Reference for the management procedures of pharmaceutical sterile workshops

1. Purpose

This regulation is specially formulated to ensure the quality of drugs and strengthen the operation management of clean rooms and purification Air conditioning systems.

(Figure 1: Pharmaceutical sterile room)

2. Scope

Sterile workshops.

3. Responsibilities

Quality Assurance Department, Production Technology Department, Engineering Equipment Department Director, Workshop Director.

4. Contents

1. Management of production personnel and clean work clothes in clean rooms

1.1 Operators in different clean level operation areas are not allowed to walk around at will. If necessary, they must change the work clothes of the corresponding work area according to the purification procedure of the clean area they enter before entering.

1.2 Clean clothes are required not to drop fibers, nor to cause fiber shedding or broken threads due to wearing, not to generate static electricity, not to attach particles, to have good filtering properties, to ensure that dust particles generated by the human body and underwear cannot penetrate, to be corrosion-resistant, to be durable to washing, disinfection and sterilization, and to have no wear and tear. Clean clothes have simple lines, no pockets, no exposed fibers at the seams, and elastic cuffs and trouser legs.

(Figure 2: Clean work clothes)

2. Management of equipment and material containers for production operations in clean rooms 

Strictly control unnecessary equipment, materials, containers, etc. from entering the clean room. The materials, containers and equipment that must be used should be kept to a minimum, and the equipment used should be as dust-free or dust-free as possible. The materials of the utensils used should preferably be made of stainless steel or other materials that generate less dust. It is best to use a pen for notes and records, and do not use chalk, notice boards, or memo boards.

3. Operation management of purification air conditioning system

3.1 Before the purification air conditioning system is activated for production, the time for early startup should be determined based on the system's own self-purification time and the time when the temperature and humidity reach constant temperature and humidity.

3.2 Adjust the Air volume according to the workshop pressure difference, and adjust the heating, humidification or cooling according to the workshop temperature and humidity. Keep the workshop pressure difference, temperature and humidity within the specified range, and regularly check and observe the condensed water volume and temperature.

(Figure 3: Clean room purification air conditioning system)

4. monitoring of clean rooms

In order to ensure the cleanliness of the clean room, the clean room must be monitored regularly:

4.1 Positive pressure measurement of clean room

The positive pressure in the clean room should be monitored regularly. The monitoring frequency is: 300,000-level clean rooms are measured once a month. Positive pressure control in the clean room means that the static pressure difference between the dust-generating clean room and the adjacent clean room, and the static pressure difference between the clean area and the outside is greater than 10Pa.

4.2 Determination of Wind speed and wind volume in the clean room

The frequency of measurement of wind speed and wind volume in the clean room is once every three months. The difference between the test air volume and the design air volume of the air inlet with a clean level of 300,000 should be within +15% of the design air volume.

4.3 Determination of temperature and humidity in the clean room

The determination of temperature and humidity in the clean room refers to the determination of indoor air temperature and relative humidity. The temperature is required to be controlled at 18-26℃ and the relative humidity is controlled between 45-65%. Before the measurement, the purification air conditioning system must have been running continuously for at least 24 hours. For places with constant temperature requirements, the measurement should be carried out continuously for 8-48 hours, with an interval of no more than 30 minutes each time.

(Figure 4: Clean room monitoring)

4.4 Cleanroom cleanliness monitoring

4.4.1 Determination of dust particles

In order to determine the air cleanliness level achieved by the cleanroom environment, it is necessary to measure it. The measuring instrument uses a dust particle counter, and the measurement frequency is generally once a quarter.

4.4.2 Determination of sedimentation bacteria

In order to determine the concentration of floating biological particles in the cleanroom air and the sedimentation density of biological particles, the cleanroom needs to be measured for sedimentation bacteria, and the measurement frequency is once a month.

5. The ceiling of the cleanroom (area) and the connection between the pipes, vents, lamps and walls or ceilings entering the room are regularly inspected. 

In order to ensure that the sterile workshop meets the GMP requirements, combined with the actual situation of the company, the production workshop is inspected irregularly once a week, and the production workshop is inspected once before production. The inspector shall implement rectification for unqualified parts.