7. Contract Production, Analysis and Other Activities
7.1 Principle. Contract production, analysis and any other activity covered by GMP must be correctly defined, agreed and controlled in order to avoid misunderstandings that could result in a product, or work or analysis, of unsatisfactory quality.
General:
7.2 All arrangements for contract production and analysis, including technology transfer and any proposed changes in technical or other arrangements, should be in accordance with the marketing authorization for the product concerned.
7.3 The contract should permit the contract giver to audit the facilities and activities of the contract acceptor or mutually agreed subcontractors.
7.4 In the case of contract analysis, the final approval for release must be given by the authorized person in accordance with GMP and the marketing authorization as specified in the contract.
The Contract Giver:
7.5 The PQS of the contract giver should include the control and review of any outsourced activities. The contract giver is responsible for assessing the legality, suitability and competence of the contract acceptor to successfully carry out the work or tests required, for approval for contract activities, and for ensuring by means of the contract that the principles of GMP incorporating QRM principles are followed.
7.6 The contract giver should provide the contract acceptor with all the information necessary to carry out the contracted operations correctly in accordance with the marketing authorization and any other legal requirements. The contract giver should ensure that the contract acceptor is fully aware of any hazards associated with the product, work or tests that might pose a risk to premises, equipment, personnel, other materials or other products.
7.7 The contract giver should review and assess the records and results related to the outsourced activities. The contract giver should ensure that all products and materials delivered by the contract acceptor have been processed in accordance with GMP and the marketing authorization; comply with their specifications and that the product has been released by the authorized person in accordance with GMP and the marketing authorization.
7.8 The contract giver should monitor and review the performance of the contract acceptor including the implementation of any needed improvements and their effectiveness.
7.9 The contract giver is responsible for ensuring that the contract acceptor understands that his or her activities may be subject to inspection by competent authorities.
The Contract Acceptor:
7.10 The contract acceptor must have adequate premises, equipment, knowledge, experience and competent personnel to satisfactorily carry out the work ordered by the contract giver. Contract manufacture may be undertaken only by a manufacturer who holds a valid manufacturing authorization.
7.11 The contract acceptor should not pass to a third party any of the work entrusted to him or her under the contract without the contract giver’s prior evaluation and approval of the arrangements. Arrangements made between the contract acceptor and any third party should ensure that information and knowledge, including that from assessments of the suitability of the third party, are made available in the same way as between the original contract giver and contract acceptor.
7.12 The contract acceptor should refrain from any activity (including unauthorized changes outside the terms of the contract) that may adversely affect the quality of the product manufactured and/or analysed for the contract giver.
The Contract:
7.13 There must be a written contract between the contract giver and the contract acceptor which clearly establishes the responsibilities of each party, covering the outsourced activities, the products or operations to which they are related, communication processes relating to the outsourced activities and any technical arrangements made in connection with it.
7.14 The contract must clearly state the way in which the authorized person, in releasing each batch of product for sale or issuing the certificate of analysis, exercises his or her full responsibility and ensures that each batch has been manufactured in, and checked for, compliance with the requirements of the marketing authorization.
7.15 Technical aspects of the contract should be drawn up by competent persons with suitable knowledge of pharmaceutical technology, analysis and GMP.
7.16 All arrangements for production and analysis must be in accordance with the marketing authorization and agreed by both parties.
7.17 The contract should clearly describe who is responsible for contracted activities, e.g. knowledge management, technology transfer, supply chain, subcontracting, testing and releasing materials and undertaking production and QC, including in-process controls, and who has responsibility for sampling and analysis. In the case of contract analysis, the contract should state whether or not the contract acceptor should take samples at the premises of the manufacturer.
7.18 Manufacturing, analytical and distribution records, and reference samples, should be kept by, or be available to, the contract giver. Any records relevant to assessing the quality of a product in the event of complaints or a suspected defect, or to investigating in the case of a suspected falsified product or laboratory fraud, must be accessible and specified in the procedures of the contract giver.
7.19 The contract should describe the handling of starting materials, intermediate, bulk and finished products, if they are rejected. It should also describe the procedure to be followed if the contract analysis shows that the tested product must be rejected.
WHO Good Manufacturing Practices For Pharmaceutical Products: Main Principles
(Annex 2, WHO Technical Report Series 986, 2014)
