분해, 오염, 교차오염을방지할수있는방식으로물품을취급하고보관한다. 7.41 Materials stored in fiber drums, bags, or boxes should be stored off the floor and, when appropriate, suitably spaced to permit cleaning and inspection. 파이버드럼, 백, 박스에보관된물품을바닥에서공간을띄워보관하며, 적절한경우에는세척과검사가가능하게적절한공간을두어관리한다. 7.42 Materials should be stored under conditions and for a period that have no adverse affect on their quality, and should normally be controlled so that the oldest stock is used first. 품질에부정적영향을주지않는조건과기간동안물품을보관하며, 가장오래된재고를가장먼저사용할수있도록관리한다. 7.43 Certain materials in suitable containers can be stored outdoors, provided identifying labels remain legible and containers are appropriately cleaned before opening and use. 적합한컨테이너에담은일부물품을야외에보관할수도있다. 다만식별표시라벨의판독성이유지되어야하고컨테이너를개봉하여사용하기전에적절하게세척한다. 7.44 Rejected materials should be identified and controlled under a quarantine system designed to prevent their unauthorised use in manufacturing. 부적합물품은그상태를표시하고허가없이제조에사용되지않게격리상태로관리한다. 7.5 재평가 (Re-evaluation) 7.50 Materials should be re-evaluated as appropriate to determine their suitability for use (e.g., after prolonged storage or exposure to heat or humidity). 물품이사용에적합한지결정하기위해물품을적절하게재평가한다 ( 예, 장기보관이후또는열이나습기에노출된이후 ). 8. 생산및공정관리 (PRODUCTION AND IN-PROCESS CONTROLS) 8.1 생산작업 (Production Operations) 47
8.10 Raw materials for intermediate and API manufacturing should be weighed or measured under appropriate conditions that do not affect their suitability for use. Weighing and measuring devices should be of suitable accuracy for the intended use. 중간제품과 API 제조용원료의용도적합성에영향을주지않는적절한조건에서원료를칭량하거나측정한다. 칭량장치와측정장치는예정용도에적합한정확성을갖추어야한다. 8.11 If a material is subdivided for later use in production operations, the container receiving the material should be suitable and should be so identified that the following information is available: 물품을나중의생산작업에투입하기위해분할하는경우, 적합한용기를사용하며다음정보를표시한다. - Material name and/or item code; 물품명칭및 / 또는물품코드 - Receiving or control number; 인수번호또는관리번호 - Weight or measure of material in the new container; and 새로운용기에담긴물품의중량또는측정량 - Re-evaluation or retest date if appropriate. 적절한경우에는재평가일자또는재시험일자 8.12 Critical weighing, measuring, or subdividing operations should be witnessed or subjected to an equivalent control. Prior to use, production personnel should verify that the materials are those specified in the batch record for the intended intermediate or API. 중요한칭량, 측정또는소분작업을입회하여지켜보거나그와동등한수준으로관리한다. 물품투입에앞서생산작업자는제조대상중간제품또는 API 제조용배치기록서에규정된물품이맞는지확인한다. 8.13 Other critical activities should be witnessed or subjected to an equivalent control. 기타중요한작업행위를입회하여지켜보거나그와동등한수준으로관리한다. 8.14 Actual yields should be compared with expected yields at designated steps in 48
the production process. Expected yields with appropriate ranges should be established based on previous laboratory, pilot scale, or manufacturing data. Deviations in yield associated with critical process steps should be investigated to determine their impact or potential impact on the resulting quality of affected batches. 생산공정의지정단계별로예상수율과실제수율을비교한다. 예전시험자료, 파일럿스케일생산자료, 제조자료에근거하여예상수율과적절한범위를설정한다. 중요공정단계에서수율일탈이발생하면, 조사를실시하여관련배치의품질에미치는영향또는영향의가능성을확인한다. 8.15 Any deviation should be documented and explained. Any critical deviation should be investigated. 모든일탈을문서화하고설명한다. 중대한일탈이발생한경우에는조사를실시한다. 8.16 The processing status of major units of equipment should be indicated either on the individual units of equipment or by appropriate documentation, computer control systems, or alternative means. 주요설비의공정상태를개개설비에또는적절한문서, 컴퓨터관리시스템, 또는기타수단으로표시한다. 8.17 Materials to be reprocessed or reworked should be appropriately controlled to prevent unauthorized use. 재가공또는재작업대상물품의허가받지않은사용을방지하기위해이들을적절하게관리한다. 8.2 시간제한 (Time Limits) 8.20 If time limits are specified in the master production instruction (see 6.41), these time limits should be met to ensure the quality of intermediates and APIs. Deviations should be documented and evaluated. Time limits may be inappropriate when processing to a target value (e.g., ph adjustment, hydrogenation, drying to predetermined specification) because completion of reactions or processing steps are determined by in-process sampling and testing. 마스터생산지시문서 (6.41항참조 ) 에시간제한이규정되어있는경우, 중간 49
제품과 API의품질보증을위해시간제한을준수해야한다. 일탈을문서화하고평가한다. 목표치에맞춰공정작업을진행할때는 ( 예, ph 조정, 수소화작업, 설정규격에맞춘건조작업 ) 공정관리 (IPC) 용검체채취및시험에의해반응또는공정단계의완료가결정되므로, 이경우에는시간제한이적절하지않을수있다. 8.21 Intermediates held for further processing should be stored under appropriate conditions to ensure their suitability for use. 추가공정을위해중간제품을보관하는경우에는용도적합성을보증하는적절한조건에서보관한다. 8.3 공정관리 (IPC) 용검체채취및관리 (In-process Sampling and Controls) 8.30 Written procedures should be established to monitor the progress and control the performance of processing steps that cause variability in the quality characteristics of intermediates and APIs. In-process controls and their acceptance criteria should be defined based on the information gained during the development stage or historical data. 중간제품및 API의품질특성을변화시키는공정단계의성능을관리하고진행상황을모니터하기위한절차문서를확립한다. 공정관리항목 (IPC) 과허용기준을개발단계에서확보한정보나과거자료를바탕으로규정한다. 8.31 The acceptance criteria and type and extent of testing can depend on the nature of the intermediate or API being manufactured, the reaction or process step being conducted, and the degree to which the process introduces variability in the product s quality. Less stringent in-process controls may be appropriate in early processing steps, whereas tighter controls may be appropriate for later processing steps (e.g., isolation and purification steps). 중간제품또는 API의특성, 반응또는공정단계, 공정에따른제품품질의변화정도에따라허용기준과시험종류 / 범위가달라질수있다. 초기공정단계에서는공정관리 (IPC) 가덜엄격할수도있지만, 후기공정단계에서는엄격하게관리하는것이적절하다 ( 예, 분리및정제단계 ). 8.32 Critical in-process controls (and critical process monitoring), including the control points and methods, should be stated in writing and approved by the quality unit(s). 50
관리포인트와방법을포함해중요공정관리 (IPC)( 및중요공정모니터 ) 사항을 문서로작성하고이를품질조직 (QU) 이승인한다. 8.33 In-process controls can be performed by qualified production department personnel and the process adjusted without prior quality unit(s) approval if the adjustments are made within pre-established limits approved by the quality unit(s). All tests and results should be fully documented as part of the batch record. 생산부서의자격을갖춘작업자가공정관리 (IPC) 를실시하고품질조직의사전승인없이공정을조정할수있다. 다만품질조직 (QU) 이승인하여설정한범위이내에서조정을해야한다. 모든시험과그결과를배치기록서의일부로충분하게문서화한다. 8.34 Written procedures should describe the sampling methods for in-process materials, intermediates, and APIs. Sampling plans and procedures should be based on scientifically sound sampling practices. 공정반제품, 중간제품, API의검체채취방법을기술한절차문서가있어야한다. 과학적으로타당한검체채취방법에근거하여검체채취계획과절차를규정한다. 8.35 In-process sampling should be conducted using procedures designed to prevent contamination of the sampled material and other intermediates or APIs. Procedures should be established to ensure the integrity of samples after collection. 검체채취대상물품과다른중간제품또는 API의오염을방지할수있는절차에따라공정관리용검체채취를실시한다. 채취이후검체의완전성을보증할수있는절차를구비한다. 8.36 Out-of-specification (OOS) investigations are not normally needed for inprocess tests that are performed for the purpose of monitoring and/or adjusting the process. 공정모니터및 / 또는공정조정을목적으로실시되는공정관리시험의경우에는일반적으로 OOS 조사작업이필요하지않다. 8.4 Blending Batches of Intermediates or APIs 중간제품또는 API 배치의블렌딩 51
8.40 For the purpose of this document, blending is defined as the process of combining materials within the same specification to produce a homogeneous intermediate or API. In-process mixing of fractions from single batches (e.g., collecting several centrifuge loads from a single crystallization batch) or combining fractions from several batches for further processing is considered to be part of the production process and is not considered to be blending. 이문서에서블렌딩 (blending) 이라함은동일규격이내의물품을결합하여균질한중간제품또는 API를생산하는공정을의미한다. 단일배치의부분들을공정중에혼합하는것 ( 예, 단일결정화배치에서여러차례원심분리하여그결과물을수집하는경우 ) 또는여러배치의부분들을추가처리를위해결합하는것은생산공정의일부로간주되며블렌딩으로보지않는다. 8.41 Out-Of-Specification batches should not be blended with other batches for the purpose of meeting specifications. Each batch incorporated into the blend should have been manufactured using an established process and should have been individually tested and found to meet appropriate specifications prior to blending. 규격에부합시킬목적으로 OOS 배치를다른배치와블렌딩해서는안된다. 블렌딩대상각배치는확립된공정으로제조되고, 블렌딩에앞서개별적으로시험했을때규격에부합함이밝혀진것이어야한다. 8.42 Acceptable blending operations include but are not limited to: 허용대상블렌딩작업은다음의경우를포함하되이에국한하지않는다. - Blending of small batches to increase batch size 배치규모의확대를위한소규모배치의블렌딩 - Blending of tailings (i.e., relatively small quantities of isolated material) from batches of the same intermediate or API to form a single batch. 동일중간제품또는 API 배치의테일링부분 ( 즉, 상대적으로소량의분리물품 ) 을블렌딩하여단일배치를만드는경우 8.43 Blending processes should be adequately controlled and documented and the blended batch should be tested for conformance to established specifications where appropriate. 52
블렌딩공정을적절하게관리하고문서화하며, 적절한경우에블렌딩배치를 시험하여설정규격에적합한지확인한다. 8.44 The batch record of the blending process should allow traceability back to the individual batches that make up the blend. 블렌딩공정배치기록서에는블렌드를구성하는개개배치를추적할수있는정보가있어야한다. 8.45 Where physical attributes of the API are critical (e.g., APIs intended for use in solid oral dosage forms or suspensions), blending operations should be validated to show homogeneity of the combined batch. Validation should include testing of critical attributes (e.g., particle size distribution, bulk density, and tap density) that may be affected by the blending process. API의물리적특성이중요한경우 ( 예, 내용고형제또는현탁제제조용 API), 블렌딩작업을밸리데이션하여결합배치의균질성을증명한다. 밸리데이션작업시에는블렌딩공정의영향을받을가능성이있는중요특성 ( 예, 입자크기분포, 벌크밀도, 탭밀도 ) 에대한시험을실시한다. 8.46 If the blending could adversely affect stability, stability testing of the final blended batches should be performed. 블렌딩이안정성에부정적인영향을미칠수있는경우, 최종블렌드배치의안정성시험을실시한다. 8.47 The expiry or retest date of the blended batch should be based on the manufacturing date of the oldest tailings or batch in the blend. 블렌드배치의유효일자또는재시험일자는블렌드가운데가장오래된배치또는테일링부분의제조일자를기준으로정한다. 8.5 오염관리 (Contamination Control) 8.50 Residual materials can be carried over into successive batches of the same intermediate or API if there is adequate control. Examples include residue adhering to the wall of a micronizer, residual layer of damp crystals remaining in a centrifuge bowl after discharge, and incomplete discharge of fluids or crystals from a processing vessel upon transfer of the material to the next step in the process. Such carryover should not result in the 53
carryover of degradants or microbial contamination that may adversely alter the established API impurity profile. 적절한관리가이루어진다면동일중간제품또는 API 연속배치에서잔류물의이월이가능하다. 예를들어마이크로나이저의내벽에고착된잔류물, 원심분리용기에잔류한습성크리스탈잔류층, 다음공정단계로물품을이전할때공정용기에서유체또는크리스탈의불완전한배출이있을수있다. 상기의이월에의해 API의불순물프로파일을부정적으로변화시킬수있는분해산물또는미생물오염물도같이이월되어서는안된다. 8.51 Production operations should be conducted in a manner that will prevent contamination of intermediates or APIs by other materials. 다른물품에의한중간제품또는 API의오염을방지할수있는방식으로생산작업을실시해야한다. 8.52 Precautions to avoid contamination should be taken when APIs are handled after purification. 정제이후에 API 를취급할때는오염되지않게주의한다. 9. API 및중간제품포장과표시라벨링 (PACKAGING AND IDENTIFICATION LABELLING OF APIs AND INTERMEDIATES) 9.1 공통 (General) 9.10 There should be written procedures describing the receipt, identification, quarantine, sampling, examination and/or testing and release, and handling of packaging and labelling materials. 포장및라벨링자재의인수, 확인, 격리보관, 검체채취, 검사및 / 또는시험, 사용승인, 취급절차를기술한절차문서를구비한다. 9.11 Packaging and labelling materials should conform to established specifications. Those that do not comply with such specifications should be rejected to prevent their use in operations for which they are unsuitable. 포장및라벨링자재는설정규격에부합해야한다. 규격에부합하지않는자재는부적합처리하여작업에투입되지않도록해야한다. 9.12 Records should be maintained for each shipment of labels and packaging 54