Good Manufacturing Practices (GMP) PDF

Good Manufacturing Practices(GMP) PPA 311 TOPIC 4  Good Manufacturing Practices(GMP) The quality of pharmaceuticals has been a concern of the World Health Organization (WHO) since its inception. The setting of global standards is requested in Article 2 of the WHO Constitution, wh...

Good Manufacturing Practices(GMP) PPA 311 TOPIC 4  Good Manufacturing Practices(GMP) The quality of pharmaceuticals has been a concern of the World Health Organization (WHO) since its inception. The setting of global standards is requested in Article 2 of the WHO Constitution, which cites as one of the Organization’s functions that it should “develop, establish and promote international standards with respect to food, biological, pharmaceutical and similar products.”  Good Manufacturing Practices(GMP) The first WHO draft text on good manufacturing practices (GMP) was prepared in 1967 by a group of consultants at the request of the Twentieth World Health Assembly (resolution WHA20.34). It was subsequently submitted to the Twenty-first World Health Assembly under the title “Draft requirements for good manufacturing practice in the manufacture and quality control of drugs and pharmaceutical specialities” and was accepted. The revised text was discussed by the WHO Expert Committee on Specifications for Pharmaceutical Preparations in 1968 and published as an annex to its twenty-second report. The text was then reproduced (with some revisions) in 1971 in the Supplement to the second edition of The International Pharmacopoeia  Good Manufacturing Practices(GMP) In 1969, when the World Health Assembly recommended the first version of the WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce in resolution WHA22.50, it accepted at the same time the GMP text as an integral part of the Scheme. In 1992, the revised draft requirements for GMP were presented in three parts Quality assurance as well as the principal components or subsystems of GMP, which are joint responsibilities of top management and of production and quality control management. These include hygiene, validation, self-inspection, personnel, premises, equipment, materials and documentation  Terms in GMP Active pharmaceutical ingredient (API): Any substance or mixture of substances intended to be used in the manufacture of a pharmaceutical dosage form and that, when so used, becomes an active ingredient of that pharmaceutical dosage form. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure and function of the body Authorized person: The person recognized by the national regulatory authority as having the responsibility for ensuring that each batch of finished product has been manufactured, tested and approved for release in compliance with the laws and regulations in force in that country. Batch (or lot): A defined quantity of starting material, packaging material, or product processed in a single process or series of processes so that it is expected to be homogeneous  Terms in GMP Calibration: The set of operations that establish, under specified conditions, the relationship between values indicated by an instrument or system for measuring (especially weighing), recording, and controlling, or the values represented by a material measure, and the corresponding known values of a reference standard. Limits for acceptance of the results of measuring should be established Clean area: An area with defined environmental control of particulate and microbial contamination, constructed and used in such a way as to reduce the introduction, generation, and retention of contaminants within the area. Contamination: The undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or on to a starting material or intermediate during production, sampling, packaging or repackaging, storage or transport.  Terms in GMP Manufacture: All operations of purchase of materials and products, production, quality control, release, storage and distribution of pharmaceutical products, and the related controls Marketing authorization (product licence, registration certificate):A legal document issued by the competent drug regulatory authority that establishes the detailed composition and formulation of the product and the pharmacopoeial or other recognized specifications of its ingredients and of the final product itself, and includes details of packaging, labelling and shelf-life Master formula: A document or set of documents specifying the starting materials with their quantities and the packaging materials, together with a description of the procedures and  Terms in GMP Production: All operations involved in the preparation of a pharmaceutical product, from receipt of materials, through processing, packaging and repackaging, labelling and relabeling, to completion of the finished product Qualification: Action of proving that any premises, systems and items of equipment work correctly and actually lead to the expected results. The meaning of the word “validation” is sometimes extended to incorporate the concept of qualification. quality assurance : is the totality of the arrangements made with the object of ensuring that pharmaceutical products are of the quality required for their intended use. Quality assurance therefore incorporates GMP and other factors, including those outside the scope of this guide such as product design and development quality control: is the part of GMP concerned with sampling, specifications and testing, and with the organization, documentation and release procedures which ensure that the necessary and relevant tests are actually carried out and that materials are not released for use, nor products released for sale or supply, until their quality has been judged to be satisfactory. Quality control is not confined to laboratory operations but must be involved in all decisions concerning the quality of the product  Terms in GMP Specification: A list of detailed requirements with which the products or materials used or obtained during manufacture have to conform. They serve as a basis for quality evaluation. Standard operating procedure (SOP): An authorized written procedure giving instructions for performing operations not necessarily specific to a given product or material (e.g. equipment operation, maintenance and cleaning; validation; cleaning of premises and environmental control; sampling and inspection).  Certain SOPs may be used to supplement product-specific master and batch production documentation. Terms in GMP Starting material :Any substance of a defined quality used in the production of a pharmaceutical product, but excluding packaging materials. Validation: Action of proving, in accordance with the principles of GMP, that any procedure, process, equipment, material, activity or system actually leads to the expected results Good manufacturing practices for pharmaceutical products (GMP) Good manufacturing practices is that part of quality assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization. GMP are aimed primarily at diminishing the risks inherent in any pharmaceutical production. Such risks are essentially of two types: cross contamination (in particular of unexpected contaminants) and mix-ups (confusion) caused by, for example, false labels being put on containers  Good manufacturing practices for pharmaceutical products (GMP) 1. All manufacturing processes are clearly defined, systematically reviewed in the light of experience, and shown to be capable of consistently manufacturing pharmaceutical products of the required quality that comply with their specifications; 2. Qualification and validation are performed at predetermined times; 3. All necessary resources are provided, including: (i) appropriately qualified and trained personnel; (ii) adequate premises and space; (iii) suitable equipment and services; (iv) appropriate materials, containers and labels; (v) approved procedures and instructions; (vi) suitable storage and transport; (vii) adequate personnel, laboratories and equipment for in-process controls;  Good manufacturing practices for pharmaceutical products (GMP) 4. Instructions and procedures are written in clear and unambiguous language, specifically applicable to the facilities provided; 5. Operators are trained to carry out procedures correctly; 6. Records are made (manually and/or by recording instruments) during manufacture to show that all the steps required by the defined procedures and instructions have in fact been taken and that the quantity and quality of the product are as expected; any significant deviations are fully recorded and investigated; 7. Records covering manufacture and distribution, which enable the complete history of a batch to be traced, are retained in a comprehensible and accessible form; 8. The proper storage and distribution of the products minimizes any risk to their quality; 9. A system is available to recall any batch of product from sale or supply; 10. Complaints about marketed products are examined, the causes of quality defects investigated, and appropriate measures taken in respect of the defective products to prevent recurrence  Qualification and validation In accordance with GMP, each pharmaceutical company should identify what qualification and validation work is required to prove that the critical aspects of their particular operation are controlled. The key elements of a qualification and validation programme of a company should be clearly defined and documented in a validation master plan. Qualification and validation should establish and provide documentary evidence that: (a) the premises, supporting utilities, equipment and processes have been designed in accordance with the requirements for GMP (design qualification, or DQ); (b) the premises, supporting utilities and equipment have been built and installed in compliance with their design specifications (installation qualification, or IQ); (c) the premises, supporting utilities and equipment operate in accordance with their design specifications (operational qualification, or OQ); (d) a specific process will consistently produce a product meeting its predetermined specifications and quality attributes (process validation, or PV, also called performance qualification, or PQ). (e) Any aspect of operation, including significant changes to the premises, facilities, equipment or processes, which may affect the quality of the product, directly or indirectly, should be qualified and validated.  Qualification and validation f. Qualification and validation should not be considered as one-off exercises. An ongoing programme should follow their first implementation and should be based on an annual review. g. The commitment to maintain continued validation status should be stated in the relevant company documentation, such as the quality manual or validation master plan. h. The responsibility of performing validation should be clearly defined. i. Validation studies are an essential part of GMP and should be conducted in accordance with predefined and approved protocols. j. A written report summarizing the results recorded and the conclusions reached should be prepared and stored. k. Processes and procedures should be established on the basis of the results of the validation performed. l. It is of critical importance that particular attention is paid to the validation of analytical test methods, automated systems and cleaning procedures.  Contract production and analysis Contract production and analysis 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. All arrangements for contract manufacture and analysis, including any proposed changes in technical or other arrangements, should be in accordance with the marketing authorization for the product concerned. The contract should permit the contract giver to audit the facilities of the contract accepter. In the case of contract analysis, the final approval for release must be given by the authorized person. The contract giver : The contract giver is responsible for assessing the competence of the contract accepter in successfully carrying out the work or tests required, for approval for contract activities, and for ensuring by means of the contract that the principles of GMP described in this guide are followed  Contract production and analysis The contract giver should provide the contract accepter 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 accepter is fully aware of any problems associated with the product, work or tests that might pose a hazard to premises, equipment, personnel, other materials or other products. The contract giver should ensure that all processed products and materials delivered by the contract accepter comply with their specifications or that the product has been released by the authorized person.  Contract production and analysis The contract accepter : The contract accepter must have adequate premises, 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 holds a manufacturing authorization. The contract accepter 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 accepter 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 accepter. The contract accepter should refrain from any activity that may adversely affect the quality of the product manufactured and/or analyzed for the contract giver. There must be a written contract between the contract giver and the Contract production and analysis 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. Technical aspects of the contract should be drawn up by competent persons suitably knowledgeable in pharmaceutical technology, analysis and GMP. All arrangements for production and analysis must be in accordance with the marketing authorization and agreed by both parties. The contract should describe clearly who is responsible for purchasing, testing and releasing materials and for 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 accepter should take samples at the premises of the manufacturer.  Contract production and analysis Manufacturing, analytical, 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. The contract should describe the handling of starting materials, intermediate and bulk products 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.  assignment what are the joint responsibilities between the heads of production and quality control in a pharmaceutical industry? What is contract manufacturing and contract analysis?.