Annual Product Review (April) is the requirement of various regulatory agencies. APR roots the monitoring of product quality as well as finding out the scope of quality improvement by controlling the critical process parameters (CPP).

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April – Annual Product Review also known equally APQR – Annual Product Quality Review and PQR – Production Quality Review, below the SOP and formats for APR preparation.

Annual Product Study (April/APQR/PQR):

Annual product written report is a documented evidence for assuring that the diverse manufacturing parameters are controlled enough which results into a finished product coming together all predetermined specification and other quality attributes. Also acts equally an indicator to identify requirement of changes in specifications or manufacturing processes or control parameters with the help of statistical review of tendency.

SOP for Annual Product Quality Review (Apr / APQR / PQR)

Purpose:

The purpose of this sop is to describe the particular process for preparation, review and approval of annual production report/ product quality review (APQR / APR /PQR) with the objective of verifying the consistency of the procedure, equipment and arrangement for meeting predetermined specifications and other quality attributes of a finished product.

Scope:

This procedure applies to all drug products manufactured to understand and review the procedure, Specification and adherence to specified standards.

Note: APR / APQR / PQR, all are same only the terms are differently used in guidelines.

References & Annexures:

  • References

    • Guideline for preparation of annual Product review of Drug Products.
    • 21 CFR Part 211.
    • Good Manufacturing Practices issued By WHO.
    • Australian code of cGMP for medical products issued by TGA.

  • Annexures:

    • Format for Annual Product Review Tracking Register

Responsibilities for grooming of Annual Product Review – Apr:

  • Quality Balls:

    • Compile and review the information from relevant departments and set up Almanac Product Review (Apr) report as per divers procedure.
    • Ready and review graphical representation.
    • Fix qualification status of relevant equipment'south & utilities and whatever other relevant details respect to Almanac Product Review.

  • Quality Control:

    • Provide electric current specification of API and Finished Product and any other relevant details with respect to Almanac Production Review.
    • Summarize results of stability monitoring program.
    • To gear up data of QC events, investigations, OOS and provide their relevant investigation and effectiveness of relevant cosmetic and preventive deportment taken.
    • To provide current specifications of packing material.

  • QA Head or Designee:

    • Review the Annual Production Review Report.
    • Responsible for assuring that all the requirements of Apr are fulfilled.
    • Ensure the compliance of APR and submit the April to corporate regulatory diplomacy for any submission.

Abbreviations and Definition of Terms used in SOP for Annual Product Review – April:

  • Abbreviations :

    • CC No.: Change Control number
    • NA: Not Applicable
    • QA: Quality Assurance
    • QC: Quality Control
    • APQR: Annual Product Quality Review.
    • APR : Annual Product Review.
    • PQR: Product Quality Review.
    • PPk : process Functioning alphabetize
    • CPP : Critical Process Parameter

  • Definition of Terms :

    • Trend: Trend is the tendency of data to exhibit an increasing / decreasing / cyclic design when the data is presented in a graphical manner. A change in a trend is ordinarily associated with some cause.

Procedure – Almanac Production Review (APR):

  • Preparation of Almanac Product Quality Review (APQR):
    • Annual production report shall fix for all finished products manufactured.
    • APR to verify the consistency of the existing process, the appropriateness of electric current specifications for
      • Raw materials.
      • Packing materials.
      • Intermediate product and
      • Finished production to place any emerging trends as too to identify product / process related improvements.
    • APR shall gear up for drug Products as per below fourth dimension line and acceptance criteria:

    • Time Line to prepare the Almanac Product Quality Review :

                     Yearly+ 3 months.

    • April shall gear up for all products manufactured in a year.
    • If more than xv batches manufactured during the review menses, Prepare graphical presentation of analytical trend information of in-process and finished product.
    • In case of less than 15 batches, instead of graphical presentation, minimum/maximum value of trend shall exist prepared and reported.
    • April tracking register shall be maintained.

    • Preparation of APR consists of three stages:

      • Collection of data / data,
      • Review of data / information and
      • Generation of review report.
    • Annual Product Reports shall contain data of all the batches manufactured for a production during calendar year from Jan to Dec.
    • Split APR / APQR shall generate in case a product is produced using dissimilar manufacturing procedure.
    • Review shall comprehend all the markets where the product is being sold.
    • In instance of a product that is manufactured in multiple strengths or different packs, combined Apr study can generate. withal each pack or force shall evaluate in separate fashion.
    • Preparation of APQR / Apr / PQR of all products shall complete till the end of showtime quarter of product ceremony.
    • To manage the preparation of APR of all products and to separate the piece of work load throughout the year,
      • April of unlike products shall plan in dissimilar months i.e. every bit per production anniversary.
        • Suppose 120 products are manufactured in year, then every month approx. ten products shall identifying for preparation of Apr.
        • The batches to exist considered for APR review shall dependent on the APR menstruum i.e. 01/01/xiv to 31/12/14 or 01/02/14 to 31/01/15 or 01/03/14 to 29/02/xv so on.
    • The next year review shall perform for side by side review period i.east. if in first year the menses was selected the 01/01/14 to 31/12/fourteen
    • And so the adjacent year Apr shall gear up for the batches manufactured during the period from 01/01/15 to 31/12/fifteen, for the products Apr falling during this stated period and same shall follow for the rest.
    • In-case of WIP for a production, APR shall complete after its final QA release.

    • General Pedagogy for training of Annual Production Review – APR :

    • Various information incorporated into the APR can present in tabulated form. Also graphs, catamenia chat, etc. can  utilise as per the requirement.
    • Apr of all products shall kept with QA department.
    • All relevant points shall discuss with the concern department/s.
    • APR shall not destroy in example of product transfer, product discontinuation or banned from govt. Say-so.
    • If the April is required to share with other locations,
      • And then the "Uncontrolled copy" shall consequence upon request.
    • If the APR is not due,
      • Than only raw trend data shall share with the new location.
    • In-case a particular product is not manufactured during a particular year,
    • Then the APR shall restrict to review of only relevant points.
    • Almanac product written report shall prepare in accordance to the following points.
      • Each April shall have a covering folio which includes
      • The Company Logo in the center of the page.
      • "Almanac Production REPORT" below the Logo.
      • The tabular array shall contain the production name, Yr and April number.
      • Subsequent pages of the APR shall bear the Header and footer.
      • Header shall bear the Logo at the top right corner of each page.
      • "ANNUAL PRODUCT Study "shall be written at elevation center of each folio.
      • Header shall contain the table at meridian of each page which shall incorporate the page no., Product proper noun, Generic proper noun and market place.
      • Footer of each folio shall contain the unique APR number on left corner of each folio.

  • The content of April shall contains

    • Objective
    • Introduction
    • Product details
    • Process flow
    • Review of manufacturing related Information:
    • Batch
      • Yield at diverse manufacturing stages:
      • Rejections:
      • Reprocessing / reworking:
    • Review of disquisitional quality parameters
    • In-process and intermediate testing results:
    • Review of Finished product testing results:
    • Out of Specification:
    • Review of
      • Events:
      • Changes:
      • Market complaints:
      • Control Samples:
      • Recall and Returns:
      • Stability Data:
      • Validation and qualification status:
      • Mail service marketing commitments:
      • Quality of APIs, Fundamental raw materials, printed packing materials,
      • Primary packaging material:
      • Technical agreement:
      • Statistical evaluation of Data:
      • Review of status against previous April:
      • Conclusion
      • Recommendation
      • Abbreviations
      • Annexures
      • Blessing
    • Objective shall describe the purpose of preparation of April.
    • Introduction shall depict the details of batches manufactured during the year.

    • Product details shall describe

      • Name of the Product,
      • Product lawmaking,
      • Generic Name,
      • Strength,
      • Therapeutic activeness,
      • Batch size,
      • Shelf life,
      • Dosage form,
      • Total number of batches manufactured,
      • Manufacturing License. No,
      • Storage condition,
      • Manufacturing and expiry date.
      • Other items tin be incorporated to product details, if required.
    • Process catamenia shall exist presented through a flow chart diagram covering all critical manufacturing steps.

  • Review of manufacturing related Information – Annual Production Review – APR:

    • Listed below are the manufacturing related parameters that will be reviewed as a role of APR, this shall cover all the stages involved in the manufacturing process (e.g. in example of tablet manufacturing procedure, stages involve are generally granulation, compression, coating and packing)

    • Critical process parameters:

      • Tabulate the data generated for critical parameters for all the batches.
      • Catechumen this data into graphical form and review the same for emerging trends / atypical blueprint in the graphs.
      • Determine whether any atypical pattern has impacted the quality of the final product.
      • Provide a brief summary in the April report based on the findings of the above points.

    • Batch yield at various manufacturing stages:

      • Tabulate the yield at various stages for all batches.
      • Generate graphs and review the aforementioned for any emerging trends.
      • Bank check whether investigation has been documented in case of batches non meeting the yield limit and cheque whether the root cause has been identified and whether corrective / preventive action/s taken were adequate.
      • Cheque if there were repeated yield related events/due south and evaluate whether the root cause identification and corrective / preventive actions were adequate or any additional deportment need to be undertaken.
      • Provide a brief summary in the APR study based on findings of the above points.

    • Batch Rejections:

      • Check
        • If any batches were rejected during the review menses.
        • Whether investigation for the batch has been documented.
        • Adequacy of root crusade identification and cosmetic / preventive deportment, if whatsoever.
        • Disposition status of the rejection batch.
      • Provide a brief summary in the April report based on findings of the above points.

    • Batch reprocessing / reworking:

      • Bank check
        • If any batches were reprocessed or reworked during the review catamenia.
        • The adequacy of root crusade identification and corrective / preventive actions, if any.
        • Whether the reprocessed /reworked batch met the specification and was charged for stability study.
        • The disposition status of the reprocessed / rework batch.
        • The impact on quality of reprocessed /rework batch.
      • Provide a brief summary in the Apr report based on findings of the above points.

    • Review of critical quality parameters:

      • Listed below are the critical quality parameters that volition exist reviewed equally a part of April.

    • Review of Finished product testing results:

      • Tabulate the belittling results for key quantitative tests conducted on the finished product batches in the Apr report
      • Convert this information into graphical form and cheque for emerging trends / atypical pattern in the graphs
      • Determine, a alter in the trend has any underlying crusade.
      • Compare the tendency versus corresponding trends obtained for in process and intermediate samples to bank check. There is, whatever correlation or a cause effect scenario.
      • Provide a brief summary in the APR written report based on the findings of the higher up points.

    • Out of Specification Results:

      • Check the log for OOS noted during the review catamenia for the production in question.
      • Determine that the all OOS properly investigated and identify the root crusade.
      • Verify the corrective preventive actions documented in the investigation reports.
      • Categorize the OOS results based on root cause to identify any recurrent design.
      • Check the deportment taken for recurrent type of OOS results are effective.
      • Provide a brief summary in the April report based on the findings of the to a higher place points.

    • Review of Events:

      • Commencement of all, Check the log for events noted during the review period for the production in question.
      • Then Verify, all the events has investigated and root cause identified and documented in the investigation written report.
      • Then Verify, the Corrective / preventive actions documented in the investigation reports have been actually been completed and the consequence report has been closed within stipulated time frame.
      • Check there, Any recurrent events and whether deportment taken for such events are constructive.
      • In-case of pending actions, check whether the delay is justified.
      • then Categorize the events based on root cause to identify any recurrent pattern.
      • Provide a brief summary in the Apr report based on the findings of the to a higher place points.

    • Review of Changes:

      • Review the changes implemented during the period (changes to manufacturing process, belittling specifications and test methods, utility process equipment should be covered every bit a minimum)
      • Check all the changes for closeness.
      • Verify the post–implementation review of the change. Information technology should adequately documented.
      • Assess, there is a cumulative impact of all the changes on the product quality
      • Then check for re-validation (if required).
      • Provide a brief summary in the April study based on the findings of the to a higher place points.

    • Review of market place complaints:

      • Bank check the log for marketplace complaints and annotation the number of complaints received for the production in question.
      • Check each complaint. For completeness of Investigation / root crusade finding.
      • Verify for corrective / preventive actions. It should documented in the investigation reports.
      • In-case of pending actions, cheque whether the delay is justified.
      • Categorize the complaints based on the root cause to identify whatever recurrent pattern.
      • Check the actions taken for recurrent blazon of complaints.
      • Provide a brief summary in the APR report based on the findings of the above points.

    • Review of control Samples:

      • A summary of periodic review of command samples (Physical observation) carried out during the review period shall be included in the APR report. Any visually aberrant findings noted for the control sample during such periodic review shall also be included in the Apr.

    • Review of Think and Returns:

      • Notation the number of batches recalled or returned.
      • Check for stock reconciliation. Reported correctly.
      • Cheque For each retrieve. For abyss of investigation/root cause identification.
      • Verify the corrective / preventive deportment documented in the investigation reports.
      • Verify the disposition status of the stock.
      • Categorize the recalls based on root cause to identify any recurrent pattern.
      • Check at that place has whatever recurrent recall or returns/ recalls and
        • Whether deportment taken for such returns/ recalls are effective.
      • In-example of pending actions, bank check whether the delay is justified.
      • Provide a brief summary in the Apr report based on the findings of the above points.

    • Review of Stability Data:

      • Check those batches that was taken up for stability study during the review catamenia and the reason for the same.
      • Review the stability information generated during the review period and note whether in that location have been any atypical / OOS/ stability failures / adverse trends.
      • Review the outcome of the completed stability studies and recommendation if whatsoever.
      • Verify whether deportment has taken for stability failures.
      • Provide whether actions has taken for stability failures.
      • Provide a brief summary in the APR written report based on the findings of the above points.

    • Review of Validation and qualification condition:

      • Verify the validation / qualification status of the manufacturing process, relevant processing equipment critical utilities such as water organization, HVAC system, compressed air, etc. Cleaning methodology, relevant belittling instruments and belittling methods.
      • For upshot of the validation do.
        • Review the validation documents(s)  i.e. for the completeness of  validation.
      • Provide a brief summary in the APR report based on the findings of the above points.

    • Review of Post marketing commitments:

      • Include a summary of variations to marketing authorization that were submitted /granted/rejected.
      • Review-
        • The postal service marketing commitments for any changes made to the registered requirements and provide a brief summary virtually the same in the Apr report.
        • Quality of APIs, Key raw materials, printed packing materials, Primary packaging fabric:
        • API Test Results: This activity will comport out by QC and report submitted to QA for review.
      • The test result will review vendor wise to determine any change which may accept a direct or indirect effect on the finished production.
      • Based upon the trend result the vendor status may change from its present status.
      • Bank check
        • There has been any change in specification, examination methods vendor for the above materials used in the product in question.
        • The condition of vendor qualification and identify vendors for which quality-audit is pending.
        • Whether there were whatsoever rejections of above materials during the review period and the name of the vendor.
      • For recurrent rejection of particular material from aforementioned vendor, cheque whether the supplier has submitted any investigation report and whether vendor's actions were verified where required.
      • In instance of drug products, trending of key belittling results of API batches shall be carried out.
      • Provide a brief summary in the Apr written report based on the findings of the above points.

    • Review of Technical understanding:

      • Verification of the requirement for technical Agreement with customers
        • It compiles and whether at that place accept been changes to the understanding.
      • Provide a brief summary in the APR written report based on the findings of the higher up points.

    • Statistical evaluation of Data:

      • Data for batch yield, in-procedure testing, intermediate testing, finished product testing should statistically evaluated to determine the maximum, minimum, Mean, standard Deviation and Relative standard deviation (RSD) values.
      • The necessary changes or freez of limits ,wherever applicable as per the recommendation past using the formula given below.

Upper control limit : (Arithmetic mean + 3 Ten standard deviation (σ)).

Lower controlled limit : (Arithmetic mean – iii 10 standard deviation (σ)).

                 In instance the UCL or LCL falls out of specification limit,

    • the minimum and/or maximum limit amid all information for a particular parameter can consider every bit
      • limit for recommendation or
      • the root cause of such variation to  identify to eliminate the aforementioned for time to come batches.

                 Process performance and Procedure performance alphabetize tin calculate every bit a part of further study of trend                                results.

Annual Product Review -APR
Process performance

                 The process performance, or Pp, measures a process's operation, which is defined as the allowable                             spread over the actual spread. ( Refer Diagram below )

Process operation: Pp= USL-LSL/6σ

                 Where Pp= process Operation,         USL= Upper Specification Limit,

                 LSL= Lower Specification Limit and    σ= Standard deviation

    • Estimation of Pp Value:

      • As Pp is inversely proportional to the standard deviation, higher the value of Pp, improve is the process performance.
      • Procedure Performance alphabetize (Ppk) value shall summate for batch yield, and to key quantitative results (Assay, Related substances, residual solvents etc.).
      • Below the formula for calculation of Two-sided specification.

Formula- one: P pk=Pp-(m-10)/3S

                 Where: Ppk = procedure Operation index

                  m=Hateful Point (USL+LSL/two)

                 x= Mean value

                 S: Standard Difference

Formula -2: Ppk= Minimum of (USL- X) / 3S or (X- LSL) / 3S

                 Where: USL: Upper Specification Limit

                 LSL: Lower Specification Limit

                 10: Hateful Data

                 Due south: Standard Deviation

    • Interpretation of PpK Value:

      • If PpK ≥ 1
      • Then the process is capable of generating 99.7 % of the product batches that are within the specification. If required, do the Further assessment.
      • If PpK ≤ 1
      • So the procedure may generate some not-conforming batches over a menstruum of fourth dimension and needs cess to identify and eliminate crusade for variability.
        • If required, do the Farther assessment in this case.
      • If PpK ≥ 1.33 :
        • Then the procedure is capable,  For normally distribution of  population.

For more than details about Process Adequacy calculation (cpk ppk value adding) Click here

    • Review of status confronting previous Apr:

      • Check for any recommendations / actions stated in previous April completed for the production.
      • Compare the trends confronting those included in the previous April for any similarities / differences, bank check whether any corrective actions completed in previous year have improved the trends during this year.
      • Provide a cursory summary in the APR written report based on the above points.

    • Decision:

      • A suitable conclusion shall drawn by reviewing the above mentioned parameters.

    • Recommendation:

      • Based on logic and statistical review, recommendation for betterment of the product and system shall describe.
      • Tools shall design to ensure the implementation of recommended action plan/southward for betterment of future batches.

    • Addendum Report:

      • Almanac product study tin reopen for incorporation of farther information under circumstance's equally listed beneath. An addendum study shall set up for further updation.
      • If any information found missing while review.
      • To include the recommendation/proposition of auditors.

Almanac Product Review Tracking Annals

Annual Product Review Tracking Register

Also visit for : Role of QA in Pharmaceuticals < Click hither )