With the third-largest concentration of biotechnology firms in the United States and thriving business-academic partnerships centered around Research Triangle Park, North Carolina is fast becoming a global center for life sciences leadership.
About 180,000 North Carolinians work in biotech research, development and manufacturing, or for companies serving the biotech industry,1 and more than 450 bioscience companies are headquartered in the state.2 In addition to currently generating $3bn of revenue annually, North Carolina biotech business is estimated to grow 10-15 percent per year. 3
There is no doubt that the state of North Carolina has established an impressive reputation in the field of biotechnology and the Golden LEAF Biomanufacturing Training and Education Center (BTEC) intends to keep it that way.
BTEC is a state-of-the-art training facility situated on the Centennial Campus of North Carolina State University and provides students with hands-on training for careers in biotechnology. Its pilot-scale biomanufacturing training center is the largest in the world and its laboratories are equipped with the same modern technology used in industry. Through development of the region’s human capital, BTEC aims to continue to attract new life science business to North Carolina.
A core component of BTEC’s educational program is pipetting technique training. Pipetting is often considered a tedious laboratory task and overlooked when strategies for higher quality and productivity are developed, yet it is strongly linked to data integrity. To demonstrate the importance of proper pipetting skills, BTEC uses the Artel PCS® Pipette Calibration System and the Artel MethodTM of pipetting technique training, offered by liquid handling quality assurance leader Artel (Westbrook, ME). Trainees have achieved significant improvement in pipetting proficiency and a greater understanding of proper technique, resulting in lasting gains in quality, precision and accuracy.
Shortly after the turn of the millennium, North Carolina was rapidly losing manufacturing jobs in its traditional industries – tobacco, textiles and furniture – but was experiencing strong demand for highly skilled workers in the fast-growing biotechnology sector. BTEC was designed as a solution, funded primarily by a grant from the Golden LEAF Foundation. This nonprofit organization administers North Carolina’s tobacco-settlement money set aside to compensate the state for costs associated with smoking-related illnesses and to provide an economic boost to areas dependent on the fading tobacco industry.
The Golden LEAF Foundation pegged BTEC as a worthwhile investment since it intends to train as many as 2,000 students each year. With strong engineering and science programs, North Carolina State University was selected as the facility’s home.
To provide a smooth transition to industry, BTEC is equipped with all of the modern laboratory and bioprocessing equipment found in typical commercial facilities. This feature also made BTEC an ideal choice for real-world training for field and operational personnel from the FDA’s Office of Regulatory Affairs who needed to facilitate inspections in North Carolina and throughout the U.S. Through the FDA Biomanufacturing Workshop, FDA trainees were exposed to a variety of pharmaceutical and bioprocessing technologies and applications that they would later inspect in the field. This training ensures that regulators are familiar with industry technologies and that both parties speak the same language. Trainees attend modules focused on bioprocess engineering, fermentation techniques and quality control/analytical technologies.
There are several laboratory methods and applications in BTEC’s QC/Analytical module that require delivery of liquid samples in specific volumes for accurate results, such as ELISA and HPLC techniques. Assay results are therefore highly dependent on operator pipetting technique. If the operator pipettes the wrong volume or his or her technique is not repeatable, the assay results may be unknowingly incorrect. To successfully complete the QC/Analytical module, it was critical that FDA trainees had an adequate level of pipetting proficiency
Nathaniel Hentz, Director of the Analytical Lab at BTEC, was familiar with the Pipetting Technique Training program offered by Artel and sought to include it in the FDA Workshop. “Artel’s Pipetting Technique Training program keeps trainees engaged and interested in the learning process, and also provides immediate feedback for lasting performance gains,” said Hentz.
Due to an FDA requirement that all trainers be pre-approved, Artel staff was not able to participate in the actual workshop and instead trained BTEC instructors on the Artel Method of training, which is a standardized, consistent teaching approach. Artel’s proven process includes a pre-training skills assessment using the PCS, instruction on the mechanical function of pipettes and various causes of failure, guidance on proper technique, and finally a post-training skills assessment.
The Artel Method also provides hands-on coaching to show trainees how numerous variables affect pipetted volumes, from choice of pipetting mode to tip insertion depth and aspiration rates. With the PCS, trainees receive rapid feedback and can immediately test their pipetting performance.
“There is no other technology available that can facilitate pipetting technique training like the Artel PCS,” said Hentz. If a gravimetric method, i.e., weighing liquid on a balance, were used for pipetting technique training, feedback would be delayed by the calculations required to generate accuracy and precision statistics. The PCS, on the other hand, automatically measures the dispensed volume and calculates and reports accuracy and precision. After each dispense, trainees can view the exact volume delivered, allowing them to see how various pipetting techniques affect volume.
Figure 1 compares the pipetting accuracy and precision of the FDA trainees before and after pipetting technique training. Remarkable improvement in accuracy and precision was evident.
The session was highly effective in demonstrating the criticality of accurate and precise pipetting for correct analytical results. “Many of the FDA trainees were surprised by how different results could be based on seemingly minor differences in pipetting technique,” said Hentz.
Keeping it Fun
After the success of the FDA workshop, BTEC faculty members purchased two PCS systems so they could incorporate pipetting technique training into their day-to-day curricula. Now, the very first laboratory class of each semester includes a pipetting skills workshop that begins with a pre-training skills assessment using the PCS. BTEC faculty members employ the Artel Method of training to teach students about the impact of improper technique and provide guidance on improving accuracy and precision before conducting a post-training skills assessment.
“The students’ ability to see the direct impact of changes in technique on accuracy and precision reinforces the importance of proper pipetting. They now understand that incorrect pipetting technique could lead to inaccurate laboratory results,” said Hentz.
Turning the interactive exercise into a mini competition has proved beneficial for knowledge retention as well as for building camaraderie. The competition also serves as an ice breaker and gets students involved and engaged in the subject matter. During the semester, students compete individually and in teams to achieve superior precision, which reflects consistency and repeatability in their pipetting technique. Students must achieve a CV (coefficient of variation, or the measure of precision) between 0.0% – 0.19% for gold medal status, between 0.20% – 0.49% for silver medal status, or between 0.50% – 1.00% for bronze medal status.
So far, all BTEC students were able to achieve medal status after undergoing pipetting technique training, but students often reverted to old habits. Continual reinforcement of Artel’s guidance on technique combined with ongoing Pipetting Challenge contests throughout the semester have helped, according to Hentz.
“I would say that 80 percent of my students retained the information about proper pipetting technique throughout the semester,” said Hentz. “In this business, that is a great batting average for first timers.”
The PCS has also proved useful as a troubleshooting technique. When unable to generate accurate results with an ELISA assay, which has numerous, complex liquid-handling steps, a student used the PCS to prove that the pipette and operator were not the sources of error. Troubleshooting efforts then rapidly focused on the assay and the problem was quickly resolved.
BTEC is also using the PCS to calibrate its pipettes. Because students often use pipettes on a short-term, semester-based cycle, they are not as careful with their instruments as their industry counterparts, so it is important that BTEC calibrate its pipettes on a frequent basis.
Ready for the Real World
After undergoing training sessions at BTEC, NC State students and FDA inspectors alike are better equipped to enter the commercial laboratory environment. In particular, BTEC is playing a critical role in changing the mindset that pipetting is an unimportant task. By showing with objective data how analytical results can be affected by poor pipetting technique, BTEC is improving laboratory quality one student at a time.
Designed to provide statewide education, economic development and job creation for the biomanufacturing, pharmaceutical and related agribiotechnology industries, the Golden LEAF BTEC is the only center of its kind in the nation. The hands-on, industry-specific education and training we will provide exists nowhere else, and will serve as a magnet for new business expansion and relocation by these industries.