Sources of Contamination & its prevention in an Aseptic Area.
Introduction:
An aseptic area is a premise in a clean area, designed, constructed, serviced and used with an intention to prevent the microbial contamination of the product.
It is important to identify the sources from which the contaminants can enter the aseptic area in order to avoid the contamination of products under operation.
The important sources of contamination in an aseptic area are as follows.
Personnel
Buildings and Facilities
Equipment and Utensils
Raw Materials
Manufacturing Process
A HVAC (Heating, Ventilation, and Air Conditioning) System.
1) Personnel:
The personnel working in aseptic area can be a potential source of microbial contamination, due to the following reasons:
Inadequate training,
Direct contact between the hands and materials.
Improper hygiene,
Unauthorised personnel entering the facility, (This is why educational visits are denied in sterile areas).
Insufficient gowning and protective equipment,
Eating, drinking, or smoking within the storage and processing areas.
2) Buildings and Facilities:
These can also be important contributors to microbial contamination due to the following reasons:
Inadequate size and organisation of the space, which lead to selection errors (such as mixups or cross-contamination between consumables, raw materials, in-process materials, and finished products),
Poor filth and pest controls,
Rough floors, walls, and ceilings,
Absence of air filtration systems,
Inadequate lighting and ventilation systems,
Poorly located vents, ledges, and drains, and
Improper washing, cleaning, toilet, locker facilities, sanitary operation.
3) Equipment and Utensils:
They are the common sources of microbial contamination due to the following reasons:
Unsuitable design, size, corrosion-causing materials, and/or adulteration with lubricants, coolants, dirt, and sanitising agents,
Inadequate cleaning and sanitisation,
Inefficient cleaning and maintenance due to their designing
Inappropriate calibration and irregular service, and
Using defective equipment.
4) Raw Materials:
These are used during production and are considered a potential source of contamination due to the following reasons:
Improper storage and handling, which leads to mix-ups or selection errors,
Microbial or chemical contamination,
Degradation due to extreme environmental conditions (like heat, cold, sunlight, moisture, etc.),
Wrong labelling.
Incorrect sampling and testing, and
Using materials not meeting the acceptance criteria.
5) Manufacturing Process:
During the manufacturing process, microbial contamination of raw materials, intermediates or packaging materials can widely occur due to the following reasons:
Absence of facilities required for manufacturing of a single product,
Improper cleaning between batches for minimising the amount of product changeovers,
Use of an open manufacturing system for exposing the product to the room environment,
Improper zoning,
Lacking an area line clearance (as per the approved procedures) after each cleaning process and between each batch, and
Lack of cleaning status labelling on all equipment and materials used within the manufacturing facility.
6) A HVAC (Heating, Ventilation, and Air Conditioning) System:
An inappropriate HVAC system is a possible source of microbial growth and also disperses the contaminants throughout the manufacturing unit. This occurs due to the following reasons:
Organic materials accumulate in or near HVAC air intakes,
Inadequate air filtration system,
Inadequate magnitude of pressure differentials, which causes flow of reversal,
Incorrect ratio of fresh air to re-circulated air,
Incapability of accessing ventilation dampers and filtering from outside the manufacturing areas, and
Non-directional airflow within production or primary packing areas. W
Methods of Prevention of Contamination:
1) Personnel:
Access to production areas by the unauthorised personnel should be restricted, and only trained ones should be allowed to enter.
Adequate personnel hygiene should be maintained.
The personnel should be given proper and regular training with respect to hygiene as well to ensure that their activities do not hamper the product quality.
Personnel entering the manufacturing area should wear protective clothing (over-garments, hair cover, beard or moustache cover, and overshoes).
Personnel should avoid touching with naked hands the exposed products or any part of equipment in contact with the product.
2) Buildings and Facilities:
In aseptic rooms, the differential air pressures should be higher than the adjacent controlled areas.
Air filtration and air change rates should be set to attain the defined clean room class.
Unidirectional (laminar flow) air flow should be maintained over critical areas at sufficient velocity to sweep particles away from the filling/closing area.
Ambient temperature and humidity should not be very high.
The ventilated cabinets, RABS (Restricted Access Barrier System), isolators systems, etc. should be used.
The areas of unequal risk are separated by UV air locks and door barriers.
All open-container processing should be performed within the isolator/RABS.
The air pressure of the changing room should be negative with respect to the
manufacturing area corridor, but positive with respect to the external adjacent areas.
The ventilation dampers, specially designed filters, and other services should be positioned such that they can be accessed from outside the manufacturing areas (service voids or service corridors) for maintenance purposes.
An impermeable barrier should be used in appropriate areas to prevent cross- contamination between two zones.
HVAC air distribution components should be used for preventing the spreading of contaminants generated within the room.
All rooms and surfaces should be maintained and monitored for viable and non-viable particulates and this facility should be re-certified on a semi-annual basis.
3) Access to Areas
Access to production, packaging, and QC areas by unauthorised personnel should be restricted.
Personnel should gain access to these areas only via changıng rooms.
Materials should be accessed via specific routes (generally air locks).
4) Building Requirements:
Smooth, crack-free, and easily cleanable floors, walls, and ceilings should be used.
Windows or viewing panels should be closed (non-opening), fixed with wall panels, and sealed to prevent accumulation of dust and microbial contaminants.
The designing of pipe work, ventilation, and light points should be such that Creation of spaces which are not easily cleanable is avoided.
Sinks of stainless steel should be present within the production areas.
5) Cleaning and Disinfection:
Time-to-time cleanliness and disinfection of the areas should be done.
Cleaning agents of proper grades should be used for minimising health risks.
Contact time, application, temperature, mechanical action, and the chemistry of cleaning agents should be considered during the cleaning process.
The cleaning agents should not be directly applied on the product.
The cleaning practices should be validated to prove that the process effectively controls microbial contamination.
6) Utilities
Water of pharmaceutical grade, microbiologically controlled and monitored should be used in the manufacturing of products.
Clean and additive-free steam should be used for cleaning and sanitisation of production tools and equipment, and to supply for autoclaves and humidification.