Preclinical CRO Services for Safety Assessment

Products intended to treat human diseases or enhance personal comfort are usually chemicals – either pure chemicals used alone, or in a mixture. They can made by chemical synthesis or purified from a natural source. In any case, there is a right amount and a right time a drug can be administered to help the body. In contrast, every chemical, even water, can be toxic if administered too quickly or in too high a concentration or amount. The purpose of preclinical studies in safety assessment is to determine the safe amounts and timing for agents that are intended to help us and ensure that for adults or even newborns or pregnant women, that the chemicals or devices will truly help and not cause adverse events.

We need to learn how the drug can be given so the right (helpful but non-toxic) amount and method of administration ensures it goes to the area of the body needed to produce a beneficial effect. A good example is inhalers for asthma, which deliver a limited amount of drug directly to the mid-lung. If too much goes into the bloodstream, such a drug races the heart. Preclinical CRO services can help optimize the delivery practices and study the right timing, dose, and manner of delivery to result in the best action. Additionally, investigators can use this data to inform potential clinical trial participants of any possible risks. Without thorough safety assessment evaluations, no new trials could be safely conducted.

Many of the same methods are used for veterinary and human studies – like receiving an annual physical from your doctor. When conducting toxicology studies, many methods are utilized including analytical chemistry, clinical pathology, bioanalytical methods, histopathology staining, statistical analyses, as well as immunology, molecular biology, and sequencing techniques. In addition, safety pharmacology studies employ sophisticated methods to measure impact on heart function, nervous system, and respiration. We learn about effects on the body including liver, kidney, blood, and immunity using samples from blood or urine, while also studying changes at the cellular level to ensure the impacts of drugs or devices have not left a silent harm in their wake. Together these preclinical CRO studies are all required by international regulators to ensure human safety before testing in human patients.

GLPs are a set of requirements for quality control systems that organizations must follow when conducting non-clinical studies to ensure the quality and validity of the data collected. For safety assessment studies to be conducted under GLP there are requirements regarding the test facility, its management, study rooms and equipment used, the role of the study director and scientists, the quality of the drug itself, the training of personnel involved on the preclinical studies, quality assurance, and the manner in which the study is conducted, recorded, and stored. Here are a few high points:

• Safety studies have a predesigned protocol in which the study director takes full responsibility for being the point of contact with the Sponsor.
• Any changes to the study protocol or study errors must be documented and categorized as to whether they impacted the quality of study interpretation.
• Quality assurance units review the data for accuracy and report directly to the laboratory site management.
• Training and training record documentation must be kept up to date to ensure staff follow all the standard operating procedures and are properly trained to conduct the studies.
• GLPs also apply to the drug product, both in its delivery vehicle and under the conditions in which it is diluted or stored, as well as quality and quantity used. Chemical studies on the full formulation must be performed to assess the stability of the drug while it’s being given to animals or to the cultured cells. This ensures that the drug or chemical is fully active when exposure is occurring.

Regulators have a responsibility to protect the public by making sure that drugs and medical products are safe and effective. In order to accomplish this, they need to be sure that the data they review is reliable and of high quality. GLPs help regulators trust the data and is required in many jurisdictions. With such complex safety assessment investigations and with data analyzed by so many people, labs, equipment, and computer programs, GLPs help ensure that all parts of a study – from initial dosing to the final report – is all properly recorded, reviewed, and stored for integrity and all study events and parameters can be accurately reconstructed.