Pilot Production

Three types of control plan are required. During the product design and development phase, a prototype control plan is required to be produced. During the process design and development phase, a pre-launch or pilot production control plan is required, and during the product and process validation phase, the production control plan is to be issued. 

To achieve the desired cast density for Octol of 1.8g/cc it is necessary that the ratio of HMX TNT be 3 1. However, at this ratio the apparent viscosity, or efflux, is strongly dependent on the polymorphic variety of HMX used and on its particle size distribution. In the initial pilot production of Octol (Ref 3) it was found that for the desired efflux of < 15 sec, 60—70% of the solid HMX must consist of the beta-polymorph having particle diameters in the range of 500—800 microns. Such precise control of particle size was not possible at that time and early Octol casts were made at approximately 50 secs efflux. The economical production of Octol with a satisfactorily short efflux time continues to present a problem in loading shells with this expl (Refs 4, 11 29)... 

This is supported by sources that suggest that a pilot production facility for VR was constructed at a facility in Stalingrad (now Volgograd) by the Soviets as early as 1956, 2 years before VX was selected for production by the United States. Research on the agent continued for an extended period as well - in 1974, a Lenin Prize was awarded to researchers who were investigating issues associated with VR. 

The title compound (with 66.5% nitrogen content) is prepared by condensing formylhydrazine (2 mols, with elimination of 2H2O) by heating to 170°C. Dining a pilot production run in a 500 1 reactor, an explosion destroyed the vessel. The heat of decomposition of the compound was determined by thermal analysis as 1.5 kJ/g, with an energy of activation of 91 kJ/mol. 

Figure 5.18 Schematic of a large scale (pilot/production) fermenter with three impellers. (From Stanbury and Whitaker 1984). Typical geometrical ratios are given in Table 5.11.

After the twentieth flight in 1974, a third Defense Council review will make a go-ahead decision on pilot production - an extra step because the Navy, to save costs, was allowed to bypass a prototype competition Ref The Common Defense Bull No 392,... 

The pilot-production program is generally a result of cooperation between the development laboratories and the manufacturing department. Technology transfer documentation applies to processes as well as to the systems being qualified and validated and their testing standards and testing methods. This documentation is important, particularly where an NDA is involved. 

A pilot production is at about a lOOx level in general, the full scale-batch and the technology transfer at this stage should comprise preformulation information, product development report, and product stability and analytical methods reports. This is the time to finalize the batch production documentation for the lOOx level. The objectives of prevalidation trials at this stage are to qualify and optimize the process in full-scale production equipment and facilities. 

MAKNII carries out tests on experimental new substances or pilot production lots (to be authorized for handling and use) by firing 10 shots from each batch in methane-air, and 10 from each lot in coal-dust (5 with and 5 without coal-dust (100 g) in mortar). 

Guillard, J., Schmitt, V., Dozias, M.J. and Besson, T. The scale-up of focused microwave assisted organic synthesis from the research to the pilot production scale, In Book of Abstracts, 216th ACS National Meeting, Boston, August 23-27, 1998, ANYL-114. 

The following operations are normally carried out by the development function prior to the preparation of the first pilot-production batch. The development activities are listed as follows ... 

The pilot-production phase may be carried out either as a shared responsibility between the development laboratories and its appropriate manufacturing counterpart or as a process demonstration by a separate, designated pilot-plant or process-development function. The two organization piloting options are presented separately in Figure 1. The creation of a separate pilot-plant or process-development unit has been favored in recent years because it is ideally suited to carry out process scale-up and/or validation assignments in a timely manner. On the other hand, the joint pilot-operation option provides direct communication between the development laboratory and pharmaceutical production. 

Usually large production batch scale-up is undertaken only after product introduction. Again, the actual size of the pilot-production (100 x ) batch may vary due to equipment and raw material availability. The need for additional pilot-production batches ultimately depends on the successful completion of a first pilot batch and its process validation program. Usually three successfully completed pilot-production batches are required for validation purposes. 

Finally, at least one qualification trial of a pilot-production (100 x size) batch has been made and shows, upon scale-up, that there were no significant deviations from the expected performance of the process... 

The steps and sequence of events required to carry out a process validation assignment are outlined in Table 8. The objective of prospective validation is to prove or demonstrate that the process will work in accordance with a validation master plan or protocol prepared for pilot-product (100 x size) trials. 

In practice, usually two or three pilot-production (100 x) batches are prepared for validation purposes. The first batch to be included in the sequence... 

As an enterprise, the IOKh was quite large and employed around 1,200 people—researchers and technicians, engineers of various specialities, pilot production workers, patent experts, librarians, and others. Apart from the academic research facilities, the Institute had a variety of analytical laboratories and services, as well as units for design and construction of new laboratory equipment. 

Burguete, M. I. Escuder, B. Luis, S. V. Mira-vet, J. F. Garcia-Espana, E. Selective monofunctionalization of polyazajnjparacydo-phanes. Tetrahedron Lett. 1994, 35, 9075-9078. Guillaume, M. Cuypers, J. Vervest, I. De Smaele, D. Leurs, S. Synthesis ofT2288 from bench synthesis to pilot production. Org. Process Res. Dev. 2003, 7, 939-941. 

Pilot Production of Modules, Outdoor Field Tests... 

Cargill Dow Polymers LLC started up its first commercial-scale plant for polylactic acid (PLA) at Blair, Nebraska, in the US in 2002. The unit has planned capacity to produce 136,000 tonnes per annum. Until then, the pilot production capacity for PLA was only 4,000 tonnes per annum. 

These examples underline the potential of organocatalytic reactions for commercial scale applications. The scale up of the corresponding reactions ranges from L-scale applications to applications on a (pilot) production scale. In the following, several types of these reactions are discussed. 

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