1 / 22

Validation Part 3: Process validation

Supplementary Training Modules on Good Manufacturing Practices. Validation Part 3: Process validation. Validation. Objectives To review: Validation, risk analysis, and critical steps of processing Points to consider in process validation of: solid dose mixing tablet compression

nixie
Download Presentation

Validation Part 3: Process validation

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Supplementary Training Modules on Good Manufacturing Practices Validation Part 3: Process validation

  2. Validation Objectives To review: • Validation, risk analysis, and critical steps of processing • Points to consider in process validation of: • solid dose mixing • tablet compression • sterilization • Finalization of validation

  3. Validation Introduction

  4. Validation Reliable, repeatable, under control • At least first 3 consecutive batches - repeatable • Must investigatefailures • The rationale should be documented if experimental method is changed • document deviations, decisions and reasoning • Does not improve processes • Should not validate bad processes

  5. Validation Design user or process requirements Install installation qualification Operate operational qualification Validate performance qualification and process validation Review periodically (+ change control) DQ, IQ, OQ and PQ

  6. Validation Critical factors or parameters • Need to be determined • Need to be monitored during validation • May affect the quality of the product

  7. Validation Setting Limits • Marketing authorization limits • stability specifications • Release specification • Validation limits Marketing authorisation limitsbased on stability specifications Batch release limits Validation limits

  8. Validation Determining critical control pointexample of a tablet granulation process • Particle size distribution of the active(s) • Blending time for the powder • Granulating time and speed, • Amount of granulating fluid-binder concentration • Drying time - final moisture content, granule particle size distribution • Granule active content and homogeneity, blending time of external phase

  9. Validation Determining critical control points

  10. Validation Solid dose mixing (1) • Homogeneity in blending – the key to quality! • Sampling strategy • Sample site, label, container • Storage • Transport • Sample thief

  11. Validation Solid dose mixing (2) • In situ analysis • Methods of analysis • Statistical analysis • inter-batch • intra-batch • within-sample-site

  12. Validation Tablet compression variables • Fill volume • Pre-compression force, compression force • Turntable speed • Dwell time • Granule size and feed • Ejection force, lubrication

  13. Validation Tablet compressionparameters • Mass • Hardness • Moisture • Friability • Disintegration • Dissolution • Thickness Tablet coating variables • Spray rate • Inlet andoutlet air temp • Coating weight

  14. Validation • Lethality of cycle • D value • Z value • F value • Fovalue min 8 Moist heat sterilization “Z”

  15. Validation Sterilization validation (1) • Sterility test • Physical measurements • Chemical and biological indicators • Loading patterns

  16. Validation Sterilization validation (2) • Cooling fluid or gas • Automated process • Leak tests • Control instrumentation • Steam quality • Heat distribution

  17. Validation Dry heat sterilization • Parameters • Air circulation, positive air pressure, HEPA filter • Advantages • microorganisms destroyed • depyrogenation possible • Disadvantages • poor heat transfer • higher temperatures for long periods

  18. Validation Process variation Controllable causes of variation may include: • Temperature, humidity • Variations in electrical supply • Vibration • Environmental contaminants • Light • Human factors • Variability of materials • Wear and tear of equipment

  19. Validation Change control • Must be a review procedure for validated processes • From time to time changes may be necessary • Documented change control procedure needed • “Like for like" changes do not require re-validation

  20. Validation Mixing validation liquid and solid dose change control and scale up • Mixer type and size • Batch size • Pilot study scale up • Limit on the proportion of the scale up

  21. Validation Finalization of validation process • Final report required • Summarize and reference protocols and results • Conclusion required: “Is the process valid” • Final report should be reviewed and approved by • the validation team • “authorized person”

  22. Validation Group Session • You are given a tablet manufacturing flow chart to study • List the critical steps that are required to be validated • List the critical equipment required to be qualified • Identify the variables and construct a table as directed

More Related