Who performs the calibration in the pharmaceutical industry?

Calibration is an integral and essential method for every process and manufacturing industry and plays a vital role in maintaining the accuracy of measuring instruments and devices.

For the pharmaceutical industry, it serves many purposes. The main reason for its importance is that measuring devices and instruments play a critical role in implementing GMP and ensuring quality. Calibration is an effective way of assuring the instrument's performance and accuracy.

The instruments can be vulnerable to deviation and errors without an effective calibration plan. It also becomes difficult to detect defective devices in a timely.

What is the calibration?

Calibration compares an instrument's output with a standard reference value whose output has been verified, free from error and deviations. If the difference between the output of calibrating and the reference instrument is within acceptable limits, the Calibration is said to be satisfactory, and the instrument can be used.

On the contrary, if the difference between the output of calibrating and the reference instrument is outside of the acceptable limit, the Calibration fails, and the instrument is not allowed to be used. In this case, this instrument must be rectified or replaced. After rectification or replacement, the instrument must be re-calibrated. Only when Calibration is satisfactory is the instrument allowed to be used.

After Calibration is performed, its documentation must be completed and maintained because regulatory and standardization bodies review the calibration records. The regulatory bodies can issue a warning if the record is not found.

Who performs the calibration?

The body who performs the calibration should be chosen carefully because it is a critical factor in affecting the overall process of calibration, which then affects the performance of instrumentation system. Like other industries, there are two methods to select calibrating body in pharmaceutical industry, and are - in - house and third party

In - house Calibration

In - house calibration is when a pharma company makes itself arrangement for calibration, and do not send instruments outside. For in-house calibration, the pharma company requires two type of arrangements regulatory and technical

For regulatory requirement, it is necessary to demonstrate that it has all the necessary resources such as Equipment, Skill, and Personal expertise. It enables the pharma company to perform calibration according to the regulatory requirement and accepted by relevant regulatory bodies.

For technical requirements, the organization must contain all necessary equipment, dedicated lab and relevant certifications. Additionally, the equipment used to calibrate other instrument and measuring devices must also be calibrated regularly by third party certified lab.

Third party calibration

In third party calibrations, the instrument are send to third party vendors or labs that have expertise and specialize in performing calibration. The third party vendor or lab must be accredited from relevant standardization bodies to demonstrate their competitiveness in performing calibration activities. . These third part are also responsible to provide relevant documentation, for regulatory bodies during their inspection.

The main advantage of hiring third party vendor or lab is that a pharma company is relieved of extensive activity of accreditation and arranging resources such as calibration equipment, lab and more importantly calibrating their master equipment from authorize certified lab.

Importance of calibration

Let's discuss the importance of calibration and see why it is performed

Regulatory requirement

Calibration is the regulatory requirement for almost all market around the world. These regulatory bodies review calibration documentation during their routine inspection and verify the calibration activity. If they find any deviation or discrepancy, they issue warning until it has been performed according to their requirement

An example of regulatory requirement is the United States FDA, 21 CFR part 820, it's sub-part "G", "production and process controls" section 820.70 "instrument measuring and test equipment" define the calibration requirement. It focuses on

• Calibration procedure  - how calibration is performed

• Calibration standards - standard to follow during the calibration activity

• Calibration records - maintaining documentation for the calibration activity.

Maintenance technique

Calibration is also an effective maintenance technique to verify the performance of instrument or a device. Its main advantage is that it provides an authentic overview of device performance, and the output of the calibration activity can be used to qualify the instrument status

Accurate and effective process

Equipment and process that uses calibrated instrument are accurate in calculating different process values and produce satisfactory results and products. The main reason is that instrument and measuring devices are getting common in latest machines and play a critical role in execution of process. Any error in instrument or measuring devices affects the output product parameters and quality attributes.

These process deviations can easily be prevented by calibrating instruments accordingly.

Types of calibration

As discussed above every instrument or measuring device that is involved in the production process requires calibration. Calibration type depends on the physical variable that an instruments measure, and commonly consists of following

Temperature calibration

It is the calibration of temperature sensor across various equipment, and it is the most common calibration type. Calibration of temperature sensor is verifying the output of a temperature sensor against the reference temperature sensor. If the difference of output remains within the limit, the calibration is pass, otherwise failed

Equipment used to calibrate temperature sensor consist of a cylindrical bath where temperature sensor to be calibrated is placed. The temperature in the bath is electrically generated, and output from sensor to be calibrated is noted and recorded.

Pressure calibration

Pressure calibration is used to calibrate pressure sensor, switches and transmitters install on the machine and used during production. Additionally gauges are also calibrated.

Pressure calibration is perform through a pump, capable of generating different pressure values. The pressure generated by the pump can be indicated by a pressure indicator installed on the pump. The pump can be manually or manually operated, depending on the model of pump.

The pressure device to be calibrated is attached the pump, with a dedicated nozzle and measures the pressure generated by the pump. The output of the calibrating pressure indicator is compared with a pump indicator

If the difference of pressure pump indicator and calibration device remains in the acceptable limit, the calibration is pass

Flow calibration

Flow calibration is the verification of instrument or devices that measure fluid flow. Flow sensors are used in processes or equipment where fluid flow is involved and product requires calculated amount of flow such as nitrogen in filling machine, or water flow in water treatment plant. Like temperature sensor, its calibration is necessary because, an erratic sensor or instrument will supply un-approved quantities of fluid, and damage the product and process.

Like other calibration type, the flow meter to be calibrated is connected to a fluid flow mechanism such as a piping network, through which controlled amount of fluid is made to flow, and calibrating instrument is attached to it. The amount of flow flowing in a pipe is compared with the instrument to be calibrated, and output verified. if the error lies in the range, calibration is said to be pass, otherwise fail.

Analytical instruments

Like process instruments and devices, analytical instruments are also calibrated as a part of a regulatory requirement and maintenance technique. Some of the analytical instruments include the following

Weighing balance

Weighing balance is used to measure the weight of any physical material, and are also required to calibrate.

For most balances calibration system is in-built in the balance. All we have to do is to place the required weight in it and activate the calibration system, and the balance will itself perform the calibration.

If the calibration is successful, it is indicated on the display and scale can be used further. If calibration is failed, it is also indicated on the display and the balance will have to send for repair or replace.

Spectrophotometer

Like weighing balance, the calibration system for spectrophotometer is in-built in the instrument, and all required is a solution of specific chemical properties that can be easily prepared in the lab. Instrument will automatically go through different phases of calibration.

In case of failure or success it will indicate on the display further processing.

Pipette

Pipettes are used in laboratory applications to add a controlled amount of liquid in a given test or analysis. They are also required calibration to gain accuracy in chemical analysis.

For calibration, controlled amount of liquid is inserted into Pipette, and is monitored for further processing.

Documentation

As discussed above, it is necessary to maintain documentation of calibration activity, which is reviewed by the regulatory authority during their routine inspection. Some common documentation is mentioned below

Calibration Certificate

It is the record and performance certificate of calibration activity of particular instrument and indicates the error range for the calibrating instrument. It also indicates

• Equipment identification i.e. Name, department / area or location of installation, calibration date

• Name of the person performing the calibration.

• At what values calibration was performed

• What was the output of instrument at a particular value

• How many times calibration was performed

• When the next calibration is required

• Calibration status i.e. Pass or Fails

Calibration tag

Calibration tag is a small piece of paper used as an identification on the machine. It indicates the calibration status of a particular machine, and indicates information such as

• Date performed

• Due date

• Performed by

About the Author

Muhammad Asim Niazi has a vast experience of about 11 years in a Pharmaceutical company. During his tenure he worked in their different departments and had been part of many initiatives within the company. He now uses his experience and skill to write interested content for audiences at PharmaSources.com.