Whenever the issue of lab results reliability or integrity of work comes up, Chris Hudalla, founder and chief scientific officer of ProVerde Laboratories, thinks of a young client of his. Abby has relied on cannabis to control her epileptic seizures since she was 13 months old. The product that his client needs for her condition is not commercially available. So, Abby’s mother grows and extracts a strain of cannabis, known as ADC, which has been demonstrated to be very effective for her seizures. Hudalla’s lab ensures the medicine Abby consumes is safe and free of toxins.
“I [have to] think of the product being potentially contaminated with pesticides or heavy metals, both of which can be cumulative in terms of their toxicity,” Hudalla says. “I always see Abby's face because, for me, I have to put her face on everything that I do. I don’t know who is going to be consuming the product, [but] I know that on the other end of this product line, there’s a face of somebody who needs to make sure that what they’re consuming is safe and not going to harm them.”
ProVerde Laboratories was established to meet the regulatory testing requirements for the cannabis program in the state of Massachusetts, in which marijuana was legalized in 2016. The lab is likely among the first ISO 17025-accredited laboratories in the United States, and it has one of the broadest scopes of testing within that accreditation. ProVerde staff test for pesticides, plants, heavy metals, residual solvents, and everything within the ISO 17025 scope, all of which Hudalla considers part of Good Laboratory Practice (GLP).
“Being ISO 17025-accredited is probably the best way to stay compliant,” Hudalla says. “It basically governs analytical testing laboratories and calibration laboratories.”
The principles of GLP are in place to assure quality and traceability in research laboratories. Adopted in 1978 in the United States, these principles safeguard the integrity of generated data. Labs must adopt these practices to ensure they are producing valuable test results, and each lab has its own set of approaches to staying compliant.
Implementing GLP through paper trails
For many labs, GLP starts with a simple task—keeping good records and being able to retrieve them when needed. “A lot of it has to do with the ability to document, and some of it is purely just organizational because in our audits we’re constantly pulling records,” Hudalla says.
“The way our organizational structure works is we have all of that documentation to have complete traceability right at our fingertips. I can show you what temperature our incubator was at 2 a.m. on November 23rd.”
So, when an auditor visits their lab, that individual can pull any test results from ProVerde’s databases. “The auditor will say ‘Show me the person who prepared this sample,’ and so we pull up the record, and he’ll say ‘Show me the training record for this person and show me the date he was trained,’” Hudalla says.
Furthermore, every test at ProVerde Laboratories has a series of environmental blanks and quality control checks. Additionally, the staff perform periodic replicates and spiked replicates of samples. Most of the procedures are modeled after the International Council for Harmonization (ICH) guidelines for good laboratory practices.
“Some of the states are now starting to implement some additional requirements that are a little bit different [from] the ICH, so we’re not replacing our current ICH protocols but we’re supplementing them with specific state requirements,” Hudalla says.
Hudalla’s lab is not alone. At Draper, a not-for-profit research and development company that focuses on the design, development, and deployment of advanced technological solutions for customers in government, industry, and academia, those in charge of the organization’s laboratories also believe in a lot of rigor and attention to detail and quality—all of which can be achieved only if proper record-keeping procedures are in place.
“We are committed to manufacturability, so we provide our customers with thorough documentation, so that they can make the transition from prototype to product,” says Chris DiBiasio, group leader for advanced manufacturing at Draper, who also manages two of Draper’s labs—the Central Machine Shop and the Additive Manufacturing Center. “It’s one of the most important things we do ... to capture all of that information for our customers. Documentation is a huge part of the quality process—and being ISO certified.”
Another important factor in staying compliant has to do with having a competent and properly trained staff. Employees in Draper’s System Assembly, and in many other departments in the company, receive specialized training for working on some of the most sophisticated and demanding programs.
“Our training requirements include internally generated curriculum addressing electrostatic discharge awareness, foreign object and debris awareness, limited-life material handling, and circuit card assembly handling,” says Justin Medernach, a manufacturing engineering supervisor at Draper, who manages the engineering group that supports the company’s 30-person Electronics Assembly Lab.
“We also certify our electronics technicians to JSTD- 001 with space addendum, IPC-A-610, IPC7711, and IPC7722,” he adds. “Our staff is knowledgeable of, and compliant with, Defense Federal Acquisition Regulation Supplement, Defense Contract Management Agency, and Defense Contract Audit Agency requirements.”
Similarly, employees at Draper’s Central Machine Shop and Additive Manufacturing Center take part in ongoing training and participate in refreshers when complex and high-visibility jobs come in.
“Training for handling strategic-grade hardware is focused on chain of custody, compliance, verification, and many other steps,” DiBiasio says. “We will actually playact certain complex jobs before going live on the shop floor.”
At ProVerde Laboratories, extensive training is coupled with generation of training records. Lab staff read and understand procedures that relate to the lab’s operations. They also work with a technician who’s been trained, and they prepare the same samples side by side and compare the results.
“We give them challenge samples,” Hudalla says. “So, we may spike a sample and give it to them without their knowledge—they don’t know what the spike level is—and so we test them that way.”
Additionally, the employees participate in expertise testing through Emerald Scientific, an organization that facilitates proficiency testing for the cannabis industry by sending challenge samples to participants. Challenge samples are distributed to labs throughout the country that participate in the testing.
The results are then fed back to Emerald Scientific, whose staff conduct statistical analysis on the data. That, according to Hudalla, is a method of comparing their laboratory abilities relative to other labs in the country.
For many labs, major noncompliance tends to be rare. When it does happen, however, the organization must put forth corrective processes to ensure they comply with ISO standards and are back on the path of GLP compliance.
“Noncompliance for us can mean using noncertified material or executing a process out of sequence,” DiBiasio says. “Our first step is to triage the problem and find the root cause. Our next step is to make a plan, which often involves the customer.”
When it comes to their System Assembly lab, Draper uses a material review board for initial assessment of a noncompliance event, a step required for some of Draper’s customers. The System Assembly lab uses a collaborative approach in instances where a noncompliance event has been discovered.
“Formal root causal analysis and appropriate corrective actions are identified, implemented, and verified,” Medernach says. “We are willing participants in formal internal and external audits in order to mitigate the risk of encountering future noncompliance.”
Similar to Draper, ProVerde Laboratories has never encountered a major noncompliance event. For minor noncompliance, they have, under ISO rules, performed what’s called a CAPA—Corrective Action/Preventive Action.
Basically, the laboratory has to document what took place and why it happened. If the lab officials are not sure why a noncompliance event occurred, they have to perform an investigation to identify the cause of the nonconformance. Once the cause is identified, they have to work toward the proper corrective action. In other words, they have to pinpoint what has to be put in place so the incident doesn’t happen again.
Often, the corrective action is as simple as a change in a procedure or a piece of equipment, or retraining an employee. “You have to document that corrective action and then have a follow-up, typically about six months later, where, once that corrective action is closed out, [it] is re-reviewed to ensure that [what] was put in place is still being maintained and that it’s still operating the way it was intended ... in terms of preventing that type of mistake or error from happening in the future,” Hudalla says. “Again, a lot of it is just about documentation.”
No matter the method, most successful lab managers agree that GLP is an indispensable tool in compliance—central to running a dependable operation and outputting valuable and reliable information that helps produce good science and safe products.
“Compliance with good laboratory practice is important in Draper’s labs because it is good business, it’s valued by our customers, and it keeps our teams sharp,” DiBiasio says. “We ask our people to be agile and prepared to change hats very quickly, and compliance is central to achieving that.”