What is eBMR and BMR as per PICS guideline?

What is BMR?

As per PICS guidelines, Batch production records should be prepared for each intermediate and API and should include complete information relating to the production and control of each batch. The batch production record should be checked before issuance to assure that it is the correct version and a legible accurate reproduction of the appropriate master production instruction. If the batch production record is produced from a separate part of the master document, that document should include a reference to the current master production instruction being used¹

BMR stands for “Batch Manufacturing Record.” It is a comprehensive document used in the pharmaceutical and manufacturing industries to provide detailed instructions and guidelines for the production of a specific batch of a product. The Batch Manufacturing Record serves as a critical reference and guide for personnel involved in the manufacturing process to ensure consistency, quality, and compliance with regulatory standards and Good Manufacturing Practices (GMP).

Why BMR is Required?

1. Data Integrity and Accuracy:
   • Provides a reliable record of raw materials, equipment, and process parameters.
   • Reduces the likelihood of data entry errors through structured documentation.
   • Supports data integrity and accurate reporting for quality control and regulatory purposes.
2. Audit Trail and Accountability:
   • Creates a comprehensive record of personnel involved in each manufacturing step.
   • Documents approvals, signatures, and reviews by authorized personnel.
   • Facilitates audit trails for regulatory audits, internal quality audits, and process reviews.
3. Quality Assurance and Compliance:
   • Ensures adherence to Good Manufacturing Practices (GMP) and regulatory guidelines.
   • Provides a documented record of manufacturing processes, materials, and controls.
   • Demonstrates product consistency, traceability, and accountability during regulatory inspections.
4. Standardization of Processes:
   • Offers clear, step-by-step instructions for manufacturing procedures.
   • Ensures consistent production of pharmaceutical products across batches.
   • Mitigates the risk of errors and deviations by providing standardized guidelines.
5. Risk Management and Deviation Handling:
   • Outlines critical control points (CCPs) and process parameters to monitor.
   • Enables prompt detection and documentation of deviations from the standard process.
   • Facilitates the implementation of corrective and preventive actions (CAPA) to address deviations.
6. Product and Patient Safety:
   • Ensures accurate labeling, dosing, and ingredient information.
   • Helps prevent contamination, cross-contamination, and mix-ups during production.
   • Supports the integrity and safety of pharmaceutical products for patient use.
7. Batch Consistency and Recordkeeping:
   • Facilitates uniformity in product appearance, quality, and performance.
   • Provides a historical record of each batch’s production and testing data.
   • Enables comparison of data across batches to identify trends and ensure continuous improvement.
8. Documentation of In-process Controls and Testing.
   • Details in-process tests and quality control checks to be performed.
   • Captures sampling procedures, testing methods, and acceptance criteria.
   • Provides evidence of compliance with quality standards and specifications.
9. Training and Knowledge Transfer:
   • Serves as a training tool for new personnel to learn manufacturing procedures.
   • Transfers institutional knowledge and best practices for consistent production
   • Enables effective knowledge sharing and skill development within the organization.
   • Facilitates data analysis for process optimization, trend identification, and root cause analysis.
10. Continuous Improvement and Data Analysis:
    • Drives continuous improvement initiatives based on historical data and insights.
    • Supports data-driven decision-making to enhance efficiency and product quality.

How BMR can be issued.

It depends upon internal SOP. The BMR request may be generated by the Planning head as per marketing demand, and in small business industries CEO can generate a request to the Authorised person or QA department for issuance of BMR of a specific product as per marketing/supply chain demand.  

As recommended the Controlled Supreme department will issue the BMR in printed form to the product-producing department head for the execution of the batch. The QA department is responsible for verifying the accuracy of header information, including batch number, product name, strength, manufacturing date, and expiry date. Accurate header information is vital for product identification, traceability, and regulatory compliance. QA personnel cross-reference the header information with approved documents and batch documentation. Header information is verified at the beginning of the batch record review process.

How to Draft a BMR

Following Fixed and attachable Key components and information typically found in a Batch Manufacturing

Fixed part and Headings of approved Format

1. Header Information:
   • Product Name
   • Generic name    
   • Batch Number
   • Strength
   • Dosage Form
   • Batch Size
   • Manufacturing Date
   • Expiry Date
   • Manufacturing Site
   • Total weight of bulk (if necessary)
   • Number of Finished packs (if necessary
2. Reference Documents:
   • Reference to Master Batch Record (if applicable)
   • Reference to Standard Operating Procedures (SOPs) used in the manufacturing process
   • The Production and QA departments collaborate to ensure that the referenced Batch Manufacturing Record (BMR) and SOPs are up-to-date and relevant to the current batch. Referencing accurate and updated documents ensures consistency, standardization, and adherence to approved procedures. QA verifies that the referenced documents are the latest versions, while Manufacturing follows the procedures outlined in the referenced SOPs. This check is performed during the review and approval of the batch record.
3. Master Formulation Ingredients and Materials
   • List of all raw materials and their quantities, including active pharmaceutical ingredients (APIs) and excipients
   • Lot or batch numbers of each raw material
   • Source and supplier information for each raw material (in case of multiple sources and locked formulation as per stability studies)
   • Dispensing Records: Documentation of the dispensing process for raw materials, including RM number, expiry,  quantity dispensed by, verified by, and the person responsible.
   • Line clearance of Dispensing area.
   • The Quality Control/ Quality Assurance department (QC/QA) department ensures that API potency is accurately calculated and raw materials are accurately listed, sourced, and dispensed. Proper documentation of raw materials and dispensing processes is crucial for traceability and quality control. QA personnel cross-check the listed materials with approved specifications and verify the accuracy of batch and lot numbers. This verification takes place prior to the start of dispensing & manufacturing of each batch.
4. Equipment and Facilities:
   • List of equipment to be used in the manufacturing process
   • Equipment identification numbers.
   • Cleaning and calibration status of equipment
   • Details of the manufacturing area or facility to be used
   • The QA departments collaborate to ensure equipment suitability and facility readiness. Properly maintained equipment and a controlled manufacturing environment are essential for product quality and safety.
   • QA conducts line clearance equipment checks, maintenance, and calibration periodically. QA reviews equipment status and facility conditions. Equipment and facility checks are conducted before manufacturing begins.
5. Processing Instructions:
   • Step-by-step instructions for each stage of the manufacturing process
   • Specific actions to be taken at each step (e.g., mixing, blending, granulation, drying)
   • Parameters to monitor (e.g., temperature, humidity, start time, end time, etc)
   • Sampling points and procedures as per sampling SOP
   • In-process control checks and tests.
   • Request Records: Documentation of any special requests or adjustments made during the processing steps. The Manufacturing department follows the detailed processing instructions, while QC/QA monitors in-process controls and tests. Proper execution of processing steps and in-process controls ensures consistent product quality. Manufacturing personnel follow step-by-step instructions, record observations, and perform in-process controls.
   • The quality Control department will perform necessary testing as per pharmacopeial monograph compliance and samples as per instructions.
   • Processing instructions are followed during the manufacturing process, and in-process controls are conducted at specified intervals as mentioned in BMR.
6. Packaging Instructions:**
   • The Packaging department is responsible for ensuring accurate packaging material usage and labeling. Proper packaging and labeling are critical for product identification, patient safety, and regulatory compliance. Packaging personnel verify the correctness of packaging materials and labels against specifications. They set up packaging equipment and follow packaging instructions. Packaging instructions are executed during the packaging process.
   • Details of primary and secondary packaging materials
   • Packaging instructions for each packaging component
   • Labels, printing, and labeling instructions. (including mfg. exp. price batch number)
7. Quality Control and in-process testing:**
   • List of tests to be conducted on intermediates, and finished products
   • Specifications and acceptance criteria for each test as per the in-process checklist
   • Sampling instructions for testing
   • In-process testing and finished product testing requests and reports
   • Sampling Records and release reports: before starting the next process of manufacturing the documented proof of the sampling process for quality control and testing, including sampling location, method, and the person responsible is mandatory for the compliance process.
   • The QC department performs testing, analyzes results, and ensures compliance with specifications.
   • Quality control testing confirms the product’s quality, safety, and efficacy. QC personnel perform specified tests, follow approved analytical methods, and record results. Sampling is conducted according to established procedures.
8. Documentation and Record Keeping:
   • Instructions for documenting observations, deviations, and any changes made during the manufacturing process.
   • Signature and initials of personnel responsible for each step
   • Space for recording results, test data, and other critical information
   • Space for authorized personnel to review and approve the BMR
   • Start time and end time of each process as recommended in standard BMR.
   • Personnel from various departments, including Manufacturing, QC, and QA, contribute to documentation and record keeping.
   • Accurate and complete documentation provides a transparent record of the manufacturing process and compliance. Personnel involved in each step document their observations, actions, and results.
   • QC and QA review and approve the documentation. Documentation is performed throughout the manufacturing process and is reviewed during batch record review
9. Yield calculation:
   • yield calculation is necessary at each step and especially at the end of packing and finished packs for the record.

Conditional Attachments of BMR

1. Critical Points and Control Measures:
   • Identification of critical control points (CCPs) and critical process parameters (CPPs)
   • Measures to control and monitor these critical points. Manufacturing, QC, and QA departments collaborate to identify, monitor, and control CCPs and CPPs.
   • Ensuring control over critical points is essential for consistent product quality and safety. Manufacturing identifies CCPs and CPPs. QC monitors these points during production. QA ensures proper controls and compliance.
   • CCPs and CPPs are identified before manufacturing begins and are continuously monitored throughout the process.
2. Deviation Handling and Corrective Actions
   • as per PICS written procedures should be established and followed for investigating critical deviations or the failure of a batch of intermediate or API to meet specifications. The investigation should extend to other batches that may have been associated with the specific failure or deviation¹.
   • Procedures for documenting and handling deviations from the standard process
   • Instructions for initiating corrective and preventive actions (CAPA) if deviations occur
   • The QA department is responsible for managing deviations and implementing corrective actions. Timely detection and resolution of deviations prevent potential quality issues and improve processes.
   • QA investigates deviations, identifies root causes, and proposes corrective actions. CAPA plans are developed and implemented. Deviations are documented and investigated as they occur, and CAPAs are initiated promptly.
3. Distribution and Archiving
   • Distribution instructions for copies of the BMR to relevant departments
   • Instructions for archiving the BMR after completion of the batch
   • The Document Control or Archival department manages the distribution and archival of BMRs.
   • Proper distribution and archiving ensure accessibility for audits, regulatory inspections, and future reference.
   • Document Control ensures accurate distribution of BMR copies. Archival ensures proper storage and accessibility.
   • Distribution occurs after batch completion, and archival takes place upon batch approval.
4. Environmental and Safety Considerations
   • Safety precautions to be taken during manufacturing and packaging
   • Handling of hazardous materials and waste disposal procedures
   • Environmental controls and consideration
   • The Environment, Health, and Safety (EHS) department oversees safety protocols and environmental controls.
   • Safety measures protect personnel, the environment, and product quality.
   • EHS ensures proper safety procedures are followed, hazardous materials are handled safely, and waste is disposed of correctly.
   • Safety considerations are in effect throughout the entire manufacturing process.

By integrating detailed departmental responsibilities, tasks, and checks, the pharmaceutical manufacturing process adheres to a comprehensive and systematic approach in accordance with GMP guidelines. This collaborative and well-structured methodology ensures product quality, regulatory compliance, and patient safety throughout every stage of the manufacturing process.

Batch Number

As per PICS guidelines, These records should be numbered with a unique batch or identification number,
dated, and signed when issued. In continuous production, the product code together with the date and time can serve as the unique identifier until the final number is allocated¹. Usually a standard SOP exist for batch number allocation.

Batch Release as per PICS.

Responsibilities of Production head

As recommended by PICS guidelines, the head of Production generally has the following responsibilities:

1. Production head must ensure the production and storage of products according to the appropriate documentation in order to obtain the required GMP quality;
2. Production head must approve and ensure the necessary instructions related to production operations and to implement.
3. Production head must ensure the production records are evaluated and signed by an authorized person
4. Production head must ensure the qualification and maintenance of production department, premises and equipment;
5. Production head must ensure the appropriate validations have been done
6. Production head must ensure the training of production department personnel and the implementation of processes as per GMP needs.

Responsibilities of Quality Control Head

As recommended by PICS guidelines, the head of Quality Control generally has the following responsibilities:

1. Quality control head is responsible for the final approval or rejection of starting materials, packaging materials, intermediate, bulk, and finished products
2. Quality control head is responsible to ensure that all necessary testing is carried out and the associated records evaluated and maintained.
3. Quality control head is responsible for the approval of specifications, sampling instructions, test methods and other Quality Control procedures approving and monitoring any contract analysts.
4. To ensure the qualification and maintenance of his/her department, premises and equipment and their validation appropriate validations.
5. Quality control head must ensure the training of QC department personnel and implementation in processes as per GMP/GLP/GDP needs.

Responsibilities of Authorised person

As per PICS guidelines, Each batch of finished product must be certified by an Authorised Person before being released for sale, supply, or export. Certification can only be performed by an Authorised Person of the manufacturer and/or importer which is described in the MA². The most responsible person is Authorised person independently releases batch after data and process review.

What is eBMR

eBMR, or electronic Batch Manufacturing Record, is a digital predefined and paperless version of the traditional Batch Manufacturing Record (BMR) used in the pharmaceutical industry. It is a technological solution that aims to streamline and modernize the documentation, recording, and management of the entire manufacturing process of pharmaceutical products.

In a traditional paper-based BMR, various departments involved in the manufacturing process manually record data, observations, and actions on paper forms. These records are then compiled, reviewed, and archived. eBMR replaces this manual process with an integrated electronic system, offering several benefits to the pharmaceutical industry:

Benefits of eBMR

1. Real-time Data Entry and Recording: With eBMR, data is entered and recorded electronically in real-time as manufacturing processes unfold. This eliminates the need for manual data transcription, reducing the risk of errors and enhancing data accuracy.
2. Improved Data Integrity: Electronic systems can be designed with built-in validation checks and automated calculations, reducing the chances of data entry errors and ensuring data integrity.
3. Electronic Signatures and Approvals: eBMR systems often incorporate electronic signatures and approvals, which facilitate compliance with regulations and ensure the authenticity of records. This adds an extra layer of security and accountability.
4. Version Control and Document Management: eBMR systems allow for efficient version control, ensuring that the latest approved procedures and instructions are readily available to users. This eliminates confusion caused by outdated paper documents.
5. Traceability and Auditing: Electronic records are easily searchable and retrievable, simplifying the tracking of materials, processes, and activities. This enhances traceability and assists during audits and regulatory inspections.
6. Integration with Quality Control (QC) Systems: eBMR systems can integrate with laboratory information management systems (LIMS) and other QC systems, enabling seamless data sharing and efficient testing coordination.
7. Faster Review and Approval Processes: eBMR systems enable real-time review and approval workflows. This reduces the time required for batch release and speeds up the overall manufacturing cycle.
8. Trend Analysis and Data Analytics: Electronic records can be used for data analysis and trend monitoring, helping companies identify patterns, optimize processes, and improve overall quality.

implementation and functioning of eBMR

The implementation and functioning of eBMR in the pharmaceutical industry involve the following steps:

1. System Selection and Configuration: A suitable eBMR software or platform is selected based on the company’s needs and regulatory requirements. The system is then configured to mirror the existing batch manufacturing processes.
2. Data Entry and Recording: During manufacturing, operators, and technicians input data directly into the eBMR system, detailing each step, parameter, and action performed.
3. Electronic Signatures and Approvals: Responsible personnel electronically sign off on each step, indicating their review, verification, and approval.
4. Real-time Monitoring: Quality control personnel can monitor the progress of manufacturing in real-time, ensuring compliance with procedures and specifications.
5. Review and Approval: Upon completion of manufacturing, the eBMR undergoes a digital review and approval process involving different departments, such as Manufacturing, Quality Assurance (QA), and Quality Control (QC).
6. Batch Release: Once the eBMR is reviewed and approved, the batch is released for packaging and distribution.
7. Archiving and Retrieval: Electronic records are securely stored and can be easily retrieved for audits, inspections, and analysis.

Important Note

eBMR offers increased efficiency, data accuracy, and compliance with regulatory requirements. It enhances transparency, reduces paperwork, and ultimately contributes to safer and more reliable pharmaceutical products. However, its successful implementation requires thorough validation, user training, and ongoing maintenance to ensure that the system remains reliable and compliant with industry standards.

• BMR and eBMR as per PICS Guideline
• Quality Management System (QMS) as per ICH, WHO, and ISPE Guidelines
• Look into HVAC in GMP as per WHO
• A Visit to Cleanrooms and Controlled Environments in Pharma GMP
• Differential Pressure in GMP Area

References

• https://picscheme.org/docview/4590
• https://picscheme.org/docview/4588