To create a safe, effective, and meets all regulatory criteria, every drug development process must go through several phases.
Rondaxe can help you in every step of drug development. Our scientists can assist you in determining your testing requirements, and our professional team can conduct the necessary tests and studies required for FDA approval.
To get you started, we’ve given an in-depth description of several phases in the drug development process, as well as the required research, below.
Target identification – selecting a biochemical process implicated in a medical state – is a common starting point for discovery. Drug candidates developed in academic and pharmaceutical/biotech research laboratories are evaluated for interactions with the drug target. For each prospective therapeutic candidate, up to 5,000 to 10,000 molecules are exposed to a rigorous screening procedure that may involve functional genomics and proteomics, as well as other screening techniques. Once scientists have confirmed interaction with the drug target, they usually verify that target by looking for activity against the medical condition for which the medication is being produced. After careful consideration, one or more lead compounds are selected.
During drug discovery, a promising candidate molecule is identified it can be used in clinical trials. First, the molecule must be described, which includes determining the molecule’s size, shape, strengths, weaknesses, the environment where it functions well, toxicity, bioactivity, and bioavailability. Analytical method development and validation will occur during characterization investigations—early-stage pharmacology research aids in characterizing the compound’s underlying mechanism of action.
Medication designers must create a formulation that guarantees appropriate drug delivery parameters. At this stage of the medication development process, it is essential to start thinking about clinical trials. Medication formulation and delivery may be continually improved until, and even beyond, the ultimate approval of the drug. Scientists test the drug’s stability in the formulation and storage and shipping conditions such as heat, light, and time. The formulation must stay potent and sterile, as well as safe (nontoxic). Extractables and leachables research on containers or packaging may also be required.
Pharmacokinetic (PK) and ADME (Absorption/Distribution/Metabolism/Excretion) studies offer valuable information for formulation experts. AUC (area under the curve), Cmax (the highest concentration of the medication in the blood), and Tmax (the time to maximum concentration) (time at which Cmax is reached). Animal PK research will be used in tandem with early-stage clinical trials to see whether animal models predict real-world outcomes.
Preclinical testing evaluates the developed drug product’s bioactivity, safety, and effectiveness. This testing is crucial to a drug’s ultimate success and is thus examined by several regulatory bodies. Plans for clinical tests and an Investigative New Drug (IND) application are developed throughout the preclinical stage of the research process. Tests conducted during the preclinical phase should be intended to assist subsequent clinical studies.
The main stages of preclinical toxicology testing are:
- Acute Studies – Acute tox studies focus on the effects of one or more doses given during 24 hours. The aim is to identify hazardous dosage levels and to look for clinical signs of toxicity. At least two mammalian species are usually examined. Acute toxicity data is used to help establish dosages for repeated dose studies in animals and Phase I human trials.
- Repeated Dose Studies – Repeated dosage studies may be classified as subacute, sub chronic, or chronic, depending on their length. The exact duration should anticipate the length of the clinical study for the new medication. Once again, two species are usually needed.
- Genetic Toxicity Studies – These investigations determine if a medication compound is mutagenic or carcinogenic. Genetic alterations may be detected using procedures such as the Ames test (conducted in bacteria). The Mouse Micronucleus Test, which uses mammalian cells to evaluate DNA damage, is one example. In addition, the Chromosomal Aberration Test and related methods identify chromosomal damage.
- Reproductive Toxicity Studies – The effects of the medication on fertility are investigated in a segment I reproductive tox investigations. Segment II and III research look for impacts on embryonic and postnatal development. In general, reproductive tox studies must be performed before medication may be given to women of childbearing age.
- Carcinogenicity Studies – Carcinogenicity studies are often required only for medicines used to treat chronic or recurrent diseases. They take time and money and must be prepared for early in the preclinical testing phase.
- Toxicokinetic Studies – These are usually designed like PK/ADME experiments, except that considerably larger dosage levels are used. They investigate the effects of hazardous medication dosages and aid in estimating the clinical margin of safety. Many FDA and ICH recommendations provide extensive information on the various kinds of preclinical toxicology studies and the proper scheduling for them with IND, NDA, or BLA submissions.
The majority of the other activities in the drug development process are supported by bioanalytical laboratory work and the development of bioanalytical methods. The bioanalytical work is critical for appropriate molecular characterization, assay creation, establishing optimum cell culture or fermentation techniques, calculating process yields, and providing quality assurance and quality control throughout the development process. It is also essential for preclinical toxicology/pharmacology testing and clinical trials.
Clinical trials are classified into three kinds of phases based on their objective:
- Phase I Clinical Development (Human Pharmacology) – Unless the FDA puts a hold on the research, a biopharmaceutical company may commence a small-scale Phase I clinical trial thirty days after filing an IND. Phase I studies are performed to assess pharmacokinetic parameters and tolerance in healthy individuals. These investigations include initial single-dose trials, dosage escalation, and short-term repeated-dose studies.
- Phase II Clinical Development (Therapeutic Exploratory) – Phase II clinical trials are small-scale trials in which 100 to 250 individuals are evaluated for a drug’s preliminary effectiveness and side-effect profile. This category also includes additional safety and clinical pharmacology research.
- Phase III Clinical Development (Therapeutic Confirmatory) – Broad-scale clinical trials evaluating safety and effectiveness in large patient groups are known as phase III investigations. While phase III studies are being conducted, preparations are being made to submit the Biologics License Application (BLA) or the New Drug Application (NDA). The FDA’s Center for Biologics Evaluation and Research is presently reviewing BLAs (CBER). In addition, the Center for Drug Evaluation and Research evaluates NDAs (CDER).