Process Validation

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By: Nikin (121 month(s) ago)

kindly give me such presentation becoz i have seminar on process[email protected]

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PROCESS VALIDATION 1 PROCESS VALIDATION Hardik Patel* Chirag Baladhiya , Paresh Desai, Parth Joshi Atmiya Institute Of Pharmacy,rajkot

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AIP PROCESS VALIDATION HARDIK PATEL 2 Contents Introduction Various regulatory requirements of validation When should a process be validated Types of process validation Priority for Process Validation Types of documentation . Process validation of some Pharmaceutical Processes

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AIP PROCESS VALIDATION HARDIK PATEL 3 Why Is Validation Required? Ø It would not be feasible to use the equipments without knowing whether it will produce the product we wanted or not. Ø Efficient use of resources is necessary for the continued success of the industry. The pharmaceutical industries are concerned about validation because of the following reasons. Ø Assurance of quality Ø Cost reduction Ø Government regulation Introduction

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AIP PROCESS VALIDATION HARDIK PATEL 4 Department /Designation Responsibility Manager Production Responsible for manufacturing of batches and review of protocol and report. Manager QC Responsible   for   analysis   of   samples collected Executive QC Responsible for samples collection and submission to QC Manager Maintenance Providing     utilities     and     engineering support Executive Production Responsible for preparation of protocol and manufacturing of validation batches Manager QA Responsible   for   protocol   authorization and preparation of summary report. Responsible Department

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Process Validation Process validation is defined as the collection and evaluation of data, from the process design stage throughout production, which establishes scientific evidence that a process is capable of consistently delivering quality products. The U.S. Food and Drug Administration (FDA) has proposed guidelines with the following definition for process validation: - “Process Validation” is establishing documented evidence which provides a high degree of assurance that a specific process consistently produces a product meeting its predetermined specifications and quality attributes” AIP PROCESS VALIDATION HARDIK PATEL 5

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AIP PROCESS VALIDATION HARDIK PATEL 6 General view of process validation

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AIP PROCESS VALIDATION HARDIK PATEL 7 Qualification Design Qualification (DQ) Defines the functional and operational specification of the instrument, program, or equipment and details the rationale for choosing the supplier. Installation Qualification (IQ) Demonstrates that the process or equipment meets all specifications, is installed correctly, and all required components and documentation needed for continued operation are installed and in place.

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AIP PROCESS VALIDATION HARDIK PATEL 8 Operational Qualification to provide a high degree of assurance that the equipment functions as intended. Component Operational Qualification of which calibration can be considered a large part. System Operational Qualification to determine if the entire system operates as an integrated whole. Process Performance Qualification: This verifies that the system is repeatable and is consistently producing a quality product. Performance Qualification (PQ) Demonstrates that the process or equipment performs as intended in a consistent manner over time. Test with materials like placebo

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AIP PROCESS VALIDATION HARDIK PATEL 9 Examples: Milling Qualification

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AIP PROCESS VALIDATION HARDIK PATEL 10 Examples: Compression Qualification

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AIP PROCESS VALIDATION HARDIK PATEL 11 • After finalizing formula, process, and specifications • Either before or after new drug application (NDA) Approval • Prefer to start during process development phase • More frequently being done before NDA approval/filing When To Validate

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AIP PROCESS VALIDATION HARDIK PATEL 12 Regulatory Requirements For Validation SECTION Deal with 21 CFR Parts 210 and 211. Current Good Manufacturing Practice Regulations for Finished Pharmaceuticals, Section 211.110 Sampling and testing of in-process materials and drug products. 21 CFR Part 820. Current Good Manufacturing Practice Regulations for medical device Section 211.113 Control of Microbiological Contamination.

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AIP PROCESS VALIDATION HARDIK PATEL 14 A) Prospective validation Also called as premarket validation Carried out prior to distribution of new product or existing product made under a revised manufacturing processes where such revision may affect product specification or quality characteristic B) Concurrent validation Study is carried out under a protocol during a course of normal production. It gives assurance of present batch being studied and offer limited assurance regarding consistency of quality from batch to batch. This may be practical approach under certain circumstances…. When previously validated process is being transferred to a third party contract manufacturer or to another manufacturing site. Where the product is a different strength of a previously validated product with the same ratio of active / inactive ingredients.

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AIP PROCESS VALIDATION HARDIK PATEL 15 C) Retrospective validation Conducted for a product already being marketed, and is based on extensive Historical data accumulated over several lots and over time. Some essential elements of retrospective validation:- Batches manufactured for a defined period Batch size/ strength/ manufacturer/ year Master manufacturing/ packaging documents Current specifications for active materials/ finished products List of process deviations, corrective actions and change to mfg documents Data for stability testing for several batches Trend analysis including those for quality related complaints

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AIP PROCESS VALIDATION HARDIK PATEL 16 All or a portion of validation that is required to be repeated when changes that affect original validation are made. Examples of changes requiring revalidation Changes to product specifications Process parameters Equipment (type, function, location, control system, major repairs) Raw materials Manufacturing materials Packaging material D) Revalidation

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AIP PROCESS VALIDATION HARDIK PATEL 17 Change Control Written procedures should be in place to describe actions to be taken if a change is proposed to a product component, process equipment, process environment, processing site, method of production or testing or any other change that may affect product quality or support system operations. All changes must be formally requested, documented and accepted by the validation team. The likely impact / risk of the change on the product must be assessed and the need for the extent of re-validation should be determined.

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AIP PROCESS VALIDATION HARDIK PATEL 18 Commitment of the company to control all changes to premises, supporting utilities, systems, materials, equipment and processes used in the fabrication/ packaging of pharmaceutical dosage forms is essential to ensure a continued validation status of the systems concerned. .

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AIP PROCESS VALIDATION HARDIK PATEL 19 Priority for Process Validation A. Sterile Products and Their Processes 1. Large-volume parenterals (LVPs) 2. Small-volume parenterals (SVPs) 3. Ophthalmics, other sterile products, and medical devices B. Nonsterile Products and Their Processes 1. Low-dose/high-potency tablets and capsules/transdermal delivery systems (TDDs) 2. Drugs with stability problems 3. Other tablets and capsules 4. Oral liquids, topicals, and diagnostic aids

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AIP PROCESS VALIDATION HARDIK PATEL 20 Validation Master Plan (VMP) Validation protocols (VP) Validation reports(VR) Standard Operating Procedures (SOPs) Types of Documentation

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AIP PROCESS VALIDATION HARDIK PATEL 21 The format and content should include: Introduction: validation policy, scope, location and schedule Organizational structure: personnel responsibilities Plant/ process /product description: rational for inclusions or exclusions and extent of validation Specific process considerations that are critical and those requiring extra attention List of products/ processes/ systems to be validated, summarized in a matrix format, validation approach Re-validation activities, actual status and future planning Key acceptance criteria Documentation format Reference to the required SOP’s Time plans of each validation project and sub-project. Validation Master Plan

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AIP PROCESS VALIDATION HARDIK PATEL 22 General information & Objective Responsibility Protocol Approval Validation Team Process Flow Chart Manufacturing Process Review of Equipments/ Utilities, Raw Materials and Packing Materials, Validation Procedure Sampling Location Documentation Acceptance Criteria Summary & Conclusion Validation Protocol

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AIP PROCESS VALIDATION HARDIK PATEL 23 Process validation of some Pharmaceutical Processes

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AIP PROCESS VALIDATION HARDIK PATEL 24 • Particle size of drug substance • Bulk density of drug substance/ excipients • Powder load in granulator • Amount and concentration of binder • Mixer speed and mixing times • Granulation moisture content • Milling conditions • Lubricant blending times • Tablet hardness • Coating solution spray rate Some Common Variables In The Manufacture Of Tablet Products

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AIP PROCESS VALIDATION HARDIK PATEL 25 Control Parameters Fixed Granulation Equipment Batch size Variable (Monitor) Mixing speeds Amount of granulation fluid Feed rate Granulation time Load Response (Test) Drug distribution Water/solvent content Appearance (size) Power consumption (amp/torque) Granulation

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AIP PROCESS VALIDATION HARDIK PATEL 26 Control parameters Fixed Bowl charge Porosity of filter bags Bowl sieve Variable (Monitor) Inlet/exhaust air temperature Product temperature Drying time Air volume Humidity of incoming air (dew point) Humidity of exhaust air Response (Test) Particle size distribution Densities Loss on drying Assay (for heat sensitive materials) Fluid Bed Drying

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AIP PROCESS VALIDATION HARDIK PATEL 27 Milling Variable Screen size Milling speed Feed rate Response Particle size distribution/shape Loose/tapped densities Control parameters

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AIP PROCESS VALIDATION HARDIK PATEL 28 Powder Blending Variable Blending time Blender speed Intensifier bar Response Content uniformity Assay Particle size distribution Powder flow Densification/Aeration

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AIP PROCESS VALIDATION HARDIK PATEL 29 Lubrication Variable Blender speed Blending time Method of addition Response Particle size distribution Loose/tapped densities Flow properties Tabletting characteristics (friability, hardness)

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AIP PROCESS VALIDATION HARDIK PATEL 30 Compression Variable Speed of press Pre-compression Compression force Feed frame (open/forced) Feeder speed Response Appearance Weight variation Hardness/friability Thickness Moisture content Disintegration/dissolution Assay/dose uniformity

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AIP PROCESS VALIDATION HARDIK PATEL 31 Pan Coating Variable Pan load Inlet/exhaust temperatures Inlet/exhaust humidities Pan speed Spray nozzle size Atomizing pressure Spray rate Spray angle Gun to bed distance Tablet core characteristics Response Percent weight gain Thickness Elegance Dissolution Assay Degradation level Residual solvent

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AIP PROCESS VALIDATION HARDIK PATEL 32 Focus on “newness” anything new like components or raw materials, equipment, process or package steps, dosage form • Adequate trials at full-size for new item • Assure raw material/component is from vendor’s routine production Complete review of pre-validation documentation Adequately identify cause and correct problems Data used in establishing operating ranges and specifications Data submitted to regulatory agencies Approaches to Improve Process Validation #1

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AIP PROCESS VALIDATION HARDIK PATEL 33 Approaches to Improve Process Validation #2 Handling out-of specification (OOS) results Identify if caused by equipment, product, normal process variation, or error or combination May require additional experimentation Pursue conservative approach, if unsure of cause Mechanism to bring development/validation issues to team management for resolution Review meetings Team approach Open, honest interactions

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AIP PROCESS VALIDATION HARDIK PATEL 34 Solution Studies of Ingredients Fill Uniformity Filter Compatibility Product Tubing Interaction Flush Volumes Cleaning / Sanitization Inert Gas Effectiveness Suspension Milling Mixing Viscosity Re suspendability Agglomeration Caking Emulsion Homogenization / Emulsification Viscosity Creaming Re emulsify Coalesce Globule Growth Liquid dosage form

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AIP PROCESS VALIDATION HARDIK PATEL 35 Semi solid dosage form Ointments / Creams Active Distribution Particle Size Mixing Emulsification Viscosity

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AIP PROCESS VALIDATION HARDIK PATEL 36 Study Question Short note on Process validation What do you mean validation and explain process validation in detail with special reference to Solid dosage form? Focus out the regulatory requirement of Process validation? Discuss type of process validation and types of documentation for process validation

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AIP PROCESS VALIDATION HARDIK PATEL 37 Referances I. R. Berry, R. A. Nash , Pharmaceutical Process Validation, Eastern Hemisphere Distribution, 3 rd edition 2003 Elsie J, Augustine O Review article:An Overview of Pharmaceutical Validation and Process Controls in Drug Development Tropical Journal of Pharmaceutical Research, December 2002; 1 (2): 115-122 Guideline on General Principles of Process Validation (, May 1987) Quality System Regulation, Title 21 Part 820 of the Code of Federal Regulations ( cfdocs / cfcfr /CFRSearch.cfm? CFRPart =820 (Apr 2003)

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