Process Validation in Manufacturing

PROCESS VALIDATION

DEFINITION documented evidence which Establishing provides a high degree of assurance that a consistently produce a specific process will product meeting specifications and quality attributes. its pre-determined (Validation of the individual steps of the processes is called the processvalidation.)

Process validation involves a series of activities taking place over the lifecycle of the product and process. This guidance describes process validation activities in three stages. Stage 1 Process Design Stage 2 Process Qualification Stage 3 Continued Process Verification

Stage1 Process Design : During this stage the commercial manufacturing process is defined based on knowledge gained through development and scale-up activities. Stage 2 Process Qualification: During this stage, the process design is evaluated to determine if the process is capable of reproducible commercial manufacturing. Stage 3 Continued Process Verification: Ongoing assurance is gained during routine production that the process remains in astate of control.

A successful validation program depends upon information and knowledge from product and process development. So that manufacturers should. Understand the sources of variation Detect the presence and degree of variation Understand the impact of variation on the process and ultimately on product attributes. Control the variation in a manner commensurate with the risk it represents to the process and product.

GENERAL CONSIDERATIONS FOR PROCESS VALIDATION An integrated team approach to process validation that includes expertise from a variety of disciplines. Project plans, along with the full support of senior management, are essential elements for success. All studies should be planned and conducted according to sound scientific principles, appropriately documented, and approved in accordance procedure with the established Homogeneity within a batch and consistency between batches are should be the goals of process validation activities.

Objectives To establish a record keeping system that considers all concept of manufacturing process which includes controlled testing. To evaluate all possible sources of variation in process. To identify all sources of variation those are possible from the materials, machines, methods and men. To evaluate the requirement for in-process testing and evaluation. To document everything that is done to follow establish procedures and protocols as closely as possible. Quality, safety and effectiveness must be designed and built in to the product. Quality must be assured.

WHEN IS VALIDATION NEEDED? Before introduction of a new method into routine use Whenever the conditions change for which a method has been validated, e.g., instrument with different characteristics Whenever the method is changed, and the change is outside the original scope of the method

WHEN SHOULD PROCESSES BEVALIDATED? The following model may be useful in determining whether or not a process should validated: A B C Is Process Output Verifiable Is Verification Sufficient & Cost Effective Verify & Control the Process YES YES NO NO E Redesign Product and/or Process D Validate

PROCESS VALIDATION: ORDER OF PRIORITY A) Sterile product and their processes 1. large volume parenterals 2. Small volume parenterals 3. Ophthalmics, other sterile products, and medical devices B) Non sterile products and their processes 1. low dose/ high potency tablets and capsules 2. drugs with stability problems 3. other tablets and capsules 4. oral liquids, topicals, and diagnostics aids

TYPES OF PROCESS VALIDATION Prospective ProcessValidation an experimental plan called the validation protocols executed before the process is put into commercial use. Most validation efforts require some degree of prospective experimentation to generate validation support data. Its is normally carried out in connection with the introduction of new drug products and their manufacturing processes.

Requirements meet cGMP Equipment requirements. / facilities should Personnel requirements. have an awakeness about the Critical processing stages and process variables are identified. At least one qualification trial (size x 100) made which shows that there is no significant deviation from expected performance of process. Batches should be run at different days, shifts and different quantities.

Retrospective Process Validation It manufacturing processes are considered stable and when on the basis of economic considerations alone and resource limitations, prospective validation programs cannot be justified. is chosen for established products whose Wherein the numerical in-process and/or end-product test data of historic production batches are subjected to statistical analysis. The equipment, facilities and subsystemsused in be connection with the manufacturing process must qualified in conformance with CGMP requirements.

Requirements Gather chronological sequence according to batch manufactured. all historical data of process/ product in Data should consists of atleast batches for analysis. last 20-30 manufactured Trim data by eliminating results of non-critical steps. Subject the resultant data to statistical analysis and evaluation. Draw the control charting & go for conclusion.

Advantages No additional samples necessory, only need history data. No additional testing required. Cost saving compared with prospective. No additional risk. No longer time need. Trained persons are easily available to perform the work. It can be adopted to various types of processes/ products. Well suited for existing product which are not validated previously.

Concurrent Process Validation It is in-process monitoring of critical processing steps and end-product testing of current production. It can provide documented evidence to show that the manufacturing process is in a state of control. It parameter and data sources disclosed in the section on retrospective validation. provides validation documentation from the test

Process Re-Validation: Required when there is a change in any of the critical process parameters, formulation, primary packaging components, raw material , major equipment or premises. Failure to meet product and process specifications in batches would also require process re-validation.

BASIC PRNCIPLE FOR PROCESS VALIDATION the individual qualification steps alone do not constitute process validation. 1. Installation Qualification (IQ) 2. Operational Qualification (OQ) 3. Performance Qualification (PQ)

1. Installation Qualification (IQ) Installation qualification establishes that the instrument is received as designed and specified, that it is properly installed in the selected environment, and that this environment is suitable for the operation and use of the instrument.

IQ considerations are: Equipment design features (i.e. material of construction clean ability, etc.) Installation conditions (wiring, utility, etc.) Calibration, preventative schedules. Safety features. Supplier documentation, manuals. Software documented. Spare parts list. Environmental conditions requirements, temperature, and humidity). functionality, maintanance, cleaning prints, drawings and (such as cleanroom

Operational Qualification (OQ): "Operational qualification (OQ) is the process of demonstrating that an instrument will function according to its operaational specification in the selected environment. The proper operation of equipment is verified by performing the test functions specified in the protocol. A conclusion is drawn regarding the operation of equipment after the test functions are checked and all data has been analyzed.

Following are the contents of equipment operation qualification: 1. Application S.O.P s, 2. Utilization List, 3. Process Description, 4.Test Instrument Utilized To Conduct Test, 5.Test Instrument Calibration, 6. Critical Parameters, 7. Test Function (List), 8. Test Function Summaries.

Performance Qualification (PQ): "Performance Qualification (PQ) is the process of demonstrating that an instrument consistently performs according to aspecification appropriate for its routine use ". PQ should always be performed under conditions that are similar to routine sample analysis. PQ should be performed on a daily basis or whenever the equipment is being used. In practice, PQ can mean system suitability testing, where critical key system performance characteristics are measured and compared with documented.

PQ considerations include: Actual product and process parameters andprocedures established in OQ. Acceptability of the product. Assurance of process capability as established in OQ. Process repeatability, long term process stability.

VALIDATION TEAM Personnel qualified by training and experience in a relevant discipline may conduct such studies. The working party would usually include the following staff members such as; Head of quality assurance. Head of engineering. Validation manager. Production manager. Specialist validation discipline: all areas.

VALIDATION LIFE CYCLE:

VALIDATION PROTOCOL The validation protocol should contain the following elements, Short description of the process. Summary of investigated. In process, finished product specification for release. Sampling plans. Departmental responsibility. Proposed timetable. Approval of protocol critical processing steps to be

THE VALIDATION REPORT The report should include at least the following Title and objective of study. Reference to protocol. Details of material. Equipment. Programes and cycles used. Details of procedures and test methods. Result. Recommendations on the limit and criteria to be applied on future basis.

IMPORTANCE OF PROCESSVALIDATION Improve the use of technology Improve the business benefits Improve operational efficiency Improve compliance with regulations Reduce the risk of failure Reduce the cost Process optimization Increased customer satisfaction

CONCLUSION: Validation is one of the important steps in achieving and maintaining the quality of the final product. If each step of production process is validated we can assure that the final product isof the best quality. Finally it can be concluded that process validation is a key element in the pharmaceutical product as the end product testing is not sufficient to assure the quality of finished product. quality assurance of

References: Sharma sumeet, Singh gurpreet. process validation in pharmaceutical industry: an overview . J Drug De & Therap; 2013, 3(4),184-88. Fraderick J. Carleton, James P . Agalloco ; validation of pharmaceutical processes; 2nd edition ,1999 New York ; page No.257-59. Berry IR, Nash RA. Pharmaceutical process validation. 2nd ed. 1993 Newyork: MarcelDekker.Inc.