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Sidebar banner 7, sidebar banner 8, sidebar banner 12, sidebar banner 18, sidebar banner 19, sidebar banner 20, sidebar banner 21, good laboratory practice – to glp or not to glp.

Scientist in laboratory

Good Laboratory Practice (GLP), are federal regulations that require implementation of a robust quality management system to ensure the validity, integrity and reliability of non-clinical safety data submitted for regulatory evaluation and approval.

US Food and Drug Administration (FDA) GLP regulations (21 CFR parts 11 and part 58) were first issued by the US in 1978 (1), and, at that time, safety data was mainly obtained from in vivo animal test systems.

Since then, researchers have continued to develop alternative ways to assess drug safety, and now, good laboratory practice regulations can be applied to all non-clinical laboratory safety studies, including in vitro and ex vivo test systems. In short, GLP-compliant studies require documentation (eg standard operating procedures) and are overseen by quality assurance units that perform process-, facility- and study-based inspections.

In this article, we provide an overview of which studies require Good Laboratory Practice (GLP) compliance, which do not, and why in some cases the choice is unclear.

Understanding the details of your prospective contract research organisation’s (CRO) GLP-compliant and non-GLP compliant study conduct is key. Once you know exactly what to expect, you can select the level of study you need to achieve your project’s objectives – and possibly, depending upon the CRO, save time and funds by choosing non-GLP.

Image 1 Scientist working in the lab with samples

Which studies require Good Laboratory Practice (GLP)?

With formal regulations in place, you’d think the answer to this question would be simple. It is, and it isn’t.

In summary, the FDA guidelines for GLP compliance are as follows:

1. Evidence that their products are safe in research and/or marketing applications (21 CFR 58.1) must be submitted by sponsors of nonclinical laboratory studies to support the safety of:

– Food and colour additives – Animal food additives – Animal drugs – Human drugs and biological products – Medical devices for human use – Electronic products

2. Non-clinical laboratory studies that must comply with FDA GLP regulations include:

– Toxicity profiles – Observed no adverse effect levels – Risks of clinical studies involving humans or animals – Potential teratogenic, carcinogenic or other adverse effects – Safe levels of use

3. Compliance with GLP regulations is NOT required for these studies:

– Discovery – Basic research – Screening – Any other in vitro studies in which the safety of the product is not being assessed

Mixed messages for drug interaction and reaction phenotyping

While non-GLP studies do not need to fulfill GLP requirements, they must still produce high-quality, reviewed and reliable data.

In particular, multiple nations’ regulatory agencies and the pharma industry have singled out in vitro drug interaction studies (such as CYP inhibition, induction or reaction phenotyping data, or transporter inhibition or substrate potential) as especially important in assessing drug safety – even though these are technically non-GLP studies.

Moreover, the pharmaceutical industry states that drug interaction studies must be “performed with high quality and consistency, particularly when the studies ultimately influence the design of clinical trials” (2). Furthermore, the US FDA recommended that these studies be carried out “in the spirit of GLP” (3), with the investigator “taking necessary steps to assure the quality and integrity of the data”.

In light of these statements, sponsors often feel they must deliver the same level of data integrity and validity for in vitro drug interaction studies as they would for non-clinical safety studies. To achieve this, when outsourcing, they frequently request GLP-compliant studies as a matter of course. But is GLP truly the only way to be certain these non-GLP studies meet the guidelines above? Depending upon the rigour of the non-GLP study conduct, perhaps not.

 Image 2 Scientist with pipette in the lab

Waste not, want not: scrutinise your options

Unnecessary GLP studies squander both time and money. Before you decide on GLP or non-GLP enzyme inhibition, enzyme induction, drug transport or drug metabolism studies, analyse your proposed CRO’s study options for in vitro and ex vivo test systems. Once you consider the exact differences between the GLP and non-GLP studies, you will be able to decide whether the CRO’s non-GLP conduct will fulfill the research objectives of your particular project. In the end, you may decide on non-GLP studies – or those in compliance with US FDA GLP regulations, Japan MHLW GLP regulations or OECD GLP guidance.

Considerations when evaluating how your prospective CRO applies GLP regulations to in vitro and ex vivo studies

Most elements of the GLP regulations are constant, regardless of test system. For in vitro studies, though, a few points require interpretation in view of intent and applicability.

It’s useful to compare:

– Specific, relevant GLP regulations from 21 CFR Part 58 – How the CRO interprets these regulations in FDA GLP-compliant studies – How the CRO handles these regulations in non- GLP studies

In vitro and ex vivo drug metabolism and drug interaction studies are critical to evaluate the safety of existing drugs or drug candidates and to assess the risk of toxicity and adverse drug-drug reactions in vivo. Nonetheless, they are not considered safety studies. In the end, the sponsor must choose whether to conduct them in GLP-compliant or non-GLP-compliant fashion.

The degree to which your chosen CRO conducts GLP and non-GLP studies identically will affect the likelihood that you will be able to utilise non-GLP drug metabolism and interaction studies.

Specific aspects of GLP versus non-GLP study conduct you may want to compare are listed below:

– Personnel roles and functions Planning Training Performance Monitoring Documentation Archiving Quality assurance – Laboratory space – Standard operating procedures – Protocol and study conduct and documentation – Equipment – Hard copy and electronic records storage, retrieval and retention – Bioanalytical method validation

Selecting a CRO that conducts GLP and non- GLP studies similarly will enable you to find new efficiencies by choosing non-GLP services for some of your drug interaction studies. When in doubt, seek technical assistance to help you decide – the result may be significant savings.

A few definitions

In vitro non-clinical laboratory study:.

A test article is applied to tissue or tissue-derived material (such as subcellular fractions) in a test tube, plate, etc. – Examples: enzyme induction studies in cultured human hepatocytes, enzyme inhibition studies with human liver microsomes or recombinant enzymes, and reaction phenotyping (enzyme mapping) with human hepatocytes, human liver microsomes and recombinant enzymes

Ex vivo non-clinical laboratory study:

A test article is administered to a laboratory animal in vivo, after which organs or tissues are removed and analysed in vitro for enzyme induction, etc. – Examples: enzyme induction studies in mice, rats, dogs or monkeys, often conducted as part of a 14-day toxicity study.

Control article:

Any food additive, colour additive, drug, biological product, electronic product, medical device for human use, or any article other than a test article, feed or water that is administered to the test system in the course of a non-clinical laboratory study for the purpose of establishing a basis for comparison with the test article. -Note: Positive and negative controls used to show that the test system is responsive under the actual conditions of the assay may not necessarily be categorised as control articles per GLP regulations.

Any material derived from a test system for examination or analysis. – Example: microsomes isolated from cultured hepatocytes treated with a test or control article.

Image 3 Scientists working with scientific data in the lab

Additional definitions and requirements for GLP Studies

Organisation and personnel.

– Specific responsibilities are assigned as per GLP regulations for non-clinical studies to: Study personnel Study director Facility management Quality assurance unit (QAU) Archivist

These responsibilities are outlined in SOPs. The study director, facility management and archivist roles are equally applied to non-GLP studies.

– Any corrective actions taken to protocols or SOPs and any GLP deviations must be documented. – One study director is responsible for the conduct of each GLP-compliant or non-GLP study and acts as the study’s single point of control. – The quality assurance unit (QAU) monitors GLP studies, reporting to management and the study director. The QAU does not monitor all non-GLP studies or records; however, the QAU does perform facility and process-based inspections of all facility operations to ensure that no deviations were made without proper documentation and authorisation. The QAU also maintains copies of all GLP-compliant and non-GLP audited protocols and a master schedule sheet (MSS) of all GLP-compliant and non-GLP audited studies conducted at the facility.

– As per GLP regulations, adequate facilities must be provided for each study. – Adequate, procedure-specific laboratory areas contain: Test article and control article receipt and storage Test article and control article storage Solution preparation Microsome preparation LC-MS-MS analysis Sterile and aseptic procedures Biohazard procedures – On-site facility archives should be maintained, but specimen archives are not required. At the close of a study, specimens may be shipped to the sponsor or another, designated storage location. Or, they may be disposed of at the sponsor’s request. These procedures are the same for both GLP-compliant and non-GLP studies.

Standard operating procedures

– SOPs covering laboratory operations as listed in the GLP regulations are maintained. These procedures cover both in vitro and ex vivo studies. – Additional SOPs cover experimental methods and procedures appropriate for specific studies (ie drug metabolism and drug interaction studies). – Management must approve all new and revised SOPs. – An archive is maintained for all historical versions of SOPs. – Hard copies are available in laboratories and electronic SOPs are available at all workstations. With a few exceptions, the same SOPs support the conduct of both GLP-compliant and non-GLP studies.

– Study personnel may use the same laboratories and equipment for all contracted studies. Thus maintenance, calibration, testing and record keeping can be equally applied to all studies in order to maintain the equipment in proper regulatory compliance. – Appropriate equipment is maintained for in vitro and ex vivo study procedures. – A Department of Maintenance & Metrology is recommended. They inspect, clean and maintain equipment. These activities are documented in equipment SOPs. – Verification and calibration may be conducted in-house by study personnel or maintenance and metrology personnel, or these tasks may be performed by equipment vendors or specialised contractors as necessary. – Where applicable all equipment use is documented in instrument logbooks. Records of equipment inspection, maintenance, testing, calibration and standardisation are archived and retained.

Test and control articles

– Full characterisation of test and control articles is not required for non-GLP studies. – Test and control articles are assigned internal tracking numbers. Information on test article receipt and distribution are stored in a central location and are archived as facility records. Copies are maintained in the study records. – Retention of test and control article samples is not required, as in-life study segments (dosing to observation) typically last less than four weeks. Test and control articles remaining after the study’s end should be returned or destroyed, as per the sponsor’s request. – Test dosing solutions are analysed for concentration and stability for GLP-compliant studies; this analysis is not required for non-GLP studies. A sponsor may provide information on the stability of test solutions; however, if the stability is unknown or has not been characterised, a fresh solution is prepared daily.

Protocol and study conduct

– Contract studies are conducted according to the applicable GLP regulations and the protocol. – Preprinted forms with selected data may be used, but these must be verified prior to the conduct of any study. The same documentation requirements are applied to both GLP-compliant and non-GLP studies.

– A final report summarising study methods and results, including applicable components listed in the GLP regulations and study protocol must be prepared. – In a GLP-compliant study report, a compliance statement stipulating the regulations followed in the conduct of the study and any GLP deviations that occurred is included. Protocol deviations are reported for both GLP-compliant and non-GLP studies. – Corrections or changes to a final report for both GLP compliant and non-GLP studies are only made through amendment as described in the GLP regulations, with prior approval from the sponsor. – Alternatives to preparing a complete final report for a non-GLP study can be offered, such as a data summary or other simplified version, according to the sponsor’s requirements.

Records storage, retrieval and retention

– All study records must be maintained in a facility archive. Records are indexed and stored either at the test facility or transferred to an offsite commercial archive facility. – Records from GLP-compliant studies should be stored in fire-resistant cabinets within a restricted access archive room. Access to the archives is controlled, and all access to the archive room and archived records is documented and logged. – Records from non-GLP studies may be stored in the same archive room with controlled access (as GLP studies), but they may not necessarily be stored in fire-resistant cabinets. – GLP studies require record retention from the time the sponsor applies for a permit or submits required documents to the FDA. Sponsors may request a specific retention period for study records at the test facility or may request that records be transferred to them after a designated period of time. Otherwise, standard record retention policies based on the specific SOP or default time periods are followed.

Electronic record and electronic signatures

– Instruments, software and networked environments generate electronic records and signatures. Relevant FDA 21 CFR Part 11 regulations are applied differently in a GLP-compliant versus a non-GLP study. – Computerised systems used in GLP-compliant studies must meet all Part 11 requirements including validation and electronic signatures, whereas computerised systems used in non-GLP studies may not be validated or include electronic signatures. – A computerised system master list identifying all systems and their validation status must be maintained. Individual system SOPs cover the use of electronic signatures and the maintenance of electronic records.

Bioanalytical method validation

– Specific SOPs define how FDA guidelines are applied in bioanalytical methods validation. – All methods used in GLP-compliant studies must be validated. Methods are tested for accuracy, precision, selectivity, sensitivity, reproducibility and stability. – Routine sample analyses are conducted using quality controls (QCs) to accept and reject runs for GLP studies, or upon request. – Non-GLP studies may follow methods that have not been validated. Typically, the same methods validated for GLP-compliant studies are used for non-GLP studies; however, in non-GLP studies, QCs are not necessarily used to accept or reject each batch.

This article originally featured in the DDW Winter 2018/19 Issue

Scott Hickman MBA, Sekisui XenoTech Director of Global Marketing, has managed the customer experience for innovative life science companies for more than 25 years.

Dr Brian Ogilvie , Sekisui XenoTech Vice-President of Scientific Consulting, is an author on numerous posters and publications and an invited speaker at many conferences.

Tim Patterson ASQ CQA, CQM, Sekisui XenoTech Quality Assurance Manager, has more than 20 years of experience working in GMP and GLP regulated environments.

1 U.S. Food and Drug Administration’s Good Laboratory Practice for Nonclinical Laboratory Studies , Title 21, Vol. 1, Part 58.

2 Bjornsson et al. The Conduct of in vitro Drug-Drug Interaction Studies: A Pharmaceutical Research and Manufacturers of America (PhRMA) Perspective , p815- 831, 2003.

3 Tucker, Geoffrey T, Houston, J. Brian and Huang, Shiew-Mei. Optimizing Drug Development: Strategies to Assess Drug Metabolism/Transporter Interaction Potential – Toward a Consensus . Br J Clin Pharmacol. 2001 Jul; 52(1): 107-117.

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GLP & Non-GLP: What’s the Main Difference?

GLP & Non-GLP: What’s the Main Difference?

Good Laboratory Practice (GLP) refers to a system of federal regulations revolving around the planning, monitoring, conducting, and reporting of non-clinical health and safety studies. GLP compliance ensures companies that submit safety data for regulatory approval follow strict standards of integrity, reliability, and validity throughout their processes.

GLP compliance is essential for many different operations, but it isn’t necessary for every non-clinical study. Learning the difference between GLP and non-GLP studies allows you to make informed choices as you navigate the research process.

GLP Compliance Requirements

GLP compliance seeks to build strict international standards that help make test data acceptable across multiple countries. Because of this, GLP regulations revolve around the organization, processes, and conditions of laboratory studies.

When a study meets GLP standards, that means there is thorough documentation of all standard operating procedures. Additionally, the lab performing the study has undergone quality assurance inspections regarding the study itself, the lab’s processes, and the overall facility where the study took place.

When Is GLP Mandatory?

The main difference between GLP and non-GLP studies is the assessment of safety. The FDA requires GLP compliance for non-clinical laboratory studies that seek to prove the safety of products such as food, animal drugs, human drugs, biological products, medical devices, and more. Studies that revolve around toxicity profiles, adverse effects, or safe levels of use must comply with GLP standards.

However, if a non-clinical laboratory study doesn’t seek to prove or assess safety, it doesn’t need to meet GLP regulations. Basic research, screenings, discovery studies, and other similar endeavors can still deliver high-quality results and information without meeting FDA standards for Good Laboratory Practices.

Reliability in Non-GLP Studies

Non-clinical laboratory studies that do not face GLP requirements still strive to meet a high level of quality and accountability. Non-GLP studies prioritize documentation, conduct safe and responsible procedures, and present reviewed, reliable data at the end of each study.

There is no right or wrong answer when choosing between GLP and non-GLP studies. In some scenarios, non-GLP procedures offer the standard of quality you need with a shorter timeframe and lower price. However, some studies require the strict attention and care of GLP regulations. By partnering with a contract development and manufacturing organization you can trust, you get the most out of your project no matter which option you choose.

Moravek has the resources and expertise to conduct custom radiolabeling projects with a high standard of quality and care. Learn more about our techniques and procedures when you work with the team at Moravek today.

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Non-GLP Toxicology Studies

Noble Life Sciences is a leading contract research organization (CRO) specializing in toxicology studies for the biotech, pharmaceutical, and biopharmaceutical industries. With our state-of-the-art facilities and highly skilled team of scientists, we provide comprehensive non-GLP toxicology services tailored to meet our clients’ specific needs.

Value of Non-GLP Studies

Non-GLP (Good Laboratory Practice) studies offer valuable insights and benefits in the early stages of drug development. While GLP studies are required for regulatory submissions, non-GLP studies serve as a cost-effective and flexible approach for initial evaluations, allowing for quicker decision-making and optimization of resources. The key value of non-GLP studies includes:

  • Exploratory Research: Non-GLP studies provide a platform to explore a wide range of doses, formulations, and exposure durations, enabling researchers to gather preliminary data and make informed decisions about further development.
  • Rapid Screening: Non-GLP studies offer the advantage of faster turnaround times, making them suitable for screening multiple compounds or evaluating early-stage candidates.
  • Customization and Flexibility: Non-GLP studies allow for customized study designs, including specialized assessments and modifications, based on the unique requirements of the compound being tested.
  • Cost-Effectiveness: Non-GLP studies are typically more cost-effective than GLP studies, making them an attractive option for companies operating within budget constraints during the early stages of drug development.
  • Decision-Making: Non-GLP studies provide critical data and insights that contribute to informed decision-making regarding the further progression of compounds in the development pipeline.

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Frequently Asked Questions (FAQs) About Non-GLP Toxicology Studies

What is the difference between glp and non-glp studies.

GLP (Good Laboratory Practice) studies are conducted according to a set of regulatory guidelines and are required for data submission to regulatory authorities. They involve strict quality control measures and detailed documentation. Non-GLP studies, on the other hand, are exploratory in nature and serve as an early evaluation tool. They are more flexible, cost-effective, and offer faster results but do not adhere to the rigorous regulatory standards of GLP studies. Contact Us

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Why should I use a GLP Lab when my study is non-GLP?

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Adhering to Good Laboratory Practices (or GLP) should become a routine aspect in the histology industry. Even if your peers adhere to this longtime practice, you've perhaps slipped in applying GLP to your studies. The same goes with following your SOPs, or Standard Operating Procedures.

SOP's can best be defined as written documents describing the performance of routine tasks and complying with governmental regulations. GLP and SOPs work side-by-side to help bring more efficiency to pharma studies in histology labs, or any scientific field.

Overlooking these likely isn't intentional on your part. What's keeping you from applying them is perhaps lack of money to properly train your employees. Also, overcrowding in your lab may occur, making it tougher to invest in proper equipment.

If you can't follow GLP or SOP standards, it's time to outsource your studies.

When Did GLP Become a Standard? Those of you new to Good Laboratory Practices should know how long GLP has existed in the United States. It all began over 40 years ago when Senator Ted Kennedy and the FDA went after many research laboratories for not conducting proper safety procedures. Many of these labs didn't have proper record keeping or training for employees either. Fraud was even rampant back then.

It took some time, though GLP became a mainstream practice by the late '70s. The FDA also began to create new positions in the 1980s to better evaluate biological research. By 1987, and after numerous revisions, the FDA finally formed GLP as we know it today. This means we're now at the 30th anniversary of modern GLP practices. Basically, it points to four main principles you need to focus on during every study.

What Are the Main GLP Principles? The "final rule" of the FDA stipulated every lab properly following GLP principles needs to employ a quality assurance department. They also should have a study plan or protocol preparation before any study takes place.

In addition, your lab should characterize test and control materials to eliminate study mistakes. You also need to retain specimens and samples in a safe environment to avoid further errors. All of these can become impossible when you're financially strained or have no room to expand. Going beyond GLP, though, is adherence to your SOPs, something establishing a benchmark for quality in all of your lab services.

What Principles Should You Apply to Your SOPs? Safety is one of the top things in your standard operating procedures , even if it's easy to become complacent when becoming busy with other duties. Lab environment control is equally important to determine a more accurate study outcome.

Your analytical method validations should also go in your SOPs so you have a uniform way to analyze your studies without confusion when hiring new staff.   Don't forget about qualification of your working standards so you hire the right technicians. All of this is probably creating stress while running your lab. Why should you outsource a lot of it rather than take risks?

Outsourcing to a Lab Using GLP Standards and SOPs

Never feel too proud to outsource, because you're saving yourself a lot of money in the long run, including the cost of amending critical mistakes after sending in your results.  All it takes is one error in a study to ruin your lab's reputation for years to come. It's the same dealing with fines because you didn't adhere to GLP standards demanded by the FDA.

Simply not following SOPs can end up creating a major safety issue that's easily amended in an outsourced laboratory.   The best outsourced labs follow all of these principles every day because they have the time and resources to train lab staff correctly.

Please contact us at HSRL , we’d like to help make your GLP or non-GLP study a success!

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  • Choose chromatographic method: MS-Technology (MS/HRMS or high-resolution HRMS)
  • Optimization
  • Definition of calibration range
  • Robustness of chromatography
  • Test for selectivity by MS check for matrix effects

GLP Validation Sample Preparation

  • Test sample stability (storage in frozen state, handling in liquid state)
  • Test analytical samples stability (storage in autosampler and freezer)
  • Test matrix effects (robustness of methods and selectivity with at least six individual matrices)
  • Determination of recovery

GLP Validation LC-MS

  • Calibration curve
  • Intra-/inter-run accuracy
  • Intra- /inter-run precision
  • Selectivity tests of MS
  • Validate peak form and carry over
  • Validate reinjection procedures

Preclinical GLP Bioanalytics*

  • Pharmacelsus acts as GLP test facility and as test site for multisite studies. QA inspection of all study phases: study plan, experimental phase, retain samples, data processing, reporting and archiving. Application of fully qualified and calibration equipment.

*According to the actual EMA/FDA/ICH Guidelines

Clinical GC(L)P Bioanalytics*

  • Close cooperation with the clinical CRO of your choice
  • Maintenance of “chain of custody”
  • QA inspection of all study phases
  • Application of fully qualified and calibrated equipment.

Instrumentation / Qualification

  • GLP certified laboratory for the categories 8 and 9
  • Use of validated computerized systems
  • Qualified equipment
  • Regular maintenance
  • Regular calibration
  • Regular/(Re)-qualification

Data / Archiving

  • PK data evaluation
  • Data are archived according to GLP guidelines

GLP retain samples are archived according to “Deutsches Chemikaliengesetz”)

Full documentation and work according standard operating procedure (SOP).

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GLP vs. Non-GLP toxicology studies: When to use which guidelines?

Since 1978, when the U.S. FDA issued the Guidance for Industry Good Laboratory Practices Regulations, Good Laboratory Practices (GLP) have been an essential part of the quest to ensure the highest standards in drug development. 

GLP regulations have ensured that nonclinical animal studies are conducted to the highest standard, but they are not always necessary in a toxicological study. Non-GLP studies, deployed at the right time, can offer huge advantages to drug developers. Here, we will explore the difference between GLP and non-GLP studies and determine when to use which. 

What are Good Laboratory Practices? 

The U.S. FDA’s guidance in 1978 was issued in response to a perceived lack of scientific integrity and quality in nonclinical toxicology studies at the time. It was proceeded by similar guidance issued in New Zealand and Denmark in 1972.

The Organization for Economic Co-operation and Development (OECD) adopted the GLP guidelines many years later, in 1992, in order to promote them at a global scale. OECD wanted to raise the quality of testing to such a level that data was acceptable across borders. 

From that point on, GLP regulations have been used worldwide to ensure nonclinical health and safety studies are planned diligently, monitored efficiently, recorded meticulously, archived methodically and reported consistently. 

When is GLP Required? 

GLP regulations are required for most nonclinical toxicological studies, including those required for IND submission. Sponsors and laboratory testing partners must comply with laws covering GLP in the United States.

GLP standards focus on the organizational process and the conditions for performing studies, and stress the importance of the following: 

  • Qualified staff working in appropriate facilities with the correct equipment and materials. Records must be kept of personnel qualifications and their duties. 
  • Establishing a quality control system, which should be documented by staff not directly involved in the study.
  • The study director has to commit to a study plan and seek authorization for any variation. 
  • Safe working conditions. 
  • A suitably sized location for the study, wherein outside elements are minimized and different activities are separated. 
  • The correct handling of test and reference substances to avoid contamination. Waste disposal should also be conducted properly to avoid jeopardizing the integrity of studies. 
  • Apparatus, reagents and test systems should be of proper quality and design, and labeling should be exact. 

When Can Non-GLP Testing be Considered?

There are some instances or stages in nonclinical testing where drug manufacturers do not need to adhere to GLP. These include general in vitro toxicology studies, genotoxicity, mutagenicity and safety pharmacology.

If a drug sponsor is looking to investigate preliminary drug safety by obtaining data on the drug’s absorption, distribution, metabolism and elimination (ADME) properties, they may decide to conduct this stage of research outside GLP requirements. This will give the sponsor a clear picture of how tolerable the drug is in various systems prior to performing a further study where GLP is required. 

Non-GLP studies at an early stage in the drug development process can minimize the risk of failure during preclinical studies, and help sponsors decide if the program is worth moving forward. Because of the decreased regulatory scrutiny, non-GLP studies can be carried out with shorter testing durations, smaller sample sizes, and faster report delivery. 

This streamlined process is possible because the following are not required: 

  • Quality assurance does not have to inspect the conduct of studies or records.
  • Analysis of the concentration of the test article dosing solutions is not required. 
  • Complete study reports are not necessary, so alternatives like data summaries are acceptable. 
  • Methodological validation through quality control is not required. 

However, it is important to note that although some studies do not need to adhere to GLP regulations, they must still produce high quality data that is reviewed and reliable. Myriad regulatory agencies and the pharmaceutical industry itself have emphasized the importance of assessing drug safety in in vitro interaction studies, even though they are technically non-GLP studies. The U.S. FDA has said that such studies should be carried out “in the spirit of GLP.” 

Because of this stipulation, drug sponsors may sometimes request GLP testing to cover their bases even when it is not strictly required. An experienced laboratory testing partner will be able to properly discern when GLP studies are required or a best practice, and what will only add time and money to the budget. 

A Final Word 

Many drug sponsors may benefit from the ease of conducting non-GLP toxicity testing at a very early stage in drug development. With less stringent requirements on sample size and testing durations, researchers are able to accelerate decisions on whether a drug development project is viable. Conducting GLP studies when they are not required can cost the drug sponsor both time and money. Therefore, it is in a drug sponsor’s best interest to work with a quality laboratory testing partner who is able to properly determine the necessity of a GPL study versus a non-GLP study. 

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Performing GLP studies in a traditionally non-GLP facility

Affiliation.

  • 1 Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709-2137.
  • PMID: 7804630

Situations can arise in which traditionally non-GLP facilities may have to be used for performing nonclinical GLP studies or parts of a GLP study. The situations may include a need for particular expertise of scientists, the analytical laboratory, or the development of an unusual product. This article describes the use of a core group model as a proactive strategic plan to bring the traditionally non-GLP facility into compliance before the GLP study is conducted. The core group team is composed of representatives of both the Sponsor and the facility where the GLP study will be conducted. The core group model uses a nine-step plan that fosters good communication, co-operative planning, and adequate preparation before initiation of a proposed GLP nonclinical study, conducted under GLP compliance, at a traditionally non-GLP facility.

  • Facility Regulation and Control / legislation & jurisprudence
  • Facility Regulation and Control / organization & administration*
  • Laboratories / standards*
  • Management Audit / methods*
  • Models, Organizational
  • Program Development / methods*

Book cover

Good Research Practice in Non-Clinical Pharmacology and Biomedicine pp 1–17 Cite as

Quality in Non-GxP Research Environment

  • Sandrine Bongiovanni 13 ,
  • Robert Purdue 14 ,
  • Oleg Kornienko 15 &
  • René Bernard 16  
  • Open Access
  • First Online: 26 November 2019

21k Accesses

4 Citations

Part of the Handbook of Experimental Pharmacology book series (HEP,volume 257)

There has been increasing evidence in recent years that research in life sciences is lacking in reproducibility and data quality. This raises the need for effective systems to improve data integrity in the evolving non-GxP research environment. This chapter describes the critical elements that need to be considered to ensure a successful implementation of research quality standards in both industry and academia. The quality standard proposed is founded on data integrity principles and good research practices and contains basic quality system elements, which are common to most laboratories. Here, we propose a pragmatic and risk-based quality system and associated assessment process to ensure reproducibility and data quality of experimental results while making best use of the resources.

  • ALCOA+ principles
  • Data integrity
  • Data quality
  • European Quality in Preclinical Data
  • European Union’s Innovative Medicines Initiative
  • Experimental results
  • Good research practice
  • Non-GxP research environment
  • Quality culture
  • Reproducibility
  • Research quality standard
  • Research quality system
  • Risk-based quality system assessment
  • Transparency

Download chapter PDF

1 Why Do We Need a Quality Standard in Research?

Over the past decades, numerous novel technologies and scientific innovation initiated a shift in drug discovery and development models. Progress in genomics and genetics technologies opened the door for personalized medicine. Gene and targeted therapies could give the chance of a normal life for genetically diseased patients. For example, adeno-associated viruses, such as AAV9, are currently used to create new treatments for newborns diagnosed with spinal muscular atrophy (SMA) (Mendell et al. 2017 ; Al-Zaidy et al. 2019 ). Similarly, the use of clustered regularly interspaced short palindromic repeats (CRISPR) (Liu et al. 2019 ) or proteolysis targeting chimeras (PROTACs) (Caruso 2018 ) is leading to novel cancer therapy developments. The broader use of digitalization, machine learning and artificial intelligence (AI) (Hassanzadeh et al. 2019 ) in combination with these technologies will revolutionize the drug discovery and clinical study design and accelerate drug development (Pangalos et al. 2019 ).

Regulators all over the world are closely monitoring these breakthrough scientific advances and drug development revolution. While they evaluate the great promise of innovative medicines, they also raise questions about potential safety risks, ethics and environment. Consequently, new ethical laws and regulations are emerging to mitigate the risks without slowing down innovation. For example, the UK Human Tissue Act became effective in 2006, followed by the Swiss Human Research Act in January 2014 (Swiss-Federal-Government, Effective 1 January 2014 ); the EU General Data Protection Regulation (No.679/2016, the GDPR) came into effect on May 25, 2018 (EMA 2018a ); and the guideline on good pharmacogenomics practice has been in effect since September 2018 (EMA 2018b ).

This is exemplified by the EMA Network Strategy to 2020 (EMA 2015 ), which aims both to promote innovation and to better understand associated risks, in order to provide patients with safe and novel drugs or treatments on the market more rapidly.

This evolving research and regulatory environment, along with many other new challenges, such as aggressive patent litigation cases, increasing burden for approval and reimbursement of new molecular entities (NMEs), challenging market dynamics and high societal pressure enforce radical changes in the research and drug development models of the pharmaceutical industry (Gautam and Pan 2016 ). In response, most of the pharmaceutical companies have refocused on portfolio management, acquired promising biotechnology companies and developed research collaborations with academia (Palmer and Chaguturu 2017 ). The goal is to speed up drug development in order to deliver new drugs and new treatments to their patients and customers. Thus, transition from research to drug development should be more efficient. To do so, robust data quality, integrity and reproducibility became essential, and the development of a quality culture across the entire value chain emerged to be critical. Indeed, while many drug development areas already applied the various good practice (GxP) standards and guidances, no recognized quality standard governed discovery and early development. Conversely, discovery activities had to comply with many regulations, such as biosafety, controlled substances and data privacy; thus, there was a real risk of exposure in non-GXP research.

In order to mitigate these newly emerging risks and speed up drug development, some pharmaceutical companies decided to develop their own internal research quality standard (RQS), based on good scientific practices and data integrity, to promote robust science and data quality. The foundations of RQS were the WHO: “Quality Practices in Basic Biomedical Research” (WHO 2005 ), first published in 2001, and the “Quality in Research Guideline for working in non-regulated research”, published by the British Research Quality Association RQA, in 2006 and revised in 2008 and 2014 (RQA-Working-Party-on-Quality-in-Non-Regulated-Research 2014 ).

Academic research institutions and laboratories are as committed as their pharmaceutical counterparts to good scientific practices but are largely operating without defined standards. Many universities hold their scientists accountable for good scientific practices, which are mainly focused on preventing misconduct and promoting a collaborative environment. Academic output is measured by the amount of publications, often in prestigious journals. Peer review of manuscripts is seen by academics as the main quality control element. During the last decade, the replication and reproducibility crisis in biomedical sciences has exposed severe quality problems in the planning and conduct of research studies in both academia and pharmaceutical industry. Academic crisis response elements include public transparency measures such as preregistration, open-access publication and open data (Kupferschmidt 2018 ; Levin et al. 2016 ).

As a result of the replication crisis, which hinges on poor quality of experimental design and resulting data, quality management now has a historic chance to be introduced in the academic biomedical world. Such a system incorporates openness and transparency as key elements for quality assurance (Dirnagl et al. 2018 ).

2 Critical Points to Consider Before Implementing a Quality Standard in Research

2.1 gxp or non-gxp standard implementation in research.

Many activities performed in discovery phase and early development are not conducted under GxP standard but need to comply with a number of regulations. Thus, the implementation of an early phase quality standard could help to mitigate the gap and reduce risk exposure. A simple solution could be to apply good laboratory practice (GLP) standards to all research activities in order to mitigate the gap of quality standard.

The classical GxP standards were often born reactively, out of disaster and severe malpractices, which compromised human health. The GLP, for example, originate from the early 1970s, when the Food and Drug Administration (FDA) highlighted several compliance findings in preclinical studies in the USA, such as mis-identification of control and treated animals, suppressed scientific findings, data inventions, dead animal replacements and mis-dosing of test animals. These cases emphasized the need for better control of safety data to minimize risk, in study planning and conduct, in order to both improve the data reliability and protect study participant life. As a result, the FDA created the GLP regulations, which became effective on June 20, 1979. The FDA also launched their Bioresearch Monitoring Program (BIMO), which aimed to conduct routine inspection and data reviews of nonclinical laboratories, in order to evaluate their compliance with the FDA GLP regulation requirements (FDA 1979 ). Thereafter, the Organisation for Economic Co-operation and Development (OECD) launched their GLP regulation in Europe. Each country, which adopted GLP into their law, tended to add some specificities to their application of GLPs.

Regulated research, which delivers data directly supporting patient safety, is one research area, where GLP were mostly implemented successfully to ensure data integrity and reliability for regulatory approval. Accredited regulatory research laboratories employ continuously trained personnel to perform mainly routine analysis, following defined standard operating procedures (SOPs). Regulatory activities are systematically reviewed/audited by quality assurance groups and inspected by regulators. Thus, developing and maintaining GLP standards needs resources from both research laboratories and regulatory bodies.

In contrast, early discovery research rarely delivers results, which directly impact human health. Therefore the implementation of GxP standards might not be required by the scope of discovery activities (Hickman et al. 2018 ). However, discovery science would benefit from the use of best scientific practices and quality standards, in order to enhance research robustness and effectiveness and proactively achieve compliance. Many discovery laboratories, hosted either in academia, small biotechs or industries, use cutting-edge technologies, constantly develop novel methods and need the flexibility that GxP standards do not offer. Furthermore, when resources are limited, as often in academia, the implementation of GxP standards is often unbearable. In addition, governmental oversight would increase the burden on the part of the regulatory agencies to come up with specific regulations, check documentation and perform additional inspections.

Therefore the main argument for not extending GxP regulation to non-GxP research is that it would stifle the creativity of researchers, slow down innovation and seriously limit early discovery research. Pragmatic, risk-based and science-driven research quality standards could fit with the discovery activities’ scope and requirement of this research activity and ensure data integrity while saving resources.

2.1.1 Diverse Quality Mind-Set

The success of the development and implementation of a research quality standard relies first on understanding the mind-set of GxP group associates and non-GxP researchers.

Experienced GxP scientists, working in conventional science performing routine well-developed and validated assays, generally apply standards consistently and straightforwardly. Risks in such GxP areas are pretty well understood and predicate rules apply. GxP researchers are used to audits and regulatory inspections. Quality assurance departments usually have these activities under strict scrutiny and help to ensure that study documentation is ready for inspection.

In early discovery, the oversight of quality professionals might be lighter. The scientists might be less familiar with audit or inspections. Thus, many pharma companies have implemented clear internal research guidelines, and a number of universities have dedicated teams both to ensure data integrity and to conduct scientists training.

Academic researchers operate under laboratory conditions similar to those in industrial non-GxP research and are united in their commitment to produce high-quality data. There are academic institutional and funder requirements to preserve research data for at least 10 years after a research project ended, many of which support scientific publications. However, there are varying levels of requirements for documentation, aside from laboratory notebooks, which are still in paper format at most universities, despite the fact that most data are nowadays created and preserved in digital format. But the documentation practices are slowly adapting in academic research laboratories: electronic laboratory notebooks are gaining popularity (Dirnagl and Przesdzing 2016 ), and more and more institutions are willing to cover licensing costs for their researchers (Kwok 2018 ). Another group of academic stakeholders are funders, who have tightened the requirements in the application phase. Grant application should include data management plans describing processes to collect, preserve data and ensure their public access. These promising developments might mark the beginning of documentation quality standards in academic biomedical research.

2.2 Resource Constraints

The development of phase-appropriate standards, which provide enough flexibility for innovation and creativity while using best practices ensuring documentation quality and data integrity, is complex and requires time and resources. Thus, both a consistent senior management support and a strong partnership between quality professionals and research groups are mandatory to succeed in both the implementation and the maintenance of the research quality standard.

Research groups, which have the right quality culture/mind-set, could require less inputs from a quality organization.

While these requirements are relatively easy to implement in a pharmaceutical setting, the current academic research environment presents a number of hindrances: usually, academic institutions transfer the responsibilities for data integrity to the principal investigators. While many universities have quality assurance offices, their scope might be limited to quality of teaching and not academic research. Internal and external funding sources do not always support a maintainable quality assurance structure needed to achieve research quality characteristics including robustness, reproducibility and data integrity (Begley et al. 2015 ). However, more and more academia are increasing their efforts to address research quality.

3 Non-GxP Research Standard Basics

The foundation of any quality standards in regulated and non-regulated environments are good documentation practices, based on data integrity principles, named ALCOA+. Thus, a non-GxP Research standard should focuses on data integrity and research reproducibility. The rigor and frequency of its application need to be adapted to the research phase to which it is applied: in early discovery, focus is laid on innovation, protection of intellectual property and data integrity. In contrast, many other elements have to be consistently implemented, such as robust method validation, equipment qualification in nonclinical confirmatory activities or clinical samples analysis under exploratory objectives of clinical protocols and early development.

figure a

3.1 Data Integrity Principles: ALCOA+

Essential principles ensuring data integrity throughout the lifecycle are commonly known by the acronym “ALCOA”. Stan Woollen first introduced this acronym in the early 1990s when he worked at the Office of Enforcement, in the USA. He used it to memorize the five key elements of data quality when he presented the GLP and FDA’s overall BIMO program (Woollen 2010 ). Since then, QA professionals used commonly the acronym ALCOA to discuss data integrity. Later on, four additional elements, extracted from the Good Automated Manufacturing Practice (GAMP) guide “A Risk-Based Approach to GxP Complaint Laboratory Computerized Systems” (Good Automated Manufacturing Practice Forum 2012 ), completed the set of integrity principles (ALCOA+). The ALCOA+ consists of a set of principles, which underpins any quality standards:

Additional elements:

In order to ensure data integrity and compliance with ALCOA+ principles, all scientific and business practices should underpin the RQS. This standard needs to contain a set of essential quality system elements that can be applied to all types of research, in a risk-based and flexible manner. At a minimum, the following elements should be contained.

3.2 Research Quality System Core Elements

3.2.1 management and governance.

Management support is critical to ensure that resources are allocated to implement, maintain and continuously improve processes to ensure sustained compliance with RQS. Roles and responsibilities should be well defined, and scientists should be trained accordingly. Routine quality system assessments, conducted by QA and/or scientists themselves, should be also implemented.

3.2.2 Secure Research Documentation and Data Management

Scientists should document their research activities by following the ALCOA+ principles, in a manner to allow reproducibility and straightforward data reconstruction of all activities. Data management processes should ensure long-term data security and straightforward data retrieval.

3.2.3 Method and Assay Qualification

Methods and key research processes should be consistently documented and available for researchers conducting the activity. Assay acceptance/rejection criteria should be predefined. Studies should be well designed to allow statistical relevance. Routine QC and documented peer reviews of research activities and results should be conducted to ensure good scientific quality and reliability. Any change to the method should be documented.

3.2.4 Material, Reagents and Samples Management

Research materials, reagents and samples should be fit for purpose and documented in a manner to permit reproducibility of the research using equivalent items with identical characteristics. Their integrity should be preserved through their entire life cycle until their disposal, which should be consistent with defined regulation or guidance. Research specimens should be labelled to facilitate traceability and storage conditions.

3.2.5 Facility, Equipment and Computerized System Management

Research facilities should be fit for their research activity purpose and provide safe and secure work environments. Research equipment and computerized system, used in the laboratory, should be suitable for the task at hand and function properly. Ideally, their access should be restricted to trained users only, and an activity log should be maintained to increase data traceability.

3.2.6 Personnel and Training Records Management

Research personnel should be competent, trained to perform their research functions in an effective and safe manner. Ideally, in industry environment, personnel and training records should be maintained and available for review.

3.2.7 Outsourcing/External Collaborations

The RQS should be applied to both internal and external activities (conducted by other internal groups, external research centres, academic laboratories or service providers). Agreement to comply with requirements of RQS should be signed off before starting any research work with research groups outside of the organization. Assessment and qualification of an external partner’s quality system are recommended and should be conducted in a risk-based manner (Volsen et al. 2014 ).

3.3 Risk- and Principle-Based Quality System Assessment Approach

The risk-based and principle-based approaches are the standard biopharma industry quality practice to balance resources, business needs and process burden in order to maximize the impact of an assessment. The risk-based approach is essentially an informed and intelligent way to prioritize frequency and type of assessment (remote, on-site) across a large group of service providers.

The principle-based trend reflects the fact that it may not be possible to anticipate and prescriptively address a myriad of emerging nuances and challenges in a rapidly evolving field. Cell and gene therapy (e.g. CAR-NK and CAR-T), digital medicine, complex drug/device interfaces and new categories of biomarkers are just some of the recent examples demanding a flexible and innovative quality mind-set:

CAR-NK and CAR-T Immuno-oncology therapy is an example where patient is treated with his own or donor’s modified cells. Multiple standards and regulations apply. Researchers perform experiments under a combination of sections of good clinical practice (GCP) and good tissue practice (GTP) in a hospital setting (Tang et al. 2018a , b ).

Digital therapeutics are another emerging biopharmaceutical field (Pharmaceuticalcommerce.com 2019 ). Developers utilize knowledge of wearable medical devices, artificial intelligence and cloud computing to boost the effectiveness of traditional chemical or biological drugs or create standalone therapies. As software becomes a part of treatment, it brings a host of nontraditional quality challenges such as health authority pre-certification, management of software updates and patient privacy when using their own devices.

For the above examples, it is important to adhere to ALCOA+ principles as no single quality standard can cover all the needs.

As quality is by design a support function to serve the needs of researchers, business and traditional quality risk factors need to come together when calculating an overall score.

A simple 3X4 Failure Mode and Effects Analysis (FMEA) – like risk matrix – can be constructed using the following example:

Suppose that:

A pharmaceutical company wants to use an external service provider and works on coded human tissue, which is a regulated activity by law, in several countries, such as Switzerland and the UK:

Quality risk factor 1. Severity is medium.

This laboratory was already audited by the quality assurance of the pharmaceutical company, and gaps were observed in data security and integrity. Remediation actions were conducted by this laboratory to close these gaps:

Quality risk factor 2. Severity is high.

The planned activity will be using a well-established method that the pharma company needs to transfer to the Swiss laboratory. Since the method need to be handoff, the risk is medium:

Business risk factor 1. Severity is medium.

The data generated by the laboratory may be used later in an Investigational New Drug (IND) Application. This is a submission critical, and it will be filed to Health Authorities.

Business risk factor 2. Severity is high.

The risk matrix is balanced for quality and business components. Final business risk is calculated as a product of two business component severity scores such as medium × high = 3 × 9 = 27. Quality risk is calculated in the same fashion.

figure b

4 How Can the Community Move Forward?

The improvement of research reproducibility is not only about process implementation but also about promoting quality culture. The research community needs to join force to build a harmonized and recognized quality culture in research, providing tools, guidelines and policies to ensure data quality and research reproducibility.

4.1 Promoting Quality Culture

A process might be far easier for building systems than building a culture of quality. Very often goals are set around cost, speed and productivity. But what is the cost of working on poor processes and with low quality?

In the Oxford dictionary, culture is defined as “The ideas, customs and social behaviour of a particular people or society” and quality as “The standard of something as measured against other things of a similar kind; the degree of excellence of something” (Oxford-Dictionary 2019 ). So what are the building blocks, which could allow the research community to build a strong quality culture and which elements could influence scientist’s behaviours to strive for research excellence?

4.1.1 Raising Scientist Awareness, Training and Mentoring

In order to embark on the quality journey, researchers should understand the benefits of embracing robust quality:

First Benefit: Help Ensure Their Sustained Success

Great science can lead to patents, publications, key portfolio management decisions, scientific advances and drug submissions. Robust processes position researcher for sustained success, preserving their scientific credibility and enabling, for example, to defend their patent against litigation, make the right decisions, answer regulator’s questions.

Second Benefit: Serve Patients and Advance Scientific Knowledge

The main researcher focus, which fuels their motivation to innovate and go forward, is to advance scientific knowledge and discover new pathways, new drugs and new treatment. Efficient processes enhance research effectiveness and lead to scientific discoveries. Data integrity supports good science, drug safety, products and treatment development for patients and customers.

Once awareness is raised, researchers need to be trained on basic documentation processes and good scientific practices to ensure data integrity and quality. Targeted training should be added on new guidelines, processes and regulations applied to their specific activities (e.g. human tissue use, natural products, pharmacogenomics activities).

4.1.2 Empowering of Associates

The best way to engage researchers is to empower them to perform some changes in order to improve processes and systems. These changes need to be documented, fit for purpose and organized within the quality framework, managed and governed by the senior management. Managers should lead by example, embrace the change in quality culture and interact more with their staff during study planning or laboratory meetings. They should also encourage people to speak up when they observe inaccuracies in the results or potential fraud.

4.1.3 Incentives for Behaviours Which Support Research Quality

A culture that emphasizes research quality can be fostered by providing appropriate incentives for certain behaviours that are aligned with the quality objectives. Such incentives can come in form of promotions, monetary rewards or public recognition. Awards for best practices to ensure data integrity could be a start. Not all incentives must be endured. Some are only necessary to introduce or change a certain practice. Incentives permit an uptake to be measured and the more visible incentives within an institution improve the reach. There is a great variability in effectiveness of a certain incentive. Questionnaires are a useful instrument to find out which incentives are effective for a certain target research population. Any incentives that do not promote quality need to be critically evaluated by the management (Lesmeister 2018 ; Finkel 2019 ).

4.1.4 Promoting a Positive Error Culture

“Error is human” and errors will happen in any research laboratory environment, no matter what precautions are taken. However, errors can be prevented from reoccurring and serve as teaching examples for quality assurance and risk management. For this to happen, a positive error culture needs to be created by leaders that embrace learning and do not punish reported errors. The possibility of anonymous reporting is a crucial element as a seed for community trust, so error reporting is not used for blaming and shaming. Next, a guided discussion of reported errors with the laboratory personnel needs to take place, and potential consequences can be discussed. Such a community effort empowers laboratory workers and makes them part of the solution.

An example of a system to manage errors is the free “Laboratory Critical Incident and Error Reporting System” (LabCIRS) software which permits to record all incidents anonymously and to analyse, discuss and communicate them (Dirnagl and Bernard 2018 ).

4.2 Creating a Recognized Quality Standard in Research: IMI Initiative – EQIPD

Large pharmaceutical companies, service providers and academia are facing the same challenges. They need to manage budget and portfolio, keep credibility and serve customers and patients. Research reproducibility, accuracy and integrity are a benefit to all. For the first time, an Innovative Medicines Initiative (IMI 2008 ) project on quality was launched in October 2017, named European Quality In Preclinical Data (EQIPD 2017 ). EQIPD is a 3-year project co-funded by the EU’s Innovative Medicines Initiative (IMI 2008 ) and the European Federation of Pharmaceutical Industries and Associations (EFPIA).

Pharmaceutical companies and academia joined forces to foster a quality culture and develop a “unified non-GxP research quality standard”, which is expect to be released in 2020 (Steckler et al. 2018 ; Macleod and Steckler 2019 ).

The aim of this project is to establish best practices, primarily in the preclinical neuroscience field but also applicable to the overall non-GxP research, that are harmonized across the pharmaceutical industry to improve data quality and reproducibility in discovery and exploratory research. The EQIPD members are working together to develop simple and sustainable solutions to facilitate implementation of robust research quality systems and expansion of knowledge on principles necessary to address robustness and quality.

4.3 Funders Plan to Enhance Reproducibility and Transparency

The NIH proposed first to implement a mandatory training regarding result reproducibility and transparency and good experimental design. Starting in 2019, the NIH research grant applications now have to include components that address reproducibility, rigor and transparency. Applications must include measures to ensure robust and unbiased experimental design, methodology, analysis, interpretation and reporting of results. More relevant biological models should be considered, and the rigor of prior research that the application is based on should be reviewed. NIH asked publishers to get more involved, promote peer-review and data disclosure. In addition, the whole research community is encouraged to work together in order to improve research reproducibility (National-Institutes-of-Health-NIH 2019 ).

European funders as well aim to enhance reproducibility, mainly by increased transparency and public data availability of research results. The most prominent EU project with that goal is the European Open Science Cloud (EOSC 2018 ). A key feature of the EOSC is that the shared data conforms to the FAIR criteria: findable, accessible, interoperable and reusable (Wilkinson et al. 2016 , 2019 ). Also at the national funder level, more calls of applications emerge that specifically address scientific rigor and robustness in non-GLP research (German-Federal-Ministry-of-Education-and-Research 2018 ).

5 Conclusion

In conclusion, the strategic collaboration between pharmaceutical companies, service providers and academia is critical to help develop both quality culture and standards in research, which could help enhance research reproducibility and data integrity. As resources are often limited, a pragmatic quality system combined with a risk-based approach could mitigate the gaps and proactively address the ever-changing regulatory environment, which continuously expands quality expectations.

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Bongiovanni, S., Purdue, R., Kornienko, O., Bernard, R. (2019). Quality in Non-GxP Research Environment. In: Bespalov, A., Michel, M., Steckler, T. (eds) Good Research Practice in Non-Clinical Pharmacology and Biomedicine. Handbook of Experimental Pharmacology, vol 257. Springer, Cham. https://doi.org/10.1007/164_2019_274

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Good Laboratory Practice for Nonclinical Laboratory Studies

Under the proposed GLP Quality System, we intend to enhance the current quality system approach for nonclinical laboratory studies. The GLP Quality System will provide additional responsibilities for testing facility management and new responsibilities for maintaining SOPs. We propose modifications to the definition of a testing facility to be applicable to all nonclinical laboratory studies, whether they are conducted at a single facility or at multiple sites. We propose amending roles and functions consistent with the revised testing facility definition. We expect that a GLP Quality System will provide the appropriate framework for building quality into a nonclinical laboratory study and will result in more reliable data for us to consider when making regulatory decisions.

Costs estimates of the rule include annual costs from the additional reporting and recordkeeping responsibilities required under the proposed GLP Quality System. One-time costs include reading and understanding the rule, updating existing SOPs, writing new SOPs, and training. We estimate annualized costs, over a 10-year period, at a 7-percent discount rate would average $51.9 million, or $51.5 million with a 3- percent discount rate. We lack sufficient information to quantify the benefits of the proposed rule, but we anticipate that it would result in better quality and more reliable data to support applications and submissions to us.

Regulatory Impact Analysis

Good Laboratory Practice for Nonclinical Laboratory Studies; Proposed Rule (PDF - 548KB)

Federal Register: Good Laboratory Practice for Nonclinical Laboratory Studies

Docket: FDA-2010-N-0548-0088

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COMMENTS

  1. GLP & Non-GLP: What's the Difference?

    Non-GLP studies can be of high quality for any other purpose. In many studies where GLP compliance is not required and for which the intensive reporting requirements and facility requirements could be an impediment, non-GLP options can represent an advantage. Quality assurance does not have to inspect the conduct of non-GLP studies or records.

  2. Non-GLP Toxicology Studies

    Non-GLP Toxicology Studies Prophylactic Vaccine Studies General Toxicology Sub-Chronic and Chronic Toxicity Studies Dose Range Finding Studies Off-Target Screening Carcinogenicity Studies Developmental & Reproductive Toxicology Ocular Toxicology Infusion Toxicology Inhalation Toxicology Musculoskeletal Bone Toxicity Studies Neurotoxicology

  3. Good Laboratory Practice

    Good Laboratory Practice (GLP), are federal regulations that require implementation of a robust quality management system to ensure the validity, integrity and reliability of non-clinical safety data submitted for regulatory evaluation and approval.

  4. Non-GLP Discovery Bioanalysis

    Non-GLP and Discovery Bioanalysis Bioanalytical Mass Spectrometry Services Ligand Binding Assay Bioanalysis Clinical Kitting Services Novel Drug Modalities and Their Bioanalysis ADME DMPK Studies Formulation & Product Chemistry Shipping Logistics: Design and Management Cell & Gene Therapy CDMO Solutions QC Microbial Solutions

  5. GLP & Non-GLP: What's the Main Difference?

    The main difference between GLP and non-GLP studies is the assessment of safety. The FDA requires GLP compliance for non-clinical laboratory studies that seek to prove the safety of products such as food, animal drugs, human drugs, biological products, medical devices, and more. Studies that revolve around toxicity profiles, adverse effects, or ...

  6. PDF Overview and Specifications of Non-GLP, Research Grade Assays

    Overview and Specifications of Non-GLP Research Grade Assays | Charles River Author: Charles River Laboratories Subject: Charles River offers a suite of standardized, fit-for-purpose non-GLP research-grade assays to address client needs across the drug continuum Keywords: non-GLP, research-grade assays Created Date: 2/7/2017 10:54:48 AM

  7. Non-GLP Toxicology Studies

    Exploratory Research: Non-GLP studies provide a platform to explore a wide range of doses, formulations, and exposure durations, enabling researchers to gather preliminary data and make informed decisions about further development. Rapid Screening: Non-GLP studies offer the advantage of faster turnaround times, making them suitable for screening multiple compounds or evaluating early-stage ...

  8. Discovery Bioanalysis

    A dedicated non-GLP bioanalytical team providing superior focus. A tiered approach to meet your assessment needs for plasma, blood and tissue analysis. An integrated solution supporting PK in-life, bioanalytical and PK/TK data analysis to expedite your results. State-of-the-art instrumentation and highly qualified scientists who are committed ...

  9. Non-GLP Bioanalysis • WuXi AppTec Lab Testing Division

    You have access to a DMPK team that supports non-GLP bioanalysis of antibodies, bispecific antibodies, recombinant proteins, biosimilars, fusion proteins, peptides, antibody drug conjugates (ADC), PEGylated peptides and proteins, hormones, oligonucleotides, gene therapy products and vaccines. Capabilities

  10. Non GLP, Non GLP study, Non GLP Preclinical Study

    Non-GLP Study Preclinical Tox (PK/TK) And Biomarker Services. Specialization in assay development, validation, and sample analysis on the following bioanalysis platform. Lab, Method Development, And Validation Services For 20+ Years. Development Validation Lab Services For Your PK, Biomarker, Or. Discovery (MSD) Assay For PK Or Immunogenicity ...

  11. PDF GLP vs. non-GLP

    This paper describes XenoTech's application of FDA GLP regulations to enzyme inhibition, enzyme induction, drug transport and drug metabolism studies in in vitro and ex vivo test systems and provides a comparison of specific FDA GLP-required elements between an FDA GLP-compliant study and a non-GLP study conducted at XenoTech. Introduction

  12. Why should I use a GLP Lab when my study is non-GLP?

    In addition, your lab should characterize test and control materials to eliminate study mistakes. You also need to retain specimens and samples in a safe environment to avoid further errors. All of these can become impossible when you're financially strained or have no room to expand. Going beyond GLP, though, is adherence to your SOPs ...

  13. G(C)LP & non-GLP Bioanalytics

    The Pharmacelsus bioanalytic team performs highest quality analyses with latest edge technology. We support our in house in vitro and in vivo studies as well as external preclinical and clinical studies with diligence and dedication.

  14. Non-GLP sample analysis for ocular biodistribution studies

    Non-GLP sample analysis for ocular biodistribution studies 10 May 2022 Traditional bioanalytical service providers are geared toward analyzing large sets of samples under various regulatory guidelines, such as large nonclinical and clinical studies, which are heavily regulated.

  15. GLP vs. Non-GLP Toxicology Studies

    Non-GLP studies, deployed at the right time, can offer huge advantages to drug developers. Here, we will explore the difference between GLP and non-GLP studies and determine when to use which. What are Good Laboratory Practices?

  16. Performing GLP studies in a traditionally non-GLP facility

    Situations can arise in which traditionally non-GLP facilities may have to be used for performing nonclinical GLP studies or parts of a GLP study. The situations may include a need for particular expertise of scientists, the analytical laboratory, or the development of an unusual product. This article describes the use of a core group model as ...

  17. Dose Formulation Analysis

    Dose confirmation analysis is an important part of any successful GLP study and is required by the United States Food and Drug Administration (USFDA) for formulations dosed in toxicology studies. We provide high quality, preclinical dose formulation analysis for both GLP and non-GLP studies, to ensure your study starts off on the right track.

  18. Quality in Non-GxP Research Environment

    This raises the need for effective systems to improve data integrity in the evolving non-GxP research environment. This chapter describes the critical elements that need to be considered to ensure a successful implementation of research quality standards in both industry and academia. The quality standard proposed is founded on data integrity ...

  19. Theralase (R) Successfully Completes Non-GLP Toxicity Analysis for

    Theralase® announced that it has successfully completed its non-Good Laboratory Practices (" GLP ") preclinical toxicology analysis of Rutherrin® for Glio Blastoma Multiforme (" GBM "). GBM is the most aggressive and most common type of brain cancer. The preclinical toxicology data collected to date has demonstrated that Theralase®'s ...

  20. Good Laboratory Practice (GLP)

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  21. Good Laboratory Practice for Nonclinical Laboratory Studies

    Under the proposed GLP Quality System, we intend to enhance the current quality system approach for nonclinical laboratory studies. ... Regulatory Impact Analysis. Good Laboratory Practice for ...

  22. Non-GLP sample analysis (ELISA)

    Non-GLP sample analysis (ELISA) Analysis Antibodies Print PDF ELISA assay development and optimization of reagents in a non-GLP setting. Analysis of samples in a variety of matrices at a medium throughput scale. Molecule or Product Type Biologics, Vaccine Industry Market Pharma Phase Nonclinical Immunosorbent: ELISA (in vitro)

  23. Theralase (R) Successfully Completes Non-GLP Toxicity Analysis for

    Theralase® announced that it has successfully completed its non-Good Laboratory Practices (" GLP ") preclinical toxicology analysis of Rutherrin® for Glio Blastoma Multiforme (" GBM "). GBM is the most aggressive and most common type of brain cancer. The preclinical toxicology data collected to date has demonstrated that Theralase®'s ...