First, the basic requirements of the "hardware" facilities 1. Production plant: There should be enough space and site-placement equipment and materials in the plant, and be rationally laid out according to the production process and the required cleanliness level. The production operations carried out in the same factory building and in adjacent plants must not interfere with each other, and products of different cleanliness levels must not be produced in the same production area. Plants and warehouses should have measures to prevent the entry of insects, birds and rodents. The clean room and clean area of ​​the plant surface should be smooth, no cracks, easy to clean. The boundary between the interior wall, the ceiling, and the ground should be curved. The surface layer should not fall off, and no dust or particulate matter should be emitted or adsorbed. The layout of the plant should be compatible with the product process, and the flow of people and logistics (the direction of the operator and the direction of the semi-finished products) should be reasonable. The pipelines and lighting power lines in the plant shall meet the relevant requirements, and the illumination in the production area shall be in accordance with the technological requirements. The factory building should be reasonably equipped with sanitary passages, safe fire protection passages, fire-fighting facilities and emergency evacuation routes for personnel, and must comply with the relevant provisions of the national public security fire-fighting department. For workshops that produce packaging materials and containers that do not require pharmaceutical cleaning, the cleanliness level must be compatible with the production workshop of the packaged drugs, and must be based on the production process, process, quality, and hygiene requirements of the packaging materials and containers. Specifically define the area and determine the cleanliness level. For example, the type I pharmaceutical packaging material directly in contact with pharmaceuticals and the PTP aluminum foil for pharmaceutical packaging needs a clean grade of 100,000, and its dust category ≥ 0.5 microns should be ≤ 3500000 cubic meters, and ≥ 5 microns should be ≤ 20000 cubic meters. The number of viable microorganisms is less than or equal to 500m3. The number of indoor air changes is ≥15 times/h. To meet this standard requirement, when designing the indoor air flow system, it mainly includes three parts. The first one is to design a suitable air flow pattern; the second is to determine the form of return air outlet. Size and layout; third to calculate the air jet parameters. The following principles are followed in the design: 1 Prevent dust particles from flying twice as much as possible, so as to reduce the chance of dust particle contamination of the production process. 2 Minimize turbulence to avoid introducing dust particles outside the work area into the work area. 3 The work area air speed should meet the air cleanliness and human health requirements, and should make the air flow to a single. The way to send clean air indoors is generally to choose a high-efficiency filter with a diffuser to send air from the indoor ceiling. The return air is a return air outlet arranged on the lower side of the single-sided wall. The windows, ceilings, and the lines, air outlets, lampshades, and wall or ceiling connections to the interior of the cleanroom should be airtight. The clean zone shall have a pressure difference greater than 9.8 Pa for outdoor or outdoor areas, a pressure difference greater than 4.9 Pa between clean areas of different cleanliness, and means for indicating differential pressure. Areas with high cleanliness levels should have relatively positive pressures on adjacent areas of low cleanliness level. The penetration of clean outdoor air is one of the causes of pollution of cleanrooms. In order to prevent the infiltration of ambient air, cleanrooms must maintain a certain positive pressure. . The positive pressure in the clean room is achieved by making the air volume in the room larger than the sum of the return air volume and the exhaust air volume. Excessive positive pressure value is beneficial to prevent the infiltration of clean outdoor air, but at the same time, due to the increase of new outdoor air volume needed, the service life of the high-efficiency filter will be shortened, and the door opening of the room will be difficult. Therefore, the positive pressure value is not appropriate. If it is too large, a positive pressure of 10-20 Pa should be maintained in the general room. In the clean area, the buffer area should be set according to the process requirements. The personnel and materials should be entered through the buffer zone corresponding to their production cleanliness level respectively. Dressing rooms should be easily accessible. In the clean workshop, when there are flammable, explosive, toxic and hazardous, high chemically active materials in the production process, the exhaust gas should be strictly separated from the clean air flow, and no cross-contamination can be caused. All products that have cleanliness requirements for the production environment, except for their production areas controlled by cleanliness levels, their auxiliary stock rooms, inspection rooms, sampling rooms, intermediate products in the production areas, storage spaces for packages, equipment and containers for cleaning The cleanliness level of the room, cleansing clothes washing, and drying room should also be adapted to the production area.
2. Production equipment: The design, selection and installation of the equipment should meet the production requirements, be easy to clean, be easy to operate and maintain, and ensure safety. The surface of the equipment used for products that are in direct contact with the drug should be clean and smooth, easy to clean or sterilize, and resistant to corrosion, and should not cause chemical changes to the product. Lubricants, mold release agents, and cleaning agents used in the equipment must not cause contamination of the product. The automated or program-controlled equipment required for production has been verified and its performance and accuracy should meet the production requirements. The scope of application and accuracy of instruments, meters, gages, scales, etc. used for production and inspection shall comply with the requirements for production and quality inspections, shall have obvious status signs, and shall stipulate the time limit for correction. The equipment shall be regularly repaired, maintained, and verified. The installation, maintenance, and maintenance of the equipment shall not affect the quality of the product. The production and inspection equipment shall establish equipment files, and shall have their own use registration to record the actual use, repair, and maintenance of the equipment. The situation is managed by someone.
3. Hygiene requirements for the production process: All employees of the company should be trained in hygiene, and all personnel entering the production area should strictly abide by the relevant health system. The production enterprise should have a hygienic and clean environment, no pollution sources in the plant and its surroundings, and the air, water quality, and site of the production area should meet the production requirements. Contaminated materials, waste and refuse conversion stations should be located far away from the production area and should be closed for handling and storage. Production workshop job positions should be based on production and clean grade requirements, formulate cleaning procedures for their plants, equipment and containers. No non-production materials can be stored in the production operation area. Smoking, eating, and bringing in daily necessities are strictly prohibited. Dressing rooms, washing facilities, disinfection facilities and toilets must not adversely affect the cleanliness level of the plant and must not store waste in the production area. The selection, style, and wearing style of work clothes should be compatible with the level of cleanliness of production operations and factories. The work clothes of different clean level factories should be strictly distinguished and must not be mixed. Work clothes should be cleaned according to the level of cleanliness requirements, using their own cleaning facilities. Cleanrooms should be regularly sterilized, and disinfectants or sterilants used must not cause pollution to equipment, raw materials, accessories, and finished packaging materials, and must prevent cross-contamination of products. Sources of cross-contamination often come from raw materials in the production process, such as dust gas, vapors, microorganisms, or clothing of workers. The severity of cross-contamination varies depending on the type of pollution source, the most harmful of which are certain microorganisms. The methods for preventing cross-contamination are: 1 Products should be produced or packaged in isolated areas. 2 Avoid producing different products at the same time in an effective isolation area. 3 Clean room equipment should pay attention to cleaning, remove the source of pollution. 5 It should be noted that the recirculation of the untreated air or the discharged gas should no longer intrude into the clean room.
Second, the basic requirements for enterprise management "software" enterprises must have the registration conditions and apply for "medicine packaging materials registration certificate" according to the procedure, after the evidence can produce or operate drug packaging materials. Each product should be formulated with the corresponding production process regulations and post operation methods, and production according to the process specification and post operation method. Each batch of products should have a production record that reflects the actual conditions of each production process. The production records should be filed according to the lot number or production date, and should be kept for one year after the product's valid period. Product records that do not have an expiration date are kept for at least three years. The production and quality management documents shall determine the specification standards, production and inspection methods for all materials, and stipulate the production, quality management standards, production and inspection methods, ensure that all production personnel and production and quality management personnel perform their duties as required, and determine for each authorized personnel. Whether the batch of products can be sold to provide the required materials will provide clues to investigate quality issues. The company shall have departments and personnel in charge of document file management, and shall have complete production management and quality management documents. The contents include the production management department, quality management department, production support department's various management systems, raw materials, accessories and packaging materials. Standards and management systems, production management documents for each product. For example: product formulation, product manufacturing process specification, job operation method, production instruction, quality management documentation for each product, etc., such as raw material packaging quality standards, inspection operating procedures, sampling and retention system, storage period of raw materials and accessories Product validation period, intermediate product management system, unqualified processing and management system. The design, installation, use, maintenance, and maintenance of plant, equipment, and testing instruments, and various health management systems for all departments. Such as: environmental, plant, equipment, personnel health system, drug packaging materials management and professional technical training system, and product production and quality management of various records, such as: material acceptance, inspection, release records, batch production Records, batch packaging records, unqualified product handling records, finished product sales, and user feedback records. There are also the management system for outbound and outbound delivery of finished products, raw materials, and packaging materials, material scrapping systems, and emergency treatment systems. The company shall establish a management system for drafting, revising, reviewing, approving, revoking, printing, and custody of documents. The documents distributed and used shall be the approved current text. Documents that have been revoked and outdated shall not appear on the job site unless they are kept for future reference. So as not to be confused with the current text.
The above describes the most basic production conditions and management requirements that must be possessed by pharmaceutical packaging companies that produce drugs that are in direct contact with them. Due to space constraints, they are not very comprehensive. The manufacturers of pharmaceutical packaging materials that have collected or renewed certificates this year shall strictly follow the regulations and rating standards for drug packaging materials approved by the State Drug Administration, and shall meet the required standards one by one. Due to the three orders and five applications of the State Drug Administration, all drug manufacturers are required to use the drug packaging materials that have been obtained by the enterprises that have obtained the "Paper Pack Material Registration Certificate." From July 1, 2001, enterprises and units that have not obtained the Registration Certificate for Pharmaceutical Packaging Material (or the License for Pharmaceutical Packaging Materials Production Enterprise) must not produce or sell pharmaceutical packaging materials in any form. Pharmaceutical production enterprises may not use drug packaging materials produced by enterprises that have not obtained the "Paper Pack Material Registration Certificate." Violators shall be investigated and handled by drug regulatory authorities at all levels according to regulations. (White Ice) (From "China Packaging News")
This year, the State Drug Administration changed the license system of original pharmaceutical packaging materials to the registration management system for pharmaceutical packaging materials, strengthened the supervision and management of pharmaceutical packaging materials, container manufacturers, and pharmaceutical packaging and use units, and provided corresponding regulations. Penalty clause. In the new system, pharmaceutical packaging materials are divided into three categories: packaging materials directly used for pharmaceuticals and used directly; packaging materials for containers of type I; direct contact with pharmaceuticals, but easy to clean, in the actual use process, after cleaning The packaging materials and containers for disinfecting and sterilizing medicines are Class II drug packaging materials; the Class III drug packaging materials are materials and containers for pharmaceutical packaging that can directly affect the quality of drugs other than Class I and II drugs. This article describes the specific work that should be done in the process of applying for the registration of drug packaging materials according to the requirements for the production quality of Type I drug packaging materials and the specific content of the State Drug Administration's "Quality Management Practice for Drug Packaging Materials Containers." And compliance requirements. The quality management specification for pharmaceutical packaging materials is “GMP†(“GMP†is the English abbreviation for Good Manufacturing Practice, and is called “Manufacturing Quality Management Specification for Pharmaceutical Packaging Materials†in the country) for pharmaceutical packaging companies. This specification requires direct contact with pharmaceuticals. The packaging materials and containers are under tight control during the entire production process, preventing operational errors, mixed contamination, and ensuring product quality. The basic spirit of the specification mainly emphasizes two major aspects. On the one hand, it is the "hardware" facility requirements for pharmaceutical packaging companies, and on the other is the basic requirements for enterprise management "software." If the company meets the above two requirements in a down-to-earth manner, the quality of the medicine packaging materials produced by the company can ensure the quality of the use of medicines, and ultimately achieve the purpose of ensuring the safety of patients' lives.