1. Module 6 | Slide 1 of 16 2013 Contract Production, Analysis and other activities Section 7 Basic Principles of GMP

2. Module 6 | Slide 2 of 16 2013 Contract Activities Objectives To review general issues To understand the responsibilities of: äContract giver äContract acceptor To understand the contract (Also referred to as “outsourced activities”)

3. Module 6 | Slide 3 of 16 2013 7.1 – 7.4 Contract Activities Principle Contract production, analysis and any other outsourced activity - defined, agreed, and controlled. Should be in writing – to avoid misunderstandings Ensure work is done to GMP and as in marketing authorization Define duties and responsibilities of parties Address batch release (authorized person) and issue of certificate of analysis

4. Module 6 | Slide 4 of 16 2013 Contract Activities Responsibilities of the Contract Giver (1) Must have a PQS in place, allowing for control and review of outsourced activities. Assess legality, suitability, competence Ensure compliance with GMP and QRM principles applied Approve contracted activities Monitor and review its performance, including improvements and effectiveness thereof. Ensure understanding of inspections by regulators 7.5. – 7.9.

5. Module 6 | Slide 5 of 16 2013 7.6 – 7.7 Contract Activities Responsibilities of the Contract Giver (2) Provide all the necessary information to the contract acceptor in order to: ähave the operations carried out correctly in accordance with the manufacturing authorization and other legal requirements äbe fully aware of any hazards with the product, work, tests that might pose a risk to premises, equipment, personnel, other materials or other products Ensure that materials and products supplied by the contract acceptor are in compliance with specifications Products are released by the authorized person

6. Module 6 | Slide 6 of 16 2013 Contract Activities Responsibilities of the Contract Acceptor (1) Must have a manufacturing authorization Must have: äAdequate premises, equipment, knowledge, experience äCompetent personnel 7.10

7. Module 6 | Slide 7 of 16 2013 7.11. - 7.12. Contract Activities Responsibilities of the Contract Acceptor (2) No subcontracting to a third party without prior approval (The contract giver must be able to undertake audits needed to reassure that the third party is competent and approve subcontracting) All the required information should be given to the third party No conflicting activities or practices that could adversely affect the product(s)

8. Module 6 | Slide 8 of 16 2013 Contract Activities The Contract (1) Written agreement defining each party’s responsibilities and technical aspects – activities, products, operations, communication process Prepared by competent persons with knowledge in pharmaceutical technology, analysis and GMP Ensure compliance with marketing authorization –Production and analysis –Batch release –COA issued by the authorized person, compliance with marketing authorization –Flow of data and information for product quality review 7.13., 7.15., 7.16.

9. Module 6 | Slide 9 of 16 2013 Contract Activities The Contract (2) Batch release, and issuing of COA described Knowledge management Technology transfer Supply chain Sub contracting Testing and release of material Production, quality control, in process control 7.14., 7.17.

10. Module 6 | Slide 10 of 16 2013 Contract Activities The Contract (3) How does it address rejected materials /products? –starting materials –intermediate and bulk products –finished products What happens if the contract analysis shows that the tested product must be rejected? 7.19.

11. Module 6 | Slide 11 of 16 2013 Contract Activities The Contract (4) Who is responsible for: Material purchasing, testing and releasing Production and quality control including in-process quality control (IPQC) Sampling and analysis In the case of contract analysis: Who takes the sample? Where is the sample taken? Describe procedure if a tested product must be rejected 7.15, 7.17

12. Module 6 | Slide 12 of 16 2013 7.18. Contract Activities The Contract (4) The contract giver should keep or have access to: Reference standards and retention samples Records of: ämanufacturing äanalysis ädistribution In case of recalls, complaints and suspected defects: äall relevant records ädescribed in SOP

13. Module 6 | Slide 13 of 16 2013 Contract Activities Group Session Identify the items that should be included in a contract Why should these items be included? What should you do if you find a contract that does not include these items?

14. Module 6 | Slide 14 of 16 2013 Contract Activities Possible Issues – I Owners insist on using unsuitable facilities Owners insist on using relatives’ facilities No time to validate new facilities Contract acceptor takes on inappropriate new product

15. Module 6 | Slide 15 of 16 2013 Contract Activities Possible Issues – II Contract acceptor does not have all specified equipment Contract acceptor uses incorrect equipment Contract acceptor does not follow agreed procedures

16. Module 6 | Slide 16 of 16 2013 Contract Activities Possible Issues – III Contract acceptor uses an alternative material supplier Contract acceptor working with out-of-date specifications