FDA Guidance on Preclinical Study to Evaluate Biotech and Pharma Drug Safety IBiotechnology-derived pharmaceuticals form a major area of drug development. Before these drugs are considered fit for human use, even for trials, they must undergo preclinical study. Several key studies are performed at this stage to ascertain the safety and efficacy of the proposed drug.
FDA guidance on this subject takes inspiration from the ICH S6 guidelines, along with various addendums and changes. The requirement for addendums is to address scientific and pharmaceutical developments made since the release of original guidelines.
Aspects of the FDA Preclinical Study Guidance
A major part of the preclinical drug development involves performing in vivo studies on animals. Necessary as they are, studies on animals create a monetary and ethical dilemma.
The guidelines hope to reduce the number of animals required for testing. There’s also an element of encouraging preclinical research services to adopt in vitro methods where feasible.
Primary Directives Of Safety Evaluation
Safety evaluation of biotech and pharma drugs employs three major principles. These are:
1.Identification of a safe dose and possible dose escalation in humans
2.Identifying the potential of toxicity in target organs and discerning if the toxicity is reversible
3.Identification of safety parameters for drug testing
In most cases, at least two animal species are involved in the preclinical study, at least one of which must be a non-rodent. This approach provides better qualitative and quantitative cross-species comparisons, enabling a more accurate translation for human use.
Safety and Efficacy Aspects of Biotech and Pharma Drug Development
In the current scenario, a preclinical CRO handles these studies in drug development. The CRO carries out the study intending to meet regulatory and pharmaceutical requirements. Key considerations for a preclinical study are parameters related to drug efficacy and toxicity. This process can involve the following studies.
PD And PK Studies
Pharmacodynamic and pharmacokinetic aspects of a drug provide information on its efficacy, ADME, and bioavailability. This study can take two approaches. In one approach, the maximum intended effects of a drug are observed with a steady intended dose.
For the second approach, the drug dosage is significantly higher than the therapeutic dosage. This higher dose forms the basis of preclinical toxicity studies. While it is possible to employ PK parameters, many preclinical CROs use toxicokinetic parameters.
These studies help decide the minimum and maximum feasible doses for the candidate drug.
Immunogenicity
Biotechnology-inspired drugs often run the risk of inducing an immune response from the subject. An immune response can lower the efficacy of a drug. In some cases, it may cause adverse reactions that can be dangerous.
The presence of anti-drug antibodies (ADA) doesn’t necessarily represent the failure or early termination of the study. Also, it may not necessarily represent the formation of antibodies in humans on exposure to the drug.
Single-Dose and Repeat-Dose Toxicity
Single-dose toxicity considers the relationship between a dose and local toxicity. Repeat-dose toxicity sees the effect of the drug over a dosing regimen. It is generally possible to include toxicokinetics in this scenario.
Immunotoxicity
Many biotech drugs are geared towards suppressing or stimulating the immune system. Therefore, a look at immunotoxicity is essential.
Reproductive Toxicity
Possible effects of a drug on the reproductive system are part of this study. This is generally dependent on other factors like the product and patient population.
Genotoxicity
Genotoxicity studies are usually not necessary for biotech-derived drugs.
Carcinogenicity
Biotech-derived drugs generally don’t need carcinogenicity studies. However, the product-specific potential for carcinogenicity may have to be considered.
|
