Overall development
When Triskel partners with a new client early in the development phase, our first step is usually to create a written strategic development plan that integrates US and EU development milestones.
The scope and detail of the strategic development plan is dictated by the client; it is a living document that evolves along with the project.
It usually includes a competitive review of the therapeutic area, including a strategic analysis of risks and choices in the full clinical development programme leading to registration, along with plans for product manufacturing from pilot product to industrial scale-up, plans for non-clinical and clinical developments, Gantt chart and cost estimates from CMOs and CROs. It is a road map for the development and the international registration of the product.
Process development
Strategy for Upstream and Downstream process optimisation
Process Flow diagram; Bottleneck identification; Medium and chromato optimisation; Continuous or Batch process rationale; Wave bag implementation; Cell separation approaches; Buffer consumption; Cleaning issues; Pre-formulation at bulk level; Fill and Finish anticipation; Freeze-drying elimination; Quality attributes
Process and analytical evolution as a function of clinical phase.
Viral clearance strategy
Risk analysis; Animal free components; Viral clearance studies; Validation approach.
Clinical trial production strategy
Internal production or Outsourcing; Final Dosage anticipation; Associated devices; Quality progress as a function of clinical trial.
New biotech facility establishment
cGMP assessment of facility
Flow reviews (raw material, product, equipment, clean/dirty segregation, people, viral segregation); waste flow and treatment; Air locks, pressure cascade; Air breaks; Risk Analysis (HACCP)
Engineering review
Concept and philosophy assessment; Piping & Instrumentation (P&I) Diagram review; Contract review; Global planning review, HVAC requirements
Dimensioning
Sizing of manufacturing equipment, Water for Injection production, Steam production
Documentation review
Review of FAT and SAT protocols; IQ/OQ protocols; Validation Matrix
Equipment qualification
Acceptance criteria review
Process validation
PQ philosophy; protocol review; Cleaning validation
System validation
PQ WFI, PQ gas, Air treatment; Risk assessment review
Manufacturing
Technology Transfer Assistance
Protocol and acceptance criteria review; Equipment suitability; Batch record review; Report review
Technology licensing assistance
Value analysis; Intellectual property assessment; Negotiation
Continuous improvement implementation
Target definition; Performance assessment; Project definition and follow-up
Capital usage optimisation
Switch to multi-products operations; Automation versus manpower; Scale –up and/or bottleneck elimination
Analytical assays : development and validation
Triskel's experts can define analytical assays, review protocols, data and validation reports for assays required for:
- characterisation, in-process control and batch-release during manufacturing development or
- non-clinical and clinical studies.
For biologics, this includes assays to determine the immunogenicity of both the medicinal product and its Host-Cell Proteins (HCPs).
CTD preparation
Triskel’s staff has the adequate knowledge and expertise to fully prepare in-house all scientific documents which constitute the Modules 2.3 and 3 of MAA, BLA or NDA submissions.
Non-Clinical
Our areas of expertise in pre-clinical development include:
Strategic advice and elaboration of efficient non-clinical development plans. The product class, proposed indication, mode of action and species-specificity can greatly affect the extent of the required development programme. As there is no pre-defined non-clinical programme for biological molecules, Triskel can assist with the preparation of abridged development plans when there are no relevant species available for a given product. The non-clinical plan includes detailed outlines of the most effective and efficient programme for initiation of a Phase I study and ultimately for submission of a MAA/BLA.
Study follow-up from protocol to report. Triskel's staff has the ability to design various study protocols for pharmacodynamic, pharmacokinetic, safety pharmacology and toxicology studies. We can perform day-to-day follow-up of the study and data analysis, and to ensure that high quality, regulatory compliant reports are issued.
Regulatory activities include the preparation of non-clinical parts of various regulatory documents: Scientific Advice request, Investigator Brochure, IMPD, CTD Modules 2.4, 2.6 and 4 of MAA, BLA and NDA.
Additional consulting activities include document review, due diligence and gap analysis of existing non-clinical development programmes and data packages.
Clinical
Triskel offers a full-range of integrated clinical development services for medicinal therapies. Our substantive areas of expertise include:
- Design and implementation of clinical development programmes
- Validation and harmonisation of prospective clinical development programmes with relevant regulatory authorities
- Review and gap analysis of existing clinical development programmes and data packages
- Protocol design of Phase I, II and III; IB, IMPD, ICF, CRFs
- Monitoring of development progress through steering committees with the client to guide and monitor CMOs/CROs or other development partners
- Analysis of clinical data (including PK and PD) and writing or review of ICH clinical study report
- Preparation, submission and maintenance of clinical trial applications/INDs
- Preparation of clinical parts of various regulatory documents: Scientific Advice, Investigator Brochure, IMPD, CTD Modules 2.5, 2.7 and 5 of MAA, BLA and NDA
- Support for EU legal representation
Regulatory
Triskel has both a full understanding of the regulatory requirements of the EMA for developing and registering medicinal products in Europe, and an excellent understanding of the differences between the requirements of the EU, US and Japanese regulatory authorities.
Our areas of expertise include:
Strategic Support:
- Evaluation of therapeutic areas and potential efficacy of novel medicinal products prior to proof-of-concept
- Strategic planning to obtain best regulatory outcome
- Design of global regulatory strategy for marketing approval
Regulatory Support throughout the product development process:
- SME status and representation (Triskel holds SME status in Europe)
- Briefing packages for Scientific Advice/Protocol Assistance or FDA meetings
- Participation in Scientific Advice / Protocol Assistance or FDA meetings at all stages of development
- Paediatric Investigation Plans (PIPs)
- Orphan Medicinal Product Designations (EU) / Orphan Drug Designation (US)
- Clinical Trial Applications (CTAs/IND) and related documents (IMPD, IB, …)
- Preparation of all CTD modules and MAA submission
- Risk Management Plans (RMPs) and Environmental Risk Assessments (ERAs)
- eCTD preparation
- Continued regulatory compliance through line extensions, variations, new indications and post-authorisation commitments
Marketing support
Triskel provides clients with marketing support along two lines:
- Post-authorisation commitments by designing Phase IV study protocols, registries, long-term safety studies and interacting with EU Rapporteurs.
- Translating the science (included in the MAA/BLA/NDA) into marketing documents by preparing publications of key registration studies and presenting data at international conferences/meetings.
