Siegfried`s One Stop Shop for partners in the pharmaceutical industry

Corporate Know-how 1/10
Siegfried’s One Stop Shop for partners in the
pharmaceutical industry – Seamless chemical and
pharmaceutical development
And at the end: One of the success sto-
Today, the majority of our customers
knowledge of over 135 years of bring-
The active pharmaceutical ingredient API
ries. A typical project according to the
ranging from small biotech to big pharma
ing products to the market. Before con-
is the common language for both, the
one stop shop was handled during the
companies are facing a constantly in-
centrating on the exclusive customers
API and DP development. Before the drug
last years. Starting with the customer’s
creasing pressure to get their products to
Siegfried was an innovative and fully inte-
product development can start their for-
inquiry to support him with a tablet for-
the market. Shorter development cycles
grated pharmaceutical company until the
mulation work the chemical development
• Environment, Health & safety
mulation for clinical phase 2 studies.
combined with an increased price pres-
late 70ies of the last century. With all our
has already spent a tremendous time on
• Customer services if needed
Siegfried drug product development de-
sure characterize the development of all
experience and innovation in the develop-
route scouting, chemical development
partment compiled together with the
new candidates. But how can we address
ment and manufacturing of APIs and drug
and finally the synthesis of the API. Usually
customer a URL of the developed formu-
this ultimate question how to accelerate
products it is more than obvious that our
the chemical synthesis consists of several
lation and set specifications to reach the
“time to market’’ while we are facing an
customers have a great benefit with all
synthetic steps and a final crystallization
goal. Since in the beginning the API was
increased price pressure? Have you ever
the services we can offer.
step to yield the API in the desired quality.
supplied by the customer the charac-
thought to bridge the gap between the
terisation and specification of the
drug substance and the drug product
future material was done by Sieg-
development cycles by their integration?
fried. After development of the
Did you always optimize the API and the
formulation and a short stability
DP development, but you never thought
screening of the best formulation
about combining these? If not, take a sec-
• Intellectual property, patents / contracts
• Regulatory affairs (DMF,CEP, Drug
product dossiers)
• Clinical / Toxicological aspects
• Strategic raw material sourcing
ager for all aspects of the project.
Our one stop concept was proven many
times resulting in the development and
commercialization of many compounds.
If additional support or special expertise is
and S
co cal
m e
er
development services brings even
sulting in the reduction of complexity:
• One-Quality-System Approach:
ly
ca l
Clini supp
al
materi
more benefits to our customers re-
We develop
your business
AP
The integration of the API and DP
t
en
world.
m
op
audited partners and experts around the
AP
ID
ev
el
n
ti o
up alisa
ci
excellent relationship to experienced and
IC
ha
rac
terisa
tion
needed in any case, Siegfried maintains an
One QA and QC responsible for all
Drug Product
development
aspects of the project.
• Under-One-Roof Concept: Short and
quick ways for information and mate-
the final formulation and pack-
ond and we will convince you about the
aging was selected and up front
advantages of Siegfried’s One Stop Shop
stability batches for clinical support
for integrated drug substance and drug
were manufactured. The final specification for the API (impurity profile,
PSD, polymorphic form) was set and the
For many years Siegfried is a well known
API development department started to
and experienced partner for pharmaceu-
develop the API for future production. The
tical companies around the world. Sieg-
Why
g
API from Siegfried was tested against the
fried is not only an established service
at one site or even in one building.
time and money on the time and
starting material supplied by the customer
provider in the field of chemical contract
cost
develop-
– no significant difference could be ob-
development, manufacturing of chemical
analytical set up for all aspects of the
ment approach. Join the group of our sat-
served. As final confirmation a test batch
intermediates and active pharmaceuti-
project. No additional cost for analyti-
isfied customers and try it out: The One
of drug product with the new Siegfried
cal ingredients, but Siegfried has also an
cal transfers and / or cross validations.
Stop Shop for partners in the pharma-
API showed the desired quality.
extensive and successful track record in
• One-Analytics Approach: One
• One Project Management: Single
point of contact and one project man-
intensive
i
separated
n
DP
development
product services has to offer.
rial flow. All departments are located
loos-
We develop your business by bridging the gap
API
development
API
Characterisation
ceutical industry. Seamless chemical and
the development and manufacturing of
In principle drug substance (API) and drug product (DP) development are based on different core
pharmaceutical development.
drug products. Siegfried has a tremendous
competences and technologies, but both disciplines share one common interface – the API.
From left to right:
Enno Schweinberger,
Quality Assurance Drug Products
Till Röhrich, Development Drug Products
Regina Thiergardt,
Development Drug substance
Thomas Müller, Business Development
coating of API to cover unpleasant colour,
•Process safety – assessment of ther-
odour and taste. Another case is the addi-
mal process safety with calorimetric
can be offered in a GMP area:
tion of surfactants or polymers (e.g. PVP,
experiments (RC1, DSC …) prior to
• Powder Blending
cyclodextrins, resins) to increase the solu-
scale up
•Wet Granulation with High Shear
bility in physiological fluids (e.g. gastric or
• Parameter screening and design of
intestinal fluid). To find the best solution
during pre-formulation phase a tight cooperation between chemists, analysts and
scale (100 g) to pilot scale (max. 35 kg)
Mixer
experiments (DOE) by means of parallel
• Fluid Bed Spray Granulation / Drying
synthesis
• Roller compaction
• Critical process parameters and
• One-pot Granulation
drug product developer is mandatory for
proven acceptable ranges based on
• Pellet Extrusion and Spheronisation
an efficient performance.
a quality risk analysis
• Tablet compression (also mini tablets)
•Reaction Kinetics: measuring of
Our capabilities in a nutshell:
• Coating (Granules, Pellets, Tablets)
reaction conversion by online Raman
spectroscopy and reaction calorimetry
•Hard Capsule Filling (Granules, Powder,
Pellets)
• Microreactor technolgy
Drug substance development can offer.
Siegfried strategic is intended to strength
en the capabilities in the combination of
Analytical
for
API and DP development and commercial
opment of APIs and key intermediates
API and drug product characterisation
supply. Initiatives are currently pursued
from gram-scale to tons yielding in
include, but are not limited to: Infrared-
to broaden our technology platform for
scaleable and robust processes which
and Raman spectroscopy, NMR, DSC /
other dosage forms and technologies e.g.
are fit for process validation and
DTG, Particles size distribution (Helos &
sterile products (injections) and eye drops.
commercialization.
Malvern), Residual solvents, Bulk / Tapped
Also an area for handling and develop-
•Process research and process devel-
methods
However, the work for the chemists is not
development times early testing of an API
the Biopharmaceutics Classification Sys-
yet finished, hence the formulation de-
for a drug product is done in parallel with
tem BCS II and are characterized by a
• Evaluation of new synthetic routes
density, Flowability, x-ray (with external
ment of formulations containing high po-
velopment is strongly depending on the
the form screening of the API. The impact
low solubility and a high permeability.
• Scale-up and pilot services.
partner), Dissolution testing, Stability /
tent drugs is under evaluation. The portfo-
physical characteristics of the API. These
of physical API characteristics on dissolu-
The solubility of an API can be improved
Compatibility trials, HPLC (NP, RP, chiral)
lio of technical assets in production will be
physical properties have a strong impact
tion behaviour or on process ability (e.g.
by changing the physical characteristics
Focus areas
for Assay, Purity, Chiral Purity, Dissolution,
enhanced by investments in micronization
on the manufacturing process and the dis-
blending, flowability, compress-ability) can
(e.g. salt, Particle size) and / or by its for-
•Handling of high potency compounds
Water content (K.F) and Loss on drying,
technology.
solution / absorption behaviour of the final
be tested at an early stage of develop-
mulation to a drug product. Since the
with an OEL = 10 to 1.0 µg / m3 on lab,
Photo stability testing according to ICH
drug product. The characterisation and
ment and helps finding the best set of
physical properties of an API can only
pilot and commercial scale
Guideline.
specification of the API salt form, crystal
specifications for the API. Siegfried is also
be optimized to a certain point the drug
•Polymorph screening: assessment
form, polymorphic form etc. have to be
experienced in the co-processing of API’s
product formulation is getting more and
of relative stability of polymorphs /
done carefully at an early stage in chemi-
(e.g. spray drying with polymer to pro-
more important. An integrated and seam-
pseudo-polymorphs
cal development to speed up the process
duce a solid solution) and testing for their
less cooperation between API and DP
for pharmaceutical development. Inte-
improved solubility. Our technical tool box
development is essential to discover the
grating and managing this interface well
compromises also all analytical testing
will save you precious development time
for the characterisation and screening of
and consequently conserve your project
budget.
The interface between API and DP development is bridged by the API characterization. A deep knowledge and understanding about salt and polymorph screening
with the corresponding analytical identification and characterisation is essential.
Two main reasons are the driver for the
API characterization: The protection of intellectual property of all possible salt and
polymorphic forms by patents and the
discovery of the most stable and effective
form. Siegfried has all capabilities and the
knowledge to guarantee the seamless API
and DP development by the integration
of the development cycles. To speed up
Another positive aspect for our customers benefiting from the one stop shop
concept is the cross functional team of
Drug product (DP) devel-
experts. Beside the specialists from the
opment department can offer a broad
chemical, the analytical and the drug
of reproducible, economic & ecological
range of oral, solid dosage forms for Imme-
product departments, the project teams
best and most cost efficient solution. In
effective crystallizations for scale up &
diate, Sustained or Modified release. (e.g.
can integrate more experts on an as
many cases the formulation of the drug
validation (incl. filtration, drying,
Granules, Tablets, Pellets, Hard gelatine
needed basis. Siegfried can extend the
polymorphs and salts of API’s:
product can cover disadvantages of the
milling, blending parameters)
capsules). Following technologies from lab
services in the following areas:
From our experience most APIs belong to
API. One example is the encapsulation or
•Crystallization techniques – design