Process control automation of multi step batch organic chemical synthesis
Escape-12, Industrial Forum, may 2002
J.N. van Wezel , Diosynth b.v., producer of active pharmaceutical ingredients
Production facilities consist of solvent tanks, reactors, centrifuges, chromatography columns,
filter-driers, mother liquor tanks, tray-driers. Many products are produced requiring over 350
different synthesis steps. A product takes roughly 10 synthesis steps on average ranging from
a few to fifty for one product. All kinds of unit processes such as Grignard, reductions,
hydrogenation, alkylation, and ethynylation are performed. Reduction of stock leads to small
campaigns.
Three levels of process control exist. The level depends on the age of the facility:
1. Fully manual control: only temperature and pressure indicators
2. Temperature and pressure control on reactors, temperature control on heat transfer
medium. Controllers grouped in PLC’s
3. Recipe control. Based on S-88, international standardisation of batch control.
Consists of nearly 60 building blocks, unit operation (operation, phase) determining
the sequential activity of one unit (e.g. reactor) until a requirement is full filled.
Cleaning e.g. is a unit-operation.
The facility is divided in seven unit types. Each unit has a number of basic functions
(heating, cooling, agitation, condensation) which are governed by the unit-operations.
Basic functions continuously control the process conditions.
Although much is automated the operator still has to perform some tasks such as
making connections for solvents or with other units, sampling/ in process analysis,
charging solids to reactors, determine continuation of automatic control on visual
effects (colour change e.g.)
Since units can be coupled in a random way the routing manager is an important
feature. All routes made are checked on correctness and connections are continuously
monitored. Breaking an active connection puts the batch program on hold.
Process graphics are shown in a central control room. Operators in the field have local
terminals with limited information and limited possibility for process interference.
For all three levels of control the operator uses a paper standard batch record (different in
each case of course), which dictates his activities and keeps track of it.
The initial alarm inflation and most other teething problems of the recipe control have been
overcome. The system has however a number of draw backs:
 Introduction of new products takes two people one month to make all the preparations
 Changes to equipment cause a lot of work and revalidation
 Much more maintenance than level 2 and much more specific know how of
application software required
 Decreased flexibility
The expected advantages:
 The capacity does not seem to have increased.
 Reproducibility is slightly improved.
 Safety has improved by the build-in emergency shut down which is in many more
instances activated but this might be counterbalanced by unexpected mistakes in the
software

Reliability of cleaning has improved. System keeps track of clean status of equipment
and pipelines.
The challenge: Develop a hybrid batch recipe control system with reduced complexity
but maintaining most of the advantages
related questions:
 What level of automation should we use for the next new production facility? How to
decide?
 where does our automation level stand in comparison to similar companies? Some seem to
refrain or to retreat from recipe-control
 does a MES/ recipe creation layer make the difference?
 is there anything between level 2 and 3?
new hopes?