Advanceutics Inc.
Advancing Pharmaceutical Development, Manufacturing, QbD, Regulatory CMC
Advancing Pharmaceutical Development, Manufacturing, QbD, Regulatory CMC
Overall Scope:
- Small molecule drug development.
- Key aspects of CMC: Drug Substance, Drug Product, Analytical, and Packaging, Quality by Design, Regulatory CMC.
Spectrum:
- CMC Development, Manufacturing, and Packaging to support.
- Early Stage: Pre Phase 1 to Initial IND and Phase 1 studies.
- Mid Stage: Phase 2 and Phase 3.
- Late Stage: Manufacturing Registration / ICH stability batches to commercial scale-up.
- Registration: NDA / MAA submission, Process Validation, PAI preperation.
- Post Approval: Manufacturing launch, post approval changes, Life Cycle Management (LCM) Initiatives.
- Bridging supply chain and other major CMC changes.
Scientific Management Consulting:
- Executive Management Team Support.
- Transitioning from Phase 2 to Phase 3.
- Advising in developing departments for Pharmaceutical Development, Manufacturing Operations, Analytical, QC, and Quality.
- Developing CMC Team Leader and CMC Teams and Sub Teams.
- Review and advise on CMC strategies and plans for:
- Initial FIH studies and Quality Sections in IND or IMPD.
- Transitioning from Phase 2 to Phase 3.
- Manufacturing Pivotal Phase 3 batches and / or ICH stability batches.
- NDA / MAA submission.
- Scale-up and Process Validation.
- Post Approval Changes.
- Life Cycle Management (LCM) Initiatives.
Pharmaceutical Development:
- Discovery Pharmaceutics: Assist lead candidate for Pharmaceutical developability assessment; Review and / or develop plans, including execution, for preclinical formulation support; Help optimize discovery-development interface; Assist / advise on planning for phase dependent pharmaceutical development plans.
- Preformulation Development: Design and manage critical preformulation studies such salt screening, form screening, pH solubility studies, solubility in solvents, drug-excipient compatibility studies, hygroscopicity studies, etc.
- Formulation Development: Design, manage and review formulation development and optimization studies for solid orals (Tablets and Capsules: ODT, IR, MR, etc) and parenteral, formulations for poorly soluble drugs, short term stability and compatibility studies, in use stability studies, temperature excursion and freeze thaw studies, transportation and shipping studies.
- Process Development: Design and manage phase appropriate process development and scale-up studies, identify CPPS, develop and rationalize IPCs.
- Specification Review: Develop and rationalize phase appropriate drug product specifications and review compliance to USP and ICH Q6A.
- Analytical Methods and Method Validation: Design, development and review of early stage analytical methods for assiting early stage dosage form development. Design, develop and review of analytical method qualification / validation protocols and reports as per ICH / USFDA requirements. Design, development and review of dissolution medium selection for the solid oral dosage forms. Troubleshooting, review and identification of degradation products in dosage forms. Troubleshooting and review of analytical issues and reports.
Manufacturing clinical, ICH stability batches, commercial scale-up and process validation batches:
- Review and improve strategies and plans to manufacture pivotal phase 3 efficacy studies.
- Review and improve strategies and plans to manufacture ICH stability batches including scale of drug product, number of drug product lots, number of drug substance lots, volume of stability data at submission, expected shelf life, etc.
- Help transition form Phase 2 to Phase 3 and IH stability batches or ICH stability to "proposed commercial" including gaps analysis and checklists.
- Review and improve strategies and plans for commercial scale-up studies.
- Review and improve strategies and plans for process validation studies, ensure compliance to new guidance, strategize when to execute PV trials, etc, implemewnt SPC and process capability analysis to demonstrate validation.
- Review broad spectrum documentation needed such as MBRs, Product Specifications, Test Methods and Test Method Validations, Manufacturing Protocols.
- Represent client companies as Person in Plant (PIP) during manufacturing campaigns.
Pre Approval Inspections and General Inspections:
- Prepare for successful PAI; identify and prepare for key questions, prepare subject matter experts (SMEs), prepare project overview to facilitate PAI inspection, etc.
Biopharmaceutics:
- Assist in design of BE studies, especially those that are highly variable drugs (HVD), to support CMC aspects.
- Assist in developing strategy for bridging major CMC changes that need in human vivo BE studies.
- Assist in developing and executing strategies to register higher strengths and seek bio waivers.
- Assist in drafting investigative formulations sub sections and dissolution summaries to support HPK-B sections.
- Developing strategies to design PK studies for LCM initiatives.
Regulatory CMC:
- Assist in developing strategy and drafting drug product sections in IND, IND amendments, and IMPD per CTD requirements.
- Assist in developing strategy and drafting background package along with questions for EOP2 CMC meeting.
- Assist in review of product specifications, stability plans, and shelf life determinations.
- Assist in developing strategy and drafting drug product sections in NDA and MAA per CTD requirements (Module 3, Module 2 QOS, Regional Information and support HPK-B sections).
- Assist in developing strategy and drafting responses to questions from FDA review cycle and EMA questions (Day 120 & Day 180).
- Assist in developing and executing strategies to plan post approval changes and associated submissions (PAS or CBE or CBE 30 or AR as well as Variations in EU), including bridging major changes with stability documentation.
Integrating QbD elements and Statistical Analysis in Development Cycle:
- Develop and integrating key elements of QbD such as Quality Target Product Profile (QTPP), Design of Experiments, Process Capability, Control Strategy, etc in development cycle.
- Statistical Process Control (SPC) and Process Capability (Cpk) at late stage development, commercial scale-up and process validation to demonstrate that the manufacturing process is in control and capable of meeting pr approved in-process controls and product specifications. Helps in quantifying the quality of manufacturing process.
- Developing and managing cost effective statistical screening and optimization DOE trials to relate independent and dependent variables, identify key independent variables, and optimize formulation and / or process development.
- Facilitate Quality Risk Assessment (QRA) using widely accepted tools and help develop comprehensive control strategy to assure the quality of product and process for routine commercial manufacturing process.
CMC Facilitation In/out Licensing:
- Out-licensing, develop slide deck to reflect CMC status; develop detailed folders and binders that can be kept in e-rooms for remote due diligence; participate in face to face meetings; prepare responses to questions.
- In-licensing: Conduct remote or in person due diligence on available information, seek answers for key questions, prepare and present due diligence summaries with recommendations.
Technical Reports and Tech Transfer Packages:
- Author comprehensive interim development reports and manufacturing campaign reports.
- Author integrated Product Development Reports to support regulatory submission and / or Pre Approval Inspections.
- Develop Tech Transfer Packages to address product transfer form one site to another or one scale to another, or to business partners.
CDMO vendor selection and Management:
- Review and advise on overall strategies for vendor selection including strategy and timing for 2nd supplier.
- Drafting Request to Proposal (RFP) for development and / or commercial projects.
- Analysis of quotes received from vendor and make recommendations.
- Assist in negotiating development agreements, quality agreements, technical agreements, and Commercial supply agreements.
Workshops and Training Courses:
- Developed training material, series of 4-6 lectures on key topics such as Preformulation, Unit Operations in Solid Dosage Forms, Optimization Techniques, Process Development.
- Can program and develop tailored workshops in Pharmaceutical Development, Manufacturing, Quality, Regulatory CMC, etc that can be 0.5 day, 1 day, or 2 days.