The document outlines requirements and guidelines for conducting an Annual Product Review (APR). Key points include: - An APR must be conducted annually for each commercial product to assess consistency, trends, needed changes, and revalidation. It involves multiple departments and communication between manufacturing, quality, and regulatory affairs. - The APR scope covers manufacturing sites, affiliates, and subcontractors. It must include production statistics, deviations, complaints, recalls, changes, process validation status, trend analysis, and recommendations. - The results are evaluated to determine if corrective or preventative actions are needed. Senior management from quality and production must approve the APR, which is then archived for audits. Checklists are

1. Annual Product Review
by
Umer Al-Fasial
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2. Quality Assurance in Pharmaceuticals
It is the totality of the arrangements made with
the object of ensuring that pharmaceutical
products are of the quality required for their
intended use.
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3. Key Functions of
Quality Assurance
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4. Annual Product Review….WHAT
Directive Statement:
▪ An Annual Product Review must be conducted for each commercial
product.
▪ The purpose of this annual review is to verify the consistency of the
process, to assess trends, to determine the need for changes in
specification, production, manufacturing and/or control procedures
and to evaluate the need for revalidation.
▪ Annual Product Reviews (APRs) are important for communication
between manufacturing, quality and regulatory Affairs, to enable
quality improvement processes.
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5. Annual Product Review….WHY
▪ "Reviews" are a critical element of any Quality Management System.
▪ Regular reviews of process and quality system performance is necessary to ensure
product quality.
▪ All regulatory authorities require "reviews“ which may be called
▪ "Annual Product Review“ (US GMP term), or
▪ "Product Quality Review“ (EU GMP term)
▪ Expectations regarding contents and objectives are more or less the same.
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6. Scope
This scope applies to manufacturing sites,
Affiliates and subcontractors
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7. ▪ Individual departments,
such as, Supply Chain,
Engineering, Production,
Quality and Compliance,
Pharmacovigilance and
Regulatory Affairs are
responsible for providing
data and participating in
the Annual Product Review
process
Responsibilities
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8. Requirements
▪ Each site must have written procedures, which must be
followed when conducting Annual Product Reviews.
▪ The Annual Product Review must cover a one year rolling
period, but does not have to coincide with a calendar year
▪ The review should normally be completed within sixty (60)
calendar days of the period close and must in all cases be
completed within ninety (90) calendar days of the period close
▪ If the production is less than 3 batches per year, an annual
product review must still be conducted and this review can
include a review performed on the 2 or 3 preceding production
years
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9. Requirements (Cont.)
▪ The number of batches to be considered is the number of
batches manufactured during the agreed annual period.
The Annual Product Review must include all batches of
product whether they were accepted or rejected or
destroyed during manufacture
▪ The Annual Product Review report must address the
assessment of data, documents and electronic records
reviewed
▪ For active pharmaceutical ingredients, the Annual
Product Review includes the manufacturing critical steps
▪ Annual Product Reviews are to take into account
previous reviews. 9

10. Requirements (Cont.)
▪ An Annual Product Review must be prepared for each
water quality grade produced at each site
▪ If one quality of water is only used for one product , the
data concerning this water can be included in the APR of
the corresponding APIs
▪ For critical utilities it is recommending either to perform
a separate APR or to include a specific chapter in the
APR of the corresponding APR
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11. APR must include, at a minimum
▪ Review of any recommendations and actions taken
from prior report
▪ "Basic statistics"
▪ Number of batches manufactured, including partially
completed batches and corresponding yields
▪ Number and percentage of batches rejected and
related reasons
▪ Number and percentage of batches reworked or
reprocessed and related reasons
▪ Critical inprocess controls, finished product results
and critical API test results 11

12. APR must include, at a minimum (Cont.)
▪ Review of "deviations from the validated state“
▪ A review of all batches that failed to meet established
specification(s) and their investigation
▪ Significant/critical deviations, Out of Specification Results and
related failure investigations (review of adequacy and
effectiveness of corrective and preventative actions taken)
▪ A review of the adequacy of all corrective actions
▪ Product quality complaints
▪ Product Recalls
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13. APR must include, at a minimum (Cont.)
▪ Critical regulatory issues
▪ Quality related issues for returned, and/or salvaged goods
▪ Changes effected (change control) and variations during the
period (e.g. process, suppliers, equipment)
▪ Changes of product specifications or methods (e.g.
analytical changes, and results)
▪ Process Validation Status
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14. APR must include, at a minimum (Cont.)
▪ Trend Analysis
▪ Trend analysis on key in-process and release testing
with graphic representation and basic statistics
recommended
▪ A review of the results of the stability monitoring
program and trend analysis on stability data
▪ Observations/Recommendations
▪ From any official inspectorate which directly concern
and relate to the product under review (i.e. not
observations/ recommendations which relate to
general quality system issues)
▪ New recommendations from this review
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15. Further Requirements
▪ Additional items must be added to the APR/PQR in line with local
regulatory requirements (e.g. EU GMP Chapter 1). All of these
topics to be covered by the review must be stated in a site procedure.
▪ The results of the APR must be evaluated and an assessment made
whether corrective or preventive action (CAPA) or any revalidation is
necessary.
▪ A conclusion statement must be written to assess if the product
consistently meets its quality attributes, and if not, what actions
need to be taken. Rationale for such CAPAs must be documented.
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16. Approval and Archiving
▪ Annual Product Reviews will be reviewed, assessed, and
approved by Senior Site Quality Management, Site
Production Management and Senior Site Management
▪ The approved documents must be archived for a suitable
period and made available (upon request) during internal
or external audits by Regulatory Authorities.
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17. Checklist to prepare the APR
▪ Are there any outstanding validation commitments or corrective and preventive
action plans from last PQR/APR ?
▪ Are the processes in a validated state or is additional validation work needed ?
▪ Is the qualification status (IQ/OQ/PQ) acceptable ?
▪ Are all critical aspects performing satisfactorily or are corrective/preventive action
plans required ?
▪ Are there any significant findings concerning specifications or test methods ?
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18. Checklist to prepare the APR (Cont.)
▪ Are there any significant findings concerning the
stability monitoring program ?
▪ Are there any significant findings concerning retain
sample examination ?
▪ Are all post marketing commitments to Authorities
met ?
▪ Are all required Technical Agreements in place and
up-to-date ?
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19. Checklist to prepare the APR (Cont.)
▪ Are there any significant findings concerning data trending of the manufacturing
process, starting materials, or packaging materials ?
▪ Are there any significant findings concerning deviations and nonconformance?
▪ Are there any significant findings concerning data trending of the manufacturing
process, starting materials, or packaging materials ?
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20. APR Principles
▪ Focus on evaluation and assessment of data and information
▪ Create a meaningful list of facts and data
▪ Reviews should focus on mid and long-term trends (e.g. intra and
interbatch) because these trends are not obvious from single batch
data
▪ Make a connection to the previous report
▪ One element of a meaningful review is the verification of selected
original records (e.g. batch record, test records)
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21. APR should confirm the state of Control
▪ 'Validated status' based on assessment of process
performance (critical / relevant process information, trends)
▪ Closure of any deviation from the validated state, especially
changes, batch failures / OOS / deviations, or complaints
/recalls
▪ Confirmation that the product is stable
▪ Confirmation that specifications and acceptance criteria are
still suitable to assure product quality
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22. Take Home Message
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23. Questions
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