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Contamination Control in

GMP Areas

GMP Training – Contamination Control in GMP Areas by www.gmpsop.com


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Training Outcome of the Module:

Alter finishing this module, you will be able to:

List the common types of physical and chemical contaminants

Describe the consequences of producing contaminated products

Identify the potential sources of contamination at your worksite

List some ways that you can prevent contamination

Potential sources of physical and chemical contamination

How your facility has been designed to control contamination?

Some practical ways to prevent contamination

Introduction

Contamination is the presence of any foreign substance

in our products. It may be:

Physical: hair, foreign objects, dirt, dust, pollens

Chemical: cleaning agents, lubricants, other products

Microbiological: bacteria, moulds, spores, yeasts

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GOOD TO KNOW - CROSS-CONTAMINATION

Cross-contamination of product is caused by either:

a. contamination of a batch with a previous batch of the same product

b. contamination with a different product through carryover or proximity of

production lines

c. contamination by a foreign starting material usually of the dispensary or in

the store

The prevention of the cross-contamination requires:

a. the proper sealing, separation and storage of raw materials

b. care in management of the dispensary so as to exclude the opening of

different lots of containers in close proximity

c. the thorough and rigorous cleaning of all equipment, utensils, transfer lines,

extraction systems and vessels after use

d. re-inspection of equipment before use and line clearances at all stages of

manufacture

e. ensuring all air conditioning systems are serviced and property maintained

Cleanrooms and cross-contamination

The prevention of cross-contamination is also accomplished by the use of

positive air barriers (to exclude other products), dust extractors and

containment hoods (to trap and remove dust) during processing. Cleanrooms

are specifically designed so the air flow patterns and room pressures protect the

product, if is very important to maintain this protection by:

Keeping doors closed (to prevent loss of pressure)

Keeping air returns clear (to maintain sweeping of air)

Cleaning extractors and filters (for efficient operation)

Checking room monitors (to verify set pressures)

Regularly maintaining/servicing the air handling units

Main sources of contamination

Environment in which the product is formulated and filled



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Equipment used in formulation and filling

Operators

Raw materials and packaging materials

Other products may cause cross-contamination

Contamination control

Not all contaminants can be seen, for example, bacterial contaminants, so strict

controls are needed to prevent contamination. You must know and follow your

company's procedures.

If you suspect that contamination has occurred, make a note on the batch

records, and tell your supervisor. This way, there is a greater chance of detecting

the contaminant.

The two ampoules on the right are contaminated. They are slightly cloudy. It is

very difficult to tell isn't it?



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Raw Materials store

Poor housekeeping in the store can lead to product mix-ups and cross-

contamination.

RAW MATERIAL STORES

Doors should be kept shut to prevent dust

and pests from entering.

Materials should be stored off the floor in a

way to prevent damage or contamination.

Spills should be cleaned up immediately.

All materials and products should be clearly

labeled to prevent mix-ups.

There should be separate storage areas for

quarantined goods and a locked area for

rejected materials.

The open container is prone to contamination

from humidity or other microbial agents in

the environment.

Staffs must be wearing protective clothing.

Poor housekeeping practices and lack of

restricted access can lead to product mix-ups

or cross-contamination.




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GOOD TO KNOW - CONTROL OVER INCOMING GOODS

Incoming goods need to be controlled.

Each lot of material must be assigned a unique identification number to ensure

traceability and checked for possible transit damage and contamination.

Once these materials are accepted into the facility, they must be stored in such

a manner that contamination is minimized.

Before use, these materials must be checked for correct identity, cleanliness,

integrity of the storage container or protective wrapping and suitability for use

in the manufacturing process.

Only by these checks can operators satisfy themselves that the material has

not been contaminated during storage end is in fact the right material to be

using,

GOOD TO KNOW - USE OF COMPUTER SYSTEMS

Often computer systems are used to control inspection and test status, In this

case, materials and products may not have physical status labels or even be

stored in separate areas. Such systems must be validated and thoroughly

documented. All operators must be trained in the use of these systems.

Maintenance department

Poor housekeeping practices by maintenance personnel can cause problems in

manufacturing.

MAINTENANCE STORES

Operators should observe requirements for

wearing clean working gowns.



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Poor cleaning and hygiene practices can lead

to contamination of product.

Never use product bottles for lubricants or

other supplies. Always label bottles clearly to

prevent mix-ups.

Spills should be cleaned up immediately.

Pest control programs should be in place for

the entire facility.

This poor repair job has created a high risk

for microbial contamination.

Dispensary

Dispensing areas have been designed to minimize the risk of contamination and

mix-up. It's important that only raw materials are dispensed by authorized

operators following standard procedures.

DISPENSARY ROOM





These two drums should never be opened at

the same time.

There should be special precautions such as

exhaust fans to prevent the generation of

dust.



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Exhaust fans are only effective if they are well

maintained and switched on. Cleaning

procedures need to specify the methods for

cleaning exhaust ducts, grilles, flues and fan

blades.

Dirty equipment can be a source of

contamination.

Filling department

Poor contamination control in the filling department can have disastrous

consequences.

FILLING ROOM





Air handling units should be installed,

operated and maintained to ensure a clean

supply of air.

Never use product bottles for lubricants.

Always label bottles clearly.

Always wear the specified work garments to

prevent cross-contamination.

Poorly maintained equipment and incorrect

machine set ups may damage product

containers.

Never return dropped product to the line.



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GOOD TO KNOW - CONTROL BY CONTAMINATION BY MACHINERY

The machinery used in manufacturing a product is an often overlooked source

of possible contamination. Possible contaminants are lubricating fluids,

wearing parts that generate metal particulates, previous product remaining as

a result of incorrect cleaning and malfunctioning equipment that smash

containers or have inefficient extraction devices fitted.

The operator using these machines can ensure that contamination of product

does not occur by ensuring that the machines are thoroughly cleaned after use

and examined for cleanliness before use. During operation, the operator

should be constantly aware that a malfunctioning machine may contaminate

product and be alert for teaks, drips from lubricating glands or wearing of

machine parts.

Machines should be kept in good running order by having periodic preventative

maintenance checks performed according to a schedule that relates to the

machine age, use, and requirement for servicing. A maintenance program that

is directed at breakdown maintenance will not minimize the possibility of

contamination of product.

GOOD TO KNOW - CONTROL OF AIR QUALITY

Contamination can occur if contaminated air comes in direct contact with the

product at the dispensing of starring materials, the formulation of the product,

or the filling of me product into the final product containers. In each case, the

contamination may be airborne particulates, other products or a starting

material of a previous product.

The sources of airborne contamination can be the air supplied to the facility,

operators working in the facility and generating the contaminant, materials

bought into the facility, or machinery used within the facility.

Control of airborne contamination is achieved by controlling the quality of air

within the facility. This relates back to the design of the facility, the air handing

system and the rooms within the facility. The type of air filtration employed



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within the facility and the air flow are important factors in controlling

contamination.

Just as important is the temperature and humidity within the facility. A facility

that is too hot or too humid rapidly causes operators to perspire and perspiring

operators are a source of particulate and microbial contamination. For these

reasons, processing rooms and storage areas should have controlled access.

The quality of air required in processing areas will be different for different

products and for different manufacturing stages of product.

Packaging department

Special emphasis needs to be given to the control of labels and pre-printed

packaging materials to prevent mix-ups and product recalls.

PACKAGING ROOM





Labels should be kept in an restricted area.

They should be kept in sealed containers and

returned to the store before the next

operation.

Never take personal medication into the

manufacturing areas.

Operations should be segregated and signs

should clearly identify the product being

packaged to prevent mix-ups.

Different products must be segregated.

Labels should be securely fixed to the

container – not the lid.



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Prevent cross-contamination by conducting a

line clearance before commencing work.

GOOD TO KNOW - CONTAMINATION BY PEOPLE

Operators are a major source of contamination.

Operators need to be disciplined in their work habits and understand and

follow all procedures relating to the manufacture of product. Operators

involved in processes where exposed starling materials or products are

handled should not be suffering from a contagious disease or have open lesions

on the exposed surfaces of the body, if this is the case, report to your

supervisor.

Strict personal hygiene of all staff, whether involved with exposed product or

not, is essential in controlling contamination. Operators should never directly

contact exposed product or clean final product containers and caps as they

could contaminate the product with skin particles, body oils and hair. Jewelry

should not be worn if the operator has contact with exposed product as it is

potentially a source of dirt and grime. Jewelry may also fall into product mixes

and remain undetected.

Protective garments should be worn when handling starting materials and

exposed product. Once garments become wet or dirty, replace them with a

clean, freshly laundered garment. Wet and dirty garments are a potential

source of contamination. Operators and support staff should take particular

care when moving between work stations to ensure they are not carrying

residual materials on their clothes or footwear.



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Air must be controlled in rooms where product is exposed to the environment.

Some important controls for cleanrooms are:

PACKAGING ROOM

Filter the incoming air

Control the temperature

Control the humidity

Have fast flowing air

Have a laminar flow

Keep the room at a higher pressure

than the surrounding areas

Keep doors shut!

Work areas should be as close to the air inlet

as practical since this is where the air will be

the cleanest.

Air should flow away from the work station

and out of the room in a smooth manner.

Doors should be kept shut to maintain the air

pressure in the room.

Do not obstruct the air outlet this will upset

the flow of air.

Keep the air supply and returns clear of

obstructions. This way, you will minimize risk

of environmental contamination.

Observe the effects when obstructions are

placed in the room, by clicking on the buttons

below.




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AIRFLOW PATTERNS AND CONTAMINATION CONTROL

There are basically two types of cleanrooms:

a. those designed to exclude particles, dirt, bacterial and other products -

these are called positive pressure rooms where the room pressure is higher

than the outer rooms.

b. those designed to contain dust generated during product processing within

the room – these are called negative pressure rooms where the room

pressure is less than surrounding rooms.

These rooms often have a dust extraction system to trap product dust.

The effective operation of either room type is dependant on keeping doors

closed and ensuring inlet filters, air return vents and dust extraction

equipment is clean and operating properly.

GOOD TO KNOW - POSITIVE PRESSURE ROOMS

Positive pressure rooms are at a higher pressure than surrounding areas - if

the door is kept closed. The rooms are designed to clean the air by exchanging

it about every 3 - 5 minutes through air filters in the inlet vents. The air is

swept across the room to outlets (returns) near the floor and door. Provided

the doors are kept shut the room should be very clean.

These rooms are used when the exclusion of bacteria and particles from the

room and product is important.

Products that are processed in these cleanroom, where bacterial exclusion is

important, include creams, oral liquids, ointments and sterile products.

GOOD TO KNOW - NEGATIVE PRESSURE ROOMS

Negative pressure rooms are used when it is more important to trap or contain

any product dust in the room or dust extractor. This is done to prevent

contamination of other processing rooms and possible cross-contamination of

other products and equipment.



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Rooms of this type usually contain a secondary extractor to collect the product

dust and sometimes filters on the return air vents and ducts. It is important

to keep doors shut, clean room and equipment regularly and maintain the

extraction systems.

Dry oral products, such as tablets and capsules, where bacteria or particles

are less of a problem, are usually processed in these rooms.

A pharmaceutical manufacturer had a product recall due to insecticide

contamination of a batch of tablets.

Several consumers had severe reactions due to the poisoning. Since insecticide

was not used in the plant, the company started a detailed investigation to trace

the source of the problem. The company rightly suspected that the problem was

one of foreign contamination.

Select what you think could be the possible sources of the problem. Explore each

possible explanation.

SOURCE OF PROBLEM

No, the company records indicated that no

insecticide was used or processed in the plant.

Possible, but the company was very careful not

to allow poisons into the factory. The pest

control company was escorted on site and not

permitted near processing rooms. They did spray

around storage rooms, however.




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No, unless the supply company made a horrible

mistake. However, the company did not check

the cleaning agent drums on receipt.

Possible, but the company was very careful to

conduct identity tests on all new materials

before use. Not every container was tested,

however.

No, the product had a tamper-evident seal, and

the severe reactions were in different regions.

Possible, the company did not use drum liner

bags, and the bulk product was in direct contact

with the inside surface of the 44 gallons storage

drums.

What actually happened

The drug maker used 44 gallon drums to store bulk powder. These drums were

supplied and recycled by a drum supplier. Among the drum supplier's customers

was an insecticide manufacturer. This was not known to the drug maker because

they had not audited the drum supplier's operations. The drum supplier did not

keep a separate stock of drums for the drug manufacturer, and did not have a

cleaning program for recycling.

Investigation also revealed that drum bag liners were not used, nor did the drug

maker have a program to inspect or clean the drums before their use in the plant

and. reasonably, their QC testing did not check for insecticide contamination.

When contaminated drums were returned by the insecticide manufacturer and

recycled via the drum supplier to the drug maker, the problem remained

undetected.



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HOW DID THEY FIX IT?

The company implemented the following corrective action to prevent

recurrence of the problem:

Purchase dedicated drums

Inspect any drums on receipt for cleanliness. Wash any that are not clean

or better still, reject.

Ensure staff inspect all equipment before use No exceptions!

Use fresh liner bags to isolate product from storage drums.



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Summary

Risks of contamination or cross-contamination arise:

From starting materials (including water)

From the environment and from uncontrolled release of dust, gases, vapors,

sprays or organisms from materials or products in process

From residues in equipment

From operators and their clothing

Contamination control is achieved by:

Having well-designed and operated facilities

Good housekeeping practices

Having written procedures for:

- handling and storing material and products

- cleaning of equipment and facilities

- preventive maintenance programs

- conducting room and line clearances

Having well-trained operators

Documenting all deviations or abnormalities



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TAKE THE TEST NOW

Number of questions: 10

No time limit

Allow you save and finish at a later date

Allow you to go back and change your

answer

Attempting each question is mandatory

Pass mark at and above 70%

Print results and certificates

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contamination control in gmp areas - gmpsop€¦ · are specifically designed so the air flow...

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