North Carolina State University s8

NORTH CAROLINA STATE UNIVERSITY GRADUATE COURSE ACTION FORM

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DEPARTMENT/PROGRAM Biotechnology COURSE PREFIX/NUMBER BIT 470/570 PREVIOUS PREFIX/NUMBER BIT 815O DATE OF LAST ACTION type date here COURSE TITLE Advanced Animal Cell Culture: Bioreactor Culture_____ ABBREVIATED TITLE Advanced Animal Cell Culture SCHEDULING Fall Spring Summer Every Year TYPE OF PROPOSAL Alt. Year Odd Alt. Year Even Other New Course Drop Course COURSE OFFERED BY DISTANCE EDUCATION ONLY ON CAMPUS ONLY Course Revision BOTH ON CAMPUS AND BY DISTANCE EDUCATION Dual-Level Course CREDIT HOURS 2 REVISION CONTACT HOURS Lecture/Recitation 2 Seminar Laboratory 4 Problem Content Prefix/Number Studio Independent Study/Research Internship/Practicum/Field Work Title Abbreviated Title GRADING ABCDF S/U Credit Hours Paul Mozdziak, Associate Professor Contact Hours INSTRUCTOR (NAME/RANK) Graduate Faculty Status Associate Full Grading Method Pre-Corequisites Restrictive Statement Description Scheduling

ANTICIPATED ENROLLMENT Per semester 8 Max.Section 8 Multiple sections Yes No

PREREQUISITE(S) BIT 466 or BIT 566 or PO 566 COREQUISITE(S) type course numbers here PRE/COREQUISITE FOR type course number(s) here RESTRICTIVE STATEMENT Students must register for both lecture and lab. CURRICULA/MINORS Required type program name here Qualified Elective Biotechnology Minor

PROPOSED EFFECTIVE DATE 10/1/06 APPROVED EFFECTIVE DATE ______

CATALOG DESCRIPTION (limit to 80 words): Principles of scaling animal cell seed-stock from frozen storage to three liter culture. Students will learn to assemble and operate a three-liter bioreactor to produce antibodies, as well as assess final product quantity using antibody techniques. This is a half-semester course.

DOCUMENTATION AS REQUIRED RECOMMENDED BY: Please number all document pages

______Course Justification Department Head/Director of Graduate Programs Proposed Revision(s) with Date Justification Student Learning Objectives ENDORSED BY: Enrollment for Last 5 Years

New Resources Statement ______Chair, College Graduate Studies Committee Consultation with other Departments Date Syllabus (Old and New)

Explanation of differences in ______requirements of dual- level courses College Dean(s) Date

APPROVED:

______Dean of the Graduate School Date

Course Justification: The proposed course is designed to be a component of the Minor in Biotechnology at North Carolina State University, and it is also will be part of the educational mission of the Biomanufacturing Training and Education Center (BTEC). The proposed course is designed to be an Advanced Biotechnology Elective that may be completed after completing BIT 466, BIT 566, or PO 566 Animal Cell Culture. The goal of the proposed course is to provide a hands-on training experience in scaling-up animal cell cultures to three liter bioreactors as well as assessing the quantity and functionality of a final end product. The course will build upon skills learned in the prerequisite, and provide valuable training experience in Bioreactor culture that will provide important technical skills that are in demand by the Biotechnology industry in North Carolina.

The availability of a training experience in animal cell culture techniques is important because animal cell culture must be performed under strict aseptic conditions. Animal cells grow much more slowly than contaminants such as bacteria, molds, and yeast making a high level of aseptic training necessary for laboratory workers employing cell culture techniques. Furthermore, animal cells cannot survive without the provision of a complex environment simulating blood plasma. The high level of aseptic technique combined with the complexity of the environment required to maintain the animal cells in vitro requires that laboratory workers possess a high level of technical knowledge to perform the in vitro methods and diagnose problems. It is important for undergraduate students to establish a solid foundation in animal cell culture techniques because in vitro techniques will only continue to be important experimental models. Furthermore, animal cell culture techniques are important procedures in commercial applications, such as in the production of monoclonal antibodies for therapeutic use and for in vitro diagnostic use, and for the vaccine production. An undergraduate training opportunity in scaling animal cell cultures up to three liters, producing a product, and assessing the quantity and quality of the product will prepare high caliber students for employment in the biotechnology industry.

Enrollment in last 5 years: This course was offered twice in 2004 and 2005, with 3 students and 2 students enrolled respectively. We anticipate increased enrollment once the BTEC opens, as this will allow for more sections of the prerequisite, BIT 466/566.

New Resources Statement: No new resources will be required. The Biotechnology Program will continue to budget for this course.

Student learning outcomes:

Upon completion of the course, students will be able to:

1. Use aseptic skills for vertebrate cell culture. 2. Scale-up animal cell cultures. 3. Describe bioreactor design and operation. 4. Produce and analyze antibodies.

Syllabus: The syllabus follows. The syllabus used for the trial (BIT 815 O) course was the same.

Explanation of differences in requirements of dual-level courses: Details describing the difference in expectations from students registered for the 500 level of this course are described in the syllabus. In brief, the 500 level students are required to write a 10 page review article pertaining to animal cell bioprocessing. This assignment results in a difference in grading from the 400 level students which is also described in the syllabus.

Consultation with other departments: This CAF was sent to Dr. Jim Knopp in the Biochemistry Department. His response is attached. Syllabus: Advanced Animal Cell Culture-Bioreactor Scale-Up

1. Instructors: Paul Mozdziak 134B Scott Hall 919-515-5544 (Office) email: [email protected]

James Petitte 363 Scott Hall 919-515-5389 (office) email: [email protected]

Office Hours: No formal office hours established; feel free to come in at anytime. If we are not in the office, please see our secretary, Joan Davis, in Room 203 Scott Hall, to make an appointment.

2. Course Goals and Objectives:

The goal of the course is to apply the skills gained in BIT 466/566 to scaling up an animal cell culture system to 3 liters to produce a protein. Understanding the establishment and maintenance of large-scale eukaryotic cell culture for protein production is another goal of this course.

Upon completion of the course, students will be able to:

1. Use aseptic skills for vertebrate cell culture.

2. Scale-up animal cell cultures.

3. Describe bioreactor design and operation.

4. Produce and analyze antibodies.

3. Textbook: Culture of Animal Cells: A Manual of Basic Technique R. Ian Freshney, 2005 $89.95

4. Course Organization–Approximately the first third of the course will be dedicated towards establishing seed-stock to inoculate bioreactors as well as preparing the bioreactor for inoculation. The second third of the course will focus on running the bioreactors, and harvesting antibody. The last third of the course will focus on assessing antibody quality, yield, and purification.

5. Attendance: Regular Attendance is expected of all students. Given the practical nature of the class, one unexcused absence from a laboratory will result in the final course grade being lowered an entire letter grade, two unexcused absences will result in a failing grade for the entire course.

Students absent during an exam or when notebooks are evaluated must have an excused absence to avoid penalty. Planned absences should be discussed with the instructor before the absence. Emergency absences should be discussed as soon as possible after the return to class. Excused absences require an excuse in writing. Medical excuses must be signed by a doctor.

Examples of acceptable planned absences are: university sponsored duties or trips, religious observances, and required court attendance. Examples of acceptable emergency absences are serious illness or injury, and death or serious illness in the family.

6. Laboratory Safety: To ensure safety during the laboratory sessions, various rules and procedures must be followed by all students. The laboratory rules will be presented during the first laboratory session. 7. Grading: There will be one cumulative final exam. A portion of the final grade will be based upon maintaining an up- to-date laboratory notebook. Students are required to obtain a bound page-numbered notebook. The students will record the objectives of each laboratory exercise, the procedures performed in each laboratory exercise, data collected/observations, and the conclusions drawn from each laboratory exercise in the notebook. Notebooks will be periodically evaluated (unannounced), during the course. The criteria for notebook evaluation will be maintaining complete and organized records for each laboratory exercise. There will also be one five to ten page laboratory report detailing the production of the antibody and the final assessment of antibody yield and quantity. Students receiving graduate-level credit (BIT 570) are required to write a 10 page review article pertaining to animal cell bioprocessing.

Grading for BIT 470 Lab Report 20% Comprehensive Final Exam 40% Class Participation 20% Laboratory Notebook 20% Total 100%

Grading for BIT 570 Lab Report 15% Paper 10% Class participation 20% Laboratory Notebook 15% Comprehensive Final Exam 40% Total 100%

Grade Ranges: A Range: A+ 97 to 100 % A 93 to 96.99 % A- 90 to 92.99 % B Range: B+ 87 to 89.99 % B 83 to 86.99 % B- 80 to 82.99 % C Range: C+ 77 to 79.99 % C 73 to 76.99 % C- 70 to 72.99 % D Range: D+ 67 to 69.99 % D 63 to 66.99 % D- 60 to 62.99 % No Credit <60 %

8. Academic Integrity: University regulations require that every course syllabus remind students that the Code of Student Conduct defines a university policy on academic integrity already pledged by each student. Instructors assume that the students' names on their submitted work imply compliance with this policy. http://www.ncsu.edu/policies/student_services/student_discipline/POL11.35.1.php

9. Students with disabilities: Reasonable accommodations will be made for students with verifiable disabilities. In order to take advantage of available accommodations, students must register with Disability Services for Students at 1900 Student Health Center, Campus Box 7509, 515-7653. http://www.ncsu.edu/provost/offices/affirm_action/dss/ For more information on NC State's policy on students with disabilities, please see the Academic Accommodations for Students with Disabilities Regulation at: ( http://www.ncsu.edu/policies/academic_affairs/courses_undergrad/REG02.20.1.php )

10. Behavior is also addressed under the Code of Student Conduct: (http://www.ncsu.edu/policies/student_services/student_discipline/POL11.35.1.php) Harassment of any kind will not be tolerated and includes behavior that is directed toward a particular person (or persons), is unwelcome and severe or pervasive, and violates criminal law, civil rights law, the NCSU Administrative Regulation on harassment, or that unreasonably interferes with the target person's employment, academic pursuits, or participation in University- sponsored activities. Additional information can be found at: http://www.ncsu.edu/provost/offices/affirm_action/policies.html Schedule

Lecture 1 Course Introduction

Review of Aseptic Technique and Core Operations

Lab 1 Safety Orientation

Aseptic Review Media Preparation

Lecture 2 Production of Monoclonal Antibodies

Lab 2 Practical Review of Core Techniques Initiation of Hybridoma Cultures

Lecture 3 Scaling Up Cultures: Options and Decisions

Lab 3 Expansion and Preservation of Cell Lines Bioreactor Set-Up

Lecture 4 Bioreactor Design and Operation I

Lab 4 Bioreactor Scale-up Monitor Cell Growth

Lecture 5 Bioreactor Design and Operation II

Lab 5 Harvest Antibody , Bioreactor Breakdown, Bioreactor Cleaning

Lecture 6 Quality Assurance and Product Analysis

Lab 6 Quality Assurance and Product Analysis

Lecture 7 Downstream Processing

Lab 7 Antibody Purification and Further Analysis

Lecture 8 Commercial Production of Therapeutic Compounds and Alternatives

Lab 8 Review Sue,

Thank you for sharing the course action form for the proposed BIT 470. I have reviewed this proposal and have no problems or concerns regarding this course.

Sue Carson wrote: > Hi Jim, > > Here's another CAF for a new BIT course. Please let me know by Monday > (Sept > 11) afternoon if you have any questions or concerns. > > Sue > > Susan Carson, PhD > Biotechnology Academic Coordinator > Teaching Assistant Professor, Botany > North Carolina State University > Biotechnology Education Facility > www.ncsu.edu/biotechnology > 6104 Jordan Hall > Box 7512 > Raleigh, NC 27695 > [email protected] > (919) 513-0330 >

-- James A. Knopp Associate Professor and Undergraduate Coordinator Department of Molecular and Structural Biochemistry Voice : [919] 515-5828 Appointments : [919] 515-5683 Fax : [919] 515-2047