Frontage boasts a comprehensive team of clinical research ba be studies experts to conduct all aspects of clinical trial studies. From feasibility evaluation and trial execution through final report submission and presentation as per sponsor specifications.
Review temperature records during sample shipping/transfer and storage to ascertain that test and reference product reserve samples were stored under protocol-specified conditions.
Design
Clinical research is an area of medical science dedicated to evaluating the safety and effectiveness of therapies, medications, vaccines, medical devices, or therapies before they become generally available for public consumption. As opposed to lab-based pure research studies conducted with test tubes or computer simulations, BA BE clinical trials contribute immensely to medical advancement as they inform medical knowledge for future generations and advance health care quality.
Sponsors or contract research organizations working for them endeavor to recruit participants with characteristics suitable for a study through various means such as patient databases, radio advertisements, newspaper ads, flyers in locations patients frequent such as doctors’ offices, personal recruitment by investigators, etc.
Clinical research ba be studies can be divided into two components, clinical and analytical. The clinical component includes recruiting participants for drug products to use during studies, monitoring participant safety during the research, collecting biological samples from them for pharmacokinetic analysis (PK), as well as processing the PK data so it can be used to calculate bioavailability and bioequivalence parameters (BE).
BE/BA trials must be designed carefully in order to avoid bias and ensure accurate results. This can be accomplished using a randomised, cross-over trial design with long wash out periods to ensure blood concentrations have fallen below detection limit between treatment groups; at least five elimination half lives should elapse during this period.
Clinical research be studies provide researchers with an invaluable means of testing new treatments to see whether they work. Researchers may use them to discover innovative approaches to diagnose, prevent, treat, or cure disease; especially when current options have proven ineffective. Furthermore, such trials provide invaluable data that could lead to the creation of safer medicines – an advancement which could enhance quality of life for millions worldwide.
Methods
Clinical research ba be studies utilize both pharmacokinetic (PK) and bioequivalence (BE) techniques as methods of investigation. PK examines how drugs enter, move within, modify and exit the body in relation to dosage or dosing intervals, while BE measures the rate and extent at which active substances in test products versus reference formulations are absorbed into bloodstream after receiving similar molar doses under similar conditions.
To successfully conduct a clinical BA/BE study, it is crucial to follow FDA regulations 21 CFR part 320. This regulation outlines requirements for pharmaceutical companies wishing to submit in vivo BE and BA data in their ANDA applications.
They include the establishment of a clinical sample repository, standard BE analysis methods and processes, as well as standardised PK data collection and statistical analysis processes. Furthermore, FDA suggests log-transforming all BE data, with this being indicated within clinical study protocols; consistent adjustments for all BE measures should also be implemented at this point.
When selecting a CRO to perform a BA/BE study, sponsors should seek the following qualities in a CRO: Transparent communication at all levels, sensitivity towards project requirements and timelines, flexibility to adapt quickly to unexpected events during its lifespan and an organization culture which matches that of their sponsor while being capable of producing high-quality results in a timely fashion.
At a clinical BE/BA study, the clinical component entails recruiting and screening subjects for participation, administering both test and reference drugs to them and monitoring their safety during the experiment. Meanwhile, its analytical component involves collecting biological samples such as blood from subjects for further analyses to ascertain drug concentration levels in those samples.
At each clinical site being inspected by the FDA, records for storage/transfer of biological samples will be thoroughly scrutinized to ensure they were kept at an ideal temperature as per clinical study protocol. Furthermore, documents related to subjects’ medical histories, resumes/curriculum vitaes, copies of certificates of training received and verification that study personnel are adequately qualified will also be carefully considered during an inspection process.
Safety
Research that involves human participants is never without risk, even with all the regulations, company policies and procedures in place to support conducting clinical trials. Issues still arise due to fast study progression, strain on resources and day-to-day factors which impede focus.
All human studies that involve medical or therapeutic interventions on patients are closely overseen by a regulatory authority (in the US this would be an Institutional Review Board (IRB), while in Europe this could be called an Ethics Committee). This body examines each study for both medical safety and protection of its participants; potentially making changes to procedures or explainers required, or even mandating that investigators submit annual “Continuing Review Reports to keep IRB up to date.
Before any drug or device can be approved by the FDA, it must first undergo rigorous preclinical testing. Once results of this testing are satisfactory, human trials can commence; unfortunately though, many drugs that enter preclinical testing never make it past this initial step into final stage clinical trials.
Sponsors and contract research organizations that conduct clinical studies must recruit volunteers for participation. Recruitment methods vary according to trial type and participant needs; these could include patient databases, newspaper and radio advertisements, flyers posted in likely places for subjects, or investigators personally recruiting volunteers for participation.
A clinical BA/BE study involves two components, the clinical portion and analytical phase. The clinical portion involves administering and monitoring safety during administration of an investigational drug product to the subjects; and processing biological samples collected during this phase to measure drug concentrations in blood and generate PK parameters such as clearance or volume of distribution.
Sponsors utilize clinical trial data collected during trials to produce periodic aggregate safety reports for submission to health authorities, providing updates on the benefit-risk profile of an investigational drug. Such reports typically conform with international guidelines such as the ICH GCP SS 5.17.3 guidance; however, substantial discrepancies were noted between approaches taken to generate and present these reports across countries and regions of the world.
Regulatory Requirements
The FDA defines a clinical BA/BE study as any human in vivo bioavailability or bioequivalence (BA/BE) test submitted to the Center for Drug Evaluation and Research.”2 This Compliance Program details procedures for FDA investigators inspecting domestic or international sites which conduct this type of investigation.
Clinical BA/BE inspections serve the primary goal of assuring that subject safety and data integrity requirements at a site are fulfilled, while noting any significant inspectional observations on an FDA Form 483, Inspectional Observations Form. It is important that these observations should be factual in nature, with supporting CFR regulations whenever possible.
Additionally, it is crucial that a BA/BE site establishes relationships with any clinical laboratories performing analytical tests required for its study, and verify if those laboratories are adequately equipped to handle all the tests specified by study documents (protocol or labeling). Finally, understanding how they manage collection of clinical laboratory test samples before their transfer for testing should also be evaluated thoroughly.
Finally, the site must identify and document procedures designed to prevent changes or modifications of original data collected for a study from occurring unauthorised changes or modifications by either researchers within its boundaries or any person outside it. This involves monitoring access to electronic formats of stored data held within its facilities as well as how those data will be sent out to sponsors or CROs for processing and transmission.
Sponsors of BA BE studies in clinical trials must take note that, under current U.S. law, only FDA-approved drugs can be transported or distributed across state lines; to transport or distribute experimental medications across state lines they must submit an IND application with the FDA.
SpinoS BioLab possesses an in-depth knowledge of both preclinical and clinical bioequivalence/bioavailability (BA/BE) studies, working closely with our clients to deliver efficient yet cost-effective testing solutions for their testing needs. With 20+ years of experience under their belts, SpinoS BioLab’s team is well versed in today’s evolving regulatory environment – helping ensure your bioequivalence/bioavailability study runs seamlessly while meeting all applicable regulations.