Follow
1.0 OBJECTIVE
To lay down a procedure for execution of process optimization activity.
2.0 SCOPE
2.1 This procedure is applicable to all the products intended to be manufactured in (Company Name).
3.0 RESPONSIBILITY
3.1 QA/Validation shall be responsible for preparation of Process Optimization Protocol (POP) for each product.
3.2 Manger R & D, Manager Production, Manger QA, Manager QC shall be responsible for review of Process Optimization Protocol before finalisation.
3.3 Head of Quality/Designee shall be responsible for approval of Process Optimization Protocol.
4.0 ACCOUNTABILITY
4.1 Executive Director Quality.
5.0 PRECAUTIONS
NA
6.0 PROCEDURE
6.1 Preparation and approval of Process Optimization Protocol (POP)
6.1.1 Master formula record shall be referred during preparation of Process Optimization Protocol.
6.1.2 During preparation of POP following guidelines are taken into consideration.
6.1.2.1 The name, strength, Batch size, Ref. MFR, Batch number of the product, Product code and a description of the dosage form (Product Information).
6.1.2.2 The name, item code, A.R. number and standard weight or measure of each active ingredient per lot unit of the drug product and a statement of the total weight or measure of any dosage unit (master formula).
6.1.2.3 The name, item code and standard weight or measure of each packing material as per the master formula.
6.1.2.4 The name, identification no., Qualification reference no. of Equipment & Utilities and Process flow diagram as per the master formula.
6.1.2.5 Manufacturing, packing and control instructions, special notations and precautions to be followed.
6.1.2.6 Actual yields with percentages shall be recorded at conclusion of each stage of the manufacturing process. The final yield limit with percentages shall be determined after completion of the validation batches.
6.1.3 Process Optimization Protocol shall be written after thorough understanding of the procedures.
6.1.4 Critical process parameters of different dosage forms will be studied for target value and optimized below and above the intended process control specification.
6.1.5 Process Optimization Protocol shall be written in a clear, unambiguous language, which is easy to understand and follow and in an orderly fashion depicting the logical sequences in a procedure. Also the critical steps shall be highlighted.
6.1.6 QA/Validation shall prepare Process Optimization Protocol for each product by using the specimen Process Optimization Protocol template (Annexure – I).
6.1.7 Draft Process Optimization Protocol shall be stamped ‘DRAFT COPY” in blue ink at right side top corner of the document.
6.1.8 Draft Process Optimization Protocol shall be circulated through Head of R&D, Head of Production and Head of QC or their designee for review & comments (if any).
6.1.9 QA/Validation shall discuss comments if any, with concerned and make the necessary changes in draft Process Optimization Protocol.
6.1.10 QA/Validation shall prepare the final copy and assign sequential number as per the document numbering procedure (SOP No.: QA003) and get the signatures of the responsible staff.
6.2 Distribution and control of Process Optimization Protocol (POP)
6.2.1 After finalization of Process Optimization Protocol with all the departments, QA shall retain the original copy of Process Optimization Protocol.
6.3 Process optimization procedure
6.3.1 The selection of number of batches for process optimization shall be defined in individual protocol. All protocols shall be as per the Format given in Annexure – I.
6.3.2 A validation/optimization team comprising Production, Quality Assurance, R&D, Validation, Quality Control and Engineering responsible for conducting and or supervising process optimization studies.
6.3.3 The optimization activity shall be carried out according to authorized product specific Protocol. A comprehensive in depth optimization study will be done for product intended to supply to the highly regulated market. Products supplied to the local market only required to fulfill the local regulatory requirements.
6.3.4 For transfer of local product from Track-I, the trial batch manufacturing will be done to assess the suitability of manufacturing the product in the new facility. Once successful trial batch is manufactured then three process validation batches will be manufactured. However process optimization can be done before process validation if it is deemed to be necessary.
6.3.5 For products supplying in the highly regulated market, process optimization with the agreed API (e.g. DMF grade) to be done.
6.3.6 The product & stage (granulation, compression/coating/capsule filling/product concentrate manufacturing & filling, packing) specific protocol shall contain; Table of content (Index), approval, objective, scope, product details, optimization team, responsibility, optimization methodology, batch/batches under optimization, list of critical equipments & utilities, list of raw materials, process flow diagram, process stages, list of critical process parameters, control variables & measuring response /justification, manufacturing and packing process, sampling plan, test parameters, acceptance criteria, environmental control, list of packaging materials, batch yield, deviation summary, process summary and conclusion.
6.3.7 The qualification status of all-relevant equipment & system and status of calibration of different gauges, thermometers, sensors, balances, etc shall be verified.
6.3.8 Training should be given to supporting staff who shall perform the optimization and shall get engaged in manufacturing activities.
6.3.9 For blend uniformity / homogeneity sample analysis the sample size of the blend material should not be less than 1X and not more than 3X of the weight of the individual dose. Samples for blend uniformity analysis (BUA) to be collected either from the High shear mixer or IBC and at least two or more time points shall be selected for optimizing the mixing time. The samples from multiple locations (Considering top, middle and bottom layer) shall be collected using sampling thief in multiple vials specifying the product name , batch number, stage of the sampling, locations, sets, tare weight, sample weight & vial number with appropriately signed & dated. These vials shall be closed and sent to QC for analysis. Based on the analytical results the mixing or blending/lubrication time to be fixed for process validation batches.
For manufacturing common blend/granules the sample quantity shall not be less than 1X and not more than 3X of unit dosage form of the lowest strength. Here X is average weight of the lowest strength of products.
For inhaler products based on the process optimization experience the slurry and product concentrate mixing time will be fixed for process validation batches.
6.3.10 %RSD value of drymix/blended samples collected for uniformity analysis during various process stage either ≤ 5.0 %(for first set sample) or ≤ 6.0 %(for second and third set sample including the first set sample).
6.3.11 %RSD value of finished products (core/coated tablets) collected for dose uniformity analysis should be used to clarify the testing results as either readily pass (RSD ≤ 4.0 %), marginally pass (RSD ≤ 6.0 %).
