CGMP on Production and Process Control PDF

CGMP ON PRODUCTION AND PROCESS CONTROL WHAT IS CGMP Good Manufacturing Practice (GMP) is that part of quality assurance which ensures that medicinal products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing au...

CGMP ON PRODUCTION AND PROCESS CONTROL WHAT IS CGMP Good Manufacturing Practice (GMP) is that part of quality assurance which ensures that medicinal products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorisation (MA) or product specification. GMP is concerned with both production and quality control. MASTER FORMULA A formally authorized master formula should exist for each product and batch size to be manufactured. The master formula should include: the name of the product, with a product reference code relating to its specification; a description of the dosage form, strength of the product and batch size; MASTER FORMULA COMPONENTS a list of all starting materials to be used ,with the amount of each, described using the designated name and a reference that is unique to that material (mention should be made of any substance that may disappear in the course of processing); a statement of the expected final yield with the acceptable limits, and of relevant intermediate yields, where applicable; statement of the processing location and the principal equipment to be used; the methods, or reference to the methods, to be used for preparing and operating the critical equipment, e.g. cleaning (especially after a change in product), assembling, calibrating, sterilizing, use; CONT detailed step-wise processing instructions (e.g. checks on materials, pretreatments, sequence for adding materials, mixing times, temperatures); the instructions for any in-process controls with their limits; where necessary, the requirements for storage of the products,including the container, the labelling, and any special storage conditions; any special precautions to be observed. PACKAGING - MASTERFORMULA Formally authorized packaging instructions should exist for each product, pack size and type. These should normally include, or make reference to: the name of the product; a description of its pharmaceutical form, strength and, where applicable, method of application; the pack size expressed in terms of the number, weight or volume of the product in the final container; CONTINUED a complete list of all the packaging materials required for a standard batch size, including quantities, sizes and types, with the code or reference number relating to the specifications for each packaging material; where appropriate, an example or reproduction of the relevant printed packaging materials and specimens, indicating where the batch number and expiry date of the product have been marked; CONTINUED special precautions to be observed, including a careful examination of the packaging area and equipment in order to ascertain the line clearance before and after packaging operations; a description of the packaging operation, including any significant subsidiary operations, and equipment to be used; details of in-process controls with instructions for sampling and acceptance limits. LINE CLEARANCE Before any processing operation is started, steps should be taken to ensure that the work area and equipment are clean and free from any Starting materials, products, product residues, labels or documents not required for the current operation. SOP- STANDARD OPERATING PROCEDURE All handling of materials and products, such as receipt and cleaning, quarantine, sampling, storage, labelling, dispensing, processing, packaging and distribution should be done in accordance with written procedures or instructions and, where necessary, recorded.  BATCH RECORDS An accurate reproduction of the appropriate master production or control record, checked for accuracy, dated and signed by authorized person Signifies authorization of production and the right formula is being used Batch numbers are assigned for traceability A numbering system to be in place approved by QA  BATCH RECORDS A batch processing record should be kept for each batch processed. It should be based on the relevant parts of the currently approved specifications onthe record. The method of preparation of such records should be designed to avoid errors. (Copying or validated computer programs are recommended.Transcribing from approved documents should be avoided.) During processing, the information should be recorded at the time each action is taken, and after completion the record should be dated and signed by the person responsible for the processing operations  BATCH NUMBERS THERE SHOULD BE AN SOP DESCRIBING THE DETAILS OF THE BATCH (LOT) NUMBERING SYSTEM, WITH THE OBJECTIVE OF ENSURING THAT EACH BATCH OF INTERMEDIATE,BULK OR FINISHED PRODUCT IS IDENTIFIED WITH A SPECIFIC BATCH NUMBER. THE BATCH NUMBERING THAT ARE APPLIED TO THE PROCESSING STAGE AND TO THE RESPECTIVE PACKAGING STAGE SHOULD BE RELATED TO EACH OTHER. THE SOP FOR BATCH NUMBERING SHOULD ENSURE THAT THE SAME BATCH NUMBERS WILL NOT BE USED REPEATEDLY; THIS APPLIES ALSO TO REPROCESSING. BATCH-NUMBER ALLOCATION SHOULD BE IMMEDIATELY RECORDED, E.G. IN A LOGBOOK. THE RECORD SHOULD INCLUDE AT LEAST THE DATE OF ALLOCATION, PRODUCT IDENTITY AND SIZE OF BATCH. BATCH RECORDS It is Documentation that each significant step in the manufacture, processing, packing or holding of the batch was accomplished including: Dates Identity of individual major equipment and lines used Specific identification of each batch of component or in- process material used. Weight and measures of components used in the course of processing In-process and laboratory control results A statement of the actual yield and a statement of the percentage of the theoretical yield at appropriate phases of processing BATCH CONTROL RECORDS Description of drug product containers and closures Inspection of the packaging and labeling area before and after use Complete labeling control records, including specimens or copies of all labeling used Any sampling performed Identification of the persons performing and directly supervising or checking each significant step in the operation Reconciliation of materials DEVIATION Deviation from instructions or procedures should be avoided as far as possible. If deviations occur, they should be in accordance with an approved procedure. The authorization of the deviation should be approved in writing by a designated person, with the involvement of the QC department, when appropriate. YIELD Checks on yields and reconciliation of quantities should be carried out as necessary to ensure that there are no discrepancies outside acceptable limits. Any significant deviation from the expected yield should be recorded and investigated Operations on different products should not be carried out simultaneously or consecutively in the same room or area unless there is no risk of mix up or cross-contamination.  STATUS LABELS At all times during processing, all materials, bulk containers, major items of equipment, and, where appropriate, the rooms and packaging lines being used should be labelled or otherwise identified with an indication of the product or material being processed, its strength (where applicable) and the batch number. Where applicable, this indication should also mention the stage of production. In some cases it may be useful to also record the name of the previous product that has been processed.  Any necessary in-process controls and environmental controls should be carried out and recorded. In-process controls are usually performed within the production area. The performance of such in-process controls should not have any negative effect on the quality of the product or another product (e.g. cross-contamination or mix up).  Normally, non-medicinal products should not be produced in areas or with equipment destined for the production of pharmaceutical products. FAULTY EQUIPMENT Means should be instituted of indicating failures of equipment or of services (e.g. water, gas) to equipment. Defective equipment should be withdrawn from use until the defect has been rectified. CLEANING Containers for filling should be cleaned before filling. Attention should be given to avoiding and removing any contaminants such as glass fragments and metal particles.  After use, production equipment should be cleaned without delay according to detailed written procedures and stored under clean and dry conditions in a separate area or in a manner that will prevent contamination Time limits for storage of equipment after cleaning and before use should be stated and based on relevant data.  Pipes used for conveying distilled or deionized water and, where appropriate, other water pipes should be sanitized and stored according to written procedures that detail the action limits for microbiological contamination and the measures to be taken. Checks should be carried out to ensure that pipelines and other pieces of equipment used for the transportation of products from one area to another are connected in the correct manner.  Measuring, weighing, recording, and control equipment and instruments should be serviced and calibrated at prespecified intervals and records maintained. To ensure satisfactory functioning, instruments should be checked daily or prior to use for performing analytical tests. The date of calibration and servicing and the date when recalibration is due should be clearly indicated on a label attached to the instrument.  Repair and maintenance operations should not present any hazard to the quality of the products. Access to production premises should be restricted to authorized personnel.  ANY QUESTIONS