1. Objective:
To ensure continuous consistent product quality, the quality of raw & packaging material from reliable vendors is essential. The purpose of this procedure is to describe the various activities and system for the approval of vendors for the active / inactive ingredients and packaging materials.
2. Scope:
This procedure is applicable for approval of all vendors (manufacturers) and suppliers of incoming Active Pharmaceuticals Ingredients (APIs), Inactive ingredients (Excipients) and packaging materials, which are required for manufacturing and packaging of finished products so as to control the purchasing of materials at (Company Name).
3. Responsibility:
3.1 QA Manager, QC Manager, Production Manager, R&D Manager and Purchase/Materials Manager shall jointly carry out vendor assessments.
3.2 Executive Director- Quality for approval and deletion of vendor.
4. Accountability:
4.1 Executive Director- Quality.
5. Precautions:
5.1 If any vendor is unable to filling up the vendor audit and development questionnaire then the vendor must provide the quality related information/ documents and based on the informations/ documents the QA team shall evaluate the vendor.
5.2 Prioritization of API’s and Primary Packing materials will be done for physical audit depending on the criticality of the materials.
6. Procedure:
6.1 All materials should be purchased only from approved vendors.
6.2 All materials should be received along with manufacturer Certificate of Analysis (COA). In case COA is not available, immediately inform to QA for his necessary advice.
6.3 No material is accepted from non approved vendor.
6.4 Vendor reaudit should be done every after 5 years. However, in case there is any quality issue/supply issue found during vendor rating (Reference 6.13.3) and product quality review report (SOP No.:QA013) then the reaudit may have to be done with prior communication and agreement with the supplier. In that case the reaudit timing will be anytime before 5 (five) years.
6.5 Procedure for approval of vendors of raw materials (active & inactive ingredients)
6.5.1 Definition of active ingredients: Active ingredients means any component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or other animals. The term includes those components that may undergo chemical change in manufacture of drug product and be present in drug product in a modified form intended to furnish the specified activity or effect.
6.5.2 Definition of inactive ingredients: All raw materials other than active ingredients are considered as inactive ingredients (excipients). Inactive ingredients are sourced either directly from manufacturer or through manufactures representative/ authorized dealers or from traders who stock the several materials from different manufacturers.
6.6 Materials department shall identify and locate the new vendor of raw materials (active/inactive ingredients).
6.7 In case the raw material is supplied by the trader/agent, shall disclose the manufacturer identity and an undertaking shall be obtained from the supplier that the material shall be supplied from the same manufacturer.
6.8 The method of approval of a vendor of raw materials (active/inactive ingredients) is done by at least one of the following methods.
6.8.1 If supplier questionnaire is not received even after repeated requests to the supplier, then the assessment of the materials can be done by the evaluating the finished product result where the material from that supplier was used.
Product analytical results of at least 5 batches to be evaluated to approve the supplier. The material will be tested up to full pharmacopeial tests.
6.8.2 Evaluation of raw materials through sample analysis from new vendors.
6.8.2.1 Materials department shall provide the approved specifications (and MOA on request) of the raw materials to the vendor and advise for the submission of three lots/batches/samples preferably consecutive along with certificates of analysis (COA) to quality assurance department. This is required to study the process capabilities of vendors with respect to consistent quality in the manufacturing process and to ensure that lot to lot variation is within acceptable limit.
6.8.2.2 QA shall arrange in-house analysis at QC as per current approved specifications and obtain the analysis report. If the three lots/batches/samples are in conformance with the specifications, the samples along with analytical reports and vendor selection form (Annexure – I) shall be sent to Research & Development (R&D) for performance test and comments. In case there is failure of one batch next consecutive three lots/batches/ samples shall be tested.
6.8.2.3 QA shall review and compile the report of QC and R&D.
6.8.2.4 QA shall forward the compiled report along with vendor selection form to Executive Director-Quality for final decision.
6.8.2.5 After receiving approval from Executive Director-Quality, QA shall inform the compliance results with a provisional approval of the vendor for the particular raw material to Materials department. This information shall also be intimated to production and Warehouse department.
6.8.2.6 In case of rejection of material or failure of performance test, QA shall inform to materials department with all relevant details for them to communicate concerned vendor.
6.8.2.7 R&D shall procure additional quantity of material through Material department if required.
6.8.2.8 Materials department after studying the comments of Quality Assurance department shall inform the vendor for the supply of the material (for production trials) in consultation with PPC/production departments.
6.8.2.9 Materials department shall also provide Vendor Audit & Development Questionnaire- Raw material (Annexure – II) to the vendor to evaluate the vendor Quality Management System (QMS). The response from the vendors shall be followed up by Materials department and on receipt shall be sent to QA.
6.8.2.10 The trial order material shall be analysed by QC and on full successful analytical test, the material shall be approved for use in production.
6.8.2.11 With the trial supply of the material, production department shall manufacture up to three batches depending on quantity available and requirement. Production and QA shall study the performance of the material and quality of the product manufactured using the material supplied by new vendor.
6.8.2.12 After complete assessment of the quality and questionnaire, the new vendor shall be included in the temporary approved vendor list and the same shall be informed to the materials and Warehouse departments by QA.
6.8.2.13 Vendor Audit
After successful completion of manufacturing and packing of at least 3 process validation batches QA department will undertake a GMP/Quality audit at the vendor’s manufacturing facilities (API) to assess the Quality Management systems and compliance to GMP requirements.
A vendor audit schedule (Annexure – VI) should be prepared before beginning of the next year. QA Manager/Quality Head will communicate to the vendor/ supplier’s QA for mutually agree on audit schedule. Once audit schedule is agreed, the QA manager/Quality Head will provide an audit agenda to the vendor/supplier’s QA Head. Audit will generally be performed as per audit agenda.
Once the audit is completed QA Manager/Quality Head will generate an audit report with a comment on the approval status (Provisional approval/ approval/Non approval). A copy of quality audit report prepared by QA shall be sent to material department for onward submission to the vendor.
Follow up with vendor for compliance to the recommendations suggested in the audit report shall be done by QA.
A desktop audit for excipients and primary packaging materials will be documented through vendor audit and development questionnaire.
The unique document numbering for Vendor Audit Report shall be done as under:
ADT_Report_SA_001
Where,
ADT_Report_SA is vendor (supplier) audit report
_ is underscore
001 is the sequential number
QA shall issue the vendor audit report number and maintain the log register as per form No. FQA/092 (Annexure – III).
6.8.2.14 Exceptions to the above procedure (for e.g., non- availability of three consecutive batch samples) are done in isolated situations and shall be justified and approved by QA. The above procedure is followed with available number of sample batches for pre-purchase approval. In few instances, direct consignment for production trials may be received and approved by R&D and QA after appropriate evaluation.
6.8.2.15 After satisfactory performance of a reasonable number of batches supplied, at least 3(three), QA shall provide permanent approval status and update the approved vendor list and provided the same to materials and to Warehouse department. However, in case one out of at least three consecutive supplied lots is rejected, further three consecutive lots to be assessed before giving the permanent approval status.
6.8.2.16 In specific cases, justified by QA, the accelerated stability study of the product manufactured from the plant trial batches shall be taken up.
6.8.2.17 QA shall review the suppliers stability study data and plant trial batches data and after approval of satisfactory results inform to supplier and include in approved vendor list.
6.8.3 Evaluation by experience of active and inactive ingredient already supplied to R&D
6.8.3.1 When the vendor is new for site but he is approved vendor at R&D for the same active or inactive ingredients, the following procedure shall be followed.
6.8.3.2 Materials department shall intimate to QA department regarding prior status purchasing and supplying the materials to R&D and indicate the approval status for the raw material. A typical certificate of analysis (COA) from the vendor indicating compliance to site’s specification shall be sent along with the information.
6.8.3.3 QA shall evaluate the details and confirm from the R&D for the specifications used, the product for which it is used, analysis results from QC of several consecutive batches, any rejections, stability issues and any other relevant information available.
6.8.3.4 QA shall incorporate the vendor in tentative vendor list of site and inform materials and warehouse department of site.
6.8.3.5 After satisfactory performance of the active or inactive ingredients at production level for three consecutive supplies, QA shall provide permanent approval status, update the approved vendor list and provided the same to materials and site Warehouse department.
6.9 Procedure for approval of overseas vendor
6.9.1 Preferably all overseas vendors for APIs shall be audited. In case it is not possible to audit then following steps shall be carried out for approval of such vendors.
6.9.1.1 The material department shall provide pre-shipment sample of API with COA to R&D for formulation trial batch.
6.9.1.2 Simultaneously, a Vendor Audit & Development Questionnaire – Raw material (Annexure – II) shall be sent to vendor to gather information on facility and GMP system.
6.9.1.3 Audit questionnaire response shall be reviewed by QA.
6.9.1.4 QC test results and 3(three) R&D trial batches results shall be reviewed.
6.9.1.5 After satisfactory review vendor can be approved and included in the approved vendor list.
6.9.1.6 If supplier questionnaire is not received even after repeated requests to the supplier, then the assessment of the materials can be done by the evaluating the finished product result where the material from that supplier was used.
Product analytical results of at least 5 batches to be evaluated to approve the supplier. The material will be tested up to full pharmacopeial tests
6.10 Procedure for approval of vendor of active or inactive ingredients for campaign /non regular and bio batches of drug products
6.10.1 Active and inactive ingredients received for campaign/ non-regular/ bio batch products are procured along with the certificate of analysis from the vendor.
6.10.2 Based on 3(three) R&D trial batches performance and QA approval the material is cleared directly to Production department for trial batches. This vendor on satisfactory production trials shall be included in the vendor list.
6.11 Procedure for approval of vendors recommended by contract manufacturer
6.11.1 The contract manufacturer shall provide details of vendor during technology transfer activity. The respective vendor shall be included as approved vendor in contract manufacturer approved vendor list.
6.12 Categorization of suppliers based on status
6.12.1 The suppliers of Raw Materials are to be categorized as Provisional, Approved & Certified based on the status of supplier evaluation procedure.
6.12.2 Based on the initial assessment of a supplier by QA following one of the procedures described in section 6.8, the supplier will be considered as provisional and will be allowed to supply commercial batches. Full testing of the materials as per the approved specification shall be done at this stage.
6.12.3 After successful completion of the testing of at least 3 consecutive batches followed by successful manufacturing of at least 3 commercial batches of the product, the supplier will be considered as Approved supplier. At this stage, reduced testing can be followed which should be limited to conducting at least the full identification tests and the critical tests (e.g. Appearance, assay, related substances, water content/LOD, Bulk/Tapped density etc.). However, full testing shall be done on every 10th batch or one batch per year.
6.12.4 Reviewing the performance of an approved supplier of supplying minimum 10 consecutive batches, it can be declared as Certified supplier, for which the testing should done as applicable for approved supplier.
6.13 Procedure for approval of vendors for packaging materials
6.13.1 Primary packaging material The packaging materials used which are in direct contact of drug product. The vendor of primary packaging materials are approved on one of the following criteria as
6.13.1.1 DMF approved source.
6.13.1.2 Evaluated by R&D during product studies including supplier Certificate of Analysis.(COA)
6.13.1.3 Recommended by contract manufacturer for their product.
6.13.2 The Vendor Audit & Development Questionnaire – packaging material (Annexure – IV) is to be forwarded to indigenous vendor and evaluated. On the basis of sample studies by R&D.
6.13.3 After confirmation from R&D and review of vendor questionnaire, vendor is included in approved vendor list.
6.13.4 Secondary packaging material
6.13.4.1 Secondary packaging materials are primarily supplied by Shuktara Printers which belongs to (Company Name) and almost 90% of the total volume is supplied by Shuktara Printers. There are also a few local secondary packaging material suppliers. Vendor evaluation of secondary packaging material supplier for their total supplies will be done every 2 years.
6.13.4.2 The Specifications shall be sent to the supplier of the material and his acceptance of the specification shall be obtained.
6.13.4.3 The samples, certificate of analysis along with traceability of certificate shall be obtained from suppliers and evaluated.
6.13.5 Vendor Audit: Vendor audit for packaging materials shall be done as per procedure described in step 6.8.2.13.
6.14 Vendors evaluation
6.14.1 Materials department shall carefully study the delivery schedule compliance and the capability of the vendor to supply the required material within the period and with the right quality.
6.14.2 The Vendor performance (Annexure-VII) shall be evaluated periodically (at least once in a year) for the API and at least once in two years for key inactive ingredients (excipients) & primary packaging materials on the basis of parameters like delivery, quality and vendor approval rate shall be given. Additionally, a review of the audit report issued (if any) & Vendor Audit & Development Questionnaire report and complaints/ non-conformity of supplied material shall be done.
6.14.2.1 QA shall assign the number for each report of supplier performance assessment as per the SOP (QA003).
6.14.3 Vendor rating
6.14.3.1 QA and materials department shall jointly do vendor rating.
6.14.3.2 Rating of vendor shall be done on the basis of quality of supplies and delivery schedules as described below.
Total number of supplies – number of rejection supplies
Quality score (%) = ——————————————————————- ×100
Total number of supplies
Total number of supplies – number of supplies delayed
Delivery score (%) = ——————————————————————- × 100
Total number of supplies
6.15 Procedure for exclusion of vendor from approved vendor’s list
6.15.1 The vendor shall be disqualified and removed from the approved vendor’s list for following reasons during regular assessment.
6.15.1.1 If consecutive 3 consignment of material fail to comply the specifications or if the quality score is below 70%.
6.15.1.2 Three out of ten consignments fail to comply the specification.
6.15.1.3 The delivery score is not met for 40% of supplies.
6.15.2 Corrective and preventive action:
6.15.2.1 The vendor shall be made aware of the reasons for his exclusion and shall agree improvement action plans.
6.15.2.2 The vendor, who has been excluded from the approved vendor’s list, may be included again by taking following corrective action and preventive actions.
6.15.2.3 Executive Director-Quality or his representatives shall conduct facility audit of the vendor in order to ensure that quality system exists in the organization.
6.15.2.4 Carry out the discussion on other non – quality issues like delivery schedule and rate etc. After satisfactory outcome of all above points the vendor shall be approved as per the new vendor evaluation procedure. (Step no. 6.8.2 and 6.9)
6.16 Re-introduction of earlier approved vendor after discontinuation
6.16.1 There can be cases of ceasing or discontinuation of vendor for Technocommercial reasons.
6.16.2 The vendors who were earlier approved but not included in current list can be considered for incorporation into approved vendor list. Materials department shall intimate to QA with this effect.
6.16.3 The system shall be as per step No. 6.8.2 and QA shall decide to re- approve the vendor after initial sample analysis only.
6.17 Procedure for approval of new material from Existing approved vendor
6.17.1 The system shall be as per step No. 6.8.2 except there is no need to sent audit questionnaire for new material approval.
6.18 Procedure for approval of new vendor for existing material
6.18.1 The system shall be as per step No. 6.8.2.
6.19 Procedure for preparation and updating of approved vendor list
6.19.1 Separate Approved vendor list shall be prepared for raw materials and packaging materials in Annexure – V.
6.19.2 The material shall be arranged alphabetically in the list.
6.19.3 In case of addition of new vendor, QA shall issue addendum list time to time to all the concerned departments.
6.19.4 QA shall jointly review and update approved vendor list on half yearly basis. (i.e. in the month of January & July every year).
6.19.5 A list of all approved vendors shall be maintained by Purchase, Materials, Warehouse, Quality Control (QC), Quality Assurance (QA) and Research & Development (R&D) etc.
6.20 Procurement of Raw Materials from approved vendor:
6.21 Materials department shall procure any raw material from one of the approved vendors for that material. The material for second approved vendor will be considered only when the first vendor fails to supply or there is a considerable price, product quality issue with the first vendor.