01

URS (User requirements Standard)

URS (user requirements standard) refers to the user's requirements for the use of equipment, workshops, hardware facilities and systems, and is the basic basis for the selection and design of equipment. Therefore, it is necessary to give a detailed description of production capacity, production process, operation requirements, cleaning requirements, reliability requirements, pollution prevention requirements, error prevention requirements, regulatory requirements, data integrity requirements, etc.
02

Equipment verification and acceptance

Equipment verification and acceptance includes factory testing, field testing, four-way verification (design verification DQ, installation verification IQ, operation verification OQ, performance verification PQ) and verification status maintenance of pharmaceutical equipment to ensure that pharmaceutical production equipment can meet the requirements of drug production. Verification is documentation that the system to be verified meets the expected standards and operational consistency, including all operations that affect quality.
The equipment management department should do a good job in acceptance and verification management. First of all, it should clarify the requirements of regulations on verification, and clarify which GMP documents are mandated by regulations; Secondly, clarify the correlation and difference between non-GMP documents and validation. URS, trial operation documents (FAT, SAT) and so on play an important role in supporting equipment confirmation and verification.

Design verification DQ is to confirm the compliance of design with GMP and use in the design phase, generally for custom systems; DQ should include user requirements criteria, design criteria, supplier evaluation, etc.

Installation verification IQ is the evaluation of the overall installation status and the inspection of calibration, maintenance, certification and data in accordance with GMP requirements.

Operational validation OQ is dynamic validation that the device can consistently and continuously meet the functional standards required by the user. Performance verification PQS are documented to be able to continuously and consistently meet pre-set standards during production under their set parameters.

Validation state maintenance is essential for equipment, processes or systems to always be in a "validated" and "controlled" state and is also required by GMP. Maintenance of validation status includes change control, retrospective validation, and revalidation. The equipment management department shall not only conduct retrospective verification of the pharmaceutical production equipment regularly, but also reorganize and verify the equipment after updating, re-using, major maintenance or technical transformation. In the process of verification, the rationality and perfection of verification scheme and content should be strengthened to enhance the accuracy of verification.

03

Device status flag management

The production equipment shall have perfect and obvious status signs indicating the performance state, running state, cleaning state and technological state of the equipment.
Precautions are as follows:

(1) All the equipment used should have a unified number, and the number should be marked on the main body of the equipment, each equipment should be designated to manage, responsibility to the person.

(2) Each equipment should be hung status signs, such as green indicates that the equipment is intact.

(3) All kinds of pipeline in addition to according to the provisions of the color, should indicate the medium and flow direction arrow.

(4) Sterile equipment should be marked with sterilization time and use date, beyond the use period, should be re-sterilized before use.

(5) When the state of the equipment changes, it is necessary to change the card in time to prevent the use of errors.

Equipment use and maintenance management

The use and maintenance management of equipment includes the use, cleaning, inspection, maintenance and repair of equipment, which ensures the correct operation and operation of equipment, reasonable technical maintenance, giving full play to the technical performance of equipment, prolonging the service life of equipment, and ensuring the best economic benefits of equipment.

01

Equipment operation and use

Operation management of equipment refers to maintenance, overhaul or correction of equipment during use, monitoring of operation status and management of related records.

It is mainly divided into:

Daily management: In order to prevent the contamination and confusion of drugs and ensure the normal operation of production equipment, users of production equipment must be engaged in the general cleaning and maintenance of equipment.

Monitoring and management of device running status: When the device runs normally, its running parameters must be within a certain range. If the parameters deviate from the normal range, product quality may be affected.

02

Equipment cleaning

The specific contents of the cleaning procedure include:

• Division of labor and responsibilities for equipment cleaning

• Cleaning methods and procedures

• Cleaning cycle: If the same equipment is required to continuously process the same sterile product, each batch should be cleaned and sterilized; Complete cleaning should be performed at least weekly or after three batches of production as if the same equipment were processing the same non-sterilized product.

• Name, composition, concentration and preparation method of the cleanser used

• Cleaning verification methods for critical equipment

• Data related to the cleaning process and post-cleaning inspection shall be recorded and filed

• The cleaning of sterile equipment, especially the parts and components that come into direct contact with the drug product, must be sterilized, dated and verified by microbiology if necessary.

03

Equipment maintenance management

Equipment maintenance management includes routine maintenance, periodic maintenance, and prior maintenance.

(1) Daily maintenance of equipment: Equipment and production management personnel shall require operation personnel to carry out inspection according to equipment maintenance SOP.

Main contents of maintenance procedures:

• Implement the charter flight responsibility system according to the position, so that each equipment, instrument, etc., is maintained by special personnel.

• Before starting the device, ensure that fastening bolts are complete and secure and safety devices are complete.

• When the device is running, observe it carefully and record it. If any exception is found, handle it in time.

• After the equipment is shut down, do a good job of cleaning, cleaning and other work.

• Frequent inspection, careful maintenance, frequent inspection, timely troubleshooting, maintain the integrity of the equipment.

• Strictly implement the operating indicators. Overtemperature, overpressure, overspeed and overload operation are strictly prohibited.

• Do a good job of anti-corrosion, anti-freezing, heat preservation (cold) and plugging of equipment.

• Keep the environment and equipment in good hygienic condition.

• Equipment lubrication strictly follow the "equipment lubrication management regulations", especially regular cleaning lubrication system and tools.

(2) Regular maintenance of equipment: the equipment management department shall issue the execution in the form of plan, and the operation and maintenance personnel shall carry out regular maintenance according to the equipment maintenance SOP. For major and medium equipment repair plans, the equipment management department shall consult with the production planning department, formulate reasonable and perfect annual major and medium equipment repair plans at the beginning of each year according to the equipment operation records and equipment conditions, and make equipment spare parts purchase and processing in advance according to the maintenance plan, so as to ensure the smooth implementation of the major and medium equipment repair plans.

(3) Equipment maintenance in advance: it means to monitor the condition of each part of the equipment through certain technical means, discover the occurrence trend of equipment failure in advance, and take measures to eliminate hidden trouble when equipment failure has not occurred. At present, equipment maintenance in domestic pharmaceutical enterprises is mainly post-maintenance, that is, maintenance is carried out after equipment failure. The cost is either interruption of drug production or rework or scrap of drugs, which seriously affects the quality of drugs. In order to meet the requirements of GMP and the development of science and technology, it has become a general trend to replace post-maintenance with pre-maintenance gradually. To determine maintenance management objectives in actual equipment management, the status monitoring of key equipment, key positions and linked production lines in the drug production process can be selected first, and the maintenance can be carried out in advance, and gradually extended to all equipment.

At present, the traditional equipment maintenance management mode of pharmaceutical enterprises has been obviously unable to adapt to today's development requirements and competition mechanism, we should effectively use the information technology, gradually establish the equipment preventive maintenance system.

Equipment lubrication management and fault management

1. Equipment lubrication management is an important part of equipment management as well as production management. In the daily management, the equipment lubrication SOP should be strictly implemented to achieve "five fixed points" (fixed point, fixed quality, quantitative, fixed personnel, timing) and "three-stage filtration". For the selection of lubricating oil and grease, equipment and production management personnel should reasonably select lubricants that meet the standards according to the provisions of equipment technical documents and lubrication parts.

2. Device faults can be divided into design faults and operation faults.

Design fault is restricted by the level, manufacturing quality and technical level of the equipment manufacturer. It is the fault caused by the inherent defects of the equipment caused by the improper design, material selection, manufacturing and assembly of the equipment, and it is the fault brought by the early management of the equipment. Operation faults are caused by equipment installation and commissioning, operation operation, daily maintenance, repair and overhaul, natural wear and other factors, and are the faults brought by the operation and management of equipment.

Equipment management personnel should classify the fault: for example, according to the fault location, cause, alarm display mode, nature, actuator, interference, etc. According to the above classification to judge the cause of failure, and then determine the maintenance personnel, improve maintenance efficiency and reduce the economic loss of enterprises.