Integrating standard operating procedures and industry notebook standards to evaluate students in laboratory courses

Authors


Abstract

To enhance the preparedness of graduates from the Biochemistry and Biotechnology (BCBT) Major at Minnesota State University Moorhead for employment in the bioscience industry we have developed a new Industry certificate program. The BCBT Industry Certificate was developed to address specific skill sets that local, regional, and national industry experts identified as lacking in new B.S. and B.A. biochemistry graduates. The industry certificate addresses concerns related to working in a regulated industry such as Good Laboratory Practices, Good Manufacturing Practices, and working in a Quality System. In this article we specifically describe how we developed a validation course that uses Standard Operating Procedures to describe grading policy and laboratory notebook requirements in an effort to better prepare students to transition into industry careers. © 2013 by The International Union of Biochemistry and Molecular Biology, 42(1):41–49, 2014.

Introduction

The Biochemistry and Biotechnology (BCBT) Major at Minnesota State University Moorhead (MSUM) was established in 1997 and has been revised to maintain consistency with the American Society of Biochemistry and Molecular Biology recommended curriculum [1, 2]. As the program has matured, the number of students interested in pursuing careers in the bioscience industry has also increased. At this time, ∼35% of graduates of the BCBT program directly seek employment in industry, 40% pursue graduate degrees, and 25% pursue professional degrees. As the number of students pursuing industry careers increased, the faculty of the BCBT major decided to engage industry experts in an effort to determine how to enhance the training of students interested in these careers. The process was initiated by interviewing industry representatives from three local bioscience companies. We interviewed a combination of seven research and production managers and quality system supervisors. These initial interviews delivered insight into the general areas of concern industry professional had and provided the ground work for further interviews with regional and national bioscience industry representatives. We first expanded our interviews to include companies from Minnesota and North Dakota. Representatives from 12 additional companies participated in interviews. Finally, we engaged a group of industry professionals in more casual conversations about entering employee concerns at two industry specific meetings; The Lifescience Alley Annual Conference in Minneapolis and the Biotechnology Industry Organization (BIO) International Convention. Lifescience Alley is the largest state-based life science trade association in the United States and membership ranges from medical device to pharmaceutical to agricultural biotechnology. BIO is the world's largest biotechnology trade association. During these interviews and conversations, it did not take long to realize that there is a clear gap between the training a typical undergraduate biochemistry major receives and what industry wants from these graduates. Early in virtually every interaction with industry professionals about hiring Bachelor's degree employees, the comment was made that it takes nine to twelve months to make a new employee fully functional within the company. During this time these new employees are receiving full pay and benefits while not being fully functional in the company. While the great majority of industry professionals understood that academic preparation cannot train students to a level that they are fully productive after a couple weeks on the job, these professionals were highly motivated to decrease the amount of time that new employees required to become fully functional. When asked what these B.S. and B.A. employees were missing in order to decrease the time of this transition, several categories became common. These common categories and specific topics are presented in Table 1.

Table 1. Skills and understanding that typical B.S. and B.A. graduates are missing to transition to bioscience industry positions
CategorySpecific topics
Understanding how to work in a regulated environmentRegulatory Language
 Good Laboratory Practices
 Good Manufacturing Practices
 Standard Operating Procedures
 Maintaining Appropriate Notebooks
Working in a Quality System/Quality Management SystemQuality Assurance
 Quality Control
 Regulatory Affairs
 Validation
Soft SkillsPresenting Summaries and Overviews
 Working in Multidisciplinary Teams
 Progress Reports
 Presenting Science to Non-scientists
 Industry and Research Ethics

With the understanding that addressing these specific industry needs would not easily be accomplished within the regular BCBT curriculum the MSUM faculty developed the BCBT Industry Certificate. The certificate program is a unique advanced training opportunity for individuals interested in pursuing bioscience, pharmaceutical, and chemistry industry careers. The program will prepare undergraduates to enter the workforce, provide training to incumbent workers for career advancement, and retrain displaced workers for new careers. Students are exposed to the careers in industry with club meetings, industry specific speakers and a number of workshops and handouts starting in their freshmen year. Providing this information along side other more traditional careers such as graduate or health professions careers helps provide students with a third viable and important option. The Biochemistry and Biotechnology Industry Certificate is a 19 credit program that can be taken either at the undergraduate or graduate level. The program is designed to help decrease the amount of time it takes for a new bachelor's graduate or a person transitioning into a new career to become fully functional in a bioscience company. The 19 credits required for the certification is two credits short of the maximal allowable by the Minnesota State Colleges and Universities system and is considerably less than the credits required for a minor. To support student involvement, some of the courses will be allowed to double count within the BCBT major. The goal of the program is to reduce the time necessary for a new employee to become fully functional in a bioscience company from 9 to 12 months to 2 to 3 months. The Industry Certificate courses and course descriptions and given in Table 2.

Table 2. Biochemistry and biotechnology industry certificate courses and course descriptions
TitleCourse description
Introduction to Working in a Regulated Biochemistry and Biotechnology IndustryThis course covers the basic structure of the regulated workplace; introduction to regulatory affairs, introduction to regulatory language: FDA and USDA; an overview of good practices: good laboratory practices (GLP), good manufacturing practices (GMP) and good clinical practices (GCP); introduction to quality systems: quality control, quality assurance, ISO9000, and six sigma; introduction to validation.
Introduction to Validation in the Biochemistry and Biotechnology IndustryThis course provides an overview of validation in the biochemistry and biotechnology industry including biopharmaceutical, biomanufacturing, and basic and clinical research. Topics will include: (1) The science of validation; (2) Qualification, calibration, and certification of equipment; (3) Validation of biological assays; and (4) Creation and Application of Validation Programs
Introduction to Quality Management Systems and Quality Risk Management in the Biochemistry and Biotechnology IndustryThis course covers the origins, history of quality and the major concepts, theories, principles and foundations; quality management systems, quality risk management, quality planning, quality assurance and improvement; the roles and responsibilities of quality assurance and quality control.
Ethics in the Biochemistry and Biotechnology IndustryThis course will cover ethical issues in the Biochemistry and Biotechnology Industry ranging from legal requirements for notebooks, issues with data falsification and misrepresentation, and issues of genetic manipulation and cloning among others. Materials include a discussion of societal and professional codes of ethics and the history and development of preclinical and clinical research ethics.
BCBT Internship or BCBT ResearchThis course is the required capstone experience for the Biochemistry and Biotechnology Certificate Program. An internship or work experience is required to complete the Biochemistry and Biotechnology Certificate. The experience can be a paid or volunteer experience. The experience needs to be approved by a faculty advisor in the Biochemistry and Biotechnology Certificate Program. Following the internship or work experience the student will be required to write a paper pertaining to the experience.

In this article we will describe how we use Good Laboratory Practices (GLP) and Good Manufacturing Practice (GMP) standards to introduce Standard Operating Procedures (SOPs) and how maintaining a quality laboratory notebook takes on elevated priority in industry.

Background and Definitions

Bioscience Industry

The biosciences are best understood as a grouping of diverse industries with a common link, the application of biological scientific knowledge. These industries fall into a broad array of higher-level industries. BIO divides the bioscience industry into five categories: (1) Agricultural feedstock and chemicals; (2) Drugs and Pharmaceuticals; (3) Medical devices and equipment; (4) Research, testing, and medical laboratories; and (5) Bioscience-related distribution [3]. Using this broad definition is meant to include a broad array of employment for science graduates in areas including biochemistry, biotechnology, molecular biology, microbiology, cell biology, and analytical chemistry.

Laboratory Notebooks

As scientists and science educators, we understand the value of maintaining quality laboratory notebooks. We teach students that notebooks are daily records of every experiment you do or that you are planning to do [4-6]. Notebooks contain your data whether good or bad, observations from your experiments, and form the basis for every scientific paper you write. Finally, we use notebooks as a record that allows successive scientists from your laboratory to reproduce your results and advance the project [7]. In the bioscience industry, this understanding is expanded to include the notebook being a vital record of your work for patent purposes and protecting intellectual property. For example, notebooks are legal records for documenting drug, biologics, and medical device research under FDA guidelines. The other aspect of a laboratory notebook that is not always considered in either industry or academia is the fact that if allegations of fraud are brought against published or patented research, your laboratory notebooks will be used to validate your findings [8].

Electronic Laboratory Notebook (ELN)

A number of processes common to industry including patenting, protecting intellectual property, QA/QC, GLP, and GMP require extensive record keeping and careful control of access to and management of data. Many biotechnology and pharmaceutical companies use electronic laboratory notebooks. There is no standard format for ELN (otherwise known as information management systems) and over 20 companies currently support or license software for their ELNs. Features of ELNs not found in standard academic or paper laboratory notebooks include: real-time monitoring of data and restricted changes by managers, live links to established protocols or SOPs, controlling workflow, and the ability to allow clients access to data mid-stream of a project. The format for uploading and securing data, figures, and databases widely varies and depending on the project and company may include additional security and supervision elements. An additional feature of some ELNs include tracking of reagents use and batch and inventory management to ensure stability and life span of reagents and samples.

Standard Operating Procedure (SOP)

The FDA defines an SOP as a written method of controlling a practice in accordance with predetermined specifications to obtain a desired outcome [9]. In regards to equipment use, SOPs give precise instructions on how a piece of equipment is to be used, maintained, and how the use and maintenance are to be documented to ensure the validity of the outcome of measurements. In regards to experiments, the development of and SOP is part of a standard documentation process that involves development of an experimental protocol, the finalization of the details in an experimental method, and the final expression of how the experiment will be performed every time it is used in an SOP [10]. While the terms experimental protocol and experimental method are frequently used interchangeably in academic research laboratories, this is not typically the case in an industry environment. An experimental protocol is the initial design of how to do a specific experiment and can be modified in an effort to optimize results. The protocol will be altered until the ideal process is identified. Once this experimental protocol has withstood the test of time it will be termed an experimental method. This experimental method is then presented, commonly in a check list format, as part of an SOP. The experiment SOP will reference all of the equipment that is used for the experiment and the SOPs for those equipment items to ensure that each experimental step is done in the same fashion no matter which trained employee is doing the experiment.

Good Laboratory Practice (GLP)

The FDA defines GLP as a quality system concerned with the organizational process and the conditions, under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived, and reported [11]. GLP also referred to as current GLP (cGLP) to imply the most current updates of GLP. GMP was developed by regulatory bodies including the FDA, EPA, and WHO to ensure that research submitted to them was not only executed in a proper fashion, but that the research was adequately documented so that any skilled scientist could follow the documentation to replicate the outcome of the experiment. This level of documentation is substantial and ultimately increases the cost of doing the research [12].

Good Manufacturing Practice (GMP)

GMPs mean the requirements found in the legislations, regulations, and administrative provisions for methods to be used in, and the facilities or controls to be used for, the manufacturing, processing, packing, and/or holding of a drug to assure that such drug meets the requirements as to safety, and has the identity and strength, and meets the quality and purity characteristics that it purports or is represented to possess. Additionally, GMPs are that part of quality assurance which ensures that products are consistently produced and controlled to quality standards [13].

Quality System/Quality Management System

A quality system is an organizational structure, procedures, processes, and resources needed to implement quality management. Quality management includes all activities of the overall management function that determine the quality policy, objectives, and responsibilities and implement them by such means as quality planning, quality control, and quality improvement within a quality system [14]. The FDA requires that a quality management system must be in place in all companies that produce medical devices, pharmaceutical compounds, and biologics to ensure that their products consistently meet applicable requirements and specifications [15].

Course Design

When the concerns of industry employers are combined with the concept of a quality management system and the implementation of GLPs and GMPs through the use of SOPs, it is easy to understand where B.S and B.A. graduates from even the best biochemistry and biotechnology programs could be challenged when transitioning into the regulated workplace. In our BCBT Industry Certificate courses we strive to convert our traditional course syllabus and course schedule into a formal SOP format to help students understand at least some of the attributes of working in an FDA regulated environment. As part of a quality system and cGMPs, an employer is responsible for ensuring that all personnel are appropriately trained to conduct their duties and that this training is fully documented and that documentation is available during FDA inspections. This is commonly accomplished through the development of an umbrella SOP that describes personnel training requirements for the different employees in the company. These training regimens are typically described in a training SOP that outlines specific tasks from maintaining notebooks to proper equipment operation to experimental methods. Each of these tasks has a specific SOP that provides appropriate operating procedures and required levels of competency as well as describing how the training needs to be documented.

To mimic an industry environment in our academic setting, after presenting a standard course syllabus to students to meet university requirements, we also present a version of the syllabus that has been converted into SOP format. This Training SOP outlines each of the sections of the course; the points associated with each section, and references to each of the SOPs that will be used in the course. Thus after the first day of the course all training materials and instructions are presented in SOP format.

BCBT 425: Introduction to Validation in the Biochemistry and Biotechnology Industry

BCBT 425 is a hybrid delivered course with the lecture and required reading components delivered on-line and the laboratory/active learning component being delivered in a traditional laboratory format. The Training SOP for this course provides a full course description including the elements related to the laboratory/active learning portion of the course. For the purposes of this article we will focus only on the laboratory notebook component and its grading. The laboratory exercises for this course are conducted as five two-week duration laboratories. The first week is typically training on the equipment and experimental methods being used and the second week is a full run of the experiment with quality system oversight.

To understand how to keep a laboratory notebook for this course and how the notebook will be graded students have to focus on two documents. The first is the Training SOP (the functional course syllabus) and the Laboratory Notebook SOP.

Training SOP

The Training SOP will inform students that: (1) They are required to keep a laboratory notebook; (2) Proper maintenance of the notebook will account for 250 of the 1,000 points available in the course; (3) Two types of laboratory notebook checks will be performed, scheduled and nonscheduled; (4) The dates for the four scheduled laboratory notebook checks (50 points each); (5) That there will be five unscheduled notebook checks (10 points each) to evaluate whether rules related to keeping notes while doing work, counter signatures, dates, descriptions, and appropriate format are being used. See the supplemental materials for the training SOP used in the course.

The Training SOP also describes each of the laboratory exercises that will be performed during the semester and the SOPS associated with each. The laboratory based exercises included in this course are: (1) Using and Writing SOPs, (2) Equipment Installation and Qualification: Digital Analytical Balances and Pipettes; (3) Pipetting Qualification and Pipette Calibration; (4) Enodotoxin Assays: Experimental Methods and Validation; and (5) Cell Proliferation/Cytotoxicity Assay Experimental Methods and Validation.

Notebook SOP

The introduction to the SOP stresses the importance of an industry notebook as a legal document and describes the basic process of using notebooks to establish intellectual property rights and file for patents.

The Scope Section of the SOP provides the basic information about the notebook and writing in the notebook. This section describes the requirement for bound notebooks and that all entries in the notebook must be made in black or blue ink. It points out that changing colors of pens to depict different aspects of an experiment or results should not be used. It also discusses the fact that in certain laboratories where a common goal is to obtain patents on products it is common to use carbonless notebook pages to generate two copies of each page immediately. This is another reason to limit the writing to a single color ink. The details of the Methods Section describe the basic structure of the notebook. Table 3 give provides those primary details. See the supplemental materials for the notebook SOP used in the course.

Table 3. Details of the methods section of the notebook SOP
CategoryDetails
That the notebook will:1. Be used by only one person
 2. Have a specific number related to the project(s) being worked on
 3. Have a Table of Contents
 a. This will be updated at the completion of each day's work
 4. Have numbers on all pages
 a. This is typically provided in quality notebooks
 5. Be stored when completed
Each experiment or work product will have:1. A Title
 2. A Purpose Statement
 3. Methods
 a. These first three sections are required to be completed prior to doing experiments etc.
 b. Must include references to SOPs for the equipment used and the specific experiment
 4. Data Collection
 5. Data Analysis
 6. Conclusions and Observations
Each page of the notebook will have:1. A Date or Multiple Dates (If you finished work in the middle of a page)
 2. Researcher Signature
 a. Pages must be signed by the research prior to continuing to the next page
 3. Counter Signature
 a. The signature of a member of your group indicating that you were present and did perform the work on that day.
Basic guidelines for keeping a notebook.1. Record information immediately
 2. Don't leave blank spaces and use space efficiently
 3. Don't modify
 4. Correct mistakes in such a way that both the mistake and the correction can be read.
 5. Explain abbreviations and special terms

Notebook Grading

As indicated in the Training SOP for the course, the notebooks will graded using both scheduled grading events and random grading events. The scheduled grading events are used to ensure that students are following basic notebook guidelines and completing the notebook according to expectations. The nonscheduled grading events are designed to serve as pop-quizzes to ensure that the students are preparing in a timely manner. The planned grading sequences for notebooks for the course are given in Table 4.

Table 4. Detail notebook grading sequence
Grading typeTimingPointsDescription
ScheduledFollow 1st Lab50Notebook Setup
   Page Setup
   Experiment Setup
   Neatness
UnscheduledEntering 2nd Lab Week 110Title, Purpose, Methods complete when entering the laboratory
   Pages signed and counter signed appropriately
UnscheduledDuring 2nd Lab Week 210Ensure that students are taking notes, recording data, signing and counter signing pages as they proceed
UnscheduledDuring 3rd Lab Week 210Ensure that students are taking notes, recording data, signing and counter signing pages as they proceed
   Are they learning to record their lab books while they work?
ScheduledFollowing 3rd Lab50Notebook Setup
   Page Setup
   Experiment Setup
   Neatness
   Quality of data documentation
   Quality of Conclusions and Observations Have students corrected earlier errors
UnscheduledEntering 4th Lab Week 110Title, Purpose, Methods complete when entering the laboratory
   Pages signed and counter signed appropriately
   Have they correct mistakes from Lab 2 Unscheduled entering lab check
ScheduledFollowing 4th Lab50Notebook Setup
   Page Setup
   Experiment Setup
   Neatness
   Quality of data documentation
   Quality of Conclusions and Observations
   Have students corrected earlier errors
UnscheduledDuring 5th Lab Week 210Ensure that students are taking notes, recording data, signing and counter signing pages as they proceed
   Are they learning to record their lab books while they work?
ScheduledFollowing 5th Lab50Notebook Setup
   Page Setup
   Experiment Setup
   Neatness
   Quality of data documentation
   Quality of Conclusions and Observations
   Have students corrected earlier errors

Discussion

The goal of the BCBT Industry Certificate is to enhance student preparation for entering industry careers. The certificate was designed to address a variety of issues identified through conversations with local and regional bioscience industry professionals. The notebook grading system described here was designed to specifically address concerns from industry professionals related to working in a regulated environment, using SOPs, and completing appropriate documentation of work efforts. The instructions for keeping laboratory notebooks are given through a Notebook SOP that provide specific expectations of how the notebook will be setup and maintained throughout the course. We chose to use traditional laboratory notebooks in the course for two reasons. First, discussions with industry leaders indicated that the electronic notebooks they use are typically highly customized. They prefer to train students using their task-specific ELN and would like to see potential employees develop the key skills of the laboratory notebook first. Several smaller companies do not use software and felt that training on ELN would not be as important in their hiring decisions. Second was that the cost of electronic notebooks was significant, ELN formats and programs constantly change and need upgrading increasing costs, and based on feedback from industry, the return on investment did not merit the investment. In this course students work from SOPs beginning with the Training SOP that serves as the functional syllabus for the course. This Training SOP also specifically details how laboratory notebooks will be graded. The grading is done through a series of scheduled and unscheduled notebook checks that allow the instructor to regularly evaluate the students' notebooks and ensure that they improve their notebook skills throughout the semester.

To date we have completed one cycle of the delivery of the certificate courses so the results are limited. In the first cycle six students completed the certificate and enrollment in the courses ranged from 12 to 16 students. We have performed limited formative assessment using interview of our stakeholders in industry, primarily with the primary local employer that hires BCBT graduates. Discussions about MSUM alumni were conducted from the instructor's perspective in aggregate and did not discuss any student's performance or grades. Only graduates were discussed with the companies. The company, Aldevron, is a biotechnology company that does DNA, protein, and antibody preparation both in a GMP and non-GMP environments. Aldevron has also recently expanded into bioscience related storage and distribution. Both of Aldevron's founding partners were part of the initial develop of the BCBT Industry Certificate. Aldevron employs MSUM BCBT graduates that were trained prior to the industry certificate program and those that have participated in industry certificate courses. Over the past 12 months Aldevron has hired three MSUM graduates that have participated in the industry certificate courses. While we are very early in the formative assessment process, we have started collecting preliminary qualitative data about our graduates from the employers and plan to interview graduates after 1 year of employment. During a recent discussion regarding the quality of the MSUM graduates hired by Aldevron, the hiring director shared the company's opinions of the new hires and their overall pleasure with the quality of these employees. The discussion provided three specific examples. The first new employee was hired in the DNA production area. Aldevron was very pleased with this employee's ability to transition into the GMP work environment and specifically with his ability to quickly deal with SOPs and the documentation requirements. The second employee was hired as a quality assurance associate in Aldevron's new storage and distribution unit. In Aldevron's critique, Werner indicated that this employee had absolutely flourished in her new position. She had quickly assimilated into the work group and had an excellent grasp of the role of the quality assurance group. Finally, the hiring director shared a conversation he witnessed following a production meeting involving the third new hire. The two participants in the conversation were both MSUM graduates, one previous to the industry certificate and the other having participated in two certificate courses. During the conversation, the established employee asked where the new employee had learned about validation. The new employee said he had taken a validation course at MSUM. The response from the established employee was that he wished they would have had that when he was in school, it would have made his job transition much easier. While these examples are an extremely small sample size from one of our local industry partners, we are none-the-less pleased with the results. The company is pleased with the new hires and their expanded skill sets. As we continue to develop and modify the curriculum for the BCBT Industry Certificate we will continue to evaluate our progress through conversations with both employers and graduates of the program.

The BCBT Industry Certificate Program was developed to help B.S. and B.A. graduates of MSUM transition into bioscience industry employment. The program was designed to address specific concerns identified through a series of interviews and discussions with local, regional, and national industry experts. These interviews identified big theme concerns like working in a GLP or GMP environment as well as detail concerns like appropriate documentation and maintaining acceptable laboratory notebooks. While we still have a great deal of assessment and program evaluation to do prior to declaring the program a success, one clear outcome of the course design is that students gain a much greater appreciation for the value of laboratory notebooks and the need for quality documentation in an industry environment.