussed in a following section. 

Product optimisation of the pack should initially focus on defining the primary packaging (sometimes referred to as primary container or immediate container ). This is most relevant to regulatory authorities because it is the primary packaging that is in direct contact with the drug product, including the closure, liner, and any other surface contacting the product. 

The exact product optimisation studies to be conducted will depend on the type of ophthalmic dosage form to be developed (liquid drops, semi-solid gel/ointment or solid device). However, the dosage form type should be clearly defined from the product design evaluation and supporting preformulation studies, to enable the formulator to focus on the most relevant product optimisation studies. 

The objectives of the process design and optimisation stages of product development have been discussed in chapter 8, Product Optimisation . For ophthalmic products, like parenterals, process development can be quite challenging because the formulation must be manufactured sterile. Quite often, it is discovered that some formulations cannot withstand a stressful sterile process such as autoclaving. Chemical degradation or changes to the formulation properties of multiphase systems, such as suspensions and gels, can occur. In all cases, the compendial sterility test requirements described in the various pharmacopoeias must be complied with. 

Product Optimisation Purpose and Scope Excipient and Pack Optimisation Considerations... 

Kinetic control is a pervading influence throughout zeolite synthesis, where the desired product is frequently metastable. Much of the know-how in this industrially important area centres around choice of the exact conditions for product optimisation, so that the... 

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