QA017: SOP FOR PRODUCT QUALITY REVIEW

OBJECTIVE:

To define the procedure for the preparation, review, and approval of Product Quality Review (PQR) in compliance with regulatory, ensuring continued process consistency, product quality, and suitability of current specifications.

SCOPE:

Applicable to all finished pharmaceutical products manufactured by Company.
This SOP covers collection, evaluation, trending, and reporting of production, analytical, and quality data generated within the defined review period.

RESPONSIBILITIES:

Designee Quality Assurance (QA):

Compile data and prepare PQRs as per defined timelines.
Ensure data integrity and traceability (ALCOA+ principles).

Head Production / Head Quality Control (QC):

To review PQRs,
To assess findings.
To prepare Corrective Action and Preventive Action (CAPA) or improvement action plans.

Head Quality Assurance (QA):

To approve PQRs.
To ensure timely completion of PQRs (within 90 days of period end).
To ensure the timely completion of CAPA or improvement action plans initiated by Production / QC.
To present key outcomes and CAPA status during Management Review Meetings.

Engineering Head:

To provide calibration / qualification status of equipment, instruments, and utilities.
To Provide Preventive maintenance status.

Designee Pharmacovigilance:

To perform safety data exchange Agreements (SDEA) and provide dasta for integration into PQR.

DEFINATIONS:

PQR: Product Quality Review — a comprehensive assessment of all quality-related data for a product within a defined period (Annually) to verify process consistency and identify opportunities for improvement.
ALCOA+: Principle for data integrity — Attributable, Legible, Contemporaneous, Original, Accurate, plus Complete, Consistent, Enduring, and Available.
RSD (Relative Standard Deviation): RSD, or %RSD, expresses the degree of variation in a data set relative to its mean value, and is a measure of precision. A lower %RSD indicates greater consistency between results. It is often used for trending critical process or analytical parameters in PQR and validation studies.
CpK (Process Capability Index): CpK is a statistical measure of how well a process can produce output within specification limits.
CAPA (Corrective and Preventive Action): CAPA is a systematic approach to identify, investigate, correct, and prevent non-conformities or potential issues.
- Corrective Action eliminates the cause of a detected deviation or failure.
- Preventive Action eliminates the cause of a potential deviation or failure.
  Each CAPA must be documented, risk-assessed, implemented within a defined timeframe, and verified for effectiveness.
Manufacturing Formula (MMF): MMF is the approved master document that specifies materials, quantities, equipment, and detailed manufacturing and packaging instructions for each product and batch size.

PROCEDURE:

Data Collection:

Data shall originate from validated, secure sources (Quality Control, Warehouses, BMR/BPR, calibration, PV database, QMS database).
Data shall traceable, authorized, and complete prior to use for PQR.
The Product Quality Review (PQR) planner shall form an integral part of the Validation Master Plan (VMP) to ensure synchronization of product review schedules with ongoing qualification and validation activities

Preparation of PQR:

PQR shall be prepared for every product and site, regardless of the number of batches manufactured.
If ten (10) or more batches are manufactured, full statistical evaluation (%RSD and Cpk) shall be performed.
For less than ten (10) batches, apply the following criteria:
- Combine data from at least the previous two consecutive years to obtain a minimum of ten batches, wherever feasible.
- If still fewer than ten batches are available after combination, perform a qualitative and narrative review covering:
  - Batch-wise yield and process consistency compared to historical data.
  - Review of deviations, OOS/OOT, change controls, and validation batches.
  - Stability data, complaints, recalls, and market feedback.
  - Comparison with previous APQR trends and identification of recurring issues.
If the total number of batches manufactured during the review period is below ten (10), statistical evaluation was not meaningful.
Qualitative assessment and comparison with historical data shall be performed.
Ensure all data, comments, and conclusions are supported with documented evidence.

Content of PQR:

Product details (generic name, strength, license numbers, shelf life, storage, markets) shall be recorded.
Table of contents shall be covered to give clarity about content
Executive summary shall be recorded.

API and Raw-Material Traceability:

For each finished-product batch reviewed, record the API batch number(s), supplier name, certificate of analysis number, and date of receipt. Verify that only approved API sources were used and that analytical release data meet established specifications.

Analytical Parameters Trending:

Evaluate and trend critical analytical parameters (assay, dissolution, related substances, moisture, uniformity, hardness, etc.) of in-process and finished products across all batches in the review period.
Batch manufacturing and packing summary with yield trends shall be recorded.
Critical process parameters and analytical results with %RSD and Cpk values shall be recorded.
Deviations, OOS, OOT, and change controls summary with CAPA implementation shall be recorded.
Supplier qualification and review of raw-material and primary-pack suppliers shall be recorded.
Equipment, instrument, and utility calibration / qualification status shall be recorded.
Process validation / continued process verification and analytical method validation shall be recorded.
Stability-study results and trend analysis shall be recorded.
Product recall, returned or reworked batches, and reprocessing data shall be recorded.
Pharmacovigilance / Market Complaints: summary of complaints, adverse reactions, field alerts, and actions taken shall be recorded.
MFR Revisions summary of any approved or pending changes shall be recorded.
Technical Quality Agreements (TQA): shall confirm and record that current and up-to-date agreements are in place.
Implementation status of previous year’s recommendations shall be checked and recorded.
Statistical Evaluation shall be recorded:
- %RSD:
  - %RSD (Relative Standard Deviation) = (SD / Mean) × 100
  - Indicates data precision or consistency.
  - Acceptable limit: ≤ 6 % for analytical parameters.

Cpk (Process Capability Index):

Cpk (Process Capability Index) = min [(USL − x̄)/(3σ), (x̄ − LSL)/(3σ)]
Indicates process capability against specification limits.
Acceptable limit: ≥ 1.33 (≥ 1.67 for critical attributes).

Trend Interpretation:

Stable – Within control limits (no shift).
Warning – Between ± 2 SD and ± 3 SD (monitor closely).
Action / OOT – Beyond ± 3 SD (investigate & raise CAPA).

For < 10 batches: Perform qualitative evaluation using historical data rather than full statistical analysis.

Attach Graphs / Charts:

For key parameters such as Assay, Dissolution, Impurity, Yield, and Stability trends.
Trends exceeding warning or action limits shall be identified.
Conclusions and Recommendations like product state of control, compliance status, and improvement actions shall be recorded.
All PQR observations must be converted into CAPAs with defined responsibility and timelines.
CAPAs shall be closed within 90 days, and effectiveness verified by QA.
A summary of key trends, Cpk data, and CAPA progress shall be presented during Management Review Meetings.
Environmental Monitoring shall be reviewed and recorded for every stage of manufacturing

Review of Plant Certification and Regulatory Status:

The PQR shall include a statement of the current GMP certification status of the manufacturing site covered under the report.

Timelines:

Data collection shall be completed within 30 days of calendar year end.
Draft PQR shall be completed within 60 days.
PQR shall be reviewed and approved within 90 days.
CAPA follow-up and closure verification shall be done within 180 days.
PQR shall be conducted once every calendar year.

Record Retention:

All records shall meet to ALCOA + principles.
PQR reports shall retain for product shelf life + 1 year (minimum 5 years).

PQR Numbering System:

The numbering pattern shall be as follows: PQR / XX / YYY Where:
- - PQR= Product Quality Review.
  - XX = last two digits of the calendar year in which the batches were manufactured
  - YYY = sequential serial number starting from 001 for that year.
Example: PQR / 25 / 004 – represents the 4^th PQR prepared for 2025.

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