Perspective On: A Contract Research Lab

When developing new chemical entities, pharmaceutical and biotech companies often employ the help of contract research organizations (CRO).

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When developing new chemical entities, pharmaceutical and biotech companies often employ the help of contract research organizations (CRO). Bioanalytical CROs assist with method development, validation and sample analyses for preclinical and clinical drug development studies.

MicroConstants, Inc. is one such organization. This CRO provides GLP-compliant bioanalytical research services, enzyme-linked immunosorbent assays (ELISA), drug metabolism and pharmacokinetics (DMPK) assays, and pharmacokinetic analysis services to pharmaceutical and biotech companies worldwide.

“We specialize in method development, method validation and sample analysis of small molecules, proteins and peptides using LC-MS-MS, HPLCUV and ELISA for drug discovery and development studies,” says David F. Beyerlein, Vice President of Global Operations at MicroConstants. “[Our organization] also assembles and distributes customized specimen collection kits for all types of clinical trials conducted throughout the world.”

“We provide contract research services to pharmaceutical and biotech companies of all sizes, from virtual firms to big pharma,” he adds. “Our clients are located all over the world—[we] have worked with over 270 clients in 27 different countries and are in various stages of the drug development process.”

Beyerlein, who co-founded MicroConstants, is responsible for managing all lab operations, project and sample oversight, information technology and purchasing operations for the organization.

Organizational structure

MicroConstants is headquartered in San Diego, California, with an additional location in Beijing, China. The facility in San Diego, where Beyerlein is located, occupies 34,000 square feet of office and laboratory space and houses 16 liquid chromatography/tandem mass spectrometry (LC-MS-MS) systems. MicroConstants San Diego has an additional 2,000 square feet of offsite archive space.


MicroConstants’ facility in Sorrento Valley (San Diego).

“[This] makes us the largest bioanalytical LCMS- MS laboratory on the West Coast of the United States,” Beyerlein says. “I oversee all the lab and office areas, with the exception of the off-site archives, where only the facilities, IT and QA departments have access.”

Responsible for managing the bioanalytical chemistry, formulation analysis, immunology, specimen collection kit production, project management, metrology (QC), purchasing, facilities, and information technology (IT) departments, Beyerlein has 40 employees reporting to him. Seven of the 40 are direct reports.

In total, the organization has more than 50 employees at the San Diego facility. More than half of the staff works in the laboratories.

“At minimum, all our laboratory employees have a bachelor’s degree in chemistry, biochemistry, molecular and/or cell biology or immunology, as appropriate for their position,” Beyerlein says of his staff. “The majority of our LC-MS-MS bioanalytical work can be best classified as analytical chemistry; however, many of the compounds we are asked to analyze are biologicals and require experience and education spanning both chemistry and biology.”

Beyerlein himself is educated in chemistry, has been in the bioanalytical chemistry field for the majority of his career and has more than 13 years of experience managing laboratory operations.

“I have been operating and maintaining mass spectrometers and training others to do so since 1994,” he says. “I cofounded MicroConstants with Dr. Gilbert Lam in 1998. Prior to that I was part of the mass spectrometry group at Covance’s facility in Madison, Wisconsin. Before joining Covance, I was a senior research and development scientist in the bioanalytical/mass spectrometry group at the Madison, Wisconsin facility of PPD-Pharmaco, where I started their bioanalytical LC-MS-MS department.”

Inventory and maintenance

On average, MicroConstants’ San Diego facility receives about 10,000 samples per month. Analyzing the samples accounts for about half of the scientific staff ’s workload. They spend the rest of their time developing and validating methods.


Temperature-controlled specimen sample storage.

With such a challenging workload, it’s important for the lab to stay organized. One aspect of ensuring that all operations are running smoothly is managing the lab’s inventory.

“Our laboratory supplies are divided into four categories: reagents, biological matrices, general lab supplies/ consumables, and chromatography products, including both highperformance liquid chromatography (HPLC) columns and solid-phase extraction plates,” Beyerlein says. “Four teams of two scientists, one primary and one backup, are designated to monitor the inventory of each of the four categories.”

When the lab reaches an inventory trigger point on a particular item, the scientist responsible will submit a purchase order request form to the organization’s purchasing department. Purchasing staff will research the item by contacting approved vendors, or by searching the Internet if the product is not distributed by an existing approved vendor.


Scientist reviewing LC-MS-MS data results.

Once the best options for an item are identified—based on quality, price and availability—the purchasing staff will submit the options to Beyerlein for approval; he will give the final go-ahead to place the order.

“Special orders—such as chiral columns, derivatizing reagents, hepatocytes or other unique biological matrices—that are required for specific client projects are typically requested by the principal investigator assigned to that client’s project,” Beyerlein says.

MicroConstants has a dedicated quality control unit called the metrology department, which handles the majority of the organization’s equipment maintenance and calibration. Any maintenance that can’t be handled internally is sent out.

“We provide in-house training for our metrologists and ensure that they have a fully stocked QC lab area with plenty of spare parts for each instrument we own,” Beyerlein says. “We outsource maintenance and/or calibration for analytical balances, balance weight sets, low-volume pipettes, fume hoods, biological safety cabinets, all fire-suppression systems and the deionized water system.”

Hiring

Once a week, Beyerlein meets with all the department heads to discuss future scheduling and resource needs. During these meetings, if the team leaders notice workload surges or special needs within a department, they reallocate resources between groups to ensure that deadlines don’t suffer while they are resolving any conflicting instrument or personnel needs.

“We project our schedule, as best as possible, for many months in advance,” Beyerlein says.

Should any team leaders determine that they might face a potential increase in workload, they will bring it up at the meetings, where the group decides on hiring the necessary personnel.

“Our training time for new scientists is at least three months of intense one-onone training, and it’s about another three months before they are allowed to work independently,” Beyerlein says.

“To hire and train a new employee, we need to accurately anticipate an increase in our workload at least four months in advance. When a need is identified, we post the open position on our website, on various employment websites, at appropriate conferences, and on professional organizations’ websites [and] job boards that target the desired candidate.”

The organization’s human resources department screens applicants based on the position requirements by reviewing resumes and conducting phone interviews.

“This process helps narrow the field to a reasonable number of candidates for inperson interviews,” Beyerlein says. “For an entry-level scientist position, we typically interview between five and 10 candidates.”

Personnel

With the right personnel in place, it’s important to ensure that they’re treated as professionals. This benefits both the employees and the company.

“One incentive we provide our employees is a flexible work schedule,” Beyerlein says. “When I interview new employees for the lab, I always tell them that science does not often follow a 9-to-5 work schedule. Some days will be longer and some will be shorter; you just can’t walk away mid-experiment.”

In addition to allowing flexibility in the work schedule, the company and its management encourage their employees to continually advance their careers. One way to do this is to facilitate participation in professional development opportunities and provide reimbursement for conference and seminar attendance.

The company offers additional incentives to keep its staff happy.

“We offer ‘Above and Beyond Awards’ for exceptional accomplishments, plan six to eight company events and happy hours each year, and have a great benefits package,” Beyerlein says. “Our benefits program includes medical, dental and vision care coverage; paid vacation, sick leave and holidays; flexible health care spending accounts; group life insurance; long-term disability insurance; and a company-matched SIMPLE IRA plan.”

Communication

The employees are also encouraged to openly communicate with each other. Managers such as Beyerlein ensure that they know what’s going on within each department.

“I not only believe in an open-door policy, but I also walk around through the lab areas and office areas to ask people how their projects are going,” he says. “Any issues that may exist get resolved much more quickly when you approach people, as opposed to just being approachable.”

Additionally, Beyerlein holds scheduled internal meetings to go over specific objectives and the associated timelines.

“I typically attend only four scheduled internal meetings each week,” he says. “My department managers [also] hold meetings with their teams and individual employees as frequently as needed throughout the week to ensure that their projects are running smoothly.”


MicroConstants scientist performing bioanalytical analysis.

To communicate with clients, the company has a dedicated project manager and a principal investigator assigned to each client.

“Many clients have scheduled weekly teleconferences, and we are available to meet with them or talk to them on the phone anytime they have questions,” Beyerlein says. “We send out weekly project updates and send data as soon as it becomes available. In some cases we are providing 24- hour turnaround on sample analysis. For these types of studies, the communication needs to be seamless to ensure that the deadlines are met.”

“Each client has different expectations, and we adjust as needed to meet those expectations. Our general philosophy is to increase the frequency of updates and communication to a point where our clients never need to contact us requesting an update,” he adds.

Challenges

In a regulated environment such as a contract lab like MicroConstants, one of the biggest challenges for the leaders of the organization is training new personnel in a timely manner. To ensure that the training process is smooth and thorough, over the years, the staff and team leaders have put together training guides for various positions and tasks. These training guides have been turned into records. Each employee is asked to fill out a record each time he or she performs a task. While the results of this practice are invaluable for training purposes, it does pose some challenges.

“Although creating more forms and records ensures that people are being trained consistently and that tasks are being performed correctly, it can definitely slow the workflow,” Beyerlein says. “Also, most people don’t like to fill out more paperwork to get their jobs done. So to streamline our documentation process without negatively impacting productivity, we have made our records as simple as possible to use.”

“At our employees’ suggestion, we set up a committee to review new records, test them before they are finally released and find ways to simplify their use,” he adds. “This helps get the employees’ buy-in on any new records or record revisions.”

But the challenges of a laboratory are many. Years ago, Beyerlein and his colleagues experienced a drop in productivity due to vendor scheduling for yearly requalification of analytical instrumentation.

“All the cost-effective vendors wanted to perform the instrument qualifications for all our systems within a three-week time frame once a year,” he says. “This created a serious hardship on the production of our laboratory during that time and also required one or two employees to work with them throughout the process to ensure that they completed the qualifications before their due dates.”

The team experienced a similar issue with the annual recalibration of temperature monitoring probes, causing the lab to reduce the frequency of the probe calibration to every two years.

“It became apparent that we needed to perform all these functions in-house,” Beyerlein says. “Our QC department wrote protocols and records for all these activities; our IT department designed a custom, validated LIMS system to track instrument maintenance, calibration and qualification; and we brought this work in-house.”

“By performing most of the qualifications earlier during the first year, we staggered them to occur throughout the year. This allowed the lab to function normally throughout the year with no significant interruption and allowed us to revise our SOPs for the temperature monitoring probes back to an annual recalibration,” he adds.

This, Beyerlein explains, is an adaptation strategy necessary for anyone running a business. “As a lab manager, it is extremely important to have the ability to recognize what isn’t working within your organization and to be able to change and/or adapt your strategy quickly,” he adds.

Ultimately, challenge is something this lab manager thrives on. A love for the job and the need to figure out solutions are the fuel that has kept Beyerlein in the bioanalytical industry for almost 20 years.

“I expect to be challenged each day by new compounds with new issues that we need to overcome and to enjoy working with my scientists to find solutions to those challenges,” he says. “To have a successful career, it is important to choose something you enjoy, and for me the mental stimulation is very motivating. I truly enjoy coming in to work.”

 

Published In

Is the Rollercoaster Ride Over? Magazine Issue Cover
Is the Rollercoaster Ride Over?

Published: March 1, 2012

Cover Story

Is the Roller Coaster Ride Over?

The laboratory industry enjoyed several years of robust growth from the late 1990s until 2003. Record research and development (R&D) investments by the biopharmaceutical industry, in combination with the doubling of the U.S. National Institutes budget, allowed for continual double-digit growth rates.