CONTRACT MANUFACTURING AND THEIR AUDITING
3. CONTRACT MANUFACTURE AND ITS AUDIT AS PER UK LEGISLATION (ORANGE GUIDE) & TGA GUIDELINE & EUROPEAN GUIDELINE &NEW ZEALAND FOOD SAFETY AUTHORITY &PIC/S GUIDE :-
Contract manufacture and analysis must be correctly defined, agreed and controlled in order to avoid misunderstandings which could result in a product or work of unsatisfactory quality. There must be a written contract between the Contract Giver and the Contract Acceptor which clearly establishes the duties of each party. The contract must clearly state the way in which the Qualified Person releasing each batch of product for sale exercises his full responsibility.(PIC/S, 2006)
There should be a written contract covering the manufacture and/or analysis arranged under contract and any technical arrangements made in connection with it.
All arrangements for contract manufacture and analysis including any proposed changes in technical or other arrangements should be in accordance with the marketing authorisation for the product concerned.(PIC/S, 2006)
3.3.1. The Contract Giver is responsible for assessing the competence of the Contract Acceptor to carry out successfully the work required and for ensuring by means of the contract that the principles and guidelines of GMP as interpreted in this Guide are followed.
3.3.2.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 authorisation and any other legal requirements. The Contract Giver should ensure that the Contract Acceptor is fully aware of any problems associated with the product or the work which might pose a hazard to his premises, equipment, personnel, other materials or other products.
3.3.3. The Contract Giver should ensure that all processed products and materials delivered to him by the Contract Acceptor comply with their specifications or that the products have been released by a Qualified Person.(PIC/S, 2006)
3.4.The Contract Acceptor:-
3.4.1. The Contract Acceptor must have adequate premises and equipment, knowledge and experience, and competent personnel to carry out satisfactorily the work ordered by the Contract Giver. Contract manufacture may be undertaken only by a manufacturer who is the holder of a manufacturing authorisation.
3.4.2. The Contract Acceptor should ensure that all products or materials delivered to him are suitable for their intended purpose.
3.4.3. The Contract Acceptor should not pass to a third party any of the work entrusted to him 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 the manufacturing and analytical information is made available in the same way as between the original Contract Giver and Contract Acceptor.
3.4.4. The Contract Acceptor should refrain from any activity which may adversely affect the quality of the product manufactured and/or analysed for the Contract Giver.(PIC/S, 2006)
3.5.1 A contract should be drawn up between the Contract Giver and the Contract Acceptor which specifies their respective responsibilities relating to the manufacture and control of the product. Technical aspects of the contract should be drawn up by competent persons suitably knowledgeable in pharmaceutical technology, analysis and Good Manufacturing Practice. All arrangements for manufacture and analysis must be in accordance with the marketing authorisation and agreed by both parties.
3.5.2. The contract should specify the way in which the Qualified Person releasing the batch for sale ensures that each batch has been manufactured and checked for compliance with the requirements of Marketing Authorisation.
3.5.3. The contract should describe clearly who is responsible for purchasing materials, testing and releasing materials, undertaking production and quality controls, 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.
3.5.4.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 must be accessible and specified in the defect/recall procedures of the Contract Giver.
3.5.5.The contract should permit the Contract Giver to visit the facilities of the Contract Acceptor.
3.5.6.In the case of contract analysis, the Contract Acceptor should understand that he is subject to Inspection by the competent Authorities.(PIC/S, 2006)
3.6.1. Inspections should be conducted in order to monitor the implementation and compliance with Good Manufacturing Practice principles and to propose necessary corrective measures.
3.6.2. Personnel matters, premises, equipment, documentation, production, quality control, distribution of the medicinal products, arrangements for dealing with complaints and recalls, and self inspection, should be examined at intervals following a pre-arranged programme in order to verify their conformity with the principles of Quality Assurance.
3.6.3. Self inspections should be conducted in an independent and detailed way by designated competent person(s) from the company. Independent audits by external experts may also be useful.
3.6.4. All self inspections should be recorded. Reports should contain all the observations made during the inspections and, where applicable, proposals for corrective measures. Statements on the actions subsequently taken should also be recorded.(PIC/S, 2006)
4. CONTRACTER AUDIT AS PER USFDA, EU, AND ISO:- (Steinborn, L., 2003)
Contractor quality-assurance audits are performed to evaluate the status of a manufacturing operation, laboratory, testing service, or any other function performed by one company for another. It is important to recognize the reasons a company employs a contract manufacturing facility so that the auditor can determine what unique elements need to be taken into consideration in performing quality audits of these facilities.
There are three critical steps in performing contractor audits.
The auditor needs to review the specifics of the contractual agreement to perform a quality audit efficiently. As European Good Manufacturing Practice (GMP) requirements have long recognized, the specific contractual relationships between the contracting parties must be in writing that clearly delineates the responsibilities of each.
The International Organization for Standardization (ISO) series and new U.S. Quality System Regulation (QSReg.) also place strong emphasis on such formal agreements. It would be substantially embarrassing for someone to audit a contract manufacturing facility only to Fnd that the contractor was not required to perform a specific function. It could be even more embarrassing and problematic if the function were necessary but neither the contractor nor the procuring company was performing the function due to misunderstandings. For example, who will retain samples of the Finished product? If the contracting company assumes that the client is retaining samples while the client is assuming that the contractor is retaining samples, none may be retained.
A contractor audit is somewhat like a supplier audit and an internal-facility audit combined. The supplier-audit approach should be employed from the planning perspective. The auditor should establish a clear purpose for the audit, obtain as much information as possible about the contractor, and employ a formal checklist. As in the case of internal audits, one needs to determine whether announced or unannounced audits should be employed.
In the cas