The conditions for the manufacture, storage and distribution of products in the pharmaceutical industry are subject to stringent standards. Depending on the application, various measurements need to be recorded and verified to prove that products have been safely produced and are suitable for sale both at home and overseas.
Traditionally, paper chart recorders have been used to measure these parameters. However, in the last 20 years, instrument manufacturers have offered a growing number of paperless recording options designed to replace their paper counterparts. As such, the regulatory framework covering the recording of data has had to change.
The rules of the game
The de facto standards for the use of electronic recording equipment in the pharmaceutical industry are set by the International Society of Pharmaceutical Engineers’ (ISPE) Good Automated Manufacturing Practice (GAMP) guidelines. Adopted by countries worldwide, these guidelines set down the main requirements that need to be considered when planning and implementing a computerised system, including paperless recording equipment, for use in pharmaceutical applications.
As the world’s largest market for pharmaceutical products, the US has led the way in developing its own interpretation of these guidelines, with the Food and Drug Administration’s (FDA) good practice rules setting the standard for companies worldwide.
Particularly important are the FDA’s Predicate Rules 21 CFR Part 210 and 21 CFR Part 211. These provide guidance on which aspects of pharmaceutical production need to be recorded, including any process control settings, details on checking of recorded data and specific requirements relating to the collection of batch production and control records.
Where these records are collected electronically, then 21 CFR Part 11 also applies, which aims to give electronic records and signatures the same weight and trustworthiness as their paper-based counterparts. A key aspect of 21 CFR Part 11 is its focus on security, particularly relating to the prevention of data tampering and the ability to identify specific individuals and events involved in the production and/or data management processes.
Security
Whereas tampering with paper charts can be easily spotted, it is less obvious where electronic data is concerned. So, in order for recorded data to be accepted as valid proof of compliance with the various standards, it is necessary to eliminate any potential for unauthorised adjustment or tampering with that data.
For this reason, any electronic data recorder should incorporate a full range of security features. These should include data access restricted to authorised individuals only; password protection to protect against unauthorised access; audit trail facility to independently attribute a time and date every time a record is created, modified or deleted; the ability to protect against unwanted loss of recorded data and use of digital signatures to show that the device has only been used by authorised persons.
Producing and storing pharmaceutical products
GAMP guidelines advise that all measurements taken during the manufacturing process should be electronically logged in compliance with 21 CFR Part 11. Factors such as temperature, humidity, air quality, time and production process characteristics can all have a significant impact on the final quality of pharmaceutical products and should be checked and recorded to ensure the optimum process environment is achieved.
A videographic recorder, such as ABB’s SM500F (Figure 1), can offer several process inputs enabling multiple sensors to be connected. These are accompanied by numerous recording channels that can each record process inputs, communications inputs, math block results, digital signals and other values, providing additional detail and functionality that do not exist in paper chart equipment.
Various paperless recorders can also provide greater functionality for batch recording. For example, when a new batch is initiated on the control system, the recorder will automatically start to record the batch, including any associated batch information. This batch data can then be easily reviewed and approved at the end of the batch.
In the case of storage, large refrigerators (in excess of 6m3) and walk-in cold rooms used in high volume operations should be fitted with an electronic temperature recording device that measures load, as well as air temperatures. The recorders can be set up to trigger warnings and activate alarms should the required process parameters be exceeded. These often incorporate a time delay and/or a hysteresis. This only triggers the alarm once the parameter has exceeded acceptable levels by a certain amount of time, helping to prevent nuisance alarms.
Multi-tasking
There are other pharmaceutical applications where multiple parameters need to be monitored and recorded that can benefit from the increased functions available with paperless recorders. For example, water purification is commonly undertaken to produce different grades of water for various processes, such as purified water; highly purified water; and water for injection.
In all of these instances, a range of instrumentation is required to meet GAMP guidelines, including conductivity meters, pH meters, temperature sensors and recording equipment. The multiple analogue inputs of the paperless recorder make them suitable for collecting sufficient and secure data to ensure these processes can be proven to meet the specific standards.
The alarm functions within a paperless or videographic recorder can be used, based upon validation data, to set off an alarm to signal significant changes from normal operating conditions. If the recorder has Ethernet communications, it may send email notifications whenever an alarm occurs for prompt attention.
Ethernet connectivity can also allow historical recorded data and alarm and audit trail information to be relayed automatically to a central database where archive and analysis, if required, can take place (Figure 2).
Time to change
There are many organisations that currently use traditional paper chart recorders that should almost certainly consider making a switch to paperless recorders as a viable alternative. Operators should be enjoying instantly accessible and secure data, not worrying about when a pen may run out or where to store paper charts. The increased functionality offered by paperless recorders should make the transition that much easie
