PROCESS AUTOMATION IN

PHARMACEUTICAL
ManufacturingINDUSTRY :
of Sterile Semi-
solids,
SVP’s, LVP’s

Presented By: Vrushabh Khaunte

Roll No: 08 M.Pharm (PQA) Sem-II
Pharmaceutical Manufacturing
Technology
CONTENT
• Introduction

• Process automation

• Machine design

• Processing a product

• Benefits of automation

• Limitations of automation

2
 0 Introduction
:
• Pharmaceutical industry has many complex processes and to control each of these

1process manually imparts a risk on quality and efficiency of the products.

• Even though high quality products are produced from good workmanship by humans,
automated systems typically perform the same manufacturing process with less
variability than human workers, resulting in greater control and consistency of product
quality.

• Therefore during any process, for example filling, all the parameters involved like
volume, pressure, temperature, flowrate will be accurately controlled.

• As a result batches always meets the specification and also it ensures:

1.Raw materials are used more efficiently
2.Energy usage is kept minimum
3
3.Cleanliness is achieved
 • There is need of
⚬ process optimization
⚬ regulatory compliance
⚬ improvements in the supply chain

-Therefore Investment in automation technologies across the pharmaceutical

industry is increasing.

• Systems used to automate process steps during the manufacture of

pharmaceuticals are continuously evolving with new instrumentation and control
products coming to market.

• Industry is becoming increasingly important for the continued success and

competitiveness of pharmaceutical manufacturers.

• Industry are ongoing automation of traditional manufacturing and industrial

practice using modern smart technology. 4
• Industry will take automation to a new level with individual management
processes expected to become automated.

• Ex, if a temperature gauge makes a higher than expected reading, the

machine will detect this and rectify the situation itself rather than
requiring an operator to intervene and make an assessment about the required
course of action.

• But but, due to regulatory constraints, the pharmaceutical industry has been
slower to adopt this type of cutting-edge technology.

• While embracing the potential for Industry is going to be critical to future

operational efficiency for all manufacturers, it may be a long time before the
industry is able to complete the digital transformation and have fully automated
and connected facilities that can take advantage of everything digital 5
manufacturing has to offer.
 Pharmaceutical manufacturing of sterile
semi-solids
Semisolid products have been manufactured for
many years for distribution as pharmaceutical
drug products, cosmetics and health supplements

• Different types of semi soilds ;

-Hydrophillic ointments
-Water emulsifying ointments
-Creams
-Gels
-Hydrophobic gels
-Pastes

6
 Parenteral dosage
form :
• Parenteral dosage forms are sterile pyrogen free preparations intended
for administration by the injection under or through one or more layers of
skin or mucous membrane

• There are mainly two types of parenteral dosage form :

A) Small Volume Parenteral (SVP)
B)Large Volume Parenteral (LVP)

7
 A) Small Volume Parenteral
(SVP) :
• These are usually ranges from 1 to 30 ml in volume that is less than
100 ml in volume.

• Mostly given as multiple doses.

• Different types of small volume parenterals are :

e.g. - Ampoules
-Vials
-Dry powder
-Prefilled syringes

8
 B) Large Volume
Parenteral(LVP)
• A single dose of injection that is:intended for I.V. use and packed in
containers labelled as containing more than 100 ml.

• LVPs are aqueous solution usually supplied in volume of at least 100ml

with sizes of 250 ml, 500 ml, 1000 ml, and 3000 ml.

• The directions usually recommended that large quantities are

administered.

• Many different LVPs are commercially available, packed in glass bottles or

in large volume
Examples of LVPs: flexible containers.
• Calcium solution
• Sodium chloride ringer sodium bicarbonate
• Electrolyte solution
• 9
Pre-mixed I.V. Admixture
 Process Automation :
• Use of digital technology to perform a processes in order to accomplish a
workflow.

• It is the use of control system such as computers to control industrial

machinery and processes reducing human intervention.

• Higher levels of automation can predict the likelihood of failures and

therefore allow for preventive maintenance.

• It includes the use of alarms as warnings when something is outside

tolerance limits or a failure of a component has occurred, thereby allowing
action to be taken as quickly as possible.

10
• In a automated operation machines are linked together by conveyer
belts in an arrangement that requires little attention from an
operator.

Feed turntable

Conveyer belt

Filling wheel

Stoppering machine

Collecting machine 11
• Automation of entire process will convey an empty dose container from its
supply carton through the entire process until it is filled, labelled and placed
in the shipping carton.

• Such automated processing lines are usually located in aseptic room with
critical portions further protected with covers and bathed with HEPA- filtered
air.

• Justified when high production rates are required.

12
 Example : MLF 5088 – Vial filling and closing machine.

• All vials are weighed directly before and after the filling station and by
comparing both these measurements, the absolute filling weight is
determined. The machine automatically adjusts volume in case of deviating
quantities.

• Vials are transported through a machine with format cells which guarantees a 13
• MLF 5088 features a combined filling station with eight dosing heads, which
enables the machine to work either with piston, peristatic or rolling diaphragm
pumps or time-pressure filling system thus covering 99% of all filling system in
use for pharmaceutical machines.

• It is also suited for combination of different barrier system like: Restricted Access
Barrier System (RABS), cRABS, and isolators.

• The transfer from intermittent to continuous transport is accomplished with help

of a segment wheel. This transport is essential for this machine equipped with
continuously working stoppering station.

• This machine is suited for integration and can be combined with an upstream
washing machine and sterilization tunnel and a downstream capping machine .
14
 • It offers an output of 400 vials per minute with
integrated 100% IPQC.

• It can fill and close injection bottles in a processing

range of 2 to 100 millilitres.

• It is suited to process pharmaceuticals in aqueous

and low viscosity solutions.

• A new method, places the containers very gently

on IPC scales.

• Due to new slim design it is completely

approachable from the front even with closed
barrier.
Ex : Pumps can be easily and safety inserted at
the filling station.

• This leads to improved handling and highest possible product safety. 15

02 Machine
design :
• A machine that replicates simple human action is an,

– effective, well integrated and automated machine.

• While designing a system that will fill, seal, and process liquid

pharmaceuticals within a cleanroom environment, the inputs of process

engineers and the people that make the machines run must be

considered. 16
• Other design considerations include :
1. Cost-effectiveness
2. Fill volume ranges and accuracy levels products
3. Manufacturing space
4. Determining where operating stations will be positioned in the system and
how parts will be fed into these stations if an assembly has to be done.
5. Choosing and achieving the optimal spacing between parts.
6. Determining how much moving mass is the total of all operations.
7. Incorporating any hand work with automatic operations (Workers cannot
time their movements to an automatic process, so indexing in an automatic

17
• Robotics simulate the motion that an operator would do with a certain tool in

hand.

• Mechanical robots are probably best suited for the repetitive, short motions

common in most pharmaceutical applications.

• Synchronization is relatively easy and they can be packaged into a standard

building block for use in a variety of configurations.

• Redundancy should be built into each unit to ensure that the system works as

perfectly as possible to protect the parts, the machine and the operator.

• The system should contain correction capabilities for minor malfunctions so

that the line stops only for safety reasons. 18

continuous motion rotatory filling
machine

Close-up of the filling heads. The filling

heads follow the moving vials.
19
• The low moving mass of flexible stainless steel carrier belts assists in ensuring

instant and safe stops. Force limitations on all motions should be incorporated

to trigger safety stops.

• Contact with any single unit is never lost by using an integrated, automated

system.

• With integrated systems quality can be addressed, commensurate with the

strict validation standards required in aseptic processing.

• Layout judgment and configuration of system is retained within the vision of

designers and a wide range of choices should be available in a good design

layout. 20
03 PROCESSING A
• There are 4 distinct methods for progression of product through

a processPRODUCT
using automated:systems:

A . Batch processing

B. Indexing motion processing

C. Continuous motion fl ow processing

D. Process layout :
1. Rotary

2. In-line

3. Reverse in-line
21
A. BATCH
PROCESSING : to handle product in batch processing include
• Some of the devices used
flat trays, special egg-crating trays, three or four-sided trays, cartridges
and pallets.

• Due to interaction of the infeed star wheel, transport belt and pusher bar,

vials can be aligned in front of the loading platform without guides.

• Each vial format is programmed and reproducible using servo motor

technology for vial count with the infeed wheel and to locate exact
information of the row on the transport belt.

22
• The infeed belt and the loading platform are aligned at the exact same
height. Therefore, there is no risk for fallen vials or accidental
misalignment during transfer to the loading platform.

• Without precise motion control and location on the batch tray, it is

difficult to continue to the next process with automatic means while
keeping track of the unit.

23
• handling and loading is relatively difficult when high speed unit processing
is required (over 120 small parts per minute).

• Trays often are taken from an old manual process and are not specifically
designed for automatic loading and precision handling.

• When using trays, the system must be laid out for returning them clean or
for their disposal.

• Cleaning trays is complicated, the tray could be non-sanitary when

returned and a lot of floor space is required and excessive particulates may
be generated.
24
 B. INDEXING MOTION
PROCESSING :
– Indexing refers to movement of a mechanical member from an initial position to
a new position quickly, easily and precisely.

• Index devices process the movement of parts and it involves discontinuous

movement.

• These machines can be designed in single- or multiple-tooling units., multiple

means that one or more parts are indexed in a station-to-station process.

• For very heavy process tooling the index mode of moving the product is the
preferred method.

25
Mechanism (indexing motion processing) :

• Components are moved to specific positions(indexed) and

the machine stops to perform an operation.

• Commonly seen in packaging lines or tablet presses.

• Ex - A blister packaging machine..

26
 • Types of indexing motion processing are :

i. Indexing table

ii. Ring table and indexer

iii. Rotatory servo positioning stage

iv. Indexing belt

27
 I. Indexing
tables
• Tables can cycle either to the left:or right or alternate without modifications.

• These table are designed for repetitive moves around a platform.

• Switching is performed by pneumatic actuation and cycle types can be

changed in any order, any number of times.

• They can consist of :

-- Motors
-- Mechanical power transmission devices
-- Encoders
-- Sensors
-- Controllers
28
• Because only the table's cycle ring rotates, it offers a large fixed central
section, making it easier to add additional components and assemblies.

• Usually they take one piece around to work areas or move relatively small
parts around table for sequential assembly task.

• Important parameters for indexing tables are :

1. Resolution
2. Repeatability
3. Accuracy
4. Allowable backlash

29
 II. Ring table and
• Ring tables are suitable forindexer :
industrial automation requiring a large central hole
and many stations or programmable positioning.

• These have similar functioning to the other rotary table, the difference is
presence of a ring instead of dial plate.

• It is particularly useful in case you need a lot of space in the central area. This
space allows to have passage of cables, the placing of assembly stations and
any equipment that would otherwise be located outside, taking away valuable
space.

• This result is a compact indexer, with performance and load capacity superior
to its competitors. 30
• Large central hole is perfect gateway for wires.

• Due to its small size it can fit on any table in every

project.

• Also it do not require extra support.

31
 III. Rotatory servo positioning
• stage
Rotary stages provide smooth, low friction : motions over a large speed
rotary
range with zero-backlash.

• Rotary positioning stages are designed for precise motor driven rotary
positioning and indexing.

• These rotary tables are intended to function independently or in conjunction

with other positioning components used in high precision and automation
applications.

• A new version of rotary servo positioning stage features higher load capacity
and improved trajectory control.

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• These are ideal for today’s high performance technology environment.
Servo System Cam Control Rotary Filling
Machine

33
 IV. Indexing belts :
• A new line of indexing belts suits high-speed indexing conveyors used to
assemble plastic spray bottle caps and other multi-component assemblies.

• These stainless steel belts resist stretching, provide repeatability and

facilitate exact positioning of tools and parts.

• Unlike traditional conveying systems, these belts can be mounted vertically.

This allows manufacturers to use both sides of the conveyor.

• These continuous-length belts improve :

– Consistency
– Minimize debris buildup
– Eliminate shutdowns which occur during cleaning other types of systems.
34
35
 C. CONTINUOUS MOTION FLOW
PROCESSING
• Continuous production is a :flow production method used to manufacture,
produce or process materials without interruption.

• Operations are performed while the vials are in motion.

• In this way an 8-second station (filling) can be set up on the same

integrated line as a 1-second station process (stoppering) without stopping
the motion of the vial.

• Continuous processing is contrasted with batch production.

• It has much more flexibility than other designs.

36
• As compared to batch production and indexing processes, this method is
steady and continuous motion of processed parts.

• It involves less particulate generation and less wear and noise.

• Process speeds up to 1,000 small parts per minute.

• Several process stations of any mix are easily provided.

• The stations must be designed with minimum mass to minimize large

acceleration forces during the follow-up motion.

• The station must return by reversing the motion to its original starting place.

37
 D. PROCESS
• LAYOUT :
An automated production line is comprised of a series of workstations linked by
a transfer system and an electrical control system.

• Each station performs a specific operation and the product is processed step
by step as it moves along the line in a pre-defined production sequence.

• This line make people free from doing tedious repetitive task and it replaces
humans performing tasks in dangerous environment.

• Following the programmed commands, an automated production line is a

process in which raw materials enter and finished products leave with little or
no human intervention.
38
• Therefore, the tasks of human are more likely to do adjustment and
supervise and monitor the operation rather than controlling it directly.

• This fast, stable and accurate production flow contributes to the reduction of
production times and its cost.

• It also minimizes costs of manufactured product, labor costs and human

errors ensuring output consistency and quality.

39
Basic process
 I. ROTARY LINE
• In the rotary configuration, the work parts are indexed around a
LAYOUT
circular table or: dial.

• The workstations are stationary and usually located around the outside
periphery of the dial.

• The parts ride on the rotating table and are positioned, in turn at each
station for its processing or assembly operation.

40
• The rotary type is commonly limited to smaller workpieces and to fewer
stations.

• There is no flexibility in the design of the rotary configuration. This

configuration usually involves a lower-cost and typically requires less
factory floor space.

• Older designs are nearly always rotary turret units. The slower units use
index turrets; the faster ones use continuous motion rotary turrets.

• Precision on turret units is easier to achieve.

• The stations must not be crowded on the periphery around the center,
especially the station where feeding devices are used for parts to be
assembled.

• But layout of the machine often is too crowded, thus hand access to the
middle of the machine can be severely limited. 41
 Working : (Rotary line layout) :
• Consists of a circular worktable around which work parts are fixed to work
holders.

• The worktable rotates to move each work part, in turn, into each
automated workstation which is located around the circumference of the
worktable. The worktable is often called a dial, and the equipment is
referred to as a dial indexing machine/ simply, indexing machine.

• It is commonly limited to smaller work parts and relatively few

workstations, and they cannot readily accommodate buffer storage
capacity. However they require less floor space, and are generally less
expensive than other configurations.
42
 II. In-line
layout
• The in-line : consists of a sequence of workstations in a
configuration
more-or-less straight line arrangement.

• The flow of work can take a few 90° turns for workpiece reorientation,
factory layout limitations and still qualify as a straight-line
configuration.

• This approach is excellent for handling bottles or syringes in a

multitask processing line-from 1 cc to 1,000 cc bottles.

• The in-line design is preferable for larger work pieces and can
accommodate a larger number of workstations.
43
• This can be fabricated with a built-in storage capability to smooth out
the effect of work stoppages at individual stations and other
irregularities.

• A common pattern of workflow for example, is a rectangular shape

which would allow the same operator to load the starting workpiece
and unload the finished workpiece.

44
Construction and principle : (in-line layout) :
• Equipment is arranged in straight line
• Material flow from one end to other without looping back.
• Ideal for linear process flow and bulk processing.

Working :
• Product moves step-by-step from preparation to packaging.

• Each equipment station adds value (ex- mixing, deaeration, filling,

capping).

Ex :
-Manufacturing lines for sterile creams, gels in tube.
-In-line homogenizers and tube fillers used to maintain sterility and
continuous flow. 45
ADVANTAGES :
• Flexibility

• Easier automatic adjustments for different sizes of bottles

• Improved accessibility to all operational stations

DIS-
ADVANTAGES :
• For some manufacturers, in-line is a nonstandard or custom approach;
it can be more expensive and delivery time can be longer.

46
 III. REVERSE IN-LINE
LAYOUT
• Reverse : sometimes used if process components must be
in-line is
inverted or the table size of the line must be designed for minimum
space requirements.

• The input and output of the processed parts are basically at the same
place which is similar to a rotary turret layout.

• A good design should allow the user to select the layout with a
commitment from the machine builder that most of the components of
the system will be interchangeable and not layout dependent.

47
 Construction and principle :(reverse in-line
• layout)
Similar to in-line but with U-turn layout at :the end.

• The product comes back towards the starting area in a looped return
path.

• Often used when space is limited areas or to keep input and

output areas close to each other.

48
 Working : (reverse in-line layout) :
• Begins like an in-line layout but after processing, product turns back towards
the origin for final step like packaging.

• Allows easy monitoring of start and end points.

• The product flows through mixing > sterilization > Filling > comes back
for sealing > labeling > packaging near the original feed zone.

Ex :
-Used in LVP bottling lines where space constraint exists.

49
 Single Station Assembly
• Assembly operationsSystem
are performed :on a base part at a single
location

• A robotic arm is sometimes used as the assembly machine.

50
 Multi station vs Single
• Station :
Multi-station assembly machine or line
–Faster cycle rate
–High production quantities
–More operations possible
–More components per assembly

• Single-station assembly cell

–Suited to robotic assembly
–Intended for lower production quantities

51
 Benefits of automation
:
1. Lower operating costs :

• Robots can alone perform the work of three to five people, depending on the

task.

• In addition to savings on the cost of labor, energy savings can also be

significant due to lower heating requirements in automated operations.

• Robots increase accuracy, which means minimal material waste during

production.
52
2. Improved worker safety :

• Automated cells remove workers from performing dangerous task

and safe-guard them from hazardous environment.

• Automation can reduce health and safety risks, eliminate manual

handling and reduce the risk of repetitive strain injury.

53
3. Increased production output :
• A robot has the ability to work at a constant speed, unattended,
24/7.

• Automated machines do not have breaks, sick leave or holidays,

and therefore even if they are only running during normal shift
hours, it can lead to a production increase.

• Automated machinery can also typically run faster and produce

more accurately made products with fewer defects.

• New products can be more quickly introduced into the production

process and new product programming can be done offl ine with no
disruption to existing processes.
54
4. Better planning :

• Consistent production by robots allows reliable prediction of

time and costs.

• This predictability permits a tighter margin on any project.

5. Optimal utilization of fl oor space :

• Robots are designed to fi t in confi ned spaces.

• In addition to being mounted on the fl oor, robots can be

mounted on walls, ceilings, and shelves.
55
6. Consistent products :
• Automated manufac turing is inherently mo re c onsistent and
accurate in produc tio n quality.

• Automatio n systems c an easily inc orporate quality c hec ks and

verifi catio ns to reduc e the number o f o ut- o f-to leranc e pro duc ts
being pro duc ed w hile allo w ing fo r statistic al pro c ess c o ntro l that
will allow fo r a mo re c o nsistent and unifo rm pro duc t.

7. Increase system versatility :

• Robots are fl exible, easily retoo led and repositio ned fo r new
production pro grams.

• Robots are able to quic kly “learn” new pro c esses.

• Robots have the ability to easily sw itc h between a w ide range o f

products w ithout having to c o mpletely rebuild pro duc tio n lines.
56
 LIMITATIONS OF
1. AUTOMATION
Technology : :
limits
• Current tec hno lo gy is unable to auto mate all desired tasks.

• Example: Assembly o f produc ts w ith inc o nsistent c o mpo nent

sizes or in tasks w here manual dexterity is required.

• There are some things that are best left to human assembly and
manipulation.

2. Economic limits :
• Certain tasks w o uld c o st mo re to automate than to perfo rm
manually.

• Automatio n is typic ally best suited to pro c esses that are

repeatable, c o nsistent and high vo lume. 57
3. Unpredictable development costs :

• The research and development cost of automating a process is difficult

to predict accurately beforehand.

• This cost can have a large impact on profitability, it is possible to finish

automating a process only to discover that there is no economic
advantage in doing so.

• With the advent and continued growth of different types of production

lines however, more accurate estimates based on previous projects can
be made.

58
4. Fear of losing jobs :
• The fear is that the rapid increases in machine working in industry will be
a loss of human jobs to machines.

• Automation have the capability to remove the middle-class jobs and

displace the working class.

• However, companies that automate their processes have the capacity to

generate more jobs. This is because they become more prosperous and
efficient and more capable to address larger numbers of projects and
properly serve to more customers.

59
5. Initial costs are relatively high :
• The automation of a new product or the construction of a new plant
requires a huge initial investment compared to the unit cost of the
product.

• The cost can be prohibitive for custom production lines where

product handling and tooling must be developed.

• A skilled maintenance department is often required to service

and maintain the automation system in proper working order.

• Failure to maintain the automation system will ultimately result in

lost production and/or defective products being produced.

60
• Here advantages seems to outweigh the disadvantages.

• There is no doubt that productivity increases with the proper

application of automation techniques.

• Automation have the potential to transform processes within

pharmaceutical manufacturing facilities hence opening the door to
fundamental performance improvements.

61
 REFERENCE :
• Lachman/Lieberman’s The theory and practice of industrial pharmacy fourth edition –
Chapter 23 Sterile products Page no. 862

• Sterile pharmaceutical products – Process engineering application: Chapter 9 The

development of integrated, automated filling and packaging equipment using hybrid
robotics Page no. 357

• https://worldindustrialreporter.com/mlf-5088-pharmaceutical-vial-filling-and-closing-machin
e/

• https://www.machinedesign.com/motors-drives/article/21826611/motion-scenarios-indexing

• https://www.productivity.com/benefits-of-automation/

62
• https://www.europeanpharmaceuticalreview.com/article/1041/trends-in-pharmaceutical-
cleanroom-technology/

• https://www.pharmaguideline.com/2016/01/isolators-and-their-use-in-pharmaceutical-
manufacturing.html

• https://www.wisdomjobs.com/e-university/production-and-operations-management-tutorial-
295/automated-flow-lines-9685.html

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Thank You!

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