Batch processes documentation procedure

A system for determining the day-to-day status of critical systems, areas, and activities will be developed. Activities such as batch production, cleaning, preventive maintenance, calibration, load sterilization, etc. will be controlled and documented by procedure in logbooks and reviewed and filed as critical processing documentation. 

The size of the quality organisation and the extent of documented procedures will vary according to the size of company. Independent of size there should be an appreciation that quality systems must be formalised to ensure material consistency. Each manufactured batch must be subjected to the same control, ideally involving pre-running start-up checks, in-process SPC... 

Process documentation— An often overlooked activity wherein the results of the development effort are delineated in sufficient detail in process documentation so that the variations in the process as a result of inadequately defined procedures are eliminated. While master batch records have long been a CGMP requirement, their adequacy is essential to the maintenance of a validated state. 

Earlier, the need for a master batch record document was discussed. This document describes the manufacturing instructions necessary to consistently produce batches of APIs that meet predetermined specifications. There will also be ancillary procedures, which wiU define all the conditions and their control parameters necessary to assime consistency from batch to batch. Isolated materials should be labeled at each step in the process. This is true not only for the raw materials but also as in-process materials are generated and isolated, the material s name, lot niunber, and its status should be clearly labeled. As stated earlier, major pieces of equipment should be clearly labeled with a unique identification number and its status (cleaned and ready to be used, to be cleaned, or in use). If a processing step is determined to be a critical processing step, it may require witnessing of its completion by a second person, with the witnessing docmnented on the batch record. 

Materials, processes, and control parameters for drug production are stated in written documents. Production personnel follow procedures and record materials used, amounts weighed, and date of operation. Equipment, reaction vessels, and the production area are cleaned and their status recorded in logbooks. Throughout the production stages, equipment conditions (e.g., pH, pressure, stirring speed, and temperature) are also recorded. Adjustments to in-process control parameters, if permitted, are entered onto batch records. 

Process simulations can be aborted for any reason that, according to procedure, would also lead to discontinuation of a production batch. However, clear documentation of the event(s) that caused discontinuation of the process simulation shall be performed and maintained. 

Operational and maintenance plans should be prepared for the computer system and its associated measurement and control instrumentation. Operational plan review will focus on system reliability, performance, diagnostic records, instrument and system I/O calibration, and the provision of critical data to support the batch record. Procedures for controlling the system (e.g., system management, security, and process operations) should be reviewed to verify that they are current, in place, and being followed. For each procedure required for the system there should be documented evidence that the relevant operatives have been trained in its use. All procedures must be written and approved according to the site procedures for writing and approving SOPs. 

Proper production process execution and performance of analytical procedures relies on comprehensive, clearly stated, and unambiguous documentation. This is necessary whether the document is used to initiate an activity (e.g., process, method, work instruction) or contains results that will be reviewed by someone else. A master batch record that can be easily misinterpreted by trained operators is a serious source of process variability. Similarly, if the analytical method is not written in a clear, concise, and sufficiently detailed manner, interpretation may be different from analyst to analyst, also resulting in higher than expected variability and perhaps an OOS result. Process and analytical documentation should be written with the user in mind and authored by individuals with intimate familiarity with the task to be carried out. The written procedures should be concise or crisp, yet contain sufficient technical detail to lead trained operators and analysts through the same set of operations with the outcome being the same when applied to the same material(s). 

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.)... 

Finally, there is the need for proper documentation, which can be in written or electronic forms. These should cover every step of the measurement process. The sample information (source, batch number, date), sample preparation/analytical methodology (measurements at every step of the process, volumes involved, readings of temperature, etc.), calibration curves, instrument outputs, and data analysis (quantitative calculations, statistical analysis) should all be recorded. Additional QC procedures, such as blanks, matrix recovery, and control charts, also need to be a part of the record keeping. Good documentation is vital to prove the validity of data. Analyt-... 

As part of the preparation for creating the CMC document, the chemical development organization (or the manufacturing organization if technology transfer has already occurred) usually produces a minimum of three large-scale batches of the subject API using the procedure to be filed in the CMC documents. The results of this three-batch exercise demonstrate that the process operation and API quality are consistent with the criteria established for the CMC document. 

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