Process developm ent time

The construction o f the commercial facility is only one part of the path to market. More importantly the development stages include the clinical evaluation stages and the time for regulatory approval. In Figure 3.6 the timelines for R&D and preclinical development were kept unchanged in the disposables approach.

Phase I/II clinical studies take 12 to 14 months of which 2 months correspond to materialisation (Dennis, 1999). It was thought that even if there is some time saving at this stage it would be negligible. Phase III takes 24 months o f which 3.5 months are for validation and 8 months are for manufacture. In this case it was deemed that the use of

disposables leads to a saving o f at least 3 months due to simpler validation and shorter downtime between subsequent batches.

It was considered here that regulatory approval remains unchanged for a disposables- based process. This may initially not be the case while regulatory agencies get up to speed with the new implications associated with disposable equipment. However a good indicator o f the longer term trend is that many companies make now use o f disposable containers for buffer preparation without additional regulatory consequences.

According to Figure 3.6 there is an overall reduction o f 1.5 years in a 10.5 years development time line. The average development time for a biopharmaceutical drug is now 7.8 years (Too et al., 2001), so this should correspond to 13.5 months earlier entry to market assuming direct proportionality.

It has to be noticed that not all drugs will allow a disposable design at the commercial stage. Effectively there is a scale limiting factor as disposable containers are currently available up to 2500 L only, which would also constitute the maximum scale o f the disposable fermenter. For drugs at a higher scale o f operation the time savings brought by disposables will be smaller and associated exclusively with the clinical trial stages. This is provided the transfer from a disposable-based Phase 111 pilot plant onto a stainless-steel-based commercial plant can be done without major regulatory obstacles.

Another interesting way o f examining the effect o f the use o f disposables on the time to market is to consider a portfolio o f drugs, all associated with typical failure rates. As the use o f disposables allows for a shorter changeover between subsequent drugs, the throughput can be higher and it may take less time to get one drug approved. Farid et al. (2000b) presented such a case study, where the use o f disposables allows for a greater likelihood o f achieving an annual throughput o f at least 5 projects, i.e. a higher chance o f getting more than a single product to market.

Research and development Preclinical development Phase I/ll clinical studies Phase III clinical studies Construct/validate facility Regulatory approval Research and development Preclinical development Phase I/ll clinical studies Phase III clinical studies Construct/validate facility Regulatory approval

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Figure 3.6 Time req u ired to develop and licence a biopharm aceutical drug fo r (top) a

conventional p la n t (a d a p ted from Burnett et a l, 1991) a n d (bottom) a disposables-

b a se d plant.

A further non-quantifiable effect has to do with cases where the only two viable options are to either build a disposable plant or to make recourse to a contract manufacturer. This can be the case for small/medium companies with limited resources. Given the present situation worldwide of a lack o f manufacturing capacity and long waiting lists among contract manufacturers (Garber, 2001) the use of disposables can clearly offer further time savings.

3.6 Conclusions

The use of disposable equipment for the manufacture o f biopharmaceuticals has many economic implications. On the capital cost side the area requirements, the complexity

and hence the cost o f such plants are lower than those o f equivalent plants based on stainless steel equipment. The reduction in building cost was estimated to be significant at approximately 30%. The absence o f fixed equipment and many utilities signifies that the contents o f such plants is also much simplified, with reduced fixed piping and associated validation. Overall the capital investment o f a disposables-based plant was estimated to be 60% o f that o f a conventional equivalent plant.

The running costs are however significantly increased when operating in a disposable format, mainly as a consequence o f new costs such as disposable equipment replacement and flexible tubing. This is despite the decrease in maintenance and in the operating costs o f utilities. The increase in running costs was estimated to be around 70% for a bacterial process and 90% for a mammalian cell process. Both these figures were shown to be heavily dependent on the costs o f disposable equipment, which in turn depend on the designs and construction materials chosen (see section 4.4.3). It is also likely that the prices o f disposable equipment will go down once the market develops, thereby reducing the negative effect o f this cost factor.

The overall effect o f a decrease in capital investment versus the increase in running costs will have to be evaluated through a net present value evaluation and will be the subject o f the next chapter (Chapter 4).

The time that can be saved when bringing a product to market was shown to be very significant, up to 1 to 1.5 years. This time saving can be translated into additional revenues, which can be o f the order o f £50 million per annum for a typical drug (Davidson, 1998).

The case study presented in Chapter 4 will seek to combine all the different factors studied in Chapter 2 and in this chapter, with the purpose o f establishing an economic comparison between conventional and disposables-based technologies.

Chapter 4 Case study: Economic comparison of