Calibration Specification for Drug Stability Test Chamber

1 scope

This specification applies to the temperature range（0～65） ℃, relative humidity rangeSurrounding（10～95）% Range of illumination（0~7000）lxRange of ultraviolet radiation illuminance（0～300）μW/cm2 The drug stability test box (hereinafter referred to asTest box) Calibration.

2 Reference document

This specification references the following documents:

JJG 245 Illuminance meter

JJG 879 UV radiometer

JJF 1032 Terminology and definitions of optical radiation measurement

JJF 1101 Calibration Specification for Temperature and Humidity Parameters of Environmental Testing Equipment

GB/T 5170.1Environmental testing for electrical and electronic productsEquipment inspection method 第 1 Part: General Provisions

GB/T 5700Lighting measurement method

GB/T 10586 Technical conditions for wet heat test chamber

Pharmacopoeia of the People's Republic of China（2025 Version 4)9001 Guiding principles for stability testing of raw materials and formulations

For all referenced documents with dates, only the version with dates is applicable to this specification; Any reference document without a date, The latest version (including all modification orders) is applicable to this specification.

3 Terminology and measurement units

3.1 term

3.1.1 Workplaceworking space

The test chamber can maintain the specified test conditions at the specified deviationThe part of space within the difference range.

[Source:GB/T 5170.1—2016 ，3.2.2]

3.1.2 Stable state stable state

The temperature, relative humidity, illuminance, and ultraviolet radiation illuminance at any point in the workspace reach the set values and are maintained at The state within the given tolerance range.

[Source:GB/T 10586—2006 ，3.4and3.14 There are modifications]

3.1.3 Temperature deviationtemperature deviation

Under the stable state of the test chamber, the temperature of each measuring point in the workspace is measured within the specified timeThe deviation between the temperature and the set temperature.

[Source:GB/T 5170.1—2016 ，3.2.4]

3.1.4 Temperature uniformitytemperature uniformity

In a stable state of the test chamber, the workspace is at a certain momentThe maximum difference in temperature between any two points. [Source:GB/T 5170.1—2016 ，3.2.8]

3.1.5 Temperature fluctuationtemperature fluctuation

In a stable state of the test chamber, the temperature at any point in the workspace varies with time within a specified time intervalThe amount of change.

[Source:GB/T 5170.1—2016 ，3.2.6]

3.1.6 Relative humidity deviationrelative humidity deviation

Under the stable state of the test chamber, each measuring point in the workspace is measured within the specified timeThe deviation between the relative humidity and the set relative humidity.

[Source:GB/T 5170.1—2016 ，3.2.5]

3.1.7 Relative humidity fluctuationrelative humidity fluctuation

In a stable state of the test chamber, the relative humidity at any point in the workspace varies with the specified time intervalThe amount of change in time.

[Source:GB/T 5170.1—2016 ，3.2.7]

3.1.8 Illuminationilluminance

The luminous flux incident on a surface element containing a point on the surfaced∅Divide by the area of the surface elementdAThe merchant. [Source:GB/T 5700—2023 ，3. 1]

3.1.9 Illuminance deviationilluminance deviation

In a stable state of the test chamber, the set values and measured average illuminance of each measuring point in the workspace are within the specified timeThe difference in value.

3.1.10 Uniformity of Illuminationuniformity ratio of illuminance

Specify the ratio of minimum illuminance to average illuminance on the surface.

[Source:GB/T 5700—2023 ，3.9]

3.1.11 Ultraviolet radiation illuminanceultraviolet irradiance

The ultraviolet radiation illuminance at a point on the surface is the ultraviolet radiation flux incident on the panel containing that pointd∅e Divide by the area of the paneldAThe merchant.

[Source:JJF 1032—2005 ，2.13 There are modifications]

3.1.12 Exposure to radiationradiant exposure

Exposure to radiation refers to the amount of radiation emitted over a specified time periodΔtInternally, the ultraviolet radiation illuminance at the designated pointEe Integrating time yieldsExposure to radiation levels.

[Source:JJF 1032—2005 ，2.15 There are modifications]

3.2 Measurement Unit

Temperature: Unit name is Celsius, symbol is℃;

Relative humidity: unit symbol is%；

Illumination: Unit name is lux, symbol islx；

UV radiation illuminance: unit name is watts per square meter or microwatts per square meterSquare centimeters, symbolized byW/m2orμW/cm2；

Radiation exposure: Unit name is watt second per square meter or watt hour per square meter, symbol isW·s /m2 or W·h/m2；

Time: Unit name is seconds, symbol iss.

4 Overview

The test chamber operates under simulated environmental conditions, with precise control of temperature, humidity, lighting, etc. through a control system Parameters, simulating various environmental conditions that drugs may encounter during actual use, in order to evaluate the stability and quality The test chamber mainly consists of a heating system, a cooling system, a humidification system, a dehumidification system, a visible light illumination system, and ultraviolet radiation Composed of lighting system and other components, the workflow is shown in the diagram 1 As shown. The test chamber is used in the pharmaceutical, medical, and biotechnology industries To investigate the drug stability of active pharmaceutical ingredients or drug formulations under the influence of temperature, humidity, illumination, and ultraviolet radiation illumination The law of time variation.

5 Measurement characteristics

The technical requirements for the test chamber are shown in the table 1.

table 1 Technical requirements for test chamber

6 Calibration conditions

6.1 Environmental conditions

Ambient temperature15 ℃~35 ℃ ;

Relative humidity: not greater than 85 %.

6.2 Load conditions

Calibration is generally carried out under no-load conditions, but it can also be performed under load conditions according to customer needs, but the load situation should be explained, The load situation should comply with GB/T 10586 Chinese 4.4 ofrequirement

6.3 Steady state operation time

The operating time of the test chamber in a stable state before calibration should not be less than2 h.

6.4 Measurement standards and other equipment

Technical requirements are shown in the table2.

table 2 Measurement standards and technical requirements for other equipment

7 Calibration Items and Methods

7.1 Calibration Items

Temperature deviation, temperature uniformity, temperature fluctuation, relative humidity deviation, relative humidity fluctuation, illumination deviation Uniformity of illumination and radiation exposure.

7.2 Calibration Method

7.2.1 Preparation before calibration

The device can be turned on normally, the button functions are normal, the screen display is clear, and there should be no defects that affect the reading.

7.2.1.1 Selection of Calibration Points

Select the commonly used temperature, humidity, illuminance, and ultraviolet radiation illuminance for the calibration point, or choose the equipment usage range Limit, upper limit, and midpoint.

7.2.1.2 Selection of shelves

Select the shelf near the geometric center in the test box as the measurement plane. When the number of shelves in the test box is odd, Select the middle shelf layer; When the number of shelves in the test box is even, selectChoose from top to bottomThe shelf of [(even/2)+1] layer Board layer.

7.2.1.3 Layout of temperature and humidity measurement points

Arrange them separately on the shelves of the test box 5 A temperature measurement point and 1 aHumidity measurement point. If there are multiple workspaces, Then each workspace should be arranged according to this requirement. Except for the center point, the distance between the positions of all other points and the inner wall of the equipment is on each side long 1/10 When encountering an air duct, this distance can be increased, but should not exceed 500mm The placement position of sensor measurement points is also It can be arranged according to the actual work needs of users.

7.2.2 Calibration method for temperature deviation

according to 7.2.1.3 According to the regulations, place a temperature standard, set the test chamber to the temperature calibration point, and start running. experiment After the box reaches a stable state, readings begin every 2minRecord data once,30min insideTotal Records 16 Group data, also The time interval and data recording frequency can be determined based on the operating status of the equipment or user calibration requirements, and recorded in the original records and calibration Please provide an explanation in the certificate. According to the formula（1）And（2）Calculate the upper and lower temperature deviations.

Δtmax =tmax - ts （1）

Δtmin =tmin - ts （2）

Where:

Δtmax ——Temperature deviation,℃ ;

Δtmin ——Temperature deviation,℃ ;

tmax ——Measure the temperature value within the specified time,℃ ;

tmin——Measure the temperature value within the specified time,℃ ;

ts ——Temperature setting value,℃。

7.2.3 Calibration method for temperature uniformity

The calibration of temperature uniformity and temperature deviation shall be carried out simultaneously, and the process shall be the same as 7.2.2The temperature standard is 30min The arithmetic mean of the temperature difference measured internally is used as the calibration result for temperature uniformity, and is calculated according to the formula （3）Perform calculations.

（3）

Where:

Δtu ——Temperature uniformity,℃ ;

ti max——Each measurement point is located at i Actual measurement in the second measurementtemperature℃ ;

timin——Each measurement point is located at iThe measured temperature in the second measurement,℃ ;

n ——Measurement frequency.

7.2.4 Calibration method for temperature fluctuation

The calibration of temperature fluctuation and temperature deviation is carried out simultaneously, and the process is the same as 7.2.2Record the temperature measurement points Indication, according to the formula（4）Calculate temperature fluctuations.

Δtj =tj max - tj min（4）

Where:

Δtj ——Temperature fluctuation,℃ ;

tj max ——WorkplacejThe measured temperature within the specified time interval,℃ ;

tj min ——WorkplacejThe measured temperature within the specified time interval,℃。

Take the maximum temperature fluctuation of each measurement point as the calibration result of the temperature fluctuation of the test chamber.

7.2.5 Calibration method for relative humidity deviation

according to 7.2.1.3Specify the placement of humidity standards and set the test chamber to the relative humidity calibrationOn time, start running. try After the box inspection reaches a stable state, begin reading every 2minRecord data once,30min Internal Records 16 Group data, The time interval and data recording frequency can also be determined based on the operating status of the equipment or user calibration requirements, and recorded in the original records Provide instructions in the calibration certificate. According to the formula（5）And（6）Calculate relative humidityThe upper and lower deviations of the degree.

Δhmax =hmax - hs （5）

Δhmin =hmin - hs （6）

Where:

Δhmax——Deviation in relative humidity,%；

Δhmin ——Deviation under relative humidity,%；

hmax ——measurement point OThe measured relative humidity within the specified time,%；

hmin ——measurement point ORelative humidity measured within the specified timeDegree,%；

hs ——Relative humidity setting value,%.

7.2.6 Calibration method for relative humidity fluctuation

The calibration of relative humidity fluctuation and the calibration of relative humidity deviation are carried out simultaneouslyCheng Tong 7.2.5Record humidity measurement Measure the point indication according to the formula（7）Calculate the fluctuation of relative humidity.

Δho =ho max - ho min （7）

Where:

Δho——Relative humidity fluctuation,%；

ho max ——Workplace O The measured relative humidity within the specified time interval,%；

ho min——Workplace O The measured relative humidity within the specified time interval,%.

7.2.7 Calibration method for illuminance deviation

Set the test chamber to illuminance calibration in an unloaded stateOn time, preheat30minAccording to 7.2.1.4regulation Layout illuminance standard; Start after the illumination of the test chamber reaches a stable stateReadings, every 2minRecord all schools once Accurate measurement values, measured at each calibration point3 Next time, take 3 The average value of the second measurement is taken as the measurement for that pointValue. If there are many If there is a workspace, repeat the above steps and close the test during the entire calibration processInspection door. According to the formula（8） Calculate the illuminance deviation.

ΔEi =Ei - Es（8）

Where:

ΔEi ——The illuminance deviation of each measurement point,lx；

Ei ——第 iA illuminance standard3 The second measurementThe average value,lx；

Es ——Illuminance setting value,lx.

7.2.8 Calibration method for illuminance uniformity

The calibration of illuminance uniformity and illuminance deviation are carried out simultaneously, and the process is the same as 7.2.7 The illuminance standard was measured to be the most accurate The ratio of the arithmetic mean of the minimum value and the measured illuminance is used as the illuminance uniformityThe calibration result of the degree, and according to the formula（9）Carry out Calculate.

（9）

Where:

Ui ——The uniformity of illumination at each measurement point,%；

Eimin ——The minimum measured illuminance at each measurement point,lx；

Ei ——The average illuminance measured at each measurement point,lx.

7.2.9 Calibration method for radiation exposure

Set the test chamber to the UV radiation calibration point and preheat it in an unloaded state 30min According to 7.2.1.4Specify the placement of ultraviolet radiation illuminance standards, and start reading after the illuminance in the test chamber reaches a stable state. Every 2min Record once, measure at each calibration point 3 Next, calculate the average value and take the minimum value from the average values of each measurement point As the ultraviolet radiation illuminance of the test chamber. If there are multiple workersTo create space, repeat the above steps throughout the entire calibration process The door of the test chamber needs to be closed. According to the formula（10）CalculateUltraviolet radiation illuminance.

In the strong light irradiation test of drug influencing factors, it is required to accumulate 240 The hourly radiation doseTo determine the radiation exposure level Fruit, according to the formula（11）Calculate the radiation exposure.

（10）

H=Eu × 240 （11）

Where:

Ei ——第iA UV radiation standard3The average value of the secondary measurements, μW/cm2 .

Eu ——UV radiation illuminance, μW/cm2 ；

H ——Exposure to radiation,W. h / m2 .

8. Expression of Calibration Results

A calibration certificate shall be issued for the drug stability test chamber after calibration. The calibration results should be reflected on the calibration certificate The certificate should include at least the following information:

a)Title:Calibration certificate ”；

b)Laboratory name and address;

c)The location for calibration (if different from the laboratory address)）；

d)Certificate identification (such as number)），Identification of each page and total number of pages;

e)The customer's name and address;

f)Description and clear identification of the subject being studied;

g)The date of calibration, if any, should be consistent with the validity of the calibration resultsWhen using relevant information, it should be stated that the object being studied is Date of receipt;

h)If it is related to the validity of the calibration results, the sampling procedure for the calibrated sample should be carried outExplanation:;

i)Identification of the technical specifications on which calibration is based, including name and code;

j)Explanation of the traceability and effectiveness of the measurement standards used in this calibration;

k)Description of calibration environment;

l)Explanation of calibration results and measurement uncertainty;

m)Explanation of deviations from calibration standards;

n)Signature, position, etc. of the issuer of the calibration certificate or calibration reportEffective identification;

o)A statement that the calibration result is only valid for the object being calibrated;

p)Without written approval from the laboratory, partial reproduction of the certificate is not allowedMing.

9. Interval between resumption of classes

Suggest that the interval between resuming classes should not exceed 1 Year. Due to the resumption of schoolThe length of the time interval is determined by the usage of the equipment Due to various factors such as the user and the quality of the equipment itself, the sending unit may independently decide to resume the school based on the actual usage situation Time interval.