Annual Product Report (APR/APQR/PQR):

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

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

Purpose:

The purpose of this sop is to describe the detail procedure for preparation, review
and approval of annual product report/ product quality review (APQR / APR
/PQR) with the objective of verifying the consistency of the process, equipment and
system 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 process, Specification and adherence to specified standards.

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

Procedure – Annual Product Review (APR):

  Preparation of Annual Product Quality Review (APQR):
 Annual product report shall prepare for all finished products
manufactured.
 APR to verify the consistency of the existing process, the
appropriateness of current specifications for
 Raw materials.
 Packing materials.
 Intermediate product and
 Finished product to identify any emerging trends as also to
identify product / process related improvements.
 APR shall prepare for drug Products as per below time line and
acceptance criteria:
 Time Line to prepare the Annual Product Quality Review :
                     Yearly+ 3 months.

 APR shall prepare for all products manufactured in a year.

 If more than fifteen batches manufactured during the review period, Prepare
graphical presentation of analytical trend data of in-process and finished
product.
 In case of less than fifteen batches, instead of graphical presentation,
minimum/maximum value of trend shall be prepared and reported.
 APR tracking register shall be maintained.
 Preparation of APR consists of three stages:
 Collection of data / information,
 Review of data / information and
 Generation of review report.
 Annual Product Reports shall contain data of all the batches manufactured
for a product during calendar year from January to December.
 Separate APR / APQR shall generate in case a product is produced using
different manufacturing process.
 Review shall cover all the markets where the product is being sold.
 In case of a product that is manufactured in multiple strengths or different
packs, combined APR report can generate. however each pack or strength
shall evaluate in separate manner.
 Preparation of APQR / APR / PQR of all products shall complete till the end
of first quarter of product anniversary.
 To manage the preparation of APR of all products and to divide the work
load throughout the year,
 APR of different products shall plan in different months i.e. as per
product anniversary.
 Suppose 120 products are manufactured in year, then every
month approx. ten products shall identifying for preparation of APR.
 The batches to be considered for APR review shall dependent
on the APR period i.e. 01/01/14 to 31/12/14 or 01/02/14 to 31/01/15
or 01/03/14 to 29/02/15 so on.
 The next year review shall perform for next review period i.e. if in first year
the period was selected the 01/01/14 to 31/12/14
 Then the next year APR shall prepare for the batches manufactured during
the period from 01/01/15 to 31/12/15, for the products APR falling during
this stated period and same shall follow for the rest.
 In-case of WIP for a product, APR shall complete after its final QA release.
 General Instruction for preparation of Annual Product Review – APR :
 Various data incorporated into the APR can present in tabulated form. Also
graphs, flow chat, etc. can  use 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 case of product transfer, product discontinuation
or banned from govt. Authority.
 If the APR is required to share with other locations,
 Then the “Uncontrolled copy” shall issue 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.
 Annual product report shall prepare in accordance to the following points.
 Each APR shall have a covering page which includes
 The Company Logo in the center of the page.
 “ANNUAL PRODUCT REPORT” below the Logo.
 The table shall contain the product name, Year and APR number.
 Subsequent pages of the APR shall bear the Header and footer.
 Header shall bear the Sun Pharma Logo at the top right corner of
each page.
 “ANNUAL PRODUCT REPORT “shall be written at top center of
each page.
 Header shall contain the table at top of each page which shall contain
the page no., Product name, Generic name and market.
 Footer of each page shall contain the unique APR number on left
corner of each page.
                 Upper control limit: (Arithmetic mean + 3 X standard deviation
(σ)).

                 Lower controlled limit: (Arithmetic mean – 3 X standard deviation

(σ)).

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

 the minimum and/or maximum limit among all data for a particular
parameter can consider as
 limit for recommendation or
 the root cause of such variation to  identify to eliminate the same for
future batches.
                 Process performance and Process performance index can calculate
as a part of further study of trend                                results.

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

                        Process performance: Pp= USL-LSL/6σ

                 Where Pp= process Performance,         USL= Upper Specification

Limit,

                 LSL= Lower Specification Limit and    σ= Standard deviation

 Interpretation of Pp Value:
 As Pp is inversely proportional to the standard deviation, higher the
value of Pp, better is the process performance.
 Process Performance index (Ppk) value shall calculate for batch
yield, and to key quantitative results (Assay, Related substances, residual
solvents etc.).
 Below the formula for calculation of Two-sided specification.
Formula- 1: Ppk=Pp-(m-x)/3S

                 Where: Ppk = process Performance index

                  m=Mean Point (USL+LSL/2)

                 x= Mean value

                 S: Standard Deviation

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

                 Where: USL: Upper Specification Limit

                 LSL: Lower Specification Limit

                 X: Mean Data

                 S: 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
 Then the process may generate some non-conforming batches over a
period of time and needs assessment to identify and eliminate cause for
variability.
 If required, do the Further assessment in this case.
 If PpK ≥ 1.33 :
 Then the process is capable,  For normally distribution of 
population.
For more details about Process Capability calculation (cpk ppk value
calculation) Click here

 Review of status against previous APR:

  Check for any recommendations / actions stated in previous APR
completed for the product.
 Compare the trends against those included in the previous APR for
any similarities / differences, check whether any corrective actions
completed in previous year have improved the trends during this year.
 Provide a brief summary in the APR report based on the above
points.
 Conclusion:
 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/s for betterment of future batches.
 Addendum Report:
 Annual product report can reopen for incorporation of further
information under circumstance’s as listed below. An addendum report
shall prepare for further updation.
 If any information found missing while review.
 To include the recommendation/suggestion of auditors.
Annual Product Review Tracking Register
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
 Format for APQR