Microsoft Word - annex 1 Korean good manufacturing practices for medicinal products in Kor Eng

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1 Enforcement Rule for Medicinal Product Safety Annex 1 "Good Manufacturing Practice for Medicinal Products" KOREAN GOOD MANUFACTURING PRACTICE REGULATION FOR MEDICINAL PRODUCTS June 30, 2016 Note: This English version translated by is not officially approved or endorsed by the Korean regulatory authority, the Ministry of Food and Drug Safety. 1

2 [Annex 1] <Revised on June 30, 2016> GOOD MANUFACTURING PRACTICE FOR MEDICINAL PRODUCTS (Article 4, Paragraph 1, Sub-paragraph 6, Items A & C ~ E, Article 48, Sub-paragraph 5, Items A & C ~ E, and Article 48, Sub-paragraphs 6, 9 & 9-2 of the Enforcement Rule for Medicinal Product Safety) 1. 용어의정의이기준에서사용하는용어의뜻은다음과같다. 가. " 관리번호 " 란제조단위를부여할수없는자재등을관리하기위하여부여한번호로서숫자ㆍ문자또는이들을조합한것을말한다. 나. " 교정 " 이란계측기, 시험기기또는기록계가나타내는값과표준기기의참값을비교하여오차가허용범위내에있음을확인하고, 허용오차범위를벗어나는경우허용범위내에들도록조정하는것을말한다. 다. " 일탈 " 이란제조또는품질관리과정에서미리정해진기준을벗어나이루어진행위를말한다. 라. " 기준일탈 " 이란시험의결과가미리정하여진시험기준을벗어난경우를말한다. 마. " 무균구역 " 이란무균작업을위한무균물질또는멸균처리된용기가노출되는장소, 무균제제를채워넣거나밀봉하는 1. Definitions Terms used in this Regulation have the following meanings. A. "Control number" means the numbers, letters or their combinations assigned to control packaging materials or other materials which cannot be controlled as a batch. B. "Calibration" means the set of operations which compare values indicated by a measuring instrument, test equipment or recording device and the corresponding true values of a reference standard to verify if the difference is within acceptable range and which, when it is out of acceptable range, conduct adjustments to make it within acceptable range. C. "Deviation" means an action done in violation of established written procedures in the course of production or quality controls. D. "Out-of-specification result" means a test result which is out of the established specification. E. "Aseptic area" means a place where aseptic materials or sterilized containers for aseptic processing are exposed, where 2

3 작업을하는장소및무균시험등의무균조작을하는장소를 말한다. 바. " 반제품 " 이란 제조공정 단계에 있는 것으로서 필요한 제조공정을더거쳐야완제품이되는것을말한다. 사. " 밸리데이션 " 이란특정한공정, 방법, 기계설비또는시스템이 미리 설정되어 있는 판정기준에 맞는 결과를 일관되게 도출한다는것을검증하고이를문서화하는것을말한다. 아. " 수율 " 이란이론생산량에대한실생산량의백분율을말한다. 자. " 수율관리기준 " 이란제조공정이정상적으로진행되었을경우 얻어지는제품별연간평균생산수율범위를말한다. 차. " 실생산량 " 이란제조공정에서실제로얻은양을말한다. 카. " 완제의약품 " 이란 모든 제조공정이 완료되어 최종적으로 인체에투여할수있도록일정한제형으로제조된의약품을 말한다. 타. " 완제품 " 이란 의약품 제조에서 모든 제조공정이 완료된 원료의약품또는완제의약품을말한다. 파. " 원료약품 " 이란 완제품의 제조에 사용되는 물질 ( 자재는 제외한다 ) 을 말하며, 완제품에 남아 있지 않은 물질을 포함한다. filling or sealing of sterile preparations are conducted, and where aseptic operations, including sterility testing, are conducted. F. "Intermediate product" means an in-process material which must undergo further production steps before it becomes a finished product. G. "Validation" means the action of proving and documenting that a specific process, method, equipment or system consistently produces results meeting pre-determined specifications. H. "Yield" means the ratio of actual production amount to theoretical production amount, stated as a percentage. I. "Yield control range" means the range of average annual production yield for each product when production processes are normally conducted. J. "Actual production amount" means the quantity which is actually produced at any appropriate processing step. K. "Drug product" means a product for human use in its finished dosage form which has completed all production steps. L. "Finished product" means a drug substance or a drug product which has completed all production steps. M. "Raw material" means any material used in the production of a finished product (except packaging materials), including those which may not appear in the finished product. 3

4 하. " 원료의약품 " 이란합성, 발효, 추출등또는이방법들의 N. "Drug substance" means any substance produced by 조합에 의하여 제조된 물질로서 완제의약품의 제조에 synthesis, fermentation, extraction or their combinations and 사용되는것을말한다. used in the production of a drug product. 거. " 원생약 " 이란동물, 식물또는광물에서채취된것으로서한약원료로사용하기위한세척ㆍ선별ㆍ절단등가공을하지않은상태의것을말한다. O. "Crude natural medicinal material" means any material which is collected from animals, plants or minerals and which has not undergone processes, such as washing, sorting and cutting, for being used as traditional Korean medicinal material. 너. " 원자재 " 란원료약품및자재를말한다. P. "Raw packaging material" means both raw materials and packaging materials. 더. " 이론생산량 " 이란원료약품의투입량으로부터이론적으로계산된반제품또는완제품의양을말한다. Q. "Theoretical production amount" means the quantity of the intermediate or finished product theoretically calculated from amounts of raw materials used. 러. " 자재 " 란포장과표시작업에사용되는용기, 표시재료, 첨부 R. "Packaging material" means any material used in packaging 문서, 포장재료등을말한다. and labeling, such as containers, labeling materials, accompanying documents and packing materials. 머. " 재가공 " 이란기준일탈한제조공정단계에있는반제품에 S. "Reprocessing" means the action of processing an 대하여이미설정된생산공정의일부공정을반복하는행위를말한다. intermediate product showing out-of-specification results by repeating one or more established production steps. 버. " 적격성평가 " 란기계ㆍ설비가설계한대로제작, 설치되고 T. "Qualification" means the action of proving and documenting 목적한 대로 작동하여 원하는 결과가 얻어진다는 것을 that a piece of equipment is manufactured and installed as 증명하고이를문서화하는것을말한다. designed, operates as intended, and actually produces desired results. 서. " 제조 " 란포장및표시작업을포함하여의약품을생산하기위하여하는모든작업을말한다. U. "Manufacture" means all operations, including packaging and labeling, to produce a medicinal product. 4

5 어. " 제조단위 " 또는 " 로트 " 란 동일한 제조공정으로 제조되어 V. "Batch" or "lot" means a defined quantity of medicinal 균질성을가지는의약품의일정한분량을말한다. products produced in the same process processes so that it is expected to be homogeneous. 저. " 제조번호 " 또는 " 로트번호 " 란일정한제조단위분에대하여제조관리및출하에관한모든사항을확인할수있도록 W. "Batch number" or "lot number" means the numbers, letters or their combinations assigned to a defined quantity of 표시된 번호로서 숫자ㆍ문자 또는 이들을 조합한 것을 medicinal products to identify the complete history of 말한다. production and distribution. 처. " 중요공정 " 또는 " 중요기계ㆍ설비 " 란제품의품질에영향을미치는공정또는기계ㆍ설비를말한다. X. "Major process" or "major equipment" means a process or equipment which may affect the quality of a medicinal product. 커. " 청정구역 " 이란부유입자및미생물이유입되거나잔류하는것을통제하여일정수준이하로유지되도록관리하는구역을말한다. Y. "Clean area" means an area where the introduction or retention of air-borne particles and microorganisms is controlled to maintain their levels below specified limits. 터. " 청정등급 " 이란청정구역의관리수준을정한등급을말한다. Z. "Cleanliness grade" means a grade assigned to define environmental control level of a clean area. 퍼. " 한약분말 " 이란완제의약품을제조하기위하여한약을가루로만든상태를말한다. AA. "Traditional Korean medicinal powder" means a powdered traditional Korean medicinal material to be used in the manufacture of a drug product. 허. " 한약엑스 " 란완제의약품을제조하기위하여한약을엑스화한상태를말한다. AB. "Traditional Korean medicinal extract" means an extracted traditional Korean medicinal material to be used in the manufacture of a drug product. 고. " 한약원료 " 란원생약, 한약, 한약분말, 한약엑스등으로서제제를제조하기위하여사용하는생약에서유래한모든원료를말한다. AC. "Traditional Korean medicinal material" means all kinds of raw materials derived from natural medicinal materials to be used in the manufacture of drug products and includes the crude natural medicinal materials, traditional Korean 5

6 노. " 동물유래원료 " 란동물의장기또는조직을추출, 여과, 농축, 건조등의방법으로제조한완제의약품의원료를말한다. medicines, traditional Korean medicinal powder and traditional Korean medicinal extract. AD. "Animal-derived raw material" means a raw material produced with animal organs or tissues by extraction, filtration, concentration, drying or other methods and used in the manufacture of drug products. 1의2. 품질경영 1-2. Quality Management 의약품제조업자는품질로인해안전성, 유효성의문제가없도록의약품을제조하여야한다. 품질목표달성은의약품제조업의경영진의책임이며, 이러한목표달성을위하여의약품의제조및품질관리에관계된의약품제조업의경영진과작업원은적절한품질보증시스템을마련하여야한다. 품질보증시스템은 Medicinal product manufacturers should manufacture drug products so as to assure that there is no safety or efficacy issue arising from inadequate quality. The attainment of quality objective is the responsibility of management. To achieve this quality objective, medicinal product manufacturer's management 제조 및 품질관리, 품질관리, 품질평가, 품질위험관리 등을 and personnel engaged in production and quality control of 포함하여적절하게시행하여야한다. medicinal products should develop appropriate quality assurance system. Quality assurance system incorporating GMP, quality control, product quality review and quality risk management should be appropriately implemented. 가. 품질보증은 의약품의 품질을 확보하는 모든 활동을 A. Quality Assurance covers all activities conducted to assure 포함한다. the quality of a medicinal product. 나. 제조및품질관리는의약품이허가된품질기준에따라일관성있게생산, 관리됨을보장하는체계이다. B. Good Manufacturing Practice is a systematic process designed to assure that medicinal products are consistently produced and controlled to the quality standards as specified in the regulatory authorization dossier. 다. 품질관리는검체채취, 규격및시험, 그리고조직, 문서화, C. Quality Control is a systematic process concerned with 6

7 출하절차와관련된체계이다. sampling, specifications and testing, and with the organization, documentation and release procedures. 라. 품질평가는공정의일관성확인, 원료약품및완제품의품질경향파악및규격의적절성확인, 제품및공정개선이필요한부분을파악하는체계이다. D. Product Quality Review is a systematic process to verify the consistency of the process and the appropriateness of current specifications for both raw materials and finished products, to identify any trends in quality of raw materials and finished products and to identify product and process improvements. 마. 품질위험관리는품질에대한위험을 평가, 관리, 공유, E. Quality Risk Management is a systematic process for 검토하는체계이다. assessment, control, communication and review of risks to the quality of medicinal product. 2. 시설및환경의관리 2. Premise and Environment 2.1 시설관리의약품 제조소는 의약품 등의 제조업 및 수입자의 시설기준령 에서정한시설기준에맞도록필요시설을갖추어야 하며, 다음각목에따라정기적으로점검하여의약품의제조및 품질관리에 지장이 없도록 유지ㆍ관리하고 해당 내용을 기록하여야한다. 가. 작업소의기계ㆍ설비는제조공정흐름에따라배치할것 2.1 Premise Medicinal product manufacturing site should have appropriate facilities and equipment in compliance with the Enforcement Decree on Facilities Standards for Medicinal Product Manufacturers and Importers. Such facilities and equipment should be regularly inspected and maintained to prevent adverse effect on production and quality control of medicinal products, as described below. Such inspection and maintenance should be documented. A. Equipment in production areas should be placed in the sequence of production processes. 7

8 나. 제조용중요기계ㆍ설비는구분할수있도록번호나코드를부여하고해당기계ㆍ설비를사용한제품명, 제조번호및제조일자를기록할것 B. Identification numbers or codes should be assigned to major equipment used in production. Information on products produced with use of major equipment, such as the product name, lot number and date of production, should be recorded. 다. 제조용수는필요한질과양이확보되도록할것 C. Sufficient quantity of pharmaceutical water with desired quality should be provided. 라. 각종배관에는각각구분될수있도록내용물과흐름방향을표시할것 D. Pipes should be labeled to indicate the contents and the direction of flow. 마. 윤활유, 냉매등이의약품의품질에영향을미치지않도록 E. Lubricants, coolants and other substances should be 관리할것 controlled so as not to adversely affect the quality of medicinal products. 바. 작업소의하수구는역류를방지할수있도록되어있어야하고정기적으로소독할것 F. Drains in production areas should be designed to prevent back flow and disinfected on a regular basis. 사. 고장등으로사용하지않는기계ㆍ설비는작업소에두지않거나사용할수없다고표시할것 G. Any defective equipment should be removed from production areas or labeled as defective. 아. 의약품의제조및시험에사용되는중요기계ㆍ설비에대하여교정및적격성평가를하여야하고, 작동절차와기준을문서화할것 H. Major equipment used in production and testing of medicinal products should be calibrated and qualified and operational procedures and specifications should be documented. 자. 생약 ( 한약 ) 을원료로사용하는의약품제조소는가목부터 I. Medicinal product manufacturing sites where natural 아목까지의기준외에다음기준에맞아야한다. medicinal materials (traditional Korean medicines) are used as raw materials should meet the following requirements, in addition to requirements of the above A to H. 1) 보관소는다음기준에따라야한다. 1) Storage areas should meet the following requirements. 가 ) 선별ㆍ정선 ( 精選 ) ㆍ세척이필요한원생약은구획하여보관할것 A) Crude natural medicinal materials requiring sorting, selection and washing should be stored in segregation. 8

9 나 ) 원료, 반제품, 완제품은필요한보관조건에따라온도및습도를조절할수있는시설을갖출것다 ) 환기 ( 통풍 ) 가잘되고직사광선을차단할수있을것라 ) 쥐, 해충, 먼지등을막을수있는시설을갖출것 2) 원생약의선별, 이물제거, 세척, 건조, 절단등의작업을위한전처리 ( 前處理 ) 작업실을갖출것 3) 한약분말및한약엑스를제조하는경우각각구획된작업실을갖출것 4) 한약엑스작업실은수증기를배출할수있는설비와세척하여사용할수있는추출시설을갖출것 5) 한약분말작업실또는한약엑스작업실에는필요한경우금속을검출할수있는금속감지기를설치할것 B) Areas for storage of raw materials, intermediate products and finished products should be provided with devices to control temperature and humidity levels appropriate for their storage conditions. C) Storage areas should be well ventilated and kept out of direct sunlight. D) Storage areas should be provided with devices to avoid rodents, insects, dusts and others. 2) A pretreatment room for sorting, removal of foreign materials, washing, drying, cutting and other processing steps of crude natural medicinal materials should be provided. 3) If traditional Korean medicinal powders and extracts are manufactured, there should be segregated production areas for individual products. 4) Production areas for traditional Korean medicinal extracts should be provided with vapor-exhausting equipment and cleanable extraction equipment. 5) Production areas for traditional Korean medicinal powders and extracts should be provided with a metal detector, if necessary. 2.2 자동화장치등의관리 2.2 Automatic System 가. 제조및품질관리에자동화장치등 [ 컴퓨터또는단품번호 A. If automatic systems are used in production and quality 부여체계 (serialization) 등의관련시스템을포함한다. 이하 control (including computers or related systems, such as 9

10 같다 ] 을사용할경우에는계획을수립하여정기적으로교정또는성능점검을하고기록할것나. 자동화장치등의기록변경은권한이있는자만할수있도록하고적절하게관리할것다. 자동화장치등에의한모든기록은별도로저장ㆍ보관하여야하고, 이경우출력물이나테이프및마이크로필름등과같은대체시스템을이용하여별도로보관된자료가유실되지않도록관리할것 serialization system), they should be regularly calibrated and inspected for performance according to a written program. Such calibrations and inspections should be documented. B. Automatic systems should be appropriately controlled to assure that data is changed only by authorized personnel. C. All data generated by automatic systems should be separately stored and maintained. In such instance, hard copy or alternative systems, such as tapes or microfilms, should be employed to assure that such data are secure from loss. 2.3 환경관리 의약품제조소는의약품제조공정중의오염을방지하기위하여다음각목에따라적절한작업환경을유지ㆍ관리하고그내용을기록하여야한다. 가. 의약품의종류ㆍ제형ㆍ제조방법및제조시설등에따라작업소의청정구역과청정등급을설정하여야하며, 그청정등급이유지되도록정기적으로점검하고관리할것 나. 공기조화장치의성능을정기적으로점검하고청정등급및작업실간의차압 ( 差壓 ) 이유지되도록할것 다. 제조조건과보관조건에적절한온도및습도가유지되도록정기적으로점검할것 2.3 Environmental Control In order to prevent contamination in the manufacture of medicinal products, manufacturing areas should be maintained and controlled to assure appropriate environmental conditions and such maintenance and control should be documented. A. Clean areas and cleanliness grades should be established, while considering types and dosage forms of medicinal products, production methods and production facilities, and clean areas should be regularly checked and controlled to maintain the established cleanliness grades. B. HVAC systems should be regularly inspected for performance and cleanliness grades and pressure differentials between rooms should be maintained. C. Temperature and humidity levels should be regularly checked to assure that appropriate conditions for production and 10

11 storage are maintained. 3. 조직 3. Organization 3.1 조직의구성 3.1 Organizational Structure 가. 제조소에서로독립된제조부서와품질 ( 보증 ) 부서를두고각각 A. A manufacturing site should have a production department 책임자를두어야하며, 이경우겸직해서는안된다. 다만, and a quality (assurance) department that are independent 방사성의약품제조업소, 의료용고압가스제조업소또는모든 from each other. There should be the head of production 품목을위탁제조하거나소분 ( 小分 ) 하는업소의경우에는 department and the head of quality (assurance) department 겸직할수있다. and they should not have additional jobs. However, they may have additional jobs, for radiopharmaceutical manufacturing sites, medicinal gas manufacturing sites, if all products are produced under contract, or if only subdivision operation is carried out at a manufacturing site. 나. 가목의책임자는법제36조제3항에따른제조관리자로서이 B. Heads of the above A should be Qualified Persons under 기준에관한충분한지식을가진사람이어야한다. Article 36, Paragraph 3 of the Act and have sufficient knowledge of this Regulation. 다. 제조소에는제조관리및품질관리업무를적절히수행할수 C. There should be an adequate number of personnel who are 있는적절한인원을배치하여야하며, 그작업원은이기준 able to appropriately perform production and quality controls. 및담당업무에관한교육ㆍ훈련을받은사람이어야한다. Such personnel should be trained in this Regulation and their particular operations. 3.2 제조부서책임자 제조부서책임자는제조공정관리, 제조위생관리및보관관리를담당하는부서의책임자로서다음각목의사항을이행하여야 3.2 Head of Production Department Head of Production Department is responsible for production process control, hygiene control, and storage control, and should 11

12 한다. 가. 제조관리를적절히하기위하여제품표준서, 제조관리기준서및제조위생관리기준서에성명을적고서명하여승인을받아갖추어두고운영하여야한다. 나. 제4.1호거목의제조지시서에의하여작업을지시하고제조지시서에따라제조되는지를점검ㆍ확인하여야하며, 일탈이있는경우에는이를조사하고기록하여야한다. 다. 제조위생관리및보관관리가규정대로되고있는지를점검ㆍ확인하여야한다. 라. 품질 ( 보증 ) 부서주관하에제조부서의중요기계ㆍ설비에대한적격성평가및공정에대한밸리데이션을실시하고이를확인하여야한다. have the following responsibilities. A. To ensure that Product Master Files, Production Control Standard Documents and Hygiene Control Standard Documents are named, signed, approved and maintained for appropriate production control; B. To instruct production operations on the basis of production instructions as specified in Section 4.1-O, to verify if production operations are conducted according to production instructions and to investigate and document deviations found during production of medicinal products; C. To verify if hygiene control and storage control are carried out in accordance with written procedures; D. To perform and verify qualification of major production equipment and validation of production processes, under management by quality (assurance) department. 3.3 품질 ( 보증 ) 부서책임자품질 ( 보증 ) 부서책임자는원자재ㆍ반제품및완제품의품질관리및품질보증을담당하는부서의책임자로서다음각목의사항을이행하여야한다. 3.3 Head of Quality (Assurance) Department Head of Quality (Assurance) Department is responsible for quality control and quality assurance of raw materials, packaging materials, intermediate products and finished products, and should have the following responsibilities. 가. 품질관리를 적절히 하기 위하여 제품표준서 및 A. To ensure that Product Master Files and Quality Control 품질관리기준서에성명을적고서명하여승인을받아갖추어두고운영하여야한다. Standard Documents are named, signed, approved and maintained for appropriate quality control; 나. 제4.2호가목의 시험지시서에 의하여 시험을 지시하고 B. To instruct testing operations on the basis of test instructions 12

13 시험지시서에따라시험이진행되는지를점검ㆍ확인하여야하며, 일탈및기준일탈이있는경우에는이를조사하고기록하여야한다. as specified in Section 4.2-A, to verify if testing is conducted according to test instructions and to investigate and document deviations and out-of-specification results; 다. 품질에관련된모든문서와절차를검토하고승인하여야한다. C. To review and approve all documents and procedures relating to quality; 라. 제2.3호의환경관리에관한사항을승인하고주관하여야한다. D. To approve and manage environmental controls as specified in Section 2.3; 마. 제6호의 밸리데이션에 관한 사항을 승인하고 주관하여야 E. To approve and manage validation activities as specified in 한다. 다만, 특별한사유로품질 ( 보증 ) 부서책임자가일부 Section 6; However, if, for specific reasons, Head of Quality 밸리데이션 업무에 대하여 별도의 관리자를 지정하는 (Assurance) Department appoints a person responsible for 경우에는그렇지않다. some validation tasks, this requirement may not apply. 바. 제7.2호의안정성시험을하여야한다. F. To conduct stability testing as specified in Section 7.2; 사. 제7.3호의제품품질평가를하여야한다. G. To conduct product quality review as specified in Section 7.3; 아. 제7.1호가목및제8.1호가목의시험성적서및제조단위별제조기록서의내용을검토하고제품의출하를승인하여야한다. H. To review test records and batch production records as specified in Sections 7.1-A and 8.1-A and to approve the product release; 자. 시험결과에따라원자재의사용여부, 제조공정의진행여부또는제품의출하여부를결정하고그결과를미리정한절차에따라관련부서에통지하여야한다. I. To approve or reject the use of raw materials or packaging materials, the process progress or product release based on test results, and to notify the results to the relevant departments according to a written procedure; 차. 부적합품이규정된절차대로처리되고있는지를확인하여야한다. J. To ensure that rejected materials are disposed of according to a written procedure; 카. 제11호의불만처리및제품회수에관한사항을주관하여야 K. To control complaints and recalls as specified in Section 11; 한다. 타. 제12호의변경관리를승인하여야한다. L. To approve change control as specified in Section 12; 13

14 파. 제13호의자율점검을계획하고추진하여야한다. M. To plan and conduct self-inspection as specified in Section 13; 하. 제조 또는 시험의 수탁자와 주요 원자재의 제조업자를 N. To assess contract manufacturers or laboratories, and 평가하여야한다. manufacturers of critical raw packaging materials; 거. 원료약품, 자재및완제품의보관관리담당자를지정하여야한다. O. To appoint a person responsible for storage of raw materials, packaging materials and finished products. 3.4 위원회각종기준서를제정ㆍ개정하고이기준을원활하게운영하기위하여다음각목의사항이포함된위원회규정을작성하고위원회를구성하여운영하여야한다. 3.4 Committee In order to establish and revise standard documents and facilitate their implementation, a committee should be organized and a written procedure for operation of the committee containing the following items should be established. 가. 위원회의목적 A. Purpose of the committee; 나. 조직 ( 위원장, 위원및간사를포함한다 ) 및임무. 필요한경우 B. Organizational structure (including the chairperson, 분야별소위원회 members and executive secretary) and responsibilities; if necessary, sub-committees may be formed for individual areas. 다. 회의운영 C. Operation of meetings. 4. 기준서의약품의 제조관리와 품질관리를 적절히 이행하기 위하여 제4.1호부터 제4.4호까지의 규정에 따른 제품표준서, 품질관리기준서, 제조관리기준서 및 제조위생관리기준서를 작성하여갖추어두어야한다. 4. Standard Documents For appropriate production control and quality control, the Product Master Files, Quality Control Standard Documents, Production Control Standard Documents and Hygiene Control Standard Documents as specified in Sections 4.1 to 4.4 should be prepared and maintained. 14

15 4.1 제품표준서제품표준서는품목마다작성하며, 다음각목의사항이포함되어야한다. 4.1 Product Master File Product Master File should be prepared for each product and should include the following information. 가. 제품명, 제형및성상 A. Product name, dosage form and appearance; 나. 허가 ( 신고 ) 연월일및허가 ( 신고 ) 사항변경연월일 B. Dates of product authorization (or registration) and changes; 다. 효능ㆍ효과, 용법ㆍ용량및사용상의주의사항 C. Efficacy effectiveness, dosage administration method and precaution in use; 라. 허가받은원료약품및그분량과제조단위당기준량, 필요한경우기준량조정에관한사항 D. Names and amounts of raw materials approved, standard amounts of raw materials for each batch, and, if necessary, adjustment of such standard amounts; 마. 제조공정 흐름도 및 상세한 공정별 제조방법과 E. Production process flow, detailed description of production 공정검사방법 ( 위탁하여제조하는경우에는위탁하는공정의범위 ) processes and in-process controls (and the scope of contracted processes, if production operations are done by another company under contract); 바. 공정별이론생산량및수율관리기준 F. Theoretical production amounts and yield control ranges for individual processing steps; 사. 작업중주의할사항 G. Precautions during operations; 아. 원자재ㆍ반제품ㆍ완제품의 기준 및 시험방법 ( 이물ㆍ곤충이 H. Specifications and test methods for raw packaging materials, 섞이거나미생물에오염되는등의우려가있는원자재는별도의기준및시험방법을설정한다 ) intermediate products and finished products (additional specifications and test methods should be established for raw packaging materials likely to be contaminated with foreign materials, insects or microorganisms.); 자. 한약원료등에관한사항 I. Information on control of traditional Korean medicinal materials; 1) 원생약및한약 1) Crude natural medicinal materials and traditional 15

16 Korean medicines; 가 ) 기원 ( 사용부위및성상 ) A) Origin (parts to be used and their appearance); 나 ) 분말또는엑스의제조를위한규격및분량 [ 포제 ( 炮製 : B) Specifications and amounts for production of powder or 한약의 치료효능을 높이고 독성과 부작용을 없애며 extract (if drugs subjected to traditional processing (all 조제나제제하는데편리하게하기위하여약제에따라 processing operations appropriately established for 적절히 하는 전체 가공과정 ) 한 약을 사용할 경우 individual medicinal materials to increase treatment 포제규격및포제방법 ] efficacy, remove toxic effects and side effects, and allow convenient use in formulation or production) are used, specifications and methods for such traditional processing); 다 ) 절단한원생약을구입하는경우시험성적서또는품질확인방법 C) If crude natural medicinal materials which were previously cut are purchased, certificate of analysis or quality verification methods. 2) 한약분말 2) Traditional Korean medicinal powders; 가 ) 원생약의품질확인방법 A) Quality verification methods for crude natural medicinal materials; 나 ) 분말의규격및시험방법 B) Specifications and test methods for powders; 다 ) 제조방법 ( 분쇄 ) 및수율 C) Production methods (pulverization) and yield; 라 ) 분말의보관방법ㆍ조건 D) Storage methods and conditions; 마 ) 작업공정별유의할사항 E) Precautions in each production process. 3) 한약엑스 3) Traditional Korean medicinal extracts; 가 ) 제조방법 ( 추출, 여과, 농축, 건조등의조건을포함한다 ) 및수율 A) Production methods (including conditions for extraction, filtration, concentration and drying) and yields; 나 ) 엑스의규격및시험방법 B) Specification and analytical methods for extracts 다 ) 엑스의보관방법ㆍ조건 C) Storage methods and conditions; 16

17 라 ) 작업공정별유의할사항 D) Precautions in each production process. 차. 제조관리및품질관리에필요한시설및기기 J. Facilities and equipment needed for production and quality control; 카. 보관조건 K. Storage conditions; 타. 유효기간또는사용기간 L. Expiry period or shelf-life period; 파. 이력관리 M. History control; 하. 작성연월일 N. Date of preparation; 거. 다음사항이포함된제조지시서 O. Production instructions, including the following information; 1) 제품표준서의번호 1) Document number of Product Master File; 2) 제품명, 제형및성질ㆍ상태 2) Product name, dosage form and characteristics properties; 3) 제조번호, 제조연월일및유효기한또는사용기한 3) Lot number, date of manufacture and expiry date or shelf-life date; 4) 제조단위 4) Lot size; 5) 사용된원료약품의시험번호, 허가받은원료약품의분량및제조단위당기준량 5) Test number of each raw material used, amounts of raw materials approved, and standard amounts for each batch; 6) 상세한제조방법, 포장공정및작업중주의할사항 6) Detailed description of production methods, packaging operations and precautions in operations; 7) 공정별수율관리기준 7) Yield control ranges for individual processing steps; 8) 제조지시자및지시연월일 8) The name of the person who orders production and the date of the order. 너. 동물유래원료에관한사항 ( 주사제로한정한다 ) P. Information on animal-derived raw materials (limited to injectable products) 1) 기원 ( 사용부위및성상 ) 1) Origin (parts to be used and appearance); 17

18 2) 제조방법 ( 추출, 여과, 농축, 건조등의조건을포함한다 ) 2) Production methods (including conditions for extraction, filtration, concentration, drying and others); 3) 규격및시험방법 3) Specification and analytical methods 4) 보관방법ㆍ조건 4) Storage methods and conditions; 5) 작업공정별유의할사항 5) Precautions in each production process. 더. 그밖에필요한사항 Q. Other necessary information. 4.2 품질관리기준서품질관리기준서에는다음각목의사항이포함되어야한다. 4.2 Quality Control Standard Documents Quality Control Standard Documents should include the following items. 가. 다음사항이포함된시험지시서 A. Test instructions, including the following information; 1) 품명, 제조번호또는관리번호, 제조연월일 1) Product name, lot number or control number, and date of manufacture; 2) 시험지시번호, 지시자및지시연월일 2) Test order number, the name of the person who orders test and the date of the order; 3) 시험항목및시험기준 3) Test items and specifications. 나. 검체 ( 檢體 ) 의채취자, 채취량, 채취장소, 채취방법및채취시주의사항 ( 무균여부등 ) 과채취시의오염방지대책 B. Persons responsible for collection of samples, amounts of samples to be taken, sampling locations, sampling methods, precautions in sampling (such as aseptic techniques), and measures to prevent potential contamination during sampling; 다. 시험결과를관련부서에통지하는방법 C. Method for notification of test results to the relevant departments; 라. 시험시설및시험기구의점검 D. Inspection of testing equipment and apparatus; 마. 안정성시험 E. Stability testing; 18

19 바. 주성분및완제품등보관용검체의관리 F. Control of reserve samples of active ingredients, finished products and others; 사. 표준품및시약의관리 G. Control of reference standards and reagents; 아. 한약원료의표본ㆍ보관에관한사항 H. Control and storage of specimens of traditional Korean medicinal materials; 자. 위탁시험또는위탁제조하는경우검체의송부방법및시험결과의판정방법 I. Methods for delivery of samples and evaluation of test results in the case of contract analysis or manufacture; 차. 그밖에제3.3호의품질 ( 보증 ) 부서책임자의의무이행에 J. Others, such as detailed procedures to fulfill the 관련된세부기준등필요한사항 responsibilities of Head of Quality (Assurance) Department as specified in Section 제조관리기준서제조관리기준서에는다음각목의사항이포함되어야한다. 4.3 Production Control Standard Documents Production Control Standard Documents should include the following items. 가. 제조공정관리에관한사항 A. Production process controls; 1) 작업소의출입제한 1) Restricted access to production areas; 2) 공정검사의방법과칭량 ( 稱量 ), 원료투입, 멸균작업등중요공정의이중점검방법 2) Methods for in-process controls and double-checking of major processes, such as weighing, addition of raw materials and sterilization; 3) 사용하려는원료약품의적합판정여부를확인하는방법 3) Verification of raw materials for their approval or rejection; 4) 재가공방법 4) Reprocessing; 5) 원생약의전처리에관한사항 5) Pretreatment of crude natural medicinal materials; 6) 한약분말 또는 한약엑스를 제조하는 경우 분말의 6) Powder particle size or extraction parameters, such as 입도 ( 粒度 ) 또는추출과정의추출용매, 시간, 온도및 solvent, time, temperature and concentration, when 19

20 농축에관한사항 producing traditional Korean medicinal powder or extract; 7) 동물유래원료를사용하는경우바이러스불활화공정에 7) If animal-derived raw materials are used, viral 관한사항 ( 주사제로한정한다 ) inactivation process (limited to injectable products). 나. 시설및기기관리에관한사항 B. Facilities and equipment; 1) 정기적인점검방법 1) Regular checks; 2) 작업중인시설및기기의표시방법 2) Identification of facilities and equipment in operation; 3) 고장등사고발생시에할조치 3) Actions to be taken in case of accidents, such as equipment failure; 4) 계측기의규격설정및교정방법 4) Specification and calibration of measuring instruments; 5) 중요기계ㆍ설비의적격성평가방법 5) Qualification of major facilities and equipment. 다. 원료약품관리에관한사항 C. Raw materials; 1) 입하시품명, 규격, 수량및포장용기의훼손여부에대한확인방법과훼손되었을경우그처리방법 1) Examinations of incoming raw materials for names, specifications, quantities and container damage, and actions to be taken when container damage is found; 2) 보관장소및보관방법 2) Storage areas and storage conditions; 3) 시험결과부적합품에대한처리방법 3) Disposal of raw materials rejected on the basis of test results; 4) 취급시의혼동및오염방지대책 ( 필요한경우미생물 4) Measures to prevent confusion and contamination during 오염포함 ) handling (if necessary, including microbiological contamination); 5) 출고시선입선출 ( 先入先出 ) 및중량또는용량이측정된용기의표시사항 5) Methods for release of materials on the First-In, First- Out basis and identification of containers for weighed or measured materials; 6) 재고관리 6) Inventory control; 20

21 7) 원생약의경우에는다음사항이포함되어야한다. 7) For crude natural medicinal materials, the following procedures should be established; 가 ) 원생약의기원, 원산지, 재배및수집, 살충제등의관리사항 A) Origin, place of cultivation, cultivation and collection methods, and control of pesticides; 나 ) 원생약의관리단위에관한기준 B) Control unit of crude natural medicinal materials; 다 ) 토사 ( 土砂 ) 등의 이물, 곰팡이 등의 미생물 오염을 C) Appropriate facilities and methods for prevention of 방지하기위한적절한시설, 방법및해당조건하에서의 foreign materials, such as soil, and microbial 저장에대한사항 contaminants, such as molds, and storage under appropriate conditions; 라 ) 충해 ( 蟲害 ) 를방지하기위하여훈증제를사용하는경우훈증제의독성에관한사항과훈증기록보존에관한사항 D) Toxicity of fumigant and maintenance of fumigation documents, if fumigant is used to prevent damage from insects. 8) 필요한 경우 자가 ( 自家 ) 사용기준 ( 품질보증방법을 8) If necessary, in-house standards (including quality 포함한다 ) 과장기보관시외부에노출되는등품질이상의우려가있는경우재시험방법 assurance methods) and re-testing methods, if quality is expected to be adversely affected owing to exposure to environmental conditions or other problems during longterm storage. 라. 자재관리에관한사항 D. Packaging materials; 1) 입하시품명, 규격, 수량및포장의훼손여부에대한확인방법과훼손되었을경우그처리방법 1) Examinations of incoming packaging materials for names, specifications, quantities and container damage, and actions to be taken when container damage is found; 2) 보관장소및보관방법 2) Storage areas and storage conditions; 3) 시험결과부적합품에대한처리방법 3) Disposal of packaging materials rejected on the basis of test results; 4) 불출방법과사용하고남아서반납된표시재료의수량 4) Methods for release of packaging materials and 21

22 확인방법 verification of quantities of labeling materials returned after use; 5) 표시기재사항의변경시하여야할조치 5) Actions to be taken when labeling information is changed; 6) 취급시의혼동및오염방지대책 ( 필요한경우미생물오염포함 ) 6) Measures for prevention of confusion and contamination during handling (if necessary, including microbiological contamination); 7) 재고관리 7) Inventory control; 8) 필요한경우자가사용기준 ( 품질보증방법을포함한다 ) 과장기보관시외부에노출되는등품질이상의우려가있는경우재시험방법 8) If necessary, in-house standards (including quality assurance methods) and re-testing methods, if quality is expected to be adversely affected owing to exposure to environmental conditions or other problems during longterm storage. 마. 완제품관리에관한사항 E. Finished products; 1) 입ㆍ출하시승인판정의확인방법 1) Procedures for verification of approval or rejection on warehousing and distribution of finished products; 2) 보관장소및보관방법 2) Storage areas and methods; 3) 출하시의선입선출방법 3) Procedures for distribution of finished products on the First-In, First-Out basis. 바. 위탁제조에관한사항 F. Contract manufacture; 1) 원자재의공급, 반제품또는완제품의운송및보관방법 1) Supply of raw packaging materials, and transportation and storage of intermediate or finished products; 2) 수탁자제조기록의평가방법 2) Evaluation of batch production records documented by contract manufacturers. 사. 그밖에제3.2호의제조부서책임자의의무이행에관련된 G. Others, such as detailed procedures to fulfill the 22

23 세부기준등필요한사항 responsibilities of Head of Production Department as specified in Section 제조위생관리기준서제조위생관리기준서에는다음각목의사항이포함되어야한다. 4.4 Hygiene Control Standard Documents Hygiene Control Standard Documents should include the following items. 가. 작업원의건강관리및건강상태의파악ㆍ조치방법 A. Control of personnel health, methods for check of health conditions and actions to be taken; 나. 작업원의수세, 소독방법등위생에관한사항 B. Hygiene instructions, such as hand washing and disinfection; 다. 작업복장의규격, 세탁방법및착용규정 C. Specifications for garments, and laundry and gowning methods; 라. 작업실등의청소 ( 필요한경우소독을포함한다. 이하같다 ) D. Methods for cleaning of production rooms (including 방법및청소주기 disinfection, if necessary) and cleaning frequencies; 마. 작업실등의청소에사용하는약품및기구 E. Chemicals and materials used in cleaning of production rooms and others; 바. 청소상태의평가방법 F. Evaluation of cleanliness after cleaning; 사. 작업소의청정도관리에관한사항 G. Control of cleanliness grades of production areas; 아. 제조시설의세척및평가 H. Cleaning and evaluation of production facilities; 1) 책임자지정 1) Appointment of persons responsible for cleaning; 2) 세척및소독계획 2) Cleaning and disinfection plan; 3) 세척방법과세척에사용되는약품및기구 3) Cleaning methods, and chemicals and materials used in cleaning; 4) 제조시설의분해및조립방법 4) Methods for disassembly and reassembly of production equipment; 5) 이전작업표시제거방법 5) Removal of previous batch identification; 23

24 6) 청소상태유지방법 6) Maintenance of clean conditions; 7) 작업전청소상태확인방법 7) Inspection of cleanliness prior to operation. 자. 해충이나쥐를막는방법및점검주기 I. Methods for prevention of insects and rodents, and inspection frequencies; 차. 그밖에제3.2호의제조부서책임자의의무이행에관련된 J. Others, such as detailed procedures to fulfill the 세부기준등필요한사항 responsibilities of Head of Production Department as specified in Section 문서 5. Documentation 5.1 문서의작성 5.1 Preparation of Documents 가. 모든문서의작성및개정ㆍ승인ㆍ배포ㆍ회수또는폐기등관리에관한사항이포함된문서관리규정을작성하여야한다. A. There should be document control procedures for preparation, revision, approval, distribution, recovery or destruction of all documents. 나. 문서는알아보기쉽게작성하여야하며, 작성된문서에는제조부서책임자또는품질 ( 보증 ) 부서책임자의서명과승인연월일이있어야한다. B. Documents should be prepared in a readily readable manner and documents should be signed and dated by Head of Production Department or Head of Quality (Assurance) Department. 다. 문서의작성자ㆍ검토자 ( 또는확인자 ) 및승인자는서명을등록한후사용하여야한다. C. Personnel who prepare, review (or verify) and approve documents should register their signatures prior to use. 라. 모든기록문서는작업과동시에작성되어야하며지울수없는잉크로작성하여야한다. 기록문서를수정하는경우에는수정하려는글자또는문장위에선을그어수정전내용을알아볼수있도록하고, 수정된문서에는수정사유, 수정연월일및수정자의서명이있어야한다. D. All records should be completed at the time each action is taken and made in the indelible ink. If any entries are corrected, a line should be drawn over words or sentences to be corrected so that original information can be easily readable. The reason for correction, date of correction, and 24

25 마. 문서를개정할때는개정사유및개정연월일등을적고제조부서책임자또는품질 ( 보증 ) 부서책임자의승인을받아야하며, 정기적으로점검하여최근에개정된것인지를확인하여야한다. 개정전의것도일정기간보존하여야한다. signature of the person who made correction should be recorded. E. When a document is revised, the reason for revision and date of revision should be recorded. The revised document should be approved by Head of Production Department or Head of Quality (Assurance) Department. Documents should be regularly reviewed and kept up-to-date. Documents of old versions should be maintained for appropriate periods. 5.2 문서의관리 5.2 Control of Documents 가. 모든기록문서 ( 전자기록을포함한다 ) 는해당제품의유효기한 A. All records (including electronic records) should be 또는사용기한경과후 1년간보존하여야한다. 다만, 별도로규정하는경우그사유와보존기한을명확하게정하여야한다. maintained for one year after expiry date or shelf-life date of the relevant product. If the maintenance period is separately established, the reason and maintenance period should be clearly defined. 나. 전자문서시스템의경우에는허가된사람만이입력, 변경또는삭제할수있으며자기테이프, 마이크로필름, 백업등의방법으로기록의훼손또는소실에대비하고, 필요시판독가능한방법으로출력하여야한다. B. For electronic document control system, only the authorized personnel should enter, modify or delete data. Magnetic tapes, microfilms, and other appropriate backup methods should be employed to prevent inadvertent loss or erasure of data. If necessary, electronic data should be output in a readable manner. 6. 밸리데이션 6. Validation 6.1 밸리데이션의대상 6.1 Scope of Validation 25

26 가. 다음의 어느 하나에 해당하는 경우에는 미리 수립된 A. Validation should be conducted according to a written 밸리데이션계획서에따라밸리데이션을실시하여야한다. validation plan, when one or more of the following events occur. 1) 새로운품목의의약품제조를처음하는경우 1) If a new medicinal product is firstly manufactured; 2) 의약품의품질에영향을미치는기계ㆍ설비를설치하는경우 2) If a piece of equipment which may affect the quality of a medicinal product is installed; 3) 의약품의품질에영향을미치는제조공정을변경하는경우 3) If a production process which may affect the quality of a medicinal product is changed; 4) 제조환경을변경하는경우 4) If the environmental condition is changed. 나. 밸리데이션실시에관한기준서, 밸리데이션실시결과및결론을종합한보고서를작성하여갖추어두어야한다. B. Written procedures for validation activities and validation reports summarizing validation results and conclusions should be maintained. 다. 밸리데이션을실시한결과제조관리및품질관리에관하여개선이필요한경우에는필요한조치를하고해당조치에대한기록을작성하여갖추어두어야한다. C. If validation studies indicate the need for improvement of production control and quality control, appropriate actions should be taken and documented. 라. 식품의약품안전처장이정하는바에따라객관적이고합리적인증거자료가있는경우에는밸리데이션을생략할수있다 D. If there are objective and reasonable evidences as specified by the Minister of Food and Drug Safety, validation may not be carried out. 6.2 공정 ( 工程 ) 밸리데이션 6.2 Process Validation 가. 의약품제조공정이미리설정된기준및품질특성에맞는제품을일관되게제조한다는것을검증하고문서화하는공정밸리데이션을실시하여야한다. A. Process validation should be conducted to demonstrate and document that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes. 나. 제품의품질에영향을미치는중요한제조공정에대해서는 B. Prospective validation should be conducted for major 26

27 예측적밸리데이션을실시하여야하되, 부득이한경우에는동시적또는회고적밸리데이션으로갈음할수있다. production processes which may affect the quality of a medicinal product. However, in exceptional circumstances, concurrent or retrospective validation may be conducted instead. 다. 공정 밸리데이션은 품목별 ( 무균제제 무균공정의 경우에는 C. Process validation should be conducted for each product (for 공정별 ) 로실시하여야한다. aseptic processes to produce sterile products, process validation should be conducted for each process). 라. 공정밸리데이션은실시시기에따라다음과같이분류한다. D. Depending on when validation is conducted, process validation is classified as follows; 1) 예측적밸리데이션 1) Prospective validation 가 ) 의약품을 판매하기 전에 실시하는 밸리데이션으로서 A) This is a validation conducted prior to commercial 기존의연구결과등을근거로품질에영향을미치는 distribution of a medicinal product. Variables which may 변동요인 ( 원자재의 물성, 조작조건 등 ) 의 허용조건이 affect the quality of products (such as physical properties 기준에맞아야한다. of raw packaging materials and operating conditions) should meet acceptance criteria based on prior study results. 나 ) 판매를 위하여 제조하는 실생산 규모의 연속 3개 B) For prospective validation, three consecutive batches 제조단위에 대하여 실시하고 분석한 다음 전체적인 should be manufactured at commercial scale and 평가를한다. 이경우 3개제조단위모두가적합하여야한다. evaluated comprehensively. All three batches should meet acceptance criteria. 2) 동시적밸리데이션 2) Concurrent validation 가 ) 부득이한사유로예측적밸리데이션을실시하지못하는 A) In exceptional cases where prospective validation cannot 경우에만 의약품을 제조ㆍ판매하면서 실시하는 be conducted due to unavoidable reasons, concurrent 밸리데이션으로서 변동요인 ( 원자재의 물성, 조작조건 validation may be conducted in the course of commercial 등 ) 이허용조건내에있어야한다. manufacture and distribution of the medicinal product. 27

28 Variables (such as physical properties of raw packaging materials and operating conditions) should meet acceptance criteria. 나 ) 판매를 위하여 제조하는 실생산 규모의 연속 3개 B) For concurrent validation, three consecutive batches 제조단위에 대하여 실시하고 분석한 다음 전체적인 should be manufactured at commercial scale and 평가를한다. 이경우 3개제조단위모두가적합하여야한다. evaluated comprehensively. All three batches should meet acceptance criteria. 3) 회고적밸리데이션 3) Retrospective validation 가 ) 원료약품의조성, 제조공정및구조ㆍ설비가변경되지 A) Retrospective validation is conducted for the medicinal 않은 경우에만 제조한 의약품에 대하여 실시하는 product of which composition, production processes, 밸리데이션으로서과거의제조및품질관리기록, 안정성데이터등기존에축적된제조및품질관리기록을근거로통계학적방법에의하여해석한다. facilities and equipment have not been changed. This validation should be conducted on the basis of statistical analysis of historical data, such as production and quality control records, stability data and others. 나 ) 실생산 규모로 제조ㆍ판매한 연속적인 10 30개의 B) Retrospective validation should be performed on 10 to 30 제조단위를대상으로실시하며그기간동안기준일탈한제조단위도포함시킨다. consecutive batches which have been commercially manufactured and distributed, including any batches which failed to meet specifications. 4) 재밸리데이션이미밸리데이션이완료된제조공정또는구조ㆍ설비등에대하여정기적으로실시하거나, 의약품등의품질에 4) Revalidation Validated production processes, facilities and equipment should be re-validated on a regular basis. Revalidation 큰 영향을 미치는 원자재, 제조방법, 제조공정 및 should be also conducted when raw packaging materials, 구조ㆍ설비등을변경한경우에실시한다. production methods, production processes, facilities or equipment which may significantly affect the quality of the medicinal product are changed. 28

29 6.3 시험방법밸리데이션 6.3 Analytical Method Validation 의약품등의품질관리를위한시험방법의타당성을미리검증하고 Analytical method validation should be conducted to demonstrate 문서화하는밸리데이션으로서품목별로실시하여야한다. and document the suitability of test methods used in quality control of medicinal products. Analytical method validation should be conducted for each product. 6.4 세척밸리데이션 6.4 Cleaning Validation 기계ㆍ설비등의잔류물 ( 전작업의약품, 세척제등 ) 이적절하게 Cleaning validation should be conducted to demonstrate and 세척되었는지를검증하고문서화하는밸리데이션으로서품목별로 document appropriate removal of residues (products from previous 실시하여야한다. operations, cleaning agents and others) from the equipment. Cleaning validation should be conducted for each product. 6.5 제조지원설비밸리데이션 6.5 Utility System Validation 제조용수공급시스템및공기조화장치시스템등의약품제조를 Utility system validation should be conducted to demonstrate and 지원하는시스템에대하여검증하고문서화하는밸리데이션으로서 document the suitability of utility systems which support the 기계ㆍ설비별로실시하여야한다. manufacture of medicinal products, such as pharmaceutical water system and HVAC system. Utility system validation should be conducted for each system and equipment. 6.6 컴퓨터시스템밸리데이션 6.6 Computer System Validation 컴퓨터시스템의 자료를 정확하게 분석ㆍ관리ㆍ기록하고 미리 Computer system validation should be conducted to demonstrate 정해진기준에맞게자료를처리한다는것을고도의보증수준으로검증하고문서화하는밸리데이션으로서기계ㆍ설비ㆍ시스템별로실시하여야한다. and document with a high degree of assurance that a computer system correctly analyzes, manages and records data and processes data according to the pre-determined specifications. 29

30 Computer system validation should be conducted for each system and equipment. 7. 품질관리 7. Quality Control 7.1 시험관리 7.1 Laboratory Control 가. 의뢰한 시험별로 다음 사항이 포함된 시험성적서를 A. For each test request, test records including the following 작성하여야한다. 시험성적서는시험의뢰서와시험지시서를통합하여작성하거나관리할수있다. information should be prepared. Test records may be prepared or managed in combination with test request and test instructions. 1) 품명, 제조번호또는관리번호, 제조연월일 1) Product name, lot number or control number and date of manufacture; 2) 시험번호 2) Test number; 3) 접수, 시험및판정연월일 3) Dates of receipt, testing and judgment; 4) 시험항목, 시험기준, 시험결과및항목별적격ㆍ부적격결과 4) Test items, specifications, results and clear statement of conformance or non-conformance for each test item; 5) 판정결과 5) Judgment; 6) 시험자의성명, 판정자의서명및중간검토자의서명 6) Name of the person who performed testing, signature of the person who reviewed test results and signature of the person who made judgment. 나. 원자재, 반제품 및 완제품은 적합판정이 된 것만을 B. Raw materials, packaging materials, intermediate products 사용하거나출하하여야하며, 일탈, 기준일탈또는편향이있는경우에는그사유를조사한후처리하여야한다. 다만, 반제품의경우에는밸리데이션, 안정성시험, 제품품질평가등을고려하여적합판정이전에사용할수있다. and finished products should be used or distributed only after they are approved. Any deviations, out-of-specification results or out-of-trend results should be investigated to identify root causes and appropriate actions should be taken. However, 30

31 다. 원자재의품질이계속적으로균질하여시험성적에충분한신뢰성이보증되는경우에는절차와기준을문서로정하여입고될때마다필요항목만검사할수있다. 다만, 확인시험및육안검사는반드시하여야하며, 정기적으로모든항목을시험하여야한다. 라. 시험기록 ( 시험근거자료를포함한다 ) 이정확하고설정된기준에맞다는것을확인하는중간검토자를두어야한다. 마. 완제품의출하승인을위한평가는제조기록서와반제품및완제품의시험결과를종합하여판정하여야한다. 바. 그래프, 계산식등시험에서얻은모든기록 ( 전자기록을포함한다 ) 은보존하여야한다. 사. 시험용검체는오염되거나변질되지아니하도록채취하여야하고, 채취과정에서원자재및반제품이오염되지않도록관리하여야한다. 채취한후에는원상태와동등하게포장하여야하며, 시험용검체가채취되었음을표시하는절차를포함한검체채취절차를마련하여야한다. intermediate products may be used before approval, while considering validation data, stability data, product quality review and others. C. If a raw material or a packaging material has consistently shown acceptable quality to assure sufficient reliability of the supplier's test results, written procedures may be developed to conduct some necessary test items on receipt of such material. However, identification test and visual examination should be conducted each time and all items should be tested on a regular basis. D. There should be a person who reviews test records (including raw data) for accuracy and compliance with established specifications. E. For release of finished products, judgment of approval or rejection should be based on comprehensive review of batch production records and results from testing of intermediate and finished products. F. All test records (including electronic records), such as graphs and calculations, should be maintained. G. Samples should be collected in a manner to prevent contamination or deterioration and sampling should be controlled so as not to contaminate raw materials and intermediates in the course of sampling. After collection, containers which have been sampled should be packaged in the manner comparable to their original conditions and 31

32 marked to show that samples have been taken. 아. 시험기기, 계측기및기록계는미리정한계획서에따라정기적으로교정ㆍ기록하여야한다. H. Test equipment, instruments and recorders should be periodically calibrated according to a written plan and such calibrations should be documented. 자. 주성분 및 완제품의 보관용 검체는 제조단위 또는 I. Reserve samples of each batch or control number of active 관리번호별로채취하고, 보관용검체중주성분은투입된 ingredients and finished products should be taken and 완제품의 마지막 제조단위, 완제품은 해당 제조단위의 retained. Reserve samples of active ingredients should be 유효기한또는사용기한경과후 1년간보관하여야한다. maintained for one year after expiry date of the last batch of finished product for which the relevant active ingredient was used. Reserve samples of finished products should be maintained for one year after expiry date of the relevant batch. 차. 주성분의 보관용 검체는 시판용 제품과 포장형태는 J. Reserve samples of active ingredients should be packed in the 동일하거나동등이상이어야하고완제품의보관용검체와 same or equivalent or better manner as for marketed 시판용 제품의 포장형태는 동일하여야 하며, 규정된 products. Reserve samples of finished products should be 시험항목 ( 무균시험, 발열성물질시험은제외할수있다 ) 을 2회이상시험할수있는양을규정된보관조건에서보관하여야한다. 다만, 시판용제품이대형포장인경우에는대형포장에소량검체를보관하거나대형포장과동일한재질의소형포장에보관할수있다. packed in the same manner as for marketed products. Reserve samples consisting of at least twice the quantity necessary to perform all the required tests (except for sterility and pyrogen testing) should be maintained under the specified storage conditions. If a product is marketed in a large packaging system, smaller amount of reserve sample may be stored in the large packaging system or the smaller packaging system of the same material as that for the large system may be used. 카. 표준품, 배지, 검체, 중요시약, 부피측정용유리기구등에 K. Control of reference standards, media, samples, critical 32

33 대한관리상황을기록하여야한다. 타. 표시재료는기재사항이변경될때마다규정에맞는지를확인하고변경된표시재료를보관하여야한다. 파. 의약품과접촉하는포장재료는의약품을변질시키거나인체에유해한재료가아닌지를확인한후사용하여야한다. 하. 제조용수는정기적으로사용점등에서제조용수를채취하여규정된시험방법에따라시험하고평가하여야한다. 거. 경시변화 ( 經時變化 : 시간의흐름에따라물리ㆍ화학적성질등이변화하는것을말한다 ) 가우려되는원료약품을장기보관하는경우재시험하여사용하여야한다. 너. 시험용동물은적절하게관리하여야하며, 각각구분하여그사용명세를기록하여야한다. 더. 실제제조ㆍ사용된검체를대상으로시험시마다시험자, 시험기기오차등을확인하는적합성시험을하여야한다. 러. 원생약은형태학적ㆍ이화학적품종관리와표본관리를하여야하며, 동일한생약이면서표본과다른경우품종에따른성분의차이, 재배시의유해물질사용여부등재배지정보수집등을통하여품질관리를철저히하여야한다. reagents and volumetric glassware should be recorded. L. On change of any information, labeling materials should be examined against specifications. New and outdated labeling materials should be maintained. M. Packaging materials coming into contact with medicinal products should be verified for adverse effects on medicinal products or hazardous effects on human bodies. They should be used only after such verifications. N. Pharmaceutical water should be regularly sampled from points-of-use and others, and tested and evaluated according to established test methods. O. If raw materials suspected to show quality changes over time (meaning change of physical chemical characteristics and others over time) are stored for a long period, they should be re-tested prior to use. P. Animals used for testing should be appropriately controlled. They should be individually identified and their use should be documented. Q. When testing samples, system suitability test should be conducted to identify any human errors or instrumental errors. R. For crude natural medicinal materials, morphological and physicochemical control of variety and specimen should be conducted. If a natural medicinal material is different from its specimen, quality control should be strictly conducted 33

34 머. 한약분말또는한약엑스를제조하는경우에는다음사항을준수하여야한다. 1) 한약분말을혼합한경우자가시험기준 ( 분말도, 생균수, 함량등 ) 을설정하여품질관리를하여야한다. 2) 한약엑스의경우자가시험기준 ( 점도, 수분, 생균수, 함량등 ) 을설정하여품질관리를하여야한다. 3) 장기간보관하는한약원료는사용기한을설정하여야하며, 정기적으로시험주기를설정하고재시험을하여그결과에따라사용기한을재설정하여야한다. through collection of information on cultivation area, such as use of hazardous substance during cultivation, difference in composition of substances between varieties and others. S. If traditional Korean medicinal powders or extracts are manufactured, the following requirements should be satisfied. 1) If traditional Korean medicinal powders are mixed, inhouse specifications (fineness, microbial count, assay and others) should be established for quality control. 2) For traditional Korean medicinal extracts, in-house specifications (viscosity, water content, microbial count, assay and others) should be established for quality control. 3) For traditional Korean medicinal materials which are stored for a long period, shelf-life dates should be established and re-testing should be conducted at regular intervals to adjust shelf-life dates on the basis of test results. 7.2 안정성시험 7.2 Stability Testing 가. 안정성 시험은 계획을 수립하여 하고, 그 결과에 따라 A. A stability testing should be performed according to a written 완제품의유효기간또는사용기간, 포장방법및저장조건을설정하여야한다. plan and stability data should be used to establish expiry period or shelf-life period, packaging method and storage conditions of a finished product. 나. 안정성시험계획서에는다음사항이포함되어야한다. B. A stability testing plan should include the following information. 34