annex 4-2 Korean good manufacturing practices for ...

1 Enforcement Rule for Medicinal Product Safety, annex 4-2 " good manufacturing Practice for Investigational Medicinal Products" < >. Enforcement Rule for Medicinal Product Safety annex 4-2 " good manufacturing Practice for Investigational Medicinal Products". Korean good manufacturing PRACTICE REGULATION FOR. INVESTIGATIONAL MEDICINAL PRODUCTS. August 21, 2014. Note: This English version translated by gmpeye is not officially approved or endorsed by the Korean regulatory authority, the Ministry of Food and Drug Safety. ggm mppeeyyee 1. Enforcement Rule for Medicinal Product Safety, annex 4-2 " good manufacturing Practice for Investigational Medicinal Products" < >. [ annex 4-2]. good manufacturing PRACTICE FOR INVESTIGATIONAL MEDICINAL PRODUCTS. (Article 24, Paragraph , Sub-paragraph 2 and Article 30, Paragraph , Sub-paragraph 9 of the Enforcement Rule for Medicinal Product Safety). 1. 1. Introduction Purpose The purpose of this Regulation is to specify good manufacturing , practice requirements, in order to assure quality, safety and , efficacy of investigational medicinal products under development.

2 Stage, to protect subjects participating in clinical trials and to assure the reliability of clinical data. 2. 2. Definitions . Terms used in this Regulation have the following meanings.. " (Order)" A. "Order" means an instructional document provided to an (Process), investigational medicinal product manufacturer by a (Package), (Ship) sponsor to process, package and ship a certain number of . units of investigational medicinal products for use in clinical trials.. " (Product Specification B. "Product Specification File" means a reference file File)" , , , containing or a list referring to files containing, all the information necessary to draft the detailed written instructions on processing, packaging, quality control ggm mppeeyyee 2. Enforcement Rule for Medicinal Product Safety, annex 4-2 " good manufacturing Practice for Investigational Medicinal Products" < >.. testing, lot release and shipping of an investigational medicinal product.

3 " (Randomization Code)" C. "Randomization Code" means a list of identification codes created in a statistically appropriate manner, in which . treatment assigned to each subject from the randomization process is identified. 3. 3. General Principles . 1 A. A person who intends to manufacture an investigational , medicinal product should comply with "GMP for Medicinal 3, Products" in annex 1 as well as requirements in annex 3. 3 2, 3 3 for biological products, annex 3-2 for radiopharmaceuticals . , or annex 3-3 for medicinal gases. However, if otherwise specified in this Regulation or if rationale appropriate for development stage of the investigational medicinal product . is provided, some requirements may not apply.. B. Specifications for investigational medicinal products , should be reinforced over development stages and various . kinds of changes should be documented and traceable.. 4 C.

4 Prior to production of investigational medicinal products, , double-blinding, randomization and others as specified in good Clinical Practice Regulation in annex 4 and clinical . trial protocol should be sufficiently considered. 4. 4. Scope ggm mppeeyyee 3. Enforcement Rule for Medicinal Product Safety, annex 4-2 " good manufacturing Practice for Investigational Medicinal Products" < >. 34 This Regulation applies to investigational medicinal products , used in clinical trials under Article 34 of the Pharmaceutical Affairs Act. In addition, this Regulation applies to repackaging . or modification of commercially available medicinal products for the purpose of using them as comparators. 5. 5. Premise and Environment . , , , , A. If a sponsor intends to make another manufacturer perform all or some parts of production, quality control, , packaging, storage and shipping of investigational , medicinal products under contract, the sponsor should assess the manufacturer for manufacturing business.

5 License, compliance with GMP regulation and others in advance. In such instance, the manufacturer should establish and document production and quality control system for the investigational medicinal product.. B. Important facilities and equipment used in production and quality control of investigational medicinal products . should be calibrated and qualified.. , C. Toxicity, potency and others may not be fully understood , for investigational medicinal products. Therefore, for , multi-product manufacturing sites, measures for , prevention of cross-contamination, such as design of , equipment and premise, test methods and acceptance . limits to be used after cleaning and consideration of ggm mppeeyyee 4. Enforcement Rule for Medicinal Product Safety, annex 4-2 " good manufacturing Practice for Investigational Medicinal Products" < >. campaign working, should be developed. If necessary, toxicity of product, easiness of cleaning and removal, and other aspects should be assessed.

6 6. 6. Organization and Responsibilities . A. If the sponsor intends to use another manufacturer for all operations under contract, the sponsor should have a , person responsible for quality assurance of investigational 36 3 medicinal products, such as lot release. This person . responsible for quality assurance should be a qualified person as prescribed in Article 36, Paragraph of the Pharmaceutical Affairs Act or a person having sufficient knowledge and experience in this Regulation.. ( ) B. The head of quality (assurance) unit belonging to the sponsor should revise the product specification file of section and make a decision of lot release under .. consideration of aspects as prescribed in section This requirement should equally apply to cases where some processing steps are contracted to another manufacturer.. C. Annual product quality review and critical material supplier assessment should be conducted within the limits.

7 Of the possible, under consideration of development stage of investigational medicinal products. 7. 7. Documentation and Specifications ggm mppeeyyee 5. Enforcement Rule for Medicinal Product Safety, annex 4-2 " good manufacturing Practice for Investigational Medicinal Products" < >. Specifications and Instructions . ( , 1 , , A. Specifications (for starting materials, primary packaging ), , materials, intermediates, drug substances and drug . , products), product master file, and processing and packaging instructions should be prepared given the . current development stage. However, if operations are not repeated, product master file and processing instructions may not be prepared.. B. Documents of the above A should be periodically re- . , , assessed and updated during development, as necessary. Each new version should take into account the latest data, . current technology used, regulatory and pharmacopeial requirements, and should allow traceability to the previous documents.

8 , C. Any changes should be carried out according to a written , , procedure, which should address any implications for . product quality and on-going clinical trials. Investigations, rationales and others should be documented. Order The sponsor should prepare the order (it may be transmitted by ( ) electronic means) while referring to product specification file and . the relevant clinical trial protocol and approve it according to a written procedure. ggm mppeeyyee 6. Enforcement Rule for Medicinal Product Safety, annex 4-2 " good manufacturing Practice for Investigational Medicinal Products" < >. Product Specification File , This file should include the following information. If necessary, . , this file can be made in the form of a list of the relevant documents. In addition, the contents may vary depending on the . nature of the investigational medicinal product and the development stage.

9 , , , (1) Specifications and test methods for starting materials, packaging materials, intermediates, drug substance and drug product;.. (2) manufacturing methods;.. (3) In-process testing and methods;.. (4) Approved label;.. , ( ) (5) Clinical trial protocols and randomization codes (if necessary);.. ( : , ) (6) Agreements with contract givers ( , technical agreements, quality agreements);.. (7) Stability data;.. (8) Storage and shipment conditions. Packaging Instructions . A. Investigational medicinal products should be normally . packed in an individual way for each subject in the clinical trial.. B. The number of units to be packaged should be specified ggm mppeeyyee 7. Enforcement Rule for Medicinal Product Safety, annex 4-2 " good manufacturing Practice for Investigational Medicinal Products" < >. , prior to the start of the packaging operations, including . units necessary for quality control and any reserve samples to be kept.

10 Sufficient controls, such as reconciliations, should take place at each stage of processing. , Processing, Testing and Packaging Records . A. Individual records should be kept in sufficient detail to , allow accurate determination of the sequence of . operations. These records should contain any relevant remarks which justify procedures used and any changes made.. B. Records should be retained for at least 5 years after 5 . completion of clinical trial in which the relevant lot of investigational medicinal product was used. 8. 8. Production Production Operations and Validation . A. Production processes for investigational medicinal , products may not be validated to the extent necessary for . commercial production. Validation of production processes for investigational medicinal products may be appropriately performed within the limits of the possible, under consideration of development stage.