GMP Botanical Drug Product Development

Advancing a Botanical-Derived Drug Product into Phase 2 Clinical Development

A clinical-stage sponsor, a botanical-derived product and a multi-vendor supply chain — bridging food-derived material controls with pharmaceutical GMP as the program advanced into Phase 2

  • Client: International clinical-stage pharmaceutical / biotechnology sponsor based in Victoria, Australia

  • Sector: Biotechnology / clinical-stage drug development - botanical-derived pharmaceutical product

  • Project type: Phase-appropriate PQS/DMS implementation, Phase 2 Quality and CMC strategy, analytical and stability development, manufacturing/vendor oversight, and regulatory documentation

  • Standards: FDA IND / 21 CFR  •  TGA/PIC/S GMP  •  ICH Q1/Q2/Q3/Q6/Q9/Q10  •  applicable pharmacopoeial requirements

  • Outcome: An initial PQS/DMS engagement expanded into ongoing Quality, CMC and regulatory support through the product's Phase 2 development

The Challenge

QSN was originally engaged to establish a phase-appropriate Pharmaceutical Quality System (PQS) and Document Management System (DMS) (SharePoint) as the client transitioned from research and development into clinical development. As the program advanced into Phase 2, the CMC package, manufacturing controls, analytical methods, specifications, stability program, vendor oversight and regulatory documentation all needed to mature alongside it. The product itself added a layer of complexity rarely seen with a conventional synthetic drug substance: it originated from naturally variable, food-grade botanical material sourced through an external supply chain, and needed to be brought under an appropriate pharmaceutical control strategy before incorporation into the clinical drug product.

The outsourced operating model compounded this. Starting material supply, drug substance and drug product manufacture, and specialist processing and analytical testing were spread across multiple external organisations, requiring clear responsibilities and traceability across organisational boundaries.

FDA feedback added further pressure — to clarify the regulatory designation and control of the botanical starting material and drug substance, strengthen contaminant and analytical controls, and firm up the Module 3 dossier.

QSN was engaged to provide integrated Quality and CMC support across the Sponsor, CMO, starting-material supplier and specialist laboratories, building a practical, risk-based control strategy appropriate to a Phase 2 program — without prematurely imposing commercial-stage requirements the available data couldn't yet support.

Our Approach

QSN's role evolved from establishing the Sponsor's PQS and DMS into integrated support spanning Quality, CMC, analytical development, manufacturing and regulatory documentation. Rather than treating these as independent workstreams, QSN coordinated activities across the interfaces that matter most in a lean clinical-stage organisation, where the boundaries between QA, CMC, Regulatory, Development and Analytical functions are rarely absolute — while Quality retained the independence needed for GMP decision-making.

Phase-Appropriate PQS and DMS

  • Established the Sponsor's phase-appropriate PQS and supporting DMS as the foundation for clinical development and GMP oversight

  • Developed procedures, forms, registers and tools across document control, data integrity/GDocP, training, vendor management, quality risk management, change control, deviations, CAPA, audits, Quality Agreements, validation and batch management

  • Designed the system around a lean clinical-stage Sponsor, allowing the PQS to mature with the program rather than requiring wholesale replacement at each clinical phase

CMC and Regulatory Strategy

  • Reviewed the evolving Phase 2 CMC package and translated regulatory feedback into practical actions across the Sponsor, CMO, suppliers and external laboratories

  • Clarified the regulatory positioning of starting material, drug substance and drug product, and aligned manufacturing and testing information with the relevant CTD Module 3 sections

  • Developed phase-appropriate justifications for attributes where development data weren't yet sufficient to establish final commercial acceptance criteria

  • Supported responses to regulatory CMC questions and implementation of resulting commitments across specifications, testing, stability and manufacturing controls

Botanical Drug Substance Control Strategy

  • Developed controls for introducing the botanical starting material into a pharmaceutical manufacturing supply chain — specifications, supplier controls, incoming testing and traceability

  • Defined the relationship between the starting material and the resulting GMP drug substance, and developed corresponding manufacturing and control narratives

  • Developed Phase 2 drug substance specifications covering identity, active content, physical characteristics, moisture, microbiological quality and other relevant attributes

  • Established phase-appropriate approaches for naturally variable material characteristics, distinguishing attributes needing defined acceptance criteria from those requiring continued monitoring

Drug Product Manufacturing and Control

  • Supported development and review of the Phase 2 drug product manufacturing and control strategy across key manufacturing and packaging operations

  • Reviewed manufacturing protocols, batch documentation, critical in-process controls and process parameters, together with sampling frequencies and escalation criteria for adverse trends or manufacturing interruptions

  • Developed and reviewed Phase 2 drug product specifications, test methods and acceptance criteria, and assessed dosage-unit uniformity and sampling strategies against applicable pharmacopoeial requirements

  • Developed visual inspection and risk-based sampling approaches for drug product and packaging defects, and supported bracketing assessments across clinical presentations

Analytical Development and Stability

  • Developed a phase-appropriate analytical validation strategy covering compendial, non-compendial and biological methods for drug substance and drug product control

  • Developed forced-degradation strategies to challenge analytical methods and confirm their ability to detect meaningful changes in drug substance and formulated product

  • Developed and reviewed Phase 2 stability protocols, including long-term, intermediate and accelerated conditions and risk-based selection of tests and timepoints

  • Developed packaging bracketing justifications to reduce unnecessary stability testing while maintaining appropriate representation of clinical presentations

Botanical Contamination and Microbiological Risk Management

  • Developed an end-to-end contaminant-control strategy spanning botanical starting material, drug substance and finished drug product

  • Evaluated appropriate analytical approaches and supported qualification of specialist external laboratories and matrix-specific method suitability

  • Reviewed microbiological specifications and specified-organism testing against applicable pharmacopoeial requirements, balancing assurance with the practical limits of small clinical batch sizes

  • Developed risk-based strategies for elemental impurities, residual solvents and nitrosamines, using supplier/process knowledge and analytical data to determine where testing was warranted versus a documented risk assessment

GMP Supply Chain and Quality Oversight

  • Qualified and risk-categorised CMOs, analytical laboratories and specialist providers using a phase-appropriate vendor-management approach

  • Reviewed vendor questionnaires, GMP licences, ISO/IEC 17025 accreditation and product-specific method suitability

  • Developed Quality Agreements and responsibility allocations across the Sponsor, CMO, starting-material supplier and outsourced service providers

  • Worked directly with CMOs, suppliers and laboratories to resolve technical and Quality questions, and provided input into clinical labelling, shipment and temperature-monitoring arrangements

Batch Release, Investigation and Quality Risk Management

  • Supported Sponsor oversight of clinical batch manufacture and release, including risk assessment of manufacturing timelines against completion of analytical testing

  • Applied formal Quality Risk Management principles to manufacturing, analytical and supply-chain issues rather than automatically imposing commercial-stage controls

  • Supported investigation of atypical manufacturing observations, including structured Is/Is Not and fishbone/root-cause frameworks

  • Provided ongoing Quality, CMC and regulatory review as data accumulated, allowing the control strategy to evolve with increasing product and process knowledge

The Outcome

  • An initial PQS/DMS engagement grew into ongoing Quality, CMC and regulatory support across the client's Phase 2 program

  • A phase-appropriate Quality framework providing GMP governance without over-building for a lean clinical-stage organisation

  • An integrated CMC strategy connecting botanical starting-material risk, drug substance and drug product controls, analytical methods, stability, vendor oversight and regulatory documentation

  • A strengthened CMC package incorporating FDA feedback, with clearer definition of material controls and manufacturing/testing responsibilities

  • Phase-appropriate specifications, controls and analytical strategies designed to provide assurance for Phase 2 while continuing to evolve as development data accumulate

  • Strengthened oversight of an outsourced manufacturing and analytical network through defined responsibilities and risk-based vendor qualification

Developing a complex or novel drug product?

Whether you're navigating a non-standard starting material, an outsourced manufacturing network, or a CMC package that needs to mature alongside your clinical program, QSN can help you build a control strategy that fits where you are today.

Check out our relevant services - Site Licensing and Accreditation, Regulatory Compliance and Auditing or QMS.

Or check out our retainer options for Audit4Life and Compliance4Life.