Considered by those in the pharmaceutical industry and others, as the gold standard for ensuring drug sponsors stick to the highest standards while going through the drug development process.
They establish a standard of practice to ensure that results from the nonclinical laboratory study reported to the FDA are valid and that the study report accurately reflects the conduct of the study.
All studies carried out in line with these standards are an essential part of the investigational new drug (IND) and new drug application (NDA) process. Sticking to the rules can take more time and more money to promulgate these standards of conduct in the lab, it needs to be thoroughly documented and carried out properly.
When this is done, it is easy to reconstruct and audit the study later. These safeguards are necessary for any definitive study, such as those used for IND and NDA submission.
While still scientifically sound, non-GLP studies don’t have stipulated regulations regarding length, sample size and analytical methods. This makes them more cost-effective for fact-finding missions specific to key areas of interest. Non-GLP studies can give drug sponsors insights into dose levels, toxicity, and more to inform further development and studies. Non-GLP studies can also be used tactically to potentially predict the results of a study that will be used for IND submission, thereby avoiding surprises.
Executive technical director and toxicologist at WuXi AppTec, Xiaoxia Li (XL), shared her perspective with Outsourcing Pharma (OSP) on when non-GLP studies are appropriate in the drug development process and how they can be designed to yield scientifically sound results while saving time and money.
OSP: What is a GLP study?
XL: A GLP study is a toxicology study that follows the Good Laboratory Practices regulations set forth by the U.S. FDA. These regulations date back to the early 1970s. At that time, the U.S. FDA had audited some drug developers—most notably Industrial Bio-Test Laboratory—and found some toxicology and safety assessments were misconducted or otherwise not providing scientifically sound data on drug safety.
GLP regulations were introduced to create standardization around non-clinical testing. The first set of regulations were introduced in 1978, and they have continued to evolve since that time. Since then, these regulations have been an essential part of the quest to ensure the highest standards in drug development. Today, GLP regulations cover in vivo and in vitro testing.
OSP: What is the difference between a GLP study and a non-GLP study?
XL: The primary difference between a GLP study and a non-GLP study is the lack of a quality assurance arm in the latter type of study. This means that non-GLP studies are not required to have a quality assurance unit (QAU) involved in the study. Per GLP requirements, a study must have a separate QAU, which contributes to time and expense.
Non-GLP in vivo studies are usually shorter in duration and use smaller number of animals. Drug sponsors should proceed with caution here, however. If a study is too short, for example, seven days for a non-GLP study versus 28 days for a GLP study, it may not accurately predict toxicity that will be seen in the 28-day GLP study required for IND submission. No recovery animals are needed.
OSP: When and why would drug developers want to deploy a non-GLP toxicology study?
XL: First and foremost, non-GLP studies can be an excellent way to guide drug development at the earliest stages. Dose range-finding studies and other preliminary studies can help scientists confirm hypotheses or avoid costly errors early on. Non-GLP studies can also help drug sponsors develop more robust GLP toxicology studies for IND submission.
Non-GLP studies can also be used as a dress rehearsal for GLP study required for IND submission. By shortening the duration, limiting the number of animals and/or eliminating the need for a QAU, drug sponsors can save time and money while still deriving scientifically sound insights.
OSP: How do non-GLP studies help drug developers determine dosing?
XL: Dose range-finding studies help drug developers select appropriate doses to be used in the subsequent GLP studies. Findings are to be further evaluated in the definitive GLP studies, which will be used to predict initial dose in human.
OSP: What types of laboratory partners can perform a non-GLP study?
XL: Any laboratory partner that can perform a GLP study can also perform a non-GLP study, but laboratories that have not been inspected and certified by the U.S. FDA can perform both types of studies. With either type of study, good scientific practices must be followed.
Large drug developers with vast resources might be more readily able to execute a non-GLP study in-house, whereas smaller drug developers may not have access to adequate resources. Both groups should consult with a quality laboratory testing partner to determine the best course of action.
OSP: How can drug developers ensure that non-GLP studies are still scientifically sound?
XL: Non-GLP studies must still be performed in the spirit of GLP. Simply put, that means that non-GLP studies must produce high-quality, reviewed, and reproducible results. That said, studies can be designed to confirm hypotheses or address narrow areas of research.
Working with a quality laboratory research partner can ensure that scientific principles are not sidestepped even if GLP regulations are no longer in force.
OSP: Are there any exceptions as to when GLP studies are required?
XL: There are some instances where drug developers can apply for exceptions to GLP requirements. For instance, some aspects of a study may apply to good manufacturing practices (GMP) regulations instead. Drug sponsors can file for exceptions in these instances.
As a rule of thumb, studies producing definitive nonclinical guidance must follow GLP requirements, including IND and NDA submissions. Studies prior to this step are not subject to such stringent regulations.
OSP: What is the main difference between GLP and non-GLP studies in the processes and procedures for safety assessment?
XI: GLP studies are required by the U.S. FDA for any non-clinical laboratory study that provides definitive guidance on the safety of a drug, medical device, or product. Studies directly addressing toxicity profiles, adverse effects, or safe doses 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 GLP standards.
Working with a quality laboratory research partner can help drug developers save time and money. By opting for non-GLP preliminary toxicology studies, drug developers can better design toxicology studies that will be used for IND submission.
