PROCESS AUTOMATION

IN PHARMACEUTICAL
INDUSTRY

By: Sharon.R.D’souza (QA-06)

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 AUTOMATION
• Automation means the use of machines and equipments for performing
physical and mental operations in a production process in place of human
being.

• It can be done at various levels of manufacturing system:-

 Handling of raw materials, semi-finished goods or finished goods.

 During production process
 Inspection and quality control operations.

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 CLASSIFICATION OF
AUTOMATION

• Process automation- deals mainly with handling of raw materials in forms

such as liquids or powders. E.g. In oil refinery, oil and gas and chemical
industries.
• Discrete automation- essentially deals with assembly of parts requiring
high levels of mechanical motion to produce consumer electronics products
and products for the automotive industries.

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 AUTOMATION IN PHARMA
INDUSTRY
• Basic purpose of process automation in manufacturing industry is:

 To increase productivity
 Improve quality of products and to reduce waste
 For safe handling of hazardous substances
 To takeaway heavy work from workers

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 MONITORING OF PARENTERAL
MANUFACTURING FACILITY
• All environmental parameters shall be verified and established at the time
of installation and thereafter monitored at periodic intervals and recorded.
The recommended frequencies of periodic monitoring shall be as follows:
 Particulate monitoring in air. 6 monthly
 HEPA filter integrity testing (smoke testing)-yearly
 Air change rates-6 monthly
 Air pressure differentials-daily
 Temperature and humidity-daily
 Microbial monitoring by settle plates and/or swabs in aseptic areas-daily
After major engineering modification to the HVAC system of any area all
monitoring shall be reperformed before production commences.

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 CLEAN IN PLACE SYSTEM (CIP)
• A CIP system is a cleaning method which is designed to clean an entire
system of equipment with appropriate cleaning agents in situ without any
disassembly of equipment component, or pipes.

Points to consider are given below:

 Design considerations for CIP system
 Selection of cleaning agents
 CIP process parameters
 Routine monitoring and control
 Maintainance and control
 Personnel and training

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 Design considerations for
CIP system
When designing equipment, pipes, cleaning agent supply apparatus, etc for
the CIP system, the following technical points should be considered:

• Equipment and piping with smooth inner surfaces should be selected and
incorporated into the CIP system to facilitate cleaning effectiveness.

• Presence of dead legs in piping connected to the equipment should be

minimized. The equipment, piping, and valves within the equipment should
have designed to have adequate slope to allow for draining of both cleaning
agents.

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 Selection of cleaning
agents
• Cleaning agents should be selected after evaluating their ability to remove
residual substances, compatibility with the manufacturing equipment ,etc.
• Eg. of cleaning agents include water, hot water, detergents, alkaline
solutions, hot alkaline solutions, and organic solvents.
• The quality of water used for final rinsing of product contact equipment
surfaces should be of same quality as water used for product formulation
• Quality control specifications of cleaning agents should be established and
documented.

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 CIP process parameters
It includes:
• Type and concentration of cleaning agents
• Flow rate of cleaning agents
• Duration of contact between the equipment and cleaning agents
• Temperature and pressure of cleaning agents
• Total cleaning time

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 Routine monitoring and
control
CIP and related records should include, but not be limited to, the following:

 Time and date

 Name of equipment cleaned
 Name and production batch number of pharmaceutical products
manufactured prior to CIP cycle.
 Name and production batch number of pharmaceutical products after
cleaning with the CIP system
 Name of CIP operators
 Operating conditions of the CIP system

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 Maintainance and
control
• Critical equipment such as pumps, which are closely related to CIP
parameters including pressure, temperature, and flow rate, should be well
controlled and subjected to maintainance at defined intervals.

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Sterilization in process (SIP)
• A SIP system is a sterilization method which is designed to sterilize an
entire system of equipment in situ without disassembly of components, or
piping. The most common sterilization agent for SIP is saturated
steam(moist heat).
• General requirements:

 Steam used in SIP process should be generated from purified water of not
less than purified water grade. Condensed water from steam should meet
specifications of water used for product formulation.
 Locations most difficult to sterilize so called “cold spots” in the equipment
should be identified, and the SAL achieved at these points should be
evaluated at appropriate intervals.

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 Key design considerations
for the SIP system
• Smoothness of the inner surfaces of the equipment
• The design must ensure the saturated steam reaches all surfaces to be
sterilized
• Heat and pressure resistance of the equipment
• Compatibility between construction material and steam quality
• Location of saturated steam inlet and steam distribution

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 Routine monitoring and
control
• Process operation records and other records on SIP operations should
include, but not be limited to the following:
• Time and date
• Name of equipment subjected to SIP
• Name of operators
• Operation condition
• Verification of compatibility of SIP conditions employed

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 Maintainance and
control
• Valves and steam traps should be subject to periodic maintainance checks
to ensure the proper injection of steam for sterilization and that condensed
water forming during SIP is properly discharged.

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 Pre-filled syringe
 A prefilled syringe is a single-dose packet of parenteral drug to which a
needle has been fixed by the manufacturer.
 Prefilled syringes are ready to use disposable syringes containing
premeasured dosage, reduces dosing errors and increases patient
compliance.
 Prefilled syringe is a delivery system designed to administer appropriate
amount of medicament to the patients.

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 Pre-filled syringe
 There are 2 major types of prefilled systems available:

 Glass-based systems: made from glass tubing

Advantages: deliver a more accurate dose of the drug to the patient, less pain
production at the injection site.
Drawbacks: breakage, potential surface reactivity, particulate contamination.

 Plastic-based systems: the most widely used prefilled plastic syringe

systems are manufactured from cyclo-olefin polymer (COP) resins.
Advantages: break resistance, design flexibility

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 FORM FILL SEAL TECHNOLOGY
• Form fill seal units are specially built automated machines in which
through one continuous operation, containers are formed from
thermoplastic granules, filled and then sealed.
• Blow fill seal units are machines in which containers are
moulded/preformed in separate clean rooms, by non-continuous operations.
• Form fill seal machines are used for manufacture of products for terminal
sterilization shall be installed in atleast Grade C environment and the
filling zone within the machine shall fulfill Grade A requirements.

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 Lyophilization
technology
 Definition:

A stabilizing process in which a substance is first frozen and then the

quantity of the solvent is reduced, first by sublimation( primary drying
stage) and then by desorption (secondary drying stage) to values that no
longer support biological activity or chemical reactions.

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Principle of lyophilization
• Lyophilization is carried out using a simple principle of physics:
sublimation
• Sublimation is the transition of a substance from solid to vapour state,
without passing through intermediate liquid phase.
• Lyophilization is performed at temperature and pressure conditions below
the triple point, to enable sublimation of ice.
• The entire process is performed at low temperature and pressure by
applying vaccum, hence is suited for drying of thermolabile compounds.

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 Process of lyophilization
• Freezing stage-the product is frozen. this provides a necessary condition for
low temperature.
• Primary drying stage-after freezing, the product is placed under vaccum.
this enables the frozen solvent in the product to vaporize without passing
through liquid phase i.e. sublimation.
• Secondary drying stage-heat is applied to the frozen product to accelerate
sublimation. Low temperature condenser plate remove the vaporised
solvent from the vaccum chamber by converting it back to a solid.
• Packing
This completes the process.

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Basic components of a
lyophilizer

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 references
• https://www.slideshare.net/NarendraEdara/aseptic-proce
• https://www.slideshare.net/rajendrarocks/seminar-on-manufacturing-facility-of-parentarals-
as-per-schedule-mssing-35349412
• https://www.slideshare.net/rajendrarocks/seminar-on-manufacturing-facility-of-parentarals-
as-per-schedule-m
• https://www.slideshare.net/ceutics1315/lyophilization-39635366
• http://www.authorstream.com/Presentation/manmanasi-2463918-packaging-sterile-
pharmaceuticals/

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THANK YOU

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