Pharmaceutical Processing Magazine

Transcription

n CONTRACT MANUFACTURING, PACKAGING, & NEW EQUIPMENT TECHNOLOGY FOR THE BIOPHARM/PHARMACEUTICAL INDUSTRY
OFFICIAL MEDIA SPONSOR OF
APRIL 2016
W W W. P H A R M P R O . C O M
IPS Technologies Tours at
INTERPHEX 2016
Technologies Featured:
• Advanced Aseptic
• Biomanufacturing
• Modular Construction
• Oral Solid Dosage
Continuous Manufacturing
• Inspection & Packaging
IPS TECHNOLOGIES TOUR GUIDE
ADVANCED ASEPTIC TECHNOLOGIES
4 Come On In, the Technology is Fine
7 Aseptic Technologies Tour: Participating
Companies
Wednesday, April 27: Begins at 10:00 am & 1:00 pm
Tour Leaders: Paul Valerio, Jason S. Collins, RA, NCARB, Jerrod Shook,
and Rob Roy, P.E.
Vendors: Bausch+Stroebel Machine Company, Inc., Bosch Packaging Technology,
groninger USA L.L.C., IMA Life North America, Inc., OPTIMA Machinery Corporation,
rommelag USA, Inc., SKAN US, Inc., and Franz Ziel GmbH
BIOMANUFACTURING TECHNOLOGIES
8 Developing Next Generation
10
Manufacturing Assets to Maximize
Flexibility and Operational Efficiency
Biomanufacturing Technologies Tour:
Participating Companies
Tour Leaders: Tom Piombino, P.E., Sue Behrens Ph.D., and Jeff Odum, CPIP
Vendors: AdvantaPure®/NewAge Industries, Inc., GE Healthcare, MilliporeSigma,
Pall Life Sciences, and Thermo Fisher Scientific
www.pharmpro.com
ORAL SOLID DOSAGE CONTINUOUS
MANUFACTURING TECHNOLOGIES
16 Adapting OSD Capital Project Design
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to Continuous Manufacturing
Oral Solid Dosage Continuous Manufacturing
Technologies Tour: Participating Companies
Tour Leaders: Mike Vileikis, Sam Halaby, and Andrew Christofides, P.E.
Vendors: GEA North America, Glatt Air Techniques, Inc., Coperion K-Tron, L.B. Bohle
LLC, Gebrüder Lödige Maschinenbau, GmbH, and O’Hara Technologies Inc.
INSPECTION & PACKAGING TECHNOLOGIES
20 Assessing, Controlling, and
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Monitoring Worker Safety in
Primary Packaging
Inspection & Packaging Technologies Tour:
Participating Companies
Tour Leaders: Kevin Swartz, Leonard Pauzer, Jr., Tina Gushue, and
Stefani Scoblick
MODULAR CONSTRUCTION TECHNOLOGIES
Vendors: ILC Dover LP, IMA North America, Inc., Marchesini Group USA,
Mediseal GmbH, NJM Packaging, and Uhlmann Packaging Systems LP
12 The Modularization Process:
TECH HIGHLIGHTS
14
Risks and Benefits
Modular Technologies Tour: Participating
Companies
Tour Leaders: John Costalas, LEED AP, and Dan Leorda, P.E.
Vendors: AES Clean Technology, Inc., Biologics Modular, LLC, and
G-CON Manufacturing, Inc.
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26
27
28
Advanced Aseptic
Biomanufacturing
Modular Construction
Oral Solid Dosage Continuous
Manufacturing
30 Inspection and Packaging
To reserve your spot, visit: http://ipsdb.com/Interphex2016/
2
APRIL 2016 ◗ pharmpro.com
Your search for biopharma experts ends here .
IPS: Your INTERPHEX Tour Hosts
IPS, in partnership with Pharmaceutical Processing, is proud to host the IPS Technologies Tours at INTERPHEX
2016 to showcase the most innovative suppliers of pharmaceutical and biopharmaceutical technologies to
the premier drug manufacturers from around the world.
IPS’ Subject Matter Experts share their years of experience and their knowledge, skill and passion to
efficiently utilize your time at the show by guiding you through the most innovative and best preforming
equipment, both tried and true and new to the market, to suit your current and future manufacturing needs.
To register for Tours, go to www.ipsdb.com/Interphex2016.
To register for Interphex and receive VIP status, to go www.interphex.com/IPS.
Right Where You Need Us
With Global Presence for a Local Execution
Subject Matter Expertise
+ Local Execution Capability
= Successful Projects
With 950 professionals dedicated to the biopharmaceutical
industry in 8 countries and 18 offices, we are where you are.
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2015
HONORABLE MENTION
Category Winner of Five ISPE Facility of the Year Awards
Consulting • Engineering • Project Controls • Construction • Qualification • Commissioning • Validation
Knowledge, Skill & Passion
888.366.7660 • www.ipsdb.com
Come On In, the
Technology is Fine
◗◗ By Rob Roy, P.E. – IPS
O
Rob Roy
ne of the most significant challenges facing
today’s parenteral drug manufacturer is how
best to evaluate and implement advanced
aseptic technologies to maintain a robust
regulatory compliance profile while optimizing cost of goods sold.
The past 15-20 years has seen the introduction and
maturation of a number of “new” technologies that
offer tangible benefits and quality improvements
for aseptic pharmaceutical fill/finish, such as barrier
isolators, 100-percent checkweigher, single-use
disposable fluid path technologies, etc. Many of these
technologies have matured to the point where the
question is no longer whether these technologies are
ready for prime time; their use in dozens or hundreds
of commercial facilities is proof.
The question now is more pointed: “Is your
company ready for these technologies?”
DISCUSSION
There exists today clear regulatory expectations
that firms employ continuous improvement (CI)
models in order to maintain their facilities in a state
of robust cGMP compliance. One of the first items on
many auditors’ lists is a review of a company’s CAPA
program, which is ostensibly designed to identify
root causes of problems and implement corrective
measures to prevent recurrence. Associated metrics—
such as number of open CAPA’s, time required to
implement corrective actions, etc.—provide excellent
insight into the quality of a firm’s QA systems.
CAPA-associated corrective measures can generally
be classified as either administrative or engineering
controls. Administrative controls involve modifying
or creating additional SOPs or work instructions to
provide redundant checks that the manufacturing
process is being executed properly. Engineering
controls, on the other hand, design the process
equipment and facility itself to ensure proper
execution of the manufacturing process. Obviously,
the latter process is more robust and results in higherquality products.
In most cases, firms have no choice but to
implement administrative controls. Especially for
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existing production facilities, a number of factors
contribute to their inability to implement the more
robust engineering controls. These factors may
include, but are not limited to:
• Requirement to maintain production
• Restrictions on capital expenditures (lack of
available funds or unwillingness to prioritize
funding)
• Regulatory concerns (not wanting to open the
filing)
• Validation concerns (“it’s already validated” inertia,
or the additional time required to validate a new
system)
To their advantage, administrative controls are
generally much faster to implement than engineering
controls, and have only an incremental impact on
Cost of Goods Sold (COGS). However, implementing
successive administrative controls can be a slippery
slope, since these additional encumbrances invariably
increase cost, difficulty of execution, and overall
complexity of operations, and thereby erode the
production capacity of the facility. Eventually, the
lack of substantive capital improvements results in a
facility that represents a significant regulatory liability
to the firm.
Therefore, the question of how and when to
implement new technologies to maintain continuous
GMP compliance is of critical importance in our
industry.
As an engineering consulting firm, IPS-Integrated
Project Services, LLC (IPS) executes dozens of concept
design/feasibility studies for clients each year. Many
of these projects include a technology assessment
phase, wherein the client asks us to assess and cost
alternative technologies as part of our scope of
services. At least in theory, this will allow the client to
select the optimal technology on a case-by-case basis,
or to decide if the “time is right” for them to adopt a
new technology.
Unfortunately, this approach often fails. Concept/
feasibility studies are typically executed in a 6- to
8-week timeframe. For those of you that are unfamiliar
with the engineering process, this means that at
most 2 weeks are available for process definition and
technology selection, so that remaining disciplines (architectural,
MEP, fire safety, etc.) can produce their design deliverables, which
are required for the key end result, i.e. an estimated project
cost. The 2-week interval is simply insufficient time for most
companies to reach an informed decision about these complex
issues, especially if the decision will impact multiple facilities
within their network.
Another misconception is that technical selection can be
sorted out during the Basis of Design (BOD) phase, which
typically follows the Concept/Feasibility Report. Unfortunately,
this approach also usually fails, due in part to the compressed
timeframe for the BOD. Since the entire BOD activity is typically
8-12 weeks total, only 2-4 additional weeks are available for
process definition and technology selection. Furthermore, there
is often reluctance on the part of project sponsors to change
the selected technologies from those that were reviewed and
presented to upper management via with the concept report.
These issues generally conspire to prevent post-Concept Report
technology changes.
Another misconception is that technology selection (e.g.
isolator vs. RABS, etc.) should be—or can be—performed on a
case-by-case basis. We seldom see companies switch from one
technology to another on a project by project basis, e.g. Project A
= Isolator, whereas Project B = RABS. Instead, we see clients who
have made the decision to go with a particular technology and
implement that technology across their manufacturing networks
over time. This again points for a need for a different technology
selection paradigm.
SOLUTION
EVALUATION & SELECTION
Companies must develop and manage an ongoing technology
assessment and selection process to evaluate and establish
corporate “standards” for these technologies. These standards can
then be applied to future projects, thus providing a sound basis
for technology selection from the very beginning for all projects.
Selecting and implementing new technologies impacts many
disciplines within an organization; adequate resources within
each discipline are required for proper evaluation.
For example, a request we often receive for aseptic fill finish
facilities is to incorporate single-use fluid path technology, either
on the formulation/bulk holding side or on the filling equipment
fluid path side. There are an increasing number of suitable
alternatives available; however, selecting amongst the various
vendors and technologies requires a significant amount of time
and corporate resources. Required owner side activities include,
but are not limited to:
• Selection of bag film material(s) & suppliers
• QA audits of potential suppliers
• Establishing specifications for single-use systems and
components
• Establishing supply chain strategy (multiple manufacturing
sites, multiple vendors, etc.)
• Determining “target products” for transfer into single-use
systems (existing portfolio)
• Establishing test protocols for extractables and leachables, as
well as stability testing
• Executing preliminary testing on target products
It is easy to see that even this partial list of activities cannot be
completed in anywhere near a 2-week timeframe. As a result, we
are unable to proceed forward on a firm basis during conceptual
design. The best we can do is to select a design basis technology
and vendor, and incorporate this in the facility design. However,
the chances of eventual realization of the selected technology
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are low, since the decision is not made by or for the client
stakeholders. Corporate politics play an important role here as
well; if the decision is not supported within the organization,
then chances of implementation are virtually nil.
As an alternative, companies need a funded, ongoing technical
evaluation and selection process that allows them to develop
an overarching technology strategy. This process is necessarily
multi-disciplinary and high level; without the support of upper
management, efforts to implement these technologies will likely
be unsuccessful. The objective of this process is to identify “best
available technologies” from a corporate perspective, and to
gather information as required for financial evaluation of these
alternatives. Certainly, some of the evaluated technologies will
prove to be “too new” or “not a good fit.” This information is
nonetheless valuable during the Conceptual Design phase, since
resources are not misdirected to evaluate these technologies.
Another key deliverable from the technology assessment
process is financial justification for these technologies. Often,
we see clients who do not understand capital costs for various
technologies. As a result, these technologies are often de-scoped
during the “Value Engineering” phase of the project. Having
an accurate understanding of these costs, as well as broad
organizational support for the expenditures, ensures their
inclusion in the project design basis.
METRICS FOR EVALUATION
As noted above, one key objective of the technical selection
process should be to optimize Cost of Goods Sold (COGS).
For many companies, this “optimization” is synonymous with
incessant downward pressure on COGS.
However, the relentless focus on lower lowering COGS fails
to take into account the quality/cost ratio of the resultant drug
product(s). Manufacturing resources are directed to lower
quality/lower COGS facilities, as witnessed by several decades of
manufacturing outsourcing. Recent quality issues at a number of
“Facility Grade” in this case is recommended as a surrogate
for product quality, since overall product quality is difficult
to measure prospectively. However, a “Facility Grade” can
be assigned prospectively, based on technology selection,
engineering controls, personnel, materials and equipment
flows, etc.
Use of an objective tool of this nature allows companies to
accurately assess their risk tolerance and establish COGS/“Facility
Grade” ratios. By comparing different facilities in network,
companies can establish benchmarks for these ratios, which in
turn can provide the financial justification for implementation of
various technologies.
CONCLUSION
In conclusion, the need for a different model to assess, justify,
and implement new technology in the aseptic fill/finish industry
is clear. Lack of continuous improvement in facilities results in
their obsolescence and associated regulatory compliance issues.
This has been a major contributing factor in the current drug
shortage issue.
As an alternative, firms are urged to adopt a long-term,
strategic, and funded technology assessment program. Such a
program necessarily requires support from upper management,
which needs to take the form of adequate funding and
headcount allocation, as opposed to “philosophical support” for
unfunded initiatives.
During the upcoming IPS/INTERPHEX Technology tours, you
will no doubt see a number of exciting new technologies that
may be a great fit for your manufacturing facilities. This would be
a great time to begin considering how to lay the groundwork for
these in your company.
Another key deliverable from the
technology assessment process
is financial justification for these
technologies
such facilities have been a significant contributor to the current
drug shortage crisis.
This COGS-only approach generally precludes introduction/
adoption of advanced technologies, due to the increased
capital costs for these systems in conjunction with the extended
timeframes that may be required for implementation. This in
turn ensures the eventual obsolescence of these facilities, which
is accompanied by a continually eroding compliance profile for
these facilities and the company in general.
As an alternative, companies can develop metrics that
combine COGS analysis with a “Facility Grade” evaluation. The
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ADVANCED ASEPTIC TECHNOLOGIES TOUR
Participating Companies & Contacts
Bausch + Stroebel Machine Company, Inc.
21 Commerce Drive
North Branford, CT 06471
203-484-9933
www.bausch-stroebel.com
Mr. Jim Nadlonek
jim.nadlonek@bausch-stroebel.com
or
info@bausch-stroebel.de
INTERPHEX Booth No. 2505B
Bosch Packaging Technology
8700 Wyoming Ave N
Minneapolis, MN 55445
USA
Matt Stien, Director of Sales
763-424-4700
sales@boschpackaging.com
www.bosch.com
INTERPHEX Booth No. 3106
Franz Ziel GmbH
www.ziel-gmbh.com
North American Sales & Service:
PharmaSystems Inc.
662 Goffle Road
Hawthorne, NJ 07506
973-636-9007
www.pharmasytemsusa.com
Paul J. Giletta
pgiletta@pharmasystemsusa.com
groninger USA L.L.C.
14045 South Lakes Drive Charlotte, NC 28273
704-295-9000
www.groningerusa.com
Matt Clifton
m.clifton@groningerusa.com
IMA Life North America, Inc.
2175 Military Road
Tonawanda, NY 14150
www.ima-pharma.com
716-695-6354
Ernesto Renzi
ernesto.renzi@imalife.com
OPTIMA Machinery Corporation
1330 Contract Drive
Green Bay, WI 43204
920-339-2222
www.optima-pharma.com
Mevluet Yilmaz
Mevluet.Yilmaz@optima-usa.com
rommelag USA, Inc.
27905 Meadow Dr., Suite 9Evergreen, CO 80439
303-674-8333
www.rommelag.com
Tim Kram
mail@rommelag.com
SKAN US, Inc.
7409 ACC Blvd., Suite 200
Raleigh, NC 27617
919-354-6380
www.skan.ch/en/
Les Edwards, Regional Director
Les.Edwards@us.skan.ch
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Developing Next Generation
Manufacturing Assets to
Maximize Flexibility and
Operational Efficiency
◗ By Jeffery Odum, CPIP - IPS
THE CHANGING PARADIGM IN
BIOMANUFACTURING
Current developments in the
biopharmaceutical industry have added
significantly to the challenges of designing,
Jeffery Odum
building, and operating biopharmaceutical
manufacturing facilities. With increasing
insights into product requirements and product characterization,
the critical path for the development of new products is shifting to
process development and manufacturing timelines where speed and
flexibility are now more critical than ever. Manufacturing systems
today must be agile enough to deliver more types of products in a
shorter timeframe with limited resources of time and capital.
Figure 1: Integrated Facility Model.
The traditional business model of highly-integrated facilities does
not allow for this needed increase in operational effectiveness. A new
business model has emerged that focuses on flexibility, operability,
and utilization where companies can adapt rapidly to changing market
conditions.
The next generation options for facility design involve the
implementation of single-use technologies and new platform
technologies along with a flexible approach to facility integration. With
QbD (Quality by Design) as a significant foundation of facility design,
these facilities will be “designed to operate” in order to provide a
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higher level of flexibility, utilization, and operational excellence.
THE ENABLING TECHNOLOGIES:
WHAT YOU SHOULD KNOW
Many companies embarking on new manufacturing assets that
implement complete or hybrid forms of Single-use Systems (SUS)
technology have little to no previous experience. As new processes
are moving through clinical development based on single-use
technology, the list of unknowns grows and the need to clarify
assumptions increases. While the process still “drives the train” for
SUS-based facilities just as it does for traditional stainless steel-based
systems, the issues become different. Product characteristics have
a greater impact on materials-of-construction and product contact
surfaces. Synergy between different vendor platforms and control of
the supply chain are more difficult. The compatibility of materials and
components, the systems for quality testing of components, and the
overall procurement philosophy around supplier qualification are key
issues of risk.
Process understanding is driven around time-and-motion
understanding of each unit operation and the impact it has on
the overall manufacturing timeline. Activity durations for set-up,
change-over, and testing are different. The Sequence of Operation is
different. The “old habits” of traditional operations will be challenged
and likely modified.
“Plan the work, work the plan.” Not a truer statement can be
made when new SUS technology is being implemented, and none
too soon. SUS technology is generally labor intensive and requires
changes/additions to the manufacturing protocols and procedures
that define the “baseline” for current manufacturing operations. For
complex processes, the orchestration of frequent changeovers, new
tube set set-up and connections, equipment/skid movement, and
waste removal must be well choreographed in order to meet tight
production schedules.
The sooner a detailed time-and-motion analysis can be executed
where the entire manufacturing operation is timed, the better
picture of complexity and timing can be developed that will show
where key procedures, details, or sequence-of-operations must be
identified. This planning effort will provide a clear picture of the
integration of manufacturing, inspection, and quality activities, as
well as their associated training needs. It will also provide valuable
information around personnel requirements to determine operations
head-count.
Closure definition and investigation are a critical aspect of system
design. Process closure analysis is more detailed and clearly a focus
of regulatory scrutiny. Managing the logistics of the numerous tube
sets introduces many aspects of “spaghetti management” that will
require a different level of project management and engineering in
order to bring value and efficiency, not to mention compliance with
many Environmental Health and Safety and cGMP regulations. The
focus must be on operational efficiency.
operation execution.
Companies may choose to either have tube sets pre-assembled
by a third party supplier (often preferred for complex tube sets)
or fabricate the tube sets internally as part of the manufacturing
operation. How connection verification is documented, the
identification of components is verified, and how proper set-to-set
interface is verified will be important. This interface verification is
similar to the scenarios experienced in the use of transfer panels and
their unique “jumper” configurations in traditional stainless steelbased facilities of the past decade. Many companies will implement
a fixture or “jig” to ensure that proper sequence of installation is
followed and verification of proper installation easily documented.
IDENTIFICATION OF TRAINING NEEDS
Single-use systems and disposable components do have unique
elements associated with their inspection, assembly, and operation.
Training personnel in the proper methods of handling SUS
components, identification of potential defects in materials and
assemblies, set-up for testing to prove integrity, and verification of
assembly configuration and closure will likely require development
of a new set of standard operating procedures (SOPs) and protocols.
The information needed for these will be developed from both
internal and external source information, process development
studies, pilot-plant and clinical operations, and vendor data.
Some of the specific needs include:
• Operator training in proper handling and assembly of tube sets
and verification of connection integrity to prove system closure
• Inspector training in the handling, visual and integrity testing of
bags, and execution of sampling techniques
• Operator training in the set-up of unit operation assemblies,
disassembly of components, and handling of solid waste
• Training in the execution of Factory Acceptance Testing (FAT)
activities around evaluation of acceptance criteria
DOCUMENTATION
Single-use technology implementation will likely require some new
forms of documentation to support validation efforts. While the audit
process for suppliers and vendors will follow more “standard” practices,
the creation of detailed sequence-of-operation documents as part of
the batch record will be somewhat outside-of-the-box from traditional
SOPs. One example of this comes in the assembly of tube sets for unit
RISK
Early identification and a clear understanding of the SUS design risk
elements is a key to the likely success of the effort. Two unique and key
areas are in closure analysis and supply chain management.
A closed system should be analyzed in three parts:
• The equipment assembly
• Examples: bioreactor, vessels, chromatography systems, etc.
• The streams in and out from the system
• Examples: compress air, media and buffers, etc.
• Connections and disconnections to the system
• Examples: valves, single-use connectors, etc.
The focus is to demonstrate the risk mitigation for each part to confirm
that the SUS operates in a closed manner that can be validated.
Another key aspect of closure analysis is to have agreement
from the team that the definition of closure is agreed upon by all
members. Closure is not a constant. Three of the often-cited definitions
recognized in the industry are:
• Closed system: A system that is designed and operated such that
the product is isolated and never exposed to the environment.
Additions to, and effluents from, closed systems must be
performed in a completely closed fashion. Transfers into or from
these systems must be validated as closed.
• Functionally closed: Closed systems that are opened between
processing operations but are “rendered closed” by a cleaning,
sanitization, or sterilization process that is appropriate or
consistent with the process requirements, whether sterile, aseptic,
or low bioburden.
• Briefly exposed operations: Open processes containing process
materials and/or product intermediates. These open processes
are rendered closed by means of an appropriate closing process.
Definition and validation of the “pre-closure” incubation phase is
critical.
With this SUS information defined, it is now the task of the design
team to execute a Process Closure Analysis.
There are a number of areas around supply chain management that
should be addressed for a SUS-based biomanufacturing project. These
include:
• Compatibility of materials
• Quality and testing standards/criteria
• Delivery
• Redundancy in the supply chain
Figure 2: Example of SUS tube set fixture for installation.
9
FACILITY DELIVERY
SUMMARY
The implementation of SUS often has as a key project goal: the
attribute of flexibility or some form of “adaptability” for future
manufacturing platforms and scenarios. A key question that must be
answered in design is “what exactly does flexible mean?” The simple
question has many potential answers.
Flexibility can focus on the multi-stage goal of manufacturing
from a single facility asset. From early stage clinical manufacturing
through launch and commercial manufacturing, the facility has to
be designed in a manner to allow for a flexible segregation strategy,
multiple manufacturing platforms, and a likely increase in scale.
To accomplish this goal, organizations are developing
manufacturing configurations around the ballroom concept, a matrix
approach of highly segregated (yet flexible) manufacturing suites, or
a hybrid solution with elements from both approaches. Any of these
options will require a synergy between the process unit operations,
operational philosophy, segregation approach, and design attributes.
Once the facility approach is defined there also needs to be a
decision made around the delivery approach and its impact on the
design attributes. Today, many SUS facilities are taking advantage of
different modular-based delivery approaches. Modular cleanroom
panel assemblies, modular units, rapid deployment pods, and the
traditional “stick-built” delivery are all viable options that have different
design requirements for infrastructure, tie-ins, accessibility, and
segregation strategy.
Next generation,
technology-driven
manufacturing
projects are
different. There is no
need to panic. But
Figure 3: Flexible ADM model layout.
it is important to
understand where
the risk elements lie, how to address their potential impact to the
project, and manage their design and delivery accordingly. Know
why you are going in this new direction.
Next generation manufacturing is here, and this year’s IPS
Biomanufacturing Technologies Tours at INTERPHEX will showcase
vendors that are
shaping the “Facility
of the Future” as the
facility of today. The
tours will be led by
biomanufacturing
subject matter
experts Sue
Behrens, PhD, Tom
Piombino, PE, and
Jeff Odum, CPIP.
Figure 4: Rapid-deployment Manufacturing
PODs. Image courtesy of Biologics Modular.
BIOMANUFACTURING TECHNOLOGIES TOUR
AdvantaPure®/NewAge Industries,
Inc.
145 James Way
Southampton, PA 18966
888-755-4370
www.advantapure.com
sales@advantapure.com
GE Healthcare
100 Results Way
Marlborough, MA 01752
800-526-3593
www.gelifesciences.com
Uzair Beg
Uzair.beg@ge.com
10
MilliporeSigma
290 Concord Road
Billerica, MA 01821
800-645-5476
www.milliporesigma.com
Thermo Fisher Scientific
1726 Hyclone Drive
Logan, UT 84321
www.thermofisher.com/sut
435-792-8500
Carsten Lau
Carsten.h.lau@thermofisher.com
Pall Life Sciences
20 Walkup Drive
Westborough, MA 01581
800-717-7255
www.pall.com/biopharm
Ian Sellick
Ian_sellick@pall.com
MARCHESINI GROUP
USA
JACOB JAVITS CENTER,
NEW YORK CITY, US
APRIL 26-28, 2016
MARCHESINI GROUP USA
43 FAIRFIELD PLACE - WEST CALDWELL, NJ 07006
TEL. 973 575 7445
INFO@MARCESHINIUSA.COM
WWW.MARCHESINI.COM
BOOTH
NO. 3125
The Modularization Process:
Risks and Benefits
◗◗ By Dan Leorda, P.E. – IPS
M
Dan Leorda
12
odularization is the process in which a
building (or part of its components or
systems) is constructed off-site—under
controlled plant conditions, using the same
materials, and designing to the same codes
and standards as conventionally-built facilities, but in
a much shorter duration and with better construction
quality management. Modularization of process and
facility systems, or complete facilities, has proven to
be a lean project delivery technique that aids in the
achievement of these goals.
The dynamic nature of technology and best practices
evolvement in the early 21st century that lead many
biopharmaceutical facility projects are integrating
some form of modularization execution in their
project delivery. The modularization concept can
manifest as prefabricated buildings, modular process
skid systems and HVAC systems, and pre-engineered
modular construction techniques in order to maximize
predictable costs, schedules, and quality benefits.
Originally applied to describe process skids,
“modular” was a connotation of a complete facility,
organized in shipping container-sized units, built at a
remote location, transported to the owner’s address,
and reassembled on site. The modules consisted of
structural frames fit-out with architectural elements,
mechanical, electrical and plumbing (MEP) systems,
and process equipment which were already integrated,
commissioned, and at times, IQ. This approach
can offer many benefits as a rapid response to
areas where construction techniques or skills for
cGMP facilities are not available.
However, this may not be the ideal solution
for most of today’s construction projects,
such as those that consist of expansions,
renovations, and upgrades to existing plants.
For these projects, facility owners can take
advantage of a customized modular project
delivery approach to reduce the overall project
schedule, shift labor hours off site to increase
quality with minimal disruption to site operations, and
gain potential cost benefits.
Modular project delivery (MPD) offers several
significant benefits. Building in a controlled
environment reduces waste through avoidance
upstream rather than diversion downstream. In
addition, this promotes sustainability through the
improved quality management throughout the
construction process and significantly less on-site
activity and disturbance.
Other benefits include:
• Enhanced quality control that is achievable in shop
fabrication versus field fabrication
• Reduced waste
• Reduced impact on current operations
• Simplified site logistics
Transferring labor hours away from the owner’s site
can: reduce cost, as design and fabrication is performed
at a lower labor cost venue; reduce pressure on facility
infrastructure, such as parking and site logistics; reduce
disruption to the owner’s operations; and reduce
numerous risks, such as the risk of accidents and
injuries on the owner’s site.
PLANNING AND EXECUTION
Lean project delivery is applied by most project teams
from concept development for new and renovated
facilities. Project teams need to immediately consider
modularization options for the project to ensure that
subsequent phases accommodate modularization
objectives. The process that is typically employed today
is depicted in the following diagram (Figure 1).
Figure 1
During project conceptualization, project teams
analyze a broad array of options and associated
impact on cost and schedule. The facility and systems
design are modified to take advantage of the selected
decisions to achieve the benefits of modularization
without the costs and disadvantages of a full-blown shipping
container module solution.
Options include:
• Prefabricated process and utility equipment, such as skidmounted clean-in-place or reheat equipment
• Pre-piped and pre-wired air-handling units (AHUs)
• Modular penthouses complete with air handlers, chillers, and
MCCs
• Modular wall systems and modular pipe racks for HVAC
piping and ductwork, plumbing, process piping, electrical,
and controls
• Large “super-skids” that are broken down for shipment and
reassembled quickly in the field
In some instances, when full-plant delivery via shipping containers
is appropriate, the owner should be aware of the limitations and
impacts of the shipping logistics and on site assembly. Increases in
engineering costs and committing to a set floor plan and equipment
list at an early stage of the project are just two of the major
considerations when deciding to execute the entire project utilizing
shipping container style modular construction.
Rather than picking an offthe-shelf cleanroom module,
better results can be achieved by
engaging designers, contractors,
and vendors during the early
phases of the design process
Where the structures of stick-built facilities are optimized for
the purpose of the facility, the structures of shipping container
modules must be optimized for two purposes: that of the facility
and the requirements of shipping a large module intermodal.
Modular projects require additional interface coordination. For
example, it requires oversight to ensure that all vendors meet
local code requirements, that construction materials used are
consistent and compatible, and that controls are integrated. It is
important to identify any potential maintenance or operational
issues and to allow for future changes and renovations. Even
logistics are challenging, as transportation and rigging of these
modules becomes a factor.
A rational approach to modular construction will reduce
waste and cost, enhance quality, and create a delivery system
that meets owner requirements, such as limiting the length of
a shutdown. Rather than picking an off-the-shelf cleanroom
module, better results can be achieved by engaging designers,
contractors, and vendors during the early phases of the design
process and leveraging their knowledge to engineer a solution
that meets the project’ unique needs and goals. The result is
a custom modular approach that is sensitive to the unique
requirements and environment of the specific project.
Modular project delivery requires a greater commitment
in Front End Loading (FEL) of a project, both in design and
construction planning. In traditional project delivery, definition
of physical details is deferred until late in the preliminary,
or schematic, design phase. In the custom modular delivery
process, early design must address target systems and layout
constraints, structural frame requirements, transportation and
constructability constraints, and flexibility for future capacity and
system expansion.
At this point, modularization opportunities can be identified
and explored for implementation. 3D modeling is ideal for
defining intent and determining overall assembled dimensions
and weight. Moving even small portions of the construction
off-site can reduce on-site craft hours, thus reducing safety risks,
while minimizing the impact on operations and improving the
project schedule.
Today’s modular wall systems—which evolved from
prefabricated PVC-sheathed aluminum frame wall and ceiling
panels—offer a high degree of flexibility. Options include
“walkable” ceiling systems and prefabricated return-air walls.
Modular wall systems can incorporate integrated electrical
lighting and receptacles, HVAC ductwork, HEPA filters, sprinkler
systems, and controls. Modular wall systems also provide added
benefit of vastly superior quality to any means and methods
available for constructing on site.
Just as a custom modular approach should be developed
in parallel with overall project design, skids can be sourced
while the site, shell, and infrastructure “stick-built” construction
takes place. Process and facility skids can be designed and built
offsite. When it makes sense, factory acceptance testing and prequalification can also be performed prior to shipping the skids.
Once on site, the integrated construction and compliance team
verifies receipt, reassembles the skids, and performs final testing
and qualification.
One option that can be beneficial for many projects is
modularization of utility generation and distribution systems.
Designed to meet the required performance specifications,
they can be prefabricated on special structural support
systems, shipped just-in-time, and assembled. The skidded
modules generally require a smaller footprint than conventional
distribution systems. These parallel activities can shave significant
time from the schedule compared to the end-to-end timelines
required for completely stick-built projects, involving multiple
trades. A construction management partner that understands the
entire plant lifecycle can help maximize the benefits of utility and
process skids.
In summary, modular lean project delivery approach that is
customized to the specific needs of the project offers a number
of significant advantages for plant renovations and expansions.
From a schedule perspective, performing activities in parallel can
reduce overall project duration and make a very favorable impact
on the critical “time from decision to delivery.”
Modular project delivery reduces disruption to the site, as well
as lay down and waste area. Fabrication in the shop, rather than
the field, results in higher quality work. By reducing labor hours
at the site, MPD improves project safety. Modular project delivery
may also reduce costs by transferring labor to lower-cost centers,
13
taking advantage of higher productivity in the shop versus the
field, and generally reducing site requirements. Throughout
the modular delivery process, a team experienced in technical
construction can maximize the schedule, quality, safety, and cost
benefits realized by the owner.
BENEFITS OF MODULARIZATION
The benefits of modularization are many, and the
quantitative evaluation of some of them is highly complex.
Two of the most obvious benefits are quality, because
more craft labor hours are expended under controlled shop
conditions instead of uncontrolled field conditions, and
safety, for the same reason. The cost of the project can be
reduced, depending on the relative cost of shop versus field
labor. If shop and field labor costs are equivalent, the cost
increases due to module disassembly for shipping must be
offset by the savings from productivity improvements in
the shop.
The Modular Construction Technologies Tour at INTERPHEX
2016 will focus on a slate of organizations that are on the
cutting edge of the advances in modularization. Modular
solutions will include modular wall systems, with and
without integrated MEP functions, process modules, superskids, and shipping container/structural functional modules.
This year’s vendors include AES Clean Technology, Inc.,
Biologics Modular, LLC., and G-CON Manufacturing, Inc.
The INTERPHEX 2016 Modular Construction Technologies
Tour will be kicked-off by Dan Leorda, P.E., and John Costalas,
LEED AP, Project Executives at IPS. If one of your objectives
at INTERPHEX is to leave with an understanding of new ways
to reduce project costs, timelines, and risks, this tour will
provide a solid return on your time invested.
MODULAR CONSTRUCTION TECHNOLOGIES TOUR
AES Clean Technology, Inc.
422 Stump Road
Montgomeryville, PA 18936
215-393-6810
www.aesclean.com
Brian Bennett
bbennett@aesclean.com
G-CON Manufacturing, Inc.
6161 Imperial Loop Drive
College Station, TX 77845
979-314-7452
www.gconbio.com
Brittany Berryman
bberryman@gconbio.com
Biologics Modular, LLC
1533 E. Northfield Dr. Suite 100
Brownsburg, IN 46112
317-456-9191
www.biologicsmodular.com
Clark Byrum
cbyrum@biologicsmodular.com
14
OSD CONTINUOUS MANUFACTURING TECHNOLOGIES
Adapting OSD Capital
Project Design to
Continuous Manufacturing
The engineering firm’s role in streamlining implementation.
◗◗ By Andrew Christofides, Michael Vileikis, Sam Halaby – IPS
T
Andrew Christofides
Michael Vileikis
Sam Halaby
16
he Food and Drug Administration (FDA), led
by Janet Woodcock, Director of the Center
for Drug Evaluation and Research (CDER),
is tirelessly and relentlessly promoting
continuous manufacturing (CM) as the best
opportunity to achieve its 21st Century Quality
Vision of “…a maximally efficient, agile, flexible
pharmaceutical manufacturing sector that reliably
produces high-quality drugs without extensive
regulatory oversight.”1
Research organizations formed from collaborations
among leading universities, multi-national drug
companies, and regulatory agencies have made great
advancements in CM technology and have seen
versions of their test bed models implemented in
cGMP manufacturing environments.
The Center for Structured Organic Particulate
Systems (C-SOPS), headquartered at Rutgers
University, which now includes four major
universities and over 40 industrial consortium
member companies, was enlisted by Dr. Woodcock
in May of 2015 to develop an “FDA Guidance in
Continuous Manufacturing,” which will serve as a CM
implementation guide for OSD manufacturers.
Less than one month ago, the FDA issued a draft
guidance on emerging technologies, which included
the formation of a group within CDER known as
the Emerging Technology Team (ETT), intended
to streamline submissions from pharmaceutical
companies seeking approval of products
manufactured using an emerging manufacturing
technology, such as continuous processing.
The C-SOPS working group developing the FDA
guidance is a collaboration of the world’s largest
pharmaceutical companies. Major equipment
manufacturers continue to develop CM processing
equipment, open testing facilities, and contribute
machinery and systems to C-SOPS for implementation
in their research labs. Finally, as capital spending on
CM technology continues to increase, engineering
firms will play a critical role in ensuring that market
adoption is not stalled because of poorly-executed
capital projects.
Engineering firms must have a comprehensive
understanding of the differences between batch and
continuous OSD operations, and take proper measures
to ensure that their capabilities are aligned with the
needs of the pharmaceutical industry in the ongoing
emergence of CM. It is the responsibility of the
engineering firm to modify the traditional OSD capital
project design and execution strategy for CM.
Identification of business drivers is nearly always
a responsible first step in planning a new facility or
retrofitting an existing plant for a new manufacturing
technology. In a CM initiative, drivers may include
the accelerated development of a breakthrough
therapy, the need to reduce cost of goods, or the
introduction of more products at lower volumes
aimed at gaining strategic access to emerging
markets. In all cases, the definition of batch size
is essential to the capacity analysis that must be
developed at the onset of the program.
In traditional batch manufacturing, batch size would
often correspond to major equipment volume or
nominal capacity, for example, the 1,200-liter fluid bed
processor or the 600-liter intermediate bulk container
(IBC). In batch production, it is not uncommon for
capacities to vary among unit operations, creating
the need for work-in-process (WIP) inventory buffers
between steps. The capacity analysis in batch
operations is further complicated by a wide array of
potential scheduling strategies, including varying
degrees of campaigning. Batch production is time
variant, and often relies on end point determination.
Weigh/dispense, typically the first major operation
in a batch facility, is driven by batch size, which the
engineer uses to estimate staging requirements
for major ingredients, as well as batch kits awaiting
downstream processing.
The engineering team must approach a CM project from
a different perspective. In CM, there are many acceptable
approaches to batch definition, including run time, volume
produced, or active pharmaceutical ingredient (API) lot. It may be
acceptable to simply define batch size by throughput, and not
commit to a specific quantity of product or duration of run time.
The CM operation is characterized by throughput, typically in kg/
hr, which—in many ways—simplifies the capacity analysis. Unit
operations are close-coupled and characterized by a common
line rate of production. WIP inventory between connected unit
operations is eliminated. Weigh/dispense is replaced by loss-inweight feeders.
The need to analyze capacity and properly consider constraints
will not be completely eliminated. A fundamental difference
between batch and CM is understanding the time to reach
steady-state, where operations are consistent “…over a period of
time where all relevant process parameters and product qualities
are not subject to variation outside of a defined range of values.”2
Similar to batch operations, equipment set-up and disassembly,
as well as major and minor cleaning times, must be estimated in
order to conduct meaningful capacity studies.
As the project moves into detailed design, the level of
automation, the plant configuration, and the nature of design
deliverables look very different in a CM project, versus traditional
batch OSD.
The following paragraphs elaborate on how engineering
firms may modify their detailed design approach for CM project
execution, and why CM projects require more sophisticated
design tools for proper execution.
AUTOMATION
The level of automation in batch OSD facilities varies greatly.
Some clients use electronic batch record systems, which
monitor critical parameters from each unit operation through
a higher level Distributed Control System (DCS). Based on the
complexity of the batch record system, unit operations may
require a permissive signal from the DCS to start operations. In
this type of highly-advanced system, each room would have a
local operator station that would interface with the DCS. Also,
all major equipment would have identified I/O interface with
the DCS over a selected communication protocol, i.e. Fieldbus,
ModBus, DH+. However, the equipment itself would still act as
an island of automation. All set points and operational queues
would be initiated from the local equipment control system.
Since a continuous manufacturing train needs to be properly
tuned and the throughput of the close-coupled unit operations
synchronized, the continuous equipment needs to not only
be monitored, but controlled by the higher level automation
system. Each unit operation will still have an independent
control system, but set points and critical parameters will be
input from the DCS and queues to delay, slow down, or pause
will all be generated from the higher level automation system.
In traditional batch operations, materials move between
unit operations in IBCs. In a continuous operation, materials
move via gravity or pneumatic transfer in a closed piping
system between unit operations. In continuous operations,
critical parameters (blend uniformity, moisture content,
particle size) are measured and analyzed in real-time between
unit operations to verify the system is operating within
predefined control limits, i.e., the process is in specification.
These measurements are collected utilizing process analytical
technology (PAT) devices, which are installed in the transition
piping between process equipment. The location of each PAT
component is critical to ensure desired functionality, as well
as accessibility for maintenance and calibration. Also, they
require power and communication wiring back to the DCS,
so determining wire-ways or conduit paths is an important
coordination step in the design process.
EQUIPMENT MODELING
It is not uncommon for batch pharmaceutical facilities to
compartmentalize or group unit operations into specific
functional areas, i.e., granulation, blending, and compression.
Furthermore, to facilitate training and scheduling and promote
consistency, many organizations standardize unit operations,
as well as the rooms that house them. For example, a standard
compression module will always include the same make and
model tablet press, deduster, and metal detector. Peripheral
containers, scales, and furniture will be arranged in a standard
configuration in the room. Personnel trained in compression
operations will be familiar with all compression suites in the
facility, and possibly the entire organization. The time required
to add new modules is minimized, because standard designs and
implementation documents already exist.
As these standard modules are configured in the facility the
corresponding technical/mechanical spaces must be added
adjacent to each process room. Technical areas support the
auxiliary mechanical, electrical and plumbing (MEP) services,
including vacuum pumps, air handling units (AHU’s), and dust
collectors, as well as electrical and control panels associated with
the process equipment.
The equipment arrangement in Figure 1 illustrates the use of
standard processing rooms with adjacent technical areas in a
traditional batch OSD facility.
Figure 1: Standard
processing rooms with
adjacent technical
areas in a traditional
batch OSD facility.
17
In CM, unit operations are close-coupled and reside in a
common production room. Although this aspect of CM is
favorable because it results in a significant reduction in cGMP
space, it becomes difficult to arrange technical equipment in an
ideal manner, with respect to desired adjacencies and proximities
to associated process equipment. The technical area becomes
a multi-operational space, similar to that of the production
suite, and minimizing pipe and cable runs and ensuring proper
accessibility and maintenance access to all equipment takes on a
new form of challenge.
will vary depending on the building construction approach.
Modular construction will require significantly less hours of labor
than traditional stick-built construction.
In contrast to a traditional batch OSD project, the deliverables
of a CM project more closely resemble those required to design
a biotech or API chemical facility, in the sense that there is a
stronger emphasis on automation deliverables and piping details.
The CM equipment is more complex because all equipment
items in a train are connected, and any change or adjustment
to a particular machine in the stack-up will alter the entire train.
The mechanical integration, support details, and provisions for
required access and egress are significantly more challenging
than in traditional batch OSD. In CM, an optimized layout is
essential, given the interconnected nature of the train and need
for perfect synchronization of all machines in the process.
BUILDING INFORMATION MODELING
Figure 2: The CM engineering services scale. The required investment in
engineering services is minimized through the application of standard
equipment platforms and modular construction.
DESIGN TOOLS AND DELIVERABLES
As illustrated by the preceding graph, the scale of engineering
hours of labor and deliverables required to execute a capital
OSD project varies depending on the level of equipment/
automation standardization and the degree to which modular
facility construction is leveraged. If standard equipment/
automation is employed, such as the GEA ConsiGma continuous
platform, then it makes sense to leverage vendor engineering,
including Piping and Instrumentation Diagrams (P&IDs), as well
as automation documentation—thereby minimizing the scope
of process engineering services required from the engineering
firm of record.
In contrast, if it is determined that some combination of
vendor offerings provides a better-suited processing system for
a particular product, then the engineering firm takes on a more
significant process integration role, thereby increasing the scope
of process engineering services required. These deliverables
will most likely include detailed P&IDs, system architecture
and connectivity diagrams, and detailed instrument, valve, and
equipment databases. At a minimum, the engineering firm must
develop sufficient documentation and data to facilitate the
integration of vendor supplied machine controls and PAT devices
with the DCS.
The magnitude of architectural and facilities engineering also
18
Leveraging Building Information Modeling (BIM) provides the
engineering firm with the best chance to deliver a successful
CM project. Three-dimensional equipment and piping
models should be developed to optimize the arrangement of
feeders, continuous mixer, mills, PAT, wet or dry granulation,
and compression equipment—all of which will be physically
connected. BIM provides the best opportunity to design support
structures to optimize the performance of highly-sensitive
gravimetric feeders, which are rendered ineffective when
exposed to external vibration or even air movement from a
misplaced fan.
Engineering firms must embrace their role in the ongoing CM
revolution in the OSD industry by investing in the collaboration,
education, and design tools necessary to ensure viability. The
scarcity of capital project opportunities to-date is indicative
that the rate of market adoption has been slower than
desired, especially from the standpoint of FDA CDER Director
Dr. Woodcock, who is taking every conceivable measure to
accelerate adoption. Engineering firms will get their chance.
When the opportunity arises, it will be incumbent on us to be
fully prepared to deliver the winning CM project.
References
1. Woodcock, Janet. “Modernizing Pharmaceutical Manufacturing
– Continuous Manufacturing as a Key Enabler” MIT-CMAC
International Symposium on Continuous Manufacturing of
Pharmaceuticals, May 20, 2014.
2. ASTM E2968-14. Standard Guide for Application of Continuous
Processing in the Pharmaceutical Industry, April 2015.
OSD CONTINUOUS MANUFACTURING TECHNOLOGIES TOUR
Coperion K-Tron
590 Woodbury Glassboro Rd.
Sewell, NJ 09080
856-589-0500
www.coperionktron.com
Theresa Antell
tantell@coperionktron.com
Gebrüder Lödige Maschinenbau, GmbH
Elsener Strasse 7-9
DE-33102, Paderborn, Germany
310-918-6772
www.loedige.de
www.modwave.com
Par Almhem
par.almhem@modwave.com
GEA North America
9165 Rumsey Road
Columbia, MD 21045
844-432-2329
www.gea.com
Tim Hoover
Tim.Hoover@gea.com
Interphex Booth No. 2421
L.B. Bohle, LLC
700 Veterans Circle, Suite 100
Warminster, PA 18974
215-957-1240
www.lbbohle.com
Martin Hack
m.hack@lbbohle.com
Glatt Air Techniques, Inc.
20 Spear Road
Ramsey, NJ 07446
201-825-8700
www.glatt.com
Mark Garber
Mark.Garber@glatt.com
INTERPHEX Booth No. 2505A
O’Hara Technologies Inc.
20 Kinnear Court
Richmond Hill, Ontario
L4B 1K8 Canada
905-707-3286
www.oharatech.com
Jim Marjeram
sales@oharatech.com
19
Assessing, Controlling, and
Monitoring Worker Safety
in Primary Packaging
◗◗ By Stefani Scoblick, Kevin Swartz, Tina Gushue – IPS
T
Stefani Scoblick
Kevin Swartz
Tina Gushue
he manufacture and use of drug products has
brought innumerable benefits to modern society.
Conversely, while some of these drug products
have a positive effect on the patient it is intended
for, they can also have negative effects on
workers exposed to the drug product as part of their job.
Effects of exposure can vary from a mild irritation to
potentially fatal interactions, even in what may appear
to be exposure to small quantities. The challenge is to
manufacture these vital drug products with maximum
social and economic benefit, while protecting workers
and the public.
When dealing with the risks of exposure to potentially
harmful drug products, it is important to point out
that worker safety and patient safety are two distinctly
different evaluations.
• Worker safety is related to protecting the people
working with or around the potentially harmful drug
products while on the job and is associated with
Industrial Hygiene (IH).
• Patient safety is related to the effects drug
administration and is associated with product quality
or cGMPs (current Good Manufacturing Practices).
Table 1 provides more information regarding
differences between IH and cGMP considerations.
Our main concern in this article is worker safety.
We will be discussing the tools that are used to help
employers protect the health of those workers who
are exposed to potentially harmful substances in the
workplace. Determining worker safety can be broken
Perspective
Industrial Hygiene
Quality (cGMP)
WHO/WHAT Exposed
Population Variables (Age,
Immunology, Fitness)
Worker
Usually healthy
Product
Introducing risk to Patient via the
product
Route of Entry
Inhalation
Dermal
Transmucosal Membranes
Ingestion
Product Cross-Contamination
by settled powder or retained
product X into/onto Product Y
Patient Ingestion, IV
Primary Exposure Mechanism(s)
or How exposure/crosscontamination occurs
- Inhalation
(Settled dust can be re-suspended
to be breathed at another time)
- Skin Absorption
contact, via wounds
- Mucous Membranes
Contaminated worker touches
mucous membranes
- Ingestion
- Mix-Up
wrong materials
- Retention
inadequate cleaning
- Mechanical Transfer
moving residue from one thing to
another
- Airborne Transfer
powder available in air and
contacts product, equipment
Basis of Standards for Risk
Assessment
Occupational Exposure Limit
(OEL) expressed by an AIRBORNE
concentration (mass per cubic meter
of air) to address primary route of
entry for exposure: Inhalation
Acceptable Daily Exposure (ADE)
expressed as mg/day
Cleaning Limit
expressed as mg/swab or mg/l to
address primary route of exposure:
Ingestion, IV
Table 1: Summary of differences for IH and cGMP considerations from ISPE Baseline® Guide: Risk-Based Manufacture of
Pharmaceutical Products (RiskMaPP) – First Edition, September 2010.
20
into three basic functions: assessing, controlling, and monitoring.
Occupational Exposure Limits (OELs) are used when assessing
worker safety. At a minimum, these limits should be set with
input from Environmental Health and Safety (EH&S), toxicology
experts, and validation experts. OELs based on science are always
defendable; however, OELs based on a company policy are a little
more difficult to justify or uphold. OELs are determined based on
the maximum permissible concentration of a chemical agent (i.e.
gas, vapor, fiber, dust, etc.) in the air which a worker may be to
exposed to regularly over their working lifetime. The OEL is intended
to be the level at or below which a given substance can be present
in the air in the workplace without resulting in adverse health effects
for workers.
OELs should be created for the various stages of the entire
production process, including primary packaging, which is most
commonly overlooked. In many cases, the potentially harmful
effects of the primary packaging processes may be diluted in
comparison to upstream operations.
When determining OELs for a given product, at a given process
stage, one of the three methods can be applied: safety factor
method, analogy method, or correlation method.
The safety factor method is used for new products that are not
similar to already existing products. This method uses an equation
{OEL = NOEL*BW or TD } containing both known and uncertain
UF *a*V
UF *a*V
data (typically from pre-clinical/clinical trials). The analogy and
correlation methods can be used when a similar compound exists
with already determined OELs. The analogy method uses the OEL
of the similar product, {OEL1 = OEL2} ; while the correlation method
applies a property multiplier (e.g. two times as potent) to the
existing product’s OEL {e.g. OEL1 = 2 * OEL2 }. The key to assessing
OELs is to determine the methods based on science, not gut feel,
and apply them universally.
1,2,3
1,2,3
Occupational Exposure Bands (OEBs), or subdivisions of the
full range of risk by product criteria, are created (reference
Figure 2) with input from EH&S, toxicology experts, and
validation experts in conjunction with the end users such as
engineering, production, and quality.
Input from the end users is required during band creation
because they are the ones responsible for implementing the
controls during processing and can determine whether the
controls can be effectively implemented. The number of control
bands and control methods should be equivalent. Two control
bands that use the same control method do not add more value
• OEL
• Carcinogenicity
than using
one band.
• Acceptable Daily Intake
• Reproductive Toxicity
When• determining
risk bands many
risk factors should be
Clinical Effects
• Developmental Toxicity
taken into
account
1). Surface
Additionally,
• Acute
Toxicity (reference list in •Figure
Acceptable
Limits
• Skin/Eye
Irritation into categories
• Absorption
grouping
of products
(e.g. hormones, steroids,
• Sensitization
• Warning Properties
oral contraceptives, etc.), rather than product properties, should
• Chronic Toxicity
• Speed of Onset
be avoided
because the potentially •harmful
effectsIntervention
may vary
• Mutagenicity/Genotoxicity
Need for Medical
within each category. An example of banding can be seen in
Figure 3.
CRITERIA
OEL Range [µg/m3]
Potency [mg/day]
Clinical Effects
Acute Toxicity
Skin and Eye Irritation
Sensitization Potential
Chronic Toxicity
Reversibility
Mutagenicity / Genotoxicity
Human Carcinogenicity Potential
Reproductive Toxicity
Developmental Toxicity
Absorption
Warning Properties
Speed of Onset
Need for Medical Intervention
FULL RANGE
CATEGORY 3
< 0.1 → 500+
<0.1 → 100+
None → Severe
None → Extreme
None → Corrosive
None → Extreme
Minimal → Severe
reversible or irreversible
none → (+) in a battery of studies
negative → confirmed animal & human
None → Severe
None → Severe
Minimal → Significant
Good → None
Immediate → Delayed
None → High (potentially life threatening)
10 - 1 µg/m3
10 - 1 mg/day
moderate
moderate
moderate to severe
moderate
severe
irreversible
(+) in a battery of studies
probable - confirmed animal
moderate
moderate
significant
poor to none
immediate to delayed
Moderate to high
Figure 3: Banding example.
Within each band, process, operational, engineering,
procedural, and administrative controls need to be assigned.
• OEL
• Carcinogenicity
Process controls should include detailed product containment
• Acceptable Daily Intake
• Reproductive Toxicity
and handling requirements. Operational controls should
• Clinical Effects
• Developmental Toxicity
include personal protective equipment (PPE) and housekeeping
• Acute Toxicity
• Acceptable Surface Limits
requirements during processing.
• Skin/Eye Irritation
• Absorption
• Sensitization
• Warning Properties
Engineering controls should be applied for each of the
• Chronic Toxicity
• Speed of Onset
following (where applicable):
• Mutagenicity/Genotoxicity
• Need for Medical Intervention
• Enclosed processes
• Local exhaust ventilation
Figure 1: Risk factors for consideration during banding.
• Room ventilation
• Ventilated balance enclosures and lab hoods
• Closed material transfers
CRITERIA
FULL RANGE
CATEGORY 3
< 0.1 → 500+
OEL Range [µg/m3]
10 - 1 µg/m3
• Air flow
Potency [mg/day]
<0.1 → 100+
10 - 1 mg/day
• Airlocks/gowning rooms
Clinical Effects
None → Severe
moderate
Acute Toxicity
None → Extreme
moderate
Procedural controls should address minimization of transfers,
Skin and Eye Irritation
None → Corrosive
moderate to severe
cleaning, decontamination, waste disposal, paperwork
Sensitization Potential
None → Extreme
moderate
Chronic Toxicity
Minimal → Severe
severe
handling, and controlled access. Lastly, administrative controls
Reversibility
reversible or irreversible
irreversible
Mutagenicity / Genotoxicity
none → (+) in a battery of studies
(+) in a battery of studies should be put in place around hazard communication, medical
Human Carcinogenicity Potential
negative → confirmed animal & human
probable - confirmed animal
surveillance, preventative maintenance, and training.
Reproductive Toxicity
None → Severe
moderate
Developmental Toxicity
None → Severe
moderate
Primary packaging controls around blistering and OSD
Absorption
Minimal → Significant
significant
operations are most often overlooked; however, awareness
Warning Properties
Good → None
poor to none
Speed of Onset
Immediate → Delayed
immediate to delayed
is growing within the industry. Several vendors already offer
Need for Medical Intervention
None → High (potentially life threatening)
Moderate to high
commercially available options for new primary packaging
Figure 2: OEB/OEL.
21
equipment, while many third-party vendors are designing
engineering controls to retrofit existing packaging lines.
Regardless of whether the equipment is new or existing, it is
important that once the vendor is selected, they become your
partner and understand your OEB controls. Your vendor should
develop a concept with you, not for you. You and the vendor
should agree to standards that can be effectively implemented
between both parties.
Once all controls are put in place, it is important to
continuously monitor them to determine whether changes
need to be made or if the current controls are adequate. Air
monitoring is typically performed using a particle counter
which compares the baseline particle count of an inactive room
to the particle count of an active room. Surface monitoring is
also performed by conducting random swab testing of work
surface and exposed equipment areas to determine true
exposure levels. Note that this is a test to determine exposure,
and is not related to cleaning validation. Medical surveillance
of workers by a medical professional is also important to
understand and communicate the health hazards, risks, and
symptoms of overexposure.
In summary, documenting your approach and understanding
the methodology used for assessment, controls, and monitoring
is vital to keep workers safe from exposure to potentially
harmful products. However, the initial assessment and controls
put in place for a product is only one part of the OEL process.
The OEL process is a dynamic process and must be revisited or
reevaluated throughout the life cycle of the drug product.
INSPECTION & PACKAGING TECHNOLOGIES TOUR
ILC Dover LP
One Moonwalker Road
Frederica, DE 19946
302-335-3911
www.ilcdover.com
Saroj Patnaik
patnas@ilcdover.com
Mediseal GmbH
Flurstrasse 65
33758 Schloß Holte-Stukenbrock
Germany
www.mediseal.de
Nadine Noske
nadine.noske@mediseal.de
Packaging Solutions
IMA North America, Inc.
7 New Lancaster Road
Leominster, MA 01453
978-537-8534
www.ima-pharma.com
Darren Meister
sales@imausa.net
NJM Packaging
56 Etna Road
Lebanon, NH 03766
603-448-0300
www.njmpackaging.com
Marla Labreche-Stallmann
info@njmpackaging.com
Marchesini Group USA
43 Fairfield Place
West Caldwell, NJ 07006
973-575-7445
www.marchesini.com
Roger Toll
sales@marchesiniusa.com
22
Uhlmann Packaging Systems LP
44 Indian Lane East Towaco, NJ 07082
973-402-8855
www.uhlmann-usa.com
Sabri Demirel
sdemirel@uhlmann-usa.com
INTERPHEX Booth No. 2505D
SETTING NEW STANDARDS
IN ASEPTIC PROCESSING
Fill-fnish new concept for nested vials,
syringes and cartridges.
New York, NY - USA April 26-28, 2016
Visit our Booth # 2545
IMA LIFE division • mktg.life@ima.it • www.ima-pharma.com
IMA LIFE NORTH AMERICA, INC. • sales@imalife.com
V I A L L O A D I N G • WA S H I N G • D E P Y R O G E N AT I N G • F I L L I N G • F R E E Z E - D R Y I N G • S TO P P E R I N G • C A P P I N G
ADVANCED ASEPTIC TECH HIGHLIGHTS
The Flexible Revolution and VarioSys® Evolution
Bausch+Stroebel’s range of products is specifically designed for the primary
packaging of pharmaceutical products. The equipment performs the cleaning,
depyrogenation, filling (liquid or powder), exterior cleaning, conveying, and
labeling operations for bottles, vials, syringes, cartridges, and ampoules. Aseptic
processing is highly regulated by cGMP, and FDA guidelines provide the foundation
for the concept and design of their production systems.
Aseptic Rapid Decontamination
Station
◗◗Bausch + Stroebel Machine Company, Inc., North Branford, CT 06471.
◗◗www.bausch-stroebel.com or call +1-858-705-6030 / +1-203-484-9933
◗◗INTERPHEX Booth No. 2505B
Franz Ziel GmbH’s portfolio comprises high-quality
systems and unique designs. Their isolators use the
least H2O2 in the industry. Ziel’s planning/production
team works side-by-side with you, and are driven by
integrity, quality, and flexibility. Their top priority is to
protect people via their high-tech systems: protecting
life with technology.
PharmaSystems, Inc. provides sales, service, and
parts for FZ in the U.S. & Canada.
FlexPro 50: Flexibility by Design
groninger’s FlexPro50 is highly flexible, allowing
customers to process nested vials, syringes, and
cartridges with one line configuration. All process
steps can be executed manually or fully automated.
By changing the filling and handling trolleys, a nest
filling line can be converted to a bulk line to allow for
flexibility with a minimal machine footprint.
◗◗groninger USA L.L.C., Charlotte, NC 28273.
◗◗www.groningerusa.com or call 704-295-9000
◗◗INTERPHEX Booth No. 3711
◗◗Franz Ziel GmbH
◗◗PharmaSystems Inc., Hawthorne, NJ 07506.
◗◗www.pharmasystemsusa.com or call
973-636-9007
Aseptic Processing & OSD Packaging
IMA is the largest
producer of
pharmaceutical
equipment
worldwide, offering
solutions for
complete aseptic,
orals and solid dose
packaging lines. They
offer solution for vial
and ampoule lines,
including washers,
depyrogenation
tunnels, liquid and
powder filling under
Isolator or RABs,
capping, and labelers.
IMA also produces
freeze dryers and
loading systems with an in-house laboratory to provide customers comprehensive
assistance with product development, scale up, and qualification.
◗◗IMA Life North America, Inc., Tonawanda, NY 14150.
◗◗www.ima-pharma.com or call 716-695-6354
24
ADVANCED ASEPTIC TECH HIGHLIGHTS
Technology Utilizing a DFS (Disposable Fill
System)
Providing advanced aseptic Blow/Fill/Seal (BFS) filing technology for
more than 50 years, rommelag provides services for container and
closure development, clinical trials, and commercial aseptic production.
The bottelpack 430 closed parison BFS machine with disposable fill
system represents the newest application into the BFS market. This
system is designed to provide advanced aseptic fill/finish for injectable
drug and biotech products.
◗◗rommelag USA, Inc., Evergreen, CO 80439.
◗◗www.rommelag.com or call 303-674-8333
Combination Filling Machines
The OPTIMA Multiuse series is a highly flexible filling and closing
machine for the processing of nested and bulk containers. The
systems can process all types of nested syringe, vial, and cartridge
formats. They are equipped with an innovative transport system that
process vial ranges from 2cc up to 30cc at production rates up to
150 products per minute without any format change parts.
◗◗OPTIMA Machinery Corporation, Green Bay, WI 43204.
◗◗www.optima-pharma.com or call 920-339-2222
Packaging Technologies: Complete Fill Finish
Solutions
Bosch Packaging Technology is the only supplier offering complete line
packages from a single source. The wide and deep portfolio of products
along with strategic partnerships allows Bosch the ability and expertise
to provide complete fill finish solutions for vial, syringe, cartridge,
ampoule, ophthalmic, tablet, and capsule manufacturing. This unique
approach ensures complete system design and integration are seamless
and provide the best possible performance and reliability. The Bosch single
supplier model includes water and steam processing, product processing,
sterilization, fill finish, single-use product pathways, dosing systems, sealing,
inspection, and a full complement of secondary packaging products.
SKAN—known for developing and validating robust, high-quality
isolators with the fastest decon cycles in the industry—continues
to innovate with barrier technology, including RABS. New
products include the flexible modular small-scale filling isolator
called the PSI-L; SARA® Material Airlocks for isolators with <20
minute cycle times; SKANFOG® SARA® Medium and Large
Material Airlocks for cleanrooms with rapid cycles under 60
minutes; and Glove Testing systems like the Wireless GT®.
◗◗Bosch Packaging Technology, Minneapolis, MN 55445
◗◗www.bosch.com or call 760-424-4700
◗◗SKAN US, Inc., Raleigh, NC 27617.
◗◗www.skan.ch/en/ or call 919-354-6380
Flexible Modular Aseptic Isolator
25
BIOMANUFACTURING TECH HIGHLIGHTS
Innovative Bioprocess
Solutions
GE Healthcare's Life Sciences business
provides bioprocessing products and
services that enable the development and
manufacture of high-quality biotherapeutics
and vaccines. The company supports its
customers in increasing speed to market,
while avoiding unnecessary costs and
improving quality and performance in
drug manufacturing. As a provider of highquality products, customized technical
and commercial services, as well as design
and construction of complete biomanufacturing solutions, they support the
biopharmaceutical industry in making health visions come to life.
◗◗GE Healthcare, Marlborough, MA 01752.
◗◗www.gelifesciences.com or call 800-526-3593
Biotech and Pharmaceutical Solutions
MilliporeSigma is the U.S. Life
Science business of Merck KGaA,
Darmstadt, Germany. They offer
a range of development tools,
consumables, stainless steel, and
single-use equipment and systems,
as well as services for the research,
development and production of
biotech and pharmaceutical drug
therapies. They partner closely
with customers to simplify the
complexities of advancing a drug to
market.
◗◗MilliporeSigma, Billerica, MA 01821.
◗◗http://www.emdmillipore.com or http://www.sigma-aldrich.com
or call 800-645-5476
Cell Culture and
Bioprocessing
Thermo Fisher Scientific
will be showcasing their
expanded suite of singleuse products, including the
Thermo Scientific imPULSE
Single-use Mixer, the DHX
Heat Exchanger, and the
inSITE Integrity Tester.
These products have been
validated to work with their
single-use films—Aegis514, CX5-14, and ASI 26/77.
Purity in
Fluid Flow
Systems®
AdvantaPure®
specializes in
manufacturing
tubing and hoses,
and molding
BioClosure®
container closure
assemblies from
platinum-cured
silicone and
AdvantaFlex®
sealable and
weldable TPE.
The company
focuses on singleuse molded tubing manifold assemblies, which offer
benefits such as the elimination of leaks, entrapment, and
contamination associated with barbed fitting tubing sets.
AdvantaPass®, a clean room wall pass-through system,
incorporates single-use disposable components to provide
aseptic transfer of fluids between manufacturing suites.
◗◗AdvantaPure®/NewAge Industries, Inc.,
Southampton, PA 18966.
◗◗www.advantapure.com or call (888) 755-4370
Integrated Continuous
Bioprocessing
Pall Life Science’s suite of technologies enables costeffective and reliable implementation of continuous
bioprocessing of biological drugs. Some of these
technologies include the Cadence™ Inline Concentrators
within the single-pass TFF (SPTFF) platform, the
BioSMB® multicolumn continuous chromatography
platform, and acoustic wave separation (AWS), a
disruptive cell culture clarification technology.
◗◗Pall Life Sciences, Westborough, MA 01581.
◗◗www.pall.com/biopharm or call 800-717-7255
◗◗Thermo Fisher Scientific, Logan, UT 84321.
◗◗www.thermofisher.com/sut or call 435-792-8500
26
MODULAR CONSTRUCTION TECH HIGHLIGHTS
Modular Cleanrooms for
Flexible Manufacturing Facilities
As an innovator of pre-engineered, standardized, and modular
construction technologies, flexible facility design and rapid
construction methods are not new to AES. Combined with flexible
modular HVAC and process utility skids, they deliver a facility that
can be configured to meet the varied demands of industry’s product
pipeline in months, not years.
• Factory-engineered modular walls and walkable ceilings
• Reconfigurable and removable walls and rooms
• Cleanroom glazing
• Available free-standing structural system decouples the facility from
host building
• Walkable ceiling serves as maintenance platform for access to
lights, valves, and control devices without interruption to on-going
processes and GMP compliance
• HVAC air distribution and process utility stations integrated into walls
• In-house design, manufacturing, installation, and commissioning
assures quality control
◗◗AES Clean Technology, Inc., Montgomeryville, PA 18936.
◗◗www.aesclean.com or call 1-888-AES-CLEAN
Biologics Modular DeployReady
Platform (DRP)
Biologics Modular designs and manufactures cGMP
modular cleanroom facilities that are tailored to the
specific needs of a company, whether that is for a
bio-manufacturing suite, an aseptic finish/fill suite,
or a compounding pharmacy suite. Their products
are based on the intermodal platform outfitted to be
fully commissioned and validated DeployReady Suites
designed to meet the various ISO standards of clean
rooms and support rooms.
◗◗Biologics Modular LLC, Brownsburg, IN 46112.
◗◗www.biologicsmodular.com or call 317-456-9191
Autonomous Cleanroom PODs
G-CON Manufacturing, Inc.’s prefabricated,
turnkey cleanroom systems represent a significant
transition to forward thinking in pharmaceutical and
biopharmaceutical processing. G-CON Manufacturing,
the innovator of autonomous cleanroom PODs,
has turned the challenges experienced by the
biopharmaceutical industry into readily deployable,
flexible, mobile, and scalable cleanroom solutions. PODs
are ideal for multi-product sites, rigorous containment
needs, and on-demand scaling of production and
laboratory space. Building on its first design in 2009,
G-CON now has a wide array of cleanroom PODs in
their product portfolio to accommodate the increasing
demands from the pharmaceutical, biopharmaceutical,
and cell therapeutic industries.
◗◗G-CON Manufacturing, Inc., College Station, TX
77845.
◗◗www.gconbio.com or call 979-314-7452
27
OSD CONTINUOUS MANUFACTURING TECH HIGHLIGHTS
Feeding & Material Handling
Innovations for Continuous
Processes
Coperion K-Tron, a Business Unit of
Coperion, has a wide range of products,
including extruders, pneumatic conveying
systems, feeders, and complete materialhandling systems specifically designed for
continuous feeding, dispensing, and batch
weighing for the most difficult to handle
pharmaceutical powders.
◗◗Coperion K-Tron, Pitman, NJ 09080.
◗◗www.coperionktron.com or call 856589-0500
Continuous Solid Dose
Manufacturing System
Glatt’s Rotary Chamber process insert allows the simple
conversion of batch processing machines to continuous
fluidized bed processors. The continuous processing is
fully automated, resulting in precise product retention
times.
MODCOS is:
• Fully-automated, stable process
• High productivity
• Demand-oriented production
• Reduced need for GMP space
• Short product development cycles
• Real-time product control and approval
• Designs:
o s-line up to 15 kg/h
o m-line up to 50 kg/h
o l-line over 50 kg/h
◗◗Glatt Air Techniques, Inc. Ramsey, NJ 07446.
◗◗www.glatt.com or call 201-825-8700
◗◗INTERPHEX Booth No. 2505A
Continuous Processing: Solid/Liquid Dose
Technology
GEA North America is a global specialist in solid and liquid dose technology.
Their experience and successful installations include systems such as batch and
continuous granulation, drying, pelletizing and coating, contained materials
handling, tablet compression, freeze drying, fermentation and liquid formulation,
separation, homogenization, and cell disruption.
◗◗GEA North America, Columbia, MD 21045.
◗◗www.gea.com or call 844-432-2329
28
OSD CONTINUOUS MANUFACTURING TECH HIGHLIGHTS
Continuous Process
Technology Center
L.B. Bohle’s team of industrial and
academic partners have developed and
implemented a modular production
line for continuous manufacturing.
This continuous processing line
includes all necessary unit operations
from feeding the API and excipients
into the system to the producing the
coated tablet as output of the system.
L.B. Bohle’s modular design allows
choosing between direct compression,
dry granulation, and wet granulation
processes.
◗◗L.B. Bohle, Warminster, PA 18974.
◗◗www.LBBOHLE.com or
call 215-957-1240
Continuous Tablet Coater
O’HARA offers a full line of continuous coaters, fulfilling
both small and large volume production demands. The
O’Hara Fastcoat™ Continuous Tablet Coater produces
more product in less time, while increasing uniformity and
reducing product damage. The company also offers a wide
range of batch tablet coaters, with interchangeable or fixed
perforated drums, as well as retrofits for pharmaceutical
processing equipment.
◗◗O’Hara Technologies Inc., Richmond Hill, Ontario,
L4B 1K8, Canada.
◗◗www.oharatech.com or call 905-707-3286
Continuous Manufacturing Technologies
Lödige, inventor of the Ploughshare® Mixer and manufacturer of solid
dose processing systems, supplies systems and solutions for a wide range of
applications, including mixing, reacting, granulation, fluid bed drying, vacuum
drying, and coating. They provide core unit operations (mixing, granulation,
fluid bed drying), as well as complete systems for continuous manufacturing,
including direct compression and continuous wet granulation and fluid bed
drying. All systems are customized to the end user’s application.
◗◗Gebrüder Lödige Maschinenbau, GmbH, Paderborn, Germany.
◗◗www.loedige.de, www.modwave.com or call 310-918-6772
29
INSPECTION & PACKAGING TECH HIGHLIGHTS
Containment and Process Solutions
ILC Dover’s innovative flexible containment solutions can
be retrofitted easily to existing processes or included in new
turnkey systems. The ILC Dover companies have expanded
to include JetSolutions for unique powder and liquid process
equipment and Grayling Industries for sanitary and industrial
packaging solutions. They have global design, manufacturing,
and support capabilities for a broad range of processes.
◗◗ILC Dover LP, Frederica, DE 19946.
◗◗www.ilcdover.com or call 302-335-3911
Monoblock Syringe Filling & Stoppering
Solution
Extrafill is a syringe tub opening, filling, and stoppering Monoblock
machine for syringes in nests, complete with an integrated weight control
system. Extrafill accommodates 2-5 stoppering stations. The tub opening
process features a Marchesini robotic arm that peels off the Tyvek cover, and
pushes the tub onto the loading belt for the syringe filling and stoppering
station. The Extrafill has a production speed of 200 syringes per minute.
◗◗Marchesini Group USA, West Caldwell, NJ 07006.
◗◗www.marchesini.com or call 973-575-7445
Tablet Packaging System
IMA’s UNILINE is a conveying, filling, and capping system that flexibly
integrates the functions required to form a complete counting line:
container loading, desiccant insertion, counting and filling, cotton insertion,
capping, coding, metal detection, and rejection. The UNILINE counting
line is extremely compact and considerably simpler than a traditional tablet
packaging line. Each container is positioned inside a dedicated housing,
ensuring traceability at every stage of the packaging cycle, from loading to
rejection.
◗◗IMA North America Inc., Leominster, MA 01453.
◗◗www.ima-pharma.com or call 978-537-8534
30
INSPECTION & PACKAGING TECH HIGHLIGHTS
Safe Packaging of Solid Dose
Mediseal offers solutions suitable for packaging
under defined climatic conditions with preset
temperature and humidity. Containment in
pharmacy ranges from simple extraction solutions
(laminar flow) to sealed systems (CIPFull
Containment) with a wide range of preventive
measures such as the use of glove-boxes. Its
consistent hygenic design provides uniformly
smooth surfaces and rounded corners as well as
ease of access to all essential areas, which makes
cleaning of equipment fast.
◗◗Mediseal GmbH, Flurstrasse 65, 33758
Schloss Holte, Germany.
◗◗www.mediseal.de or call +49 5207 888-0
Aseptic Filling and Solid Dose
Packaging Solutions
Manufacturer of pharma and biotech packaging
solutions, NJM Packaging will be exhibiting the
Dara Moduline™ Aseptic Filling machine, which
incorporates the standard isolator technology of
a single design, processing either vials, bottles,
syringes or cartridges for automatic filling of any
liquid or powder in sterile conditions. In addition,
their Cremer CFS-622*4 Cremer tablet counter
has a new modular concept, servo driven, with
accurate counts.
◗◗NJM Packaging, Lebanon, NH 03766.
◗◗www.njmpackaging.com or call 603-448-0300
Blister Equipment with
Containment Systems
Uhlmann designs containment solutions which
strictly separate operator and product to package
solid dose products safely. Standard machines
that have regularly proven their worth with stable
processes, as in the case of the blister line BEC 300,
are often used as a basis.
• Reliable protection of staff
• Prevention of product contamination and
elimination of environmental impact
• Components are tried and tested
• Few, small, and lightweight format parts for
efficient product changeovers
• Easy to clean due to smooth, sloping surfaces
◗◗Uhlmann Packaging Systems, LP, Towaco, NJ
07082.
◗◗www.uhlmann-usa.com or call 973-105-8855
◗◗INTERPHEX Booth No. 2505D
31
“Off-the-shelf solutions?
No thank you. After all, our
customers are something
special.”
Daniel Drossel
Mechanical Engineering Technician
(Design department)
Each customer has its very own special requirements. That’s why we,
at Optima, manufacture flling lines that are fne-tuned to our clients’
particular needs while ofering the benefts of an integrated and
complete line: The complete machine package including high-precision
functionalities, backed by consistent documentation and supported by an
optimized and tailored software solution – in addition to a central point of
contact who is passionate about your every concern… We are experts in
special solutions, after all.
INTERPHEX New York | April 26-28, 2016 | Booth # 3103
Member of
OPTIMA pharma GmbH | 74523 Schwaebisch Hall | Germany | www.optima-pharma.com
OPTIMA Machinery Corporation | Green Bay, WI, 54304 | USA | www.optima-usa.com

Pharmaceutical Processing Magazine

Transcription

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