Protocol Approval :
Protocol shall be prepared by Quality Assurance or Technology Transfer department and Shall be Reviewed by Production, Quality Control, Regulatory affairs (for regulatory filling) , Qualified person or customer (if required) and Approved by Quality assurance. Before start of the activity protocol shall be approved and Training shall be imparted to the concern personnel .
Reason for Validation :
Reason for validation contains why validation has to performed or taken for __________product.
The objective of this protocol is to validate the manufacturing process [i.e Blend, compression and coating] of Product ______________ by studying three consecutive batches produced in accordance with the Batch Processing or Manufacturing Record using qualified equipments and utilities in production, ________ Company with location.
The scope of this protocol is limited to validate the manufacturing process Blend, compression and coating of Product ________ by using qualified equipments in Production Block, for a batch size of _______ Tablets equivalent to ______ Kg.
Reason for Validation :
First commercial Validation batches to US or Europe or other Market
Execution Team or Responsibility :
Identify representatives from different departments and record the same in Process validation Report. Responsibilities of various departments are given below. Production to Manufacturing of product as per batch record, Quality Assurance shall Monitoring, Sampling and reviewing the validation activities, Technology transfer for Process monitoring and Evaluation and Quality control for Testing of sample
Product Information :
Product Information shall contains Product name, generic name, storage condition, category i.e antibiotic or other etc and shelf life. For shelf life note shall be mentioned as Shelf life is tentative and will be re-ascertained based on the real time stability data.
Product description and Manufacturing Formula :
Raw materials to be used in the manufacturing shall be procured from the approved vendors and shall meet all the specifications.
Product description contains label claim, Batch size and Shelf life
Manufacturing formula contains Sr. Number, Item Code, Name of Ingredients, Specification, Label claim, Source of Ingredients, Qty. mg/ Capsule/tablet and Qty./Batch etc.
Process Flow Diagram :
Process Flow Diagram contains the processing steps of the product which include Dispensing of Materials, Sifting, Milling, Dry mixing , wet mixing, Drying, Blending, Compression or Capsule filling, Coating, Inspection etc.
Rational for selection of critical steps, its process parameters for validation and list of critical process variable :
Speed of blender (RPM) and blending time are the critical variables in blending process as step involves the blending of all the materials together,The speed of compression machine is critical in obtaining tablets of desired physical characteristics and the speed of machine affects the Weight variation and uniformity of dosage units, Coating involves Speed of coating pan, speed of peristaltic pump, Inlet temperature, Exhaust temperature, atomization pressure used during coating process are critical, needs to be controlled to have better uniformity in coating.
Critical Process Variables which includes CPP (Critical process Parameters) and CQA’s (Critical Quality Attributes). CPP includes Blending & Lubrication time and RPM of Blender, Compression and Capsule Filling machine speed etc. CQA’s includes Blend Uniformity (BU), Dissolution, Uniformity of dosage units by mass variation and Related substances.
List of equipment / instruments used :
List of equipment / instruments used in the Manufacturing process, Operation SOP Number, Qualification status, Calibration status and Preventive maintenance status etc and same shall be recorded in report.
Sampling and Testing plan :
Sampling and Testing plan which contains the Variables like Blender speed and Blending time in Blending stage, Different speed challenges and Hopper Study at Compression and Capsule Filling Stage, pan speed, spray rate, Inlet temperature and exhaust temperature at Coating stage.
Sampling plan which includes Quantity of sample to be collected in each stage
Control/Evaluation parameters which includes Blend uniformity, assay, Loss on Drying, Bulk and tapped density, Sieve analysis etc. at blend stage and Assay, Uniformity of dosage units (by mass variation), Dissolution and complete analysis at compression and capsule Filling stage and coating stage.
Environmental Control :
It includes the temperature and Relative Humidity which is required at Dispensing / Sifting / Blending/compression/capsule filling/coating/inspection stage
Batch Yield at Various Stages :
The details of yield at all stages of the manufacturing shall be recorded in the report i.e at Blend , Compression, capsule filling, Coating and inspection stage etc.
Stability Study Requirement :
Batches of finished drug product of ____________ will be kept on stability as per the stability protocol. It specifies the required numbers of batches to be taken for stability.
Review of deviation, out of trend results, out of specification results and CAPA:
Any observation or change that is required to be made in the Validation batch shall be noted in the history sheet of the Batch record. The change shall be noted in the report.
Change control will be raised for any changes to be done in specifications or in the BAtch record based on the data of the Validation batch, with scientific justification without affecting the registered specifications of the product.
The manufacturing process of __________ shall be revalidated as per SOP whenever there is a change in manufacturing formula / manufacturing process/ Ingredient manufacturer / manufacturing equipment / manufacturing site. The implementation of these changes shall be carried out as per change control system.
Summary and conclusions:
Conclusions shall be made on the validity of the manufacturing process in individual runs and on the three consecutive validation runs. It is based on the result obtained after execution of the batches which includes the critical parameters and shall be recorded in the Validation report.
Reference Documents :
Reference Documents shall include Master Formula record, Batch Manufacturing record, Specification (Blend, Intermediate & Finished etc.) which are required in the batch or product. Always referred current version of all documents.
Mention the Abbreviation of the words used in the protocol for easy understanding and for better clarity.