Product optimisation stages

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... 

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. 

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. 

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. 

The primary objective of the process design and optimisation stages of product development is to ensure that manufacturing operations supporting Phase III studies, and ultimately commercial manufacture, are carried out under optimal conditions. The product should consistently comply with specifications. 

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. 

Optimisation of biomass production would require a large inoculum, comprising 10% of each inoculum stage. However, this involves many transfers which increases the risk of contamination. 

An essential stage in the production of an effective sensor is an understanding of the device sensitivity with a view to its optimisation. 

An industrial grade, skid-mounted unit (see Fig. 11.2) has been operating successfully at Occidental Chemical s Delaware City mercury cell plant since September 1997. Operating results have met both the expectations of the client and Kvaerner. This chapter discusses the operating experience at OxyChem and the resulting optimised commercial product, the Kvaerner Chemetics Sulphate Removal System or SRS . The acceptance in the market-place has been excellent four systems have been ordered and three are in the process of manufacture, with operations commencing later in 2000. Approximately 50 firm price proposals have been issued in the past two years. Several of these evaluations are in the final stages and will lead to the sale of units in the near future. 

The evolution and optimisation of a formulation is an experimental stage that will be conducted on small batches of the material. For a drug with a tablet weight of 250 mg, test batches would t)rpically be 0.5-1 kg, providing up to 4000 tablets for analysis, performance testing and initial stability studies. Similar scales will be used in the optimisation of the product s packaging. 

When wet processing procedures are employed the final product usually has to be isolated in dry powder form before use. This is normally achieved by a combination of filtration and drying processes. In some instances a washing stage also has to be incorporated to remove soluble material, either initially present in the raw material or introduced by the production process (as in many precipitations). All of these procedures can have a significant impact on the process costs and need to be carefully optimised. 

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