Automated process control for pharmaceuticals

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    Automated Process Control System

Course Name: Pharmaceutical Engineering – II
Course Code: PHR 412
Section: 2

Presented To:
Dr. Sohel Rana
Department of Pharmacy

Presented By:
A T M Omar Farooq
The automated control of a process
Automated process control is used extensively from oil
refining, chemical processing, electrical generation to the
food and beverage and pharmaceutical industries Such
systems typically deal with analog signals from sensors and
meters that are transmitted to specialized computers which
cause the temperature, pressure, flow etc to be continually
adjusted, and thus involve analog to digital conversion.

Automatic control systems are composed of three

Sensor(s), which measure some physical state such as temperature
Responder(s), which may be simple electrical or mechanical systems or complex special
purpose digital controllers or general purpose computers.
Actuator(s), which affect a response to the sensor(s) under the command of the
responder, for example, by controlling a gas flow to a burner in a heating system

Why Automated Control System

Automatic control systems enable us to operate our
processes in a safe and profitable manner. Control
systems achieve this "safe and profitable" objective by
continually measuring process variables such as
temperature, pressure, level, flow and concentration -
and taking actions such as opening valves, slowing
down pumps and turning up heaters - all so that the
measured process variables are maintained at operator
specified set point values.

The overriding motivation for automatic control is safety, which encompasses the safety
of people, the environment and equipment.

Advantages of Automated Process Control
   o The design of a process and associated control
     system makes human safety the primary objective.
   o As automated system allows protection of
     environment and plant equipment, control
     objectives can focus on the profit motive.
   o Automated process monitoring and control can
     provide a cost effective means of collecting
     meaningful process data.
   o   Reduction of labour
   o   Flexibility to change the batch process control as the process changes.
   o   Stable plant operation with reduced operational errors and rejected products.
   o   Automatic controller increases the reliability of the operative control of the
       equipment and increases the ability of a machine to be interfaced into a computer
       controlled process.
   o   It is easier to comply with cGMP, GLP and FDA guidelines.
   o   Laboratory scientists are freed from the mundane manual methods of data
       collection, analysis, and control, and can focus on essential research and
   o   Automated process control and data management allows easy expansion.
   o   A good software solution enables FDA-compliant systems for labs and pilot
       plants, with full security and tracking features
   o   Greater efficiency and shorter time to market the product.
   o   A technician can monitor many reactors from one station, or respond to alarms
   o   A researcher can check on and adjust experiments from her office, create reports,
       and be automatically notified by email or pager when problems arise.
   o   Instrument resources can be shared. E.g. one expensive gas analyzer can serve
       many reactors.

For example, at one facility, a bioreactor automation system is controlling a high-pressure
liquid chromatograph and recording result. At another, an in-situ microscope with
attached camera takes images of cells in the bioreactor. The system controls the camera
and microscope, displays and stores images, and automatically analyzes certain cell
features in the images. Automation software allows these kinds of subsystems to be
integrated into the larger process.

Drawbacks of the old manual methods
In the old manual process control system to monitor the development process, scientists
walked around the lab recording data on a clipboard from each instrument, and then
manually entered all the data into a spreadsheet. Based on their analysis of this
aggregated data, they returned to each controller to adjust the recipe process by hand, in
order to optimize the recipe for maximum
effectiveness and best yield.

   o This may lead to poorly controlled process
     variables and can exhibit large variability in a
     measured process variable. Also, data
     collection in this way can be a laborious and
     very costly task.
   o Lack of ability of simultaneous data collection
     at multiple key process locations
   o Manual methods make FDA compliance
     difficult, because changes cannot be recorded and tracked, procedures cannot be
     repeated exactly, and systems are less secure.
   o In old manual method the sensed information about temperature, pressure, and
     humidity was manually recorded by a supervisor in charge. This often results in
     data entry errors.

Automation of process variables
A process variable is the current status of a process under
control. Measurement of Process Variables is important in
controlling a process.

At the heart of industrial process control is the measurement
of certain variables, such as temperature and pressure, used in
manufacturing processes to transform raw materials into
finished products. Measurements made by sensors, meters, or
other measuring instruments on the manufacturing process
line are sent by a transmitting device to an indicator or recorder for display and/or to a
controller where the data are compared to a pre-established set of parameters. The
controller calculates the difference between the measured data and the programmed
"setpoint" values and, if necessary, adjusts the process variables to conform to the desired
parameters. This feedback-and-response cycle is called a loop, and continuous, repeating
loops are performed during the industrial process to ensure product quality, efficient use
of raw materials, and process safety.

Flow and Level Instruments:

The most common flow meters are differential-pressure, turbine, mass-flow, variable-
area, magnetic, and positive-displacement meters. Flow meters are used to measure the
rates of flow of fluid chemicals, gases, liquids containing particulate matter (slurries),
water. Level instruments can be used to determine the amount of raw materials available
for production purposes they are typically installed in tanks, hoppers, or other storage

Pressure Instruments:

The vast majority of products manufactured by industry
firms are the result of processes that use pressure to
perform work. Punch presses and boilers are typical
pressure-based industrial process machines. Pressure
measuring instruments such as gauges and pressure
transmitters operate hydraulically, pneumatically, or
electronically to measure pressure, absolute pressure,
vacuum pressure.
Temperature and Primary Temperature Instruments:

More than half of all measured process variables undergo some form of temperature
measurement during the manufacturing process. Accurate temperature measurements are
critical in processes where slight temperature variances can destroy final product quality.
The four basic temperature-measuring instrument types are thermocouples, resistance
thermometers, thermal radiation meters, and non-glass filled systems, such as industrial
mercury-filled thermometers. Primary temperature instruments are the sensors that
receive and measure the initial temperature data in the process control loop.

Gas and Liquid Analyzers:

Analyzers of gas and liquid in continuous on-stream industrial processes are often
classified according to the nature of the interaction between the gas and liquid to be
measured and an external source of energy. Analyzers allow molecular-level
measurement of process materials without interruption of the process for sample
extraction. Analyzers are used to measure industrial effluents and waste products,
viscosity of liquids used in mixing processes and food
processing, the acidity or alkalinity of process materials.

Humidity Instruments:

The pharmaceutical industry is one of the largest users of
humidity measurement equipment. Most drugs are sensitive to
variations in humidity and moisture levels, so these need to be
considered and controlled for the final products to be consistent
in quality and performance. Humidity should be controlled
during all phases of drug development. Instruments such as
hygrometers and psychrometers measure the water vapor
content of air in such industrial applications as test chambers, pharmaceutical packaging,
heat treating, and industrial drying.

Other Process Control Instruments:

This category includes instruments for measuring such process variables as specific
gravity, density, viscosity, weight, or force.

The process variables that must be monitored and controlled in all distillation processes
      Temperatures
      Pressures
      Flow rates
      Levels and compositions
These process variables within a distillation system affect one another, whereby a change
in one process variable will result in changes in other process variables. Thus, during
distillation control one should be looking at the whole distillation column rather than on
any particular sections only.

Each column has a control system that consists of several control loops. The loops adjust
process variables as needed to compensate for changes due to disturbances during plant

How is the process variables automated?
Pressure is often considered the prime distillation control variable, as it affects
temperature, condensation, vaporization, compositions, volatilities and almost any
process that takes place inside the column. Column pressure control is frequently
integrated with the condenser control system. Reboilers and condensers are integral part
of a distillation system. They regulate the energy inflow and outflow in a distillation

   1. Condenser and Pressure Control
The 3 main methods of pressure and condensation control are:
              Vapor flow variation
              Flooded condenser
              Cooling medium flow variation.

Vapor Flow Variation:

The simplest and direct method for column producing a vapor product. The pressure
controller regulates the vapor inventory and therefore the column pressure. An important
consideration here is the proper piping of the vapor line to avoid liquid pockets.

Flooded Condenser:

This method is used with total condensers generating liquid product. Part of the
condenser surface is flooded with liquid at all times. The flow of condensate from the
condenser is controlled by varying the flooded area. Increasing the flooded area (by
reducing flow) increases the column pressure (less surface area for condensation).

Cooling Medium Flow Variation:

Pressure can also be controlled by adjusting the flow of coolant to the Operation using
cooling water can cause fouling problems at low flow condition, when cooling water
velocity is low and outlet temperature is high.
   2. Temperature Control
Column temperature control is perhaps the most popular way of controlling product
compositions. In this case, the control temperature is used as a substitute to product
composition analysis. Ideally, both top and bottom compositions should be controlled to
maintain each within its specifications.

In practice, simultaneous composition control of both products suffers from serious
"coupling" (interaction) between the 2 controllers, resulting in column instability. In the
system shown, suppose that there are concentration changes in the feed conditions that
result in lower column temperature. The top and bottom temperature controllers will
respond by decreasing reflux and increasing boil-up respectively.

If the actions of the 2 controllers are perfectly matched, and response is instantaneous,
both control temperatures will return to their set points without interaction.

However, the 2 actions are rarely perfectly matched, and their dynamics are dissimilar -
usually the boil-up response is faster.

The interaction can be avoided by controlling only 1 of the 2 product compositions.
Another advantage is that, should the analyzer become inoperative, the temperature
controller will maintain automatic control of the process.

   3. Feed Preheat Control

Feed preheat is usually practiced for heat recovery or to attain the desired vapor and
liquid traffic above and below the feed tray. The objective of the preheat control system
is to supply the column with a feed of consistent specific enthalpy. With a single-phase
feed, this becomes a constant feed temperature control; with a partially vaporized feed, a
constant fractional vaporization is required.

   4. Reboiler Control
This is required to provide good response
to column disturbances, and to protect the
column from disturbances occurring in the
heating medium. The reboiler boil-up is
regulated either:

        To achieve desired product purity
        To maintain a constant boil-up
In a typical reboiler control (see Figure ), the control valve is located in the reboiler steam
inlet line.

For inlet steam controlled reboiler, the heat transfer rate is regulated by varying the
steam control valve opening, thereby changing the steam condensing pressure and

When an additional boil-up is required, the valve opens and raises the reboiler pressure,
which increases the temperature, and in turn increases the boil-up rate.

An alternative is to control the condensate flow, i.e. by putting the control valve on the
condensate line. The main disadvantage is that this scheme has poorer dynamic
response than the previous scheme.

   5. Analyzer Control
On-line composition is usually measured by gas chromatographs.
Other analyzers include infra-red and ultra-violet analyzers, mass
spectrometers, refractive index analyzers, etc. An example of an
analyzer is shown in the Figure.

Analyzers have the advantage of directly measuring the product
quality, but also have the drawbacks of high maintenance and
slow dynamic response.

Digitalization of pharmaceutical Industry
Pharmaceutical and healthcare industries are highly regulated industries in each and
every nation around the globe. Every nation has a governing body like USFDA, TGA,
and M.H.R.A, Schedule-M etc. that assures that the medicines are manufactured under
strict guidelines to ensure highest quality of manufactured products. However assuring
high quality products requires that the manufacturing facility is monitored 24x7 and this
monitoring requires the use of high end networking technology. Currently pharmaceutical
plants capture this information using a number of scalar sensors that measure
temperature, pressure, humidity etc.

Computer Assistance Manufacturing Technology
The pharmaceutical industries are subject to a variety of laws and regulations regarding
the patenting, testing and marketing of various drugs. The work load is very high and the
increasing complexity is a great concern in the
industry. With the advent of sophisticated computer
technology, pharmaceutical companies have actively
sought the use of computer technology to assist.
These have improves the quality, efficacy, speed and
also simplifies the work of pharmaceutical industry.

Computer Aided Manufacturing (CAM)
Since the age of the Industrial Revolution, the manufacturing process has undergone
many dramatic changes. One of the most dramatic of these changes is the introduction of
Computer Aided Manufacturing (CAM), a system of using computer technology to assist
the manufacturing process.

Computer-Aided Manufacturing (CAM) is the use of computer software and hardware in
the translation of computer-aided design models into manufacturing instructions for
numerical controlled machine tools.

Through the use of CAM, a factory can become highly automated. A CAM system
usually seeks to control the production process through varying degrees of automation.
Because each of the many manufacturing processes in a CAM system is computer
controlled, a high degree of precision can be achieved that is not possible with a human

Computer Aided Manufacturing is commonly linked to Computer Aided Design (CAD)
systems. The resulting integrated CAD/CAM system then takes the computer-generated
design, and feeds it directly into the manufacturing system; the design is then converted
into multiple computer-controlled processes, such as drilling or turning.

Persons interested in manufacturing technology
should possess:

      Mechanical aptitude
      Good basic math skills
      Ability to work well with others
      An interest in design and computer
Benefits of using CAM
  1. It can be used to facilitate mass customization. The process of creating small
     batches of products that are custom designed to suit each particular client.
     Without CAM, and the CAD process that precedes it, customization would be a
     time-consuming, manual and costly process. The automatic controls of the CAM
     system make it possible to adjust the machinery automatically for each different

  2. The ideal state of affairs for manufacturers is an entirely automated
     manufacturing process. In conjunction with computer-aided design, computer-
     aided manufacturing enables manufacturers to reduce the costs of producing
     goods by minimizing the involvement of human operators.

  3. It enables manufactures to make quick
     alterations to the product design, feeding
     updated instructions to the machine.

  4. Many CAM software packages have the
     ability to manage simple tasks such as the re-
     ordering of parts, further minimizing human
     involvement. Though all numerical controlled
     machine tools have the ability to sense errors
     and automatically shut down, many can actually send a message to their human
     operators via mobile phones or e-mail, informing them of the problem and
     awaiting further instructions.

  5. All in all, CAM software represents a continuation of the trend to make
     manufacturing entirely automated. While CAD removed the need to retain a team
     of drafters to design new products, CAM removes the need for skilled and
     unskilled factory workers. All of these developments result in lower operational
     costs, lower end product prices and increased profits for manufacturers.

Problems with Computer-Aided Manufacturing
  1. The setting up the infrastructure to begin with can be extremely expensive.

  2. Computer-aided manufacturing requires not only the numerical controlled
     machine tools themselves but also an extensive suite of CAD/CAM software and
     hardware to develop the design models and convert them into manufacturing
     instructions – as well as trained operatives to run them.
  3. The field of computer-aided management is fraught with inconsistency. While all
     numerical controlled machine tools operate using G-code, there is no universally
     used standard for the code itself.

  4. The lack of standardizations may not be a problem in itself; it can become a
     problem when the time comes to convert 3D CAD designs into G-code.

Applications of CAM

  1. The field of computer-aided design has steadily
     advanced over the past four decades to the stage at
     which conceptual designs for new products can be
     made entirely within the framework of CAD
     software. From the development of the basic design
     to the Bill of Materials necessary to manufacture the
     product there is no requirement at any stage of the
     process to build physical prototypes.

  2. Computer-Aided Manufacturing takes this one step
     further by bridging the gap between the conceptual
     design and the manufacturing of the finished
     product. Whereas in the past it would be necessary for design developed using
     CAD software to be manually converted into a drafted paper drawing detailing
     instructions for its manufacture, Computer-Aided Manufacturing software allows
     data from CAD software to be converted directly into a set of manufacturing

  3. CAM software converts 3D models generated in CAD into a set of basic
     operating instructions written in G-Code. G-code is a programming language that
     can be understood by numerical controlled machine tools – essentially industrial
     robots – and the G-code can instruct the machine tool to manufacture a large
     number of items with perfect precision and faith to the CAD

  4. Modern numerical controlled machine tools can be linked
     into a ‘cell’, a collection of tools that each performs a
     specified task in the manufacture of a product. The product
     is passed along the cell in the manner of a production line,
     with each machine tool (i.e. welding and milling machines,
     drills, lathes etc.) performing a single step of the process.

  5. A single computer ‘controller’ can drive all of the tools in a single cell for the
     sake of convenience, G-code instructions can be fed to this controller and then left
     to run the cell with minimal input from human supervisors.
Applications of Computer-Aided Manufacturing

Description: Automated process control is used extensively from oil refining, chemical processing, electrical generation to the food and beverage and pharmaceutical industries Such systems typically deal with analog signals from sensors and meters that are transmitted to specialized computers which cause the temperature, pressure, flow etc to be continually adjusted, and thus involve analog to digital conversion.