Lauren Lavelle

Taking the time to comply with lab data integrity practices during the COVID-19 pandemic in a resourceful and operative manner is crucial for pharmaceutical laboratories. 

spoke with Bob Voelkner, vice president of Sales and Marketing at LabVantage Solutions; Charles Fracchia, CEO of BioBright and vice president of Data, Dotmatics; John Maier, director of labs data management at PPD Laboratories; and Kimberly Remillard, senior manager of Regulatory Affairs for Digital Science at Thermo Fisher Scientific about the best practices for lab data integrity during the COVID-19 pandemic.

 Are there any new regulations regarding lab data integrity? How do current and/or new regulations apply to research going on for COVID-19 therapies?

 The most recent regulations or standards for data integrity came in 2018, when FDA published updated guidance for industry on ensuring data integrity and compliance with CGMP [current good manufacturing practice] (1). At the same time, the World Health Organization and [the United Kingdom’s] MHRA issued guidance on data integrity, which is largely in line with FDA’s (2, 3). Today, the need for organizations dealing with COVID-19 to comply and adhere to the FDA guidance is no different than any other organization developing and manufacturing new drug products. The goal of data integrity is to assure the safety of, and therefore increase the confidence in, all pharma products being created and produced. Data integrity takes on heightened importance, as new COVID therapies and vaccines are on the fast track to market and prospective patients want assurances of the integrity of the drugs being offered to them. Operating a compliant lab in this environment, with data integrity at its foundation, is vital.

 (1), defines data integrity as ‘the completeness, consistency, and accuracy of data.’ While there haven’t been any new regulations regarding lab data integrity, the good clinical practice (GCP) principle that requires data to be attributable, legible, contemporaneous, original, accurate, and complete (ALCOAC) applies to all clinical trials including ongoing research for COVID-19 therapies. In order to meet the accelerated timelines of COVID-19 trials, study setup timelines have been minimized while maintaining data integrity by employing innovative technologies and processes such as:

A single global lab database to eliminate the need to merge and harmonize data

Simplified protocol definitions to improve study database quality and shorten startup timelines

Interactive web-based portals for investigators with electronic lab requisitions to significantly improve the completeness and accuracy of the data on entry

Interactive web-based portals and dashboards to enable study sponsors and project teams to monitor study wide data in real time

Powerful interfaces that combine lab data with the clinical development database in real time and continuously cleanse the data to streamline study closeout.

 In response to COVID-19, researchers and regulators have found it necessary to adjust priorities and protocols to meet new restrictions and practices for researchers, patients, and healthcare workers. Several guidance documents have been published to provide direction on how to adjust to the new conditions while maintaining data integrity and patient safety. The guidance documents make it clear that the same ALCOA+ data integrity principles apply in addition to ensuring patient safety, protection of personal data, and data validity for any trial interruptions or protocol changes. With interruptions in protocols and new remote methods of monitoring being utilized, data integrity is becoming even more critical to ensure research data maintains its validity.

Specific documentation is required to detail why protocol changes, deviations, or alternative processes are implemented, including why protocol-specified data may be missing. All alternative approaches must maintain trial participant safety and trial data quality and integrity, while minimizing missing data.

In addition to changes needed in the clinical trial and research space, fast track Emergency Use Authorizations allow for exemptions from certain GMP controls in the manufacturing area. Data integrity is critical to help reduce risk with the use of these GMP exemptions. For example, data integrity to show traceability and adequate control of source materials, data around batch records, and testing must be in place. Validation to support the consistency of the manufacturing process, including computerized systems validation, is also critical to ensure data integrity can be maintained.

Applying data integrity principles during the research and development of COVID-19 therapies to ensure the data complete, accurate, consistent, trustworthy, and reliable will support regulatory submission efforts and contribute to patient safety. Digitalization of the laboratory with integrated technologies such as a laboratory information management system (LIMS) to manage the workflow of data can add efficiency and traceability and help to ensure data integrity principles are met.

How challenging or difficult is it to comply with lab data integrity regulations during the COVID-19 pandemic?

Accelerated startup and overall timelines of COVID-19 trials have presented a significant challenge to ensuring compliance with lab data integrity regulations. We have been able to significantly reduce our setup timelines by utilizing specialized global rapid implementation teams along with the innovative technologies and processes previously mentioned.

During study execution, the sheer volume of subject and sample data collected within the condensed timelines has made real-time data monitoring and reconciliation critically important to the success of COVID-19 trials. To facilitate this, we have implemented innovative analytical tools that proactively monitor study data integrity and notify lab and clinical teams of investigator and procedural non-compliance before it impacts timelines.

During the COVID-19 pandemic, new protocols and methods for monitoring are often necessary and need to be implemented quickly. More remote data collection and management activities are occurring in the effort to minimize risk of COVID-19 for researchers, trial participants, and manufacturers alike. Due to this, it is critical that data integrity is maintained to ensure the validity of the study data as well as the protection of the patient information. Digitalization of the laboratory workflow using validated systems can reduce the risk of data integrity issues. Permission controlled systems with controlled workflows, integration to reduce potential points of human error, access across sites, and enhanced security features can all work together to support the data integrity and validity of research data. Use of secure cloud-based LIMS systems can help to connect not only the instrument data within your lab, but also allow for connectivity between sites.

I would argue it’s really only challenging or difficult for those labs that aren’t equipped with the right tools and solutions. Lab-dedicated software, like an LIMS, is designed to ensure the integrity of all the data gathered by the system. This includes dynamic auditing, so even data in temporary memory is audited prior to being committed to permanent/durable memory. These automated, connected LIMS eliminate manual data entry and risks of transcription errors or purposeful manipulation of data.

Largely speaking, because the regulations haven’t changed, the compliance hasn’t changed either. There are COVID-19 specific challenges that have arisen, largely due to the fact that fewer people are working on site, personnel density restrictions, access to certain facilities (in particular manufacturing) has been heterogeneous from company to company, and even between sites of the same company. Challenges of this kind have affected our industry particularly hard due to the acute need for the work itself. It is certain that the importance of having a safe and efficacious vaccine, alongside the politicization of the vaccine availability, have negative effects on the environment surrounding the development. Even before the pandemic hit, there have been reports of data integrity bypasses and fraud. Pressure due to the pandemic has only increased existing trends in this environment and combined with a generalized lowering of the public’s trust in any vaccine, this makes data integrity and compliance a crucial aspect of the response.

How do you suggest other organizations improve/enhance their lab data integrity activities (specifically, workflow, day-to-day operations, etc.), and how can this particularly help companies that are trying to develop a COVID-19 therapeutic?

 Data integrity relies on a combination of people, technology, and processes. Robust processes are necessary to ensure consistency and quality assurance. A good culture of quality will help to ensure the human resources involved in the laboratory will execute the processes in the correct way. And the right technology to meet the needs of the laboratory and regulations such as 21 

] Part 11 can help to reduce the risk of human error and process deviations.

Whenever possible, integrating the laboratory with validated digital systems to meet your workflow needs will help to reduce the risk of data integrity issues. The same principles will apply whether digitalized or not; however, more checks and monitoring may be required for systems which are not digitally controlled. Ensuring all data specific and attributable, including clearly and specifically documenting any changes or missing data, is key to be able to show the integrity and validity of your data.

 In order to improve lab data integrity activities, companies must review their existing practices and replace wherever possible error-prone, manual steps in the reporting of results and tracing of individual steps. With a robust, automated, informatics system taking care of recording and tracking vital laboratory or manufacturing information, a company can reduce the chances of having data integrity issues. Crucially, companies must also assess their systems’ cybersecurity posture, because with increased automation and informatics also comes a potential for external manipulation. Unfortunately, the vast majority of bioinformatics or laboratory informatics tools have very poor cybersecurity practices and hygiene and create a large opportunity for third parties to steal and modify data in said systems, and understanding the weaknesses and avenues that could cause deviations or data manipulations are absolutely key for companies. This is particularly true if —as the FBI has warned (4)—the company has publicly announced efforts in search of a COVID-19 therapeutic. Finally, we strongly recommend that companies set up a process to review new data and results that are being put into the record. This practice, common in clinical environments, needs to be performed by a person who is not familiar with the specific experiment, ideally even a disinterested third party. This will create human oversight and catch errors such as missing data, ambiguous results, unsupported conclusions, and more. Enacting this practice will ultimately give the executives, the company’s team, and even the public a level of safety in trust in the result that is sorely needed in this moment.

 Organizations can improve lab data integrity by implementing systems and processes that reduce the level of effort to set up and validate the lab database by utilizing a single global database; limit the amount of data captured to only those elements required for analysis; employ robust quality controls that QC [quality control] data on entry, when modification are made and prior to reporting; and provide innovative web-based tools that facilitate electronic data capture (electronic lab requisitions) and real-time data access to investigators and clinical team members for continuous data review and reconciliation.

 One critical way to ensure product quality is to prevent data integrity lapses at the outset, so proper lab automation is key. For companies that have abandoned traditional, paper-based record-keeping practices or deficient legacy IT systems, in favor of preconfigured and prevalidated LIMS built specifically for today’s regulated labs, they’re already on the right track. Such a LIMS enables automated connection to lab instruments so that results can be directly recorded into the LIMS, not only speeding the process, but increasing data integrity.

It’s worth noting that modern LIMS, which should be 100% browser-based, can help lab directors and managers to physically distance laboratorians who can work with tablets or other mobile devices.

 What trends are driving the need for data integrity in the laboratory setting?

 Besides the politicization and fraught recent history of data integrity that was discussed above, the next most important trend affecting data integrity is the deluge of data that is now commonplace in our industry. In processes where thousands of data points per day was the norm, we now routinely see workflows that generate millions of data points per day, both qualitative ones (such as images) and quantitative ones (e.g., assays). This dramatic uptick in data volume is a blessing for data-driven research, but it is also an unprecedented challenge to verify, validate, and commit [these] data to record. The need for automated tools is now clear, and such tools must be aware of automation capabilities and be hardened against cyber manipulations or we risk the robustness and trust of the whole system in this transition.

 The continuous push to bring therapeutics to market quicker and more cost effectively will continue to drive innovation and system integration throughout all phases of the clinical trial life cycle and in the laboratory setting, to ensure data integrity is maintained. We will continue to develop improved analytical tools and are beginning to explore artificial intelligence predictive models to improve subject, site, sponsor, and lab compliance, which in turn will help enhance data integrity, reduce study timelines, and ultimately drive down costs.

Data Integrity and Compliance with Drug CGMP

, www.fda.gov, accessed Nov. 9, 2020.
2. MHRA, 

‘GXP’ Data Integrity Guidance and Definitions

, www.gov.uk, accessed Nov. 9, 2020.
3. WHO, 

, www.who.int, accessed Nov. 9, 2020.
4. CISA, “FBI and CISA Warn Against Chinese Targeting of Covid-19 Research Organizations,” Press Release, May 13, 2020.

Lauren Lavelle is the assistant editor for 


Vol. 44, No. 12
December 2020
Pages: 36-40

When referring to this article, please cite it as L. Lavelle, “Complying with Lab Data Integrity Practices During COVID-19,” 

Articles

Pharmaceutical laboratories must keep lab data integrity practices in mind in order to properly handle the effects of the COVID-19 pandemic.

Complying with Lab Data Integrity Practices During COVID-19

	Taking the proper steps to comply with current good manufacturing practices (cGMPs) for aseptic and sterile processing in an efficient and effective manner is necessary for pharmaceutical manufacturing facilities and labs. 

 spoke with Ulrich Herber, senior global product specialist manager for Microbial Solutions, Charles River, and Sade Mokuolu, group product compliance manager, Watson-Marlow Fluid Technology Group, about best practices for GMPs in aseptic and sterile manufacturing and in quality control laboratories.

 Why is it important for organizations engaged in aseptic/sterile processing activities to practice GMPs?

First and foremost, practicing GMPs ensures a safe, efficacious, and high-quality product that preserves the safety of the end-user: the patient. However, practicing GMPs also ensures that the risk of contaminating the product is reduced or detected and controlled quickly. This ultimately maximizes operational efficiency, eliminates waste, and improves an organization’s bottom line.

 cGMPs are important to ensure that pharmaceutical products meet high quality standards and are safe and effective. As producers of high-value medicinal products, non-compliance with regulations could risk consumers’ health, failing to achieve regulatory approvals, and significant loss of revenue. It is therefore important to not just comply with cGMP regulations, but also be able to demonstrate that you have. GMPs are necessary to demonstrate that there are good control procedures built in during the manufacturing process to prevent errors that cannot be eliminated through quality control of the finished product. Without GMPs, it is impossible to be sure that every unit of medicine is of the same quality as the units of medicine tested in the laboratory.

 How challenging or difficult is it to comply with GMP regulations?

GMP regulations are well defined and focus essentially on the five P’s: People, processes, procedures, premises, and products. Once there are appropriate controls and ongoing verification of these aspects has been established, it should not be difficult nor challenging to comply to the GMP regulations. The heart of GMP is the establishment of well-written procedures for each operation. These written procedures give us the controls necessary to minimize the chance of mix-ups and errors in manufacturing a product. By carefully following written procedures, it serves to provide evidence of compliance with the GMP regulation, but more importantly, it helps to ensure the consistent quality of drug products. Even though the GMP regulations are well defined, following them precisely can be a challenge for a number of companies, as frequently highlighted in the warning letters (known as 483s) that FDA [the US Food and Drug Administration] publishes regularly.

 By and large, GMP regulations are not new to the pharmaceutical industry. Many companies not up to date with current best practices can mistakenly find it overly challenging to comply, but this is not necessarily the case; in fact, it is often easier to exceed minimum requirements very simply.

	For example, many new GMP requirements focus on improving the integrity of quality testing data while also reducing subjectivity in analysis and reporting. Many labs are quick to accept the first, most simple option as a solution: applying the ‘four eyes principal.’ Unfortunately, while straightforward to implement, it is not scalable nor is it a true solution. What if the lab performs more tests of the assays requiring two analysts to score the result, and thus, require more time from not one, but two analysts? What if the analysts get different results? What if both analysts get the answer wrong? In many cases, the cause for non-GMP compliance is the test method itself being outdated. These can often be solved by modernizing the traditional test method with rapid or alternative methods and using instrument-based analyses.

	Additionally, microbial identification techniques continue to evolve as more information becomes known due to advances in science. Many traditional, bench-based methods for identification, such as gram-stain or phenotypic identification, have been proven to be incapable or error-prone in identifying certain species or groups of closely related species, such as 

 complex. Many labs feel that they must continue to use outdated techniques because implementing a new technology can be cost-prohibitive and resource intensive, even though outsourcing their identification to a specialized identification lab is a proven, reliable, and more cost-efficient option.

 What equipment/instruments does your facility rely on when coordinating aseptic/sterile processing activities?

 Utilizing rapid and/or alternative test methods can be a solution that labs can rely on for aseptic/sterile processing. These instruments allow a lab to automate many processes including the assay, the results analysis, and data reporting. Many alternative and rapid methods can replace traditional methods that can pose a risk of non-compliance with GMPs. These include the use of FDA-licensed, cartridge-based LAL [Limulus amebocyte lysate] test methods and instruments to replace antiquated gel-clot methods, or using ATP [adenosine triphosphate] bioluminescence to replace visual turbidity analysis in final product sterility testing. Both of these technologies replace traditional, error-prone assays with automated technology.

 A recent amendment to European guidelines for the manufacture of sterile products, Annex 1 includes the requirement to reduce contamination sources in aseptic processing (1). It details that wherever possible, interventions should be performed aseptically and how the risk of product contamination could be reduced by the use of pre-sterilized closed systems.

 How do you suggest other organizations improve/enhance their aseptic/sterile processing activities (specifically, workflow, day-to-day operations, etc.)?

 Day-to-day improvements to lab workflows are easily achievable through implementing more automation in the microbiological quality control lab. This speeds the time to result of many assays, which creates higher throughput in the lab’s general operation. It also reduces stress and anxiety on your lab’s staff by reducing the chances of error, the need for retests, and the potential burden of performing investigations for root cause. These alone can greatly improve the overall value, utility, and employee satisfaction in an organization.

 The draft version of Annex 1 has placed a significant emphasis on applying appropriate contamination controls during drug product manufacturing. It describes how contamination risks could be minimized through the use of pre-assembled sterilized equipment.

	A further way of enhancing aseptic/sterile processing is to reduce risk through automation. A particular critical unit operation during biomanufacturing is the final filling of the drug product. To this end, equipment such as an automated vial filler and capping unit could be used to provide an aseptic environment and control of process steps.

 Are there any best practices you can recommend for new organizations (e.g., at a start-up), specifically on how to practice and comply with GMPs?

 For new companies, there are a number of ways to comply with GMP regulations. The increasing use of pre-sterilized systems such as single-use assemblies offers a number of advantages that include: no cleaning validation; easy product changeover, particularly for multi-product facilities; and no cross contamination. Additionally, working with a reliable and trusted supply partner with knowledge of GMP regulations means that prevalidated components are easily incorporated into processes and they can also provide effective support and verification of their supply chain.

 Startup organizations often mistakenly feel they don’t have the expertise or capacity to implement rapid methods in the beginning and trust the ease and comfort of traditional methods. However, they fail to realize that as a startup, they have the perfect opportunity to innovate and use modern methods in the beginning, rather than try to overcome inertia and reliance on these methods later. Investing the time to gain the knowledge and experience of using the best available methods early will set up startups for success for years down the road. Using rapid, alternative methods not only ensures GMP compliance right out of the gate, but ensures successful business operations by optimizing production, improving product quality, and reducing risks.

EudraLex, Volume 4, EU Guidelines to Good Manufacturing Practice Medicinal Products for Human and Veterinary Use

, Annex 1, Manufacture of Sterile Medicinal Products, December 2017.

	Pharmaceutical Technology Europe
	Vol. 32, No. 5
	May 2020
	Pages: 28-29

	When referring to this article, please cite it as L. Lavelle, “Good Manufacturing Practices: Aseptic and Sterile Processing,” 

Organizations involved in aseptic and sterile processing activities must make an effort to comply with current good manufacturing practices.


Good Manufacturing Practices: Aseptic and Sterile Processing

In nonclinical settings, good laboratory practices (GLPs) ensure the quality of the studies conducted, including the integrity of the data collected. Features needed for compliant data management include detailed final study reports, the proper storing of all raw data, documentation, and protocols, and a responsible archivist to maintain responsibility for the stored data (1).

	Development and manufacturing laboratory operations, such as quality control, have additional/different data requirements. Good lab practices rely on a study director as a single point of contact for all open-ended studies on product performance for submission to FDA for pre-market approval. As the study is being conducted, a quality assurance unit inspects each phase to oversee the integrity of the studies and compliance or non-compliance with the GLPs and records them in an index. In contrast, good manufacturing practices (GMPs) don’t require a single point of contact and depend on a quality control unit to approve and reject certain methods and procedures to determine whether products and samples meet manufacturing requirements (2).

	Bio/pharma laboratories have access to a range of services and tools designed for accurate and quick sharing of data. To ensure proper data integrity procedures, the software, systems, and services should match the intended process.

	Laboratory information management systems (LIMS) are software systems intended for the management of lab samples and data to improve record keeping and reporting, and to automate and streamline workflows (3).  Because of their organized nature, LIMS are equipped for accurate and quick data sharing via data backup and mining and configuration tools.

	An additional software system intended for lab data management is an electronic lab notebook (ELN). Intended for documenting research, ELNs manage and store lab research data while allowing for collaboration between members of a lab group or outside resources contributing to the lab work (4). Most platforms are also accompanied by content creation tools, workflow suitability, and integration tools for connecting to other software or online services.

	The latest version of the Matrix Gemini LIMS from Autoscribe Informatics works to provide a range of labs with proper business and operational needs through configurable workflows (5). The system can mirror lab workflows and Matrix configuration tools while leaving the underlying code unchanged, making it easier for labs to upgrade product versions. It also allows users to download the specific configurations of their system and send them to the Autoscribe support team for assistance.

	“LIMS investments are typically for a five to 10-year period, often longer. A truly configurable solution makes it simpler to meet changing business requirements, as well as adopt new processes, instruments, and systems as the lab evolves. This ‘future proofs’ your investment and ensures a lower cost of ownership over the lifetime of the LIMS,” said Tim Daniels, marketing manager for Autoscribe, in a press release. “A truly configurable LIMS provides every laboratory the certainty of longevity without sacrificing the flexibility to adopt the new technology and integration being driven by current Laboratory 4.0 initiatives.”

	LabWare’s ELN is a paperless solution for the testing of GMP samples alongside standard operating procedures (SOPs) and standard test methods by quality control labs (6). The notebook can be incorporated into Labware’s LIMS to offer access to quality data, product specifications and control limits, training certifications, instrument calibrations, and standard or solution data.

	The software also includes a compliance view that monitors the statuses of the methods as quality control analysts complete each step. Supervisors are notified when adverse events occur in the lab so problems can be corrected immediately.

	NuGenesis Lab Management System from Waters Corporation uses synergistic data, workflow, and sample management capabilities to track product lifecycle from discovery to manufacturing (7). The system is equipped to link data such as sample submission and results review, stability testing, scientific search, multi-vendor software connection, laboratory inventories, data retention and legal hold, and laboratory execution methods to the businesses it is providing for. It can also adapt to different informatics environments and enable software integration and standardization without long deployment times.

	Garrett Mullen, senior product marketing manager, Laboratory Management Informatics at Waters Corporation, said the NuGenesis Lab Management System is comprehensive and can readily adapt to informatics environments to easily link data from the lab to the business operations of a company so the organizations can see and know more about the lab processes (8).

	Agilent’s SLIMS can manage all lab data through a web browser or cloud host so individual labs can tailor it to their own LIMS preferences. The system features sample management, an ELN, and workflow management capabilities (9).

	Additionally, the system provides complete transparency for any lab sample, a workflow solution combined with protocols and external analysis platforms, an ELN module for digital note-taking and follow-up of experiments, and a sequencing tool kit.

	The most recent version of the platform, SLIMS 6.4, provides an authentication module for account creation, additional analytical workflows, and instrument calibration for equipment expiration date tracking and to provide consequences for protocol steps (10).

	BIOVIA’s LIMS is purpose-built to maintain the necessities of the lab management process. The system requires no custom coding and uses its own internal system administrator to organize applications, workflows, and procedures, eliminating the need for external consultants and programmers (11).

	It also features automatic workflow validation that produces a complete validation document for the application, workflow, or procedure, and a fast deployment time that reduces the validation time from months to weeks.

	Also from BIOVIA is the BIOVIA Inventory, a web-based platform for lab materials, equipment, supplies, and reagents mangement that can be used as a standalone or with an ELN (12).

	The program works to lessen lab inventory and supply spoilage, restrict the opening and preparation of new materials when supply is already available, prevent the use of expired products, and oversee controlled and radio-labeled substances.

	SampleManager LIMS software from Thermo Fisher Scientific can readily adapt to various lab methods and processes while working in conjunction with several software systems including enterprise research planning and manufacturing execution system software (13).

	The system also allows for portability through a mobile app, which gives analysts the opportunity to use the system anywhere in the lab. The app uses tablet cameras and barcode scanners to scan samples and locations and lets users directly upload methods, SOPs, and results.

	1. FDA, Code of Federal Regulations, Title 21, fda.gov, April 1, 2019.
	2. Microchem Lab, “What is the Difference between GLP and GMP Laboratory Testing Regulations?,” microchemlab.com, Jan. 29, 2020.
	3. Cloud LIMS, “What is a LIMS?,” cloudlims.com, Nov. 19, 2018.
	4. The Gurdon Institute, “Electronic Lab Notebooks-for prospective users,” gurdon.cam.ac.uk, Dec. 3, 2019.
	5. Autoscribe Informatics, “Configurable LIMS Highlighted at PITTCON,” Press Release, Jan. 1, 2020.
	6. LabWare, “Pharmaceutical Manufacturing,” labware.com, Jan. 27, 2020.
	7. Waters Corporation, “NuGenesis Lab Management System,” waters.com, Jan. 27, 2020.
	8. Waters Corporation, “Waters’ NuGenesis Lab Management System Becomes Industry’s Most Adaptable and Comprehensive Information Management Platform,” Press Release, April 29, 2014.
	9. Agilent, “SLIMS,” agilent.com, Jan. 27, 2020.
	10. Agilent, “SLIMS Version 6.4 has Arrived,” agilent.com, Jan. 27, 2020.
	11. BIOVIA, “BIOVIA LIMS,” 3dsbiovia.com, Jan. 30, 2020.
	12. BIOVIA, “BIOVIA Inventory,” 

, Feb. 4, 2020.
	13. Thermo Fisher Scientific, “SampleManager LIMS,” coreinformatics.com, Jan. 30, 2020. 


		Vol. 44, No. 2
		February 2020
		Pages: 46-47

		When referring to this article, please cite it as L. Lavelle, “Data Management Practices,” 

Data management is crucial in bio/pharmaceutical laboratory settings from discovery steps through clinical studies and varies based on the development phase.