User Requirement Brief and Concept Designs

February 16th, 2018 by

User Requirement Brief and Concept Designs

Our clients want to manufacture life-changing products and harness the very latest in science breakthroughs for the benefit of mankind. To do this they must have access to the right facilities. When the build or buy decision has been made in favour of a capital project expansion, eXmoor helps to plan and realise the critical early phases:

  • URB (User Requirement Brief)
  • Site selection
  • Concept Design
  • Feasibility Study
  • 3D visualisations
  • Contractor Selection.

 URB (User Requirement Brief)

The URB is the foundation document for the whole capital project, a document our clients come back to time and again. We bring together the key stakeholders to challenge and understand from them what the facility is required to do. This includes the overall business objectives as well as the high level business need (basis of the business case) and the technical need (number, size, variability of products/processes to deliver the business case).

We then develop this into a technical solution which describes the number and type of rooms required to deliver the technical need for manufacturing, R&D, GMP and non GMP support, plant and utilities and admin. The URB is signed off by all key stakeholders and is used at multiple points in the project to ensure that, from design to realisation, your facility delivers.

Site Selection

We quickly gather/develop a facility/site requirements brief (FRB) which is sent to landlords and real estate agents as a description of the type of building/site required.

The FRB includes: project background, building/site purpose, occupancy requirements, geographical search locations, process requirements, accommodation schedule, travel/logistics requirements, building form, physical space requirements and size including expansion, building section and ceiling void requirements, building utilities, floor loading, regulatory requirements, commercial requirements and constraint. This demonstrates serious intent to potential real estate agents or landlords, quickly allows us to rule in and rule out options which in turn supports successful negotiations.

Concept Design

The concept design is the design solution to the URB and is the first time you see your facility on paper with process designs and architectural plans/sections/elevations. With our knowledge, experience and structured process, we believe we do this better than anyone else. Working together we make sure we have found the best design option to deliver your URB.

We deliver a robust and appropriate technical package alongside an associated capital cost estimate,  execution strategy and plan in order to achieve: internal sanction, initial discussions with the Competent Authority and an invitation to bid for detailed design and build  contractors. We have worked on greenfield, retrofit, NHS, charity-funded, privately-funded and first-of-its-kind facilities at all scales and using a range of biomanufacturing technologies.

Feasibility Studies

If you’re not ready to commit to a concept design but want a quick understanding of what your facility might consist of, look like and cost, let us carry out a feasibility study for you. This can take as little as two weeks and result in professional and visual outputs suitable to present at board level.

3D Visualisations

Process architecture layouts and 3D visualisations help board members to visualise what their investment will look like and aid users to envisage their operations. We design in 3D using REVIT and have modelled all commonly used process equipment to make the resulting 3D model photo-real.

Example 3D visualisation:

Click here for more information on computer generation of the CRMI Hong Kong stem cell facility.

Contractor Selection

In the UK we have experience of working with most of the detailed design and build companies and have a robust assessment process to select the most appropriate organisation for the work and then importantly identify and mitigate any shortfalls.

QP (Qualified Person)

February 16th, 2018 by

 QP (Qualified Person)

Our GMP compliance team includes a number of QPs experienced in the manufacture of a wide range of novel biotherapeutic molecules and Advanced Therapy Medicinal Products.

Our QPs are contracted by many of our clients to perform the legal responsibilities of a QP as defined by EU legislation.

Uniquely, our consultant QPs combine experience across both operational and capital projects making them suited to evaluating technologies and manufacturing processes, assisting with process and analytical development and ensuring GMP compliance from the early initiation phases of a concept design all the way through to the final operational and regulatory licensing of a manufacturing facility.

Through this engagement, our QPs have built a strong relationship with the UK’s MHRA and have experience with other competent authorities within the EU and USA. Their combined experience provides an unrivalled knowledge and expertise of working within the challenging and exciting world of ATMPs.

Process Development Consultancy

February 16th, 2018 by

Process Development

Our advanced therapy clients face the challenge of successfully developing and manufacturing medicinal products from patient or donor cells. Such products need to show good safety, consistent quality and clinical efficacy while meeting market demands with a competitive selling price.

We can help you in the assessment of your current manufacturing process to identify possible improvements and define a process development strategy appropriate to your stage of development. We also offer the opportunity to perform process development work in our state of the art facility in Bristol. We facilitate the definition of the development program and comparability analysis with prioritisation based on risk and cost analysis of the process, from early clinical to commercialisation.

As the manufacturing process needs to be robust, reproducible and suitable to meet commercial market demands, this requires:

  • Knowledge of the product and process including a target product profile and knowledge of the process’ design space
  • A documented process development program with proof that process changes do not impact product safety, quality or effectiveness
  • Cost of Goods (CoG) analysis of current and adapted process and business impact
  • A manufacturing strategy that fits with the need to supply different geographic locations and assure worldwide supply.

In close collaboration with our clients, we can perform an FMEA or gap analysis, to identify and value the problems and the solutions. This enables our clients to define the process development options to mitigate risks.

When working towards later stage clinical development and commercial manufacture, we can perform cause and effect analyses to determine process variability and identify criticality in process parameters and quality attributes. Such analysis helps to define the product specifications as well as a process characterisation profile which facilitates trending of the manufacturing process.  This approach will enable you to effectively improve your production process to have a consistent and (cost) effective manufacture of your product.

Manufacturing Strategy

February 16th, 2018 by

Manufacturing Strategy

Defining your manufacturing strategy can be a complex task with many variables impacting the outcome. Our team of experienced consultants can help you with various aspects of your strategy planning, including:

Build or Buy Analysis

A critical decision in the development of a manufacturing strategy is whether to ͞build or buy manufacturing capacity. This may need to be assessed and revisited at each stage of clinical development and for different products.

We have the experience and independence to assist with this decision and will ensure the criteria for ultimate selection fits with your organisation’s overall business objectives. There are many factors to consider in making the choice, not all related to cost, although availability of capital is often a key driver early in a company’s lifecycle. Other factors include protection of the process particularly if no process or product IP is involved, extent of the overall product portfolio, risk of clinical failure, required timing of manufacture, availability of in-house resources and manufacturing readiness of the process.

We have experience over multiple projects of assessing, selecting and managing contract manufacturing capacity in the EU and US in different configurations to suit different needs including academic GMP Contract Manufacturing Organisations (CMOs), commercial CMOs and hotel-type CMOs. This gives us up to date generic pricing including both the CMO and the client elements required to achieve successful technology transfer and ongoing successful production. It also gives us knowledge of the market competence for different kinds of cell and gene therapies.

CMO Search and Selection

We have significant experience of helping clients in the selection of CMOs. We take a structured approach, comparing CMOs using a ranking system based on clients’ needs. In this system, we rank and compare the responses to our clients’ key requirements, questions and quotations resulting in an objective comparison of potential CMOs. If needed, we can perform part of the CMO selection process so that clients’ can remain anonymous until later stages. After selection, we can assist or advise in contractual and quality agreement negotiations and technology transfer to the CMO

Technology Transfer Management

We provide clients with the technical guidance and project management for transfer of technology to the CMO. Technology transfer typically consists of the following phases:

  • Preparation of a complete technology transfer package and advice on the content
  • Kick-off meeting using a proven methodology to run through specifications, materials, process, QC and equipment requirements per unit operation followed by theInformation exchange phase
  • Demonstration of the process at the client’s premises and observation of the process at the CMO’s premises
  • Documentation preparation,material ordering and arrangement of starting materials, method transfer
  • Qualification or validation of QC assays. Qualification of operators, process and aseptic procedures
  • Clinical readiness.

During each phase we help our clients define clear deliverables and identify and provide solutions to any problems, so the best outcome is achieved.

Cost of Goods (CoG) Analysis

We can use our CoG analysis to forecast the cost of manufacturing your ATMP.  This can include all the costs from donation to administration or it may focus on specific elements within the manufacturing process. We use a cash flow basis which includes all the major costs (facility, staffing, materials and production volumes) and how they might vary over time.  In this way we can predict the impact of proposed changes to manufacturing steps and production volumes.  A particular strength is our ability to gather costs from across our multi-disciplinary team; for example capital and staffing costs from the project and process engineers, direct costs from the cell therapy consultants and the PD lab, and regulatory costs and risks from our compliance experts.

We explore potential cost changes using sensitivity analysis and this can be used to guide process development and manufacturing strategy decisions as well as providing improved cost certainty for the business plan.  The sensitivity analysis can also be used to model the impact of some risks and their potential mitigation. Periodically, the CoG analysis can be used to reconfirm projected costs as the investment proceeds.

Due Diligence

eXmoor can strengthen your diligence team with expertise in CMC, Quality and process engineering to help you get a better insight in the value connected to the opportunity as well as the risks and costs. We can help writing the diligence report and assist in further development of the opportunity.

We can add value by assessing the GMP compliance of a production process and plant, the scalability of a production process towards the projected market demand, the current capacity of the production facility, providing a gap analysis of the diligence package provided and estimate the CoG for production, testing and distribution. This will help you to better understand the opportunity as well as the work to be done and the associated costs.

We can provide you with a high level process development plan based on the assessment of the process, an overview of the changes required to the production plant to meet capacity demands and/or GMP guidelines, an estimate of costs and timelines associated with the proposed plans, a projection of the CoG of the product in the adapted process, a strategy to close the gaps observed, with a priority list, time needed and associated costs.

Bioprocess Engineering

December 30th, 2017 by

Bioprocess Engineering

Taking a novel process or product from laboratory research to GMP manufacturing at scale is a complex task. Application of process engineering fundamentals to any process is necessary to meet the often, strict criteria for safety, capital/operating costs, capacity, performance and sustainability.

Our team of highly experienced engineers can lead the process and utilities design on behalf of our clients and offer continued support throughout the project lifecycle. We have extensive experience in specification, design, commissioning and qualification gained in the pharma, biotech, cell and gene therapy industries.

We are currently supporting our clients in:

Capacity Scheduling and Optimisation

Project feasibility, facility and equipment strategy is informed by the definition of processes. We have developed methods for high-level capacity analysis to estimate the number of cleanroom suites that are required and detailed scheduling to take a deeper dive into equipment and people utilisation to identify and resolve bottlenecks. We aim to do this in a way that can be understood by all project stakeholders.

Single-use Technology and Stainless-steel System Implementation

Our engineers have extensive experience in the implementation of reusable and disposable technologies and the retrofit of existing facilities that can take advantage of the ever-evolving single-use technology sector. Cost benefit analysis, operational, utilities requirements, biocompatibility and supply chain experience are all leveraged to help our clients decide on which strategy is most suited for their manufacturing facility.

Equipment Specification

We support the definition, selection, procurement and commissioning of the whole range of process equipment from lab instruments including upstream and downstream unit operations, EMS (Environmental Monitoring Systems), clean utilities generation and distribution and isolator technologies.

Process Safety, Risk Evaluation and Mitigation

Meaningful risk assessment requires the input of Subject Matter Experts. Our process engineers have a background in process and operational safety, process economics and experience of the likelihood of failures due to equipment and/or human factors. A pragmatic approach with the GMP compliance team ensures that risks are identified early on and thus mitigations are inherent in the subsequent design.

Clean Utilities, CIP and SIP Specification and Qualification

Where process scale or compatibility requires the need to select in-house clean utilities generation and re-usable equipment, then our combined experience over hundreds of projects in traditional pharma and biotech can be drawn upon. Our engineers give courses on pharmaceutical waters and keep up to date with ISPE guidance as well as pharmacopeia requirements via our QP colleagues.

Effluent Treatment Systems

With specialist experience gained from designing and realising high containment facilities and processing involving genetically modified organisms, potentially infectious patient-derived materials and animal health products, we can provide containment audit, specialist vendor selection and segregation advice for air, solid and liquid treatment systems.

CPrep – Cell Preparation

December 30th, 2017 by

CPrep – Cell Preparation

From cryopreserved cell/gene therapy product to filled syringe ready for administration:

  • Thaws, washes to remove DMSO, concentrate, syringe fill
  • Aseptic
  • Automated
  • Gentle
  • R&D version for method optimisation
  • GMP version with Batch Manufacturing Record
  • Benchtop GMP ready Processor and separate R&D or GMP Consumable
  • Current version accepts Aseptic Technology AT-Closed Via® 2ml vials and delivers into BD 3ml Luer-lok™ Tip syringes.

Typical results:

Regulatory Considerations

  • The new EU Advanced Therapy Medicinal Product (ATMP) guidelines, Eudralex Vol 4, Part IV, Good Manufacturing Practice for Advanced Therapy Medicinal Products states: “reconstitution activities can be performed at the administration site outside a GMP environment” subject to a number of caveats.
  • The Processor is GMP equipment and forms part of the Cell Therapy Manufacturers (CTM) licensed process
  • The Disposable is a GMP consumable and is manufactured, assembled, wrapped, labelled and sterilised by a reputable single use supplier.

Potential Applications

  • At the Point of Care (PoC), allowing expensive, short shelf life cell therapies to be transported and stored frozen and then thawed when everything is ready for administration. This also reduces the risks and costs of current manual methods
  • Initiation of cell culture from a cell bank in a GMP facility with a standard repeatable process
  • Thawing of cell samples for QC with a standard repeatable process.

GMP Compliance

December 30th, 2017 by

GMP Compliance

All our QPs (Qualified Person) provide GMP Compliance support both internally and externally across all of eXmoor’s client portfolio and are experienced in being able to interpret regulatory guidance requirements including the EU, US, PIC/s, and apply this to an individual client’s needs. Key to this is the development of a coherent suite of GMP compliance and qualification documentation aimed at ensuring and demonstrating regulatory compliance from concept through qualification to successful regulatory licencing.

The URB (User Requirement Brief) is the starting point on this journey. Every facility concept design ends with a full quality review against both detailed GMP standards and the URB, ensuring that the proposed design meets both user and regulatory expectations.  This is normally followed by a presentation of the concept design to the Competent Authority. We help our clients define the qualification and validation strategy for the whole project. The compliance team has experience in developing a detailed Validation Master Plan (VMP) ensuring a solid and comprehensive foundation is laid in accordance with regulatory expectations.

User Requirement Specifications (URS) are written for Direct Impact Systems in collaboration with our team of process engineers. We can ensure essential elements of quality are built in at this stage. The URS is used as a point of reference throughout the qualification stages and through into full operational use.

Our compliance team can help you oversee the ongoing qualification process from design qualification through installation qualification, operational qualification and performance qualification for equipment, facilities, utilities or systems.

We can also support the review of existing and development of new Pharmaceutical Quality Systems (PQS) either in association with a new capital project or as a standalone project. We can perform audits of medicinal product manufacturers, contract test houses and material suppliers to support the qualification of suppliers for our clients.

GMP auditing is a key part of any manufacturers PQS and provides assurance that the suppliers are managed and controlled. Our experience of working with all the relevant regulatory Agencies enables us to provide an audit that is focused on client needs and takes into account the Regulators’ concerns.

Commercialisation Lab

December 29th, 2017 by

Commercialisation Lab

Process and Analytical Development

eXmoor offers a range of process and analytical development services targeted at improving the commercialisation of cell and gene therapy products.

We offer a structured technology transfer process to identify areas for process development and apply risk-based and design-of-experiment (DoE) tools to help prioritise and structure experimental work.

Services range from establishment of research grade cell banks, adherent and suspension-based cell culture, cell selection (enrichment/depletion using magnetic or elutriation techniques), media screening and selection, bioreactor process development, harvest optimisation, all forms of bench scale downstream processing including batch chromatography, cross-flow, dead-end filtration and cryopreservation.

We have extensive analytical capabilities to qualify and run a wide range of assays including qPCR, HPLC, metabolite analysis, automated cell counting and cell cycle analysis, various fluorescent and luminescent plate-based assays and finally flow cytometry and cell imaging through partnership with the University of the West of England (UWE).

The link between our Consultancy and the Lab ensures that in all our projects we keep focussed on the end game of a commercially viable, manufacturable process.

Technology Development

  • Struggling to find GMP equipment to manufacture your unique atmp (advanced therapy medicinal product)?
  • Want to develop IP to protect your novel manufacturing process?
  • Uncertain how to modify your R&D process to comply with GMP?

As a team of engineers and scientists, we understand ATMPs and GMP.  With our experience in the field, our network of specialist providers and our UK based laboratory and workshop we can help with:

  • Defining your requirements (strategically and tactically, technically and commercially)
  • 3D designing and printing potential solutions
  • Prototyping
  • Testing with your cells
  • Organising your GMP supply chain
  • GMP audits and compliance
  • Project management.

Maybe you need to: develop a new process, trial new equipment or analytics, combine unit operations, close couple to avoid losses, automate, close, scale out or scale up.