This bar hi-lights the seven phases within the drug development process. To learn more about each phase click the "i" icon.
Select a category bar to expand the content. You will notice that the colors correspond to the associated phase. Click on one of the colored boxes under the category bar to open for more information.
By clicking on the phase color block within the category you will be able to explore the goals and definitions, criteria, sample content requirements and guidelines. You can also download a PDF of the sections for that phase.
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Discovery
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Preclinical Development
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Phase 1: Clinical Trials
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Phase 2 (2a/2b): Clinical Trials
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Phase 3: Clinical Trials
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Registration
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Launch/Post Registration
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Lead chemical series identified. Decision to enter lead optimization Identify unmet user needs, confirm that market requirements & key program assumptions merit advancement to full development.
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DELIVERY
Data sufficient to determine lead candidate. This can be developed from in vitro studies, as well as data from animal models. -
CLINICAL
None, given the early stage of development. -
REGULATORY
None, given the early stage of development. -
COMMONLY ENCOUNTERED DEVELOPMENT RISKS
None, given the early stage of development.
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Lead optimization completed. Decision to develop selected preclinical candidate(s) and enter IND-enabling studies
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DELIVERY
User needs / capabilities / acceptance and market assessments are key inputs into product attributes• Conduct user assessment of the market opportunity for the new product idea• Define use case for improving the current standard of care• Articulate the potential for delivering customer value• Assess and estimate COGS targets (tied to forecast quantity/volume)E.g. better clinical outcomes, better economic outcomes, meet / exceed patient adherence, etc. -
CLINICAL
None, given the early stage of development. -
REGULATORY
Regulatory strategy for approval (e.g., geographical filing location, technology type, etc.) guides choice of CMC product design inputs• Research prior approval packages for similar drug-device combination products• Consider pricing strategy if product will be covered under national health insurance plans• Assess intended primary mode of action (FDA) and associated regulatory pathway• Engage in early and frequent interactions with the NRA in target countries to inform regulatory path and strategy -
COMMONLY ENCOUNTERED DEVELOPMENT RISKS
CMC: Insufficient evaluation of the impact of the chemical characteristics of the Active Pharmaceutical Ingredient (e.g., stability) and its interactions with a device component/excipients/non-API components may result in manufacturing process challenges (e.g., specialized tooling requirements, inability to use commercially available equipment etc.) for design prototypes.
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Initial nonclinical pharmacological, efficacy and safety/toxicity studies and initial drug characterization completed. Initial GMP manufacture process defined. Pre-IND / IND meeting conducted. Decision to enter phase 1 trials
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DELIVERY
Preliminary COGS targets set for the intended use case guide CMC and manufacturing plan• Conduct user assessment of the market opportunity for the new product idea• Define use case for improving the current standard of care• Articulate the potential for delivering customer value• Develop high level cost-effectiveness, demand forecasts and COGS targets• Draft package requirements and Instructions For Use (IFU) based on user needs and preliminary prototype -
CLINICAL
Learnings from market assessment and ethnographic studies influence clinical protocols (e.g., understanding device/user needs in clinical settings)• Incorporate inputs from regulatory interactions into the clinical development plan• Ensure user (e.g., provider, healthcare workers etc.) training to administer combination product is adequately reflected in clinical protocols• Evaluate prior combination product development experience as part of site selection and CRO selection process• Provide estimates of number of products required to support clinical trial -
REGULATORY
For FDA demonstrate compliance with all CGMP regulations (21 CFR 4) applicable to each of the constituent parts included in the combination product• Engage regulatory experts from Drug, Device, and Combination Product sectors involved in Regulatory planning and interactions with NRA• Collaborate with NRA to determine further regulatory and clinical requirements for clinical trials and marketing in intended countries• Incorporate requirements of IND, IDE, and Combination Product regulatory requirements, as guided by the intended market NRAPlan to handle monitoring and reporting of adverse events and safety issues during clinical trials and post-authorizations. -
COMMONLY ENCOUNTERED DEVELOPMENT RISKS
CMC: Risk management plan (e.g., lack of Quality Systems Regulation) fails to diagnose patient use-related problems until later in the design process, resulting in challenging (and costly) remediation processRegulatory: Lack of a clear path to approval due to constant evolution of regulatory landscape for certain technology types (e.g., classification as a combination product) may result in product registration delays due to retroactive completion of regulatory requirements
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Phase 1 safety criteria met, feasibility of full scale manufacture and clinical readiness assessed. Decision to enter phase 2 trials
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DELIVERY
Delivery assessments (target market and demand forecast) are inputs to manufacturing scale and COGS estimates• Conduct market assessments with early prototypes, and develop target market and demand forecasts based on these assessments• Review user interface requirements in early prototypes• Draft package requirements and update Instructions For Use (IFU) based on user needs and prototype -
CLINICAL
User capabilities / acceptability verified in the clinical trial influence CMC design risk assessments• Incorporate inputs from regulatory interactions into the clinical development plan• Ensure user (e.g., provider, healthcare workers etc.) training to administer combination product is adequately reflected in clinical protocols• Evaluate prior combination product development experience as part of site selection and CRO selection process• Provide estimates of number of products required to support clinical trial -
REGULATORY
CMC Risk assessment activities are influenced by regulatory requirements for Design Reviews• Continue to engage with regulators (as needed)• Ensure regulatory agency buy-in on Design Verification and Validation Plans• Update regulatory documents and plans -
COMMONLY ENCOUNTERED DEVELOPMENT RISKS
CMC: Insufficient specifications (e.g., lack of appropriate quality infrastructure, acceptable quality levels, in-process controls or release criteria) may result in product reproducibly failing to meet CQAsRegulatory: Lack of regulatory agreement on Verification & Validation plan may necessitate additional studies impacting timeline
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Optimal dose / regimen established, and tech transfer to commercial facility planned or completed. Decision to enter phase 3 trials
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DELIVERY
Updated market assessments and demand forecast informs manufacturing capacity required, Summative Human factors Studies and Instructions for Use are inputs into development of field training materials• Review product performance with key stakeholders (e.g., procurers, healthcare workers, patients)• Draft package requirements and update Instructions For Use (IFU) based on user needs and porotype• Review IFU and test with focus groups (as appropriate) -
CLINICAL
Phase 2 clinical trials offer an opportunity to confirm user experience / preferences assessed in summative human factors study• Incorporate inputs from regulatory interactions into the clinical development plan• Ensure user (e.g., provider, healthcare workers etc.) training to administer combination product is adequately reflected in clinical protocols• Evaluate prior combination product development experience as part of site selection and CRO selection process• Provide estimates of number of products required to support -
REGULATORY
Regulatory agreement on the acceptability of Design Verification and Validation results triggers capital investments for manufacturing scale up• Engage with regulators on suitability of results from Design Verification and Validation phase• Update regulatory documents and plansPlan to handle monitoring and reporting of adverse events and safety issues during clinical trials and post-authorizations -
COMMONLY ENCOUNTERED DEVELOPMENT RISKS
CMC (Quality)• Out-of-specification verification and validation results may necessitate costly product re-design and / or process modification• Lack of definition of design space and plan development may hinder the control of quality critical process parameters and delay process understanding
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Decision to File: Clinical safety and efficacy demonstrated in phase 3 trials. Decision to file for licensure
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DELIVERY
Plan for market preparation efforts (Launch plan, FAQs, user / provider education etc.) draw on product attributes and IFU (e.g., stability, sterility, use conditions etc.)• Refine COGS targets to inform commercial scale manufacturing• Refine cost-effectiveness estimates and pricing expectations in preparation for PQ / launch• Develop communications / launch strategy regarding clinical trial outcomes, cost-effectiveness relative to existing standard of care etc.• Draft training / educational materials in preparation for launch -
CLINICAL
Adverse events and complaints outcomes during the clinical trial will inform the post-marketing surveillance and pharmacovigilance strategy• Support regulatory filing by providing necessary evidence for effectiveness of combination product (based on Phase 3 clinical trial outcome)• Confirm post-marketing commitments with National Regulatory Agencies in filing geographies -
REGULATORY
Preparation of relevant CMC package, and supporting materials for a pre-filing meeting with the regulatory agency• Update regulatory documents and plans based on outcomes of pivotal Phase 3 clinical trials• Prepare regulatory submission documents for commercial product• Conduct pre-licensure meeting(s) in country of manufacture (as applicable) -
COMMONLY ENCOUNTERED DEVELOPMENT RISKS
CMC (Quality):• Lack of evidence in reproducibility of product quality during the design transfer process poses regulatory challenges for product filing. For example, as a remediation path, the regulatory agency might require additional bridging studies between pilot and final manufacturing processes• Lack of updated COGs estimate through refreshed manufacturing strategies and clear plan identifying additional supply sites to be added to the supply network may lead to inadequate supply at affordable prices for excipients, API, disposables and packaging components
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Prequalification / Local Registration: WHO PQ achieved. Local registration (if required) pursued. Decision to launch
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DELIVERY
Execute on market preparation plan (Launch plan, FAQs, user / provider education etc.) leveraging product attributes and IFU (e.g., stability, sterility, use conditions etc.)• Execute on launch strategy• Refine health provider / end user training materials and plan• Set delivery and country implementation plans, including adequately addressing expectations for post-launch monitoring -
CLINICAL
None, clinical evaluation of the product candidate is complete. Pharmacovigilance addresses potential post-marketing commitments -
REGULATORY
None, regulatory submissions have been completed by this phase of development -
COMMONLY ENCOUNTERED DEVELOPMENT RISKS
Post-marketing commitments, Supply Chain Planning challenges• Lack of sufficient scale (e.g., PV database infrastructure, staff, Quality and PV Agreements, process and procedures etc.) to meet complaint and adverse events reporting laws and regulations in marketed geographies may hinder the continuous monitoring of product risk• Insufficient processes for commercial supply S&OP where demand is not understood and continuity of supply is not ensured, may deteriorate relations with suppliers as they are unable to manage the demand on their sites, recover overheads, etc.
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