2. Sanitation and Hygiene
Objectives
Review measures to ensure good sanitation in:
Premises and personnel
Equipment and apparatus
Processes, materials and containers
To review measures to ensure good personal hygiene
3. Sanitation and Hygiene
Scope
High level of sanitation and hygiene practised – in every aspect of
manufacturing. It covers:
Personnel
Premises
Equipment and apparatus
Production materials and containers
Products for cleaning and disinfection
All potential sources of cross-contamination
4. Sanitation and Hygiene
Personal Hygiene (1)
Health examinations:
Before and during employment
Periodic eye examinations for those who do visual inspections
Training:
Practices in personal hygiene
Written procedures and instructions
Signs in areas
5. Basic Principles of GMP
Written procedures and
instructions - to wash hands
before entering production
areas
Some also use disinfectants
6. Basic Principles of GMP
Wash hands before entering
production areas
Signs in areas (e.g. changing
rooms)
7. Sanitation and Hygiene
Personal Hygiene (2)
Illness or open lesions:
May affect the quality of products
Should not handle starting materials, intermediates or finished
products, etc.
Instruction and encouragement to report to supervisors
Direct contact between product and operator:
Should be avoided
Starting materials, primary packaging materials, intermediate and
bulk product
8. Sanitation and Hygiene
Personnel Hygiene (3)
Protection of product from contamination:
Clean clothes appropriate to personnel activities
Including hair covering (e.g. caps)
Check change rooms/changing facilities
Hand washing, signs, drying of hands
Used clothing stored in separate closed containers while awaiting
cleaning
Laundering of clean area clothing according to an SOP and in an
appropriate facility
Procedure for disinfecting and sterilizing when required
9. Sanitation and Hygiene
Personnel Hygiene (4)
Smoking, eating and drinking not allowed in production areas,
laboratories and storage areas
No chewing (e.g. gum), or keeping food or drinks allowed
No plants kept inside these areas
Rest and refreshment areas should be separate from
manufacturing and control areas
10. Sanitation and Hygiene
Design of Premises
Design
Walls, floors, ceilings, ledges, drains, air supply, dust
extraction
Prevention of build-up of dirt and dust to avoid unnecessary risks
of contamination
Cleaning programme, appropriate cleaning, cleaning records
Effective cleaning and disinfection
choice of materials and chemicals, validation
Drains – prevent backflow
11. Basic Principles of GMP
Protection from insects,
birds, vermin and weather
from receipt of raw
materials to dispatch of
released product
12. Sanitation and Hygiene
Avoidance of Cross-Contamination (1)
Special precautions should be taken to prevent generation and
dissemination of dust
Proper air control – supply and extraction, suitable quality
Due to uncontrolled release of:
dust, gas, particles, vapours, sprays, organisms, residue,
insects
13. Basic Principles of GMP
Measures that can be taken to
prevent cross-contamination also
include:
Segregated areas
Ventilation systems
Airlocks
Clothing
Closed processing systems
Cleaning and decontamination
14. Sanitation and Hygiene
Avoidance of Cross-Contamination (3)
Campaign production:
Separation in time
Followed by appropriate cleaning
Validated cleaning procedure
15. Sanitation and Hygiene
Avoidance of Cross-Contamination (4)
Ventilation systems and airlocks
Appropriately designed ventilation system with air supply
and extraction systems
Supply or incoming air should be filtered
Recirculation of air versus 100% fresh air supply
Proper airflow patterns
Pressure differentials
Appropriately designed airlocks
16. Basic Principles of GMP
Appropriately designed
ventilation system with air
supply and extraction
systems
Supply or incoming air
should be filtered
Detailed modules in the
supplementary training deal
with recommendations for
HVAC systems
17. Sanitation and Hygiene
Avoidance of Cross-Contamination (5)
Clothing
Protection of operator and product
Highly potent products or those of particular risk - need for
special protective clothing
Personnel should not move between areas producing different
products
Garments need to be cleaned
18. Sanitation and Hygiene
Avoidance of Cross-Contamination (6)
Cleaning and decontamination
Procedure for removing soil and dirt
Remove all cleaning chemical residues or disinfectant
residues
Remove and/or reduce micro-organisms
Validated (known effectiveness of the procedure)
Use cleanliness status labels
Test for residues
19. Sanitation and Hygiene
Avoidance of Cross-Contamination (7)
Closed processing systems
For example: totally enclosed water purification systems
Tanks fitted with appropriate filtration - without
removable lids
Present special cleaning difficulties, sometimes use
clean-in-place (CIP)
20. Sanitation and Hygiene
Production Operations – Sanitation (1)
Cleaning and cleaning validation
Degree of cleaning depends on whether consecutive batches
are of same or different product
Check cleaning agent is fully removed
If possible hot water alone used for cleaning
all cleaning and disinfecting solutions carefully prepared and
expiry dated
Final rinse with purified water, or water for injection (for sterile
products)
Full records kept
21. Sanitation and Hygiene
Production Operations – Sanitation (2)
Full records kept
Water systems
Water - major constituent of most products
SOP for cleaning and sanitization of the water purification system
should include distribution line
Validation and removal of disinfectant before reuse
22. Sanitation and Hygiene
Production Operations – Sanitation (3)
Maintenance and repair
activities inevitable in manufacturing area
Should present no risk to product
Whenever possible, all planned maintenance outside normal
operating hours
Emergency work in working area followed by thorough clean down
and disinfection before manufacturing recommences
Area clearance by QC
Editor's Notes
In this session, we are going to deal with an area of importance to the good functioning of a pharmaceutical factory, sanitation and hygiene.
This will be a quarter-day session with the following approximate timings:
Presentation 45 minutes
Group session 45 minutes
Group feedback 30 minutes
Test paper 30 minutes
(Timings are approximate and should be adjusted to suit the class and the course structure.)
There are three main objectives to this session:
Firstly, we are going to look at the measures that need to be taken to ensure good sanitation during manufacturing. These relate primarily to the premises, the equipment and the process to prevent any type of contamination.
Secondly, we are going to look at the measures that need to be taken to ensure that good levels of hygiene are achieved during manufacturing. These relate primarily to the personnel.
Finally, we are going to relate everything back to the issues particularly relevant to your country. During the group session, you will be looking at the key factors that you need to be aware of during your inspections. We will be presenting you with some photographs to list all the sanitation and hygiene problems that you can.
The WHO GMP refers to sanitation and hygiene in part one, section 4. It makes the point that all aspects of manufacturing are affected by one or both of these factors.
Consideration must be given to all personnel, both direct operators and other staff who enter the manufacturing area for whatever purpose.
Then there are the premises in which manufacturing takes place. The level of attention to this aspect will vary with the operation that is carried out.
All equipment and apparatus used in manufacturing must be controlled, together with production materials and the containers in which they are held.
Production materials (if not handled properly) and the containers (if not properly cleaned) can contribute to dirt and contamination in the factory.
Secondary materials, such as cleaning agents and disinfectants, must be controlled to ensure that they do the job for which they are designed but do not cause any contamination to the product. Cleaning tools, such as mops and brushes, must also be controlled.
To summarize, the aim of sanitation and hygiene measures is to eliminate all potential sources of contamination and cross-contamination from all areas where the product is at risk.
Having dealt with sanitation, we now move on to the hygiene of the personnel involved in manufacturing. This is covered in the WHO GMP texts in part one, section 10.
The recruitment process for direct operators in particular should include a medical examination. This should be repeated on a regular basis during the employment period. The definition of “regular” will obviously depend on the activities being undertaken and the products being processed.
Induction training for new operators should include basic training in personal hygiene and should state the level of hygiene that is required for working in manufacturing areas. There should be written procedures covering the need to wash hands before entering a manufacturing area. In addition, signs should be posted in the changing rooms to reinforce this.
Explain the use of disinfectants as appropriate, before entering production areas
Explain the use of signs in washing areas, toilet facilities - before entering production areas
Staff who have an illness or open lesions that are likely to present a risk to the product, should not be allowed to carry out operations that involve handling of starting materials, intermediates or finished products until the condition has cleared up. Since not all illnesses are going to be obvious, operators must be trained to recognize such risks themselves and be willing to report any illness to the area supervisor.
Direct contact between the operator and the product should be avoided wherever possible. If direct handling is unavoidable, then gloves should be worn and, if appropriate, these should be disinfected after being put on.
Products should be protected from contamination. There should be procedures for cleaning of garments/clothes. Clothes can become a source of contamination and cross-contamination. These should be cleaned regularly according to validated procedures. Where relevant, caps, masks, gloves etc should be worn. Be on the lookout for dedicated shoes. How often are these cleaned, and how?
Check change rooms/changing facilities
Hand washing, signs, drying of hands
Used clothing stored in separate closed containers while awaiting cleaning
Laundering of clean area clothing according to an SOP and in an appropriate facility
Procedure for disinfecting and sterilizing when required
Smoking, eating and drinking should not be allowed in any manufacturing area, including laboratories and storage rooms. Chewing of gum should also be banned. There should be no plants kept inside any factory areas.
Rest and refreshment areas should be separate from manufacturing areas.
Sanitation is covered as part of the general discussion of premises in part one, section 11 of the WHO GMP text.
As discussed (or will be discussed) in the module on premises, the design of any area depends on the activities that are going to be performed there. However, in general terms, all areas should be designed in such a way that prevents the build-up of dirt and dust. This includes the absence of ledges and unnecessary surfaces, sealing of all joints in ceilings, coving at floor and ceiling and installation of a ventilation system that provides an appropriate flow of air.
There are a number of aspects to be covered in looking at cleaning. An effective programme should be designed that covers both cleaning and disinfection. The frequency of each will vary with the function of each area and the particular activities undertaken there. There must be a written procedure (SOP) covering the programme, who is responsible for carrying it out, the materials to be used and methodology. The procedure should be appropriate to the area being cleaned. For example, the procedure for cleaning the warehouse would not be appropriate for cleaning a sterile area.
There should also be a written record of cleaning that has been performed.
While drains are inevitable in some manufacturing areas, they should be kept to a minimum and should certainly not be located in sterile areas. Their design must prevent the possibility of back-flow. Open channels should be easy to clean and disinfect.
There should be maximum protection against the entry of insects or other animals. In loading bays in particular, there needs to be protection against the weather.
In part two of the WHO GMP, section 15 covers the measures that need to be taken to avoid cross-contamination.
Proper air control – supply and extraction, of suitable quality should be provided. Filtration is often needed. Contaminants can be due to uncontrolled release of dust, gas, particles, vapours, sprays, organisms, residue, insects, operators,
Explain the concept of air locks, and how these other measures can prevent contamination and cross-contamination
The trainer should also give emphasis to the use of campaign processing.
Explain what it means, the number of batches in a campaign, and what level and method of cleaning is appropriate.
Refer also to the need for cleaning validation where relevant.
An important measure against cross-contamination is the design of the ventilation system. All incoming air should be filtered to an appropriate standard to achieve the grades of cleanliness specified for the room being supplied. The use of appropriate pressure differentials and air extraction, together with airlocks, is one of the main ways of achieving control over cross-contamination. (Airflow patterns and equipment design are other considerations.) Additionally, the recirculation of air must be examined carefully. If a ventilation system supplies 100% fresh air, then different rooms can be used for different products at the same time. However, if a system includes recirculation, then all rooms supplied by that system must be processing the same product, or the air must be filtered to an appropriate standard. If no filters are installed, then all ductwork will have to be cleaned during product changeover.
Refer here only to the HVAC system and the supplementary training material on HVAC
Clothing relates to the protection of both the operator and the product. For highly potent products or those that create a particular risk of cross-contamination, special protective clothing needs to be worn. Decontamination processes for these clothes need to be in place. For all manufacturing areas where there is any risk of the product contaminating the clothing, the simple precaution of not moving between areas producing different products should be adopted.
Cleaning should be a procedure for removing soil and dirt. It should not add or leave behind anything, including cleaning, chemical or disinfectant residues.
It must remove or reduce micro-organisms.
Cross reference to the module on validation can be mentioned if questions arise on how and what is cleaning validation.
Increasingly, facilities are being designed with closed processing systems. This trend is obviously one that should be encouraged, as it is a major element in the avoidance of cross-contamination.
We have already talked about cleaning of premises. Another important point is the cleaning of the equipment in which products are manufactured. The degree of cleaning will depend on whether consecutive batches are of the same product or of different products. It is important that any cleaning agent introduced is also fully removed so that it does not contaminate the product. Wherever possible, hot water alone should be used for cleaning. The final rinse should be with purified water or water for injection in the case of equipment used for processing sterile products.
A validation programme should be based on the worst case situation, e.g. a relatively insoluble material that is active at low levels of concentration. Additionally, full records should be kept of cleaning and sanitation.
The sanitation of water systems is particularly important, as water is such a major constituent of most products. Water heated >75oC and recirculated is a good sanitising agent. Water for Injection is usually stored at much higher temperatures.
There should be a written standard procedure for cleaning and prevention of contamination, which should include not just the purification system but also the distribution pipework. The procedure should be validated, especially the removal of disinfectant before the system is put back into use. This is important because formaldehyde and peracetic acid are often used to disinfect water systems
Repair and maintenance activities are inevitable in a manufacturing area. However, they should be carried out in a way that does not present any risk to the product. Therefore, whenever possible, all planned maintenance should be done outside of normal operating hours. Any emergency work in a working area should be followed by a thorough clean down and disinfection of the area before manufacturing recommences, AND area clearance by QC