The term Clinical Development is used to describe the process from early development and pre-clinical studies through to product licensure and post approval maintenance. The main activities undertaken during this stage are Clinical Trials; these are used to determine the effect of a candidate molecule on volunteers and patients to see if a new drug or device is safe and effective for use. Clinical Trials are also used to compare existing treatments to determine which is best, and to study different ways to use the standard treatments, so they’re more effective, easier to use and decrease side effects. Trials may also be performed to assess treatments in new, or different, population groups, e.g. children.
Clinical studies are strictly controlled and can only take place after a satisfactory review of the quality of the non-clinical safety data, and Health Authority and Ethics Committee approval is granted in the host country. A New Drug Registration must be approved before Clinical Trials are conducted according to a protocol, which is a guideline describing the types of volunteers and patients who may enter the study, the schedule of tests and procedures, drugs, dosages, duration of study, and the outcomes to be measured. A strict process of receiving Informed Consent must be followed for each volunteer.
Clinical Trials comprise different, specific, phases referred to as Phase I, Phase II, Phase III, and Phase IV. Each phase is designed to answer questions regarding the safety, efficacy and use of the target molecule.
Different phases of Clinical Trials
• Phase I Clinical Trials or Safety Studies collate pharmacokinetic safety data following the administration of pre-set doses of the target molecule. This allows Maximum Tolerated Dose (MTD) to be determined. These trials are usually conducted with a limited number of participants.
Multiple Ascending Dose (MAD) studies improve understanding of the pharmacokinetics, and pharmacodynamics effects. Groups of patients receive multiple low doses of the candidate molecule, while samples are collected at various time points to determine drug processing kinetics information.
• Phase II Clinical Trials assess how well the drug works, and continue Phase I safety assessments in a larger group, usually 20-300 volunteers and patients. Most new drug candidates tend to fail to progress beyond Phase II studies due to unplanned or toxic effects.
• Phase III Clinical Trials or Pivotal Clinical Trials are designed to be the definitive assessment of how effective the drug is, in comparison with current ‘gold standard’ treatment. Phase III studies are randomised, controlled, multicentre trials, on a large patient population of 300 to 3000+ volunteers and patients, over a long period of time. These are the most expensive, time-consuming, and difficult trials to design and run, especially in therapies for chronic medical conditions. Full cGMP must be in place by the time Phase III studies are performed.
Phase III trials will often continue while the regulatory submission is pending, allowing patients to continue to receive possibly lifesaving treatment until the drug is approved and can be obtained by purchase. If these trials prove satisfactory the results are usually combined into a comprehensive description of the methods and results of human and preclinical studies, manufacturing procedures, formulation details, and shelf life. This collection of information makes up the “Regulatory Submission” submitted in eCTD format.
• Phase IV or Post-Marketing Trials follow Product Licensure and involve the safety surveillance, pharmacovigilance, and on-going technical support of a drug. This will typically be communicated as the post approval commitments to the Board of Health. This is designed to detect any rare or long-term adverse effects over a much larger patient population and longer time period of time.
• Phase V refers to comparative effectiveness research and community-based research. This helps new clinical treatments become integrated in widespread public health practice. cGMP must also be considered throughout the clinical development stage as it must be implemented prior to Phase III clinical trials.
How Woodley BioReg can help with Clinical Developments
Woodley BioReg offers a range of services to clinical and product development clients through medical and clinical advice, management, support, and registering new pharmaceutical, biopharmaceutical, healthcare, and over-the-counter products globally. To ease the process of clinical trials, helping companies achieve product licensure.
For more information on Clinical Development, Clinical Trials and Clinical Studies, please contact us.