SOP for Process Validation Program
1.0 OBJECTIVE:
To lay down a procedure for process validation of products to ensure that a specific process will consistently produce the product meeting its pre-determined specifications and quality attributes.
2.0 SCOPE:
The scope of the Standard Operating Procedure (SOP) covers the procedure for performing the process validation of products and requirements to be covered in protocol approval, Protocol issuance, report preparation, Summary preparation and certification for the product under process validation.
3.0 RESPONSIBILITY:
3.1 Quality Assurance (QA) personnel to prepare Protocol in coordination with Production & Pharma research and compilation of report.
3.2 QA to execute the validation protocol in coordination with Production.
3.3 IPQA personnel to perform sampling as per the protocol.
3.4 Quality Control (QC) laboratory to analyze the samples and report the results.
3.5 Head Production and Head QA to review and approve the protocol and report or in conjunction with pharma research (need based).
4.0 PROCEDURE:
4.1 Definition:
4.1.1 Process Validation: Documented evidence which produce high degree of assurance that a specific process will consistently produce product meeting its predetermined specification and quality characteristic.
4.1.2 Based on the time when the particular validation is performed shall be classified in to the following:
4.1.2.1 Prospective Validation: Validation carried out during the development stage by means of a risk analysis of the production process, which is broken down into individual steps. These are then evaluated on the basis of past experience to determine whether they may lead to critical situation.
4.1.2.2 Concurrent Validation: Validation carried out during routine production of product intended for sale. This is carried out for product, which is rarely manufactured and costly. This involves validation of one successful batch with extensive sampling.
4.1.2.3 Retrospective Validation: Involves the examination of past history of production on the assumption that the composition, procedure and equipment remain unchanged.
4.1.2.4 Re-validation: Involves the repeat of the initial process validation to provide assurance that change in the process and or / in the process environment whether intentional or unintentional, do not adversely affect process characteristics and product quality.
4.2 Methodology:
4.2.1 Preparation of Protocol.
4.2.1.1 The content which shall be covered under the Process Validation
Protocols are as under but not limited to this,
• Protocol Approval sheet
• Index
• Objective
• Scope
• Overview
• Responsibility
• Procedure
• Batches under validation
• List of equipment with identification number and capacity details, calibration schedule.
• List of raw materials and standard quantity.
• Process flow diagram with various processing stages and sub stages, control variables (as whatever applicable).
• Sampling plan and procedure
• Environmental control during various stages.
• Training record of personnel.
• Summary and conclusion.
• Report Approval
4.2.2 Sampling Procedure to be employed during process validation/ or as per Technical Analytical Document (TAD) (whichever Applicable).
4.2.2.1 Sampling of the blend shall be done as per the sampling plan in individual protocol but following shall be considered in general
• At least 10 sampling location shall be identified while sampling of the blend from mixer.
• At least 3 replicate samples from each location shall be collected. Sample size shall be based on the process and product requirement, which may vary from 1X to 10X (i.e. Dosage unit range). Samples quantity larger than 3X can be used with adequate justification.
4.2.3 The various process variables and product variable which may be evaluated during process validation are as under
4.2.3.1 The various process parameters (whichever applicable) to be evaluated during Granulation stage shall be Time, Speed, FBD inlet temperature, Drying Time etc. The various product variables (whichever applicable) to be verified are LOD, Ampere Load at the end point, Blend uniformity, Bulk density, etc. as per formulation need.
4.2.3.2 The various process parameters (whichever applicable) to be evaluated during Compression stage are Compression force, Speed of compression machine. The various product variables (whichever applicable) to be verified are Appearance, Average weight, Uniformity of weight, Hardness, Friability, Thickness, Disintegration, Dissolution, Assay etc., along with the limits shall be mentioned.
4.2.3.3 The various process parameters (whichever applicable) to be evaluated during Coating stage are Air pressure, RPM peristaltic pump, Bed temperature, inlet air temperature, spray rate, coating pan rpm etc. along with the limits according to BMR and Product specification. The various product variables (whichever applicable) are Appearance, Average weight, Weight gain, DT, etc.
4.2.3.4 The various process parameters (whichever applicable) to be evaluated during Capsule filling are speed of the machine, size of the capsule, etc. The various product variables (whichever applicable) are Appearance, Average weight, DT, Lock Length, Uniformity of weight, etc.
4.2.3.5 Study and sampling details of the Tablet / Capsule Packing machine at maximum and minimum speed when sealing temperature is maximum and minimum.
4.2.3.6 Any other process variables shall be studied.
4.2.4 Process Validation Protocol numbering shall be done as per the sop for Document numbering system.
4.2.5 All the equipment/ systems/ facilities to be used during the process validation shall be qualified.
4.2.6 Calibration status of all the applicable instruments shall be confirmed.
4.2.7 Process validation for a product shall include the testing of the extremes of the ranges of the desired process parameters.
4.2.8 The process validation protocol shall be written/ prepared and approved prior to starting manufacturing.
4.2.9 Process validation Protocol shall be prepared according to Master Manufacturing Document (MMD) / Technical Manufacturing Document (TMD) / Batch Manufacturing Record (BMR) and Product Specification. With a Reference of code Number and Specification number wherever applicable.
4.2.10 Protocol number, effective date of execution of protocol, Overview, objective and scope shall be given in the protocol.
4.2.11 Details of responsibility for protocol preparation and approval shall be mentioned in individual protocol.
4.2.12 In general, a minimum of three consecutive full-scale batches / Validation Batches shall be taken for process validation.
4.2.13 Validation batches can be released for distribution once all validation data has been reviewed and on the basis of Stability data if found acceptable by Head-QA.
4.2.14 Process validation shall be done for each strength and batch size of each product. Protocol and report shall be prepared separately.
4.2.15 Any deviation in process validation shall be justified and shall be duly approved by Head QA.
4.2.16 A product/process will be considered validated when Validation batches meet the acceptance criteria established in the validation protocol.
4.2.17 If a batch fails to meet acceptance criteria established for that particular product a full investigation of the cause of failure must be conducted and corrective action shall be taken and shall be implemented.
4.2.18 The decision regarding repeat the batch manufacturing, to implement a process change or repeat the sample analysis shall be made by Head QA, and Production and it will be based on the findings of the investigations. If required necessary inputs shall also be taken from Pharma Research (need based).
4.2.19 Validated processes are considered to be in a state of control. As long as conditions and control parameters unchanged, they continue in their validated state. Any changes must be handled through a change control program. The changes will be reviewed by change control committee.
4.2.20 Re-validation will be performed under following criteria depending upon the recommendations of change control committee.
4.2.21 Criteria for re-validation but not limited to this,
• Change in Batch Size.
• Change in location of product manufacturing site.
• Change in Major Equipment or major part of the equipment impacting the product quality.
• Change in Manufacturing formula.
• If there is any change in the Regulatory requirements.
• Periodic re-validation shall be done at a frequency of once in five years.
5.0 ANNEXURES :
Nil