NANO PILOT · 2017-12-01 · Compliance with GMP NANO PILOT BROCHURE. Three different processes will be es-tablished for the production of three different nanopharmaceuticals. State

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A Pilot Plant for the Production of Polymer based Nanopharmaceuticals in Compliance with GMP

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PRESENTATION

AN INDUSTRIAL NEED TO COVER

OBJECTIVES OF THE PROJECT

3.1 Objectives based on industrial needs

3.2 Scientifi c objectives

WORK PLAN

PROJECT PARTNERS

CIDETEC

National University of Ireland, Galway

University of Santiago de Compostela

Sylentis

Micronit

Chemtrix

Mejoran

Spinverse

ADERA-Ultra Traces Analyses Aquitaine

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A Pilot Plant for the Production of Polymer based Nanopharmaceuticals in Compliance with GMP

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NANOPILOTBROCHURE

Three different processes will be es-tablished for the production of three different nanopharmaceuticals.

State of the art production processes including micro reactors and highly advanced characterization techniques will ensure the quality of the nano-drugs.

Existing laboratories owned by the coordinator, will be adapted and cer-

tifi ed within this project to enable the operability of the pilot plant.

4 research groups, 3 SMEs and 2 industries have joined forces in NanoPilot. Nine partners that have a signifi cant track record in knowledge creation and innovation in their respective domains to guarantee the success of the proposed project.

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A P I L O T P L A N T F O R T H E P R O D U C T I O N O F P O LY M E R B A S E D N A N O P H A R M A C E U T I C A L S I N C O M P L I A N C E W I T H G M P

A Pilot Plant for the Production of Polymer-based Nanopharmaceuticals in Compliance with GMP.NanoPilot has received funding from the European Union Framework Programme for Research and Innovation Horizon 2020. The objective of this four-year long project is toset-up a pilot plant operating under Good Manufacturing Practice (GMP) for the produc-tion of polymer-based nanopharmaceuticals. The pilot plant will accelerate the develop-ment of nanomedine, currently in its infancy within the pharmaceutical sector.

In this brochure you will fi nd a detailed description of each partner, its role within the project and contact details.

... TO

C

LINICAL TRIALS

GMP

PROD

UCTION & BATCH RELEASE

Q&AQUALITY SYSTEM

TRAINED PERSONNEL

FACILITIES &EQUIPMENTS

MAN

AGEM

ENT & BUSSINES PLAN

FROM LAB...

GMP Compliance

1. NANOPILOT

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The European Technology Platform for Nanomedicine has recorded more than 700 SMEs/Industries working in the fi eld of Nanomedicine, a number that doubles when including research institutions. Experts in the fi eld have recognized the high potential of innovation, however in most cases, clinical validation is still required.

The production of innovative nanopharmaceuticals in quantity and quality (GMP) required for them to enter clinical trials remains a challenge. Production cannot easily be implemented in existing manufacturing plants, specialized and optimized for the production of conventional drugs.

In addition, small companiesusually do not have the resources to up-scale and implement GMP manufacturing of their potential nanopharmaceutical. This can limit the capacity of these organizations for advancing their research, and as a consequence, slow-down the

development of innovative nanopharmaceuticals to treat different diseases.

In this context, it is urgently needed to provide those SMEs with the tools that can help them with the validation of their technologies.

2. An industrial need to cover

BasicResearch

PrototypeDesign orDiscovery

PreclinicalDevelopment

Clinical Development

EMA Approval and Launch Preparation

GCP/ICH-EGLP/ICH-S

GMP/ICH-QNANOPILOT

ApprovalMarketApplication

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NanoPilot will set-up a fl exible and adaptable pilot plant operating under GMP for the production of small batches of polymer-based nanopharmaceuticals, which exhibit signifi cant potential in the fi eld of drug-delivery particularly for the design of second-generation nanopharmaceuticals.

3.1.1 Production of small GMP batches for clinical trials

3.1.2 Flexibility and Adaptability

The pilot plant will provide the small quantities of products that technology developers will require for full pre-clinical and fi rst clinical validation.

A design which will look for a compromise between: specialization, fl exibility and economic viability.

The big pharma will require technology which is robust and translatable, that has completed full toxicological preclinical phase and had been validated in fi rst clinical trials. That technology must fulfi ll strict regulatory require-ments.

3.1.3 Focused on Regulatorycompliance

3.Objectives of the project

3.1 OBJECTIVES BASED ON INDUSTRIAL NEEDS

HCCanada

FDAEE.UU

SFDAChina

MHWJapan

TGAAustralia

EMAEurope

EachcountryAfrica


3.1.1 Production of small GMP batches for clinical trials

3.1 OBJECTIVES BASED ON INDUSTRIAL NEEDS

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3.2.1 Production of three different nanopharmaceuticals

3.2.2 Integration of microfl uidics in the plant

3.2.3 Implementation of highly advanced characterization techniques

Three different processes will be established for the production of three different nanopharmaceuticals, selected on the basis of their TRL and positive commercial evaluation.

Asymmetrical Flow Field Flow Fractionation (A4F) is increasingly used as a mature separation method to size sort and characterize nanoparticles in native conditions, and offers the possibility to analyze a wide variety of macro-molecules and particles ranging from the nanometer to the micrometer range with high resolution.

Benefi ts of this technology include:

A short interfering RNA (siRNA) nanoformulation for the topical treatment of ocular pain asso-ciated with dry eye syndrome (DES).

A HIV nanovaccine for intra-nasal administration.

Hyaluronan based spheres. A treatment for interstitial cystitis/painful bladder syndrome (IC/PBS).

3.2 SCIENTIFIC OBJECTIVES

INCREASED PROCESS CONTROL

INCREASED PROCESS SAFETY

SMALL FOOTPRINT

RAPID and ROBUST

ECONOMICAL

PARABOLIC FLOW PROFILE

ACCUMULATION WALL

EXT. FIELD DIFUSION

FLOW FLOW

Principle of particle size fractionation in A4F

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The work plan has been divided in 8 Work Packages, including Research, Technology and Development, Management, Piloting, and Dissemination - Exploitation and Trai-ning activities.

WP1

Definition of nanopharma-ceuticals and design of their GMP production pro-cess

WP5

Validation of manufacturing processes and production of nanopharmaceuticals in compliance with GMP

WP3

Training system implementation

WP7

Development of a business and dissemination plan

WP2

Adaptation of the facilities to a nanopharmaceuti-cals production pilot plant working in compliance with GMP

WP6

Shipping and batch release

WP4

Quality system implementation

WP8

Management

4.Work Plan

WP7 & WP8MANAGEMENT & BUSSINES PLAN

WP4

WP2 W

P3

FACILITIES ADAPTATION

QUALITYSYSTEM

TRAINING

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CLINICAL TRIALS

WP5

PRODUCTION

WP6

BATCH RELEAS

E

WP1

DEFINITION OF REQUIR

EMEN

TS

FROM LAB...

GMPCertified


5.Project PartnersThe NanoPilot consortium consists of 9 partners from 6 Member States. Scientists with a sound research background CIDETEC, National University of Ireland, Galway, University of Santiago de Compostela and ADERA-UT2A, all of them with a good track on translational research, will collaborate with 3 SMEs: Micronit, Mejoran and Spinverse, and 2 industrial partners: Sylentis and Chemtrix.

Each partner will have a distinctive role in the project and will ensure that the project results will be exploited in an effi cient manner. NanoPilot targets a specifi c research objec-tive using a sharply focused approach while at the same time it includes a coherent set of activities dealing with multiple issues related and providing state-of-the-art responses to the main challenges identifi ed in the call.

The collective expertise, commitment and prior research track record of these organizations, which were specifi cally selected for their diverse experience and essential compe-tencies as well as for their complementarity, guarantee the project success.

Spain: CIDETEC / University of Santiago de Compostela / Sylentis / Mejoran France: ADERA-UT2A

Ireland: National University of Ireland, Galway The Netherlands: Chemtrix Germany: Micronit Finland: Spinverse

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5.1 CIDETEC

CIDETEC is a Technology Centre belonging to the IK4 Research Alliance, specialises in generating and transferring knowledge and technology in the areas of materials, surfaces and energy.

The Biomaterials Unit in CIDETEC will be in charge of NanoPilot. The group is specialist in the synthesis of biomaterials focused in the synthesis of polymer nanoparticles, intelligent colloids, hydrogels and bioactive surfaces with application in the fields of biomedicine, biotechnology and food among others.

500m2 labs, including 350m2 of classified laboratories prepared for GMP production, are dedicated at CIDETEC to the development of various bio-materials.

www.cidetec.es

CIDETEC will be in charge of the Pi-lot Plant and will scale up the nanosys-tems. It is the project coordinator. CIDETEC carries out translational research in the field of nanomedicine.

Main tasks:

Project coordination.

Pilot Plant setting-up.

Scaling-up and GMP manufacturing.

MAIN ROLE WITHIN THE PROJECT

CONTACTDr. Iraida Loinaz (project coordinator)BDM of CIDETEC Nanomedicinee-mail: [email protected]

Dr. Ana B. Benito Researcher - Biomaterials Unit in CIDETECe-mail: [email protected]


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5.2 NATIONAL UNIVERSITY OF IRELAND, GALWAY

The Centre for Research in Medical Devices (CÚRAM) is a national research centre which is based on an academic-industry-clinician partnership model that is focused on translating biomaterial-based solutions to the clinic to address unmet clinical needs. Collaborative projects with the medical device industry focus on developing and leveraging CÚRAM’S unique biomaterial platform technologies, novel product and process development taking the form of providing design input to support and enhance industries existing portfolio through product enhancements, adding value to the in-dustries existing technology, creating disruptive technologies and trouble-shooting biomaterial-based issues in medical devices.

www.nuigalway.ie

CONTACT

Prof Abhay Pandit

Director, Centre for Research in Medical Devices (CÚRAM),


e-mail: [email protected]


NUI Galway will validate its technology during the project by transferring hyaluro-nan particles production process into the pilot plant. Final GMP batch produced will be used to advance their research. CÚRAM carries out translational research in the field of biomaterials.Main tasks:

Provision of technology and composition of a nanopharmaceutical prototype.

Definition of requirements/specifications of the nanopharmaceuticals.

Identification of provisional production parameters and in process controls needed.

MAIN ROLES WITHIN THE PROJECT

USC will validate its technology during the project by transferring a HIV nanovaccine production process into the pilot plant. USC will use the final GMP batch produced to advance their research.

Main tasks:

Provision of technology and composition of a nanopharmaceutical prototype.

Define requirements/specifications for nanopharmaceutical scale-up.

Develop strategy scale-up of nanopharmaceutical.

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NanoBioPharmaceuticals Research Lab (University of Santiago de Compostela) is headed by Professor María José Alonso and considered a world leader in the field of Drug Delivery.

We are particularly involved in the translation of ideas from the university through novel pharmaceutical technology. Our scientific research involves the use of nanotechnologies for the design of innovative nanomedicines. Our overall goal is to design and develop novel nanostructured materials intended to transport drugs across biological barriers and deliver them to the target tissue. Within this broad area, we are specialized in the asso-ciation of delicate molecules, including peptides, siRNA and antigens to these nanocarriers.

www.usc.es

5.3 UNIVERSITY OF SANTIAGO DE COMPOSTELA

CONTACT

Prof Abhay Pandit

Director, Centre for Research in Medical Devices (CÚRAM),



CONTACTProf. María José AlonsoHEAD of NanoBioPharmaceuticals Research Labe-mail: [email protected]

Dr. Desirée Teijeiro Osorio Scientific Project Manager at NanoBioPharmaceuticals Research Labe-mail: [email protected]


Sylentis is a Pharmaceutical company, belonging to the Zeltia group, focused on the development of compounds based on the mechanism of RNA inter-ference (gene silencing).

Sylentis was founded in 2006 and during this time has been able to take two compounds into clinical trials, making Sylentis the first European company to reach clinical development of a RNAi compound.

Sylentis brings together innovation, talent and science with the aim of developing the best possible treatment for people suffering from eye conditions.

www.sylentis.com


SYL will validate its technology during the project by transferring a RNAi-based nano-formulation production process into the pi-lot plant. SYL will use the final GMP batch produced to advance their research. Partner SYL will contribute to the startup of the Pilot Plant and support the consortium in obtaining regulatory approval of the Pilot Plant.

Main tasks:

Provision of technology and compostion of a RNAi-based nanoformulation

Contribute to achieve regulatory approval of the plant.

Define requirements/specifications of the nanopharmaceutical scale-up

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5.4 SYLENTIS

CONTACTAna Isabel Jiménez, Ph.D COO and R&D Directore-mail: [email protected]

Covadonga Pañeda, Ph.D R&D Managere-mail: [email protected]

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5.5 Micronit

CONTACT PERSON

Dominique Bouwes (Business Director)

Micronit GmbH

Konrad-Adenauer-Allee 11

44263 Dortmund, Germany

Phone: +49 (0)231 88 68 077

E-mail: [email protected]


Micronit will design and manufacture ad-vanced micro chips / continuous fl ow reac-tors. These chips will include mixing devices that will ensure the control of the production.

Main tasks:

The design of the microfl uidic chips/arrays /micro reactors in collaboration with the partners.

The fabrication for the application in the industry, with and without integration of sensors to allow analytical methods.

Micronit GmbH is your independent and leading pure-play foundry ser-vice provider for MEMS/NEMS and microfl uidic products, who supports you fl exibly with the development and fabrication of your individual microchip s in glass and/ or silicon. Micronit stands for customer spe-cifi c personal expert advice on micro- and nanotechnology. Due to its unique development and manufacturing capabilities Micronit uses the interconnection of multidisciplinary techniques for customised devices according to your needs. All components and microchips are produced in state-of-the-art clean rooms with guaranteed 100% IP-security. This way micronit provides the optimal support in the development and production of individual chips.

www.micronit.de


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5.6 CHEMTRIX

We combine expertise in the field of (chemical) engineering and chemistry to help our customers to benefit from Flow Chemistry. Our exper-tise enables us to offer scalable and flexible Flow Chemistry solutions. We focus on delivering the customer higher profits by accessing new chemical possibilities, via a safe and reliable scale-up from lab to production.

www.chemtrix.com


CHEMTRIX will generate the continuous flow reactor prototypes for GMP production of two of three nanopharmaceuticals in the project.

Main tasks:

Evaluation of nanopharmaceutical production process(es) for translation to micro fluidic devices.

Input into the design of micro fluidic devices for production of selected nanopharmaceuticals for process assessment, optimisation and production.

Design, engineering and adaptation of peripherals required for performance of the syntheses under continuous flow within the demonstrator unit.

Training of users on continuous flow processes and the use of micro fluidic reactors.CONTACT

Dr Charlotte Wiles

E-mail: [email protected]

Phone: +44 1482 466459 +31 4670 22600

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5.7 MEJORAN

We are experts in Bioinformatics, Laboratory Information Management Systems (LIMS), Instrumentation and GxP Compliance services for Biotechnological and Pharmaceutical industries. Our main objective is to help our customers meet their objectives in the shortest time and we make it possible thanks to our deep knowledge in science, quality compliance and bioinformatics processes.

www.mejoran.es


Mejoran is a consultancy that will help partner CIDETEC in the design and the adaptation of their facilities. Mejoran will carry out training activities related to the Quality System (QS) and will implement the QS and Laboratory Information Management System (LIMS).

Main tasks:

Quality Systems implementation (GMP).

Laboratory Information Management Systems (LIMS).

Lab automation and automation processes.

CONTACT

Carolina Egea, MBA, PMP

Director-Mejoran Lab Automation


Francisco Arenal, Ph.D

Quality Lead- Mejoran Lab Automation



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5.8 SPINVERSE

Spinverse is the Nordic leader in innovation consulting, specialized in driving open innovation ecosystems, arranging funding and commercializing emerging technologies.

Founded in 2004, Spinverse employs 30+ professionals in Europe and is partner of a global technology consulting network with 23 offices. Our technology and business experts drive our clients’ R&D&I and business undertaking to develop game-changing solutions.

We offer services to various clients: Large multinational companies, SMEs and start-ups as well as multi-stakeholder partnerships, universities and governments e.g. in the field of automation, chemicals, clean-tech, elec-tronics, energy, ICT, life science, machinery and medical industry.

www.spinverse.com


Spinverse in its role as Work Package Leader will be in charge of the business plan for the pilot plant and will assist the coordinator in the dissemination and exploitation of the achievements and results.

Main tasks:

Business plan development

Dissemination and exploitation plans and strategies

CONTACT

Terhi Marttila

Project Manager


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5.9 ULTRA TRACES ANALYSES AQUITAINE

Nanomaterials seem to open new huge opportunities for innovation but, at the same time, raise questions on possible hazards for environment and human health. Having analytical tools allowing their characterization and quantification becomes of primary importance.

We offer to you 3 different approaches depending on the technique used: DLS (Dynamics Light scattering) A4F (Asymmetrical Flow Field Fractionation) coupled to UV (Ultraviolet-Visible), MALLS (Multi-Angle Laser Light Scattering) and RI (Refractive Index) detectors and Hyphena-tion to ICP-MS (Inductively Plasma Mass Spectrometry).

www.ut2a.fr

CONTACT

Mathieu Menta


MAIN ROLES WITHIN THE PROJECT

ADERA-UT2A will support CID in the characterization and Quality Assurance of the production processes. ADERA-UT2A operates in compliance with GLP and will act as an external characterization laboratory. They will use A4F-MALLS-ICPMS technique for characterization.

Main tasks:

Development of the physicochemical characterization of nanopharmaceuticals by A4F-UV-MALLS-RI-ICPMS.

Sample analysis according to GLP during the process, in process controls, and finally, at the end before the batches release.

Share its expertise to help partners to set up GLP conditions.


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Project data

Copyrights Photographies: CIDETEC, National University of Ireland Galway, University of Santiago de

Compostela, Sylentis, Micronit, Chemtrix, Mejoran, Spinverse, ADERA-UT2A

Project acronym: NanoPilot

Grant Agreement no: 646142

Start date: January 1st, 2015

End date: December 31st, 2018

Project budget: 6.28 M Euro

Type: Research and Innovation Action


Project coordination:

Dr. Iraida Loinaz BDM of CIDETEC Nanomedicine

+34 943 30 90 22


For further information www.nanopilot.eu

Documents

NANO PILOT · 2017-12-01 · Compliance with GMP NANO PILOT BROCHURE. Three different processes will be es-tablished for the production of three different nanopharmaceuticals. State