Russian Good Distribution Practices Pharmaceutical Regulations, Part 4
Requirements for Calibration of Measurement Instruments
After looking at the general key elements of Russian Good Distribution Practices in the first blog, of our series, the storage requirements in the second, and the transportation or in-transit related elements in the third, let’s conclude this series with a deeper dive into the calibration requirements for Russian domestic and international distribution as well as, some key points to focus on when choosing your measuring equipment.
On this specific topic, the Russian GDP regulations have the following requirements for both storage and transportation environments:
- “Equipment that is part of measuring instruments shall undergo primary verification and/or calibration prior to installation and after repair; during operation, it shall undergo periodic verification and/or calibration according to the requirements of the legislation of the Russian Federation on ensuring the uniformity of measurements1”
- “The repair, maintenance, verification and/or calibration of the equipment shall be performed in compliance with the approved schedule, in such a way that the quality of the medicinal products is not negatively affected.”
- “The repair, maintenance, verification and/or calibration of equipment and measuring instruments shall be appropriately reflected in documents that are archived and stored in compliance with the law on archiving of the Russian Federation.”
Temperature monitoring devices are considered to be a critical component for compliance to meet Good Distribution Practices. The term “critical component” applies since the recorded time and temperature data is a key element in proving that the condition of temperature-sensitive medicinal products meets proper electronic record, security, and storage regulatory requirements for the accept/reject decision at the final destination. It is critical to ensure that the measurement instrument utilizes a pre-defined and pre-accepted level of accuracy measured against the predefined points of a very precise reference measurement instrument.
In Russia, the approval of weighing and measuring instruments must follow a specific process, directed by the Federal Technical Regulation and Metrology (Rosstandart). In this case, it is a state institution in charge of controlling the instrument and verifying its margin of inaccuracy. The certificate attests that the metrological instrument has passed all the necessary predefined technical and metrological tests and complies with the requirements of the current legislation in the Russian Federation.
The Sensitech® family of dataloggers, the TempTale® Ultra product portfolio of has passed all the required Russian tests and can provide the Certificate of Metrology upon request from one of our customer representatives.
The Certificate of Metrology is a key point when shipping or storing medicinal products within Russia, but the products may be distributed outside of Russia. In this case, some additional international requirements will be relevant. Although, most countries’ GDP guidelines and specifically calibration and qualification requirements are quite similar in nature, the requirements and tests might differ slightly, as compliance can be assured by using country-specific standards. It is consequently important to match all country requirements and check that all areas of the supply chain are covered without any gap.
As reference, the following items also apply when shipping to and from the European Union according to the EU GDP guidelines:
- Calibration of equipment should be traceable to a national or international measurement standard. Appropriate alarm systems should be in place to provide alerts when there are excursions from pre-defined storage conditions. Alarm levels should be appropriately set and alarms should be regularly tested to ensure adequate functionality.
- A risk assessment of delivery routes should be used to determine where temperature controls are required. Equipment used for temperature monitoring during transport within vehicles and/or containers should be maintained and calibrated at regular intervals at least once per year.
- If temperature-controlled vehicles are used, the temperature monitoring equipment used during transport should be maintained and calibrated at regular intervals.
When shipping to and from or transiting through the United States of America, USP <1079> and USP <1118>’s requirements should be applied.
- “Calibration ensures that measurements such as temperature and humidity meet recognized standards. Calibration frequency may be determined by the device manufacturer, device workload, operational demands, and/or damage that require repairs.
Instruments or devices used for qualification or monitoring of set criteria must be calibrated to recognized standards such as those from the National Institute of Standards and Technology (NIST) and those found in Monitoring Devices—Time, Temperature, and Humidity 〈1118〉.”2, 3
- “Calibrations should be performed with appropriate frequencies to support ongoing use. Monitors used in manufacturing, storage, and transport of drug products should be properly qualified by their users to ensure that the monitors have been received and maintained in proper working order. It is acceptable to use the calibration performed by the device's manufacturer based on the certificate of calibration and expiration date.”
- “Any monitor takes time to respond to a change in the temperature or humidity. Measurement responsiveness typically is defined in a device's specifications for its operating range. Different data recording intervals are appropriate for different monitoring applications and should be based on supply chain length (for example, transportation via ocean may require 30-min intervals, but 15-min intervals may be suitable for air transport). Most commonly, time accuracy is expressed as a ± percentage of total duration of the recording period. For pharmaceutical applications, a ±0.5% time accuracy is adequate.”
In conclusion, when choosing a supplier for measurement instruments, some of the questions you should ask yourself and the suppler:
- Does the supplier have a Quality System in place?
- Is calibration testing done for each individual device vs. a sample of devices at a batch or lot-level using an Acceptance Quality Limit (AQL) for approval? (Calibration testing of each device vs a sample of a batch)
- Is calibration testing done as a complete device or as a system vs. is the sensor tested without the other working electronic components?
- What is the number of calibration points across the operating range?
- What is the reference standard being used?
- What is the level of accuracy specification?
- What is the reference equipment used for the calibration?
- What is the availability of the certificate of calibration? (self-service or upon request)
Sensitech calibrates and tests every single device through a 3-point NIST®-traceable calibration process, which is accredited by ISO/IEC. This method sets the temperature sensors to three different set points and the device must perform within ±0.5°C in terms of accuracy. The monitor receives a Certificate of Calibration demonstrating an accuracy specification of ±0.5°C or better.
Many other datalogger companies only use the Acceptable Quality Level (AQL) calibration test. Calibration with AQL tests require only a sample of devices be tested, and if the sample passes the test, then the whole lot passes as meeting the accuracy standard. AQL is technically the standard for testing calibration, but it still is not the most accurate method of testing. Be aware of statements such as: “Our Company performs a 100% temperature calibration of all sensors.” In actuality these companies are only calibrating the sensor not the device as an integrated system. Additionally other companies explain that the measurement accuracy and functionality are verified and documented with a system calibration of the device via an AQL sample test after final assembly. They are not calibrating each and every device as a full system.
For questions about the Russian “Rules for Proper Storage and Transportation of Medicines” or information about Sensitech’s thermal mapping studies, visit our Professional Services site or contact us.
- Refers to Articles 13 and 18 of Federal Act No. 102-ФЗ, dated 26 Jun 2008, on Ensuring the Uniformity of Measurements (Legislative Assembly the Russian Federation, 2008, No. 26, Art. 3021; 2014, No. 26, Art. 3366; No. 30, Art. 4255)
- Revised USP <1079>, published June 1st 2020, effective December 1st, 2020
- USP <1118>, effective December 1st, 2014