Good manufacturing practice pdf

GMP

1. By Lakshmi GOOD MANUFACTURING PRACTICE

2. GMP refers to the integrated management control system inclusive of the “methods used in, and the facilities and controls used for the manufacturing, packing, storage, and installation of the finished devices intended for human use. To assure that such devices will be safe and effective. Definition

3. Manufacturing processes are clearly defined and controlled. All critical processes are validated to ensure consistency and compliance with specifications. Manufacturing processes are controlled, and any changes to the process are evaluated. Changes that have an impact on the quality of the drug are validated as necessary. Instructions and procedures are written in clear. ( Good Documentation Practices ) Operators are trained to carry out and document procedures. Records are made, manually or by instruments, during manufacture that demonstrate that all the steps required by the defined procedures and instructions were in fact taken and that the quantity and quality of the drug was as expected. Deviations are investigated and documented. Records of manufacture (including distribution) that enable the complete history of a batch to be traced are retained in a comprehensible and accessible form. Complaints about marketed drugs are examined, the causes of quality defects are investigated, and appropriate measures are taken with respect to the defective drugs and to prevent recurrence. F ew basic principles of GMP

4. GMPs are enforced in the United States by the US FDA, under Section 501(B) of the 1938 Food, Drug, and Cosmetic Act (21 USCS § 351). The regulations use the phrase "current good manufacturing practices" (cGMP) to describe these guidelines. Courts may theoretically hold that a drug product is adulterated even if there is no specific regulatory requirement that was violated as long as the process was not performed according to industry standards. As of June 2010, a different set of cGMP requirements apply to all manufacturers of dietary supplements. G uideline versions

5. The World Health Organization (WHO) version of GMP is used by pharmaceutical regulators and the pharmaceutical industry in over one hundred countries worldwide, primarily in the developing world. The European Union's GMP (EU-GMP) enforces similar requirements to WHO GMP, as does the Food and Drug Administration's version in the US. Similar GMPs are used in other countries, with Australia, Canada, Japan, Singapore and others having highly developed/sophisticated GMP requirements. In the United Kingdom, the Medicines Act (1968) covers most aspects of GMP in what is commonly referred to as "The Orange Guide", which is named so because of the color of its cover; it is officially known as Rules and Guidance for Pharmaceutical Manufacturers and Distributors.

6. Within the European Union, GMP inspections are performed by National Regulatory Agencies In the United Kingdom by the Medicines and Healthcare products Regulatory Agency (MHRA)). in the Republic of Korea (South Korea) by the Korea Food & Drug Administration (KFDA). In Australia by the Therapeutical Goods Administration (TGA). In South Africa by the Medicines Control Council (MCC). In Brazil by the National Health Surveillance Agency Brazil (ANVISA). In Iran, in India gmp inspections are carried out by state FDA and these FDA report to Central Drugs Standard Control Organization. Pakistan by the Ministry of Health . Each of the inspectorates carry out routine GMP inspections to ensure that drug products are produced safely and correctly; additionally, many countries perform pre-approval inspections (PAI) for GMP compliance prior to the approval of a new drug for marketing. Enforcements

7. The regulations in this part contain the minimum current good manufacturing practice for preparation of drug products for administration to humans or animals C urrent good manufacturing practice for finished pharmaceuticals

8. Quality control is the part of GMP that is concerned with sampling, specifications, testing, documentation, and release procedures. Quality control ensures that the necessary and relevant tests are carried out and that raw materials, packaging materials, and products are released for use or sale, only if their quality is satisfactory. Quality control is not confined to laboratory operations but must be incorporated into all activities and decisions concerning the quality of the product. It has a responsibility and authority to approve or reject all components, drug product containers, closures, in process materials, packing material, labeling, and drug products. R esponsibilites of Quality Control unit

9. Adequate facilities, trained personnel, and approved procedures are available for sampling, inspecting and testing of raw materials, packaging materials, intermediate bulk and finished products, and, where appropriate monitoring environmental conditions for GMP purposes; Samples of raw materials, packaging materials, and intermediate, bulk, and finished products are taken according to procedures approved by the quality control department; Test methods are validated; Records demonstrate that all the required sampling, inspecting, and testing procedures were carried out, and any deviations are recorded and investigated; Records are made of the results of the inspection and testing of materials and finished products against specifications; The procedures for product release include a review and evaluation of relevant production documentation and an assessment of deviations from specified procedures No drug is released for sale or supply prior to approval by the quality control department; Sufficient samples of raw material and finished product are retained to permit future examination if necessary. Basic requirements of QC unit

10. Quality assurance is a wide-ranging concept that covers all matters that individually or collectively influence the quality of a drug. It is the total of the organized arrangements made with the objective of ensuring that drugs are of the quality required for their intended use. Quality assurance therefore incorporates GMP, along with other factors that are outside the scope of these guidelines. A system of quality assurance appropriate for the fabrication, packaging, labelling, testing, distribution, importation, and wholesale of drugs should ensure that: Contd. Responsibilities of QA unit

11. Systems, facilities and procedures are adequate and qualified; Production and control operations are clearly specified; Analytical methods and critical processes are validated; Arrangements are made for the supply and use of the correct raw and packaging materials; All necessary control on intermediates, and any other in-process monitoring is carried out; Outsourced activities are subject to appropriate controls and meet GMP requirements; Fabrication, packaging/labelling, testing, distribution, importation, and wholesaling are performed in accordance with established procedures; Drugs are not sold or supplied before the quality control department has certified that each lot has been produced and controlled in accordance with the marketing authorization and of any other regulations relevant to the production, control and release of drugs; Satisfactory arrangements exist for ensuring that the drugs are stored, distributed, and subsequently handled in such a way that quality is maintained throughout their shelf life;

12. The quality risk management system should ensure that: the evaluation of the risk to quality is based on scientific knowledge, experience with the process and ultimately links to the protection of the patient the level of effort, formality and documentation of the quality risk management process is commensurate with the level of risk. The effectiveness, applicability, and continuous improvement of the quality management system is ensured through regular management review and self-inspection; An annual product quality review of all drugs should be conducted with the objective of verifying the consistency of the existing process, the appropriateness of current specifications for both raw materials and finished product to highlight any trends and to identify product and process improvements .

13. Building and Facilities. Design and construction features Lighting Ventilation, air filtration, air heating and cooling Sewage and refuse Washing and toilet facilities Sanitation Maintenance Equipment Equipment design, size, location. Equipment construction Equipment cleaning and maintenance Automatic, mechanical, and electronic equipment. Filters contd … S ome other guidelines

14. There shall be a written procedure describing in sufficient detail the receipt, identification, storage, handling, sampling, testing, and approval or rejection of components and drug product containers and closures . Upon receipt and before acceptance drug product containers shall be examined visually for appropriate labeling as to contents, containers damage or broken seals and contamination. Testing and approval or rejection of components, drug product containers. Use of approved components, drug product containers. Retesting of approved components, drug product containers. Rejected components, drug product containers. Drug product containers shall not be reactive, additive/ absorptive so as to alter safety, identity, strength, quality or purity of the drug beyond the official or established requirements. . Control of components and drug product containers

15. Written procedures; deviations Charge – in of components. Calculation of yield Equipment identification Sampling and testing of in process materials and drug products. Time limitations on production. Control of microbial contamination. Reprocessing. P roduction and process control

16. Materials examination and usage criteria Labeling issuance Packaging and labeling operations. Drug product inspection. Expiration dating Distribution procedures. P ackaging and labeling control

17. Equipment cleaning and use log. Component, drug containers and labeling records. Each batch production and control records Production record review Laboratory records Distribution records Compliant files Records of returned drug product Drug product salvaging Contd… R ecords and reports

18. General laboratory controls Testing of intermediate and APIs Validation procedures and analysis Certificate of analysis Stability Monitoring of API s Expiry and retest Dating Rejection and re use of materials. Traceability of Distributed APIs and Intermediates. Repacking relabeling and holding of APIs and intermediates. Complaints. Contract manufactures

19. Quality Appropriate GMP concepts should be applied in the production of API for use of clinical trials with in a suitable mechanism of approval of each batch. Equipment and facilities. Control of Raw materials. Production of APIs Validation Changes Documentation APIs for use in C l inical Trails.

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