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Northern New England Hub at New Hampshire Community Technical College


Ann Gnagey, Biotech Coordinator, Vermont Technical College. P.T. Vasudevan, Chemical Engineering, University of NH ... Leica Microscopes (4) ... – PowerPoint PPT presentation

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Title: Northern New England Hub at New Hampshire Community Technical College

Northern New England Hub at New Hampshire
Community Technical College
N. New England Learning Community (NHCTC members)
  • Sonia Wallman, Director of Biotechnology
  • Deb Audino, Biomanufacturing Faculty
  • Robert OBrien, Biomanufacturing Facility Manager
  • Tim Dubuque, NBC2 Webmaster/Multimedia Guru
  • David Miller, IST Faculty
  • Kari Britt, Biomanufacturing Intern
  • Hope Townes, Biomanufacturing Intern
  • Laura Tyson, Biomanufacturing Intern

N. New England Learning Community
  • Lonza, Portsmouth, NH
  • Glycofi, Lebanon, NH
  • Stryker, Lebanon, NH
  • Bentley Pharmaceutical, Exeter, NH
  • Bio-Concept, Derry, NH
  • Wyeth, Andover, MA
  • Biotecture Design, Meredith, NH
  • PFI/Parsons Engineering
  • Pall Euroflow, Portsmouth, NH
  • Bioprocessing, Scarborough, ME
  • Wunderlick-Malec, Portsmouth
  • TolerRX, Inc., Cambridge, MA
  • NH Biotech Council
  • Rockingham Economic Development Council
  • Ann Gnagey, Biotech Coordinator, Vermont
    Technical College
  • P.T. Vasudevan, Chemical Engineering, University
    of NH
  • Carolyn Kelley, Biotech Coordinator, Seacoast
    School of Technology
  • Ken Franson, Kingswood Regional HS, Wolfeboro, NH
  • Rich Parent, Biotech Coordinator, Milford High
    School, Milford, NH

N. New England Learning Community Job Foci
  • Metrology coordinated by Robert OBrien, NHCTC
  • Maintains, tests, troubleshoots and repairs a
    variety of circuits, components, analytical
    equipment and instrumentation. Calibrates
    instrumentation and performs validation studies.
    Specifies and requests purchase of components.
    Analyzes results and may develop test
    specifications and electrical schematics.
    Performs continuous monitoring of equipment
    status, condition and location. Prepares required
    documentation for the recording and notification
    of events and changes related to equipment such
    as calibration certificates, deviations, out of
    tolerances and installation reports. Knowledge
    and understanding of measurement parameters and
    experience working in a GMP environment is
  • Process Development coordinated by Deb Audino,
  • Responsible for evaluating and scaling-up
    manufacturing processes in order to improve
    product yield and reduce overall costs of
    production. Executes small-to-medium scale
    production work, which may involve cell culture,
    fermentation, purification, chromatography, and
    developing QC protocols. Additionally, assists
    with maintenance of production equipment. May
    research and implement new methods and
    technologies to enhance operations and may assist
    in validation of production processes.
  • Facilities coordinated by Sonia Wallman, NHCTC
  • Performs monitoring, repair, and preventive
    maintenance activities on critical systems and
    facility equipment. Troubleshoots, installs, and
    modernizes new and existing systems, including
    refrigeration equipment, water systems, HVAC
    systems, and electrical systems. Documents
    repairs, adjustments, and replacement of
    equipment and/or components per GMP standards.
    May also provide input and corrections to SOPs
    and assist engineering in the evaluation of new
    equipment or technology. Knowledge of major
    trades, such as carpentry, electrical, plumbing,
    and HVAC refrigeration, including the ability to
    interpret blueprints, technical manuals, and
    specifications, is required.

Calibration Metrology
  • System approach
  • Monitor Verify Validate
  • Periodic maintenance
  • Periodic calibration
  • SOP
  • Documentation
  • Traceability
  • The Real Problem
  • Wear
  • Misuse
  • Hands on component
  • Calibration of pH meter
  • Calibration of the balance scale
  • Calibration of pipette
  • Calibration Air sampler

Calibration Metrology
  • Features of a calibration management system CMS
  • Identifies instruments that can be calibrated
  • Determines calibration requirements for
  • Requirements for a CMS
  • Instrument requirements unique identification
  • A recorded history and current calibration status
  • Use appropriate for the function of the
  • Calibration standards and test equipment
  • Standards Organizations
  • ISO - International Origination for
  • ANSI - American National Standards Institute
  • UPC - United States Pharmacopeia

Calibration Metrology
  • Training
  • Ensure that all personnel involved with
    calibration are properly trained
  • Training records must be maintained
  • Change Control
  • Updates and refinements of the calibration system
    must be done in a methodical and documented
  • Electronic Records
  • Management of electronic records for paperless
    calibration operations
  • Auditing
  • Periodic audits assure that the calibration plan
    is being followed

Calibration Metrology
  • Aseptic
  • Volume
  • Temperature
  • Electrical
  • Measurement
  • If a parameter is not measured, it cannot be
  • Statistics
  • Method for handling data and drawing conclusions
  • PM
  • Ensure correct results are capable of being
  • Aseptic Practices
  • Used while performing calibration to avoid
    inadvertently cross-contaminating

Calibration Metrology
  • Equipment
  • Autoclave
  • pH Meter
  • Pipette
  • Temperature
  • IR Thermometer
  • Transducers/ RTD
  • Thermocouples
  • Freezers, Refrigerators
  • Hot plate
  • Incubator
  • Pressure Calibration Meter
  • Biological Safety Cabinet
  • Microscope
  • Humidity
  • Tachometer
  • Centrifuge
  • Digital Multimeter

Calibration and Monitoring
Calibration Metrology
  • Lecture and Hands on Lab components presented at
    Bio-man July 2006 129 Slide power point
  • 20 Registered Participants
  • Participants calibrated a balance utilizing the
    calibration SOP
  • Validation / Monitoring of the autoclave
  • Participants performed the biological indicator
  • The students were able to observe a previously
    biological indicator that had been incubated the
    required time and temperature
  • Equipment purchased on a DOL grant was
    incorporated into the development of the
    Calibration Metrology for the NSF grant

Calibration Metrology
  • Future Areas of development
  • Additional SOPs for PM need to be completed prior
    to calibration SOPS can be developed for
  • The need for additional equipment purchases will
    need to be evaluated
  • One area utilized this year was behavioral Video
    that was very beneficial for an participant to
    review video of a process being performed
  • This behavioral video aspect is being looked at
    to see if it can be incorporated into calibration
  • Possibility of development of an data base in
    Microsoft Access

Process DevelopmentOverview
Independent Student Projects Designed to
Create Curriculum for Process Development
Modules UPSTREAM Modules Comparison of Cell
Types Comparison of Medias Comparison of Culture
Vessels DOWNSTREAM Modules Increase the
purity of proteins Design purification
schemes Scale up purification
Process DevelopmentStudent Externs-Past
Independent Projects
Purification of tPA Improve the purification of
tPA by adding an affinity chromatography step
Yield Function Ease of
Kari Britt
Process DevelopmentStudent Externs-Current
Independent Projects
  • Compiling the Pichia pastoris HSA Core Production

This process yields an ample supply of HSA which
can be used in a process development focusing on
scaling up purification to a 1L column
Process DevelopmentStudent Externs-Current
Independent Projects
Cloning tPA into Pichia Cells Comparison of tPA
production in CHO vs Pichia cells Yield
Function Ease of purification
Process DevelopmentStudent Externs-Current
Independent Projects
  • Make competent cells
  • Transform Invitrogen plasmids into competent
  • Isolate plasmids
  • Make cDNA library from CHO cells expressing tPA
  • Add EcoR1 linker
  • Cut plasmids with EcoR1
  • Ligate cDNA fragments and plasmids
  • Transform plasmids into competent cells
  • Screen for correct plasmid using colony
  • Sequence positive clones for mutations
  • Transform plasmids into Pichia
  • Screen for tPA production in Pichia cells

Process DevelopmentStudent Externs-Current
Independent Projects
Production of Herceptin Antibodies are the
fastest growing type of biopharmaceutical
Process DevelopmentStudent Externs-Current
Independent Projects
  • Learn Mammalian Cell Culture with CHO Cells
    Expressing tPA
  • Aseptic Technique
  • Counting cells and determining viability with
    Tyrpan Blue Assay
  • Scaling up the culture
  • Grow the Hybridoma Cells Expressing Herceptin
  • Purify Herceptin using a Protein A Affinity

Process DevelopmentStudent Externs-Future
Independent Projects
Scale Up the Purification of HSA
Process DevelopmentStudent Externs-Future
Independent Projects
  • Evaluate Wave Disposable Bioreactor with
  • Spinner Flasks and Bioreactors

Rationale for the NH Pilot Plant
  • To support a case study on the design,
    construction, and validation of a
    biomanufacturing facility to be used in the NBC2
    global Biomanufacturing course
  • To provide students with visual access to a
    biopharmaceutical manufacturing facility
  • To give some graduates of NHCTCs biotechnology
    program actual experience in biopharmaceutical
  • To provide some experienced individuals for
    biomanufacturing companies
  • To support the development of biopharmaceuticals
    for eventual commercial manufacture

Rationale for the NH Pilot Plant
  • Rationale comes directly from NHCTCs involvement
    with biomanufacturing education and training and
    our desire to expand our Virtual WorkplaceTM
    concept to include familiarity with the
    operations of a cGMP Pilot Plant.
  • Design a cGMP Pilot Plant that uses easily
    validated, completely disposable equipment and
    supplies for upstream and downstream processing
    for ease of cGMP compliance.
  • Document design and construction of the cGMP
    Pilot Plant to be used in the NBC2 global
    curriculum addressing a general understanding of
    the construction and operation of a cGMP
    biopharmaceutical manufacturing facility.

NH Pilot Plant Funding
  • Work with county and federal agencies to fund the
    construction of the Pilot Plant, a process
    development lab and offices for incubatees
  • Work with John Rafuse, AIA and MEP person to
    design the Pilot Plant
  • Work with NHCTC-Stratham/Pease architects in the
    construction of the Pilot Plant
  • Work with industry partners to equip a fully
    disposable Pilot Plant
  • Pall Filtron will provide TFF equipment
  • Fisher Scientific will provide some disposable
    supplies and equipment for the Pilot Plant and
    equipment for QC and process development
  • Nalge Nunc may provide a variety of disposable
  • Looking for other industry partners to provide
    downstream processing disposable equipment and

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Pilot Plant Flow Diagram
Pilot Plant Walls and Doors Plan
Pilot Plant View from Outside
Pilot Plant Interior Shot
NHCTC as the Center for NBC2 Activities
  • NHCTC is the site for
  • The annual NBC2 NVC meeting in March
  • The annual 5 day BIOMAN conference in July or
  • Northeast Region of Bio-Link
  • Value-added NBC2 activities stemming from NHCTC
    Department of Labor grants, one to build capacity
    for education and training at NHCTC and another
    to develop the infrastructure for biotechnology
    and biomanufacturing education and training in
    New Hampshire

The NH BET Facility
  • A 5,000 square foot facility for biotechnology
    education and training with a wet lab for
    Discovery Research, a Biomanufacturing Suite and
    a Core Facility for shared equipment
  • Constructed to resemble a vertically integrated
    biotechnology company with the tools, processes
    and regulatory structure for Discovery Research,
    Process Development and Biomanufacturing.
  • Providing education and training in Industrial
    Biotechnology for all levels recent high school
    graduates, UNH students, career changers,
    displaced workers, women returning to work,
    incumbent workers, faculty and teachers

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Biomanufacturing Equipment
  • Multiscan ELISA Plate Reader
  • Drummond Automatic Pipettors (4)
  • Ohaus Balances (4)
  • Conductivity Meter
  • Orion pH and Conductivity Meters (4)
  • Applikon 3 liter process controlled
  • Bioreactors (4)
  • New Brunswick Bioflo 3000 process
  • controlled bioreactor
  • Bio-Rad Liquid Chromatography Systems (4)
  • Millipore 2L chromatography columns
  • Nova 300B analyte analyzer
  • MET One laser particle counter
  • Millipore air sampler
  • Bio Tek Microplate Reader
  • Sanyo Dual CO2 Incubator
  • Sanyo Top Loading Autoclave
  • UVP Digital Photodoc System
  • Invitrogen Mini-Cell SDS-PAGE Gel Boxes (4
  • Bio-Rad HPLC System
  • Forma biological safety cabinet
  • Hot Plate/Magnetic Stirrers
  • Microfuges
  • Rainin Pipetman
  • Household (non-defrosting) refrigerator
  • Freezers (-20 and -86 degrees C)
  • Cellstar dry shaking incubator
  • Market Forge autoclave
  • Millipore Milli Q water system
  • Bellco spinner bottles
  • Bellco magnetic stirrers
  • Olympus BX40 uv-visible video microscope
  • Olympus CK2 inverted microscope
  • Leica Microscopes (4)
  • Dell laptops with remote observation software for
    Applikon bioreactors, Bio-Rad LC system, Biolog
    system and Microplate Reader (4)
  • Applied Biosystems GeneAmp PCR system
  • Sigma refrigerated centrifuge
  • Sanyo incubator

Synergistic Activities
  • Member of the Advisory Group of the Biotechnology
    Labor Market Initiative, a DOL funded project
    (identify the industry, the jobs and salaries,
    the sources of education, career ladders/latices,
    etc. and build website to communicate this
  • Formation of the Northeast Biomanufacturing
    Institute offering short courses for incumbent
    workers (part of DOL grant that created the
    Center of Expertise in Biomanufacturing, part of
    the National Center for the Biotechnology
  • Northeast Region Director of Bio-Link (the
    Bio-Link webmaster resides here)
  • Work with AACC and FAS, Ireland re
    biomanufacturing education and training,
    workforce, and apprenticeships

Synergistic Activities, continued
  • Development of the Registered Apprenticeship in
    Biomanufacturing (part of DOL grant that created
    the Center of Expertise in Biomanufacturing)
    NBC2 involved in Regionalization of the
    Biomanufacturing Apprenticeship program-we are
    looking at the Biomanufacturing Apprenticeship as
    a long-term internship for students (this was not
    listed as a deliverable because we thought it was
    an impossible task).
  • NHCTC Biotechnology Strategic Enrollment Program,
    John Grady, Consultant (part of DOL Grant that
    created Center of Expertise in Biomanufacturing)
    Targets Apprentices, NHCTC System CCs, Industry,
    Four Year Colleges and Universities

Student Profile 1994-2006
  • Total number of graduates323
  • Total number of graduates at work268
  • Total number of graduates at biomanufacturing
  • Companies employing biomanufacturing graduates
    Lonza-NH, Wyeth-MA, Superior Controls-NH,
    Amgen-RI Amgen-CA, Genzyme-Alston-MA, Marine
    Polymer Technologies-MA, TKT(Shire)-MA,
    Arqule-MA, Bioprocessing-ME, IDEXX-ME,
    Bio-Concept-NH, East Coast Validation-NH,
    Roche-NJ, Formatech-MA, Beckton-Dickinson-MA,
    Igenex-CA, Repligen-MA, Hyaluron-MA, Alerchek-NH,
    GlycoFi (Merck)-NH, Genentech-CA, Valicor-MA,
    Dakota Systems-MA, Millipore-NH, BiogenIdec-MA,
  • Companies currently providing Biomanufacturing
    Apprenticeships Lonza-NH, Bentley
    Pharmaceuticals-NH, NH BET Center-NH
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