AFGHANISTAN. Basic health concerns like acute respiratory infections and diarrhoeal diseases
Welcome to NNE Pharmaplan’s offering
cata-logue ‘What we do’ – a catacata-logue about how
we help our customers improve people’s
lives around the world.
Our reason for being is ‘Engineering for a
healthier world’. We cannot claim to save
lives or cure diseases. We do not produce any
medicine, but we put all our engineering and
consulting capabilities behind the companies
that do – our customers. And by supporting
our customers, we play our part.
Our customers work with us because we are
born out of their industry. Over the past 80 years
we have matched technical knowledge with
industry experience and worked out simple or
complex solutions according to our customers’
needs.
We trust you will be inspired and find numerous
examples of how we can help address many
of the challenges our customers face in everyday
working life.
That’s what we do!
Best regards
Part I Segments and offerings
17 Biopharmaceuticals
18 Biotech
26 Sterile & aseptic
37 Vaccines
45 Pharmaceuticals
46 Active pharmaceutical ingredients
52 Oral solid dosage
59 Medical devices
60 Medical devices and drug delivery systems
67 Industrial biotech
74 GMP compliance
84 Sustainability & environment
92 Containment & cleanroom
100 Logistics and facility layout
108 Laboratories
114 Manufacturing information systems
120 Performance and organisation
Part II Working with us
130 A healthy decision platform
132 Fast and flexible projects
134 Intelligent revamps
136 Reliable execution
138 Efficient sourcing
140 Pure knowledge
143 NNE Pharmaplan offices
144 Extended content
146 Keyword index, categorised
148 Keyword index, alphabetised
Today’s surgical patient faces a number of risks including medical errors, aggressive bacterial infections and after-surgery
Engineering for a healthier world
With global reach and local knowledge and
an emphasis on being close to our
custom-ers, NNE Pharmaplan delivers tailored
solutions based on the idea of engineering
for a healthier world.
Through new and innovative products, the
pharma and biotech industries make the world
a healthier place.
At NNE Pharmaplan, we focus on the pharma
and biotech industries, and our mission is to
contribute to a healthier world through the
services we deliver to our customers. When we
deliver consultancy or projects, we help bringing
products faster to market, decreasing the overall
cost of production and ensuring patient safety.
We share our customers’ commitment to
improving the lives of patients everywhere.
And as the pharmaceutical industry evolves, it
constantly develops new products, technologies
and business practices. We take pride in staying
on top of these issues:
•
We are dedicated to the industry – more
than 97 percent of our revenue comes
from pharma and biotech companies
•
We are dedicated to our customers – more
than 80 percent of our turnover is repeat
business
•
We are close to our customers – globally,
locally and often on site
•
We play a major role and are very active in
professional societies for the pharmaceutical
industry, such as ISPE, PdA, ECA and others
•
Most importantly, we are committed to
help-ing our customers realise successful projects
Listening to our customers
We aim at understanding our customer at all
levels to ensure our overall strategic development
matches yours and that our services meet your
business drivers and not just our contract. We aim
to proactively learn about the process, conditions
and user requirements for your individual projects
and we listen to your directions and feedback in
close, daily dialogue during projects.
We are not perfect, but we are always striving
to increase our knowledge and awareness. So,
if you ever feel that we’re not living up to these
goals, please tell us – we will listen.
Customer satisfaction
We measure customer satisfaction on nearly
all projects – and we set very ambitious targets.
In fact, customer satisfaction is a mandatory KPI
in all NNE Pharmaplan units, and it’s measured
and reported on a monthly basis to our Executive
Management. Our customer satisfaction
meas-urements include cooperation, delivery and
professional quality.
Long-term relationships
We build customer relationships that go far
beyond the individual project. Establishing an
on-going dialogue with our customers is more
important than winning a new project. We value
the small projects that make our customers’
daily life easier just as much as we like the large
greenfield projects.
We wish to maintain a strong relationship with
the individuals who are working with our
solu-tions and we endeavour to ensure a globally
consistent approach – no matter where in the
world you work with NNE Pharmaplan.
10 – INTRODUCTION Project references Offices (Cambridge) (Kinsale) (Morrisville) (Berwyn) (Bad Homburg) (Selangor) Boston Cork
Research Triangle Park
Chartres Basel Philadelphia San Francisco Moscow Tianjin TEDA Kuala Lumpur Bangalore Noida Stockholm Uppsala Lund Shanghai Lyon Copenhagen Kalundborg Hillerød Guangzhou Brussels Montreux Paris São Paolo Frankfurt
Project references Offices (Cambridge) (Kinsale) (Morrisville) (Berwyn) (Bad Homburg) (Selangor) Boston Cork
Research Triangle Park
Chartres Basel Philadelphia San Francisco Moscow Tianjin TEDA Kuala Lumpur Bangalore Noida Stockholm Uppsala Lund Shanghai Lyon Copenhagen Kalundborg Hillerød Guangzhou Brussels Montreux Paris São Paolo Frankfurt
12 – INTROdUCTION
develop, establish, improve
NNE Pharmaplan’s expert consultancy and
engineering services can help you maintain
optimal production processes.
The daily life in pharmaceutical production
is both interesting and challenging: do you
establish the capacity yourselves or buy it? Or
do you contract production or development? At
what scale do you work? do you invest for the
long haul or wish to minimise the immediate
spending? What technologies do you deploy?
Are there new opportunities that you should
consider? In short, how do you implement your
business strategy of today – or tomorrow?
Very few operational facilities stay as they
were designed and built. With the operational
experience comes the possibility of continuous
improvements. New production technologies or
product developments open up for further
opti-misation – addressing the different bottlenecks
in the production. Mergers, consolidations,
expansions, product transfer, contract
manufac-turing, regulatory actions or new regulations are
all examples of changing conditions that require
adaptations to new products or processes.
The product and the process
The focus of all these efforts is to ensure and
maintain optimal production processes. NNE
Pharmaplan focuses not only on the general
engineering processes involved but also on the
particular technologies and business conditions of
each segment. We know the differences
be-tween the various pharma and biotech segments
and their products and processes and build our
services on broad product and process know-how
and experience.
Supporting functions
Yet, pharmaceutical production is not only about
products and processes. The supporting functions
have to be in good shape as well. Compliance
and sustainability are critical factors requiring
special attention, critical utilities, environmental
measures, safety, logistics, quality control and
information systems. And last, but not least, the
organisation and the people are vital.
Offering map
Our offering map to the right gives an overview
of all our fields of expertise – process as well as
supporting functions. The offering map presents
our core offerings. We have dedicated specialists
in each field and up to date know-how as well
as vast experience to base our solutions on.
In the following chapters, we address core
chal-lenges in each of these areas and show how NNE
Pharmaplan can contribute to the development,
establishment and improvement of your product
manufacturing.
INTROdUCTION – 13
... and for the entire manufacturing life cycle
develop an optimal
approach to achieve
the required production
capabilities
Augment the
efficiency and quality
of ongoing operation
through optimisation
and support
design and establish
facilities all the way
to efficient and
compliant service
Develop
Establish
Improve
Biopharma-
ceuticals Vaccines ceuticalsPharma- Medical devices Industrial biotech
Offerings for all pharma/biotech segments
Biotech Vaccines pharmaceutical Active ingredients
Oral solid dosage Sterile & aseptic
GMP compliance Sustainability & environment
Containment & cleanroom Logistics and facility design
Laboratories
Manufacturing information systems Performance and organisation
Industrial biotech Medical devices
and drug delivery systems
Our service philosophy
Passionate and committed to working in your industry
Valuable insight Consistent and fast execution Superior outcomes
We deliver
Highlights
Fast track Multiproduct revamps and quality by designRisk-based approach
Turnkey facilities
– IV, vaccines Single-use technology Automation and IT
Cost-effective operation
and facilities Personalised drugsand treatment ASTM E2500 verification Studies • Feasibility analyses • Conceptual designs • Master plans Ramp-up • Production ramp-up • Training • Process validation, cleaning validation Support services • Sourcing • Cleanroom testing • Troubleshooting • Revalidation • Specialist staff • Single use • Quality by design • Site selection design • Architecture • Automation • Construction management • Commissioning • Quality • Risk management
• New products and technologies • debottlenecking • Automation upgrades • Fast upgrades with minimal
interruption
Analyses
• Technology transfer • Manufacturing sciences • development support • design for manufacturing
Solutions
• Automation and IT solutions • Cleanrooms
• Turnkey facilities • Process modules
Operational excellence
• Process optimisation • Output, uptime and cost improvements
• Lean & Six Sigma • Change management • Leadership and people
development
• Continuous improvement methods
USA. The number of people with haemophilia in the United States is estimated at 20,000.
About 400 babies, mostly males, are born with haemophilia each year.
Biopharmaceuticals
The immense growth and rapid
develop-ment in the biopharmaceutical segdevelop-ment
pose multifarious challenges. At NNE
Pharmaplan, we see a wide array of
new and interesting opportunities.
With their remarkable therapeutic benefits,
biopharmaceuticals have the potential to
improve patients’ lives all over the world. a
number of previously incurable diseases can
now be cured, or at least treated. the life
expectancy and quality of life have improved
for patients with diseases like multiple sclerosis,
cancer and arthritis. and more and more rare
diseases can be addressed with increasingly
specialised drugs.
Biopharmaceutical activities are on the rise in
many pharmaceutical companies – in fact
bio-tech and vaccines have been a major driver of
the wave of mergers and acquisitions in recent
years. and we expect the changes in
biophar-maceutical manufacturing to continue. old as
well as new large-molecule products are being
produced in increased titers and often decreased
batch sizes.
at NNe pharmaplan, we see the new
manufac-turing paradigm of combining new single-use
biotech technology with proven stainless steel
solutions as a challenging and interesting area.
actually, new products produced in smaller
volumes will ultimately develop into personalised
drugs. New, smaller and more flexible
multi-product facilities are becoming popular as
adapt-ability becomes a business plan prerequisite and
the significant capital costs of first generation
facilities become prohibitive. and personalised
medicines that target smaller patient groups are
uniting with single-use technology.
Biopharmaceuticals and aseptic processing were
the roots of our business and have been our
core expertise throughout the years.
18 – Biotech
Biotech
Cost effective productivity is always a top
priority, and whether it requires
establish-ment of new facilities or improveestablish-ment of
existing production, NNE Pharmaplan can
deliver the optimum solution.
Whether your product is a novel cell or
gene-based therapy or an established therapeutic
protein, the driving forces are competition,
flexibility and efficiency: competitive produc-
tion of mature biotech products including the
generic versions, flexibility to use existing
capacity for new or modified products, and
efficient pilot launch and small-scale produc -
tion for bringing new products to market.
While this optimisation can ensure rapid
production for clinical trials and boost
produc-tion capacity for one or more products, the
underlying challenge remains the same:
cost-effective production is required in order to bring
biopharmaceutical therapies to the world.
at NNe pharmaplan we are at the forefront of
knowledge in this exciting journey and our
project and customer portfolios represent global
best practices and landmark facilities. We are
leading when it comes to fast establishment of
new facilities, but we are equally resourceful
when your issue is optimising existing facilities.
Whether your facility requires de-bottlenecking
for a high-titer process, transition from single to
multiproduct capability, a global automation
strategy for a multivendor skid installation or
you simply need to establish a cost-effective
operation with novel process technologies, we
deliver a competitive edge that provides
in-creased productivity.
over the years, NNe pharmaplan has been an
integral part of the biologics revolution. From
the first insulin treatments to today’s
break-through technologies in gene and cell therapy,
tissue engineering and transgenic products, NNe
pharmaplan continues to deliver innovative and
creative solutions for our customers.
NNe pharmaplaN services Featured iN this chapter: Getting a high throughput development facility at low cost Building versus buying
Delivering high stakes revamp Flexible, fast, modular
Get strategic with single-use technologies Next generation biotech facilities Single-use technology catalogue Yield increases create new bottlenecks
200 percent increase through bioprocess optimisation Automated approval of chromatography runs Plasma fractionation
Challenges in advanced therapy facilities
Powerful example of modern modular
engineering and design
the candidacy of the Novoseven
®facility was
based on the following features:
•
designed to support the fast-track modular
approach
•
met an undefined demand for a life-saving
drug by including a modular designed,
expandable production area
•
characterised by simplicity and transparency
to ensure a safe working environment
the facility was chosen among 28 outstanding
pharmaceutical facilities from five continents.
the nine-member judging panel chose the
Novoseven
®plant as the winner for several
reasons: “creative design within a super
fast-track timeline for project execution,
applica-tion of modular engineering for greater control
and flexibility, and dramatic and pleasing
architectural features throughout the facility.”
the plant is now helping Novo Nordisk lead the
way in breakthrough medicines for the
treat-ment of haemophilia, as well as inspiring the
construction of similarly innovative facilities.
Groundbreaking plant received
the Facility of the Year Award 2005
When Novo Nordisk decided to build a new
facility dedicated to the production of
haemo-philia medicine, the company turned to NNe
pharmaplan for its innovative approach to
design and engineering. the plant needed to
be an integrated facility for mammalian cell
fermentation, recovery and purification.
Demonstrating global leadership
the facility was built as a fast-track project in 18
months using modular engineering – including
comprehensive parallel construction of
inde-pendent process modules and off-site testing of
each process module. the result was a
ground-breaking facility that initiated a modular
engi-neering approach with customised solutions for
the life sciences industry.
once the facility was complete, it soon became
a candidate for the prestigious Facility of the
Year award. the award is given to a
pharmaceu-tical manufacturer with a facility project that
demonstrates global leadership – through
cutting-edge engineering, innovative new
technology or advanced applications of existing
technology.
20 – Biotech
BuilDiNG vErSuS BuYiNG
Bringing a biopharmaceutical product to market requires careful consideration of whether to build or buy manufacturing capacity. the timelines involved in building a facility are still so long that for most bio-pharmaceutical products it is necessary to start construction before final clinical proof of the therapeutic is available. otherwise, you run the risk of not having sufficient capacity for market entry. on the other hand, the large capital investment may prove premature in case the clinical proof does not materialise. the alternative is to buy capacity at a contract manufacturing organisation (cmo) well in advance of market entry. this ensures capacity at a premium but still defers the larger facility investment.
this classic building versus buying decision was at the centre of our concept study for a company with a promising therapeutic protein in clinical phase three development. Based on our reference library of fast-track facility projects, we estimated the realistic construction phase for the building scenario (with a buffer interval) and could then deter-mine what up-front, low-capital investment activities could be in place before clinical
GETTiNG A hiGh ThrouGhPuT
DEvEloPmENT FACiliTY AT low
CoST
We recently worked with a customer on an initiative to expand development capacity. the customer was having trouble meet-ing demand when their pipeline began to rapidly expand after they released a series of blockbuster biopharmaceutical drugs. our customer wanted to achieve high through-put development capacity to support a
proof was available. Based on these activities and our reference timeline, our customer could compare the building and buying scenarios in order to get an overview of their options.
our final, optimised scenario was a hybrid where buying capacity was employed as the first phase strategy in order to build
cal trials. We used economic considerations, room layouts, workflows and 3d configura-tion of process suites to support the decision process.
single-use technology became a more inte-gral part of the strategy because of its advan-tages in retrofit scenarios and its reduced demands on area and installations. in the last design iteration, we used a permanent 3d configuration of single-use processing that showed involved user groups how the activities could be accommodated in the retrofitted facility.
as the scope progressed more to a single-use technology solution, it became clear how the goal of high throughput development capac-ity could be realised in facilities that other-wise would not have had sufficient space. the combined effect resulted in a project that progressed much faster, had much more capacity, required less capital investment and made fewer overall interruptions on the production site.
up sufficient storage to cover the gap in capacity until building production capacity was initiated after clinical proof. in this way our customer obtained a production strategy that relied on a low level of capital invest-ment while still ensuring sufficient and timely capacity for market entry well beyond the launch phase.
growing number of products projected to reach the market in the near future. a new development facility was the ideal choice, but the budget was limited, so to get the most out of their funds and organisational capacities, the expansion had to be done in several buildings on the same site.
We worked with research, development and production user groups to align process tech-nology across functional areas to seamlessly scale-up the production of material for
clini-FlExiBlE, FAST, moDulAr
at NNe pharmaplan, two of our key con-cepts are fast-track and modular engineer-ing. a great example of this is a turnkey facility we built in malaysia. the facility, con-structed in prefabricated modules, produces mammalian cell-based therapeutic proteins and monoclonal antibodies.
We chose a modular design in order to meet the main requirements from the customer. one of the customer’s success criteria was high flexibility as the customer wanted to be able to grow according to market and industry demands. another requirement was cGmp-compliance enabling the customer to adhere to strict international standards and provide products and services globally. so we installed and pre-tested the equipment and systems in europe in a controlled environ-ment before shipping them to malaysia. in addition, the customer had a very short timeframe, which NNe pharmaplan met by installing the modular facility on site within six days.
since the facility is located in a complex that also houses the company headquarters and laboratories, another advantage of this
modular approach was that the construction of the facility caused no major disruptions to the company’s other operations.
today, the facility is our customer’s flagship. it became malaysia’s first Gmp-compliant biotech facility – and took our customer to the forefront of the country’s biotech sector.
DElivEriNG hiGh STAkES rEvAmP
When one of our customers needed to rapidly transform one of its cell culture facili-ties from being a single-product facility to a multi-product production facility, they looked to NNe pharmaplan to design, engineer and manage the entire revamp project. this major overhaul affected the site infrastruc-ture, facility expansion and upstream and downstream processes – and it involved a team of nearly 100 engineers.
the deadline for the start of the facility’s multi-product production was inflexible and the existing production needed to meet output goals before the shutdown for recon-struction. so the clock was ticking from day one. Biotech revamp projects come with the added complexity of sterile manufacturing, cleaning and sterilisation in place (cip, sip) and automation requirements. and the new design also needed to reflect experiences from the existing production translated to the multi-product case.
our modular approach was mandatory in this complex project as parallel execution on almost all fronts was necessary to meet the challenge. the approach allowed for decou-pling of activities so that inevitable changes had only minimal impact on other areas. as the project progressed, it became clear that the scope was broader than anticipated in the front-end study. additional upgrades were added and our initial capacity gap ana-lysis revealed that the black and clean utility systems would need to have more users and larger capacities than first assumed. an effective, detailed design phase enabled us to carry out a fast and efficient pit stop phase that lasted less than six months. in this period more than 18,000 welds and over 800 instruments were installed along with the process equipment. With a scope that expanded by 50 percent after start-up and an extremely compressed time schedule, we were able to deliver the project on time and on budget with 550,000 accident-free hours of hard work.
22 – Biotech
NExT GENErATioN
BioTECh FACiliTiES
When you’re planning to launch new bio-pharma products, you need to balance risk, cost and time and deal with issues such as:
• deciding whether to build a new facility
or upgrade an existing one
• achieving flexibility for multiple products • establishing a layout that guaranties
optimal utilisation of the process areas
• meeting cGmp requirements to be able
to produce in the existing facilities
• introducing single-use technologies to
reduce investment cost and simplify installation
GET STrATEGiC wiTh
SiNGlE-uSE TEChNoloGiES
single-use technology is on track to revolu-tionise biopharmaceutical production. the advantages are many. investment and vari-able cost reductions are the most commonly cited benefits, but they represent only one part of a strategically important decision in production technology.
our position on single-use versus stainless steel is that a structured and in-depth evalu-ation of technologies and their implicevalu-ations is necessary, since the drug manufacturer essentially shifts responsibility over to the single-use suppliers. Whether the issue is product quality, operator safety, production capacity or facility design, our experience shows that the scope is always broader than first envisioned and that our structured ap-proach will benefit any implementation.
single-use technology introduces new front-end considerations such as process compat-ibility, leachables/extractables, film selection, back-up suppliers, waste management and more – and the manufacturer’s Qa system is extended to cover not only raw materi-als but materi-also production technology. at NNe pharmaplan, our stage gate model approach to the strategic use of single-use technology allows you to capture these critical aspects of this new production paradigm at the right level. and our model will benefit your entire facility and all the business functions involved in your manufacturing operation.
We can quickly evaluate cost advantages based on a modular engineering approach. By evaluating various process designs in terms of cost – as a function of the percent-age of process equipment that is installed as single-use technology – we are able to develop trend curves for cost advantages of single-use technology in a typical bioprocess
40 35 30 25 20 15 10 5 0 0 20 40
% Single-use process modules Project-specific trend curve
% C os t re du ct io n re la tiv e to t ra di tio na l 60 80 100
scope. You can then use the trend curves to quickly forecast the savings for alternative configurations. this type of fast approach can give you a 360° evaluation of single-use technology’s impact on a facility area, hvac, process equipment, utilities and automa-tion costs without getting caught up in the details too early in the process.
For a customer in need of a new greenfield mab facility, we reduced the installation scope drastically based on an operation scheme where the process followed a natural flow in time and movement, solu-tions prepared just-in-time into single-use bags, rolled across process corridors and parked at bays for through-the-wall transfer to process rooms. the result was a facility design based on lean workflows through optimised locations for solution prepara-tion and storage, minimised transport and staging distances and appropriate segrega-tion between process steps, people and product.
in another case, our customer’s legacy facility needed to be upgraded to support viral clearance claims in downstream processing for introduction of a new product in this case the team used fast 3d models to build design variants and evaluate their conse-quences for the process suites – the models were also used for manufacturing teams to verify the concept. the conceptual design package included production scheduling, room layouts, work flows and only minimal structural changes to the existing facility. We also obtained a reduction in variable costs in the range of 10-20 percent and an optimised buffer preparation and storage work flow.
SiNGlE-uSE TEChNoloGY
CATAloGuE
in a market where new products and new consolidations frequently surface, a structured approach to technology evalu-ation is necessary to ensure an objective evaluation. at NNe pharmaplan, technology implementation expertise and hands-on experience with process technologies are trademarks of our process group, which has collected information in an evaluation format that rates technologies and companies with respect to technical approach, process experiences and also strategic considerations, such as geographical locations and number of production sites.
several of our customers have made strategic single-use technology decisions based on our technology catalogue, and we have audited suppliers and tested the technologies. We maintain excellent supplier relationships in
order to get the latest information about new developments. By a series of workshops, we will take you through and evaluate all the technology/supplier combinations. together, we’ll then select the preferred technologies
YiElD iNCrEASES CrEATE
NEw BoTTlENECkS
You need to fit new high-titer mab proc-esses into an existing facility. But your facility was designed and built for a legacy product that didn’t feature these high yields. ad-vances in cell lines, media composition and bioreactor control strategies have resulted in significantly increased upstream yields – so now it’s the downstream processes that are the bottleneck in your mab facility. What do you do?
if you have a new business case that covers multiple new processes with a wide range of yields, it might exceed the scope of your facility. it then becomes a challenge to fit a multi-product process into a facility that was built for a single product, without imposing constraints on the facility’s ability to accom-modate future, yet unknown processes. the problem is that increased yields will most likely lead to increased buffer consumption, process pool volumes and cycle times. in one large facility project, we worked inten-sively with a customer who was facing this very challenge. But they also had the added difficulty of a building that was already constructed, meaning that certain limitations on infrastructure and layout were already
downstream design that could do the job without being too excessive with respect to installation and area demands. our modular engineering approach gave the customer the flexibility to actually go back and reintro-duce the legacy process into the facility in combination with the high-titer processes – without causing major changes to the layout or support systems.
present. so we performed a detailed flexibil-ity study based on assumptions about likely process parameters for reference processes and their implications for process operations and support system dimensions.
after a series of downstream workshop sessions, we optimised and value engineered the facility’s design and ended up with a
for further testing in a pilot plant scale. From this structured approach, we can prioritise the testing effort so that your pilot plant capacity and resources will be applied in the most optimal manner.
24 – Biotech
200 PErCENT iNCrEASE
ThrouGh BioProCESS
oPTimiSATioN
When building a greenfield biotech facility, capacity analysis and time scheduling are crucial as the entire facility design relies on them. these steps can also help minimise the impact on your existing production or facility start-up, so they are especially critical when you need to revamp your facility to increase capacity or to accommodate a major process change.
as process development usually continues while a new facility is being engineered and built, changes are an inherent feature of biotech facility projects. this complexity comes with the biotech territory and changes in yields, retention times, chromatography capacities or cip procedures can lead to situ-ations where the production target cannot be met or the facility not fully utilised. this situation ultimately results in your facility not being able to support the treatment demand for a serious illness. But quickly setting up a team to provide a well-informed overview of
AuTomATED APProvAl oF
ChromAToGrAPhY ruNS
purification of bioprocess streams by column chromatography is a key step in the manufacturing of many biopharma-ceuticals. But this process step is subject to variations that originate in the differences in bed height, resin lifetime, fouling, packing efficiency, etc. at NNe pharmaplan, we have a great deal of experience with high resolution and separation chromatography processes in industrial Gmp settings. apart from design, specification, installation and qualification of equipment, we can also design and implement automation and batch execution systems for purification processes.
in a recent project, our customer needed to ensure that column runs were approved in a timely manner and on an unbiased uni-form basis in a 24/7, large-scale operation. they wanted to maximise batch throughput and focus their limited operator resources on the most critical tasks. our automation experts saw the potential for introducing an automated approval algorithm that would
bottlenecks, solutions and consequences can ensure the success of your project.
over the past 20 years, we have made over 100 detailed capacity analyses for our cus-tomers. today our toolbox includes in-house developed applications as well as Biosolve and superpro/schedulepro, but deep process knowledge and facility understanding are the real core tools. We are constantly improving our toolbox to offer you the best optimising services for:
• Batch size and dividing in sub-batches
make the automation system approve all typical column runs without further action and would only notify the operators in case of exemptions.
in this setup, we used historical data to programme the algorithm to recognise atypical runs and only accept chromatog-raphy runs that fall into the normal range. the algorithm identifies atypical events by comparing durations of up to 20 segments in the chromatography charts – this is actu-ally optical density as a function of flow value, not time, thus making this curve check independent of time.
the implementation of the automated approval of chromatography runs has ensured that the customer’s atypical runs are never introduced to the product pool and that operator time is focused on these atypical runs only. and that’s not all. some of the other automated chromatography applications include individual column load calculation based on titer and bed height and calculation of gel performance to determine gel lifetime and regeneration events.
• Batch execution including defining cycles
at chromatography steps
• optimised gel load • tank sizes
• Buffer consumption • utility consumption • cip of equipment
With the right tools, your revamp project can increase capacity by more than 200 percent in your existing building shell. our optimisa-tion projects have produced capital invest-ment savings of up to 29 percent.
1800 1600 1400 1200 1000 800 600 400 200 0 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 Year
Capacity and production need Capacity and production need
kg p ro du ct kg p ro du ct 1800 1600 1400 1200 1000 800 600 400 200 0 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 Year
PlASmA FrACTioNATioN
Blood fractionation companies live in an interesting time: an increased focus on rare diseases, growing demand, and decreased plasma availability, competition with recom-binant products, patient safety, and complex regulations are all putting pressure on the blood plasma fractionation segment. manufacturing therapeutic proteins by blood plasma fractionation requires many purifition steps and process vessels. this makes ca-pacity expansion prohibitive in terms of cost and space. at NNe pharmaplan, we have gained extensive expertise from working with 70 percent of the leading companies within the blood fractionation industry. as an example, we have supported a major plasma fractionation manufacturer who wanted to double their production capac-ity by expanding an existing building. our engineers worked with the customer as part of a fully integrated project team to deliver a design that could achieve this goal – and meet the company’s budget and timeframe.
the project team came back with a series of design iterations and investigations that sup-ported how single-use technology and in-line dilution of concentrated buffers could reduce costs in the multi-vessel, multi-purification steps process.
inside the facility, we also helped improve working conditions by decreasing manual operations such as vessel cleaning and solutions preparation. By adopting this new production technology strategy, our cus-tomer was able to save significantly on the initially projected costs – and they also got an improved project timeline.
ChAllENGES iN ADvANCED
ThErAPY FACiliTiES
advanced therapies represent an exciting new segment in biopharmaceuticals. as the general trend moves away from ‘blockbuster’ drugs to more personalised drugs, gene therapy, cell therapy and tissue engineering can be seen as a subset with its own hurdles. it’s an attractive market, but it also holds a number of challenges. the financial issue is clear: the cost of a product typically increases as volume decreases so these therapies are relatively expensive and governments and
insurance companies are yet to provide clear reimbursement standards. performing clinical trials with a smaller, more specific patient population can be more effective, but it’s also more difficult to arrange. and manufac-turing poses a basic logistical problem – the therapy will need to be supplied to a small number of patients that are located globally, so the facility may have to include facilities for administering the therapy too.
at NNe pharmaplan, we have worked on a number of projects within the field of advanced therapy so we can help you
overcome some of these obstacles. When one of our customers in south Korea had to set up a new production facility for cell therapy, they asked us for help based on our expertise in process technology for patient-specific cell therapeutics and Gmp compliance.
the customer provides cell therapy for the regeneration of damaged heart tissue in the case of chronic or acute heart damage. the autologous cell therapy works by culturing the patient’s own stem cells in vitro at the production facility and transferring them to the damaged tissue area when a sufficient culture density is reached.
through a series of workshops, we delivered a facility design that took into account the customer’s special requirements for quality and their business case for advanced therapy medicinal products. one of the critical requirements for this kind of facility is to avoid patient-to-patient cross contamination. so we developed a flexible concept that included 10 production suites (class B) in the first project phase – and provided the customer the possibility to increase this to 30 produc-tion suites in subsequent expansion phases.
26 – Sterile & aSeptic
Sterile & aseptic
Aseptic and sterile processing is complex,
both in terms of technology and regulatory
requirements. We can help you identify
the best solution, taking into account all
relevant aspects.
contamination is a killer and the world of
fin-ished drug products is complex and challenging.
aseptic handling is essential for the integrity of
all pharmaceutical products and devices.
aseptic handling also adds a layer of
complex-ity to the pharmaceutical production processes
– from formulation and preparation until the
product is filled in its final container. traditionally
this has been done in a conventional cleanroom,
but today a number of technologies are
avail-able (isolator, raBS (restricted access barrier
systems), single-use systems and sterile transfer
of materials) to ensure a high sterility
assur-ance level (Sal). in the inspection field, vision
system techniques further enable the industry
to achieve high productivity and high product
quality.
Other steps in the process, including labelling
and packaging, are also undergoing rapid
de-velopments. Fuelled by counterfeit complaints,
labelling and traceability requirements are on the
rise. and the implementation of efficient
logis-tics systems, including automated guided
vehi-cles (aGV) and automated warehouses, present
new challenges for the integrated operation of
facilities and the use of technology.
at NNe pharmaplan, we have deep insight into
aseptic and sterile fill and finish processes. this
includes our first-hand experience operating
in these environments, extensive knowledge
of regulatory developments, practical
experi-ence integrating the different technologies and
awareness of the industry’s most recent
develop-ments. We can advise you on the mix of
tech-nologies that makes the most sense financially
for your company. and we can help you balance
your investment costs, operational costs,
regula-tory requirements and risks.
NNe pharmaplaN SerViceS Featured iN thiS chapter: High-tech aseptic facility helps meet regulations and save costs EU GMP pushes the use of technology
Finding the right contract manufacturers Infusion solutions worldwide
Optimised formulation delivers capacity increase Complexity in freeze drying
Full-scale delivery of freeze drying isolator line
Wash and sterilisation – an integral part of aseptic operations Campaign filling – a more efficient way
Packaging challenges Inspection technologies Fighting counterfeit drugs
Microdosing – a new siliconisation technology Internal logistics and material handling Contamination – finding the root cause Single-use in filling operations: the future?
Operational excellence in design recognised
in 2009, hameln pharma’s sterile production
plant designed by NNe pharmaplan was
award-ed the prestigious international iSpe Facility of
the Year award in the Operational excellence
category.
For more than 50 years the German company
hameln pharma has been a specialist contract
manufacturer of parenteral solutions and
sus-pensions. hameln pharma’s activities involve the
manufacturing and marketing of liquid
pharma-ceuticals, primarily for hospitals and intensive
medicine.
New sterile production plant
NNe pharmaplan helped hameln pharma
estab-lish the 9,200 m² sterile production plant that
won the award for operational excellence. Well
before the engineering and construction phases,
hameln pharma contacted NNe pharmaplan in
order to set the qualification concept, conduct
a risk analysis and prepare the validation master
plan. NNe pharmaplan was also responsible for
reviewing and reworking the conceptual design,
the basic design, process engineering and
quali-fication.
the award jury highlighted the facility’s lean
production concepts, which were implemented
throughout the design and construction of this
facility. For example, the u-shaped structure of
the filling systems reduced traffic in the
high-est class of cleanroom, increasing the plant’s
productivity.
Significantly increased production capacity
the innovative, flexible sterile facility was built
and put into operation after a project time of
only 25 months at hameln pharma’s
head-quarters in hameln, Germany. the facility has
increased the company’s production capacity
significantly and created space for the
imple-mentation of innovative technologies.
28 – Sterile & aSeptic
FINdING tHE rIGHt
CONtrACt MANUFACtUrErS
investing in your own filling and packaging capacity may be a costly way to produce your final product. in a number of situations, contract manufacturing is a better option. NNe pharmaplan can help customers search for and screen contract manufacturing or-ganisations (cmO), and advise the customer in the selection process. Based on our many years of experience in the pharma and biotech industries, our global presence, our representation in numerous trade associa-tions and a list of customers from all over the world, we have a vast network of industry experts and contacts in the industry. in ad-dition to this, we have a number of reliable database sources to draw on.
We conduct each cmO search to find the company that can produce the exact product that you need. many customers will have very specific requirements for the cmO. criteria often include technical or compliance requirements, cultural and language-related considerations or which countries have ap-proved the cmO.
Based on these criteria we will present the candidates to you, pointing out their strengths and weaknesses, and making it as easy as possible for you to make the best choice.
We are also able to arrange visits and perform audits of the selected cmO to verify that it is in compliance with current Good manufacturing practice. Our auditors come from a background of regulatory authori-ties such as the iSO and the Fda, and also include people with experience of working in quality and production.
after the final cmO selection, we offer to help you with contract negotiation to ensure you get the best possible conditions for col-laboration with the cmO.
EU GMP PUSHES tHE
USE OF tECHNOlOGy
the eu Gmp’s new annex i, manufacture of Sterile medicinal products, emphasises in particular the process of freeze drying. the regulations require freeze-dried vials to stay in grade a conditions until final closing – giving rise to potential area classifications and operator interventions issues as well as
HIGH-tECH ASEPtIC FACIlIty
HElPS MEEt rEGUlAtIONS ANd
SAvE COStS
implementing a modern and efficient aseptic processing facility requires advanced knowledge of the available technologies – including their benefits and pitfalls – as well as thorough understanding of the regulations that govern the industry. this makes balancing the interpretation of current regulations with new technological developments a key challenge.
in a state-of-the-art, large-scale aseptic fill finish project in Japan we provided regula-tory and technological know-how to a cus-tomer to ensure the right choice of process technology.
Because the new fill finish plant will distrib-ute products to the world market, it must comply both with european, uS and Japa-nese regulations. But the customer had an
additional challenge: they operate in a very competitive market and so the entire project was cost-driven.
We helped the customer choose the best available technologies, including selecting restricted access Barriers (raBS) technology over isolators wherever possible. this resulted in significant investment savings. in addition, we designed the air flows to achieve the right air change level in the complicated room setup and used simulation software to create an energy-efficient yet fully compliant hVac installation.
Once these decisions had been made, we carried out conceptual, basic and detailed design and were responsible for the overall project management, including infrastructure and process automation. We also man-aged both the construction and the design qualification. after completion of the facility, we support the customer with start-up and optimisation services.
concerns for the environment, monitoring and vial integrity assurance.
all this means that you need to consider your technology carefully: is isolator technology necessary? Will restricted access barriers (raBS) be sufficient? do you need to auto-mate the loading and unloading of freeze dryers? and how will the different solutions affect your investment and operational costs?
INFUSION SOlUtIONS
WOrldWIdE
the manufacturing of pharmaceutical forms demands high standards when planning pro-duction facilities. even established pharma companies can benefit from an experienced, reliable partner.
NNe pharmaplan has completed more than 40 plants for the manufacturing of infu-sion solutions in more than 30 countries worldwide – including technology transfer for standard solutions.
Our expertise includes plants for the manu-facturing of infusion solutions and filling into various forms of primary packaging such as glass bottles, plastic bags and bottles (blow fill seal technology) ranging from 100 ml to 1000 ml, or pVc and polyolefin bags for irrigation solutions up to 5,000 ml.
OPtIMISEd FOrMUlAtION
dElIvErS CAPACIty INCrEASE
an integrated and automated formulation area can be the key to high throughput and consistent quality. designing and install-ing systems that can handle the diverse substances and amounts with accuracy, traceability and without interruptions require specialist knowledge and thorough proc-ess understanding to create the correct interfaces to steps further down the line and especially to the utility systems.
We offer our customers extensive know-how in infusion manufacturing technology, including:
• the generation and distribution of water
for injection (WFi)
• Solution preparation and storage • manufacturing bottles or bags • Filling bottles or bags • Sterilisation of the products • inspection and packaging
We also provide production manuals (stand-ard operating procedures) and quality control manuals as well as training of staff at a similar plant. and we prepare both standard infusion and plasma expander solutions and parenteral nutrition solutions (including fat emulsions).
the complexity of formulation and filling tanks is partially due to the intricate system of pipes leading materials to and from the tanks and the huge number of valves, con-nections, sampling points, etc. that are also part of the tank system. consequently, cleaning-in-place (cip) and sterilisation-in-place (Sip) of the tanks – specifically impor-tant due to the criticality of the formulation process – are complicated and very time-consuming. in fact, the time spent on cip/ Sip renders a machine capacity utilisation rate of only 30-40 percent for most formulation areas. Optimisation options include a more
flexible system with mobile tanks and off-line cip/Sip, where such a system is appropriate. due to the above utilisation rates, companies are often on the lookout for solutions that can improve efficiency to obtain shorter batch change-over time or reduce the cost of goods sold (cOGS). to NNe pharmaplan, the basis of optimisation is flexibility, thorough process understanding and industry-specific experience. We can challenge your produc-tion setup, equipment choice and flow in order to achieve a more flexible and efficient production setup.
For customers with many different prod-ucts and batch sizes, we have incorporated flexible systems with mobile tanks that can be taken in and out of the process and cleaned and sterilised away from the process to render the formulation area free for use with other tanks. companies with a narrow product range will often benefit from more integrated systems optimised with a number of tanks that fit the rest of the production line. Such systems can also have integrated computer and/or batch control. at NNe pharmaplan, we have implemented highly automated systems with integrated recipe control, raw material tracking, batch report-ing and even integrated data acquisition from different in-process controls like ph, temperature and others.
Our projects range from semi-manual to high-grade automation and our services from process engineering up to the supply of a complete plant on a turnkey basis.
30 – Sterile & aSeptic
WASH ANd StErIlISAtION
– AN INtEGrAl PArt OF ASEPtIC
OPErAtIONS
For pharmaceutical companies and hospitals involved in sterile and aseptic production, wash and sterilisation is a crucial part of ensuring that products live up to the require-ments for high quality and safety. having the right equipment to meet your needs and fit in with your existing process equipment is the cornerstone of any wash and sterilisation process.
Wash and sterilisation equipment includes washing machines, autoclaves and closure processing equipment (cpe). as opposed to washing machines and autoclaves, cpe can be used in interaction with isolator filling technology to process caps, rubber stop-pers, pitons and glass beads and feed them directly onto the isolator filling lines using aseptic containers without breaking the class a aseptic environment.
at NNe pharmaplan, we are experienced in designing and establishing wash and sterili-sation in complete pharma plants for active pharmaceutical ingredients (api) and aseptic production. We focus on the correlation between wash and sterilisation and other production processes such as filling, quality assurance and the utility areas, which helps us work out what to consider and who to talk to in order to achieve the best solution possible.
FUll-SCAlE dElIvEry OF FrEEzE
dryING ISOlAtOr lINE
at one of our customer’s facilities, the freeze dryer is connected to an isolator filling line. to keep the vials in the isolator environment, the vials are transported and loaded into the freeze dryer by an automated load system. the automated loading system is able to load the entire freeze dryer shelf by shelf in a con-trolled environment supervised by a Scada (Supervisory control and data acquisition) system. We worked with the customer to prepare the complete design and functional specifications.
after assembly at the vendor site, all func-tions were tested and the equipment was shipped to the customer’s site. due to difficult handling and building construction, the equipment was lowered through the roof into the production area. the weight of
COMPlExIty IN FrEEzE dryING
Freeze drying is one of the most complex processes in pharmaceutical and bio-tech production, and it poses numerous technological and regulatory challenges to manufacturers. technologically, the process is a challenge because many freeze dried materials are composed of multiple elements
the complete installation was more than 30 tonnes. in order to optimise the space in the cleanroom area, all the technical installations and the condenser were placed on the floor below the chamber and maintenance was thus removed from the production area. When the freeze drying cycle is completed, the chamber is automatically emptied by the unloading system that consists of a cart on rails embedded in the floor. the cart can empty an entire vial package (½ shelf size) at a time. the vials are moved to a buffer rack to ensure fast unloading. From there they are automatically transported to the capper and then taken to a lower class area.
the entire installation was managed, planned and tested by NNe pharmaplan, and we ensured the necessary qualification documentation for all the equipment. with variable or unpredictable freezing and drying behaviours.
at NNe pharmaplan, we have more than 25 years of experience with freeze drying projects, from small size pilot plants (includ-ing liquid nitrogen cool(includ-ing systems) to large-scale production plants with fully automated control of all cycles, including cleaning and Sterilisation in place (cip/Sip) and filter tests. We have a dedicated team focused on recent trends, quality and regulatory issues, and we collaborate with leading suppliers of freeze dryers. Suppliers are evaluated during audits and project cooperation, where quality and expertise are constantly assessed.
Our objective is to deliver integrated solu-tions and know-how in order to find your optimal solution that is sustainable and ensures a fast time to market.
included a capacity analysis, a description of batch separation activities and a cost/ benefit and risk analysis.
3. the implementation phase – in which the campaign period was validated with three times media fill – carried out on the last day in the campaign.
4. the evaluation phase. Based on calcula-tions, the process was designed to facili-tate seven and a half days of campaign-ing to comply with the customer’s goal for a 20 percent increase in capacity, and this goal was reached within six months of operation. accordingly, six months after the implementation new goals were set for production. these involved increasing the campaign filling period from seven and a half to 21 days. this was implemented over the course of the following two months. today, the facility runs the isolator for 21 days without opening it. this has resulted in a total ca-pacity increase of more than 30 percent. Overall, the project was a huge success for the customer. it turned out to be a low-cost project (our consultant hours and a loss of only three days of production for media fill) that yielded a very high increase in capacity, so the payback time was very short. Fur-thermore, the risk was very low due to full separation (change/sterilisation of wet parts) between batches.
tor filling line had been producing only one batch after each full decontamination of the isolator.
the filling line and isolator had been ramped up prior to 2006, which had resulted in several improvements and very stable performance. But a lot of time was still spent on batch change-over. Between every batch, the isolator was decontaminated and the filling system was cleaned and sterilised in place (cip/Sip). each batch change-over took between 24 and 30 hours.
Based on this, the customer had three main success criteria for the project:
• increasing of the Overall equipment
ef-ficiency (Oee) of the isolator filling line
• reducing the cost of Sold Goods (cOSG) • using the isolator filling line as an isolator
and not as a conventional cleanroom We gathered a few process specialists to carry out the project, which was divided into four phases:
1. the idea phase – which clarified the project’s objectives and areas for improve-ment.
2. the analysis phase – which included simulating current and future batch change-over with a model built out of lego blocks to help the team visualise the filling line and isolator. this phase also
CAMPAIGN FIllING
– A MOrE EFFICIENt WAy
For many companies, the time it takes to change over between batches is a bottleneck in the production process. most of the time lost between batches is due to cleaning, which is complex and time-consuming. however, you can save time using campaign filling.
With campaign filling, you can fill more than one batch between each session of full cleaning/decontamination. and between batches in each campaign, some reduced cleaning can be carried out.
the campaign approach represents a signifi-cant opportunity to minimise the costs of non-production activities such as clean-ing, sterilisation and machine assembly. ultimately, campaign filling can increase the number of batches produced per year, and thus increase your annual production capacity.
regulatory requirement
although the campaign approach is now becoming common practice in aseptic proc-esses, there is still a lack of clarity about what regulatory authorities accept and expect in terms of validation.
Some concepts, however, are frequently dis-cussed in the regulatory guides and can help clarify the expectations of the main regula-tory authorities. the Fda guide, Sterile drug products produced by aseptic processing, recommends that “Factors associated with the longest permitted run on the processing line that can pose contamination risk” are addressed during the media fill programme and, “When appropriate, time limits should be established for each phase of aseptic processing,” and these limits “Should be supported by data”.
eu Gmp (annex i) similarly states, “the interval between the sterilisation and use of components, containers and equipment should be minimised and subject to a time-limit appropriate to the storage conditions.”
Successful campaign filling implementation
in 2006, NNe pharmaplan implemented campaign filling in an isolator for an aseptic manufacturing company. For the six years the facility had been in operation, the
isola-32 – Sterile & aSeptic
PACkAGING CHAllENGES
the majority of problems on packaging lines are related to poor line clearance, so it’s important to create a design that mitigates these issues. design considerations for a line layout should include the ability to manage quick change-over, perform line clearance between product batches and clean the line in an easy and controlled manner.
at NNe pharmaplan, we have carried out numerous layout studies for both new and existing packaging areas. in preliminary phases, we can support the packaging component development and suggest op-timised solutions and setups. By using lean manufacturing concepts in the packaging area, we can further optimise your running production.
Because of our many years of experience in the industry, NNe pharmaplan has thorough knowledge of the different packaging ma-chine providers – both in terms of technolog-ical capabilities and their ability to administer large machinery deliveries. accordingly, we can help you choose the provider and the equipment that will best suit your specific production.
We can also help you choose the right pack-aging material for your production process, packaging line and equipment, or we can
adjust your packaging line to tie in with your product and packaging material. Our team will work with you on the specification, in-stallation and qualification of your packaging equipment and processes.
NNe pharmaplan also offers a broad range of other engineering and consulting services related to packaging, for example:
• labelling and coding on primary,
second-ary and tertisecond-ary packaging materials and carriers
• Blister packaging of tablets, vials, devices
and protective packaging
• cartoning in end, and top load flow wrap
and pouch packing, wraparound and wallets
• case packing in shipper boxes or bulk
shipments
• palletising – integrated or stand-alone • test and verification technology involved
in the above mentioned processes
• internal product handling, buffers, robots
and transport systems
• packaging of high potency drugs
INSPECtION tECHNOlOGIES
in pharma and biotech manufacturing, and particularly in regards to parenterals, inspection is a crucial part of ensuring that finished products respect patient safety and live up to relevant quality and safety require-ments. consequently, inspection is subject to increasingly tight regulatory requirements for quality. a precise inspection process is
key to ensuring quality, but it is also critical to ensuring a high throughput. too strict inspection may weed out products that are actually satisfactory and therefore should not be discarded. Such false rejects lead to an output – and a turnover – that is lower than it could be.
NNe pharmaplan has experience within a wide range of products (suspensions,
solu-tions, lyophilised) and containers (cartridges, vials, syringes, ampoules) as well as numer-ous inspection technologies.
Our experience includes fully automated visual inspection machines, table inspections, leak detection (instead of visual inspections for chips and cracks), closure inspections using high voltage, vacuum or headspace analysis, checking of different (device) assem-blies, OcV (optical character verification) of label imprints and reading/checking of data matrix codes to prevent counterfeit products. With our many years of inspection technol-ogy experience, NNe pharmaplan is familiar with all main suppliers of machinery and can offer advice on which providers to choose. We’re also at the forefront when it comes to new inspection technologies, so we can provide you with consulting on traditional as well as innovative solutions.
FIGHtING COUNtErFEIt drUGS
Fake drugs are a cruel reality in the pharma and biotech industries. counterfeit medicines are found everywhere in the world, and are as common in developed countries as they are in developing countries. they also exist on the internet where consumers, in good faith, look for the cheapest price for drugs they might not otherwise be able to afford. counterfeiting pharmaceutical products is a multi-billion dollar industry and, each year, customs officers impound more and more shipments of counterfeit drugs intended for sale on the internet. in fact, the level in 2007 showed an increase of nearly 400 percent compared to 2005/2006.
the list of counterfeit drugs is growing: malaria and hiV treatments, heart medicine, anti-depressives, heparin, cough medicine and more. even low-cost generic drugs and devices in the low-earning segment are subject to counterfeit.
Bogus products range from random mixtures of harmful toxic substances to inactive, ineffective preparations. they can result in treatment failure, severe disablement, organ failure and even death. Some contain a de-clared, active ingredient and look so similar to the genuine product that they deceive health professionals as well as patients. But in every case, the source is unknown and its content unreliable.
eliminating counterfeit drugs is a consider-able public health challenge. Numerous countries already have laws in place to try and put a stop to the production and import of counterfeit drugs, and health authorities, pharmacies, distributors and suppliers of pharmaceuticals are collaborating on anti-counterfeit initiatives to control the problem. the victims of counterfeit drugs are, first and foremost, consumers, but also pharma and biotech companies suffer under counterfeit-ing, which is a huge threat to their business and their trademark. moreover, as the origi-nator of the product, the manufacturer has an obvious role to play in product authenti-cation and supply chain control efforts. the solution is to make authentic products easily verifiable, which also makes it easier to identify fake products. many pharmaceuti-cal companies have added visible security features to their packaging. these include
holograms, embossing, special ink and two-dimensional bar codes. however, these visible features not only provide minimal security, they also require trained personnel to carry out authentication.
many companies use barcodes to iden-tify item level packaging because they are familiar with the technology, and because barcodes are inexpensive to print and apply. however, when a barcode is pre-printed as part of a product’s packaging, it cannot be used to identify counterfeit products because they do not provide item level identification and are susceptible to easy reproduction.
more sophisticated technologies have been developed to facilitate security printing and authentication. the common basis for these technologies is to apply a unique identifica-tion code to each individual pack, which will be checked by the pharmacist behind the counter before dispensing the product to the customer. if the pharmacist’s scanner identi-fies a duplicate code, it will trigger an alarm, and perhaps initiate an investigation into the source of the counterfeit product.
automated identifications, or auto ids, are types of identification that machines can read, and they include:
• Barcodes
• two-dimensional codes
• radio frequency identification (rFid) tags • Optical character recognition (Ocr)
each type has a number of sub-types, which all have pros and cons, leaving you with a vast number of options and a difficult deci-sion to make.
We can help you choose the technology that best meets your needs. We can also carry out the design and installation to make sure it is fully integrated with your production line. We do all the footwork to help you get started and bring you up-to-speed with a complete solution.
as well as an effective measure against counterfeit drugs, modern identification technologies represent a number of other benefits:
• application to electronic pedigrees,
sup-ply chain management, reverse logistics and inventory control
• assurance that information is read
auto-matically and correctly every time
• less redundancy as information can be
reused in different places
• less monotonous and lengthy registration
work
• easy track-and-trace of product
34 – Sterile & aSeptic
MICrOdOSING – A NEW
SIlICONISAtION tECHNOlOGy
millions of patients all over the world rely on daily self-injections. this not only makes them dependent on high quality medicine, but also on easy-to-use self-injection devices that enable easy, controlled administration. this requires an even friction between the plunger and glass as it moves through the container.
the amount of silicone oil on the inside of the pharmaceutical glass is critical. it deter-mines the level of resistance in the container, and thus controls how easy or difficult it is to activate and empty the injection device. the silicone coating ensures efficient emptying of the container and eliminates dosage errors and waste, so improving siliconisation is key to im
