Chapter 42: Master Batch and Completed Batch Records

Clearly written, detailed batch records are critical to ensuring product quality. The master batch record (MBR) accurately describes the production processes required to make the product the same way every time, to meet the defined product specifications. MBRs are written and approved by the department that manufactures the product and are approved by the quality unit (QU). MBRs should be written to precisely describe the required information for trained operators to execute consistently.

Issuance

The MBR contains a section for documenting issuance of production batch records (PBRs) generated from the MBR. This section provides signature spaces for the person who generated the PBR and for a second person who verifies the PBR. Their signatures indicate that the PBR is of the correct current version and that it is an accurate, legible copy of the MBR.

Yield

Include the expected (theoretical) yield at key processing steps in the MBR. Actual yields are tracked in the PBR to ensure that product is not unexpectedly lost in processing. Production yields should be predictable, within acceptable tolerances, if the manufacturing process is in control. Calculation of percentage of theoretical yield is performed by one person and verified by a second person. If the percentage of theoretical yield is not within the defined range, an investigation is conducted to determine the reason for the unexpected result.

Critical Step Verification

Significant processing steps that are critical to product quality should be verified by a second person to ensure that they are performed in accordance with the batch record, creating product that meets predetermined specifications. For example, addition of materials to a batch of product is performed by one person and verified by a second person.

Processing Instructions

The instructions in the MBR for making the product should include identifying information describing the product, a list of all of the materials that are used to make the product, including quantity, and the location and equipment used to make the product. The identifying information can include the name of the product, the processing step (for example, fermentation of product X), the concentration or strength of the product, and an identification number.

The MBR includes processing steps in the order in which they must occur. Identify any critical processing parameters that could impact product quality and the allowable ranges around these parameters that must be maintained, such as pressure, temperature, elapsed time, and speed in revolutions per minute. Example: Set centrifuge to run for 15 ± 1 minutes at 7500 ± 200 rpm.

The MBR includes in-process samples that are taken to check product quality against defined acceptance criteria. Conductivity or pH is frequently checked during processing to determine if the levels are appropriate before performing the next step. Example: pH acceptance criteria is 6.8 ± 0.2.

The processing instructions include packaging and labeling requirements. The primary packaging (product container) and secondary packaging (cartons, shipping boxes, and shrink-wrap) are included in the list of materials required for the batch. Labeling text is documented to ensure that the product is accurately identified. Requirements for the label material are included that describe the type of label that will adhere securely to the product while remaining legible throughout storage and distribution of the product to the customer.

Storage conditions of the intermediate or finished product, with any storage time limits, are included in the batch record to ensure that the product is stored in conditions (temperature, humidity, protection from light) that maintain the quality of the product.

Hold Times

Any time limits for processing steps, hold times between steps, and maximum length of time to perform the total process that could impact product quality are included in the batch record. Sampling and testing requirements to measure product attributes to determine whether the product meets specifications are included in the MBR. When a PBR is issued from the MBR, a unique identification number is assigned to the PBR, often called a batch number. The issuer signs and dates the PBR to indicate it is an accurate, legible reproduction of the approved MBR, and a second person reviews the PBR to confirm its accuracy.

Completed Batch Records

As the PBR is used to make a batch of product, several items need to be documented at the time the significant processing steps are performed:

• Date (and time, if important) of execution, with the date and initials of the persons who performed and checked the step

• Equipment used

• Weight, lot number, and actual quantity of materials used

• Actual measured values of the critical processing parameters

• Samples collected and results for in-process and release tests

• Actual yield where theoretical yields are identified

• Description of packaging, labeling, and labels, as well as a sample of the label

• Documentation of any deviation and its related investigation if the deviation has potential impact to product

Review and Disposition of PBR

The responsibility for review and disposition of the product by examination of the PBR should be defined in a written procedure. Production personnel are responsible for reviewing PBRs, ensuring they are completed and signed, and that any related deviations are documented and investigated.

QU personnel are responsible for reviewing and approving the completed batch records and releasing or rejecting product. Part of the QU’s review is to ensure that any deviations and related investigations that could impact product, and any out-of-specification (OOS) test results, are satisfactorily addressed. The QU ensures that the product complies with established specifications before any product is released from the organization’s control.