Q11 Development of APIs Training Introduction - TRIPHASE Pharma ...

ICH Q11 – Development &manufacture of drugsubstancesKeith McDonaldGroup ManagerMedicines & Healthcare products Regulatory Agency (UK)©2011 ICH International Conference on Harmonisation of Technical Requirementsfor Registration of Pharmaceuticals for Human Use© 2011 ICH 1

ICH Q11 – Development & Manufacture ofDrug SubstancesDisclaimer:• The information within this presentation isbased on the presenter's expertise andexperience, and represents the views of thepresenter for the purposes of a trainingworkshop.© 2011 ICH 2

ICH Q11 – Development & Manufacture ofDrug SubstancesOutline• Background to ICH Q11• Overview of Q11 at Step 3• Next steps of ICH process© 2011 ICH 3

ICH Q11 – Development & Manufacture ofDrug SubstancesWhat is the purpose of ICH Q11 ?A new tripartite high level technical guidance harmonising thescientific and technical principles relevant to design,development and manufacture of drug substances as part ofa total control strategy designed to ensure product qualityand consistency.o Harmonisationo Facilitate innovative development over the productlifecycle in order to improve product and processunderstandingo No new regulatory requirementso Utility for regulators & industry© 2011 ICH 4

ICH Q11 – Development & Manufacture ofDrug SubstancesWhy is a new ICH guideline for activesubstances required ?• ICH Q Round-table – Washington 2007o Region specific data packages and data presentationo Differences in data requirement between regions presentadministrative burden to industryo Inefficient use of industry & regulatory authority resources• Application of concepts of the new quality paradigm (ICH Q8,Q9 & Q10) to drug substance• Facilitate innovation in approaches to development andcontrol of drug substance manufacturing processes, enabledby application of on-, at- and in- line analytical technologiescoupled with robust risk management strategies© 2011 ICH 5

ICH Q11 – Development & Manufacture ofDrug SubstancesWhat is the scope of ICH Q11 ?• In scope: 3.2.S.2.2 – 2.6 of CTDo New Chemical Entities – as defined in ICH Q6Ao Biotechnological/Biological Products – as defined in ICH Q6B• Not in scope:o Clinical trial materialso Regional post approval change requirements© 2011 ICH 6

ICH Q11 – Development & Manufacture ofDrug SubstancesDoes Q11 impact other ICH guidance ?• Addresses principles & concepts of Q8, Q9 & Q10 inrelation to drug substance• Specific guidance applicable to substances ofbiotechnology provided in Q5 series• Additional guidance to ICH Q series but does notcreate new regulatory requirements.© 2011 ICH 7

ICH Q11 – Development & Manufacture ofDrug SubstancesWhat topics are covered in ICH Q11 ?• Introduction & scope• Manufacturing Process Development• Description of the Manufacturing Process & Process Controls• Selection of Starting Materials and Source Materials• Control Strategy• Process Validation/Evaluation• Where to file information in CTD• Lifecycle Management• Illustrative Examples• Glossary© 2011 ICH 8

ICH Q11 – Development & Manufacture ofDrug SubstancesManufacturing Process Development• Identifying CQA for drug substance in relation to drug producttarget product profile• Defining a suitable manufacturing process• Defining a robust control strategy to ensure process performanceand drug substance quality• Systematic evaluation, understanding and refining of themanufacturing processoUse of risk assessment tools, prior knowledge and experimentationto identify the material attributes and process parameters that canhave an effect on drug substance CQAoDetermining the functional relationships that link material attributesand process parameters to drug substance CQA© 2011 ICH 9

ICH Q11 – Development & Manufacture ofDrug SubstancesManufacturing Process Development• What data/information to submit ?o Summary overviewo Level of detail – pivotal v non-pivotal studieso Relevance of development studies to the commercialprocesso Effect of scaleo History of batches produced to date & linked to significantdevelopments in the manufacturing processo An applicant may adopt either a traditional or enhancedapproach to development of the process or a combinationof both© 2011 ICH 10

ICH Q11 – Development & Manufacture ofDrug SubstancesDescription of Manufacturing Process• Flow chart and sequential procedural narrativesimilar to M4Q• Any proposed design space described here.Example 3.© 2011 ICH 11

ICH Q11 – Development & Manufacture ofDrug SubstancesStarting / Source Materials• Different perspectives for NCE as compared to substances ofbiotechnology• For biotech substances, advice concerning cell banks is givenin Q5A, B & D• For NCE –o Considerations for selection of a given molecule in the syntheticsequence as the regulatory starting materialo Reassurance that the defined process and control strategy,operating within GMP will consistently provide drug substanceof the required qualityo Example provided to illustrate application of considerations© 2011 ICH 12

ICH Q11 – Development & Manufacture ofDrug SubstancesStarting Materials• What information to provide in the regulatorysubmission ?o NCE – synthetico NCE – semi-synthetico Biotech substance© 2011 ICH 13

ICH Q11 – Development & Manufacture ofDrug SubstancesControl Strategy ‐ Considerations• Controls on material attributes (including raw materials, startingmaterials, intermediates, reagents, primary packaging materials forthe drug substance, etc.);• Controls implicit in the design of the manufacturing process (e.g.,sequence of purification steps (Biotechnological/BiologicalProducts), or order of addition of reagents (Chemical Products));• In-process controls (including in-process tests and processparameters);• Controls on drug substance (e.g., release testing).© 2011 ICH 14

ICH Q11 – Development & Manufacture ofDrug SubstancesControl strategy• Control strategy applies irrespective of developmentapproach adopted (traditional or enhanced)• Point of application of control may differ dependingon the nature of the attribute requiring control andprocess knowledge as a result of developmentstudieso Sterility assuranceo RTRT© 2011 ICH 15

ICH Q11 – Development & Manufacture ofDrug SubstancesControl strategy –what information tosubmit• Description of Manufacturing Process & Process Controls(3.2.S.2.2)• Control of Materials (3.2.S.2.3)• Control of Critical Steps & Intermediates (3.2.S.2.4)• Container Closure System (3.2.S.6)• Control of Drug Substance (3.2.S.4)Example of presentation of an overview of this information forNCE & biotech substances is provided© 2011 ICH 16

ICH Q11 – Development & Manufacture ofDrug SubstancesProcess validation/Evaluation• High level overview of approaches to PV• Includes optionality for ‘traditional 3 batch’ approach andcontinuous process verification approach described in Q8.• All manufacturing processes to be validated prior to productcommercialisation• Differences in data requirements at time of MAsubmission/approval depending on molecularcomplexity/characterisation (NCE v biotech) and depending onnature of process ( e.g aseptic processing)© 2011 ICH 17

ICH Q11 – Development & Manufacture ofDrug SubstancesProcess validation / Evaluation• Biotech specific aspects:o PV studies include studies at commercial scale in addition toparticular studies (e.g virus removal) conducted at small scale.o When platform manufacturing experience is utilised, thesuitability of the control strategy should be demonstrated andthe drug substance manufacturing process should beappropriately validated at the time of the marketingauthorisation application. Full scale validation studies shouldinclude data derived from the final manufacturing process andsite(s) used to produce the product to be commercialised.© 2011 ICH 18

ICH Q11 – Development & Manufacture ofDrug SubstancesWhere to submit using CTD• Quality risk management & process development• Critical Quality Attributes• Design Space• Control Strategy© 2011 ICH 19

ICH Q11 – Development & Manufacture ofDrug SubstancesLifecycle Management• Continual improvement of the drug substance manufacturingprocess is facilitated via quality systems elements & managementresponsibilities described in Q10• Periodic re-evaluation of control strategy including any design spacewithin the product quality review• Knowledge management across the product lifecycle – incl supplychain• Science and risk based approach to evaluation of impact of processchanges• Specific guidance for changes to biotech processes – link to Q5E• Proposals for management of specific future changes can beincluded in the original pre-approval dossier – Example 2• Regional requirements for post approval changes apply© 2011 ICH 20

ICH Q11 – Development & Manufacture ofDrug SubstancesExamples• Linking Material Attributes & Process Parameters toDrug Substance CQAs – Chemical Entity• Use of Quality Risk Management to SupportLifecycle Management of Process Parameters forBiotech Unit Operation• Presentation of a Design Space for BiotechnologicalProduct Unit Operation• Selecting a Starting Material in an NCE Synthesis• Presentation of the Elements of a Control Strategyfor NCE and biotech substances© 2011 ICH 21

ICH Q11 – Development & Manufacture ofDrug SubstancesGlossary• Platform Manufacturingo The approach of developing a production strategy for anew drug starting from manufacturing processes similar tothose used by the same applicant to manufacture otherdrugs of the same type (e.g as in production ofmonoclonal antibodies using predefined host cell, cellculture and purification process, for which there existsconsiderable experience)© 2011 ICH 22

ICH Q11 – Development & Manufacture ofDrug SubstancesNext steps• Public Consultation Periodso USAo Japano EU• Timetable to Step 4• Implementationo See IWG Q&Ao No new regulatory requirementso Optionality in approaches to manufacturing processdevelopment© 2011 ICH 23

Thank You!©2011 ICH International Conference on Harmonisation of Technical Requirementsfor Registration of Pharmaceuticals for Human Use© 2011 ICH 24