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1 1996년 3월런던 CPMP/QWP/486/95 COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) 완제의약품제조가이드라인 (NOTE FOR GUIDANCE ON MANUFACTURE OF THE FINISHED DOSAGE FORM) Re-Issue* Discussion in the Quality Working Party June 1995 Approval by the CPMP September 1995 Date for Coming into Operation 1 April 1996 * 주 : 본문의명확화와오자수정에따라 1996 년 4 월재발행 1

2 MANUFACTURE OF THE FINISHED DOSAGE FORM Note for Guidance Concerning the application of Part 2, section B of the Annex to Directive 75/318/EEC, as amended by Directive 91/507/EEC, with a view to the granting of a marketing authorisation. [EMEA status as of April 1996] 1. 서론 (INTRODUCTION) According to Directive 65/65/EEC, an application for a marketing authorisation shall contain a brief description of the method of preparation. 디렉티브 65/65/EEC에의거하여판매허가신청서류에는제조방법을간략하게기술해야 한다. This is described in more detail in the Annex, Part 2 of Directive 91/507/EEC, which states: 디렉티브 91/507/EEC 파트 2의부록에보다상세하게기술되어있으며, 다음과같이규정되어있다. "The description of the method of preparation [...] shall be drafted in such a way as to give an adequate synopsis of the nature of the operations employed. " 제조방법은작업방법의특성을적절하게요약하여설명하는식으로작성한다. For this purpose it shall include at least: 이를위하여적어도다음사항이포함되어야한다. mention of the various stages of manufacture, so that an assessment can be made of whether the processes employed in producing the pharmaceutical form might have produced an adverse change in the constituents, 의약품생산과정에서구성물이부정적인영향을받는지평가할수있도록각제조단계를기술해야한다. in the case of continuous manufacture, full details concerning precautions taken to ensure the homogeneity of the finished 2

3 product, 연속제조인경우에는완제품의균질성보장을위한주의사항을상세하게기술해야 한다. the actual manufacturing formula, with the quantitative particulars of all the substances used, the quantities of the excipients, however, being given in approximate terms in so far as the pharmaceutical form makes this necessary; mention shall be made of any substances that may disappear in the course of manufacture; any overage shall be indicated and justified, 실제제조처방을기술하며이때성분별투입량에대한상세한설명, 의약품의특성때문에필요한경우에는대략적인첨가물의양을기술한다. 제조과정에서사라지는성분도언급한다. 과량투입시에는이를명기하고그타당성을제시한다. a statement of the stages of manufacture at which sampling is carried out for in-process control tests, where other data in the documents supporting the application show such tests to be necessary for the quality control of the finished medicinal product, 완제품의품질관리에공정관리시험이필요함을보여주는데이터가신청서류에 있는경우, 공정관리시험을위해검체를채취하는제조단계를설명한다. experimental studies validating the manufacturing process, where a non-standard method of manufacture is used or where it is critical for the product, 비표준제조방법을채택하거나제품에중요한경우에는제조공정밸리데이션실험. for sterile products, details of the sterilisation processes and/or aseptic procedures used." 무균제품인경우에는멸균공정및 / 또는무균절차에대한상세한설명." This Note for Guidance provides guidance on the background and the interpretation of some aspects of the text of the Directive. 이문서는디렉티브본문일부의배경정보와해석가이드라인을제공한다. This Note for Guidance does not pertain to biological medicinal 3

4 products such as vaccines, sera, toxins and allergens, products derived from human blood and plasma as well as medicinal products prepared biotechnologically. 이가이드라인은백신, 혈청, 독소및알레르기유발물질, 사람혈액및혈장유래제품, 그리고생명공학적의약품등생물학적의약품에는적용되지않는다. 2. 판매허가신청서류와 GMP(THE APPLICATION FOR MARKETING AUTHORISATION AND GMP) Medicinal products on the market in the EC should be produced under the EC Rules for Good Manufacturing Practice (GMP), see Directive 91/356/EEC. EC에서판매되는의약품은 EC GMP 기준에따라생산해야한다 ( 디렉티브 91/356/EEC 참조 ). Many general elements of GMP and quality assurance do not need to be described in the application for marketing authorisation. Examples are qualifications of key personnel, cleaning procedures for the production equipment and production areas, final packaging and labeling procedures etc. 제품판매허가신청서류에 GMP 및품질보증에관한사항을상세하게기술할필요는없다. 주요인물의자격, 생산설비와생산지역의세척절차, 최종포장및라벨작업절차등이그예이다. In general, the dossier for marketing authorisation should contain only those elements of the quality assurance which are specific for the medicinal product, whereas non product related elements of the quality assurance fall within the field of GMP, consequently, no description is necessary in the application for a marketing authorisation. 일반적으로판매허가신청서류에는해당의약품에특이적인품질보증요소만을기술하며, 제품과관계없는품질보증요소들은실제현장에서 GMP 차원으로실시되므로, 허가신청서류에는그사항을기술할필요가없다. This Note for Guidance addresses the items that should be presented in the application for a marketing authorisation. For items not to be covered by the application for a marketing authorisation, the 4

5 obligation for adherence to the EC GMP principles is implicit. 이가이드라인문서는판매허가신청서류에기술해야하는사항만을다룬다. 판매허가 신청서류의대상이되지않는사항은 EC GMP 기준을준수해야한다. 3. MF(MANUFACTURING FORMULA) The intended batch size should be indicated. 예정배치규모를표기한다. An application for a variable and/or alternative batch size should be justified. Consistent conformity of the finished product to all the specifications should be made plausible. 변형및 / 또는대체배치규모를채택하고자한다면, 그타당성을밝혀야한다. 완제품이모든규격에일관되게부합할수있어야한다. The names and quantities of all ingredients used in the course of the manufacture should be stated. This includes ingredients which are removed from the product during the production process, such as solvents. Substances that may not always be used should also be mentioned, such as acids and alkalis for ph adjustment. Overages must be indicated in quantitative terms and justified in the section on Development Pharmaceutics. 제조과정에서사용되는모든성분의명칭과양을명기한다. 용매처럼생산과정중에제품에서제거되는성분도포함한다. ph 조정을위한산 / 알칼리같이항상투입되지않는성분도명기한다. 과량을투입하는경우에는그양을표기하고의약품개발부분에서그타당성을제시해야한다. For each ingredient, the allowed upper and lower acceptance limits for the actual quantity of each ingredient from the nominal quantity of the batch manufacturing formula should be stated. 성분별로해당배치제조의기준량에대비한각성분의실제상 / 하한허용기준을명기한다. For active ingredients, these acceptance limits should be within 95 to 105% of the nominal quantity; for excipients, acceptance limits of 90 to 110% of the nominal quantity are acceptable without further justification. 5

6 활성성분인경우에는허용기준을기준량에대비하여 95 ~ 105% 로한다. 첨가물은 기준량대비 90 ~ 110% 정도면별도의타당성증명을할필요가없다. Wider acceptance limits may be acceptable but should be justified by showing that batches with a composition close to the upper and lower proposed acceptance limits remain within the finished product specifications. 허용기준을더넓게정할수있지만, 그런경우에는상 / 하한기준에근접한조성으로제조해도최종제품규격에부합함을보여주는식으로타당성을증명해야한다. When that the quantity of an active ingredient to be used is calculated from the actual assay value of the batch of that active ingredient ("factorisation"), this has to be indicated. If another ingredient is used to keep the total mass per batch equal to the quantity provided for in the batch manufacturing formula, this should also be indicated. 활성성분투입량을그활성성분배치의실제정량분석값에근거하여계산을통해정한다면, 이를표시해야한다. 배치 MF에제시된양과동일하게배치당총중량을유지하기위해다른성분을투입한다면, 이또한표시해야한다. 4. 제조공정설명 (DESCRIPTION OF THE MANUFACTURING PROCESS) A description of the manufacturing process should be given. 제조공정을설명한다. A proposal to allow alternative steps in the manufacturing process (for instance: two alternative sterilisation methods for the container) should be accompanied by evidence showing that all processes proposed will consistently produce a finished product in compliance with the specifications. 제조공정중에서대체단계를허용하고자한다면 ( 예, 용기멸균방법이두가지있는경우 ), 제시된모든방법으로처리해도최종제품이규격에일관되게부합한다는점을보여주는증거를제시해야한다. If relevant (see below), the apparatus to be used has to be described. The in-process controls and corresponding acceptance limits need to be described as well, when relevant (see below). 6

7 해당되는경우에는 ( 아래참조 ) 사용할장치도설명한다. IPC 와허용기준또한기술할 필요가있다 ( 아래참조 ). The various steps in the manufacturing process and corresponding inprocess controls should also be shown in a flow-chart. 제조공정단계와해당 IPC 를흐름도로제시한다. The presented data on the manufacturing process, apparatus and inprocess controls are binding for the future manufacturing of the medicinal product, unless authorisation for changes is given by the Competent Authority. 관계당국이변경승인을하지않으면, 제조공정, 장치, IPC 사항을향후의약품제조시에준수해야한다. It is in the interest of both the applicant and the regulatory authorities to avoid unnecessary applications for variations. Very detailed descriptions of the manufacturing process, apparatus and inprocess controls should therefore be avoided. 불필요한변경신청을피하는것이신청업체와규제당국모두에게바람직하다. 그러므로제조공정, 장치, IPC를매우상세하게설명하지않도록한다. In selecting the necessary level of detail the following should be considered: 구체성의정도를정할때는다음사항을검토한다. the testing at release of the finished product, 최종제품출하승인시험 the description of the manufacturing process and apparatus, 제조공정및장치 the in-process controls and validated acceptance limits. IPC 와밸리데이션된허용기준 Together these should provide a high degree of probability that each unit of every batch of the finished product, will be in conformity 7

8 with the specifications. 이모든정보를통해완제품각배치의제품이모두규격에부합할것이라는점을충분히 제시할수있어야한다. So, if the consistent quality of a medicinal product can be fully safeguarded by the implicit" production under GMP and testing of the finished product at release, the description of the manufacturing process need not be comprehensive, and apparatus and in-process controls need not to be described. GMP에의거한생산과완제품의출하시험에의해의약품의일관된품질이충분히보장될수있다면, 제조공정을포괄적으로설명할필요가없으며, 장치와 IPC도기술할필요가없다. However, many quality parameters that are tested at release do not provide sufficient certainty of the quality of the whole batch from a statistical point of view, because the quality parameter may not necessarily be homogeneous within the batch. 그러나배치의전체제품에걸쳐품질변수가반드시균질할수는없기때문에, 통계적관점에서보면출하시점에서시험한품질변수로는전체배치의품질을충분히확신할수없다. An example is the homogeneous distribution of the active ingredient in solid and semi-solid dosage forms, i.e. content uniformity. Testing at release alone does not provide sufficient certainty for the content uniformity of the whole batch from a statistical point of view. 고형제및반고형제제품인경우에활성성분의균질한분포, 즉함량균일성이그예라고할수있다. 통계적측면에서보면출하시점의시험만으로는전체배치의함량균일성을충분히확신할수없다. So, the apparatus to be used and the appropriate in-process controls (i.e. mixing time, mixing speed etc.) and the validated acceptance limits for these in-process controls (see below) must be proposed in the application file. 그러므로사용장치와적절한 IPC( 즉, 혼합시간, 혼합속도등 ), 그리고이들 IPC 항목의밸리데이션된허용기준 ( 아래참조 ) 을신청서류에기술해야한다. Another example is sterilisation. For all sterilisation processes, 8

9 appropriate in-process controls and their acceptance limits are to be described in the application file, see below. 또다른예가멸균공정이다. 모든멸균공정에대하여적절한 IPC 및허용기준을신청서류에기술해야한다 ( 아래참조 ). 5. 제조체인 (DESCRIPTION OF THE MANUFACTURING CHAIN) An account shall be given of the sites at which each stage of the manufacturing and assembly operations takes place. Different manufacturing sites belonging to the same company shall be mentioned as separate units. The company responsible for the final approval of the release of the product onto the market shall be specified. 제조및조립작업각단계가실시되는사업장을설명한다. 동일회사에속하는여러제조사업장이있다면, 이를각기별도로기술한다. 제품의최종출하승인책임회사를명기한다. 6. 제조공정밸리데이션데이터 (VALIDATION DATA OF THE MANUFACTURING PROCESS) Validation studies that are used to identify critical steps in nonstandard manufacturing processes are part of the Development Pharmaceutics, and should be described in Part IIA of the application file. 비표준제조공정의핵심단계를파악하기위한밸리데이션실험은의약품개발의한부분에해당되며, 이를신청서류의파트 IIA에서기술해야한다. Examples are: new dosage forms, the manufacturing of liposomes, etc. 새로운제형, 리포솜제조공정등이이에해당된다. Irrespective of these Development Pharmaceutical process validations, process Validation results of the actual production process must be described in Part IIB if conformity to the finished product specifications cannot be guaranteed to an acceptable degree of statistical certainty by testing the finished product at release. This holds also for standard manufacturing processes. 의약품개발부분의공정밸리데이션정보와관계없이, 최종제품을출하시에시험하는것으로최종제품규격에부합한다는점이통계적확신을줄정도로보장되지않는다면 9

10 실제생산공정의밸리데이션결과를파트 IIB 에서기술해야한다. 표준제조공정도 마찬가지이다. Examples are mixing, granulation and emulsifying processes of solid and semi-solid dosage forms and non-pharmacopoeial sterilisation procedures, see below. 고형제및반고형제의혼합, 과립, 유화공정과약전에규정된것과는다른멸균절차등이그예이다 ( 아래참조 ). Process validation data obtained with closely related medicine products may be acceptable. 밀접한연관관계의다른의약품에서확보한공정밸리데이션데이터도인정할수있다. Please note that notwithstanding a successful process validation, the quality parameters related to the validated process should be specified under the release specifications and end-of-shelf-life specifications. For instance, sterility should always be specified at release and end-of-shelf-life, notwithstanding a successful validation of the sterilisation process. Also, the content uniformity of solid and semi-solid dosage forms should be specified in the release and end-of-shelf life specifications, notwithstanding a successful process validation with respect to homogeneity. 공정밸리데이션의성공적완료와는별개로, 밸리데이션된공정과관련된품질변수를출하승인규격과유효기간규격에명기해야한다. 일례로멸균공정밸리데이션이만족스럽게완료되었다고해도, 출하승인시점과유효기간만료시점에무균시험을실시해야한다. 또한균질성과관련된공정밸리데이션의완료와관계없이, 출하승인규격과유효기간규격모두에고형제와반고형제의함량균일성을명기해야한다. It may be acceptable to refrain from the routine testing at release of such a specification ("parametric release"), see the Note for Guidance "Specifications and Control Tests on the Finished Product". With respect to parametric release in relation to sterilisation, the text of the Ph. Eur. "Methods of preparation of sterile products" is to be observed. 출하시점에이규격에따라정기적으로시험하지않는방법도인정될수있다 (" 변수기반출하승인 (parametric release)"). ( 최종제품의규격및품질관리시험가이드라인참조 ). 멸균공정과관련한변수기반출하승인은, 유럽약전의 " 무균제품제조방법 " 에 10

11 제시된사항을준수한다. 7. 특별항목 (SPECIAL ITEMS) 7.1 멸균방법 (Method of sterilization) The choice of the method of sterilisation should be justified under Development Pharmaceutics, Part IIA. 멸균방법의선정이유를파트 IIA 의약품개발항목에설명한다. According to the text of the Ph. Eur.: "Methods of preparation of sterile products", terminal sterilisation in the final container is to be preferred. Refraining from terminal sterilisation in the final container should be justified in the application file. 유럽약전 " 무균제품제조방법 " 에기술된바에따라충전제품의사후멸균이바람직하다. 사후멸균을하지않는다면, 그이유를신청서류에서설명해야한다. In Part IIB the actual sterilisation process to be applied should be described. 실제멸균공정을파트 IIB 에서기술한다. All sterilisation processes should be carried out according to the instructions of the Ph. Eur. In the application file, an explicit statement should be made that the instructions of the Ph. Eur. are followed. 모든멸균공정은유럽약전에기술된바에따라실시한다. 유럽약전의방법을준수했다는문구를신청서류에명시해야한다. According to the Ph. Eur., all sterilisation procedures should be validated and be carried out under the EC GMP-rules. However, in the application file for marketing authorisation for some sterilisation procedures no, or only limited validation data and data on the bioburden of the product prior to the sterilisation need to be presented, see below. 유럽약전에따라모든멸균절차를밸리데이션해야하며, EC GMP 기준에따라멸균해야한다. 그러나판매허가신청서류에서는일부멸균공정에대하여밸리데이션데이터가전혀필요없거나제한된데이터만이필요할수있으며, 그리고멸균이전단계의 11

12 바이오버든데이터를제시할필요가있다 ( 아래참조 ). In the case of terminal sterilisation in the final container by heat using a reference condition of the Ph. Eur., only the time and temperature of the cycle and the acceptance limits of the corresponding in-process controls need to be provided in the application file. 유럽약전의조건에따라사후열멸균을하는경우, 허가신청서류에는사이클의시간과온도, 그리고해당 IPC 허용기준만을제시할필요가있다. So, this holds for sterilisation by saturated steam at a minimum of 121 C for 15 min. and by dry heat at a minimum of 160 C for at least 2 hours. 최소 121 C에서 15분간포화스팀으로처리하는멸균과최소 160 C에서적어도 2시간건열로처리하는멸균이그렇다. In accordance with the Ph. Eur., these conditions should be met within all units. However, the validation data showing that all units are subjected to these conditions are normally not required in the application file. They may be requested by the competent authorities in certain circumstances. 유럽약전에따라모든물품이이조건에노출되어야한다. 그러나모든물품이이조건에노출된다는점을보여주는밸리데이션데이터를신청서류에포함시킬필요는없다. 경우에따라관계당국이이런데이터를요구하는수도있다. For terminal sterilisation cycles in the final container by heat with a time and/or temperature below the values of the reference conditions of the Ph. Eur., not only the acceptance limits for the in-process controls for time and temperature should be stated, but also the maximum acceptable bioburden before sterilisation. 유럽약전의조건보다떨어지는온도및 / 또는시간동안열로사후멸균하는경우, 시간및온도에대한 IPC 허용기준을기재하고멸균이전단계의최대허용바이오버든을제시한다. The results of the validation of the sterilisation cycle with regard to the effectiveness in terms of the Sterility Assurance Level (SAL) obtained should be presented in the application file. 12

13 무균성보증수준 (SAL) 측면에서멸균사이클의효과에관한밸리데이션결과를신청서류에 기술한다. For sterilisation by filtration the maximum acceptable bioburden prior to the filtration must be stated in the application. In most situations NMT 10 CFU's/100 ml will be acceptable, depending on the volume to be filtered in relation to the diameter of the filter. If this requirement is not met, it is necessary to use a pre-filtration through a bacteria-retaining filter to obtain a sufficiently low bioburden. 제균여과인경우에는여과이전단계의최대허용바이오버든기준을신청서류에명기한다. 대개는필터직경대비여과액량에따라 10 CFU/100 ml 이하면적합하다. 이기준에부합하지않는다면, 제균급필터로예비여과를실시하여바이오버든을충분히낮출필요가있다. The type of bacteria-retentive filter, and its pore size should also be described in the application. Pore sizes of 0.22 μm or less are acceptable without further justification, in accordance with the Ph. Eur. A proposal to use a larger pore size in combination with an additional sterilisation step has to be validated and justified in the application file. 제균급필터의유형, 구멍크기또한기술한다 μm 이하의구멍크기이면유럽약전에따라추가로타당성을입증할필요없이적합하다. 구멍이더큰필터를사용하고추가멸균단계를도입하고자한다면, 밸리데이션을실시하고이의타당성을신청서류에서제시해야한다. Results of media filling fall within the field of GMP and need not be presented routinely in the application for marketing authorisation but may be requested by the competent authorities in certain circumstances. 메디아필결과는 GMP 영역에속하는것으로판매허가신청서류에포함시킬필요는없지만, 경우에따라서관계당국이요구할수있다. For sterilisation by gamma and electron radiation, see the Note for Guidance "The Use of Ionization Radiation in the Manufacture of Medicinal Products". 감마선및전자조사에의한멸균인경우, " 의약품제조에서이온화방사선조사의활용 " 13

14 가이드라인을참조한다. For sterilisation by ethylene oxide, the provisions laid down in the Note for Guidance "Limitations to the use of Ethylene Oxide in the manufacture of medicinal products" should be followed, i.e. its use as a sterilisation method is only acceptable if no other method of sterilisation is available. EO 가스멸균인경우에는 " 의약품제조에서 EO 가스활용의제한 " 가이드라인에제시된사항을준수한다. 즉다른멸균방법이없는경우에만이방법을채택할수있다. The application for marketing authorisation should contain a description of the apparatus, quantitative data on the mixture of gases to be used, data on the bioburden prior to sterilisation, the time of exposure of the gas, the temperature and humidity prior to and during the sterilisation cycle, and the conditions for the removal of ethylene oxide. All these conditions should be monitored by suitable in-process controls that are to be described together with the acceptance limits for these in-process controls. 판매허가신청서류에는장치, 사용가스의양, 멸균이전단계의바이오버든, 가스노출시간, 멸균사이클이전및사이클동안의온도와습도, EO가스제거조건등에대한설명이포함되어야한다. 이모든조건을적절한 IPC로모니터해야하며, IPC 사항과그허용기준을기술해야한다. Results of the process validation should be presented to justify these acceptance limits for the in-process controls. The results should demonstrate both an acceptable assurance, of sterility and removal of ethylene oxide to an acceptable level. IPC 허용기준의타당성이공정밸리데이션결과에제시되어야한다. 이밸리데이션결과는허용무균수준과 EO 가스제거수준의달성을증명해야한다. Limits of NMT 1 ppm of ethylene oxide (if applicable, measured by means of a simulated use extraction method) and NMT 50 ppm of ethylene chlorhydrin (or any other halogenated ethylenehydrin) are acceptable without further justification, once sterilisation by ethylene oxide has been justified. 일단 EO 가스멸균법의타당성을제시하면, EO 1 ppm 이하 ( 해당되는경우에는모의사용추출법으로측정 ) 와에틸렌클로르히드린 50 ppm 이하 ( 또는기타에틸렌히드린할로겐 14

15 화합물 ) 의기준이면추가의타당성제시없이인정할수있다. Notwithstanding successful process validation, a limit for residual ethylene oxide, and the corresponding validated analytical method, should be included in the product release- and end-of-shelf-life specifications. 공정밸리데이션이성공리에완료되어도, 잔류 EO 기준과밸리데이션된잔류 EO 분석방법을제품출하승인규격과유효기간규격에포함시켜야한다. 7.2 잔여제품의재가공 (Re-processing of residual product) Procedures for the re-processing of residual product of non-biological medicinal products fall within the field of GMP and need not to be described in the marketing authorisation dossier. 비생물학적의약품잔여제품의재가공절차는 GMP 영역에속하는것이며, 판매허가신청서류에기술할필요가없다. 7.3 용매또는가스의제거 (Removal of solvents or gases) If toxic gases or solvents are used in the manufacture of the finished product, release and end-of-shelf-life specifications for maximum acceptable residues of these solvents or gases should be proposed for the product. A justification for the proposed limits can be presented if required in Part IIA, Part IIB or IIE of the file. Both toxicological and technological aspects should be discussed in this justification. 최종제품제조시에독성가스나용매를사용한다면, 이용매나가스의최대허용잔류량기준을출하승인규격과유효기간규격에포함시켜야한다. 필요한경우에는파트 IIA, 파트 IIB, 파트 IIE에서예정기준의타당성을제시할수있다. Stages of the manufacturing process which affect the levels of such materials in the product should be controlled by in-process controls and the acceptance limits for these in-process controls should be validated. The results of these process validations should be presented in the application for marketing authorisation; see the paragraph in 7.1 above on ethylene oxide sterilisation. 제품에존재하는이들성분의농도에영향을미치는제조공정단계를 IPC로관리해야 15

16 하고이 IPC 의허용기준을밸리데이션해야한다. 이러한공정밸리데이션결과를판매 허가신청서류에서기술한다. 상기 7.1 의산화에틸렌멸균법을참조한다. 7.4 직접포장자재의세척 (Cleaning of primary packaging material) Washing procedures of the primary containers and closures normally fall within the field of GMP and are not needed routinely in the application for marketing authorisation but may, in certain circumstances, be requested by the Competent Authority. 직접용기및마개의세척절차는 GMP 영역에속하는것이며판매허가신청서류에기술할필요는없지만, 경우에따라서는관계당국이요구할수있다. 7.5 직접포장자재의멸균 (Sterilisation of primary packaging material) Where applicable, the sterilisation procedure of the primary containers and closures should be described, and, when necessary, validated according to the paragraph on sterilisation. 해당되는경우에는직접용기및마개의멸균절차를기술해야하며, 필요하면멸균방법에서기술한사항에따라밸리데이션을해야한다. 7.6 생산지역 (Production areas) Details on the production area, i.e. specifications for the microbiological quality of the areas and freedom from particles in the air normally fall within in the field of GMP and are not needed routinely in the application for marketing authorisation but may, in certain circumstances, be requested by the Competent Authority. 생산지역에대한세부사항, 즉생산지역의미생물학적품질기준, 부유미립자기준등은 GMP 영역에속하는것이며, 판매허가신청서류에서기술할필요는없다. 그러나경우에따라서는관계당국이요구할수있다. 16

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