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GMP-SERVICES & KNOW-HOW IN DEVELOPMENT
- GUIDED BY INNOVATION AND EFFICIENCY
Overview of companies
Quasaar & MJR PharmJet
May / June 2016
Page 2 | 25.05.2016 Joint Know-how
Service partner for Life Sciences
Quasaar GmbH
Outsourcing Partner for the Life Science
Industry
Scalable and efficient solutions for the lab
Stability testing in all dimensions
Product control / quality management
Efficient and proven GMP-systems
Choice between GMP or development stage
State-of-the-art analytics and lab works
Experienced in GMP processes – being
embedded into a development environment
ensures transfer of technologies
MJR PharmJet GmbH
Specialist for the development of product
or system applications
Formulations on active ingredients & excipients
Applications and barrier testing models
Specialist for challenging compounds
Critical, sensitive molecules
Hardly soluble compounds, etc.
Pharma, medtech und cross-over
Focus on application system
Scaling-up and process qualification
Method development and validation
Specialists for all kind of required analytical
technologies and pharmaceutical formulations
(added value: particle technologies)
In more detailed on pages 3 – 19 & 42 - 48
Specialists for all kind of particles and how to
manufacture them
Generating particles in a very precise way,
analyzing them in a competent way and
understanding how they interact and work
In more detail on pages 20 – 41 & 42 - 48
The GMP and the development
area are separated in two legally and organization-
wise independent companies
Page 3 | 25.05.2016 Intro Quasaar
Your outsourcing partner
Page 4 | 25.05.2016 Intro Quasaar
Innovation and efficiency – Added Value Quasaar
SERVICE OFFER QUASAAR
Attractive pricing model
Comprehensive, state-of-the-art
analytical techniques
Large volume capacity, versatile
stability center
Certified cooperation, all systems
and processes under GMP
Project stage / R&D to GMP -
interface to be defined by each
customer project
Fast track from GMP to R&D
Special expertise in all types of
particulate systems
Quality control and analytical support
Batch release analysis (release by QP on demand / EU – Retest)
Analytical support
Stability studies – storage (analytical investigations on demand)
Stress – and compatibility testing
Formulation screening
QC for API, raw material and excipients
Technology transfer
Method optimization (incl. robustness investigations)
Method transfer – concepts for GMP
Validation & qualification, design & performance
Cleaning validation, transport validation
Design & Performance of risk analysis
Method development & implementation into regulatory environment
Special techniques / methods (among more)
Added Value Quasaar: characterization of all kinds of particulate systems
Material Science – physical-chemical methods
Microbiology, Synthesis, Process optimization in cooperation with partners
Further services (among more)
GMP-Archiving, storage of retention samples, transport logistic
QP Services, preparation/execution of audits
Consulting and training concerning quality management, quality assurance, etc.
Page 5 | 25.05.2016 Benefits Quasaar
Pricing differentiated by customer needs – Quasaar
solutions quite often more efficientPRICING
Hourly rates vary by
- Involvement of personnel
- Involvement of installed technical base
- Technical complexity
- Additional training & consulting
Examples of typical hourly rates
- € 95 base lab staff (pure documentation)
- € 100–125 (depending on equipment class)
- € 150 – 200 technical / academic experts
Quotations react on
- Individual project needs
- Individual customer needs
Pricing in the stability center
- Cost go by volume in units of 10 l
- Initial registration costs by time and effort
Attractive relation volume to cost
- due to large-volume climate chambers
- Suitable for high volume sku’s (incl. bulk)
- RFID-technology currently build-up
Prices for samples in the stability chambers
- € 0,80 – 1,0.- per l per month in standard
ICH-climate conditions
Quotations react on
- Individual project needs / customer needs
Analytical Laboratory Stability Center
Project performance based on KPITaylor-made pricing quotations on request
Page 6 | 25.05.2016
All customer requests realizable
ANALYTICAL TECHNIQUES
Benefits Quasaar
• Several redundant HPLC/UPLC stations
• All common methods realizable
• Technical upgrades and additional capacity on
demand
• Detectors: UV-VIS, PDA, refractive index
• Drug Release / Kinetics
• Paddle & Basket & special devices
• SUPAC studies
• Automated systems
• IVIVC
• Special dosage forms
• Biopharmaceutical characterization
• GC, GC-HS (residual solvent)
• (GC-MS / ICP-MS)
• Spectroscopy (UV, IR, fluorescence)
• Compendium methods (USP, EP, CHP
etc.)
• Water determination (Karl-Fischer etc.)
• volumetric/coulometric
• Oven method
• Pharmaceutical-technical methods• disintegration
• resistance to crushing
• friability
• appearance, opalescence, turbidity
• density, pH-value, osmolality
• leakage tests
• Special analytical methods for
investigation and characterization of
particles
Established base techniques in the analytical lab
Further techniques on request – can be realized based on a smooth internal GMP supply
yet within the still initial project activities
Page 7 | 25.05.2016
State-of-the-art outlay
Technical operations
efficient in design
All relevant climates
Capacity for small to big
units incl. as bulk ware or
on palettes
Easy scaling-up
500 m3 to be enlarged to
2000 m3
Extra warehouse for
retain samples
Up-coming:
500 m3 GMP-archive
Large and state-of-the-art capacity for stability
studiesSTABILITY CENTER
Available conditionsStandard / ICH climatic conditions
25°C/60% r.h. 280 m3
30°C/75% r.h. 180 m3
40°C/75% r.h. 50 m3
Refrigerator and freezer storage
-20°C ± 5 °C
5°C ± 3 °C
-80°C for special deep freeze samples
Available special conditions
25°C/40 % r.h.
30°C/65 % r.h
30°C/35 % r.h.
Cyclic conditions or transport validation
- 20 °C to 150°C
Benefits ÜberherrnTechnical characteristics
Redundant control systems for
temperature and humidity
Storage capabilities for palettes, barrels
or bulk ware
Protected against excess temperature
and humidity
Monitoring system Yokogawa
Alert system includes SMS & E-Mail
Benefits Quasaar
Page 8 | 25.05.2016
How we collaborate with you
WORKING FOR OUR CUSTOMERS - I
GMP-Zertifikat
Quasaar
Built-up of collaboration
1. Agreed definition of basic concept for outsourcing cooperation
2. Ratification of secrecy agreement, exchange of relevant
documents
3. Quotation built on feasibility evaluation and compilation of
techniques and equipment to be used
4. Integration of all relevant GMP documents, ratification QAA /
service agreement
5. Audit
6. Definition of project team & time schedule plus capacity check
On-going collaboration
7. Installation of methods (if needed optimization & validation)
8. Sample logistic & storage of samples for stability tests
9. On-going work on tests and analysis
10. Certificates and stability reports, reporting of results to the
customers
11. Performance monitoring by KPI
12. Regular Jour Fixe with the customer team
Benefits Quasaar
Page 9 | 25.05.2016
IT safety and data communication within a project
WORKING FOR OUR CUSTOMERS - II
Benefits Quasaar
Data back-up
What will be backed up?
Analytical raw data and documents
Separate, Quasaar-exclusive server established
Commercial data and documents on separate ERP server
Where and when will be backed up?
Backup files: 2 times a day (12:00 / 16:00) to back-up server
Backup VMs: 1 times per day back-up server
Backup: analytical raw data and documents 1 times per week
on Blue-ray Disc
RawdataServer
FileServer
ERPServer
Back-upServer
Data transfer / communication
Technical data connection fiber optic network / internet
Up / Down synchronous lines 100-300 Mbit
Redundant connections to the fiber optic network
Direct entry of data into customer systems (LIMS, SAP)
Establishing local clients (IT) at Überherrn site
Archiving of relevant hardcopies in Quasaar system
Telecommunication: 8-24 parallel trunks (fiber optic)
Page 10 | 25.05.2016
Efficient Quality System guarantees GMP-compliant
workflows & proceedingsQA ELEMENTS QUASAAR - I
Benefits Quasaar
Quality Manual (QSH)
SMF, VMP, SOPs
Raw data, protocols, templates
Documentation
Change Management
Training
RiskManagement
Qualification
Validation
Deviation
Self inspection
Audits and inspections
Complaints
CAPA-Management
Lab evaluation,
Root cause analysis
OOX
(OOS, OOE, OOT, OOC)
Q
A
Page 11 | 25.05.2016
Quality Assurance, the basis for customer
satisfactionQA ELEMENTS QUASAAR - II
Benefits Quasaar
Elements QM - System
Document management
• All computerized systems are validated
acc. GAMP5
• Redundant data archiving
• Document system
• Quality Manual, SMF, VMP
• SOPs, testing specifications
• Raw data, protocols, templates
Deviation management established
• Traceability
• Central management by QA
GMP-compliant training & documentation
• Internal training
• External training
• Advanced training & education
• Surveillance
Risk management
• FMEA / FTA / Ishikawa
Qualification
Supplier & subcontractors
Equipment
Validation
• Methods
• Processes
• Computerized systems
Compliance with
regulatory requirements
Customer
satisfaction
Patient safety
Continuous
improvement
Product quality
Data integrity
Document management
Compilation
Steering
Distribution
Archiving
Sample monitoring
Registration
Storage
Stability
Qualification monitoring
Training
Supplier & subcontractors
CS and equipment
Regulatory guides
Audits und inspections
Deviation
Lab evaluation (root cause analysis)
OOX
Audits and self inspections
Customer complaints
CAPA-Management
Page 12 | 25.05.2016
Each project deserves specific attention
Project management
Customer orientation in outsourcing by Quasaar
Quasaar project management – embedded into the
customers project management
Long-standing experience with outsourcing
situations – gathered at both sides
Own management systems for continuous process
optimization
Highly qualified staff – including an own training
High dedication to deliver on time
Trusted relationships to authorities and customers
Interface development to GMP
Quasaar operates an established interface between
the GMP lab and the development lab
The Quasaar lab works within an environment for
pharma development
Well defined separation between development stage
and GMP
According to the customer needs
Development domain and GMP domain maintain
separate QM systems
Quasaar management highly experienced in GMP
Campus Überherrn provides further competencies to
lean on by a prolific network of partners
Highly flexible in the set-up of the desired test
design and the required documentation
Direct transfer of data into the customers IT systems
CHOICE BETWEEN GMP OR DEVELOPMENT STAGE
Benefits Quasaar
Page 13 | 25.05.2016
Characterization of particulate systems
SPECIAL KNOW-HOW ON PARTICLES
Bild S. 29 oben
Business Plan 24.03.2016
MJR PharmJet GmbH
Benefits Quasaar
*) EFSA: European Food Safety Authority
Methods for analyzing the particulate structure
Particle size (laser diffraction, Sympatec)
Zeta-Potential (Malvern)
Electron microscopy SEM / TEM (on request)
Particle counting, sieve analysis, Micro-Flow Imaging
and many more
Typical topics with particles
Particle size
Particle contamination, - count
Particle-based formulations
Particle size distribution
EFSA* threshold 100 nm
Agglomeration or disintegration, leakage
effects
Specific drug release profiles
Residual solvent in particulate systems,
elemental impurities
Encapsulation efficiency
Customized HPLC methods
Surface properties
and many more
Page 14 | 25.05.2016 Know-how Quasaar
Particles impose specific challenges
WHY UNDERSTANDING PARTICLES IS IMPORTANT
Particle range defined in regulatory guidelines (>100 nm, absence of particles >10 μm) does not
cover state-of the-art particle technology (100 nm – 1000 nm)
Not all relevant methods / equipment for characterization of nanoparticles are established in GMP
and other quality systems to be applied
Thorough characterization of particles important, because of great impact of particle
characteristics on product performance, bioavailability, efficacy and other properties
Need for own validation and qualification concepts and development of dedicated equipment
Long-term stability effects of particles must be evaluated (agglomeration, disintegration, leakage
effects…)
Toxicological effects of need to be investigated and an uncritical particle size range defined
Page 15 | 25.05.2016 Know-how Quasaar
Topics for our customers - I
TYPICAL CUSTOMER PROJECTS
Maintenance and variations support, GMP and analytical support
Life Cycle Management "old methods" because of new regulatory requirements, check validation
documents - concept to update the validation (including robustness)
Comparative studies SUPAC for relevant changes in production/formulation (validation of the
relevant methods)
Scientific assessment concerning monograph methods (e.g. Chinese Pharmacopeia), planning
and implementation of relevant validation or verification activities
Compatibility tests drug / excipients, generic methods for evaluating, implementing studies with
small batches of the final dosage form (production of batches MJR-PharmJet)
Development of concepts for qualification, implementation and compilation of GMP-compliant
documentation
Stability and analytical support in development projects - project team consisting of R&D of the
customer, MJR PharmJet for formulation (particulate systems, small batch sizes) and Quasaar to
develop the relevant criteria (e.g. encapsulation efficiency, residual solvents, drug release etc.. )
and many more
Page 16 | 25.05.2016 Know-how Quasaar
Topics for our customers - II
TYPICAL CUSTOMER PROJECTS
Quality Control
Batch release analysis for finished products, active ingredients and excipients (full analysis,
reporting, certificate)
QC of raw materials incl. method optimization and validation of methods according to current
GMP requirements and transfer back to the customer (protocol & report, laboratory training)
Biopharmaceutical characterization and comparison of finished product (pH solubility profiles,
release profiles)
Qualification and auditing of suppliers
GMP-compliant quality control of excipients, risk-based approach validation of analytical methods
Stability
Storage of large-volume batches at ICH conditions (parenteral products, veterinary drugs, bulk),
creation of the GMP documentation stability (storage plans, cumulative stability reports)
Performing of stress tests to proof stability-indicating properties of analytical methods
Determination of shelf life for standard substances and reagents, qualification of standard
substances
and many more
Page 17 | 25.05.2016 Know-how Quasaar
Scientific projects and a very competent network
ensure continuous innovationCOMPETENCE
Additional partner within a scientific
network – additional competence and
techniques
Mecadi GmbH
APV Arbeitsgemeinschaft, FG
Qualitätssicherung und Analytik
Technische Universität
Braunschweig
HTW Saarbrücken (Ibo-Institut,
Ri-Comet)
Helmholtz Institut (HIPS)
IBMT Fraunhofer, BioCryo
Synnovating GmbH
NanoBioNet
…
Recent Publications Quasaar-Team
The Transfer of Analytical Procedures
Influence of X-ray as PAT-Method on Drug Products
GMP-Berater, Kapitel 14G Ergebnisse außerhalb der Spezifikation
(OOX-Ergebnisse)
GMP-Berater, Kapitel 14B Substanzen im Labor
In-situ Drug Release Monitoring with a Fiber Optic System
Partikelmessung von F&E bis GMP
GMP-Berater, Kapitel 14H Dokumentation im Labor
GMP-Berater, Kapitel Geräte im Labor (in Erstellung)
Recent scientific projects – often with competent partners
Development of new methods and techniques for determining and
predicting stability data (IBMT Fraunhofer)
Use of RFID technology in the pharmaceutical environment (Ibo Institute,
Ri-Comet)
Nano-formulations in the context of biological barriers (MJR-PharmJet)
Development of analytical instruments to test innovative dosage forms
Increasing efficiency in the laboratory environment (Synnovating AG)
Permeation and new methods for leakage testing for packaging materials
(Mecadi)
Page 18 | 25.05.2016
Dr. Christoph Jacobs
Study of chemistry, PhD in pharmaceutical and medical
chemistry
> 15 years GMP expertise in an industrial environment
Head of the API expert team with a provider of analytical
services (Across Barriers GmbH)
Head of QC with set-up and expansion of the QC lab
(PHAST GmbH)
Highly experienced with audits by FDA, European or local
authorities
Expert in dissolution studies and many other QC -
methods
Regular expert speaker about analytical methods under
GMP requirements
Know-how Quasaar
Management team with expertise and competence
MANAGEMENT
Dr. Markus Limberger
Study of chemistry, PhD in pharmaceutical and medical
chemistry
> 15 years GMP expertise in an industrial environment
Focus on drug QA
Many fold project experiences from collaborations with
almost all renown research driven pharma companies
> 10 years Head of Technical Management of a GMP service
provider (PHAST GmbH), installation of GMP and QM
systems
Regular expert speaker about QA and pharma analytics,
member of the respective committee within APV (an industry
association)
Author of several related publications (GMP Berater Verlag)
Page 19 | 25.05.2016 Innovation & Efficiency
Benefits Quasaar
Combination of flexibility and expertise in a regulated environment
Project team with many fold management experiences in outsourcing
GMP trained team
Well sufficient capacity in laboratory and stability center – further scaling-up possible
Definition of the interface between development stage and GMP according to customers
requirements
Seamless transfer of R&D results into the GMP domain
Analytical lab embedded into an environment for research and product development
Flow of samples and data in continuously optimized processes – and very efficiently
Sustainable quality ensured by integrated staff management and own training efforts
Handling of CTM (Clinical Trial Material), specific qualification/validation projects or teaming-up
within larger programs - as examples - available as service as well.
SUMMARY
Page 20 | 25.05.2016 Intro MJR PharmJet
Partner for your development projects in pharma or
medtech
Winner 2014Best Innovation
in Formulation
Page 21 | 25.05.2016 Intro MJR PharmJet
CRO for challenging compounds
SERVICE SPECTRUM OF MJR PHARMJET FOR PHARMA
MJR PharmJet offers
Development partner in R&D projects
based on milestone payments
Specialty – formulation of challenging
API’s
Wide range of conventional methods for
the production of drug products (solid,
semi-solid and liquid)
Production and development of
particulate systems (micro /
nanoparticles)
Solutions with different micro channel
reactors including Micro Jet Reactor
Combination of micro channel reactors
with conventional methods
Optimization of existing formulations
Formulation optimization with Quality by Design methods (QbD)
Improvement of stability and production, excipient replacement due to
regulatory or QA issues- also with nanoparticle alternatives
Improvement of pharmacokinetics – if required
Novel formulations
Pharmaceutical end formulations - especially of challenging API’s
Formulation of Orphan Drugs
Micro channel reactor technology for chemical synthesis
Development of whole particulate systems
R&D services
Development of test systems for:
Detection of impurities
End formulation evaluation
Nanoparticle screening studies for NCE’s
Solubility studies (i.e. for new API’s) and dissolution
Solubility and dissolution studies for micro and nano particulate systems
IVIVC
Further offers
Patent screening for development feasibility
Lab services for clinical trials and CTM preparation
Production of small scale batches for stress and compatibility testing
Page 22 | 25.05.2016
Contributions by MJR PharmJet can be decisive to
start many development stepsVALUE CHAIN PHARMA DEVELOPMENT
Pharma
MJRparticle-
based
screening
of
NCE’s
MJRparticles
for
in-vitro tests
MJR(particle based)
formulation
of the final
galenic formMJR
production
clinical
trial samples
MJRtechnology -
transfer and
design of
production process MJRset-up of
micro channel reactor
production plant
Lead
discovery
Pre-clinical
evaluationFormulation
development
Clinical
phases
Registration
processProductionScaling-up
Page 23 | 25.05.2016
Micro reactors and other innovative methods for the
formulation of challenging API’sTECHNOLOGIES MJR PHARMJET
Pharma
Solutions by MJR PharmJet
MJR PharmJet offers almost every
type of innovative methods for the
pharmaceutical development
MJR PharmJet finds for almost all of
the challenging API’s (with low
solubility, unstable, toxic in high doses,
…) a solution
MJR PharmJet offers symbiosis
between modern micro reactor
technologies and other pharmaceutical
processes
MJR PharmJet has huge experience in
transfer of the methods and processes
to its customers - in case of micro
reactor applications with an usually
uncomplicated scaling-up
Innovative methods for pharmaceutical development
For low soluble substances
Wet granulation
Hot Melt Extrusion (HME)
Nano and micro particle development in micro reactors
Nanoparticle development in micro reactors
Complexation
Spray drying / lyophilization
For unstable substances
Encapsulation
Integration in matrix particles
Conventional technologies for scale-up
High pressure homogenization
Batch processes
Further innovative methods – uncomplicated scale-up possible
Micro reactors
Micro mixer
Continuous mixer
Page 24 | 25.05.2016
Exceptional results with nano and micro particles
Oral Formulations
Improved bioavailability
No “Fed / Fasted” variability
Taste masking
Improved stability for sensitive substances
Controlled or delayed release
Parenteral formulations
No need for solubilizers
No need for surfactants
Immediate dissolution after injection
Increased stability
Low volume applications possible
Pulmonary formulations
Controlled drug delivery to lung
Increased activity
Improved absorption
Nanoparticle in suspension
Ready to use after filtration
Through lyophilization further stabilized and showing
very good redispersibility
PHARMA APPLICATIONS
Pharma
Realization of all steps
Step 1: Development of particle
Step 2: Development of end formulation
Step 3: Transfer to scale-up and production at
Customer/Partner
Manufacturing method selected
specifically (via micro reactor or other
methods)
Later a very efficient integration to
existing production processes
CTM production / early GMP production
for scaling-up possible
Competence for next steps is
established on the campus - early
integration of Quasaar as GMP-Partner
possible
Development of «Drug Delivery Systems»
with micro or nano particles
Technology licenses for finished drugs manufactured by using the special equipment of the micro jet reactor via leon nanodrugs GmbH
Page 25 | 25.05.2016 Micro Reactor
How micro reactors work
REACTION PRINCIPLE
Optimized mixing
Minimal mixing time
Jet velocity 100 m/sec
Mixing time < 0.1ms
Reactant 1 Reactant 2
3 cm
Example here: Special type Mikro Jet Reaktor; diameter nozzle Ø 50-1000 μm
1. Continuous precipitation
Carrier Gas
inert / reactive
Stable particles (+ gas + liquid)
in suspension or emulsions
2. One-step reaction
3. Parallelization and serialization
4. Optimization by control of process parameters like temperature,
pressure, flow rates, solvent composition etc.
Page 26 | 25.05.2016
Application of micro reactors – highly beneficial in
formulation development
Batch size independent results
Volume can be reduced
Good control of processes
Mixing velocity optimized
Chemical synthesis by stoichiometric feeding of reactants very well controllable
Production run as a continuous process – and via parallelization with high through-put
Scaling-up in further development steps well enabled
Also two step synthesis via the gas possible
Also for sensitive reactions, the micro reactor offers a highly suitable environment.
Several types of micro reactors are available today.
For each application, the best suitable type of reactor can be selected.
The Micro Jet Reactor was the first of this kind and MJR PharmJet has lots of expertise with it.
ADVANTAGES MICRO REACTORS
Micro Reactor
Page 27 | 25.05.2016
From simple particles to complex shell systems
CASCADING THE PROCESSES
„naked“(nano) particles
Core/shell particles
Multilayered(nano) particles
Nano emulsions
Coatednano-emulsions
Specific advantages compared to
the Wet Nano Mill:
- Less harsh to sensitive
compounds
- Very narrow particle size
distribution
- Faster processes
- Lower production costs
Micro Reactor
Micro reactor processes in the
generation of particles provide:
- Continuous production
- Controlled reaction
- High quality particles
- Tight control over particle size
Page 28 | 25.05.2016
Many types of micro - and nanoparticles can be
made in the micro reactor
Emulsions
Liposomes
(Nano) particles with a lipid-solid composition
Inorganic nanoparticles
(Nano) particles of active ingredients – w/o shell
(Nano) particles built-up by a polymer matrix
Particles used in modified release of API
TYPES OF PARTICLES
Nano- / micro particles – w/o shellBiocides
Insoluble metal oxides / specifically generated
Poorly soluble API
EmulsionsParticles made of lipophilic or oleic compounds will be
improved in
Uniformity / homogeneity, composition and color, and
their processing; applicable to
flavor additives, fragrances, or in general oils & waxes
Encapsulated nano / micro particles
- improved stability of sensitive compounds
- taste masking
- improved handling in production processes p.ex. by
higher dispersibility
Applicable to
- pigments / colorants
- food additives like vitamins, Omega-3 fatty acids, etc.
- fragrances
- agro-chemicals
Micro Reactor
Page 29 | 25.05.2016
Also for medtech and cross-over products new
types of solutions are available
Potential application areas
In-vitro diagnostics
In-vivo diagnostics
Concepts within theragnostics or
companion diagnostics
Ready-to-use (RTU) parenteral
products
Particles as carrier systems (as
examples) for
Active ingredients
Tracer
Compounds for imaging
Applications within or by help of
medical devices
Cross-over applications
Plus more
APPLICATIONS MEDTECH/PHARMA
Medtech
Current projects MJR PharmJet
Drug targeting with iron oxide
particles
Pulmonary drug targeting with
extended release nanoparticles
Transdermal therapy with
nanoparticles
Drug targeting through blood brain
barrier
Page 30 | 25.05.2016
Medtech profits from MJR PharmJet’s competence
in the design of whole systems
First examples from the medtech arena
Ready-to-use (RTU) parenteral drug formulations
Particle as carrier system for API’s
Integration of surface technologies from chemical
nanotechnology (for stents p.ex.)
Contrast agent
Specialized surfaces
Implants
Antimicrobial
Biocidal copper derivatives to be used in patients
(also as silver replacement)
Particles to release an API in wound healing
With antibiotics – applied to skin wounds
To fight a bacterial biofilm in the oral cavity
Nano-hydroxyapatite for dental care
Transfer of know-how and expertise from the
pharmaceutical development field
TRANSFER OF PARTICLE TECHNOLGIES INTO MEDTECH
Medtech
Highly controlled manufacturing of SPION’s with the
MJR technology
(= Super Paramagnetic Iron Oxide Nanoparticles)
Manufacturing of SPION’s in micro reactor
Construction of encapsulation (LbL – Layer by Layer) in
micro reactor
Magnetic nanoparticle (specially SPION’s)
Adapted to the physiologic environment with outer shells
Super para-magnetic for use in MRI etc. and stable
Bi-functional SPION‘s for optical imaging and MRI
Tracer conjugated SPION‘s as MRI – nano props with
different tracers (antibodies, carbohydrate chains,
aptamers and other oligonucleotides, peptides,
polymers, etc.)
Nano particles as carrier for radio nuclides for
diagnostics or therapy
Bi-functional nanoparticle for PET + MRI
Page 31 | 25.05.2016
State-of-the-art test systems and technologies
available at MJR PharmJet
CaCo - 2
Skin models
Barrier models
Dissolution of API’s from nanoparticles
Magnetic mobility of nano particles
ELISA-methods
Cytotoxicity evaluations
Migration evaluations
Microbiological evaluations
Biofilm models
Mucus models
SOME SPECIFIC MEDTECH TECHNOLOGIES
Medtech
Page 32 | 25.05.2016
High-through-put screening of poorly soluble lead
compounds – enabled by nano particlesAPPLICATION EXAMPLE
Application Examples MJR PharmJet
•Application route
•Definition of project objective
•Desired properties
Selectionof excipients
•Physical-chemical characteristics of target substances
•Application route
Definition of particle type •High throughput
screening with low amount of API
•> 500 trials in few weeks
Particle-based screening
•Diafiltration
•Lyophilization
•Wet granulation
End formulation studies
Advantages
Ideally suitable for R&D-labs
working with innovative and thus
not yet characterized substances
und lead structures
Very small amounts of the lead
compound or NCE / API sufficient
Initial and seminal results quite
early and fast available for further
orientation of the research project
Result
Early (wrong) bias against poorly
soluble, but otherwise promising
lead substances avoided
Page 33 | 25.05.2016
Improved dissolution of an otherwise poorly soluble
API
Problem
Low solubility dependent low bioavailability
Dissolution kinetics should be improved
API dose should be decreased
Task
Screening for the best possible formulation to improve the
bioavailability
Solution
3 different formulation
Wet granulation
Hot melt extrusion
Nanoparticle
Best dissolution profile using nano particle formulation
0
20
40
60
80
100
0 10 20 30 40
Dis
so
lution
/ %
Time/ min
Dissolution with 1% SDS in water, 50 rpm
Crude API Wet granulation
Hot melt extrusion Nanoparticle formulation
APPLICATION EXAMPLE
Application Examples MJR PharmJet
Page 34 | 25.05.2016
Extended release of a well soluble API – avoiding the
initial «burst» release after injection
Problem
API for a ready to use suspension
«Burst» effect should be prevented – good soluble API
Extended Release of the system
Task
Ready to use ER suspension of a good soluble API
Solution
With Micro Reactor in following steps
PLGA micro particles (in polymer matrix)
Lyophilisation
ER Formulation
Dissolution rate adjustable with different polymers (F1, F2, F3)
Stable formulation
0102030405060708090
100110
0 50 100
Dru
g re
leas
e/
%
Days
F1
F2
F3
APPLICATION EXAMPLE
Application Examples MJR PharmJet
Page 35 | 25.05.2016
Drug eluting stents with nanoparticles
Out of the development platform for combined
products
Advantage of polymeric nanoparticles
Homogenous coating of stents
Extended release of API
Controlled application of API
Optimal API dosing
Enhanced stability
Advantage of micro reactor
High API loading into polymeric systems
Homogenous release through homogenous particle
size
APPLICATION EXAMPLE
Application Examples MJR PharmJet
Page 36 | 25.05.2016
Antibiotics in wound treatment – good penetration in
nano particle formAPPLICATION EXAMPLE
Problem
Biocides and antibiotics are only moderately effective in plaster matrix
In the beginning to much API
Biofilm caused by the wound bacteria inhibit the penetration of
antibiotics
Task
Antibiotics should be integrated in a particle matrix– The particles
should penetrate into the wounds and realize the long term release of
the API
Solution
Matrix nanoparticle optimized for
Penetration into the wounds
Does not interfere with the wound healing and non-toxic
Release of antibiotics
Trials
Favorable matrix
Appropriate antibiotics
Barrier models
Wound model
Combination with plaster
(Center for Biofilm Engineering©
Cooperation with divers Institutes
Robert Koch Institute
Charité Berlin
Freie Universität Berlin
Application Examples MJR PharmJet
Page 37 | 25.05.2016
In-vitro diagnostics with magnetic nanoparticles
Versatile system for Diagnostics
Advantage of magnetic nanoparticles
Easy visualization by MRT or EM
Moving of particles in magnetic field (lab on a chip)
Easy separation of particles by magnetic field
Easy quantification of bound substrate by magnet-
relaxometry
Advantage of micro reactor
High volume production of controlled particle size
Coating with various surface agents possible
Functionalization of surface with various molecules
possible
SPION’S - I
Application Examples MJR PharmJet
Ferrofluid
Nanoferrit
Page 38 | 25.05.2016
SPIONS – can perfectly manufactured in the micro
reactorSPION’S - II
SPION’s = Super Paramagnetic Iron Oxide Nanoparticles
Task
Manufacturing of γ-iron oxide and at the same time coupling of
physiologically active / relevant substances
Solution
Production of complex structure in micro reactor using several
steps
Step 1: Synthesis of γ-iron oxide
Particle size: 20 – 30 nm
Homogeneity: PDI < 0,2
Concentration in water: 2% - 20% adjustable
Step 2: Coating of SPION
Polyanions or rather polycations or various silans
Molecular imprinting
Biopolymers
Step 3: Functionalization / activation agent integration
Step 4: Coupling of tracer for the desired diagnostics
TEM / picture of SPION
nanoparticles
Particle size distribution
of SPION 30 nm
with a PDI of 0.197
Application Examples MJR PharmJet
Page 39 | 25.05.2016
SPIONS – coupled to a tracer for innovative imaging
and other medtech – pharma applicationsSPION’S - III
SPION’s = Super Paramagnetic Iron Oxide Nanoparticles
Use in medtech & pharma
For Imaging, p.ex. MRI diagnostics, where NMR seeks to
replace the radio nucleotide, but the signal of usual NMR is
limited
Imaging in combination with fluorescence dyes (see picture)
As drug delivery vehicle - moved by magnetic forces
Control of particles at tumor side
For Hyperthermia therapy
For various combinations of therapies
Tracer can be
Antibodies
Aptamers / Oligonucleotides
Peptides
Specific carbohydrate structures
Simple polymers
Application Examples MJR PharmJet
Polymeric
cover
Drug
Fluorescence
dye
Polycations
SPION
Page 40 | 25.05.2016
Dr. Akif Emre Türeli
CSO MJR PharmJet GmbH
Studies of pharmaceutical sciences in Turkey
10 years experience in international nano technology
industry
Drug formulation specialist
Developer of many fold innovative applications of the
Micro Jet Reactor for the formulation of drugs
Co-founder and shareholder of Instillo Group
Know-how MJR PharmJet
Management team with expertise and competence
MANAGEMENT
Dr. Bernd Baumstümmler
CEO MJR PharmJet GmbH
25 years of experience in pharma and biotech
Product Manager with Abbott
Technology Advisor in biotechnology for Hessische
Technologiestiftung
Project Manager Mediport Venture Capital, Berlin
Several positions in Biotech and pharma start-ups, usually as
COO/CEO
Founder of the Instillo Group
Page 41 | 25.05.2016
Benefits MJR PharmJet
Upon involvement at early stages in the development process, MJR PharmJet can find solutions
also for poorly soluble or sensitive substances
MJR PharmJet can ensure a seamless transfer of results into the highly regulated GMP regime
via Quasaar
MJR PharmJet is proud to think of issues in application systems instead of sole compounds – be
it in pharma, be it in medical technology
Deep understanding of the special challenges in medical technologies
Embedded into a network of research and development – working at the very recent topics in
medical technology
Several model systems to test particulate systems available
Optimization of formulations, QbD (Quality by Design), reformulations of products to bring-up the
product to actual standards or for life cycle management
All suitable and state-of-the-art formulation techniques available
Strong expertise in the development and application of particulate systems
SUMMARY
Know-how MJR PharmJet
Page 42 | 25.05.2016 Joint Know-how
The campus in Überherrn
The commonly shared campus
at Überherrn is provided and
managed by Instillo GmbH.
Page 43 | 25.05.2016
Combined competencies – highly beneficial for the
customer QUASAAR – MJR PHARMJET
Outsourcing partner
for the Life Science industry
Partner for the development of
product & system solutions
Method development &
validation
Efficient and proven GMP
system
Experts for the application
of all kind of analytical
methods – with all kind of
formulations
Also experts in handling of
all kind of particles
Experts in the handling of all
kind of particles and their
generation, i.e.
Precise manufacturing of
particles, specific analytics,
understanding the efficacy
Partner for early stage
development works
Very high quality level in
R&D
Synergies
Common development of methods, where
suitable
Seamless transfer from R&D into the regulated
GMP regime for production and control
Fast and easy transfer of know-how and
technologies from R&D into GMP
Synergies lead to faster projects and lower
costs
Commonly shared overhead services via the
“Shared Service Center” by Instillo GmbH
Joint Know-how
Page 44 | 25.05.2016
State-of-the-art labs on the campus
CAMPUS ÜBERHERRN
GMP area of labs Quasaar
Development lab nanoSaar
Joint Know-how
Access to GMP area only via chip card control
Development lab MJR PharmJet
Page 45 | 25.05.2016
GMP area - clearly separated
CAMPUS ÜBERHERRN
Access control
- Chip system
- Restricted key list
Monitoring system to control room temperature
- Sensor system
- Fully closed rooms
Pest control at critical points
Stability Center
Office building
Reception
GMP lab QuasaarDevelopment lab nanoSaar
Utilities
GMP resp. Quasaar-domain
Joint Know-how
Development lab MJR PharmJet
Page 46 | 25.05.2016
Combined know-how on the campus and beyond
NETWORK OF COMPETENCIES
Including many fold external partner via the network of all companies on the campus
Joint Know-how
MJR PharmJet GmbH
CRO for pharma
Formulation development
for exacting substances –
with all suitable methods
Cooperation partner to
medtech companies
Application of the MJR
patents & technologies
in medtech
Quasaar GmbH
Outsourcing partner
QC & product control
Stability studies
Analytics & methods
Technology transfer
GMP-support
nanoSaar AG
Applications: Consumer,
non-Pharma and
cosmetics and other
Promotion of the
technology in specialty
chemicals & technical
applications
License models as well
as product supply on
choiceCompetence Center on the Campus Überherrn
Cost synergies
via the combined
group of
companies
Transfer of know-
how and
competencies
across the group
Fast track from
R&D to GMP
BEST OF 2016MIKROSYSTEMTECHNIK
MJR PharmJet also received the Gips-Schüle Award 2015 in Research: “Nano particles in the environment friendly production of solar cells”
nanoSaar also was a finalist (one of 4) with «Innovationspreis der Deutschen Wirtschaft 2016»
CPhI Pharma Awards
Winner 2014Best Innovation in Formulation
Page 47 | 25.05.2016
The Überherrn premises
LOCATION / CAPABILITIES
Well located for logistics
D, F, Benelux within easy reach
5 min to motorway A 620, 10 min to A32/A4
(F)
40 min to Luxemburg airport
25 min to TGV/ICE
Paris – Saarbrücken - Frankfurt
Characteristics for the campus
12’000 m² total premises
5000 m² buildings
350 m² office space
1000 m² laboratory area –
further expandable
500 m3 stability center –
further expandable
Very modern energy concept
- photovoltaic arrays
- Batteries (also for safety reasons)
- Block heat and power plant
based on existing industrial premises.
Campus is operated by instillo GmbH.
Industrial area „Im Häsfeld“
Comotorstr. 2
Visitors: Industriestr. 1B
66802 Überherrn
Joint Know-how
Page 48 | 25.05.2016
Contact
MJR PharmJet GmbH
Dr. Bernd Baumstümmler
T +49 (6836) 9691 100
M +49 (176) 32205115
Industriestraße 1B
66802 Überherrn
www.instillo.de
Quasaar GmbH
Dr. Markus Limberger
T +49 (6836) 9691 212
M +49 (162) 9677500
Comotorstr. 2
66802 Überherrn
www.quasaar.de
Your Partner in Outsourcing & Product Development