} padding: 0; -ms-flex-direction:column; width: 32%; With respect to identification of Established Conditions in the manufacturing process, the Step 2 draft contained a recommendation that Established Conditions include inputs (e.g., process parameters, material attributes) and outputs (that may include in-process controls) necessary to assure product quality. For manufacturing process parameters, the draft introduced a new key process parameters (KPPs) category, in addition to the familiar critical process parameters (CPPs) category as defined in ICH Q8. Japan has taken a proactive approach to gaining experience with PACMP, with MHLW/PMDA starting a pilot program for PACMP in April 2018 prior to ICH Q12 reaching Step 4.10 color: #fff; } } The ICH Q12 Guideline on Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management and its Annexes reached Step 4 of the ICH Process at the ICH meeting in Singapore on 21 November 2019.. ICH Q12 provides an opportunity to reduce registered detail requiring regulatory action while providing regulators the necessary transparency to review a products process as illustrated in Figure 3. margin: 0;
ICH Q12 Pharmaceutical Product Lifecycle Management - Part II If you want to ask a question or request information from EMA, please Send a question to the European Medicines Agency. Positive improvements have been observed in the acceptance and implementation of international standards by various regulatory agencies in Latin America. .ispeak-filters .form-item { TECHNICAL AND REGULATORY CONSIDERATIONS FOR PHARMACEUTICAL PRODUCT LIFECYCLE MANAGEMENT . max-width: 100%; Established condition and PLCM documents will need to be aligned with the Japanese Application Form. Seven key areas were identified as topics of interest: ISPE webinar participants were most interested in hearing about experiences with the FDA established conditions Pilot Program (Figure 4). The goal is to harmonize post-approval changes, to facilitate scientific innovation, and help to mitigate drug shortages.
PDF Step 4 document -to be implemented 6 February 2020 color: #fff; .section-about .region--featured-bottom .form-submit { background-color: #0a67a2; border: solid 2px #ececec; As individual companies have begun to implement established conditions and ICH Q12 concepts, it has become clear that there is some divergence in approaches and associated terminology that have been communicated to health authorities. Following critical feedback received during the draft review, the final version of ICH Q12 clarified that the Product Lifecycle Management document should be placed in 3.2.R or for some regions in Module 1 (e.g., Japan). background: linear-gradient(to right, rgb(88, 31, 109) 2%, rgb(128, 55, 155) 100%); display:none; Pfizer is currently exploring opportunities to implement ICH Q12 tools in global registration applications. endstream
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Proposed reporting categories for established conditions were based on (a) potential risk to product quality, (b) experience in changing the proposed established condition, and (c) capability of PQS in managing changes and an effective continued process verification (CPV) to provide ongoing assurance the process remains in a state of control. However, in the final version, the summary of the product control strategy was removed to simplify the Product Lifecycle Management document and make it applicable across all ICH regions. Established conditions and corresponding reporting categories were therefore assessed for the relevant drug product sections of the dossier. Changes to the equipment using the same design and operating principle reduced from NL to NR. } Post-approval Change Management Protocol is a regulatory tool providing prospective transparency and expectations for regulatory reporting categories for specific postapproval changes.
Established Conditions: Implementation Post- ICH Q12 - BioProcess The guidance reflects key lessons learned from the 2019 FDA Pilot on Established Conditions,12 /* hide topics on page */ ICH guideline Q12 on technical and regulatory considerations for pharmaceutical product lifecycle management 1. .flex.flex-3-col { The International Council for Harmonisation (ICH) guidance for industry Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management and its Annexes (ICH Q12, May 2021) provide a framework to facilitate the management of postapproval chemistry, manufacturing, and controls (CMC) changes in a more predictable and efficient manner. color: #fff; 68 ICH Q12 defines established conditions (ECs) as legally binding information considered 69 necessary to assure product quality. The performance-based approach was set apart to highlight its primary focus on the Established Conditions related to process outputs. 0
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PDF Note on EU implementation of ICH Q12 - European Medicines Agency For example, for drug substance synthesis, process parameters impacting an impurity observed at intermediate stages but not in the final drug substance can be considered as KPPs. margin: 0 auto; /* fix flex col 3 */ Funded by the European Commission from 2019, the Smart Pharmaceutical Manufacturing Project (SPuMoNI)1 border-color: #08acd5; .homepage-feature-banners .field-items .field-item:nth-child(2) .banner-text::before {
ICH Q12 Implementation from an Industry Perspective - A3P } Thus, the terms implicit and explicit were eliminated in the final version, with the added clarification that some Established Conditions with reporting categories may already be defined in the regional legal frameworks, and a market authorization holder (MAH) may use one or more approaches detailed in the guideline to propose their own Established Conditions and reporting categories. Furthermore, regardless of the approach used, manufacturing process descriptions in Module 3 are expected to remain suitably detailed and to include both Established Conditions and supportive information. endstream
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<. Lack of alignment for data expectations regarding necessary information and level of detail in the regulatory dossier is also a challenge and will need to be addressed. margin-left:60px; The science- and risk-based approach utilized by GSK was based on the failure modes effects analysis (FMEA) technical risk assessment evaluating criticality of the parameters and controls. padding: 0; Pfizers science- and risk-based approach was based on rigorous risk assessments, overall control strategy, process understanding, product knowledge, enhanced analytical method development, and a robust PQS.14, The small molecule active ingredient synthesis included robust starting material controls and multiple in-process controls to ensure drug substance quality. This is a highly discussed topic in context of the planned new ICH Q12 Guideline "Lifecycle Management". 1.
/* fix flex col 3 */ color: white; .flex.flex-3-col { /* view for ispeak top filter */ During the Step 2 draft review and consultations, it became evident that the three-tiered approach to classify the criticality of process parameters has been adopted throughout the industry. . An example of a Product Lifecycle Management document, with a few important clarifications based on public comments, was moved into Annex IF. ,3 Following the pilot, the PACMP was introduced into the regulation as the Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices and will come into effect in 2021. /* style Affiliate/Chapter Officer/Board Add or Remove Sponsor Request Form fields */ This transformational guideline has a wide scope of applicability across pharmaceutical drug substances and products (both chemical and biological), drug-device combination products that meet the definition of a pharmaceutical or biological product, as well as both new molecular entities and authorized products.1. #webform-submission-affiliate-chapter-add-or-remove-add-form div.tabledrag-toggle-weight-wrapper,.field-suffix { background: #00aad4; } .homepage-feature-banners .field-items .field-item:nth-child(2) .field-name-field-banner-heading, border-top: 1px solid #d2d2d2; } background: #00aad4; It also clarifies the relationship between ICH Q12 PACMPs and FDA comparability protocols, explains how to translate ICH Q12 postapproval change reporting categories to the existing FDA supplement categories, and illustrates the use of a PLCM document with specific examples. .tabs.tabs-strip .tabs-title a { ICH Q12 includes regulatory tools and enablers with associated guiding principles that should enhance industrys ability to manage postapproval changes and increase transparency between industry and regulatory authorities, supporting innovation and continual improvement. He is a motivated leader that effectively Connie Langer is a chemical engineer and director at Pfizer Global Product Development in Groton, CT. She has 24 years of increasing responsibility in the ICH Q12: A Transformational Product Life-Cycle Management Guideline, https://database.ich.org/sites/default/files/Q12_Guideline_Step4_2019_1119.pdf, Appendix comparing the Step 2 draft and the final guideline, https://database.ich.org/sites/default/files/Q8_R2_Guideline.pdf, https://database.ich.org/sites/default/files/Q9_Guideline.pdf, https://database.ich.org/sites/default/files/Q10_Guideline.pdf, https://database.ich.org/sites/default/files/Q11_Guideline.pdf, https://cdn.ymaws.com/www.casss.org/resource/resmgr/wcbp_speaker_slides/2017_WCBP_NasrMoheb.pdf, https://pink.pharmaintelligence.informa.com/PS140943/EMA-Fee-Revisions-Expected-To-Resolve-ECs-Objections-To-ICH-Q12-Guideline, https://www.ema.europa.eu/en/documents/comments/overview-comments-received-ich-guideline-q12-technical-regulatory-considerations-pharmaceutical_en.pdf, https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-manufacture-finished-dosage-form-revision-1_en.pdf, https://database.ich.org/sites/default/files/Q12_Annexes_Step4_2019_1119.pdf, Thermal Buffering in Temperature Mapping & Monitoring, The Digital Validation Handbook Your Guide to Faster, More Accurate Validation, Introducing EU Annex 1: Understanding the Newest Regulatory Requirements. }
PDF Lifecycle management workshop - European Medicines Agency ICH Q12 defines established conditions (ECs) as those elements in an application considered necessary to assure product quality, such as critical manufacturing process parameters for the drug substance or product. } The implementation of ICH Q12 is intended to provide a framework to facilitate the management of postapproval CMC changes in a predictable and expeditious manner, demonstrate how enhanced product knowledge and process understanding improve regulatory flexibility for postapproval changes, and reinforce the importance of an effective change management system through the product life cycle. EMA/CHMP/ICH/78332/2020 .
PDF Q12 Step 5 Technical and regulatory considerations for pharmaceutical Implementation of ICH's Q12 Guideline will promote innovation and continual improvement in the biopharmaceutical and pharmaceutical sectors and strengthen quality assurance and reliable supply of product, including proactive planning of supply chain management. .tabs.tabs-strip { guidance provides a framework to facilitate the management of CMC changes in a more predictable and efficient manner, building on the science- and risk-based approaches outlined in the prior ICH Quality GuidelinesICH Q8(R2), Q9, Q10, and Q11. 5630 Fishers Lane, Rm 1061 .tabs.tabs-strip .tabs-title a[aria-selected='true'] { FDA perspectives highlighted during the ISPE ICH Q12 webinar were in line with issues facing industry related to ICH Q12 implementation. -ms-flex-direction:column; /* contact form */ FDA 5 20 ICH Q12FDA NDABLAANDAEstablished Conditions, EC EC ICH Q12 display: none; #views-exposed-form-on-demand-webinars-block-1 { margin-top: unset; .tabs.tabs-strip .tabs-title a { ICH Q8Q11 provided the framework for science- and risk-based approaches; however, technical and regulatory gaps prevented the realization of postapproval flexibility. padding-right: .5rem; border-bottom: 1px solid #d2d2d2;
ICH Q12: Implementation Considerations for FDA-Regulated Products PDF Implementation Considerations for Food and Drug Administration-Regulated The examples of Post-approval Change Management Protocols for chemical and biological products were moved into Annexes ID and IE, respectively, but otherwise remained largely unchanged. Minimal and enhanced approaches were grouped together as parameter-based approaches because they are primarily focused on the Established Conditions related to process inputs. } Send a question to the European Medicines Agency. border: solid 1px #fff; is critical to achieve the full potential of the ICH Q12 concepts. /* hide topics on page */ .field-node--field-magissue-pdf { max-width: 100%; Finally, the final version of the guideline emphasized that submission of the Product Lifecycle Management document is critical when a market authorization holder wishes to use any of the ICH Q12 risk-based approaches to define and propose their own Established Conditions with associated reporting categories. This guideline addresses the commercial phase of the product lifecycle (as described in ICH Q10); and it both complements and adds to the flexible regulatory approaches to post-approval CMC changes described in ICH Q8(R2) and Q10 Annex 1. Proposed reporting categories for established conditions were based on process and product knowledge, as well as Amgens established PQS utilizing a risk-based approach. Further assessments for slightly severe were based on product and process knowledge (i.e., process characterization data). /* style Affiliate/Chapter Officer/Board submission Update form fields */ Toward that goal, Health Canada planned to launch stakeholder consultations in 2021 to gather feedback on the final elements of the implementation of the Q12 guidance in Canada. } width: 100%; #webform-submission-officer-submission-form-add-form div.tabledrag-toggle-weight-wrapper,.field-suffix { /* fix file attachment spacing */ } .tabs.tabs-strip .tabs-title a:hover { The analytical methods to assess the drug substance and drug product included six different procedures for which established conditions were based on the method principle, method-specific performance criteria (i.e., validation criteria per ICH Q2,15 background: #f2f2f3; max-width: 20rem; According to the ICH website, the current ICH Q12 IWG work plan foresees the completion of training program preparation later this year, followed by the initiation of training activities in late 2021.4. @media (max-width: 860px) { .homepage-feature-banners .field-items .field-item:hover .banner-text:before { Most of the companies surveyed have relied on the enhanced approach as defined in ICH Q12.
Implementation of ICH Q12 Guideline - ISPE This leads to relevant information of established conditions and non-established conditions to be included in the Module 3 CTD sections S.2.2 and P.3.3 when the enhanced ICH Q12 approach is implemented. and take 10 or more years. 844 0 obj
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/* default color for event banner links when there is no secondary color selected */ } was associated with the importance of robust criticality assessments and effective communication of results and data to regulators in support of the proposed established conditions. But early indications are that it will amass information clutter of its own. .flex.flex-3-col .flex-item { The PAS submission was submitted as part of the US FDA Office of Policy for Pharmaceutical Qualitys established conditions Pilot Program.12 display: inline-block; With the implementation of ICH Q12, Post-approval Change Management Protocol can help ensure robust change management globally by providing a consistent approach to regulatory reporting categories across ICH regions. Search for FDA Guidance Documents, Recalls, Market Withdrawals and Safety Alerts, Search General and Cross-Cutting Topics Guidance Documents, ICH Q12: Implementation Considerations for FDA-Regulated Products, Chemistry, Manufacturing, and Controls (CMC).
ICH Q12 Technical and regulatory considerations for pharmaceutical section II of the ICH Q12 guidance, may differ across regions depending on regional legislation; /* fix file name width */ The ICH Q121 } display: block; /* homepage lead banner adjustments */ Note on EU implementation of ICH Q12 (guideline on technical and regulatory considerations for pharmaceutical product lifecycle management) This explanatory note is published in parallel to the ICH Q12 Step 5 guideline (EMA/CHMP/ICH/804273/2017) and annexes (EMA/CHMP/ICH/831751/2017) which were adopted by CHMP in .
PDF ICH Q12: Post Approval Change Management Protocol (PACMP) - PQRI Regarding PACMPs, there is currently no similar concept in Japan and therefore, a change in the national regulations will be required to implement it. Members of the pharmaceutical industry want the US Food and Drug Administration (FDA) to align reporting categories with the International Council for Harmonization (ICH) Q12 guideline on postapproval changes while others seek clarity on how manufacturers can use postapproval change management protocols (PACMPs) to support a lower reporting category. display: none; Product life-cycle management (PLCM) document: Central repository for established conditions, reporting category for making changes to approved established conditions, PACMPs (when proposed), and any post-approval CMC commitments. padding: 0; To achieve that goal, the first step was to develop a more granular risk assessment and filtering tool that would permit moving beyond the current binary critical process parameter (CPP)/noncritical process parameter (nCPP) paradigm and provide a clear framework for determination of established conditions and associated risk-based reporting categories for all process parameters using the enhanced approach. Introduction 1.1. margin-top: unset; The ATP can support two potential routes per ICH Q12 [9, 18]: (1) a post-approval change management or (2) product life cycle management. Lack of global convergence and alignment on implementation approaches, as well as legislative constraints, will give rise to divergent implementation strategies among health authorities. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.
Analytical Quality by Design, Life Cycle Management, and - Springer This increased flexibility, expected to be . However, the long-term expectation is that use of ICH Q12 will decrease the need for postapproval filings and agency interactions. .featured-tabs .hp-view-row .node--type-training-courses .icon { background: linear-gradient(to right, rgb(88, 31, 109) 2%, rgb(128, 55, 155) 100%); margin-bottom: 15px; At Step 4 of the Process the final draft is recommended for adoption to the regulatory bodies of ICH regions. Finally, each risk-based category of process parameters was mapped to the appropriate postapproval reporting category (Figure 2). } which means that one must always default to the requirements laid down in the current EU Variations Regulation and associated EU Variations Guidelines. padding: 1.5rem; Eli Zavialov, Ph.D., is a Senior Director, CMC Regulatory Affairs at GlaxoSmithKline. The European Medicines Agency (EMA) was one of the first global health authorities to adopt ICH Q12 in January 2020 and to issue its implementation guidance in March 2020.8 #webform-submission-affiliate-chapter-add-or-remove-add-form div.tabledrag-toggle-weight-wrapper,.field-suffix { Appendix comparing the Step 2 draft and the final guidelineis available as a download. margin: 0; This is expected to facilitate an improved operational and regulatory flexibility upon its implementation. providing detailed recommendations on how to define, submit, and maintain the proposed established conditions. background-color: #e5f7fb; A comparison of the reporting categories in the PLCM versus current FDA guidance16 display:none; color: #fff; Implementation of ICH Q12, particularly from a regulator perspective, was the next most common topic. display:none; The global pandemic has demonstrated that now, more than ever, we need to work toward a global solution and prioritize the harmonization of technical requirements. margin-bottom: 15px; Industry participants had the opportunity to ask questions and provide live feedback to the presenters during the ISPE webinar. } Recent engagements between industry leads and health authorities have highlighted key issues faced by regulators and sponsors in implementing ICH Q12, and defined a potential path to a more harmonized approach to postapproval change management in the future. The enhanced approach was based on an understanding of the interaction between process inputs and quality attributes of the molecule. to propose established conditions and corresponding reporting categories in a PLCM document that included established conditions across the full scope of Module 3. display:none; border-left: 1px solid #d2d2d2; background: #f2f2f3; } /* style Affiliate/Chapter Officer or Headshot Submission Update form fields */ According to ICH Q12, established conditions "are legally binding information considered necessary to assure product quality," and they reflect a company's commitment to manufacture and control the drug product and ensure appropriate, consistent, and sustainable quality, safety, and efficacy for the patient. Overall, these themes highlight areas of opportunity for future improvements as implementation of ICH Q12 progresses.
Why 'Established Conditions' CMC Approach Could Generate More width:100%; [CDATA[/* >