By Eddy Azad
Pharmaceutical products have significant impact on the well-being of consumers. As such, it stands to reason that stringent requirements and standards be set firmly in place for their manufacture. The U.S. FDA has adopted a risk-based approach to establish and enforce regulations for pharmaceutical development, manufacturing, and quality assurance. Mandatory regulations (e.g. cGMP and 21 CFR Part 11) and voluntary frameworks, such as process analytical technology (PAT), are defined to ensure final product quality through proper design, analysis, and control of manufacturing operations. To ensure product integrity and quality, it is essential to have consistent records of operations and procedures, process settings and variables, production events and conditions, and finally quality and performance attributes of raw and in-process materials.
Traditionally, for batch operations, these records were — wholly or in part — collected, managed, and represented manually. As with most manual operations, there were concerns with accuracy, consistency, and repeatability. With the arrival of 21 CFR Part 11 and PAT came a clearer regulatory roadmap (and framework) for transitioning to EBRs. There are many advantages to electronic record keeping:
- improved regulatory compliance
- improved accuracy, consistency, and repeatability
- improved information accessibility and real-time analysis
- improved incident and root cause evaluation
- improved capacity utilization and yield
- improved process capability and reliability
- improved product quality.
The challenge now lies in negotiating the various issues related to infrastructure, existing systems, workflow, regulations, training, and the availability of a flexible solution to address these issues effectively, economically, and nondisruptively.
TYPES OF DATA TO BE COLLECTED
The electronic record requires the inclusion of the designated information for each batch. Consistent, accurate, and secure data is a fundamental characteristic of the batch record. Such data must include, but is not limited to:
- work order information
- product information
- production targets
- operator information
- environmental conditions
- details of batch steps, stages, and phases
- batch process variables
- operator observations and comments.
WHAT IS A COMPLIANT EBR?
It is extremely important to understand what constitutes a compliant electronic batch record system. Also, it raises considerable questions: What level of electronic data capture is required? How is this data captured? How is it retrieved, analyzed, and reported? How is the integrity of data ensured? While these questions sound simple, their not-so-trivial answers are critical to having the right solution in place.
Furthermore, based on a validated product manufacturing protocol, there are standard operating procedures or instructions in place that must be carefully followed. All exceptions/alterations must be clearly noted and approved by authorized personnel. For example, the instructions may require a detailed and step-by-step cleaning process that precedes the start of any batch operation.
As both the environmental conditions and batch-specific process variables can affect the quality and compliance of the product, it is required to have a complete record of their values throughout the process. You will need to capture the value of the required process variables, at specification-defined intervals, and provide a complete historical record — including the specification limits within which each process variable must be maintained. The historical process variable trends may be studied versus other process-relevant parameters and settings to gain valuable insight for documented process and quality improvement.
In order to provide in-depth context and contrast, specifically for traceability and corrective actions, clear and concise notes must be available. Such notes and observations may play a critical role in root cause analysis and tracing of production anomalies. Such meticulous and organized management of the recorded data (including observations/notes) makes it possible to quickly and effectively analyze batch records and respond in kind.
Also, within regulated industries (and for businesses interested in the methodical management of their manufacturing operations), it is critical to establish a clear means of monitoring and controlling changes to:
- system configuration, settings, and business rules
- operational setpoints
- pass/fail criteria
- collected (actual) data
- reported data
- access rights.
THE IMPORTANCE OF REAL-TIME NOTIFICATION
As great as it is to have a comprehensive historical record of the environmental and batch process-specific variables, it is as important to have to-the-point, real-time notification of process anomalies and deviations from defined protocols. You need to be able to alert the responsible personnel (as opposed to indiscriminate broadcasting of process alarms) — through their choice of delivery mechanism (e.g. email, page, SMS) — with specific messaging to expedite proper decision making and corrective action in real time. This has a profound impact on improved quality and productivity.
Collecting the necessary batch process data is an important part of developing effective electronic batch records. Applying the correct analytics and business rules to turn raw data into actionable intelligence is equally important. The actionable intelligence is typically manifested in the form of reports. The electronic reports can offer significant benefits if they are timely, accurate, user-configurable (personalization), flexible, accessible, and secure. Having these types of reports also offers a way for you to effectively deliver the needed information to satisfy both regulatory and operational requirements. With the delivery of accurate, timely, and secure information, users across a wide spectrum of disciplines (e.g. production, maintenance, quality, planning, IT, regulatory) can work together to efficiently meet operational excellence and quality-by-design goals.
About the Author
Eddy Azad is CEO of Parsec Automation Corp. (www.parsec-corp.com), which produces TrakSYS, a real-time performance management (RPM) and enterprise manufacturing intelligence (EMI) software. Azad speaks worldwide to industry forums and user groups on the subjects of Lean manufacturing, Six Sigma, overall equipment effectiveness (OEE), RPM, MES, and EMI and how these can be applied to improve asset utilization and operational efficiency, increase capacity with no new capital equipment, reduce production costs, and improve profitability for manufacturers.