EMagazine Pharmaceutical Europe : From Syringe to Autoinjector - FARMASI INDUSTRI
Volume 40 Number 6
Blow-Fill-Seal
PLUS: Technology
Data Integrity
Training
Using Modular
Construction
JUNE 2016 Volume 40 Number 6
PHARMACEUTICAL TECHNOLOGY
From
Syringe to
Autoinjector
Building a Better
Self-Injection
Solution
JUNE 2016
PharmTech.com
PEER-REVIEWED
Qualifying Personnel to Visually
Inspect Cleaned Equipment, Part II
SINGLE -USE SYSTEMS
Integrating Single-Use Systems
FORMULATION
Customizing HPMC
API SYNTHESIS & MANUFACTURING
Adoption of Continuous Processing
Advancing Drug Delivery
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(Design department)
Each customer has its very own special requirements. That’s why we,
at Optima, manufacture illing lines that are ine-tuned to our clients’
particular needs while ofering the beneits of an integrated and
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EDITORIAL
Editorial Director Rita Peters [email protected]
Senior Editor Agnes Shanley [email protected]
Managing Editor Susan Haigney [email protected]
Science Editor Adeline Siew, PhD [email protected]
Manufacturing Editor Jennifer Markarian [email protected]
Science Editor Randi Hernandez [email protected]
Community Manager Caroline Hroncich [email protected]
Art Director Dan Ward
Contributing Editors Jill Wechsler [email protected]; Jim Miller
[email protected]; Hallie Forcinio [email protected]; Susan J. Schniepp
[email protected]; Eric Langer [email protected];
and Cynthia A. Challener, PhD [email protected]
Correspondent Sean Milmo (Europe, [email protected])
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EDITORIAL ADVISORY BOARD
Pharmaceutical Technology publishes contributed technical articles that undergo a
rigorous, double-blind peer-review process involving members of our distinguished
Editorial Advisory Board. Manuscripts should be sent directly to the managing editor. Below is a partial list
of the Pharmaceutical Technology brand editorial advisory members. The full board, which includes advisory
members from Pharmaceutical Technology Europe, can be found online at PharmTech.com.
James P. Agalloco
President,
Agalloco & Associates
Larry L. Augsburger, PhD
Professor Emeritus
University of Maryland
David H. Bergstrom, PhD
Senior Vice-President,
Pharmaceutical Development &
Corporate Quality Assurance
Antares Pharma, Inc.
Phil Borman
QbD Lead & Data Management &
Analysis Manager
GlaxoSmithKline
Rory Budihandojo
Lachman Consultants
Metin Çelik, PhD
President,
Pharmaceutical Technologies
International (PTI)
Zak T. Chowhan, PhD
Consultant, Pharmaceutical
Development
Suggy S. Chrai, PhD
President and CEO,
Chrai Associates, Inc.
Roger Dabbah, PhD
Principal Consultant,
Tri-Intersect Solutions
Robert Dream
Managing Director
HDR Company
Tim Freeman
Managing Director,
FreemanTechnology
Sanjay Garg, PhD
Professor and Director,
Centre for Pharmaceutical
Innovation and Development,
University of South Australia
R. Gary Hollenbeck, PhD
Chief Scientific Officer,
UPM Pharmaceuticals
Ruey-ching (Richard) Hwang, PhD
Senior Director,
Pharmaceutical Sciences,
Pfizer Global R&D
Gurvinder Singh Rekhi, PhD
Department of Pharmaceutical and
Biomedical Sciences,
The University of Georgia College
of Pharmacy
Mansoor A. Khan, PhD
Professor & Vice Dean
Irma Lerma Rangel College of
Pharmacy, Texas A&M Health
Science Center
Susan J. Schniepp
Fellow
Regulatory Compliance Associates
Heidi M. Mansour, PhD
Assistant Professor
College of Pharmacy
& The BIO5 Research Institute,
University of Arizona–Tucson
Jim Miller
President,
PharmSource Information
Services Bio/Pharmaceutical
Outsourcing Report
David R. Schoneker
Director of Global Regulatory Affairs,
Colorcon
Aloka Srinivasan
Principal Consultant,
PAREXEL International
Read board members’
biographies online at
PharmTech.com/
pharmtech-editorialadvisory-board.
Colin Minchom, PhD
Senior Director Pharmaceutical
Sciences, Shire Pharmaceuticals
R. Christian Moreton, PhD
Partner, Finnbrit Consulting
Fernando J. Muzzio, PhD
Director, NSF Engineering
Research Center on Structured
Organic Particulate Systems,
Dept. of Chemical and Biochemical
Engineering, Rutgers University
Moheb M. Nasr, PhD
Vice-President, CMC Regulatory
Strategy, Global Regulatory Affairs,
GlaxoSmithKline
Garnet E. Peck, PhD
Professor Emeritus of Industrial
Pharmacy, Purdue University
Pharmaceutical Technology
East Coast Sales Manager Joel Kern [email protected]
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tSend news and product releases to [email protected]
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SALES
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JUNE 2016
P h a r mTe c h . c o m
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June 2016 Volume 40 Number 6
Pharmaceutical Technology is the authoritative source of peer-reviewed research
and expert analyses for scientists, engineers, and managers engaged in process
development, manufacturing, formulation and drug delivery, API synthesis, analytical
technology and testing, packaging, IT, outsourcing, and regulatory compliance in the
pharmaceutical and biotechnology industries.
On the cover
COVER STORY
18 Building
a Better
Self-Injection Solution
Experts discuss the key considerations
in the development of an autoinjector.
Cover Design by Dan Ward;
Images: Jared Eygabroad/Getty Images
ON PHARMTECH.COM
FEATURES
FORMULATION
VIEWPOINT
24 Customizing HPMC to
39 PAT: “Gateway Drug”
Minimize Drug Variability
to the 21st Century for
the Pharma Industry
The authors evaluated the
performance and robustness of
controlled-release tablets made
with HPMC blends of unimodal and
bimodal molecular weight distribution.
API SYNTHESIS & MANUFACTURING
30 Steps Closer
to the Adoption of
Continuous Processing
Application of flow chemistry for smallmolecule API synthesis continues to
expand thanks to research efforts.
Process analytical technology paved
the way for continuous manufacturing.
SINGLE-USE SYSTEMS
42 Integrating
Single-Use Systems in
Pharma Manufacturing
Industry experts discuss the benefits and
challenges of using single-use systems
in pharmaceutical manufacturing.
FACILITY DESIGN
45 Deciding When to
Use Modular Construction
Different types of modular systems
have advantages and disadvantages.
What’s Behind NIH’s
Quality Problems?
Drug manufacturing lapses
undermine NIH research programs.
www.pharmtech.com/what-s-behindnih-s-quality-problems-0
Any Chance for “Cures”
Legislation This Year?
Biomedical innovation
legislation may stall in 2016.
www.pharmtech.com/any-chancecures-legislation-year
EU on a Mission to Boost R&D
In a move to encourage drug
development, EU regulators are
offering scientific advice to companies
on major efficacy, safety, and quality
issues at an early stage.
www.pharmtech.com/eu-missionboost-rd
Continued on page 8
PEER-REVIEWED RESEARCH
EQUIPMENT CLEANING
34 Qualifying Personnel to Visually Inspect Cleaned
Equipment, Part II: Small vs. Large Group Training
This article presents recommendations based on a program that was set up to qualify
members of a large, diverse team at one oral solid-dosage-form manufacturing facility.
PharmTech.com
Continued from page 6
NEWS & ANALYSIS
FROM THE EDITOR
REGULATION
& COMPLIANCE
10 Industry
US REGULATORY WATCH
14 Modern
Moves Closer
to Continuous
Manufacturing
Manufacturing
Comes of Age
With technology advances, continuous
manufacturing shows steady progress
to more widespread adoption.
FDA and bio/pharma companies
get serious about continuous
manufacturing to ensure product quality.
STATISTICAL SOLUTIONS
ASK THE EXPERT
47 Demonstrating a
58 Make Data Integrity
Integral to CGMP Training
State of Control
Do you have acceptable control of your
instruments and analytical procedures?
TROUBLESHOOTING
49 Examining
Blow-Fill-Seal Technology
for Aseptic Processes
DEPARTMENTS/
PRODUCTS
12 Product Spotlight
55 Showcase/Marketplace
57 Ad Index
Susan Schniepp, distinguished
fellow at Regulatory Compliance
Associates, discusses training
personnel on data integrity.
Industry experts discuss common
considerations and recent technological
advancements in blow-fill-seal technology.
OUTSOURCING OUTLOOK
52 Watch Out
for the Hangover
Acquisition binges often lead
to hangovers; here’s what to watch out for.
PHARMACEUTICAL TECHNOLOGY (Print ISSN: 1543-
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PharmTech.com
Industry Moves Closer to
Continuous Manufacturing
Pharmtech.com/pt/forum
PharmTech.com/forum
Rita Peters
With technology advances, continuous manufacturing
shows steady progress to more widespread adoption.
C
ontinuous manufacturing of pharmaceuticals is one of five manufacturing technology areas of emerging
priority, according to an April 2016 report on advanced manufacturing issued
by the National Science and Technology
Council (NSTC), a government organization that sets national goals for federal
science and technology investments (1).
FDA has been actively encouraging
bio/pharmaceutical companies to adopt
continuous manufacturing processes as
part of efforts to update manufacturing
facilities, improve quality and efficiencies, and ultimately, reduce drug shortages. The National Science Foundation
(NSF), National Institutes of Health,
National Institute of Standards and
Technology, Department of Defense,
and the Biomedical Advanced Research
and Development Authority (BARDA)
are also promoting the use of continuous manufacturing.
In addition, as FDA has accelerated
approvals of breakthrough drugs, it has
identified the need for earlier scale-up
chemistry, manufacturing, and controls (CMC) work. To meet the development needs, FDA outlined a plan to
develop an understanding these new
technologies, in advance of the review
process, in its draft guidance, Advancement of Emerging Technology Applica-
Rita Peters is editorial
director of Pharmaceutical
Technology. Send your
thoughts and story ideas
to [email protected].
10
Pharmaceutical Technology
JUNE 2016
tions to Modernize the Pharmaceutical
Manufacturing Base (2), published in
December 2015.
Progress, but work to be done
There has been some progress in continuous manufacturing. In April 2016,
FDA approved a continuous manufacturing line, which replaced an existing
batch process, for the manufacture of
PREZISTA (darunavir) 600 mg tablets
by Janssen Supply Chain in Gurabo,
Puerto Rico. The development of the
continuous process that integrates all
manufacturing steps (weighing, milling, blending, compression, and coating)
into one single line is a result of a fiveyear partnership with Rutgers University and the University of Puerto Rico.
The Janssen Supply Chain conversion is a positive step forward in the
move to continuous manufacturing.
On the biologics drug manufacturing
side, with more complex manufacturing processes, progress has been slower
and incremental. At INTERPHEX
2016 in April, equipment manufacturers displayed systems that fit process
development and scale-up continuum
that could help drug companies move
forward in these efforts. Several equipment manufacturers displayed systems
that could work in a progressive chain,
eliminating some batch process steps.
Single-use systems are key components of the adoption of continuous
manufacturing. Complexity and scale,
however, are two stumbling blocks to the
implementation of single-use systems on
the commercial manufacturing scale,
according to participants in a panel discussion hosted by Pharmaceutical Tech-
P h a r mTe c h . c o m
nology and BioPharm International. The
time needed to develop a process is often
underestimated because the process is
more involved than people expect. In
addition, single use is not practical to use
for very large volumes, such as 10,000 L;
practical use of the system, versus volume, must be considered.
A continuous supply of consumables is
vital to both batch and continuous manufacturing processes. At INTERPHEX,
suppliers reported increased demand for
custom formulations and packaging, and
quality control reports. Several suppliers
reported facility expansions to increase
capacity and offer redundant operations
to ensure a continuity of supply of vital
materials in the event of manufacturing
problems at another facility. Another
trend is a shift toward in-line dilution
and systems that provide access to large
volumes of buffers without having to expand buffer storage areas.
With a goal to provide a continuous
supply of quality drugs to patients, the
bio/pharma industry is seeing some
incremental progress. It is up to bio/
pharma companies to see that this
trend continues.
References
1. Executive Office of the President, National Science and Technology Council
“Advanced Manufacturing: A Snapshot
of Priority Technology Areas Across the
Federal Government,” by the Subcommittee for Advanced Manufacturing of
the National Science and Technology
Council (April, 2016).
2. FDA, Draft Guidance–Advancement of
Emerging Technology Applications to
Modernize the Pharmaceutical Manufacturing Base (Rockville, MD, December
2015). PT
JORG GREUEL/PHOTODISC/GETTY IMAGES
FROM THE EDITOR
PRODUCT SPOTLIGHT
Washdown Duty
Ribbon Blenders
Acoustic Separator
Streamlines Clarifications
Washdown duty ribbon
blenders from Ross, Charles &
Son can be used to mix dry
blends such as grains, powders,
pellets, and flakes. Small
amounts of liquid may be
sprayed throughout the batch
during the blending cycle for
uniform distribution. Wet
applications such as pastes,
slurries, and suspensions can
also be prepared in these
blenders. The blenders feature a horizontal agitator with
characteristic inner and outer helical ribbons pitched to move the
materials in a well-balanced axial and radial flow pattern. The
blenders are equipped with all washdown components including the
motor, safety limit switch, variable frequency drive, stuffing boxes,
and knife gate discharge valve. The dust-tight cover includes a
charging port with safety grating, and the U-shaped trough is
surrounded by a 100-psi ASME-stamped jacket for heating/cooling.
The Cadence Acoustic
Separator (CAS) from Pall Life
Sciences enables the
purification of bioprocesses
fluids without the use of
primary depth filters or
centrifuges. CAS was
developed by FloDesign Sonics
and is licensed by Pall. CAS’s acoustic wave separation (AWS)
technology applies acoustic forces across a countercurrent flow of
bioprocess fluid to generate three-dimensional standing waves that
trap cells in their nodes. The cells in the bioprocess fluid will
agglomerate and eventually sediment as it loses its buoyancy.
The CAS does not cause any significant increase in temperature or
damage to cells or proteins. The CAS system allows for the reduction
of 75% of the filtration area and associated buffer volume
requirements. AWS technology is applicable for the clarification of
biologic products, including recombinant therapeutic proteins and
monoclonal antibodies. In addition, the CAS is a single-use
clarification system that enables continuous processing.
Ross, Charles & Son
www.mixers.com
Pall Life Sciences
www.pall.com
Dropper Eliminates Need
for Isolation and Insertion
Sensors Allow for
Bluetooth Connectivity
The MD-Dropper Cap from HealthStar is a new
dropper bottle technology for blow-fill-seal (BFS)
technology. The design produces metered-dose
eye drops with standard BFS technology,
without the added step of isolation/insertion
technology. The containers are molded using
standard BFS manufacturing machines and
procedures. Cycle times are maintained at
normal BFS output levels, typically around 12
seconds. The pre-assembled and sterilized
containers are snapped onto the BFS containers
post manufacturing in a cleanroom
environment. The contents of the bottle are
never in contact with the MD-Dropper Cap until
activated by the patient.
HealthStar
www.healthstaronline.com
The ArcAir communication
package from Hamilton
Company enables Bluetooth 4.0
wireless connectivity in all
environments. The Bluetooth
capability allows users to view or
control Hamilton Arc Sensors
from devices including smart
phones and tablets. ArcAir apps
are available online for Android
and iOS platforms. The arc
sensors are measuring tools that
contain a built-in microprocessor and provide direct digital and
analog communication. The ArcAir mobile application for Arc pH,
dissolved oxygen, and conductivity measurement can communicate
wirelessly with up to 30 individual sensors at the same time. Hamilton
also offers a Bluetooth version of its GMP Compliance Package,
which works with ArcAir Advanced and provides centralized
management of users and validation reports for calibration,
verification, configuration, and communication within the GMP
guidelines for all Arc sensors.
Hamilton Company
www.hamiltoncompany.com
12
Pharmaceutical Technology
JUNE 2016
P h a r mTe c h . c o m
Unifying SFE/SFC Workflows
Sample Prep to Analysis in One Click
Nexera UC on-line SFE-SFC is the first system
to break the technology barrier between automated
sample pre-treatment and chromatographic analysis
using supercritical mobile phase.
Automatic extraction of up to 48 samples
with seamless transfer to SFC/MS provides:
Q
Rapid separation harnessing the unique characteristics of
supercritical mobile phase
Q
Efficient separation of isomers and enantiomers
Q
High-sensitivity detection using a variety of separation modes
www.ssi.shimadzu.com/UC
Q
Split-less introduction to MS for enhanced trace analysis
Order consumables and accessories on-line at http://store.shimadzu.com
Shimadzu Scientific Instruments Inc., 7102 Riverwood Dr., Columbia, MD 21046, USA
Q
Reduced environmental impact and mobile phase cost
compared to typical organic solvents
Learn more about Shimadzu’s Nexera UC.
Call (800) 477-1227 or visit us online at
Jill Wechsler is Pharmaceutical Technology’s
Washington editor, tel. 301.656.4634,
[email protected].
Modern Manufacturing Comes of Age
FDA and bio/pharma companies get serious about continuous manufacturing to ensure product quality.
he need for more efficient methods to produce breakthrough therapies and biosimilars, along with strategies to
manufacture conventional drugs more economically and reliably, is sparking industry investment in more sophisticated and
innovative systems for making drugs and biologics. The shift
to personalized or precision medicine and cellular and gene
therapies puts a premium on fast production of small batches
of cutting-edge medicines. At the same time, pressure to
reduce manufacturing costs and to avoid shortages and recalls
demands more reliable methods for ensuring the quality of
large batches of conventional drugs.
At a Congressional briefing on breakthrough therapies in
April 2016 (1), Janet Woodcock, director of FDA’s Center for
Drug Evaluation and Research (CDER), noted that the need
to achieve more streamlined product development for
breakthroughs and other complex biopharmaceuticals is
prompting a shift away from batch processing to continuous
m a n u f a c t u r i n g (C M ) s y s t e m s . A c c e l e r a t e d p r o d u c t
development means that manufacturers have less time to
refine processes, putting a premium on flexible systems able
to produce small batches quickly and efficiently. More flexibility
in stability testing also has become accepted for breakthrough
products that have small lots sizes and are consumed quickly
and thus have less need for two-year stability profiles upfront.
FDA encourages investment
Regulatory decisions are encouraging industry adoption of
new manufacturing technologies after years of reluctance. In
August 2015, FDA approved for the first time a 3D printed pill,
a form of the epilepsy drug Spirtam (levetiracetam) produced
by Aprecia Pharmaceuticals of New Jersey; it disintegrates
more rapidly in the patient’s mouth to aid those who have difficulty swallowing (2).
In a landmark decision on a manufacturing change, FDA
authorized a switch from batch production to a continuous
manufacturing process at Johnson & Johnson’s Janssen
plant in Guarbo, Puerto Rico (3). J&J expects its new CM line
for producing the HIV drug Prezista (darunavir) will reduce
manufacturing and testing cycle time by 80% and cut waste by
a third. Entire batches will not have to be discarded if a problem
appears, and the process requires only two rooms instead of
seven. J&J expects to make three-fourths of its high-volume
products through continuous manufacturing within a decade.
Vertex has drawn attention to its CM process for producing
its cystic fibrosis drug Orkambi (lumacaftor/vacaftor), approved
by FDA in 2015. The firm announced an agreement with
contract manufacturer Hovione to establish a CM plant in New
Jersey that will expand production for Vertex and give Hovione
the capability of offering similar services to other clients (4).
14
Pharmaceutical Technology
JUNE 2016
P h a r mTe c h . c o m
According to press reports, GlaxoSmithKline is building a CM
facility in Singapore, and Eli Lilly is investing in a CM operation
in Cork, Ireland. Amgen has been shifting to more flexible
production operations for its protein-based drugs for several
years, most notably at a $200-million plant in Singapore
that features modular designs and continuous processing.
Amgen also is working with contract manufacturer Patheon to
develop additional capacity for innovative production of new
therapies in additional global markets.
I n d u s t r y ex p e r t s a r e e n c o u r a g i n g s u c h m ove s , a s
seen in a May 2015 report from Deloitte on “Advanced
Biopharmaceutical Manufacturing” (5). The study summarizes
how continuous manufacturing, single-use systems, and other
technological innovations are transforming drug production,
noting that the need to devise more effective drug-delivery
systems and combination products makes manufacturing
“more central to the effectiveness of medicine.” Pharma
companies thus are collaborating more with component
manufacturers and technology developers to devise portable
manufacturing components that can be deployed quickly to
critical locations.
Policy support
Such industry investment decisions are gratifying to Woodcock
and other FDA officials, who have been urging pharma adoption of modern manufacturing for years, most visibly as part of
the agency’s 2002 Pharmaceutical cGMPs for the 21st Century
initiative. A 2004 guidance urged adoption of a process analytical technology (PAT) framework for innovative pharmaceutical
development that builds quality testing into pharmaceutical
manufacturing processes (6).
Manufacturers, however, were reluctant to invest millions
of dollars in such systems without assurance that innovation
won’t slow product approval or draw objections from plant
inspectors. CDER’s Office of Pharmaceutical Quality (OPQ)
has renewed the quality manufacturing campaign by offering
early advice on innovative systems and coordinating review
and inspection to avoid delays. CDER published guidance
in December 2015 outlining how its Emerging Technology
Team (ETT) will coordinate assessment of new manufacturing
technologies to facilitate approval of such systems and
processes (7).
S o f a r t h e E T T h a s p a r t i c i p a t e d i n m o r e t h a n 25
meetings with sponsors to discuss manufacturing design
and development issues and to offer recommendations for
submission content for innovative technologies. The aim,
says OPQ director Michael Kopcha, is to identify and address
“potential roadblocks” and prevent delays related to adopting
promising new technologies.
GLOBE: ZOONAR RF/GETTY IMAGES
T
The Obama administration also is encouraging investment in
advanced manufacturing technologies to facilitate efficient and
reliable production of both conventional drugs and innovative
cellular products and regenerative medicines. A report issued in
April 2016 by the White House National Science and Technology
Council identifies these topics as areas of “emerging priority”
that warrant further federal government investment and publicprivate collaboration to move forward (8). Cutting-edge biologics
require process control methods able to overcome technical
challenges in developing new enzymes and proteins that can lead
to regenerative therapies able to repair or replace non-functioning
tissues and organs. And continuous manufacturing, which is
widely used in the food, chemical, and petroleum industries, has
the potential to provide multiple benefits for pharmaceutical and
biotech manufacturers, including smaller size plants, less raw
materials, streamlined storage and testing requirements, reduced
product waste, and shorter manufacturing cycles.
The White House panel notes that such systems may be
particularly important in producing medical countermeasures
and treatments for infectious diseases, which often demand
rapid responses to emerging threats. Modular and plug-andplay equipment with reusable, flexible, or interchangeable
SEE US AT AACC
BOOTH #3949
16
Pharmaceutical Technology
JUNE 2016
P h a r mTe c h . c o m
parts are especially important for producing specialty orphan
or breakthrough drugs and emergency treatments. Support
for advancing bio/pharma manufacturing methods already is
coming from the National Institutes of Health, the Department of
Defense, the National Institute of Standards and Technology, and
the Biomedical Advanced Research and Development Authority
(BARDA) in the Department of Health and Human Services. And
FDA is working with BARDA to support enabling technologies that
encourage commercial adoption of continuous manufacturing.
Many of these is sues were discus sed in A pril at a
conference on continuous manufacturing in Baltimore, MD,
sponsored by the International Society for Pharmaceutical
Engineering (ISPE). Panels addressed whether CM creates
unique considerations for process validation, managing
deviations in real time, and use of sensors and monitoring
systems. Key issues for CM implementation include batch
definition, materials traceability, and control strategy support
for integrated drug specifications. CM for bioprocessing,
moreover, involves new approaches for dealing with
deviations, ensuring microbial control, and using inline
measurements to confirm proper process performance.
A related challenge is that all these innovations require
manufacturers to identify and train specialized workers to
have the expertise and experience needed to operate and
manage modern production systems.
References
1. J. Wechsler, “Modern Manufacturing Required for Breakthrough
Drugs,” PharmTech.com, April 15, 2016, www.pharmtech.com/
modern-manufacturing-required-breakthrough-drugs-0
2. Aprecia Pharmaceuticals, “FDA Approves the First 3D Printed
Drug Product,” Press Release, Aug. 3, 2015, www.multivu.com/
players/English/7577251-aprecia-pharmaceuticals-spritam/
3. L. Yu, “Continuous Manufacturing Has a Strong Impact on Drug
Quality,” FDAVoice blog, April 12, 2016, http://blogs.fda.gov/
fdavoice/index.php/2016/04/continuous-manufacturing-hasa-strong-impact-on-drug-quality/?source=govdelivery&utm_
medium=email&utm_source=govdelivery
4. Hovione, “Hovione and Vertex Partner in Continuous Manufacturing,” Press Release, March 10, 2016, www.hovione.com/
press-room/press-release/hovione-and-vertex-partner-continuous-manufacturing
5. Deloitte, “Advanced Biopharmaceutical Manufacturing: An Evolution Underway,” White Paper, www2.deloitte.com/content/dam/
Deloitte/us/Documents/life-sciences-health-care/us-lshc-advanced-biopharmaceutical-manufacturing-white-paper-051515.pdf
6. FDA, Guidance for Industry PAT—A Framework for Innovative
Pharmaceutical Development, Manufacturing, and Quality Assurance (CDER, CVM, ORA, September 2004).
7. FDA, Advancement of Emerging Technology Applications to Modernize the Pharmaceutical Manufacturing Base, Draft Guidance (CDER,
December 2015), www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM478821.pdf
8. Subcommittee for Advanced Manufacturing, “Advanced Manufacturing: A Snapshot of Priority Technical Areas Across the
Federal Government,” Executive Office of the President, National Science and Technology Council, April 2016, www.whitehouse.gov/sites/whitehouse.gov/files/images/Blog/NSTC%20
SAM%20technology%20areas%20snapshot.pdf PT
The Parenteral Drug Association presents the...
WASHINGTON, DC –
2016 PDA
Data Integrity Workshop
September 14-15, 2016 | Washington, DC
Renaissance Washington, DC Downtown Hotel
Exhibition: September 14-15
#2016Data
Register
before
August 2
and save
up to $200
The 2016 PDA Data Integrity Workshop, ofered three times in three global locations, will explore the multiple facets of
data integrity, such as quality culture, human behavior, training needs and technology requirements.
Gain a broad perspective on cause and efect and common factors involved in data integrity issues, and benefit
from round table discussions and case studies addressing implementable, best practices for preventing, detecting,
mitigating and remediating data integrity issues.
Submit a poster abstract for presentation at one of the 2016 PDA Data Integrity Workshops!
Abstracts on data integrity issues and industry standards and best practices are highly appreciated.
To learn more and register, please visit pda.org/2016dataeast
To explore all dates and locations for this important workshop, please visit pda.org/2016data
Cover Story: Autoinjectors
including the importance of human
factor engineering.
Building a Better
Self-Injection Solution
Q&A by Adeline Siew, PhD
Experts discuss the key considerations
in the development of an autoinjector.
S
elf-administration is fast becoming
a trend in today’s healthcare as the
pharmaceutical industry continues to tap into the potential of autoinjectors as a drug-delivery solution that
can offer improved patient experience
and compliance. As a result, the market
for autoinjectors is expanding rapidly,
driven primarily by two factors, says
Kevin Deane, medical device expert at
PA Consulting Group, “the proliferation of biologic compounds, which are
filling pharma’s pipelines, and the need
to move drug administration away
from clinics and hospitals into home
use and self-administration.” Deane
notes that Humira (adalimumab) and
Enbrel (etanercept), which are among
the top five best-selling drugs, are
self-administered by patients using
autoinjectors.
18
Pharmaceutical Technology
JUNE 2016
“The autoinjector market grows
because pharmaceutical and biologic
companies are constantly looking to
differentiate their drug-device offerings and provide intellectual-property
(IP) protection against competition,”
highlight Oli Gould, design team
manager, R&D, and Gareth Walker,
human factors specialist, both from
Owen Mumford. It is crucial that product differentiation goes beyond the
molecule, especially when facing the
patent cliff. According to Gould and
Walker, custom-developed autoinjectors can provide opportunities for patented product differentiation, thereby,
helping companies to maintain their
margins and market share.
In this article, Deane, Gould, and
Walker discuss the different aspects
involved in developing an autoinjector,
P h a r mTe c h . c o m
PharmTech: Can you discuss the challenges of developing an autoinjector?
Gould and Walker (Owen Mumford): The
key challenges encountered in the development of an autoinjector are the competing requirements, which include size,
cost, and mass. With design freedom in
these parameters, one can be confident
of achieving any reasonable requirement.
But this is seldom the case. At a minimum, size and mass can directly influence usability and therefore combination
product efficacy.
Ensuring user safety is, of course, the
primary concern. Being intelligent in how
one achieves that level of safety, or indeed,
exceeding established safety benchmarks
will benefit the end-user and can set one
apart from the competition.
Efficacy is, generally, a close second in
priority and, dependent upon the treatment, may be inseparable from safety. Efficacy broadly groups accuracy, reliability,
and usability. Some of the greatest challenges in autoinjector development come
from doing more to achieve excellence in
safety and efficacy (particularly in usability) whilst maintaining a cost-effective
product solution.
Time to market is always an important factor in product-based organizations. Driven by more stringent regulation and increased expectations of
pharmaceutical partners, the rigor in
developmental investigations, in combination with increasing complexity of
device solutions, puts a strain on project timescales.
Deane (PA Consulting): The key challenges in developing an autoinjector are cost of goods, drug viscosity,
and freedom within a crowded IP
landscape.
The requirement to minimize the
cost of goods drives the designer to
minimize the number of parts in
the device. This is most effectively
achieved by placing multiple functions
on each part, but this adds to the complexity and increases the importance
JARED EYGABROAD/GETTY IMAGES
Development challenges
The Parenteral Drug Association presents...
2016 PDA Universe of Pre-filled
Syringes & Injection Devices
October 17-18, 2016 | Huntington Beach, CA
Hyatt Regency Huntington Beach Resort and Spa
Exhibition: October 17-18 | 2016 PDA Drug Delivery Combination Products Workshop: October 19 | Courses: October 20-21
Exploring the latest trends in devices,
connectivity, safety and compliance
Register
before
August 5
and save
up to $600!
The 2016 PDA Universe of Pre-illed Syringes & Injection Devices brings together industry and regulatory experts to tackle the most
pressing issues and latest advancements in pre-filled syringes.
During the course of this Conference, you will learn how to identify, address and explain key challenges in the development,
approval and manufacture of drug delivery combination products to peers and management, recognize potential liabilities and
opportunities within your organization with regard to pre-filled syringes and more!
For more information and to register, visit pda.org/2016prefilled.
Immediately following this event, PDA will host the 2016 PDA Drug Delivery Combination Products Workshop. Pharmaceutical and
medical device professionals will share the challenges they have faced or are currently facing through sessions on topics such as:
Human Factors/Risk Management
Future Solutions to the Patient
Experience/Challenges with Drug
Delivery Devices
Design Verification Testing, Critical
Quality Attributes, Release &
Stability Testing
Design/Technology Transfer
Clinical Studies/Level of Design
Controls Phase I, II & III
GMPs, Inspections & Change
Management
Learn more and register at pda.org/2016combo.
And, on October 20-21, PDA’s Education Department will hold two courses complementing what you have learned:
Understanding and Addressing Technical, Quality, and Regulatory Challenges for Drug Delivery Combination Products (October 20)
Essential Elements of Extractables and Leachables: From Material Extraction to Final Report (October 21)
Learn more and register at pda.org/2016PrefilledCourses.
#2016prefilled
Cover Story: Autoinjectors
of design for manufacture and assembly activities.
Drug viscosity can prove a challenge
both at high and low viscosities. At
high viscosity, a high power source is
required to ensure the injection time is
acceptably short for the user. Retaining
such high loads throughout the shelf life
of the device and ensuring the device
still functions, are challenging and require extensive modeling and accelerated aging to simulate high stress and
long life. At low viscosity, the challenge
is lengthening the injection time to
avoid pain, but at the same time, avoiding device stall as friction loads dominate the injection. Both of these aspects
can be partially solved by modification
of the needle size, but this change is not
available to the designer.
The IP landscape for autoinjectors is
crowded, particularly in the space offering the simplest and most reliable
device architecture. A sleeve actuated
autoinjector, which is becoming the
standard embodiment, is not a complex device. The function can be fulfilled with a small number of parts,
and thus, there are a limited number
of mechanisms that will provide the
functionality. As a result, there are limited opportunities to innovate without
infringing existing IP. To overcome
this design constraint and avoid the
need to license, the designer is driven
to move to less elegant design solutions,
typically introducing additional parts
or suboptimal mechanisms, with a
knock-on impact on molding and assembly complexity as well as the inevitable impact on cost of goods.
the user is exposed to inconsistent injection depths and variable injection
times. Moreover, there is a risk of damaging the syringe, presenting a safety
risk to the user. The designer can solve
some of these problems with complex
mechanisms (e.g., electromechanical
closed-loop feedback systems), but to
effectively integrate the syringe requires extensive testing and characterization. The characterization is complicated by the lack of access to multiple
syringe manufacturing batches (both
unfilled and filled) and the difficulty
of capturing the force to expel the drug.
Access to multiple batches can be impossible if the drug is in development,
and filling is not representative of the
production fill. Even in later stages, getting hold of multiple batches to assess
process variability is difficult due to the
mismatch in syringe and autoinjector
production volumes. This issue necessitates that characterization activities continue throughout the development.
Capturing the force to expel the
drug is challenging as the typical
autoinjector power source, a spring,
generates a decaying force during the
delivery of the dose. Some theoretical
modeling is possible, but limited in its
validity. Empirical testing presents its
own challenge as standard test equipment does not exist. Dynamic force
testers are available but have limited
functionality. Thus, typically a combination of constant force, constant
velocity, and device power pack testing
is used to measure the force to expel
the drug.
Cartridges require the same force
characterization, but the geometry
Prefilled syringes and cartridges
specification is much tighter. The adPharmTech: How can prefilled syringes ditional challenge of the cartridge is
and cartridges be effectively integrated designing the interface with the needle.
into an autoinjector?
In its simplest form, this design can be
Deane (PA Consulting): The prefilled user applied (which has associated ussyringe was never designed to be ability challenges and user safety risks).
mounted within an automated deliv- In the more complex form, the device
ery device such as an autoinjector. As must automatically couple the needle
a result, the geometry and emptying to the cartridge, piercing the septum
force are poorly defined and controlled. as part of the injection process.
Unlike a person, an autoinjector canGould and Walker (Owen Mumford): The
not adapt to this variability and thus, resistance from the stopper to move20
Pharmaceutical Technology
JUNE 2016
P h a r mTe c h . c o m
ment within the container (from friction), strength of the container, resistance of the needle shield to removal,
and general geometry (including relative position of the stopper in particular) are key parameter considerations
when integrating prefilled syringes
and containers into an autoinjector.
However, what may be an even more
important consideration than the
nominal state of these parameters is
their natural manufacturing variations. For example, many autoinjectors
make use of a compression or torsion
spring to evacuate the container and
thus, the force exerted decreases as the
fluid is evacuated. Conversely, a stopper within a poorly lubricated container may increase its resistance as it
reaches the end of evacuation. The design of the autoinjector must allow for
this change, and any variation, within
its design.
The strength of a container is often
a key consideration also. We’re seeing
a trend in increasing formulation viscosities as drug technologies change
and the frequency of injection reduces.
These more viscous f luids require
greater delivery loads and more stress
on the container as a result. Well-engineered support for the container and
control over impact velocities are necessary to maintain container integrity.
Regulatory guidelines
PharmTech: Human factors are a key
consideration when developing a drug
delivery device, such as an autoinjector. What guidelines have regulators
such as FDA and EMA provided on
this aspect?
Gould and Walker (Owen Mumford): The
development of medical devices is
governed by a number of regulations
that can sometimes be baffling in their
complexity. Even within the realms of
regulations relating to human factors,
ease of comprehension is sometimes
overlooked. To address this aspect
and help manufacturers understand
the regulatory requirements, a number of guidance documents have been
created. Most recently, in April 2016,
The Parenteral Drug Association presents...
ARLINGTON, VA –
2016 PDA Workshop:
Current Challenges in Aseptic Processing,
Potential Changes in EMA/PIC/S Annex 1 Revision
Addressing the Unanswered Questions of How to Use Risk- and Science-Based Approaches
to Meet Global Health Authority Expectations and Improve Aseptic Processing
October 26-27, 2016 | Arlington, VA
Hyatt Regency Crystal City
Exhibition: October 26-27
#2016annex
Register
before
September 9
and save
up to $200
Workshop Theme: Points to Consider in Modern Aseptic
Manufacturing – with Special Reference to the On-going Revision of
the European GMPs for Sterile Medicines
The 2016 PDA Workshop: Current Challenges in Aseptic Processing, Potential Changes in EMA/PIC/S Annex 1 Revision will serve as
a forum for industry and regulatory professionals to discuss science- and risk-based approaches that support modern aseptic
processing and control strategies, and explore critical topics that may be addressed in the revised EU GMP Annex 1 guidance.
This interactive Workshop is a unique opportunity to engage with peers, industry leaders and experts on a wide range of topics, including:
6
Physical Environment and
Environmental Monitoring
6
6
Personnel and Material
Transfer
Process Simulation
6
Cleaning, Disinfecting,
Sterilization and Critical
Utilities
6
Aseptic Processing
Moving Forward
Make sure you are a part of this important conversation that will shape the future of aseptic processing.
For more information and to register today, please visit pda.org/2016annex1east
To ofer you the mo
Blow-Fill-Seal
PLUS: Technology
Data Integrity
Training
Using Modular
Construction
JUNE 2016 Volume 40 Number 6
PHARMACEUTICAL TECHNOLOGY
From
Syringe to
Autoinjector
Building a Better
Self-Injection
Solution
JUNE 2016
PharmTech.com
PEER-REVIEWED
Qualifying Personnel to Visually
Inspect Cleaned Equipment, Part II
SINGLE -USE SYSTEMS
Integrating Single-Use Systems
FORMULATION
Customizing HPMC
API SYNTHESIS & MANUFACTURING
Adoption of Continuous Processing
Advancing Drug Delivery
Through Superior Polymer Design
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(Design department)
Each customer has its very own special requirements. That’s why we,
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EDITORIAL
Editorial Director Rita Peters [email protected]
Senior Editor Agnes Shanley [email protected]
Managing Editor Susan Haigney [email protected]
Science Editor Adeline Siew, PhD [email protected]
Manufacturing Editor Jennifer Markarian [email protected]
Science Editor Randi Hernandez [email protected]
Community Manager Caroline Hroncich [email protected]
Art Director Dan Ward
Contributing Editors Jill Wechsler [email protected]; Jim Miller
[email protected]; Hallie Forcinio [email protected]; Susan J. Schniepp
[email protected]; Eric Langer [email protected];
and Cynthia A. Challener, PhD [email protected]
Correspondent Sean Milmo (Europe, [email protected])
485 Route One South, Building F, Second Floor, Iselin, NJ 08830, USA
Tel. 732.596.0276, Fax 732.647.1235, PharmTech.com
EDITORIAL ADVISORY BOARD
Pharmaceutical Technology publishes contributed technical articles that undergo a
rigorous, double-blind peer-review process involving members of our distinguished
Editorial Advisory Board. Manuscripts should be sent directly to the managing editor. Below is a partial list
of the Pharmaceutical Technology brand editorial advisory members. The full board, which includes advisory
members from Pharmaceutical Technology Europe, can be found online at PharmTech.com.
James P. Agalloco
President,
Agalloco & Associates
Larry L. Augsburger, PhD
Professor Emeritus
University of Maryland
David H. Bergstrom, PhD
Senior Vice-President,
Pharmaceutical Development &
Corporate Quality Assurance
Antares Pharma, Inc.
Phil Borman
QbD Lead & Data Management &
Analysis Manager
GlaxoSmithKline
Rory Budihandojo
Lachman Consultants
Metin Çelik, PhD
President,
Pharmaceutical Technologies
International (PTI)
Zak T. Chowhan, PhD
Consultant, Pharmaceutical
Development
Suggy S. Chrai, PhD
President and CEO,
Chrai Associates, Inc.
Roger Dabbah, PhD
Principal Consultant,
Tri-Intersect Solutions
Robert Dream
Managing Director
HDR Company
Tim Freeman
Managing Director,
FreemanTechnology
Sanjay Garg, PhD
Professor and Director,
Centre for Pharmaceutical
Innovation and Development,
University of South Australia
R. Gary Hollenbeck, PhD
Chief Scientific Officer,
UPM Pharmaceuticals
Ruey-ching (Richard) Hwang, PhD
Senior Director,
Pharmaceutical Sciences,
Pfizer Global R&D
Gurvinder Singh Rekhi, PhD
Department of Pharmaceutical and
Biomedical Sciences,
The University of Georgia College
of Pharmacy
Mansoor A. Khan, PhD
Professor & Vice Dean
Irma Lerma Rangel College of
Pharmacy, Texas A&M Health
Science Center
Susan J. Schniepp
Fellow
Regulatory Compliance Associates
Heidi M. Mansour, PhD
Assistant Professor
College of Pharmacy
& The BIO5 Research Institute,
University of Arizona–Tucson
Jim Miller
President,
PharmSource Information
Services Bio/Pharmaceutical
Outsourcing Report
David R. Schoneker
Director of Global Regulatory Affairs,
Colorcon
Aloka Srinivasan
Principal Consultant,
PAREXEL International
Read board members’
biographies online at
PharmTech.com/
pharmtech-editorialadvisory-board.
Colin Minchom, PhD
Senior Director Pharmaceutical
Sciences, Shire Pharmaceuticals
R. Christian Moreton, PhD
Partner, Finnbrit Consulting
Fernando J. Muzzio, PhD
Director, NSF Engineering
Research Center on Structured
Organic Particulate Systems,
Dept. of Chemical and Biochemical
Engineering, Rutgers University
Moheb M. Nasr, PhD
Vice-President, CMC Regulatory
Strategy, Global Regulatory Affairs,
GlaxoSmithKline
Garnet E. Peck, PhD
Professor Emeritus of Industrial
Pharmacy, Purdue University
Pharmaceutical Technology
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European Sales Manager Linda Hewitt [email protected]
European Senior Sales Executive Stephen Cleland [email protected]
Executive Assistant Barbara Sefchick [email protected]
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SALES
Publisher Mike Tracey [email protected]
JUNE 2016
P h a r mTe c h . c o m
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June 2016 Volume 40 Number 6
Pharmaceutical Technology is the authoritative source of peer-reviewed research
and expert analyses for scientists, engineers, and managers engaged in process
development, manufacturing, formulation and drug delivery, API synthesis, analytical
technology and testing, packaging, IT, outsourcing, and regulatory compliance in the
pharmaceutical and biotechnology industries.
On the cover
COVER STORY
18 Building
a Better
Self-Injection Solution
Experts discuss the key considerations
in the development of an autoinjector.
Cover Design by Dan Ward;
Images: Jared Eygabroad/Getty Images
ON PHARMTECH.COM
FEATURES
FORMULATION
VIEWPOINT
24 Customizing HPMC to
39 PAT: “Gateway Drug”
Minimize Drug Variability
to the 21st Century for
the Pharma Industry
The authors evaluated the
performance and robustness of
controlled-release tablets made
with HPMC blends of unimodal and
bimodal molecular weight distribution.
API SYNTHESIS & MANUFACTURING
30 Steps Closer
to the Adoption of
Continuous Processing
Application of flow chemistry for smallmolecule API synthesis continues to
expand thanks to research efforts.
Process analytical technology paved
the way for continuous manufacturing.
SINGLE-USE SYSTEMS
42 Integrating
Single-Use Systems in
Pharma Manufacturing
Industry experts discuss the benefits and
challenges of using single-use systems
in pharmaceutical manufacturing.
FACILITY DESIGN
45 Deciding When to
Use Modular Construction
Different types of modular systems
have advantages and disadvantages.
What’s Behind NIH’s
Quality Problems?
Drug manufacturing lapses
undermine NIH research programs.
www.pharmtech.com/what-s-behindnih-s-quality-problems-0
Any Chance for “Cures”
Legislation This Year?
Biomedical innovation
legislation may stall in 2016.
www.pharmtech.com/any-chancecures-legislation-year
EU on a Mission to Boost R&D
In a move to encourage drug
development, EU regulators are
offering scientific advice to companies
on major efficacy, safety, and quality
issues at an early stage.
www.pharmtech.com/eu-missionboost-rd
Continued on page 8
PEER-REVIEWED RESEARCH
EQUIPMENT CLEANING
34 Qualifying Personnel to Visually Inspect Cleaned
Equipment, Part II: Small vs. Large Group Training
This article presents recommendations based on a program that was set up to qualify
members of a large, diverse team at one oral solid-dosage-form manufacturing facility.
PharmTech.com
Continued from page 6
NEWS & ANALYSIS
FROM THE EDITOR
REGULATION
& COMPLIANCE
10 Industry
US REGULATORY WATCH
14 Modern
Moves Closer
to Continuous
Manufacturing
Manufacturing
Comes of Age
With technology advances, continuous
manufacturing shows steady progress
to more widespread adoption.
FDA and bio/pharma companies
get serious about continuous
manufacturing to ensure product quality.
STATISTICAL SOLUTIONS
ASK THE EXPERT
47 Demonstrating a
58 Make Data Integrity
Integral to CGMP Training
State of Control
Do you have acceptable control of your
instruments and analytical procedures?
TROUBLESHOOTING
49 Examining
Blow-Fill-Seal Technology
for Aseptic Processes
DEPARTMENTS/
PRODUCTS
12 Product Spotlight
55 Showcase/Marketplace
57 Ad Index
Susan Schniepp, distinguished
fellow at Regulatory Compliance
Associates, discusses training
personnel on data integrity.
Industry experts discuss common
considerations and recent technological
advancements in blow-fill-seal technology.
OUTSOURCING OUTLOOK
52 Watch Out
for the Hangover
Acquisition binges often lead
to hangovers; here’s what to watch out for.
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PharmTech.com
Industry Moves Closer to
Continuous Manufacturing
Pharmtech.com/pt/forum
PharmTech.com/forum
Rita Peters
With technology advances, continuous manufacturing
shows steady progress to more widespread adoption.
C
ontinuous manufacturing of pharmaceuticals is one of five manufacturing technology areas of emerging
priority, according to an April 2016 report on advanced manufacturing issued
by the National Science and Technology
Council (NSTC), a government organization that sets national goals for federal
science and technology investments (1).
FDA has been actively encouraging
bio/pharmaceutical companies to adopt
continuous manufacturing processes as
part of efforts to update manufacturing
facilities, improve quality and efficiencies, and ultimately, reduce drug shortages. The National Science Foundation
(NSF), National Institutes of Health,
National Institute of Standards and
Technology, Department of Defense,
and the Biomedical Advanced Research
and Development Authority (BARDA)
are also promoting the use of continuous manufacturing.
In addition, as FDA has accelerated
approvals of breakthrough drugs, it has
identified the need for earlier scale-up
chemistry, manufacturing, and controls (CMC) work. To meet the development needs, FDA outlined a plan to
develop an understanding these new
technologies, in advance of the review
process, in its draft guidance, Advancement of Emerging Technology Applica-
Rita Peters is editorial
director of Pharmaceutical
Technology. Send your
thoughts and story ideas
to [email protected].
10
Pharmaceutical Technology
JUNE 2016
tions to Modernize the Pharmaceutical
Manufacturing Base (2), published in
December 2015.
Progress, but work to be done
There has been some progress in continuous manufacturing. In April 2016,
FDA approved a continuous manufacturing line, which replaced an existing
batch process, for the manufacture of
PREZISTA (darunavir) 600 mg tablets
by Janssen Supply Chain in Gurabo,
Puerto Rico. The development of the
continuous process that integrates all
manufacturing steps (weighing, milling, blending, compression, and coating)
into one single line is a result of a fiveyear partnership with Rutgers University and the University of Puerto Rico.
The Janssen Supply Chain conversion is a positive step forward in the
move to continuous manufacturing.
On the biologics drug manufacturing
side, with more complex manufacturing processes, progress has been slower
and incremental. At INTERPHEX
2016 in April, equipment manufacturers displayed systems that fit process
development and scale-up continuum
that could help drug companies move
forward in these efforts. Several equipment manufacturers displayed systems
that could work in a progressive chain,
eliminating some batch process steps.
Single-use systems are key components of the adoption of continuous
manufacturing. Complexity and scale,
however, are two stumbling blocks to the
implementation of single-use systems on
the commercial manufacturing scale,
according to participants in a panel discussion hosted by Pharmaceutical Tech-
P h a r mTe c h . c o m
nology and BioPharm International. The
time needed to develop a process is often
underestimated because the process is
more involved than people expect. In
addition, single use is not practical to use
for very large volumes, such as 10,000 L;
practical use of the system, versus volume, must be considered.
A continuous supply of consumables is
vital to both batch and continuous manufacturing processes. At INTERPHEX,
suppliers reported increased demand for
custom formulations and packaging, and
quality control reports. Several suppliers
reported facility expansions to increase
capacity and offer redundant operations
to ensure a continuity of supply of vital
materials in the event of manufacturing
problems at another facility. Another
trend is a shift toward in-line dilution
and systems that provide access to large
volumes of buffers without having to expand buffer storage areas.
With a goal to provide a continuous
supply of quality drugs to patients, the
bio/pharma industry is seeing some
incremental progress. It is up to bio/
pharma companies to see that this
trend continues.
References
1. Executive Office of the President, National Science and Technology Council
“Advanced Manufacturing: A Snapshot
of Priority Technology Areas Across the
Federal Government,” by the Subcommittee for Advanced Manufacturing of
the National Science and Technology
Council (April, 2016).
2. FDA, Draft Guidance–Advancement of
Emerging Technology Applications to
Modernize the Pharmaceutical Manufacturing Base (Rockville, MD, December
2015). PT
JORG GREUEL/PHOTODISC/GETTY IMAGES
FROM THE EDITOR
PRODUCT SPOTLIGHT
Washdown Duty
Ribbon Blenders
Acoustic Separator
Streamlines Clarifications
Washdown duty ribbon
blenders from Ross, Charles &
Son can be used to mix dry
blends such as grains, powders,
pellets, and flakes. Small
amounts of liquid may be
sprayed throughout the batch
during the blending cycle for
uniform distribution. Wet
applications such as pastes,
slurries, and suspensions can
also be prepared in these
blenders. The blenders feature a horizontal agitator with
characteristic inner and outer helical ribbons pitched to move the
materials in a well-balanced axial and radial flow pattern. The
blenders are equipped with all washdown components including the
motor, safety limit switch, variable frequency drive, stuffing boxes,
and knife gate discharge valve. The dust-tight cover includes a
charging port with safety grating, and the U-shaped trough is
surrounded by a 100-psi ASME-stamped jacket for heating/cooling.
The Cadence Acoustic
Separator (CAS) from Pall Life
Sciences enables the
purification of bioprocesses
fluids without the use of
primary depth filters or
centrifuges. CAS was
developed by FloDesign Sonics
and is licensed by Pall. CAS’s acoustic wave separation (AWS)
technology applies acoustic forces across a countercurrent flow of
bioprocess fluid to generate three-dimensional standing waves that
trap cells in their nodes. The cells in the bioprocess fluid will
agglomerate and eventually sediment as it loses its buoyancy.
The CAS does not cause any significant increase in temperature or
damage to cells or proteins. The CAS system allows for the reduction
of 75% of the filtration area and associated buffer volume
requirements. AWS technology is applicable for the clarification of
biologic products, including recombinant therapeutic proteins and
monoclonal antibodies. In addition, the CAS is a single-use
clarification system that enables continuous processing.
Ross, Charles & Son
www.mixers.com
Pall Life Sciences
www.pall.com
Dropper Eliminates Need
for Isolation and Insertion
Sensors Allow for
Bluetooth Connectivity
The MD-Dropper Cap from HealthStar is a new
dropper bottle technology for blow-fill-seal (BFS)
technology. The design produces metered-dose
eye drops with standard BFS technology,
without the added step of isolation/insertion
technology. The containers are molded using
standard BFS manufacturing machines and
procedures. Cycle times are maintained at
normal BFS output levels, typically around 12
seconds. The pre-assembled and sterilized
containers are snapped onto the BFS containers
post manufacturing in a cleanroom
environment. The contents of the bottle are
never in contact with the MD-Dropper Cap until
activated by the patient.
HealthStar
www.healthstaronline.com
The ArcAir communication
package from Hamilton
Company enables Bluetooth 4.0
wireless connectivity in all
environments. The Bluetooth
capability allows users to view or
control Hamilton Arc Sensors
from devices including smart
phones and tablets. ArcAir apps
are available online for Android
and iOS platforms. The arc
sensors are measuring tools that
contain a built-in microprocessor and provide direct digital and
analog communication. The ArcAir mobile application for Arc pH,
dissolved oxygen, and conductivity measurement can communicate
wirelessly with up to 30 individual sensors at the same time. Hamilton
also offers a Bluetooth version of its GMP Compliance Package,
which works with ArcAir Advanced and provides centralized
management of users and validation reports for calibration,
verification, configuration, and communication within the GMP
guidelines for all Arc sensors.
Hamilton Company
www.hamiltoncompany.com
12
Pharmaceutical Technology
JUNE 2016
P h a r mTe c h . c o m
Unifying SFE/SFC Workflows
Sample Prep to Analysis in One Click
Nexera UC on-line SFE-SFC is the first system
to break the technology barrier between automated
sample pre-treatment and chromatographic analysis
using supercritical mobile phase.
Automatic extraction of up to 48 samples
with seamless transfer to SFC/MS provides:
Q
Rapid separation harnessing the unique characteristics of
supercritical mobile phase
Q
Efficient separation of isomers and enantiomers
Q
High-sensitivity detection using a variety of separation modes
www.ssi.shimadzu.com/UC
Q
Split-less introduction to MS for enhanced trace analysis
Order consumables and accessories on-line at http://store.shimadzu.com
Shimadzu Scientific Instruments Inc., 7102 Riverwood Dr., Columbia, MD 21046, USA
Q
Reduced environmental impact and mobile phase cost
compared to typical organic solvents
Learn more about Shimadzu’s Nexera UC.
Call (800) 477-1227 or visit us online at
Jill Wechsler is Pharmaceutical Technology’s
Washington editor, tel. 301.656.4634,
[email protected].
Modern Manufacturing Comes of Age
FDA and bio/pharma companies get serious about continuous manufacturing to ensure product quality.
he need for more efficient methods to produce breakthrough therapies and biosimilars, along with strategies to
manufacture conventional drugs more economically and reliably, is sparking industry investment in more sophisticated and
innovative systems for making drugs and biologics. The shift
to personalized or precision medicine and cellular and gene
therapies puts a premium on fast production of small batches
of cutting-edge medicines. At the same time, pressure to
reduce manufacturing costs and to avoid shortages and recalls
demands more reliable methods for ensuring the quality of
large batches of conventional drugs.
At a Congressional briefing on breakthrough therapies in
April 2016 (1), Janet Woodcock, director of FDA’s Center for
Drug Evaluation and Research (CDER), noted that the need
to achieve more streamlined product development for
breakthroughs and other complex biopharmaceuticals is
prompting a shift away from batch processing to continuous
m a n u f a c t u r i n g (C M ) s y s t e m s . A c c e l e r a t e d p r o d u c t
development means that manufacturers have less time to
refine processes, putting a premium on flexible systems able
to produce small batches quickly and efficiently. More flexibility
in stability testing also has become accepted for breakthrough
products that have small lots sizes and are consumed quickly
and thus have less need for two-year stability profiles upfront.
FDA encourages investment
Regulatory decisions are encouraging industry adoption of
new manufacturing technologies after years of reluctance. In
August 2015, FDA approved for the first time a 3D printed pill,
a form of the epilepsy drug Spirtam (levetiracetam) produced
by Aprecia Pharmaceuticals of New Jersey; it disintegrates
more rapidly in the patient’s mouth to aid those who have difficulty swallowing (2).
In a landmark decision on a manufacturing change, FDA
authorized a switch from batch production to a continuous
manufacturing process at Johnson & Johnson’s Janssen
plant in Guarbo, Puerto Rico (3). J&J expects its new CM line
for producing the HIV drug Prezista (darunavir) will reduce
manufacturing and testing cycle time by 80% and cut waste by
a third. Entire batches will not have to be discarded if a problem
appears, and the process requires only two rooms instead of
seven. J&J expects to make three-fourths of its high-volume
products through continuous manufacturing within a decade.
Vertex has drawn attention to its CM process for producing
its cystic fibrosis drug Orkambi (lumacaftor/vacaftor), approved
by FDA in 2015. The firm announced an agreement with
contract manufacturer Hovione to establish a CM plant in New
Jersey that will expand production for Vertex and give Hovione
the capability of offering similar services to other clients (4).
14
Pharmaceutical Technology
JUNE 2016
P h a r mTe c h . c o m
According to press reports, GlaxoSmithKline is building a CM
facility in Singapore, and Eli Lilly is investing in a CM operation
in Cork, Ireland. Amgen has been shifting to more flexible
production operations for its protein-based drugs for several
years, most notably at a $200-million plant in Singapore
that features modular designs and continuous processing.
Amgen also is working with contract manufacturer Patheon to
develop additional capacity for innovative production of new
therapies in additional global markets.
I n d u s t r y ex p e r t s a r e e n c o u r a g i n g s u c h m ove s , a s
seen in a May 2015 report from Deloitte on “Advanced
Biopharmaceutical Manufacturing” (5). The study summarizes
how continuous manufacturing, single-use systems, and other
technological innovations are transforming drug production,
noting that the need to devise more effective drug-delivery
systems and combination products makes manufacturing
“more central to the effectiveness of medicine.” Pharma
companies thus are collaborating more with component
manufacturers and technology developers to devise portable
manufacturing components that can be deployed quickly to
critical locations.
Policy support
Such industry investment decisions are gratifying to Woodcock
and other FDA officials, who have been urging pharma adoption of modern manufacturing for years, most visibly as part of
the agency’s 2002 Pharmaceutical cGMPs for the 21st Century
initiative. A 2004 guidance urged adoption of a process analytical technology (PAT) framework for innovative pharmaceutical
development that builds quality testing into pharmaceutical
manufacturing processes (6).
Manufacturers, however, were reluctant to invest millions
of dollars in such systems without assurance that innovation
won’t slow product approval or draw objections from plant
inspectors. CDER’s Office of Pharmaceutical Quality (OPQ)
has renewed the quality manufacturing campaign by offering
early advice on innovative systems and coordinating review
and inspection to avoid delays. CDER published guidance
in December 2015 outlining how its Emerging Technology
Team (ETT) will coordinate assessment of new manufacturing
technologies to facilitate approval of such systems and
processes (7).
S o f a r t h e E T T h a s p a r t i c i p a t e d i n m o r e t h a n 25
meetings with sponsors to discuss manufacturing design
and development issues and to offer recommendations for
submission content for innovative technologies. The aim,
says OPQ director Michael Kopcha, is to identify and address
“potential roadblocks” and prevent delays related to adopting
promising new technologies.
GLOBE: ZOONAR RF/GETTY IMAGES
T
The Obama administration also is encouraging investment in
advanced manufacturing technologies to facilitate efficient and
reliable production of both conventional drugs and innovative
cellular products and regenerative medicines. A report issued in
April 2016 by the White House National Science and Technology
Council identifies these topics as areas of “emerging priority”
that warrant further federal government investment and publicprivate collaboration to move forward (8). Cutting-edge biologics
require process control methods able to overcome technical
challenges in developing new enzymes and proteins that can lead
to regenerative therapies able to repair or replace non-functioning
tissues and organs. And continuous manufacturing, which is
widely used in the food, chemical, and petroleum industries, has
the potential to provide multiple benefits for pharmaceutical and
biotech manufacturers, including smaller size plants, less raw
materials, streamlined storage and testing requirements, reduced
product waste, and shorter manufacturing cycles.
The White House panel notes that such systems may be
particularly important in producing medical countermeasures
and treatments for infectious diseases, which often demand
rapid responses to emerging threats. Modular and plug-andplay equipment with reusable, flexible, or interchangeable
SEE US AT AACC
BOOTH #3949
16
Pharmaceutical Technology
JUNE 2016
P h a r mTe c h . c o m
parts are especially important for producing specialty orphan
or breakthrough drugs and emergency treatments. Support
for advancing bio/pharma manufacturing methods already is
coming from the National Institutes of Health, the Department of
Defense, the National Institute of Standards and Technology, and
the Biomedical Advanced Research and Development Authority
(BARDA) in the Department of Health and Human Services. And
FDA is working with BARDA to support enabling technologies that
encourage commercial adoption of continuous manufacturing.
Many of these is sues were discus sed in A pril at a
conference on continuous manufacturing in Baltimore, MD,
sponsored by the International Society for Pharmaceutical
Engineering (ISPE). Panels addressed whether CM creates
unique considerations for process validation, managing
deviations in real time, and use of sensors and monitoring
systems. Key issues for CM implementation include batch
definition, materials traceability, and control strategy support
for integrated drug specifications. CM for bioprocessing,
moreover, involves new approaches for dealing with
deviations, ensuring microbial control, and using inline
measurements to confirm proper process performance.
A related challenge is that all these innovations require
manufacturers to identify and train specialized workers to
have the expertise and experience needed to operate and
manage modern production systems.
References
1. J. Wechsler, “Modern Manufacturing Required for Breakthrough
Drugs,” PharmTech.com, April 15, 2016, www.pharmtech.com/
modern-manufacturing-required-breakthrough-drugs-0
2. Aprecia Pharmaceuticals, “FDA Approves the First 3D Printed
Drug Product,” Press Release, Aug. 3, 2015, www.multivu.com/
players/English/7577251-aprecia-pharmaceuticals-spritam/
3. L. Yu, “Continuous Manufacturing Has a Strong Impact on Drug
Quality,” FDAVoice blog, April 12, 2016, http://blogs.fda.gov/
fdavoice/index.php/2016/04/continuous-manufacturing-hasa-strong-impact-on-drug-quality/?source=govdelivery&utm_
medium=email&utm_source=govdelivery
4. Hovione, “Hovione and Vertex Partner in Continuous Manufacturing,” Press Release, March 10, 2016, www.hovione.com/
press-room/press-release/hovione-and-vertex-partner-continuous-manufacturing
5. Deloitte, “Advanced Biopharmaceutical Manufacturing: An Evolution Underway,” White Paper, www2.deloitte.com/content/dam/
Deloitte/us/Documents/life-sciences-health-care/us-lshc-advanced-biopharmaceutical-manufacturing-white-paper-051515.pdf
6. FDA, Guidance for Industry PAT—A Framework for Innovative
Pharmaceutical Development, Manufacturing, and Quality Assurance (CDER, CVM, ORA, September 2004).
7. FDA, Advancement of Emerging Technology Applications to Modernize the Pharmaceutical Manufacturing Base, Draft Guidance (CDER,
December 2015), www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM478821.pdf
8. Subcommittee for Advanced Manufacturing, “Advanced Manufacturing: A Snapshot of Priority Technical Areas Across the
Federal Government,” Executive Office of the President, National Science and Technology Council, April 2016, www.whitehouse.gov/sites/whitehouse.gov/files/images/Blog/NSTC%20
SAM%20technology%20areas%20snapshot.pdf PT
The Parenteral Drug Association presents the...
WASHINGTON, DC –
2016 PDA
Data Integrity Workshop
September 14-15, 2016 | Washington, DC
Renaissance Washington, DC Downtown Hotel
Exhibition: September 14-15
#2016Data
Register
before
August 2
and save
up to $200
The 2016 PDA Data Integrity Workshop, ofered three times in three global locations, will explore the multiple facets of
data integrity, such as quality culture, human behavior, training needs and technology requirements.
Gain a broad perspective on cause and efect and common factors involved in data integrity issues, and benefit
from round table discussions and case studies addressing implementable, best practices for preventing, detecting,
mitigating and remediating data integrity issues.
Submit a poster abstract for presentation at one of the 2016 PDA Data Integrity Workshops!
Abstracts on data integrity issues and industry standards and best practices are highly appreciated.
To learn more and register, please visit pda.org/2016dataeast
To explore all dates and locations for this important workshop, please visit pda.org/2016data
Cover Story: Autoinjectors
including the importance of human
factor engineering.
Building a Better
Self-Injection Solution
Q&A by Adeline Siew, PhD
Experts discuss the key considerations
in the development of an autoinjector.
S
elf-administration is fast becoming
a trend in today’s healthcare as the
pharmaceutical industry continues to tap into the potential of autoinjectors as a drug-delivery solution that
can offer improved patient experience
and compliance. As a result, the market
for autoinjectors is expanding rapidly,
driven primarily by two factors, says
Kevin Deane, medical device expert at
PA Consulting Group, “the proliferation of biologic compounds, which are
filling pharma’s pipelines, and the need
to move drug administration away
from clinics and hospitals into home
use and self-administration.” Deane
notes that Humira (adalimumab) and
Enbrel (etanercept), which are among
the top five best-selling drugs, are
self-administered by patients using
autoinjectors.
18
Pharmaceutical Technology
JUNE 2016
“The autoinjector market grows
because pharmaceutical and biologic
companies are constantly looking to
differentiate their drug-device offerings and provide intellectual-property
(IP) protection against competition,”
highlight Oli Gould, design team
manager, R&D, and Gareth Walker,
human factors specialist, both from
Owen Mumford. It is crucial that product differentiation goes beyond the
molecule, especially when facing the
patent cliff. According to Gould and
Walker, custom-developed autoinjectors can provide opportunities for patented product differentiation, thereby,
helping companies to maintain their
margins and market share.
In this article, Deane, Gould, and
Walker discuss the different aspects
involved in developing an autoinjector,
P h a r mTe c h . c o m
PharmTech: Can you discuss the challenges of developing an autoinjector?
Gould and Walker (Owen Mumford): The
key challenges encountered in the development of an autoinjector are the competing requirements, which include size,
cost, and mass. With design freedom in
these parameters, one can be confident
of achieving any reasonable requirement.
But this is seldom the case. At a minimum, size and mass can directly influence usability and therefore combination
product efficacy.
Ensuring user safety is, of course, the
primary concern. Being intelligent in how
one achieves that level of safety, or indeed,
exceeding established safety benchmarks
will benefit the end-user and can set one
apart from the competition.
Efficacy is, generally, a close second in
priority and, dependent upon the treatment, may be inseparable from safety. Efficacy broadly groups accuracy, reliability,
and usability. Some of the greatest challenges in autoinjector development come
from doing more to achieve excellence in
safety and efficacy (particularly in usability) whilst maintaining a cost-effective
product solution.
Time to market is always an important factor in product-based organizations. Driven by more stringent regulation and increased expectations of
pharmaceutical partners, the rigor in
developmental investigations, in combination with increasing complexity of
device solutions, puts a strain on project timescales.
Deane (PA Consulting): The key challenges in developing an autoinjector are cost of goods, drug viscosity,
and freedom within a crowded IP
landscape.
The requirement to minimize the
cost of goods drives the designer to
minimize the number of parts in
the device. This is most effectively
achieved by placing multiple functions
on each part, but this adds to the complexity and increases the importance
JARED EYGABROAD/GETTY IMAGES
Development challenges
The Parenteral Drug Association presents...
2016 PDA Universe of Pre-filled
Syringes & Injection Devices
October 17-18, 2016 | Huntington Beach, CA
Hyatt Regency Huntington Beach Resort and Spa
Exhibition: October 17-18 | 2016 PDA Drug Delivery Combination Products Workshop: October 19 | Courses: October 20-21
Exploring the latest trends in devices,
connectivity, safety and compliance
Register
before
August 5
and save
up to $600!
The 2016 PDA Universe of Pre-illed Syringes & Injection Devices brings together industry and regulatory experts to tackle the most
pressing issues and latest advancements in pre-filled syringes.
During the course of this Conference, you will learn how to identify, address and explain key challenges in the development,
approval and manufacture of drug delivery combination products to peers and management, recognize potential liabilities and
opportunities within your organization with regard to pre-filled syringes and more!
For more information and to register, visit pda.org/2016prefilled.
Immediately following this event, PDA will host the 2016 PDA Drug Delivery Combination Products Workshop. Pharmaceutical and
medical device professionals will share the challenges they have faced or are currently facing through sessions on topics such as:
Human Factors/Risk Management
Future Solutions to the Patient
Experience/Challenges with Drug
Delivery Devices
Design Verification Testing, Critical
Quality Attributes, Release &
Stability Testing
Design/Technology Transfer
Clinical Studies/Level of Design
Controls Phase I, II & III
GMPs, Inspections & Change
Management
Learn more and register at pda.org/2016combo.
And, on October 20-21, PDA’s Education Department will hold two courses complementing what you have learned:
Understanding and Addressing Technical, Quality, and Regulatory Challenges for Drug Delivery Combination Products (October 20)
Essential Elements of Extractables and Leachables: From Material Extraction to Final Report (October 21)
Learn more and register at pda.org/2016PrefilledCourses.
#2016prefilled
Cover Story: Autoinjectors
of design for manufacture and assembly activities.
Drug viscosity can prove a challenge
both at high and low viscosities. At
high viscosity, a high power source is
required to ensure the injection time is
acceptably short for the user. Retaining
such high loads throughout the shelf life
of the device and ensuring the device
still functions, are challenging and require extensive modeling and accelerated aging to simulate high stress and
long life. At low viscosity, the challenge
is lengthening the injection time to
avoid pain, but at the same time, avoiding device stall as friction loads dominate the injection. Both of these aspects
can be partially solved by modification
of the needle size, but this change is not
available to the designer.
The IP landscape for autoinjectors is
crowded, particularly in the space offering the simplest and most reliable
device architecture. A sleeve actuated
autoinjector, which is becoming the
standard embodiment, is not a complex device. The function can be fulfilled with a small number of parts,
and thus, there are a limited number
of mechanisms that will provide the
functionality. As a result, there are limited opportunities to innovate without
infringing existing IP. To overcome
this design constraint and avoid the
need to license, the designer is driven
to move to less elegant design solutions,
typically introducing additional parts
or suboptimal mechanisms, with a
knock-on impact on molding and assembly complexity as well as the inevitable impact on cost of goods.
the user is exposed to inconsistent injection depths and variable injection
times. Moreover, there is a risk of damaging the syringe, presenting a safety
risk to the user. The designer can solve
some of these problems with complex
mechanisms (e.g., electromechanical
closed-loop feedback systems), but to
effectively integrate the syringe requires extensive testing and characterization. The characterization is complicated by the lack of access to multiple
syringe manufacturing batches (both
unfilled and filled) and the difficulty
of capturing the force to expel the drug.
Access to multiple batches can be impossible if the drug is in development,
and filling is not representative of the
production fill. Even in later stages, getting hold of multiple batches to assess
process variability is difficult due to the
mismatch in syringe and autoinjector
production volumes. This issue necessitates that characterization activities continue throughout the development.
Capturing the force to expel the
drug is challenging as the typical
autoinjector power source, a spring,
generates a decaying force during the
delivery of the dose. Some theoretical
modeling is possible, but limited in its
validity. Empirical testing presents its
own challenge as standard test equipment does not exist. Dynamic force
testers are available but have limited
functionality. Thus, typically a combination of constant force, constant
velocity, and device power pack testing
is used to measure the force to expel
the drug.
Cartridges require the same force
characterization, but the geometry
Prefilled syringes and cartridges
specification is much tighter. The adPharmTech: How can prefilled syringes ditional challenge of the cartridge is
and cartridges be effectively integrated designing the interface with the needle.
into an autoinjector?
In its simplest form, this design can be
Deane (PA Consulting): The prefilled user applied (which has associated ussyringe was never designed to be ability challenges and user safety risks).
mounted within an automated deliv- In the more complex form, the device
ery device such as an autoinjector. As must automatically couple the needle
a result, the geometry and emptying to the cartridge, piercing the septum
force are poorly defined and controlled. as part of the injection process.
Unlike a person, an autoinjector canGould and Walker (Owen Mumford): The
not adapt to this variability and thus, resistance from the stopper to move20
Pharmaceutical Technology
JUNE 2016
P h a r mTe c h . c o m
ment within the container (from friction), strength of the container, resistance of the needle shield to removal,
and general geometry (including relative position of the stopper in particular) are key parameter considerations
when integrating prefilled syringes
and containers into an autoinjector.
However, what may be an even more
important consideration than the
nominal state of these parameters is
their natural manufacturing variations. For example, many autoinjectors
make use of a compression or torsion
spring to evacuate the container and
thus, the force exerted decreases as the
fluid is evacuated. Conversely, a stopper within a poorly lubricated container may increase its resistance as it
reaches the end of evacuation. The design of the autoinjector must allow for
this change, and any variation, within
its design.
The strength of a container is often
a key consideration also. We’re seeing
a trend in increasing formulation viscosities as drug technologies change
and the frequency of injection reduces.
These more viscous f luids require
greater delivery loads and more stress
on the container as a result. Well-engineered support for the container and
control over impact velocities are necessary to maintain container integrity.
Regulatory guidelines
PharmTech: Human factors are a key
consideration when developing a drug
delivery device, such as an autoinjector. What guidelines have regulators
such as FDA and EMA provided on
this aspect?
Gould and Walker (Owen Mumford): The
development of medical devices is
governed by a number of regulations
that can sometimes be baffling in their
complexity. Even within the realms of
regulations relating to human factors,
ease of comprehension is sometimes
overlooked. To address this aspect
and help manufacturers understand
the regulatory requirements, a number of guidance documents have been
created. Most recently, in April 2016,
The Parenteral Drug Association presents...
ARLINGTON, VA –
2016 PDA Workshop:
Current Challenges in Aseptic Processing,
Potential Changes in EMA/PIC/S Annex 1 Revision
Addressing the Unanswered Questions of How to Use Risk- and Science-Based Approaches
to Meet Global Health Authority Expectations and Improve Aseptic Processing
October 26-27, 2016 | Arlington, VA
Hyatt Regency Crystal City
Exhibition: October 26-27
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Register
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Workshop Theme: Points to Consider in Modern Aseptic
Manufacturing – with Special Reference to the On-going Revision of
the European GMPs for Sterile Medicines
The 2016 PDA Workshop: Current Challenges in Aseptic Processing, Potential Changes in EMA/PIC/S Annex 1 Revision will serve as
a forum for industry and regulatory professionals to discuss science- and risk-based approaches that support modern aseptic
processing and control strategies, and explore critical topics that may be addressed in the revised EU GMP Annex 1 guidance.
This interactive Workshop is a unique opportunity to engage with peers, industry leaders and experts on a wide range of topics, including:
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Physical Environment and
Environmental Monitoring
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Personnel and Material
Transfer
Process Simulation
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Cleaning, Disinfecting,
Sterilization and Critical
Utilities
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Aseptic Processing
Moving Forward
Make sure you are a part of this important conversation that will shape the future of aseptic processing.
For more information and to register today, please visit pda.org/2016annex1east
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