The computer-driven system should be able to generate audit trail reports and provide detailed, time-stamped information about each step in the electronic records process.

The effectiveness of pharmaceuticals depends on their ability to properly dissolve in the fluids of the gastrointestinal tract prior to the absorption of the drug’s active ingredients in the patient’s bloodstream.

The bioavailability of the pharmaceutical essentially determines the extent of the drug’s therapeutic benefit. Substandard bioavailability could limit the effectiveness of the treatment and potentially put the patient in danger.

Dissolution testing is routinely undertaken during drug development to provide critical information about the drug release, to ensure batch-to-batch consistency and to predict the drug release profile.

The dissolution rate of an oral dosage form largely depends on the quality and purity of the raw materials that have been used in its production, as these essentially determine whether the drug is able to travel within the body and break down its active ingredients at the appropriate time.

Data transfers from meter to computer with select software. (Credit: Thermo Fisher Scientific)

Water is one of the most important components used in the processing, formulation, and manufacture of pharmaceutical products and its purity will impact the dissolution profile and, subsequently, the bioavailability of the drug. As such, to maintain adherence to global microbiological quality standards, the purity of pharmaceutical grade water must be monitored and confirmed prior to its use.

Ion concentration, conductivity, dissolved oxygen, temperature, and pH measurements of water are all critical steps in the daily routine workflow of pharmaceutical laboratories, allowing them to ensure water is of the appropriate grade and therefore suitable for its intended use.

Generating accurate, precise and repeatable critical water quality values should be a top priority for pharmaceutical laboratories to ensure pharmaceutical integrity. Drug development facilities are required to take all necessary measures to facilitate the production of highly reliable quality control data.

This could include utilizing high performance equipment and well trained personnel, as well as ensuring best practices are maintained and adhered to at all times. Part of this can involve compliance with the stringent requirements of the U.S. Food and Drug Administration (FDA) 21 CFR Part 11 regulation for electronic records and signatures.

Signatures are required as part of standard protocols to ensure that various protocols, and quality control measures, are undertaken correctly and in compliance with required regulations in order to provide a traceable paper trail.

This is especially important in the drug development industry where problematic batches, or insufficient quality control, could have significant consequences in terms of patient care.

Ensuring Regulatory Compliance

The U.S. FDA 21 CFR Part 11 regulation details the criteria under which electronic records, electronic signatures and handwritten signatures executed on electronic records can be considered trustworthy and equivalent to paper records and handwritten signatures on paper.

The introduction of this regulation has enabled pharmaceutical laboratories to efficiently manage their records and signatures, while removing the potential for human error and reducing operational costs.

However, in order to comply with the regulation, it is necessary for laboratories to implement certain controls and procedures over the course of the creation, modification, maintenance, and transmission of electronic records and signatures to ensure their authenticity, confidentiality, and safety.

This is an ongoing challenge and the only way to achieve regulatory compliance is to exert full computational control over all ion concentration, conductivity, dissolved oxygen, temperature, and pH meters. To do so, it is necessary to utilize a software platform that has been specifically designed to offer multiple levels of security to help establish and maintain optimal data validity and integrity.

VersaStarPro pH/ISE meter kit. (Credit: Thermo Fisher Scientific)
Maintaining Data Integrity

The solution to the ongoing data integrity challenges faced is a computer-driven system capable of controlling all of the functions and settings of laboratory quality control equipment, such as calibration, measurement, and reporting. This will ensure data accuracy, reliability and consistency is retained throughout.

The system should be able to generate audit trail reports and provide detailed, time-stamped information about each step in the creation, modification, and deletion of electronic records. In this way, authorized personnel will be able to review the documentation process at any given stage, identify problems or inaccuracies, and address them early on before they have the chance to escalate and become a costly issue.

In order to ensure that the integrity of the data stored within such a system is maintained, access needs to be limited to authorized members of personnel through a password-protected function.

Customization of individual users’ levels of access allows lab managers to tailor the involvement of personnel based on their experience and seniority. For example, more junior members of the lab will only need access to the basic data collection functionality, whereas the most senior staff can be given full system access to allow them to undertake the more complex and sensitive activities.

These strict security measures will ensure individuals can be held accountable for each action they perform under their electronic signatures, and as such the potential for records being tampered will be minimized.

A competent paperless record keeping system should be able to generate precise and comprehensive copies of electronic records and signatures, which would be easily available for review and inspection by the U.S. FDA upon request.

It is also necessary to ensure that the chosen software has been designed to facilitate the transfer of measurement and calibration data from the meter to a computer for further analysis. This function will allow data to be easily stored, viewed, and downloaded into PDF reports for easy referencing and handling.


The pharmaceutical industry needs to have strict protocols in place, especially in terms of quality control, to ensure that the drugs which are taken to the market are safe for use and will have the desired on-target effect with high bioavailability. As a vital part of the drug development process, it is important to ensure that the water used is of the appropriate quality in order to maintain the integrity of the compound.

To achieve this, there are several regulations that need to be complied with, including the U.S. FDA 21 CFR Part 11 regulation that allows pharmaceutical laboratories to create, modify, maintain, and transmit electronic records and signatures to decrease the potential for human error associated with handwritten paper trails.

Electronic signatures and records facilitate a standardized method of quality control that is fully accountable. However, careful consideration should be given to the type of system used to generate and maintain reliable electronic measurements, calibration data, and audit trails.

Such a system can help laboratories achieve regulatory compliance, while ensuring data integrity and consistency are preserved at all stages of the pharmaceutical manufacturing process.

About the Author
Ricki Hartwell is the Product Line Manager, Electrochemistry Lab Meters, at Thermo Fisher Scientific, Chelmsford, MA; 978-232-6000.

This story can also be found in the January/February 2018 issue of  Pharmaceutical Processing.

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