Regulatory guidelines for Electronic Batch Record

The pharmaceutical industry generates sizable data during the entire manufacturing life cycle, mainly due to regulatory regulations, to ensure and prove the efficiency, safety, and reliability of the production process & product.  

Among many critical documentation is the electronic batch record, which records the batch process and represents how production went during each stage of the production process. 

Its advanced version is the Electronic Batch Record, which automates the traditional batch record and fills the loopholes of the conventional system. 

What is an Electronic Batch Record?

Electronic Batch Record is a software system or a set of digital tools that automatically updates the batch record as the production progresses on the production floor. The electronic batch record takes input from several input variables across different process stages and is integrated into the software system. 

The batch record updates itself every time there is progress and records in an electronic format & paperless manner.

In simple words, the electronic batch records can be considered an electronic version of the traditional paper batch, where each step has been modified to work in an automated manner. Additionally, it can integrate with other Software and transfer data between different software systems installed at different departments.

An electronic Batch record contains the history of the production process of a particular product with every minute detail. It includes information such as the raw material, equipment, manufacturing method, testing results, date and the personnel involved in the manufacturing process, much like the traditional batch record that aims to prove to regulatory bodies that it has followed every necessary GMP and other regulatory guidelines. 

The traditional method of developing and maintaining batch records has been on paper, where personnel manually create and enter the required queries. For obvious reasons, it becomes difficult to maintain and retain these records, with endless storage requirements and dedicated resources to make them error-free.

Additionally, these resources are prone to human error that can affect the pharma manufacturer's approval during the regulatory review.

To address the errors above and alike, manufacturers are turning towards electronic batch records that automate the batch recording process.

Electronic Batch Record is the latest development of digital transformation or Pharma 4.0, which is rapidly getting traction. It allows pharma manufacturers to align their product manufacturing process with other digital solutions, such as laboratory automation and warehouse management systems, to increase safety, quality and productivity within a pharm organization.

Electronic Batch Record Architecture

Like other software systems, the electronic batch record consists of an architecture that defines the overall functioning and essential components. Please note that the names can differ from developer to developer, but their overall function and purpose remain the same.

Let's briefly describe these.

Recipe Management

The electronic batch record system allows personnel to create predefined formulations or recipes previously tested, approved and followed during the product manufacturing process.

Its main advantage is that it guides throughout the manufacturing process and ensures accurate and correct ingredients have been used and the process is free from deviations. It also helps to trace the manufacturing process during product failure or recall by pinpointing the cause and its stage.

This safety feature (which we will discuss later) prevents unauthorized persons from creating, editing, and deleting recipes and limits them only to authorized persons.

Production records

The Electronic Batch Record measures and records every process conducted during manufacturing, with the help of different input variables, in an automated manner without human involvement.

The best part is that the record cannot be altered, as with the manual records. It enables production personnel to assess errors or shortcomings if the product becomes erratic or recalled.

This feature is an integral FDA requirement that must be implemented in any software system being used in department. 

Inventory Records

Inventory records in electronic batch records help solve inventory issues in pharma manufacturing. It automates the inventory process and provides real-time details of the available items to enable the manufacturing department, quality operations, and supply chain to plan and execute their roles promptly without problems such as inventory repetition, shortage, and expiry.

It also helps to trace items as they enter the warehouse by providing real-time details through different stages and departments. It also prevents unapproved items from entering the manufacturing cycle, reducing errors in the production process and the final product's defects.

Integration with Laboratory Management System

An essential part of electronic batch records is their ability to determine the quality status of every product at the beginning and at different levels of the manufacturing process. It has become possible because of the EBR's ability to integrate with the onsite laboratory management system, LMS, coordinating with tests performed in the laboratory and reviewing results as they become available, without relying on humans for these functions. 

Integration helps optimize and speed up the QC results in an automated manner. In manual systems, tests and report generation depend on humans, which takes time and can lead to errors. Integration also reduces batch approval time, preventing loss due to test results, report generation, and sending results to the production department.

Electronic batch Records retrieve the results directly from the LMS, enabling them to make timely decisions for batch approval.

Documentation Management

As stated earlier, documentation is an integral part and requirement of the pharmaceutical industry, and the pharma manufacturer is responsible for creating, verifying and recording all the required documentation.

Traditional practice for batch records had been to manually develop, verify, and record documentation. This system generates a large amount, explicitly requiring dedicated resources for safe storage. It also requires safety resources to protect and to ensure their availability, during the regulatory body review

Electronic Batch Record solves this problem and simplifies the documentation process by organizing, managing and controlling vast volumes of documents in a software system (Computer). Every document, such as logs, production records, and quality results, can be displayed electronically in a variety of formats (PDF, Docs and Excel). 

It also allows relevant personnel to access these documents in a single place, at go.

Supplier Management

With Electronic Batch Records, you can manage your supplier activities efficiently. It enables you to evaluate suppliers and prevent items from being sent to unapproved suppliers.

Equipment Management and Logging

Electronics Batch Records can link equipment pieces involved in manufacturing with relevant production processes and advanced features, such as real-time monitoring, automated decision-making and selecting appropriate equipment for performing a specific manufacturing process task.

It can record the monitoring values required for the production process. It can also integrate with in-process instruments such as a weighing scale and pH meter to adjust the product variables, simultaneously recording in the batch record - a common requirement for manufacturing documentation in the pharmaceutical industry.

Equipment management can also improve equipment performance by planning for preventive maintenance, which is scheduled maintenance. Further enhancement in technology can lead to predictive maintenance, where a maintenance schedule is generated if the equipment is close to failure.

EBR can also be used for optimizing Overall Operational Excellence - OEE, a widely accepted parameter for improving the equipment's productivity.

Integration with a variety of Software

Electronic Batch Records can integrate with other software systems commonly used in the pharmaceutical industry to interact, transfer data and make collaborative decisions. An example includes ERP, which incorporates production records & status with the supply chain to make practical forecasts and product distribution decisions.

Regulatory guidelines for Electronic Batch Record

Like other software systems and functions, regulatory bodies have guidelines for the Electronic Batch Record. For the sake of this article, we will focus on United States FDA.

The FDA has its guidelines titled "21 CFR 211.188" for batch production and records, which generally encompasses production procedures. 

However, for electronic records (applicable to all types, departments and functions in pharmaceutical organizations), the FDA has its dedicated guidelines, titled "Part 11, Electronic Records; Electronic Signatures - Scope and Application"

Let's describe some essential highlights of the 21 CFR part 11. 

Scope:

This guideline applies to 

● Records that are to be maintained in electronic format, in place of paper format & relied on to form regulated activities under predicate rule requirements

● Electronic signatures equivalent to handwritten signatures, initials and general signings

General Controls

Some general controls advised under this section are described below.

● Limiting unauthorized access control

● Operational system, device and authority checks

● Personnel using electronic records and systems have the required education, skill & expertise to develop, maintain, and operate these systems.

● Polices in written format to make personnel accountable, using these systems. They must also show adherence to these policies.

● Developing controls for system documentation

● The essential requirement for electronic signature as described in other guidelines, such as in 11.50, 11.70, 11.100, 11.200, and 11.300, must also be followed

General Rules

● The pharma product manufacturer is responsible for validating Electronic Batch Record system before making it part of an entire organization's system.

● Time-stamped audit trails must be part of the computerized system in electronic batch records. 

● All copies of records must be available for investigation during regulatory body review under appropriate FDA guidelines.

● The organization should make arrangements to present records throughout the retention period.

About the Author:

Muhammad Asim Niazi

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.