Hygienic Conditions of Clean Rooms and Air Quality Classification in Medical Device Production

To minimize the risks of microbiological, chemical and physical contamination in the manufacture of medical products (stents, balloons, catheters, biopsy sets, etc.) to be sterilized by ethylene oxide, gamma rays or heat treatment, is required.

Many of these requirements depend on the design of the cleanroom, the skills, training and behavior of relevant personnel. Kalite Quality assurance ında is of paramount importance in the manufacture of sterile products and must be carried out according to carefully prepared, validated production methods and procedures.

Sterile medical devices; It must be manufactured in clean rooms where personnel or production materials can enter through controlled control. Clean areas should be designed in accordance with the cleaning-disinfection conditions and be fed with filtered air with appropriate efficiency.

Air Quality

The various processes for production, preparation, washing, packaging and sterilization of the product should be carried out in separate areas within the clean area.
The clean areas used for the production of medical products are classified according to the prescribed air properties from ISO Class 1 to ISO Class 9 according to EN ISO 11644.
Particle values ​​given in the table are the criteria in which the product is in contact with the environment and must be met in the surrounding environment.
In order to minimize the risk of particulate and microbial contamination of the medicinal products or materials produced, each manufacturing process requires an appropriate level of air purification.

EN ISO 11644 AIR CLASSIFICATION SYSTEM FOR MANUFACTURING STERILE PRODUCTS

Maximum allowable number of particles in 1 cubic meter of air
ISO CLASSES	0.1 mikron	0.2 mikron	0.3 mikron	0.5 mikron	1 mikron	5 mikron			Air microbiology CFU/ m3
Iso Class 1	10	2
Iso Class 2	100	24	10	4
Iso Class 3	1000	237	102	35	8
Iso Class 4	10000	2370	1020	352	83
Iso Class 5	100000	23700	10200	3520	832	29			<1-10
Iso Class 6	1000000	237000	102000	35200	8320	293			<10
Iso Class 7				352000	83200	2930			<100
Iso Class 8				3520000	832000	29300			<200
Iso Class 9				35200000	8320000	293000

Staff and Clothing

Clean areas should have a minimum number of personnel who can optimally maintain the production process. This is important to ensure aseptic conditions in the environment. Inspections and controls should be carried out as far as possible from outside the area.
All personnel employed at such sites, including personnel responsible for cleaning, disinfection and maintenance, shall receive the necessary training in the proper manufacture of sterile products, including the basic aspects of hygiene and microbiology.
Compliance with standards is essential for personnel hygiene and cleaning.
Personnel working in the production of sterile products should be informed of sources of microbial, chemical or physical contamination and instructed to report any situation that may cause abnormal spreading.
Personnel should undergo periodic health checks. Decisions regarding measures to be taken for personnel that may pose a microbiological hazard should be taken by a qualified person assigned to this task.
Wristwatches and jewelery should not be worn in clean areas and particulate cosmetics should not be used.
Do not enter into clean areas with clothes worn outside. Personnel entering clothing change rooms should wear standard protective clothing from the factory. Changing clothes and washing should be done according to the written procedure.
Clothing and clothing quality should be appropriate to the process and working areas and should be worn to protect the product from contamination.
Clothing should meet the air class criteria of the areas where the personnel work.
Clean-area clothing should be washed or cleaned in such a way that it does not collect contaminated particles and does not release these particles into the environment. It is preferred to use a separate washing facility for such garments. Improper cleaning or sterilization may result in damage to the fibers of the garments, which may increase the risk of particle formation of the garments. Washing and sterilization procedures should be carried out according to written procedures.
Gloves should be disinfected regularly during the procedure and masks and gloves should be changed at least every working period. In some cases it may be necessary to use disposable clothing.
Design of Clean Areas

In clean areas, all surfaces should be smooth, permeable and non-cracking to minimize the accumulation or scattering of particles or microorganisms and to allow repeated application of cleaning agents and disinfectants.
In order to reduce the accumulation of dust and to facilitate cleaning, there should be no recesses, protrusions or cracks on the ceiling, floor, counter and equipment surfaces.
Flat protrusions such as equipment, containers, shelves and shelves should be minimal. Doors must be carefully designed and there should be no recesses or protrusions that cannot be cleaned.
Suspended ceilings must be sealed to prevent interference from the space left on them.
The pipes and air ducts must be installed in such a way that they do not form indentations which are difficult to clean.
Sinks and drains should be avoided wherever possible and should not be located in areas where aseptic procedures are performed.
It must be designed and installed and maintained to minimize the risk of microbiological contamination. They must be easily cleaned and connected with active traps and equipped with air breaks to prevent backfire. Any surface channel on the base should be open and shallow, easy to clean and the connection to drainages outside the area should be such that microbial dishes do not leak.
The dressing rooms must be designed separately to separate the phases of the dress change.
It must be effectively washed with filtered air.
In some cases it may be desirable to use separate dressing rooms for entry and exit. Hand washing facilities should only be provided in the locker rooms.
The doors of the air lock must not be opened at the same time when entering clean areas. To prevent the opening of more than one door at the same time, mutual locking system or visual and / or audible warning system must be operated.
The positive pressure should be maintained under all operating conditions and the clean area should be washed effectively compared to the surrounding areas by the introduction of filtered air.
Special attention should be paid to the protection of risky areas.
In some operations, it may be necessary to have decontamination facilities and purification for air discharged from clean areas.
Routine microbiological and particle count tests should be performed in the ventilation system.
A warning system should be provided to indicate that the air supply system has failed. In areas where pressure differences are important, devices measuring pressure differences should be installed. These pressure differences should be recorded regularly.

Conveyor belt and so on. continuous systems should not move from a process area of ​​low-class air cleaning to a higher level of clean area unless they are constantly disinfected.
Equipment connections and installations should be located and designed so that maintenance and repair can be carried out outside the clean area as far as possible. If sterilization is required, this should be done after the complete installation of the equipment in question.
Where equipment is maintained in a clean area, if the prescribed cleaning and / or asepsis standards cannot be maintained or maintained during maintenance, the area should be cleaned and disinfected where necessary before the process is repeated.
All equipment, including sterilizers, air filtration systems, water treatment systems, distillation devices, must be subjected to planned cleaning, disinfection, maintenance and validation. The use of these devices after maintenance operations must be approved by the quality control.
Water treatment units should be designed, constructed and maintained to ensure reliable quality water production. These units must not be operated above their designed capacity.
Hygiene-Sanitation-Sterilization Processes

Sanitation of clean areas is particularly important. These areas should be cleaned frequently and appropriately according to a written program approved by the quality control department.
If disinfectants are used, more than one type of disinfectant should be used. Regular monitoring programs should be conducted to determine the development of resistant strains.
Water should be produced, stored and distributed in such a way as to prevent the growth of microorganisms. (For example, water should be circulated permanently at temperatures above 70 ° C.)
Disinfectants and detergents should be monitored for microbial contamination, diluted solutions should be stored in pre-cleaned containers and should not be added to partially emptied containers.
Fumigation of clean areas (gas disinfection) may be useful to reduce microbiological contamination in unreachable areas.
During operations, clean areas should be monitored by microbial counting at planned intervals;
Where aseptic studies are performed, the frequency of analysis monitoring should be increased and system validations may be required after non-production processes such as cleaning and fumigation.
Care should be taken that validations do not pose a danger to the operations to be carried out.
Water resources, water treatment equipment and treated water should be regularly monitored for chemical and biological contamination and, where appropriate, endotoxins. Monitoring results and records of any operations performed should be kept.
Activities in clean areas, especially aseptic processes, should be kept to a minimum in order to prevent high amounts of particles and organisms from dispersing as a result of excessive mobile activities, and personnel movements should be controlled and methodical. Ambient temperature and humidity should not be high enough to cause discomfort due to the nature of clothing worn in clean areas.
Microbiological contamination in starting materials should be minimal. The biological burden should be monitored before sterilization. Where monitoring is identified as necessary, the specifications should include microbiological quality requirements.
Precautions should be taken to minimize contamination at all process steps, including prior to sterilization.
There should be a "pre-sterilization contamination limit" determined depending on the efficiency of the method used and the risk of pyrogen presence.
The effectiveness of any new procedure should be validated and validation should be repeated at regular intervals. In case of any significant change in process or equipment, validation should be repeated.
All sterilization processes should be validated. The sterilization method applied must comply with the applicable ISO standards or International Medical Standards.
Before any sterilization process is carried out, its suitability for the product must be demonstrated to achieve the desired sterilization conditions at all points for each type of loading to be processed. This work should be repeated at planned intervals, at least once a year, or when significant changes are applied to the equipment. Records of results should be kept.
For effective sterilization, all material must be subjected to the required treatment and the process should be designed to ensure that it is obtained.
Methods should be available to distinguish between sterilized and non-sterilized products.
Each basket, tray or other carrier carrying the products or device parts must be clearly labeled with the name of the material, serial number and whether or not it has been sterilized.Where applicable, indicators such as autoclave strips may be used to indicate whether a series or sub-series has undergone a sterilization process. However, they cannot reliably prove that the series is truly sterile.

Samples taken for sterility testing should be able to represent the whole series, but should include samples from sections with the highest risk of contamination.
After sterilization, necessary tests should be performed to determine gas residues and / or levels of reaction products.