1. M.Pharm – Sem – III Department of Quality Assurance VENDOR CERTIFICATION 1

2. Content: Definition Categories Benefits of certification Steps involve in certification cGMP requirement for vendor certification Standard procedure for conducting Quality Audit References 2

3. DEFINITION: 3 Vendor certification is a supplier-customer partnership,and can only be successful with the full involvement and agreement of both partners OR It is the combination of activities required to ensure that a vendor will meet the professional and regulatory expectation of the sponsor OR It is the system that assure that a supplier’s product is produced under controlled condition,resulting in consistent quality conformance

4. SPONSOR VENDOR (contract manufacturer) VENDOR (contract labeler) VENDOR (contract packager) Supplier of manufacturing materials Supplier of labeling materials Supplier of packaging materials contract Relationship between sponsor, vendor and supplier 4

5. Characteristic of vendor categories 5 Vendors are mainly categorized into 4 different categories, CATEGORY – 1 generally regarded as EXPERTS ‘short lived’ in development cycle contracted to perform limited scope of work “minimal monitoring” Example: Supplier customizes a formulation tank. Sponsor reviews and approves the blueprints prior to manufacturing. Then IQ and OQ is planned upon receipt to verify acceptability

6. CATEGORY – 2 Well known suppliers of standard containers,closures,raw materials and excipients Certified to an International Standards Organization (ISO)-9000 quality management system Enhanced monitoring is suggested Example: Well-known supplier of containers/closures supplies multiple lots per year of vials to the sponsor. The sponsor has no historical quality concerns with the supplier. Testing will be conducted upon receipt to verify acceptability of materials. 6

7. CATEGORY – 3 Category 3 vendors may be category 2 vendors who are experiencing quality issues with current incoming inventory or have shown a trend of non-conformance over the last 12 months Can be contract laboratory operations that provide routine analysis, sometimes in large quantities The risk of non-conformance of these vendors is greater than with category 2 vendors advanced monitoring program and an annual audit schedule are recommended. 7

8. CATEGORY – 4 They are sole-source API manufactures intense monitoring is suggested in this category Examples: A contract manufacture is supplying clinical trials supplies. Since this is the first time that the product is being manufactured at a larger scale, the sponsor has elected to be on site for each event for monitoring and consultation 100% of the lot will be visually inspected for release upon receipt by the sponsor 8

9. 9 CATEGORY OF VANDORTYPE OF VENDOR SUPPLIERMONITORIG NEEDED Category 1 1.Supplier of manufacturing supplies i.e. catalog items 2.Supplier of customized manufacturing supplies Minimal Category 2 1.Raw material, excipients supplier 2.Container/closure supplier Enhanced Category 3 Similar to category 2 vendors but risk of non conformance is more Advance Category 4 1.Contract manufacturer- clinical trial supplies 2.Contract packager 3.Contract manufacturer- API Intense COMPARATIVE REVIEW :

10. Why to qualify vendors ? 10 Used to determine if the vendor is appropriate for the scope of work Critical attributes of a partner relationship are 1) Supplier or customer commitment to a long term relationship 2) Information sharing 3) Joint agreement on specifications and performance standards 4) Performance measurement and feedback 5) Customer confidence in the supplier’s manufacturing capability quality, cost, and development These attributes will vary depending on the status of the supplier- customer relationship

11. Benefits of the Certification : 11 Pharma firms not have to carry out their own quality audit of the vendor Vendors will give assurance that customers of the product will not have to carry out their own quality audit of their systems or products Rapid and efficient qualification process prior to sale and delivery/acceptance of a system Reduced cost

12. Steps involve in certification process : 12 CUSTOMER TEAMS : Team includes representative from manufacturing,package engineering, purchasing and quality assurance team Also from some other disciplines like finance, research and development Function : 1)define the objectives and potential benefits 2)write a process that can be used as a basis for discussion with suppliers

13. SUPPLIER SELECTIONS supplier’s history in terms of quality, delivery, and support service as well as the importance of the specific material to the business chance of success with a supplier who already has a high commitment to quality and customer service INITIAL SUPPLIER CONTACTS The proposed process will be discussed with the supplier After agreement on the concept the individual components of the process can be reviewed and adapted for mutual satisfaction 13

14. Process Elements : 1.Supplier process 2.Specifications 3.Process evaluation  Supplier process Customer team should visit the supplier’s plant to gain an understanding of the production process and the key elements which impact on the achievement of quality standards Where a material may be supplied from more than one plant of the supplier, each plant must be treated as a separate entity for certification purposes 14

15.  Specifications Detailed review should be made of product specifications with particular reference to legal requirements (compendia, FDA, etc.) Done to increase the level of assurance on more critical parameters Example : 1) In packaging components where improvements in some areas can dramatically impact on line speeds and efficiency 2) particle size of powder ingredients. 15

16.  Process evaluation Supplier must have suitable equipment to monitor the process and this equipment must be routinely calibrated and test methods validated Statistical process control techniques should be applied to demonstrate that the process remained under control, within acceptable operating ranges, throughout each production run Process control data for several batches should be chosen at random and reviewed to confirm supplier compliance 16

17. Process and Specification Changes Any proposed changes must be clearly documented, with reasons and supporting data, and be reviewed and accepted by the customer prior to introduction Some changes may require customer evaluation and even FDA approval before acceptance Changes require, prior review and agreement with the supplier For example, if the customer wants to make any replacement of a packaging line, there would need to be discussions with the supplier of the packaging components and the customer regarding changes 17

18. Customer Inspection After it has been confirmed that a supplier has a controlled process, there usually will be a period when both parties evaluate material quality and compare data This provides the needed assurance that supplier and customer have comparable evaluation ability and minimizes future potential for disagreements that are due to test results Vendor certification provides a strong basis for the application of reduced testing by the customer If the supplier’s process is under control, evaluation by the customer Is necessary to evaluate any changes during shipment 18

19. Supplier Reporting Since vendor certification is a partnership, it is important that both supplier and customer are kept informed of each other’s difficulties The supplier must notify the customer of any typical situations or process deviations prior to shipping material so that any additional testing or evaluations may be performed Supplier should also provide certificates of compliance or certificates of analysis for every batch—formatted in a manner which is acceptable to the customer The customer should also provide feedback to the supplier with respect to compliance with specification, performance in use, and delivery service 19

20. Decertification Certification results in a high level of reliance on the supplier : reduced incoming inspection, reduced inventories, higher output Any failure by the supplier for matching the customer’s requirement, may lead to decertification of that supplier for that material Depending on the nature of the problem it may be possible to work with the supplier to reestablish certification 20

21. CGMP REQUIREMENTS FOR VENDOR QUALIFICATION  Divided into two sections 1) Site Qualification 2) Site follow-up Site Qualification : Vendors selected are evaluated for compliance with the appropriate set of regulations The results of the audit will be reviewed and the need for a ‘‘site follow-up visit’’ Site qualification visits are generally performed on a cyclical basis; at least once every 24 months is suggested unless the supplier becomes problematic continuous monitoring program is also an essential component 21

22. BENEFIT : ability to evaluate the systems that the vendor uses to produce regulated work product. If a systems ‘‘gap’’ is detected in any of the quality systems the sponsor should request corrective action prior to initiating the work RISK : Here the systems review is theoretical, not practical No ‘‘real’’ data can be reviewed prior to initiating the work The systems cannot be adequately tested without ‘‘real’’ data 22

23. SITE FOLLOW-UP : Carried out during the course of the project Examples of issues that will usually result in site follow-up include 1) lack of adherence to standard operating procedures 2) lack of appropriate documentation of training, major renovations to the physical structure of the facility 3)if standard operating procedure (SOP) or data integrity questions arise during the course of the study or project 23

24. 24 BENEFIT : Ability to evaluate the systems that the vendor uses to produce regulated work product in ‘‘real time’’ with data generated for a specific project RISK : Any corrections that may be needed will not occur in a timely manner due to late identification of deficiencies will delay the project

25. FACTORS TO BE CONSIDER WHEN PLANNING FOLLOW UP VISIT : The relationship and experience with vendor The extent of vendor experience with the sponsor scope of work The sponsor’s regulatory commitments and compliance requirements The associated risks if project fails 25

26. STANDARD PROCEDURE FOR CONDUCTING QUALITY AUDIT : Standard procedures for conducting the quality audit should be addressed in the Vendor qualification program An audit cycle includes 1.The preparation of an audit 2.Performance of the audit 3.Reporting of the results of the audit 4.Audit closure or follow-up requirements 26

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28. Step1: Preparing for the Audit most critical part of the audit takes longer to complete than performing the actual audit By putting more time into the preparation phase, the performance of the audit will proceed smoothly. effective audit plan will include the following elements: Purpose for the audit Scope of the audit Resources required of the sponsor to complete the audit Number of auditors Type of auditor or expertise required Assignment of a lead auditor to take responsibility for the audit Reference documents to be used in planning and performing the audit 28

29. Step 2: Performing the Audit The performance of an audit begins with an introductory meeting wherein all parties are introduced and the agenda is discussed The performance of an audit is the collection of evidence and verification of information through, o Interviews o Examination of documents o Direct observation of activities, processes, and conditions o Review of raw data related to critical documents 29

30. Step 3: Reporting the Results Audit report should present a summary of the results or findings of the audit This includes both positive findings and any areas identified for improvement Written summary prior to leaving the vendor’s facility allows the vendor to begin working on the corrective action plans lead auditor is responsible for submitting the formal report in a timely fashion Final audit report should be prepared within 2 weeks from the date of the audit 30

31. Step 4: Audit Closure, Corrective Action, and Follow-Up After audit, vendor is responsible for developing a corrective action plan to address any weaknesses or deficiencies identified by the sponsor’s auditors It is the sponsor’s responsibility to ensure that the corrective actions are effective and implemented in a timely manner The sponsor must verify all commitments through the course of routine monitoring 31

32. COMMON PITFALLS IN VENDOR QUALIFICATION 32 Not establishing the habit of routine update meetings Overestimating the capabilities of the vendor Having a false sense of confidence that the vendor will maintain itself at the same level throughout the contractual relationship Underestimating the resource-intensiveness of maintaining a vendor Qualified Not switching vendors when appropriate Not dealing with situations of non-conformance in a timely and effective manner Overburdening the supplier, as though you were its only client

33. 33 Underestimating the amount of time and effort it takes to initially qualify a vendor Failing to understand how systems work within the vendor’s organization Failing to periodically authenticate raw data provided by the supplier Cont..

34. REFRENCES GMP for pharmaceuticals ( a plan for total quality control from manufacturer to consumer ) volume-109.5 th edition Sidney h. Willing Laboratory auditing for quality regulatory compliance,volume 150, Donald c.signer et.al “Pharmaceutical Process validation” second edition, revised and expanded; Marcel Dekker series; Pg.No.347-372.Elizabeth M. Troll, Karen L. Hughes. 34

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