Product optimisation packaging

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. 

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. 

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. 

As soon as the cause of the instability is known, means can be found to improve the shelf-life of the product. So, in case of oxidation effects, antioxidants could be added, and the oxidative risk could be minimised by reducing oxidising substances, varying production parameters or optimising the packaging of a product. 

A logical approach to packaging optimisation is, first of all, to define the packaging function, followed by selection of the materials, then testing the performance of the packaging to ensure that it will meet all the product design and functional requirements that were identified in the Product Design Report. 

Specifications will be required for the pharmaceutical active ingredient, any excipients used in the formulation, packaging components, and for the finished product (at time of manufacture and over the shelf-life). In all cases, the specifications tests and limits will evolve during development, as illustrated in Table 8.4. It is clearly beneficial to have full specifications in place for the start of the Phase III pivotal clinical studies, when the product and process should have been optimised, to ensure that there is equivalence between the product used in Phase III and the commercial product. 

Using the non-palletised methods and depalletising to optimise transit vehicle space, warehouse space, etc. substantially increases manual handling. This can be reduced by the use of mechanical transfer systems (lifts, hoists, chutes, roller conveyors, etc.). Placing loads directly onto the floor in warehouses, vehicles, etc. is not recommended for pharmaceutical products. It is therefore advisable to try to raise the packaging off the floor by the use of boards, duck boards, hardboard, slip pallets, slip sheets, etc., but these may cause other problems. 

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