The validation of Pharmaceutical and Medical manufacturing machines has been a hot issue for nearly ten years. As a result, many machine manufacturers are now offering validatable machines and much existing manufacturing equipment has been retrospectively validated by the industry itself.

So much for the machines, but what about the process - that is the bringing of the machine and the manufacturing or packaging materials together. Simply concentrating on chosen running conditions may be adequate for raw validation, but full optimisation will provide major benefits in both improved efficiency and prediction of problems with packaging materials.

Doyen believes a process can only be validated if the entire operating characteristics of the machine and materials are thoroughly understood. The activity of optimising the process will provide an in-depth understanding of the entire operating process, not just a snapshot of the chosen operating range. In the case of a heat sealing machine, the relationship between the temperature and pressure at a given speed or dwell is shown in Figure 1. The area within the lines A, B, and C is normally termed the safe operating envelope. Line A is the lower limit when the seal fails due to a combination of low temperature and pressure, Line B is the upper limit where the material characteristics are unacceptably changed by heat, and Line C is the upper limit of pressure where either material characteristics are corrupted due to excess pressure or the pressure limit of the machine is reached.

Knowledge of this envelope allows the optimal positioning of the normal operating box (coloured red in the diagram). This box defines the normal range of machine uncertainty of pressure (Dimension X) and the temperature (Dimension Y). The Y dimension for temperature will include the normal operating range, the indicated and actual errors, the temperature profile of the element, and uncertainty on measurement. The X dimension for pressure will include sealing roller rubout or platen flatness, uncertainty in the pressure application, and wear of the sealing surface.

If the box XY will not fit in the operating envelope, the process will be unstable. In these cases, the machine control must be improved (to reduce dimensions XY), or the material changed, or the process slowed or dwell increased (to increase the size of the envelope).

If the outer perimeters of the envelope say points D, E, F and G are determined, these can be used to further understand the process. The pairs D and F can be plotted against speed or dwell. Thus, the parameters that created points D and F for a given speed are defined at different speeds or dwell. The typical results are shown in Figure 2. As the process speed is increased (or dwell reduced), the distance between the pairs D and F is reduced, making the process more critical. When the distance between D and F are such that the operating envelope is smaller than the operating box ( XY) the process becomes unstable. In the case shown, the pressure for points D and F are kept the same as in the first test.

The monitoring of points D and F during goods inwards inspection of material will give warnings of changes in batch characteristics that may go unobserved until production is attempted. Statistical significance testing can be applied to predict changes in the operating envelopes. These tests can also be conducted by material manufacturers before shipment.

Optimisation, instead of just validation will give full understanding of the process, ensure that the machines work in a safe operating envelope, predict material problems before they arise in production, and provide clear acceptance parameters for material suppliers.