Annual Product Review - Prashant Mengshetti Product... · ¾Market complaints and related investigations. ¾All rejected batches / product failures and related investigations. ¾All

ANNUAL PRODUCT REVIEWANNUAL PRODUCT REVIEW

ByBy-- Prashant S MengshettiPrashant S [email protected]@gmail.com

What is APR ?What is APR ?An organized and comprehensive review An organized and comprehensive review of all production, analytical, stability, of all production, analytical, stability, complaints, changes, deviations, recalls complaints, changes, deviations, recalls and customer data associated with a and customer data associated with a pharmaceutical product so as to monitor pharmaceutical product so as to monitor the drug product quality and improve the drug product quality and improve where necessary. where necessary.


Why are APR’s required ?Why are APR’s required ?GMP RequirementGMP Requirement--Requirements for APRs are found in Requirements for APRs are found in 21 CFR 211.180(e) and include:21 CFR 211.180(e) and include:

Written procedure Written procedure Review of every batch (or representative) to determine the need Review of every batch (or representative) to determine the need for for changes in specifications or manufacturing or control procedureschanges in specifications or manufacturing or control proceduresReview of complaints Review of complaints Review of recalls Review of recalls Review of returned or salvaged products Review of returned or salvaged products Review of investigationsReview of investigations


OBJECTIVEOBJECTIVE

To assess drug product performance To assess drug product performance annually and to determine need for any annually and to determine need for any change in drug product specification and change in drug product specification and or manufacturing process and control or manufacturing process and control procedures.procedures.


BenefitsBenefits

Assess needed changes in product specifications.Assess needed changes in product specifications.

Assess needed changes in manufacturing or control Assess needed changes in manufacturing or control procedures.procedures.

Determine if validation or revalidation is needed.Determine if validation or revalidation is needed.

Identify product improvement or cost reduction opportunities.Identify product improvement or cost reduction opportunities.

Confirm change control systems.Confirm change control systems.

Provide a preparation tool for FDA inspections.Provide a preparation tool for FDA inspections.

Communicate product and process status to managementCommunicate product and process status to management


Content of APRContent of APRAnalytical and Inspection dataAnalytical and Inspection dataCritical process parameters.Critical process parameters.Review of YieldReview of YieldMarket complaints and related investigations.Market complaints and related investigations.All rejected batches / product failures and All rejected batches / product failures and related investigations.related investigations.All deviations, incidents, OOS and related All deviations, incidents, OOS and related investigations.investigations.All change controls.All change controls.Results of the stability monitoring program.Results of the stability monitoring program.Any product recall and related information.Any product recall and related information.Returned goods and salvaged goods.Returned goods and salvaged goods.


Content of APRContent of APRControl sample review of the product.Control sample review of the product.Batches taken for reprocessing/reworking, if Batches taken for reprocessing/reworking, if any.any.Different pack size of the product offered in the Different pack size of the product offered in the market.market.If any experiment is conducted to improve yield If any experiment is conducted to improve yield or quality of product in consultation with R&Dor quality of product in consultation with R&DPurified water & environmental monitoring Purified water & environmental monitoring Status of Technical agreementStatus of Technical agreement


Content of APRContent of APRStatus of process & Cleaning validationStatus of process & Cleaning validationStatus of TSE / BSE CertificationStatus of TSE / BSE Certification(For Hard gelatin capsule)(For Hard gelatin capsule)

Adverse Drug Events Adverse Drug Events


Analytical and Inspection dataAnalytical and Inspection dataFinished product & in process analytical data of relevant Finished product & in process analytical data of relevant critical parameters as mentioned below,but not limited critical parameters as mentioned below,but not limited to, shall be evaluated for all the batches. to, shall be evaluated for all the batches.

Tablets:• Water Content / Moisture Content • Dissolution/Dissolution Profile • Hardness• Disintegration Test • Impurities/Related Substances • Residual Solvent• Assay • Total Microbial Count.


Analytical and Inspection dataAnalytical and Inspection dataCapsules: Capsules:

i) Water Content / Moisture Content i) Water Content / Moisture Content i) Dissolution i) Dissolution iii) DTiii) DTiv) Impurities / Related Substances iv) Impurities / Related Substances v) Assay.v) Assay.

Pellets: Pellets: i) Water Content / Moisture Contenti) Water Content / Moisture Contentii) Drug Release in Acid Phaseii) Drug Release in Acid Phaseiii) Drug Release in Buffer Phaseiii) Drug Release in Buffer Phaseiv) Assayiv) Assayv) Impurities/Related Substancesv) Impurities/Related Substancesvi) Dissolution vi) Dissolution


Analytical and Inspection dataAnalytical and Inspection dataSoft Gel CapsulesSoft Gel Capsules ::--

i) Water Content / Moisture Contenti) Water Content / Moisture Contentii) LOD of shell ii) LOD of shell iii) DTiii) DTiv) Impurities / Related Substancesiv) Impurities / Related Substancesv) Assayv) Assay

vi) Total Microbial Count.vi) Total Microbial Count.

Powder Powder ::--i) Water Contenti) Water Contentii) Assay ii) Assay iii) Impurities/Related Substances.iii) Impurities/Related Substances.


Analytical and Inspection dataAnalytical and Inspection dataGelGel ::--

i) pH i) pH ii) Density ii) Density iii) Assay iii) Assay iv) Impurities/Related Substances iv) Impurities/Related Substances v) Viscosity v) Viscosity vi) Total Microbial Count. vi) Total Microbial Count.

Ointment/Cream :Ointment/Cream :--i) pH i) pH ii) Assay ii) Assay iii) Impurities/Related Substances iii) Impurities/Related Substances v) Total Microbial Count.v) Total Microbial Count.


Analytical and Inspection dataAnalytical and Inspection dataLiquid Liquid ::--

i) pH i) pH ii) wt. /ml or Specific Gravityii) wt. /ml or Specific Gravityiii) Viscosityiii) Viscosityiv) Assay iv) Assay v) Impurities/Related v) Impurities/Related SubstancesSubstancesvi) Total Microbial Count.vi) Total Microbial Count.


Analytical and Inspection dataAnalytical and Inspection data

InjectablesInjectables ::--i) pH i) pH ii) wt./ml or Specific Gravityii) wt./ml or Specific Gravityiii) Viscosityiii) Viscosityiv) Assay iv) Assay v) Impurities/Related v) Impurities/Related SubstancesSubstancesvi) Particulate mattervi) Particulate mattervii) Colourvii) Colourviii) Sodium Chloride content viii) Sodium Chloride content (if any)(if any)ix) Bacterial Antitoxin Test.ix) Bacterial Antitoxin Test.


Critical Process ParametersCritical Process ParametersExample of Tablet Example of Tablet

Critical Process Parameters During Granulation Stage :Critical Process Parameters During Granulation Stage :--

Mixing :Mixing :--Impeller (amperage) finalImpeller (amperage) finalChopper (amperage) finalChopper (amperage) final

Drying :Drying :--Duration of drying Duration of drying Inlet temperature Inlet temperature Outlet temperature Outlet temperature Loss on dryingLoss on drying


Critical Process ParametersCritical Process ParametersCritical Process parameters during Compression stage:Critical Process parameters during Compression stage:

HardnessHardnessThicknessThicknessDTDTIndividual weight variationIndividual weight variationAverage weightAverage weight

Critical Process parameters during Coating Stage:Critical Process parameters during Coating Stage:Inlet temperatureInlet temperatureOutlet temperatureOutlet temperatureAtomisation pressureAtomisation pressureSpray gun distanceSpray gun distancePan RPMPan RPMWeight buildup per tabletWeight buildup per tablet


Review of YieldReview of YieldFor each batch compile the percentage yield For each batch compile the percentage yield

obtained at all critical stages and total percentage obtained at all critical stages and total percentage yield of the batch. yield of the batch.

Statistical graphs for Analytical data, Statistical graphs for Analytical data, Inspection data and Yield shall be prepared.Inspection data and Yield shall be prepared.


Market complaints & related investigationsMarket complaints & related investigationsIn this section if any market complaints are came In this section if any market complaints are came during this review period and related investigation to during this review period and related investigation to be mentionedbe mentioned

All rejected batches / product failures & All rejected batches / product failures & related investigationsrelated investigations..

In this section if any market complaints are came In this section if any market complaints are came during this review period and related investigation to during this review period and related investigation to be mentionedbe mentioned

All deviations, incidents and OOSAll deviations, incidents and OOSSummary of all deviations, Incidents and OOS during Summary of all deviations, Incidents and OOS during the time frame of the APR.the time frame of the APR.


All change controls.All change controls.Summary of all change controls during the time Summary of all change controls during the time frame of the APR.frame of the APR.

Results of the stability monitoring program.Results of the stability monitoring program.The APR also covers all stability parameters of all The APR also covers all stability parameters of all batches on stability, which represents the batches on stability, which represents the manufactured batches for distribution. These data is manufactured batches for distribution. These data is trended, reviewed and compared from previous trended, reviewed and compared from previous years APRs to assure that no negative trend has years APRs to assure that no negative trend has developed and the expiry period is still appropriatedeveloped and the expiry period is still appropriate

Product recall and related informationProduct recall and related informationAny Batches withdrawn or recalled or regulatory Any Batches withdrawn or recalled or regulatory alerts made for the marketed product during the time alerts made for the marketed product during the time frame of the APR are listed along with the reason for frame of the APR are listed along with the reason for the withdrawal or recall.the withdrawal or recall.


Returned goods and salvaged goods.Returned goods and salvaged goods.Summery of Returned goods and salvaged goods,Summery of Returned goods and salvaged goods,if anyif any

Control sample review of the product.Control sample review of the product.Summery of Control sample of the product.Summery of Control sample of the product.

Batches taken for reprocessing/reworkingBatches taken for reprocessing/reworkingSummery of Batches taken for reprocessing or Summery of Batches taken for reprocessing or

reworking,if any.reworking,if any.

Different pack size of the product offered in the Different pack size of the product offered in the market.market.

Summery of different pack size of the product.Summery of different pack size of the product.


If any experiment is conducted to improve yield If any experiment is conducted to improve yield or quality of product in consultation with R&Dor quality of product in consultation with R&D

Purified water & environmental monitoringPurified water & environmental monitoring

Status of Technical agreementStatus of Technical agreement

Status of process & Cleaning validationStatus of process & Cleaning validation

Status of TSE / BSE Certification Status of TSE / BSE Certification

Adverse Drug EventsAdverse Drug Events


Summary & ConclusionSummary & ConclusionWhich shall detail the actions based on the review, Which shall detail the actions based on the review, comments and recommendations made in each comments and recommendations made in each section.section.


FDA Inspections: Expectations for Annual Product ReviewsFDA Inspections: Expectations for Annual Product Reviews

The following can sum up current FDA expectations for APR prograThe following can sum up current FDA expectations for APR programs:ms:Develop a comprehensive SOP Develop a comprehensive SOP –– the SOP should be comprehensive and the SOP should be comprehensive and specific. specific. Follow the SOP Follow the SOP –– failure to follow the SOP will almost always result in failure to follow the SOP will almost always result in concerns from investigators. concerns from investigators. Include all required and “expected” elements in the APR. Include all required and “expected” elements in the APR. Identify and implement corrective or improvement actions Identify and implement corrective or improvement actions –– the routine the routine assignment of corrective or improvement actions signals that youassignment of corrective or improvement actions signals that you take the take the process seriously, and as originally intended by the authors of process seriously, and as originally intended by the authors of the GMP the GMP regulations. regulations. FollowFollow--up on actions up on actions –– a system to assure that actions occurred and were a system to assure that actions occurred and were effective is essential. effective is essential. Assure that the quality unit reviews and approves the APR Assure that the quality unit reviews and approves the APR –– most firms most firms require QA approval on APRs. require QA approval on APRs. Involve management in the process Involve management in the process –– the higher the level of involvement the higher the level of involvement and interest in the process, the more APRs can be used as a tooland interest in the process, the more APRs can be used as a tool for process for process control and product improvement.control and product improvement.


Presentation ByPresentation By

Prashant S MengshettiPrashant S MengshettiB.B.Pharm,Pharm, MS MS (Pharma Tech)(Pharma Tech)

Quality Assurance DepartmentQuality Assurance DepartmentE mail E mail -- [email protected]@gmail.com

[email protected]@gmail.com


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Annual Product Review - Prashant Mengshetti Product... · ¾Market complaints and related investigations. ¾All rejected batches / product failures and related investigations. ¾All