High level or sanitation and hygiene should be practiced in every aspect of manufacturing pharmaceutical products. The scope of sanitation and hygiene covers personnel, premises, equipment and apparatus, production materials and containers and anything that could become a source of contamination to the product. Potential sources of contamination should be eliminated through an integrated comprehensive program of sanitation and hygiene.
Every person entering the manufacturing areas should wear protective garments appropriate to the operations to be carried out.
Personal hygiene procedures including requirement of using protective clothing should apply to all persons entering production areas, whether they are temporary or full-time employees or non-employees on company property, e.g. contractor’s employees, visitors, senior management and inspectors.
To assure protection of the product from contaminations as well as the safety of the personnel, they should wear clean body-coverings appropriate to the duties they perform, including appropriate hair covering. Soiled uniforms and soiled cleaning cloths (if reusable) should be stored in separate closed containers until properly laundered.
Detailed hygiene programmes should be established and adapted to the different needs within the manufacturing area. They should include procedures relating to the health, hygiene practices and clothing of personnel. These procedures should be understood and followed in a very strict way by every person whose duties take him into the production and control areas. Hygiene programmes should be promoted by management and widely discussed during training sessions.
All personnel should receive medical examination upon recruitment. It must be the manufacturer's responsibility that there are instructions ensuring that health conditions that can be of relevance to the quality of products come to the manufacturer's knowledge. After the first medical examination, examinations should be carried out periodically for the work and personal health. Visual inspectors should also undergo periodic eye examination.
All personnel should practise good personal hygiene. They should be trained in the practices of personal hygiene. A high level of personal hygiene should be observed by all those concerned with the manufacturing processes.
Any person shown at any time to have an apparent illness or open lesions that may adversely affect the quality of products should not be allowed to handle starting materials, packaging materials, in-process materials, and pharmaceutical products until the condition is improved.
All personnel should be instructed and encouraged to report to their immediate supervisor any condition (plant, equipment or personnel) that they consider may adversely affect the products.
Direct contact should be avoided between the operator's hands and the exposed starting materials, intermediate and bulk products as well as with any part of the equipment that comes into contact with the products.
Personnel should be instructed to use the hand-washing facilities and to wash their hands before entering production areas. Signs to this effect should be posted.
Smoking, eating, drinking, chewing or keeping plant, storage of food, drink, smoking material or personal medicines should be restricted to specific areas and not permitted in production, laboratory, storage areas and other areas where they might adversely influence product quality.
Special requirements for sterile products are covered in Annex 1.
Premises used for manufacturing pharmaceutical products should be suitably designed and constructed to facilitate good sanitation.
Adequate employee’s washing and well ventilated toilet facilities should be provided and easily accessible to manufacturing areas.
Suitable facilities should be provided in appropriate locations, for storage of employee clothing and personal property.
The preparation, storage and consumption of food and beverages should be restricted only to specific areas, such as lunch room. These facilities should meet sanitary standards.
Waste material should not be allowed to accumulate. It should be collected in suitable receptacles for removal to collection points outside the buildings and disposed of safely and in a sanitary manner at regular and frequent intervals.
Rodenticides, insecticides, fumigating agents and sanitizing materials should not be permitted to contaminate equipment, starting materials, packaging materials, in-process materials or finished products.
There should be written procedures for use of suitable rodenticides, insecticides, fungicides, fumigating agents, and cleaning and sanitizing agents. Such written procedures should be designed to prevent the contamination of equipment, components, pharmaceutical product containers, closures, packaging, labelling materials, or finished products and should be followed. Rodenticides, insecticides, and fungicides should not be used unless registered and used in accordance with the relevant regulation.
There should be written procedures assigning responsibility for sanitation and describing in sufficient detail the cleaning schedules, methods, equipment, and materials to be used in cleaning the buildings and facilities; such written procedures should be followed.
Sanitation procedures should apply to work performed by contractors or temporary employees as well as work performed by full-time employees during the ordinary course of operations.
Any unhygienic practice within the manufacturing areas or in any other area where the product might be adversely affected, should be forbidden.
Special requirements for sterile products are covered in Annex 1.
EQUIPMENT CLEANING AND SANITATION
Equipment should be cleaned both inside and outside after use according to established procedure and should be kept or stored in a clean condition and be checked for cleanliness prior to each use to ensure that all products or materials from the previous batch are removed.
Vacuum or wet cleaning methods are to be preferred. Compressed air and brushes should be used with care and avoided if possible, as they increase the risk of product contamination.
Cleaning and storing of mobile equipment and storing of cleaning materials should be done in rooms separated from processing areas.
Written procedures in sufficient detail should be established, validated and followed for cleaning and sanitizing equipment and containers used in the manufacture of pharmaceutical products. These procedures should be designed to prevent equipment contamination by cleaning or sanitizing agents and should at least include responsibility for cleaning, cleaning schedule, method, equipment and materials used in cleaning operations, the method of disassembling and reassembling equipment as appropriate to assure proper cleaning and where necessary sterilization, removal of previous batch identification, protection of clean equipment from contamination prior to use.
Record of cleaning, sanitizing, sterilization and inspection prior to use should be kept properly.
Disinfectants and detergents should be monitored for microbiological contamination; dilutions should be kept in previously cleaned containers and should only be stored for defined periods unless sterilized.
VALIDATION OF CLEANING AND SANITATION PROCEDURES
In all instances, the cleaning, sanitation and hygiene procedures should be validated and periodically assessed to ensure that the effectiveness of the procedures meet the requirements.