Susan J. Schniepp, distinguished fellow for Regulatory Compliance Associates, provides simple answers to frequently asked questions regarding 21 CFR Part 11 and electronic batch records.
Q. What is a master batch record (MBR)?
A. The MBR is the controlling document for pharmaceutical manufacturing. It contains the instructions and specific manufacturing processes needed to produce a particular product.
Additionally, the MBR ensures the ingredients needed to produce a product are correct. Each ingredient is added in the correct order, and the mixing and stirring used to produce the product are conducted in correct sequence.
Master Batch Record
For example, the MBR would list an ideal ingredient amount for the product. The completed electronic batch record would indicate the actual amount used for the individual batch. Moreover, electronic batch records are a requirement of 21 CFR Part 11 and is listed in Batch Production and Control Records section.
Q. Who is responsible for issuing the batch record to production?
A. Undeniably, world class companies have a document control department that is responsible for issuing the MBR to production. This department may or may not report to the quality department. Simultaneously, the most important item about releasing the batch record to manufacturing is that it needs to be tied to an actual production run.
21 CFR Part 11 Requirements
The pharmaceutical industry has very specific compliance requirements tied to traceability. The link that ties the MBR to the completed batch record is the lot number assigned to the product being manufactured. Naturally, each manufacturing run must have a different lot number for traceability and recall purposes.
Q. Can I release a batch record that has open investigations/deviations associated with it?
A. The 21 CFR Part 211 regulation states:
“There shall be a quality control unit that shall have the responsibility and authority to approve or reject … drug products, and the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated”.
Consequently, the errors referred to include errors that occur during the manufacturing process.
Batch Production Record
If you are releasing a product that has electronic batch records associated with an open deviation/investigation then, in my opinion, the “error” has not been thoroughly investigated. Therefore, the bottom line is I would not recommend this practice.
21 CFR Part 11 Audit Trail Requirements
Unquestionably, audit trail documentation is vitally important when assessing risk if production goes awry. In my opinion, there is too much risk associated with releasing a product to the field with open investigations or deviations. Further, if the investigation result indicates the product has not achieved the specified quality attributes, by releasing it you have risked patient safety and may need to recall.
Q. In what order should I review information from electronic batch records?
A. I think we need to be clear on what we are discussing when releasing the batch record. Certainly, it includes a review of the incoming raw materials that include the active ingredient(s), excipients, primary packaging, and labeling.
21 CFR Part 11 Compliance
The batch record process for 21 CFR Part 211 compliance should verify these items were properly received and sampled. Nevertheless, each item should be put into quarantine until the incoming quality group established their suitability for use. Finally, this includes testing of the water used in manufacturing the product.
Critical to Quality
The review should confirm that all the materials used were appropriately discharged. Equally important, using calibrated equipment in a suitable environment. Without a doubt, cleaning manufacturing rooms before the start of the batch is critical to quality (CTQ).
FDA Electronic Signatures
The main focus of 21 CFR Part 11 compliance should be the details of the batch manufacturing itself. For instance, attention needs to be paid to make sure that any deviations during this phase of production have been resolved. In contrast, it is also important for FDA electronic signatures to ensure operators signed in the appropriate places indicating they performed the work.
21 CFR Part 11 Summary
Finally, there should also be an indication that another employee or a supervisor who witnessed the work. This is particularly important when verifying the right ingredients were discharged to the line to make the right product with the right dosage amount.
Lastly, many companies use a checklist to make sure all the elements of the master batch record are included in the product batch record. This is a widely accepted current good manufacturing practice (CGMP) in the pharmaceutical industry. Therefore, you should have confidence in releasing product batches when coupled with a thorough review of the contents.
Article details
Pharmaceutical Technology
Vol. 46, No. 12
Pages: 34
About RCA’s Pharmaceutical Services
Regulatory Compliance Associates (RCA)® has helped thousands of pharmaceutical companies meet regulatory, compliance, quality assurance, and remediation challenges. With more than 20 years of experience with FDA, Health Canada, EU and global regulatory agencies worldwide, RCA offers leading pharmaceutical consultants that can help you navigate through the challenges associated with evolving industry regulations.
Our team of over 500 seasoned FDA, Health Canada and EU compliance consultants and regulatory affairs experts can understand the complexities surrounding the pharmaceutical industry and the unique inner workings of the regulatory process.
Client Solutions
Whether you’re in the product planning, development or pharmaceutical lifecycle management stage or need a remediation strategy for a compliance crisis, RCA® Inc. will guide you through every step of the regulatory process and create a customized approach depending on your product and your pharma company’s individual needs. Our clients include:
- Companies new to FDA, Health Canada or EU regulations and the pharmaceutical industry
- Start-up organizations with novel submissions to 510(k) submissions from multi-national corporations
- Investment firms seeking private equity due diligence for pre-acquisition and post-deal research
- Law firms seeking expertise in the remediation of warning letters, consent decrees, 483’s or import bans
Regulatory Affairs
Regulatory affairs is Regulatory Compliance Associates® Inc.’s backbone and we fully understand the complexities of the pharmaceutical and biopharmaceutical industries. Our expertise spans all facets and levels of Regulatory Affairs, from Regulatory Support for New Products to Life Cycle Management, to other services like Outsourced Regulatory Affairs, Submissions, Training, and more.
As your partner, we can negotiate the potential assessment minefield of pharmaceuticals with insight, hindsight, and the clear advantage of our breadth and depth of knowledge and experience. We offer the following four regulatory affairs services for pharmaceutical companies.
- New Product Support
- Product Lifecycle
- Other Regulatory Services
Compliance Assurance
The regulations process surrounding pharmaceutical companies can be tricky for even the most experienced industry veteran to understand, and just one misstep could mean significant and lasting consequences for your business. At RCA® Inc., we offer the experience and resources necessary to guide you in quality compliance.
- Assessments
- Audits
- Regulatory Agency Response
- Preparation and Training
- Inspection Readiness
Quality Assurance
Regulatory Compliance Associates® Inc.’s Quality Assurance services include assessments, strategy, implementations, staff augmentations, and identification of quality metrics to ensure continuous improvement, aligning with your business needs and goals. Our consultants are quality experts with experience spanning major corporations and start-ups. We know firsthand how to achieve, maintain, and improve quality, and we excel in transferring this knowledge to your organization.
- 21 CFR Part 11
- Data Integrity
- Manufacturing Support
- Facility Support
Remediation
Regulatory Compliance Associates® Inc. has significant experience and a proven approach to managing FDA Warning Letters, Consent Decrees, Remediation and other serious regulatory situations. We know how to partner with executive, legal, and communication teams, and will assist management with a response that will be accepted by the regulatory agency and be realistic to execute.
We can develop a comprehensive proof book of documented objective evidence demonstrating the corrective actions taken to remediate non-compliant issues. In addition, RCA can help prepare a comprehensive strategy to assist in your remediation efforts, drive continuous improvement, and maintain compliance with the regulations.
- Regulatory Action
- Warning Letter
- 483 Observation
- Oversight Services
About RCA
Regulatory Compliance Associates® (RCA) provides regulatory compliance consulting to the following industries for resolution of compliance and regulatory challenges:
We understand the complexities of running a life science business and possess areas of expertise that include every facet of R&D, operations, regulatory affairs, quality, and manufacturing. We are used to working on the front lines and thriving in the scrutiny of FDA, Health Canada, MHRA and globally-regulated companies.
As your partners, we can negotiate the potential minefield of regulatory compliance and regulatory due diligence with insight, hindsight, and the clear advantage of our unique expertise and experience.
- Founded in 2000
- Headquartered in Wisconsin (USA)
- Expertise backed by over 500 industry subject matter experts
- Acquired by Sotera Health in 2021
About Sotera Health
The name Sotera Health was inspired by Soteria, the Greek goddess of safety, and reflects the Company’s unwavering commitment to its mission, Safeguarding Global Health®.
Sotera Health Company, along with its three best-in-class businesses – Sterigenics®, Nordion® and Nelson Labs®, is a leading global provider of mission-critical end-to-end sterilization solutions and lab testing and advisory services for the healthcare industry. With a combined tenure across our businesses of nearly 200 years and our industry-recognized scientific and technological expertise, we help to ensure the safety of over 190 million patients and healthcare practitioners around the world every year.
We are a trusted partner to more than 5,800 customers in over 50 countries, including 40 of the top 50 medical device companies and 8 of the top 10 pharmaceutical companies.
To begin the Regulatory Compliance Associates® scoping process today, please enter your information in the blue form below and click the submit button at the bottom of the webpage.