How to review the design drawings of the clean room in the pharmaceutical industry?

2019-04-24 13:41:06   Editor: Yan Hong shares    0

In order to meet the process specifications, quality and safety, and cost-effective and practical construction of the biological clean room - the construction party must do the process audit, design drawing review, installation quality supervision, phased verification, etc. when constructing the clean area. Clean room construction is a complex and multi-professional cooperation project involving nearly ten majors in technology, construction, water supply and drainage, HVAC, electric power, self-control, etc., and construction and installation work has special requirements.

In order to prevent technical and quality problems in the project, the design drawings must be carefully reviewed by relevant professionals. The audit work should be comprehensive and rigorous (the principle and structure of each technology are not introduced here), so that the ideal operation effect can be achieved after the completion of the project, which has a multiplier effect. If the review of the drawings is not strict, it will inevitably result in unsatisfactory operation after the completion of the project. For example, the humidity of the common clean area is unqualified; the pressure difference and the airflow manifold are adjusted after repeated adjustments; the self-cleaning time is extended, and the construction is also under construction. In the process, the amount of change is increased, causing the project cost to exceed the budget, and some projects have a 30% or more increase in budget. It can be seen that the review of design drawings is not only a matter of project quality, but also has a huge impact on construction costs. The following is a brief description of the main points of discussion in the process of reviewing the experience in my work practice.

Process compliance

The process layout must be judged in detail with the process technology, production, quality and other departments. The engineering department mainly analyzes the layout of functions, equipment parameters and performance, including the flow of people, the setting of dressing rooms, the logistics direction and the scale between functions. The number of personnel and facilities should be noted in the locker room. The process, production and quality departments should focus on crushing, sieving, granulating, mixing, tableting, filling, insourcing, outsourcing or preparation, fermentation, filtration and purification, sterilization, filling, sealing, according to the product process and production capacity. The smoothness of the process of rolling and inner packaging, eliminating the return of the process route and reducing cross-contamination. If you need an explosion-proof function, pay attention to whether the setting of the venting surface is compliant. The total area and length and width dimensions of each function should be clarified, and the height of the room should be determined according to the height and operation of the equipment. Determining the length and width of the room is a prerequisite for the reasonable arrangement of the delivery, return, and exhaust vents. The main function is preferably rectangular. Determine the differential pressure data between the functions and pay attention to whether the opening of the function door meets the requirements of the control differential pressure. Determine the number of air changes between functions, and discuss the return air, fresh air ratio, and dust collection and trapping method (whether or not the weighing cover is used) and the exhaust ratio.

The more detailed the discussion of the drawings at this stage, the more the parameter setting of the clean air conditioning unit and the determination of the duct direction will be more helpful, and will be more in line with the actual needs of the process.

Enclosure structure

Discuss whether the color steel plate is a mechanism plate or a manual; the core material is rock wool, glass magnesium hollow or aluminum honeycomb; the thickness of the steel plate and the color of the top coat; the door and window (is the hollow glass window or the ordinary purification window); the lamp (the embedded LED plate or Ordinary purification lamp); material requirements for floor (epoxy, PVC, colored sand, etc.).

Purifying air conditioning unit

First of all, we will discuss setting up several clean air conditioning units, either centralized or decentralized. It is recommended that the air volume of the centralized air conditioning system be no more than 40 000 m3/h. The wind volume has caused difficulties in adjusting the system pressure difference. It is better to use a decentralized purification air conditioning system in the new sterile preparation workshop. Note that the unit setting of the decentralized air volume system is generally on the upper level of the clean room (that is, one floor is required), which will increase part of the building area and be considered in advance in the building structure. Non-clean areas are mainly fan coils or multiple connections, and it is not necessary to install air conditioning units.

Figure 1 Common functional combinations of air purification treatment units

The clean air conditioning unit usually consists of a fresh air section, a new return air mixing section, a primary effect filtration section, a table cold water retaining section, a runner dehumidification section, an intermediate flow section, a secondary return section, a humidification section, a wet membrane section, and a heating section. The composition of the sterilization section, the outlet section, and the like (see Figure 1) are selected according to the conditions of the dosage form, the amount of exhaust air, and the local meteorological temperature and humidity. According to Article 42 of the GMP2010 version, “The factory shall have appropriate temperature and humidity”, Article 48 “The pressure difference between the clean area and the non-clean area and between different levels of clean areas shall be greater than 10 Pa. If necessary, the same clean area level The pressure gradient of the functional zone should also be maintained between different functional areas. The temperature and humidity of each function and special room must be clearly defined according to the process specification.

Because the temperature, wind speed, particles and colonies in the current purification project can basically meet the requirements, the humidity and pressure difference and the airflow streamline are difficult to reach the standard. This should focus on the treatment method of the supply air humidity, whether it is the use of a surface cooler or a direct expansion machine or a rotary dehumidifier, the parameters of the air cooler (area, number of rows, location), the slope of the water retaining plate , the water seal height of the drain pipe and the parameters of the fan (air volume, head, speed). If the direct expansion machine is selected, it is necessary to consider whether the length of the refrigeration pipeline is reasonable; if the rotary dehumidification unit is selected, it should be considered whether it is used in the fresh air section or in the mixing section. According to the humidity requirements of the workshop and the state of the first and second return air, it is discussed whether the fresh air is concentrated. Dehumidification. To discuss the advantages and disadvantages of various dehumidification methods in this project. The amount of dehumidification should be discussed in detail. What is the dehumidification amount of the design (when the relative humidity of fresh air is 95%)? Can the unit be completed? Refer to the same industry's unit parameters, leaving enough margin. If you do not understand the dampness map, please ask the professional to calculate. The humidity in the clean area of the pharmaceutical factory is generally controlled at 45-65% HR. The reasonable chilled water system can meet the requirements of dehumidification. When the local room requirements are below 35% HR, the wheel dehumidification is required. Dehumidification is a complicated process. It is necessary to combine theory with practice to achieve good results. Never copy other people's drawings.

What is the way to humidify (steam, pure steam, electrodes, ultrasonic spray, etc.)? Note that steam humidification will increase the room temperature and make a choice depending on the dosage form. On this basis, it is necessary to make necessary selections for functions such as disinfection (dry and wet ultraviolet).

After the above conditions are determined, the functional sections required for the air conditioning unit are determined and sized. Steam pipe valves (including steam traps) and automatic control systems must be determined to use high-quality products, domestic products often fail and have a short life, and the quality of imported products is relatively reliable. It is necessary to review whether each professional design drawing has a description of the installation node map, the construction method and the selection of the atlas. For example, the installation structure diagram of the B-class area FFU, the maintenance structure installation node map, and the like.

Calculate the size of the air conditioning box, calculate the size and quantity of the air conditioning box, and calculate the chilled water temperature and the configuration parameters of the chiller after calculating the total cooling and heat load. Water-cooled, air-cooled, and lithium bromide units have their own advantages and disadvantages, and are considered comprehensively based on the load conditions, the floor space of the workshop, and the favorable conditions of power allocation, water source, heat source, and gas.

Figure 2 Analysis of the settings of the send, return and exhaust vents

Primary, medium and high efficiency filter selection

Determine the initial resistance value of the initial and intermediate effects, and determine the type and initial resistance value of the high-efficiency filter (the H13-14 grade liquid tank without separator high-efficiency filter is currently used) to determine the wind speed of the high-efficiency filter tuyere.

Delivery, return, exhaust system

The settings of the sending, returning and exhausting ports should be analyzed in detail, because the differential pressure adjustment of many projects is very difficult. The reason is that the direction of the air duct, the position of the variable diameter and the position of the tuyere have not been carefully designed (see Figure 2), resulting in cleanliness. The airflow lines in the room are incorrect and the pressure difference is not up to standard, so it needs to be adjusted frequently. The auditing process is to perform system-by-system auditing along the main air duct to each function, such as pipe diameter, variable diameter position, tuyere size, and tuyere position. Is it CAV (constant air volume) or VAV (variable air volume) air supply? Is the CAV supply air set with a residual pressure valve? For some rooms with strict pressure difference requirements, the VAV variable air volume venturi damper group can be used for air supply. The return air line should pay special attention to whether the return air outlet is on the long side of the room. The wind speed at the return air outlet should not be too large, as far as possible in the diagonal or opposite side of the clean room. At the same time, avoid placing it in areas with high cleanliness requirements or equipment. It is strictly forbidden to share the return air duct in the clean room with different pressure difference (the current design is basically independent return air duct). The exhaust duct is mainly to check whether the exhaust vent is as close as possible to the pollution source, and whether it is divided into two layers. The exhaust ventilator is currently equipped with a medium efficiency filter and does not require a check valve.

It is worth noting that the return air outlet or part of the air outlet is open on the wall panel, and the rigidity of the wall panel is weakened, so the opening should be strengthened. Want to discuss whether the duct is connected by angle iron flange or common board flange? This is related to the duct leakage rate.

Power and automatic control

Calculate the load of the power system, it is not too redundant, and the power socket setting does not need too much. Whether the setting parameters and quantity of the local or remote control instrument meet the process control requirements, whether DDC or PLC system is used. To discuss the design of the automatic control system, focus on equipment models, specifications and brands.

Water supply and drainage pipeline setting

It should be noted that the pipes with hot water discharge should be made of cast iron or stainless steel. The drain pipes with gas generated should be installed with floor drains with exhaust structure. The floor drain of explosion-proof workshops should be selected for explosion-proof type. These are easy to neglect. The setting of the fire-fighting facilities, the function of the clean area of the solid preparation can still be arranged with spray facilities, and the sterile preparation and the negative pressure workshop are absolutely not allowed. If the plant area exceeds the fire protection design regulations, communicate with the design unit and the local fire department.

After the above work, we will discuss the level of project cost, and we cannot pursue high quality and non-transitional design blindly. We must adhere to the principle of "reasonable, safe, and economical"