Seminar onPresented by:- Guided by:-Mr. Avinash Mane Mr. S.G.KilledarM.Pharm (Q.A.- 1) Asso.Prof.in Pharmacognosy Bharati Vidyapeeth College of Pharmacy Kolhapur
ContentIntroductionDefinitionScope of validationImportance of validationTypes of validationLimitation of validationProcess validationTypes of process validationConclusionReferences.
IntroductionThe proof of validation is obtained through the collection and evaluation of data .Beginning from the process development phase and continuedthrough in to the production phase.validation is necessary include Process qualification, material,equipment, system, personnel.The control of the entire process for repeated batches or runs.
Definition“ Validation is a documented program which provide a highdegree of assurance that a specific process will consistentlyproduce a products to meeting it’s Pre-determined Specificationand quality attributes”
Scope of validationPharmaceutical validation is vast area of work and it practically coverevery aspect of pharmaceutical process activities. Following area oroperation will point out for pharmaceutical validation, Analytical test Product design. method. Equipment validation. Cleaning Instrument validation. calibration. Facilities. operator. Raw material. Manufacturing operation Process utility Packaging services. material.
Importance of validation Every activity in any business unit is done to get some benefit fromthat.Validation activity must give the industry some advantages, somebenefit & Some added value. Reduction Process of optimization Quality cost Assurance of Safety Quality
Reduction of quality cost : Preventive cost : To prevent failure or reduce the appraisal cost 1. Quality planning. 5. Process validation 2. Training. 6. Self inspection. 3. Calibration. 7. Documentation. 4. Sanitation 8. Review of data. Internal failure cost : Non-confirming material . 1. Reject. 3. Re-inspection. 2. Rework. 4. Re-test. External failure cost : Non- confirming condition after the product left the company ownership.1.Recall. 2. Complaints. 3.Return due to Quality problem
process optimization :Make the process effective, efficient, perfect or useful as possibleat the minimum cost.Trained qualified people are the key element in any process, thusgreatest impact on improving efficiency and productivity.In this content GMP training program that include how to do thejob correctly, easily and repeatedly.
Assurance of quality :Validation is a extension of quality assurance, in other wordsvalidation and process control are the heart of GMP.Without validated and controlled process it is impossible toproduce quality product consistently.
Safety : Validation can also result in increased operation safety.e.g. gauges used in equipment that is designed to operate at certain temperature, and pressure must be reliable i.e. they must be calibrated.
Limitation of validationValidation has a practical limit and related cost, hence while decidingthe limit of validation, we need to balance between the process costand the benefits derived from such limit.e.g. The cost of controlling weight variation in tablet or capsule, if 1 person keep limit of 5% & other person keep at limit 0.5% using high tech.& high cost. We must see what benefit, benefit is not much then we decide the limit.
Process validationDefinition:- “The collection and evaluation of data from the process design stage throughout production which establishes evidence that a process is capable of consistently delivering quality product”Process validation involves a series of activities taking place over thelifecycle of the product and process.
Phases of validation Design Qualification Installation Qualification Phases Of validation Operational Qualification Performance Qualification
Design qualification :Design qualification is the responsibility of the authorized projectteam.Responsible for the creation of the facility.People should be consist of various area like engineering, productionquality management, project, person etc.Senior knowledgeable and mature person should head of this team.E.g. Typical room data sheet contain following information. 1. Name of the room 6. Lighting intensity. 2. No. of the room. 7. Sound level. 3. Normal human population. 8. List of equipment. 4. Temp, Humidity. 9. Doors,window,surface. 5. Class of air. 10. Vacuum, steam, drainage.
Installation Qualification:The protocol is insure that the system equipment and its componentare installed correctly and to the original manufacturerspecification.Major calibration of equipment, accessory equipment, or utilitiesshould be performed in this step.
Operational Qualification:This step proceed after the installation qualification.This should be done mainly to see if there is any problem related tothe lighting, drainage, men and material movement, sewage andsanitation, cleaning and maintenance .
Performance Qualification:This is the final step of validation.Evaluate the premises suitability with : Equipment in operation. Material being handled. People working. Various sound may be produced. Dust is getting generated. Heat is getting generated. Filtered getting chocked.Take care of all possible practical problems.
Prospective Validation :Prospective validation is done during the Product developmentstage.When we developed a new mfg process and formula each stepwill be validated to achieve desire result.On the basis of past experience to determine whether they mightlead to critical situation.
Conti…Unsatisfactory process must be modified & improve until thevalidation exercise prove them to be satisfactory.Essential in order to limit the risk of error occurring on theproduction scale.Every aspect from laboratory scale to commercial scale isdocumented on record of Process validation.e.g. Injectable preparation.
Concurrent Validation :Concurrent validation is carried out during production.This time the in-process quality control parameter are also decides& monitor for use of regular production, final control & stability.If initial batches use same type of equipment then revalidation maynot be required only IPQC test are enough.IPQC test should be carried out for every batch to see the processis moving forward in the excepted direction.
Conti…Process & procedure should undergoes periodic critical revalidationto ensure that achieving the desire result.The verification of process parameter are evaluated for the mfg.facilities batch after batch if any changes is required.The premises and equipment to be used have been validatedpreviously and then decision to carry out concurrent validation.
Revalidation :“Revalidation is needed to ensure that changes in the process and in process environment whether intentional or unintentional do not adversely affect process characteristics and product quality” e.g. Change in : Formula. Equipment. Procedure. Quality of raw material. Physical variation. May required revalidation process.
Types of Revalidation : Revalidation after any changes bearing on product quality. Periodic revalidation carried out at schedule interval.
Revalidation after any changes bearing on product quality. Change in Change in Change in Change inStarting material. Packaging material. Process. Equipment. Density Replacing plastic Mixing time Conventional Viscosity. by a glass. Drying temp. granulator Particle size. Cooling regimen. Replaced by Crystal type. Rapid mixer Modification of granulator or active ingredients. Fluid bed processor.
Periodic revalidation carried out at schedule interval.It is well known that the process changes may occur gradually evenif experienced operator works correctly, similaraly equipment mayalso causes gradually changes.Periodic revalidation is based on review of historical data.i.e. data generated during in process & finished product testing.Any change in master formula & method, batch size etc.Has preventive maintenance been performed in accordance with theProgram & time schedule.Have the (SOPs) been properly updated.Have the (SOPs) been implemented.Have the cleaning & hygiene program been carried out.
Retrospective validation: Establishing documented evidence that a system does what if purposeto do based on a review and analysis of historical data and informationobtained during production of marketable products.This validation includes:Batch documents.Process control chart.Maintenance log book.Record of personnel changes.Finished product data.Storage stability result.
Conclusion. Validation is obtained through beginning from the process development Phase and continued through in to production phase.which provide high degree of assurance that will consistentlyproduce a product meeting its predetermine specification andquality attributes. may used to achieve reduction of cost, process optimization,assurance of quality and safety. Process validation involves series ofactivity taking place over the Lifecycle of the product and process.