WHO GMP for Pharmaceutical Products: Main Principles

Transcription

1 제약업계의품질경영 : 원칙과필수요소 (Quality management in the medicines industry: philosophy and essential elements) 1 In the medicines industry at large, quality management is usually defined as the aspect of the management function that determines and implements the quality policy, i.e. the overall intention and direction of an organization regarding quality, as formally expressed and authorized by top management. The basic elements of quality management are: 일반적으로제약업계의품질경영은품질과관련하여조직의전반적인의도와방향을최고경영진이공식적으로표현하고승인한 " 품질방침 (quality policy)" 을결정하고구축하는관리업무로정의된다. 품질경영의기본요소는다음과같다. an appropriate infrastructure or quality system, encompassing the organizational structure, procedures, processes and resources; 조직구조, 절차, 공정, 자원을포괄하는적절한인프라스트럭처또는 품질시스템 " systematic actions necessary to ensure adequate confidence that a product (or service) will satisfy given requirements for quality. 제품 ( 또는서비스 ) 이지정품질기준을충족시킨다는적절한신뢰를확보하는데필요한체계적인행위. The totality of these actions is termed QA. Within an organization, QA serves as a management tool. In contractual situations, QA also serves to generate confidence in the supplier. The concepts of QA, GMP, QC and quality risk management (QRM) are interrelated aspects of quality management and should be the responsibility of all personnel. They are described here in order to emphasize their relationship and their fundamental importance to the production and control of pharmaceutical 1 Good manufacturing practices for pharmaceutical products, Part One. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirtysecond report. Geneva, World Health Organization, 1992, Annex 1 (WHO Technical Report Series, No. 823); and in: Quality assurance of pharmaceuticals. A compendium of guidelines and related materials. Volume 2, 2nd updated edition. Good manufacturing practices and inspection. Geneva, World Health Organization, 2007; and in: Quality assurance of pharmaceuticals. A compendium of guidelines and related materials. Geneva, World Health Organization, 2010 (CD-ROM). 1

2 products. 이러한행위의총체를 " 품질보증 (QA)" 이라고한다. 조직에서 QA는관리도구역할을한다. 계약상황에서 QA는공급업체에대한신뢰를확보하는데기여한다. 품질경영에서 QA, GMP, QC, QRM(quality risk management) 개념은상호밀접하게연계되어있으며모든작업자의책임이다. 의약품생산및관리에서이들의관계와근본적인중요성을강조하기위해하나씩자세히설명한다. 1. 제약품질시스템 (Pharmaceutical quality system) 1.1 Principle. The manufacturer must assume responsibility for the quality of the pharmaceutical products to ensure that they are fit for their intended use, comply with the requirements of the marketing authorization and do not place patients at risk due to inadequate safety, quality or efficacy. The attainment of this quality objective is the responsibility of senior management and requires the participation and commitment of staff in many different departments and at all levels within the company, the company s suppliers and the distributors. To achieve this quality objective reliably there must be a comprehensively designed and correctly implemented pharmaceutical quality system (PQS) incorporating GMP and QRM 원칙. 의약품이목적용도에적합하고판매허가기준에부합하며부적절한안전성, 품질또는유효성때문에환자를위험에처하지않도록, 제조업체는의약품품질에책임을져야한다. 이와같은품질목표의달성은고위경영자의책임이며, 회사의여러부서와모든부문의직원과공급업체와유통업체가참여하고준수해야한다. 이품질목표를신뢰성있게달성하기위하여, GMP와 QRM을통합한제약품질시스템 (PQS) 을포괄적으로설계하고정확하게구축해야한다. 1.2 Senior management has the ultimate responsibility to ensure an effective PQS is in place, is adequately resourced, and that roles, responsibilities, and authorities are defined, communicated and implemented throughout the organization. Senior management s leadership and active participation in the PQS is essential. This leadership should ensure the support and commitment of staff at all levels and sites within the organization to the PQS. 효과적인 PQS를구축하고적절한자원을확보하며역할과책임, 권한을규정해조직전체에전파하고추진할궁극적인책임이고위경영자에게있다. PQS의 2

3 구축과운영에있어서고위경영자의적극적인참여와리더십이필수적이다. 이와 같은경영자의리더십은조직의모든부문이 PQS 를지원하고준수하게한다. 1.3 Quality management is a wide-ranging concept covering all matters that individually or collectively influence the quality of a product. It is the totality of the arrangements made with the object of ensuring that pharmaceutical products are of the quality required for their intended use. Quality management, therefore, incorporates GMP and other factors, including those outside the scope of this guide, such as product design and development. 품질경영은개별적으로또는집단적으로제품의품질에영향을주는모든사안을대상으로하는광범위한개념이다. 의약품이목적용도에필요한품질을갖추도록하는것을목표로하여만든조직화된제도의총합이다. 그러므로품질경영은 GMP 이외에도제품디자인과개발등이가이드의범위를벗어나는기타요소도포괄하는것이다. 1.4 GMP applies to the life-cycle stages from the manufacture of investigational medicinal products, technology transfer, and commercial manufacturing, through to product discontinuation. The PQS can extend to the pharmaceutical development life-cycle stage and should facilitate innovation and continual improvement and strengthen the link between pharmaceutical development and manufacturing activities. All parts of the PQS should be adequately resourced and maintained, including being provided with sufficient competent personnel, suitable premises, equipment and facilities. 임상시험의약품제조부터기술이전과상업적제조를거쳐제품이완전히중단될때까지, 전체라이프사이클단계에 GMP가적용된다. 하지만제약품질시스템의범위가의약품개발단계까지확장될수있으며, 혁신과지속적개선을촉진하고의약품개발과제조활동사이의연계를강화한다. 충분한수의적합한작업자, 시설, 설비를포함하여, PQS의모든부분에적절한자원을갖추고유지한다. 1.5 The PQS appropriate to the manufacture of pharmaceutical products should ensure that: 의약품의제조에적절한 PQS 는다음사항을보장해야한다. a) product realization is achieved by designing, qualifying, planning, implementing, maintaining and continuously improving a system that allows the consistent delivery of products with appropriate quality 3

4 attributes; 적절한품질특성을갖춘제품을일관되게제조할수있는시스템의설계, 적격성평가, 계획, 구축, 유지관리, 지속적개선에의해제품실현이달성된다. b) product and process knowledge is managed throughout all lifecycle stages; 라이프사이클전체단계에걸쳐제품과공정지식을관리한다. c) pharmaceutical products are designed and developed in a way that takes account of the requirements of GMP and other associated codes such as those of good laboratory practice (GLP) and good clinical practice (GCP); GLP와 GCP 등다른관련기준과 GMP 기준을고려하여의약품을설계하고개발한다. d) production and control operations are clearly specified in a written form and GMP requirements are adopted; 생산및관리작업을문서형태로명확히규정하고 GMP 기준을채택한다. e) managerial responsibilities are clearly specified in job descriptions; 관리책임을직무기술문서에명확히규정한다. f) arrangements are made for the manufacture, supply and use of the correct starting and packaging materials, the selection and monitoring of suppliers and for verifying that each delivery is the correct material from the approved supply chain; 올바른출발물질과포장자재의제조, 공급, 사용을위한대책, 공급업체의선정과모니터를위한대책, 그리고각각의물품이승인받은공급체인을통해납품된것임을확인하기위한대책을구비한다. g) all necessary controls on starting materials, intermediate products, and bulk products and other in-process controls, calibrations and validations are carried out; 출발물질, 중간제품, 벌크제품에대한모든필수관리활동과기타공정관리 (IPC), 교정및밸리데이션을실시한다. h) the finished product is correctly processed and checked, according to the defined procedures; 최종제품을규정된절차에따라올바르게가공하고점검한다. i) pharmaceutical products are not sold or supplied before the authorized persons (see also sections 9.11 and 9.12) have certified that each production batch has been produced and controlled in accordance with the requirements of the marketing authorization and any other 4

5 regulations relevant to the production, control and release of pharmaceutical products; 각생산배치가판매허가기준과의약품의생산, 관리, 출하승인에관련된기타규정에따라생산 / 관리되었음을 AP(9.11 & 9.12 참조 ) 가증명하기전에의약품을판매하거나공급해서는안된다. j) processes are in place to assure the management of outsourced activities; 아웃소싱활동의관리를위한절차를구비한다. k) satisfactory arrangements exist to ensure, as far as possible, that the pharmaceutical products are stored, distributed and subsequently handled so that quality is maintained throughout their shelf-life; 유효기간동안품질을유지할수있도록의약품을보관하고유통시키고, 이후에취급하도록하는만족스러운대책을최대한구비한다. l) there is a procedure for self-inspection and/or quality audit that regularly appraises the effectiveness and applicability of the PQS; PQS의효과와적용상태를주기적으로평가하는품질감사및 / 또는자체실사절차를구비한다. m) product and processes are monitored and the results taken into account in batch release, in the investigation of deviations and, with a view to taking preventive action to avoid potential deviations occurring in the future; 제품과공정을모니터하고그결과를배치출하승인, 일탈조사, 그리고미래의일탈발생방지를위한예방조치수립시에반영한다. n) arrangements are in place for the prospective evaluation and approval of planned changes and their approval prior to implementation taking into account regulatory notification and approval where required. After implementation of any change, an evaluation is undertaken to confirm that the quality objectives were achieved and that there was no unintended adverse impact on product quality; 필요한경우에는규제기관보고및승인절차를고려하여, 예정변경사항을구축하기전에미리평가하고승인하는대책을구비한다. 변경을추진한다음에는평가를실시하여, 품질목표가달성되었는지확인하고, 제품품질에의도하지않은부정적인영향이없음을확인한다. o) regular reviews of the quality of pharmaceutical products are conducted with the objective of verifying the consistency of the process and identifying where there is a need for improvement; 5

6 공정일관성확인및개선이필요한부분의파악을위해의약품품질검토를주기적으로실시한다. p) a state of control is established and maintained by developing and using effective monitoring and control systems for process performance and product quality; 공정성능과제품품질의효과적인모니터및관리시스템을개발하고활용해, 관리상태를확립하고유지한다. q) continual improvement is facilitated through the implementation of quality improvements appropriate to the current level of process and product knowledge; 현공정 / 제품지식수준에적절한품질개선을통해지속적개선을추진한다. r) there is a system for QRM; QRM 시스템을구비한다. s) deviations, suspected product defects and other problems are reported, investigated and recorded. An appropriate level of root cause analysis is applied during such investigations. The most likely root cause(s) should be identified and appropriate corrective actions and/or preventive actions (CAPAs) should be identified and taken. The effectiveness of CAPAs should be monitored. 일탈, 제품결함의심상황, 기타문제점을보고하고조사하고기록한다. 조사시에적절한수준의근본원인분석을실시한다. 가능성이가장큰근본원인을파악하고적절한시정조치 / 예방조치 (CAPA) 를파악하고추진한다. CAPA의효과를모니터한다. 1.6 There should be periodic management reviews, with the involvement of senior management, of the operation of the PQS to identify opportunities for continual improvement of products, processes and the system itself. Unless otherwise justified, such reviews should be conducted at least annually. PQS 운영실태의주기적경영검토를실시하여제품, 공정, 시스템자체의지속적개선기회를파악한다. 주기적경영검토시에고위경영자가관여한다. 달리타당성을제시할수없으면, 이와같은검토를최소한연 1회실시한다. 1.7 The PQS should be defined and documented. A quality manual or equivalent documentation should be established and should contain a description of the quality management system including management responsibilities. 6

7 PQS 를규정하고문서화하다. 품질매뉴얼또는이와동등한문서를확립하며, 경영진의책임을포함해품질경영시스템을이문서에서설명한다. 품질리스크관리 (Quality risk management) 1.8 QRM is a systematic process for the assessment, control, communication and review of risks to the quality of the medicinal product. It can be applied both proactively and retrospectively. QRM은의약품품질리스크의평가, 통제, 커뮤니케이션, 검토를위한체계적인업무절차이다. 사전적으로나사후적으로 QRM을적용할수있다. 1.9 QRM should ensure that: QRM의기본원칙은다음과같다. the evaluation of the risk to quality is based on scientific knowledge, experience with the process and ultimately links to the protection of the patient; 과학지식과공정경험을바탕으로하고궁극적으로는환자보호와연계하여품질리스크를평가한다. the level of effort, formality and documentation of the QRM process is commensurate with the level of risk. QRM 업무의활동, 형식적절차, 문서화수준은해당리스크의수준에부합해야한다. 제품품질검토 (Product quality review) 1.10 Regular, periodic or rolling quality reviews of all pharmaceutical products, including export-only products, should be conducted with the objective of verifying the consistency of the existing process and the appropriateness of current specifications for both starting materials and finished product, to highlight any trends and to identify product and process improvements. Such reviews should normally be conducted and documented annually, taking into account previous reviews, and should include at least: 기존공정의일관성과출발물질및최종제품규격의적절성을확인하고, 경향성을파악하며, 제품 / 공정개선이필요한부분을찾아낼목적으로, 수출용제품을 7

8 포함하여모든의약품의정기적, 주기적또는지속적품질검토를실시한다. 이전 검토사항을고려하여품질검토를일반적으로연간단위로실시하고그결과를 문서화하며, 최소한다음항목을포함해야한다. a) review of starting materials and packaging materials used for the product, especially those from new sources and in particular the review of supply chain traceability of active substances; 제품제조에사용된출발물질과포장자재, 특히신규공급업체로부터납품받은것. 특히활성성분의공급체인추적성. b) a review of critical in-process controls, and finished product results; 중요 IPC와최종제품결과 c) a review of all batches that failed to meet established specification(s) and their investigation; 확립된규격에부합하지못했던모든배치및이의조사내용 d) a review of all significant deviations or non-conformances, the related investigations and the effectiveness of resultant CAPAs taken; 모든중요일탈사항또는부적합사항, 관련조사내용, 그에따른 CAPA의효과 e) a review of all changes made to the processes or analytical methods; 공정또는분석방법의모든변경사항 f) a review of dossier variations submitted, granted or refused; 제출했거나승인을받았거나거절당한허가문서변경사항 g) a review of the results of the stability monitoring programme and any adverse trends; 안정성모니터프로그램결과와이상경향 h) a review of all quality-related returns, complaints and recalls and the investigations performed at the time; 모든품질관련반품, 불만, 리콜과조사내용 i) a review of adequacy of any other previous corrective actions on product processes or equipment; 앞서추진했던제품공정또는설비관련시정조치의적절성 j) post-marketing commitments for new dossiers and variations to the dossiers; 신규허가문서및허가문서변경과관련된사후관리사항 k) the qualification status of relevant equipment and utilities, e.g. heating, ventilation and air-conditioning (HVAC), water or compressed gases 8

9 and a review of the results of monitoring the output of such equipment and utilities; 관련설비와유틸리티 ( 예, HVAC, 용수, 압축가스 ) 의적격성평가및상기설비와유틸리티의산출물모니터결과 l) a review of technical agreements to ensure that they are up to date. 기술계약의최신상태유지여부 The manufacturer and, where different, marketing authorization holder, should evaluate the results of the review and an assessment should be made as to whether CAPA or any revalidation should be undertaken, under the PQS. CAPAs should be completed in a timely and effective manner, according to documented procedures. There should be procedures for the ongoing management and review of these actions, and the effectiveness of these procedures should be verified during self-inspection. Quality reviews may be grouped by product type, e.g. solid dosage forms, liquid dosage forms, or sterile products, where scientifically justified. Where the marketing authorization holder is not the manufacturer, there should be a technical agreement in place between the various parties that defines their respective responsibilities in producing the quality review. The authorized person responsible for final batch certification, together with the marketing authorization holder, should ensure that the quality review is performed in a timely manner and is accurate. 제조업체와판매허가보유자가다른경우에는각기검토결과를평가하며, PQS에의거하여 CAPA나재밸리데이션이필요한지여부를파악한다. CPAP를절차문서에따라적시에효과적인방법으로완료한다. 이들조치의지속적인관리및검토를위한절차를구비하며, 자체실사과정에서이절차의효과를확인한다. 과학적타당성이있는경우에는품질검토를제품유형별로묶어서할수도있다 ( 예, 고형제, 액제, 무균제품등 ). 판매허가보유자와제조업체가다른경우, 제품품질검토와관련하여각당사자의책임을규정한기술계약서를체결해야한다. 최종배치인증을책임지는 AP는판매허가보유자와함께, 품질검토를적시에정확히수행하도록해야한다. 9