Batch production record, specification

Documentation and records (systems, specifications, raw materials, intermediates, labeling, packaging materials, master production and batch records, laboratory control records, batch production record review)... 

In the United States, drug GMPs were formally introduced in 1963 and included the regulation of computer systems. 21 CFR Part 211.2(b) emphasized computer backups and documentation, including keeping hardcopy of master formulas, specifications, test records, master production and control records, batch production records (batch production and control records), and calculations. 

Standard operationg procedures (SOPs) incomplete, not current, or not available to the operators in the production area Batch production records incomplete, not recorded at time of operation, or not specific enough to document significant process steps Cleaning procedures not validated or not including all processing equipment and transfer implements (scoops, etc.)... 

Mother liquors containing recoverable amounts of excipients are frequently re-used. Secondary recovery procedures for such excipients are acceptable providing the recovered excipient meets its specifications and recovery procedures are indicated in batch production records. Secondary recovery procedures for reactants and intermediates are acceptable provided that the recovered materials meet suitable specifications. 

Strict controls should be exercised over labels issued for use in labeling operations. Labels issued for a batch should be carefully examined for proper identity and conformity to the specifications in the master or batch production records. The results of this examination should be documented. 

Any aspect of producing an API, from the receipt of all incoming materials from outside vendors right through to the last distribution of released material, must be appropriately recorded. Systems must be in place so that each specific lot of intermediate or API is reviewed and approved by QC before it is released. Effective systems need to be in place to both detect an unexpected result, and then to investigate it. Batch production records, or a sound sampling thereof, as well as all other quality related records such as stability data complaints and so forth should be reviewed at least annually to ensure that in-process controls, procedures, and final product specifications are adequate and tightened where appropriate. 

The instructions embedded in computer program(s) either provide information on what the operators are supposed to do, or information on how the equipment or processes are intended to function. For example, for manufacturing operations, the batch production and control records may provide procedures, controls, instructions, specifications, and precautions to be followed when using computer systems. These programs may also contain control data for product formulation, batch size, yields, and automated in-process sampling/testing procedures. 

Some products have specific control requirements for the environment, as indicated during development. Relative humidity, temperature, and even light-level restrictions are parameters that may need to be controlled. If there are control requirements, they should be indicated in the batch record. Documenting the actual results of environmental conditions should be a requirement of the batch record. This can be accomplished by either routine monitoring with a calibrated instrument and then recording these results on a log sheet or by attaching data generated by a recorder (e.g., strip chart, circular chart). 

CFR Part 210 and Part 211 specifically sections 211.186, Master Production and Control Records, and 211.188, Batch Production and Control Records. 

Production records Processing records and production logs Product specification sheets for existing and new products Bleed runs used to purge equipment which cannot be cleaned before use Best-before dates or batch numbering systems... 

Drug product containers and closures specifications In-process materials Packaging material Labeling specifications Drug products specifications Procedures and specifications Batch production and control records, including Products from contractors Production records Packaging records... 

Sources of Information for Material Balance. There are many sources of information in establishing material balances for the various unit operations within the plant. Data may be obtained from sample analysis and measurements of raw input materials, raw material purchase records, material and emission inventories, equipment cleaning and validation procedures, batch composition records, product specifications, operating logs, standard operating procedures, and manuals. 

The decision to release a batch of sterile product for use should take account not only of the specific production records and results of tests performed on that batch, but also the cumulative test records and information gathered before and during its manufacture from the monitoring of the environment personnel, intermediate products, equipment and processes. 

Batch Packaging Records should be kept for each batch or part-batch processed and should be based upon the currently approved version of the Master Packaging Instruction and prepared from it by a method designed to avoid transcription errors (photocopying or some similar method is to be preferred). The Record should carry the quantity of bulk product to be packed, the planned quantity of finished product and should bear a batch reference number, which is specific to a particular packaging run. The batch number which appears on the finished product should be this number, or one which may be easily related to it... 

Any production, control, or distribution record specifically associated with a batch of API should be retained for at least one year after the expiration date of the batch. For APIs with retest dates, records should be retained for at least three years after the batch is completely distributed to either internal or external recipients. 

Written procedures should be established and followed for the review and approval of batch production, control, and laboratory records, including packaging and labeling, to determine compliance of the API or intermediate with established specifications before a batch is released or distributed. 

When carrying out a batch distillation on a binary mixture it is very useful to have a quick and user-friendly analysis of the overheads. It is even better if the analysis can be performed on the plant without the need to take a sample to the laboratory and the process operator has a continuous record of the progress of the batch. A record of this sort can be provided by an on-line specific gravity (i.e. density corrected for temperature) meter. Many binary pairs such as mixtures of methanol, acetone and THF with water have large density differences between the organic distillate and water. This property can be used to control the split between reflux and product flow rates. 

Production and service provision - Operate production and service provision under controlled conditions, maintain batch records, validation processes that cannct be verified, maintain identification and traceability of materials, address specific requirements for sterile products, provide suitable conditions for storage and distribution... 

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