VAL-105 Raw Material Evaluation Process

5.1 Evaluation Overview

In case multiple sites are sourcing the same drug substance / raw material from the same manufacturer, only one evaluation study needs to be conducted.

In the case of new material sources, the evaluation must provide sufficient data to fully characterize the material that is to be received in future purchases.

5.2 Evaluation Initiation

5.2.1 Once requirement in raw material change is identified, the Change Requestor shall raise a change control in accordance with SOP QMS-125 Change Management System.

5.2.1.1 All approved Raw Material Evaluation (RME) activities will be assigned to the RME Team.  The team will co-ordinate, strategize and set project time lines based on stock coverage and conversion date.

5.2.2 Once the Site Change Control is approved by the Plant Technical Team (PTT), the Change Requestor shall raise a RME document (Form 725 Raw Material Evaluation) and complete Section 1.1, Change Description, of the Raw Material Evaluation Document.

5.2.2.1 All Semi-finished goods and finished goods that use the proposed material, manufactured by the site and Third Party Contract Manufacturer shall be listed in the RME document.

5.2.3 An RME Number is then assigned to the RME Document (e.g. RME XX- YY).  The RME number is issued by Procurement.  The number is controlled and obtained via the RME number logbook.  The first two numbers denote the sequential order and the last two the year; e.g. 04 for 2009 etc.

5.2.4 The relevant section of the RME document should then be circulated by Procurement for assessment and determination of the evaluation strategy by the relevant departments.

5.3 Evaluation Execution

The outcome of the assessment shall be documented in the RME document raised in the Evaluation Initiation stage.

Any deficiencies identified during the assessment must be addressed.  The person who conducted the assessment will sign off the relevant section of the RME document after all deficiencies identified have been resolved.  The signature indicates the task has been accurately performed as per requirement.

Any relevant supporting documentation shall be attached to the relevant section of the RME document with page number clearly labelled.

5.3.1 Procurement

5.3.1.1 Obtain three (3) lots of evaluation samples (three (3) different manufacturing lots) of the proposed material with C of A’s.

5.3.1.2 Forward the C of A’s to Manufacturing Compliance department for review.

5.3.1.3 Forward the C of A’s to Quality Operations Laboratory for evaluation testing.

5.3.2 Manufacturing Compliance

5.3.2.1 All the affected countries in which the finished products are marketed shall be identified and documented.

5.3.2.2 Review of the RMSTR for the current material shall be conducted to ensure the current material is compliant to the applicable current monograph.  Any differences identified should be documented and addressed prior to proceeding to Step 5.3.2.3.

5.3.2.3 Review of C of A for the proposed material shall be conducted to ensure it is compliant with the applicable current monograph and existing Raw Material Specification Test Report.  Any differences identified should be documented and addressed prior to proceeding to Step 5.3.2.4.

5.3.2.4 Create the RMSTR for the proposed material and ensure it is compliant with applicable current monograph and existing RMSTR.

5.3.2.5 Assess PCP / PCR submissions requirement and complete the relevant section in the RME document (Form 725).

5.3.2.6 Stability requirements shall be verified against market requirement and recorded.

5.3.3 Quality Assurance

Ensure no drug products manufactured using proposed material are released for sale until all relevant evaluation and qualification / validation requirements are met.

5.3.4 Third Party Contract Manufacturing Quality Assurance Group

5.3.4.1 Obtain all relevant supporting documents from affiliate users using the proposed materials.

5.3.4.2 Verify the manufacturer and/or supplier of the proposed material has been audited for manufacturing and/or supplying the proposed material.  Record audit detail in the relevant section in the RME document (Form 725).

5.3.4.3 Verify the proposed material is used by Third Party Contract Manufacturer and Verify the proposed material is used in Semi-finished goods at SITE, Site followed by further processing by Third Party Contract Manufacturer.  Record the outcome in the RME document (Form 725).

5.3.4.4 Communicate qualification/validation and stability requirements with the Third Party Contract Manufacturer, Procurement and Supply Planner.

5.3.4.5 Ensure qualification/validation studies have been completed by the Third Party Contract Manufacturer.

5.3.4.6 At the completion of all validation studies by the Third Party Contract Manufacture, Third Party Contract Manufacturing Quality Assurance Group informs all relevant departments that the validation has been completed.

5.3.4.7 If this material is currently used or evaluated by other sister site manufacturing facility then only one site must perform an evaluation.

5.3.4.8 Request and obtain any relevant evaluation data from the identified sister site and document the strategy in comments section of the RME document (Form 725).  The evaluation data obtained will form part of the RME document (Form 725).

5.3.5 Quality Operations Laboratory

5.3.5.1 Review and approve the RMSTR for the proposed material and ensure it is compliant with applicable current monograph and existing RMSTR.

5.3.5.2 Perform full testing on three batches of the proposed material as per the approved RMSTR for the proposed material.

5.3.5.3 Where full testing results can be obtained from another sister site facility, review the data and ensure it is in compliance as per the current site, site RMSTR for the proposed material.  Perform any additional testing as deemed necessary by the RME team (e.g. Particle Size, Bulk Density and Flow Characteristics.

5.3.5.4 In the case where the recommended number of evaluation samples are unattainable, or changes are being addressed retrospectively, then an alternate strategy must be agreed upon by the RME team before proceeding.  This alternate strategy should be documented in the Comments section of Section 5.1 of the Raw Material Evaluation Document (Form 725).

5.3.6 Environmental Health & Safety

Environmental, Health and Safety Considerations are assessed and/or reviewed and documented in section 6 of the RME document (Form 725).

5.3.7 Validation / Technical Services

5.3.7.1 Validation requirement assessment shall be performed base on the functionality, criticality and evaluation test results of the proposed material.  Assessment outcome shall be documented in Section 7, 8 and 9 of the RME document (Form 725).

5.3.7.1.1 For all API changes, the site shall manufacture drug product lots using the proposed material to demonstrate that there are no adverse variations within the product or process specifications as a result of the change in the material source.

5.3.7.1.2 At least one lot of each finished product containing the proposed material should be assessed.  However, in the case of the finished product which has more than one dosage, one batch of the lowest and one batch of the highest dosage is required to be validated.  Where formulations are considered to be equivalent, a family approach may be used.

5.3.7.1.3 For all excipients, the requirement to qualify the batch will be assessed on a case-by-case basis.

5.3.7.2 Validation requirement shall be approved as per approving procedure of the RME document (Form 725).

5.3.7.3 Technical Services Project Chemist raises Technical Service Alert Form (TSAF) for all batches under validation evaluation.  Validation of the proposed material should be performed as per SOP VAL-115 Process Validation for Liquids and Solid Dose Manufacturing.

5.4 Evaluation Document Closure

5.4.1 Any recommendations for completing the evaluation (including PCR submissions, validations) may be entered into database and the commitment numbers clearly stated in the RME document (Form 725) in the Recommendations section.

5.4.2 The RME document (Form 725) is circulated to the Procurement Manager, Validation / Technical Services Manager, Quality Assurance Manager, Quality Control Manager for approval of the evaluation outcome.

5.4.3 Completion of the RME document (Form 725) indicates one of the following:

5.4.3.1 The evaluation is complete with no additional recommendations.  The proposed material is suitable for use at SITE, Site for the drug products listed in Section 1 of the RME document (Form 725).  Or,

5.4.3.2 The proposed material is suitable for use in additional evaluation activities detailed under Section 8 of the RME document (Form 725); e.g. validation.

5.4.4 The Change Control cannot be closed until all recommendations listed in Section 8 of the RME document (Form 725) are completed.

5.5 Implementation

5.5.1 Supply Planner orders a commercial quantity of the proposed material for validation (if required) and/or manufacturing.  Supply Planner shall make a note in  the material database defining the Purchase Order (PO) as an evaluation material then alert the Receiving Dock / Warehouse.

5.5.2 Upon receipt of the delivery, the Receiving Dock / Warehouse shall check the PO notes and receipt the material against its RMSTR.  The delivery shall be sub-lotted with an “Evaluation” and coloured “Evaluation” labels shall be applied to the Goods Received Report and each container of the delivery.

5.5.3 Upon successful testing by the Quality Control Laboratory, a ‘Complete’ status is assigned in the material database to the delivery.

5.5.4 Supply Planner shall perform lot management allocations to the assigned batches.

5.5.5 Schedule validation batches and issue Manufacturing Instructions (MI) and/or Packaging Instruction (PI) as per process validation requirement for the change.

5.5.6 Distribute TSAF to relevant departments to inform validation activities with relevant departments.

5.5.7 Submit Stability Request Form with MI / PI when requested by Quality Control Laboratory.

5.5.8 When the validation batch(es) are ready to Release for Sale, Quality Assurance staff shall inform the Quality Assurance Manager prior to changing the status of the material from “Complete” to “Approved” in the material database to facilitate batch release.  The remainder of the material is then returned to “Complete” status.

5.5.9 At the completion of all successful validation studies, Technical Services shall inform all relevant departments that the evaluation process is complete.

5.5.10 Quality Control Laboratory Manager then changes the raw material status in ‘Complete’ to ‘Approved’ and issues the “Approved” labels.

5.5.11 Supply Planner then complete and submit a Form-505 Document Creation or Change Request to replace the current material with the approved proposed material in the documentation database.

5.5.12 Once the Document Creation or Change Request Form is processed, the Receiving Dock / Warehouse shall then deface the coloured “Evaluation” labels and the status of the evaluated material shall be changed to “Approved” in the material database and the “Approved” labels to be placed on the raw material container/s.

5.5.13 Once all recommendations from the RME document (Form 725) have been completed, the Change Control raised during the Evaluation Initiation stage can be closed by the Change Requestor.