OBJECTIVE:

• The objective of process validation is to establish documented evidence that a manufacturing process, when operated within defined parameters, is capable of consistently producing a product that meets its predetermined quality attributes and specifications.

SCOPE:

• This procedure applies to:
  • • All new products prior to commercial batch release.
    • Existing products when significant changes occur (formulation, equipment, process, scale, site, or regulatory requirement).
    • All dosage forms (solid, liquid, parenteral, topical, etc.) manufactured at this facility.
    • Re-validation activities triggered by major deviations, regulatory requirements, or equipment upgrades.

RESPONSIBILITIES:

• Validation Team:
  • • Shall prepare process validation protocol.
    • Shall ensure the implementation of procedure as per protocol.
    • Shall compile the report based on various results
• Quality Assurance (QA):
  • Shall ensure that all applicable SOPs and analytical Test methods are followed,
  • Shall ensure that all validation activities are implemented in accordance with the approved manufacturing records, cGMPs, and applicable SOPs.
• Production:
  • Shall ensure that all SOPs applicable to the execution of the validation are followed.
  • Shall ensure that proper personnel training, facilities, equipment are in place and materials are released and available for use.
• Quality Control (QC):
  • Shall ensure that all methods have been properly transferred and validated.
  • Shall ensure all personnel executing testing are trained.
  • Shall ensure test the samples as per the validation protocol and standard test procedure.

DEFINATIONS:

• Critical Process Parameter (CPP): ACritical Process Parameter is a process variable (e.g., temperature, mixing speed, pressure, pH, compression force, coating spray rate) that, when varied beyond its defined acceptable range, has a direct and significant impact on a Critical Quality Attribute (CQA) and, therefore, on product quality, safety, and efficacy.
• Critical Quality Attribute (CQA): A Critical Quality Attribute is a physical, chemical, biological, or microbiological property or characteristic of an intermediate or finished product that must be within an appropriate limit, range, or distribution to ensure the desired product quality, safety, and efficacy.
•  Quality Risk Management (QRM): Quality Risk Management (QRM) is a systematic process for the assessment, control, communication, and review of risks to product quality, patient safety, and regulatory compliance, throughout the lifecycle of a pharmaceutical product.

 PROCEDURE:

Validation Planning:

• QA shall prepare an Annual Validation Master Plan (VMP) listing all products and processes requiring validation or re-validation for the coming year.

• Validation activities shall be prioritized based on:
  • Risk to product quality and patient safety (as per QRM assessment).
  • Regulatory commitments or new product launches.
  • Major process or equipment changes.

• The VMP shall include:
  • Product name and dosage form.
  • Type of validation (prospective, concurrent, re-validation, ongoing).
  • Target dates for protocol preparation, execution, and report completion.
  • Responsible departments.
• QA shall review progress against the plan quarterly. Deviations from plan shall be justified and documented.

Protocol Preparation:

• The Process Validation Protocol shall be prepared by QA in coordination with Production, QC, and other support department.
• The protocol shall include the following details:
  • Objective & scope — reason and extent of validation.
  • Responsibilities of all participating departments.
  • Process description & flow diagram identifying critical steps.
  • Identification of CPPs & CQAs using Quality Risk Management tools (e.g., FMEA, Risk Matrix).
  • Sampling plan specifying number, location, frequency, and method of sample collection.
  • Statistical approach for evaluation of results (e.g., confidence limits, control charts, process capability).
  • Acceptance criteria for all CQAs and process parameters.
  • Deviation management procedure and CAPA requirements.
  • Yield & reconciliation limits.
  • Annexures — data collection sheets, logbooks, templates.
• QA shall review and approve the protocol prior to execution.
• Each protocol shall carry a unique identification number controlled by QA.

Execution of Validation Batches:

• A minimum of three consecutive batches shall be executed under normal manufacturing conditions unless otherwise justified by risk assessment.
•  All equipment, utilities, and instruments used must be qualified and calibrated.
• Only approved and released raw and packaging materials shall be used.
• Production shall execute the process as per approved BMR/BPR and protocol.
• QA shall monitor all critical steps (e.g., blending, granulation, drying, compression, coating, filling).
• In-process controls (IPC) such as weight variation, hardness, assay, viscosity, etc., shall be performed and documented in real time.
• Any deviation from the protocol or process parameters shall be immediately reported to QA and recorded in the Deviation Log.
•  Environmental parameters shall be monitored during validation batches.
• On completion of each batch, yield and reconciliation shall be verified and documented.

Types of Process Validation:

Prospective Validation:

• • • Conducted before commercial production begins.
    • Demonstrates that the designed process and parameters are capable of consistent output.
    • Based on developmental data, risk assessment, and pilot/engineering batches.
    • Performed for new products or after major process redesign.

Concurrent Validation:

• Executed simultaneously with routine production under QA supervision.
• Data from these commercial batches provide evidence of process control before final approval.
• Applied when immediate product supply is required, but process knowledge is adequate.

Re-validation:

• Performed when there are changes that may affect process performance, such as:
• • • Change in equipment, scale, or site.
    • Modification of manufacturing parameters.
    • New raw material or supplier.
    • Major deviation impacting CPP/CQA.
    • Perform it after 3 years to reconfirm process consistency.

Continued / Ongoing Process Verification (CPV/OPV)

• Conducted throughout the product lifecycle after validation completion.
• Involves routine data collection and statistical analysis of CPPs and CQAs from commercial batches.
• Detects trends and verifies that the process remains in a state of control.
• CPV data are reviewed during Annual Product Quality Review (PQR) and management review meetings.

Report Preparation:

• After completion of validation batches, a Process Validation Report shall be prepared by QA.
• The report shall include:
• • • Objective and scope of validation.
    • Summary of each batch executed.
    • Detailed data and observations for all CPPs and CQAs.
    • Statistical evaluation (trend charts).
    • Deviations and CAPA summaries.
    • Conclusion regarding process consistency and compliance.

• The report shall be reviewed and approved by QA, Production, QC, and Head – Manufacturing before final release.
• QA shall archive the approved report and update the Validation Master List.

Ongoing Process Verification (CPV/OPV):

• QA, in coordination with Production and QC, shall define parameters for ongoing monitoring (e.g., yield, rejection rates, in-process results, environmental data).
•  Data shall be collected for every commercial batch and entered into the CPV Trend Sheet.
• Statistical trending tools such as control charts, regression analysis, and process capability indices (Cp/Cpk) shall be applied.
• QA shall review CPV data quarterly or semi-annually to detect any drift or trend.
• Any abnormal trend shall trigger a root cause analysis and re-validation if necessary.
• CPV outcomes shall be discussed in Management Review Meetings and reflected in the APQR.

Process Validation Protocol and report Numbering:

• The process validation protocol shall be numbered as PVP/XXXYYY/ZZ/001
  where:
• • • PVP = Process Validation Protocol
    • XXXYYY = Product Code with product strength
    • ZZ = Year (25)
    • AAA = serial number of protocols

• The process validation report shall be numbered as PVR/XXXYYY/ZZ/001
  where:
  • PVP = Process Validation report
  • XXXYYY = Product Code with product strength
  • ZZ = Year (25)
  • AAA = serial number of reports.
• Retention policy for Process Validation protocol and report: Retain for the entire commercial life of the product + minimum 1 year after product discontinuation / expiry of last batch.

REFERENCE:

• EU-GMP Annex 15 – Qualification and Validation
• ICH Q8, Q9, Q10
• WHO TRS 937 Annex 3
• Company SOPs on Change Control, Risk Management, Documentation, CAPA

RECORDS:

 REVISION HISTORY.