As the Director of Regulatory Affairs, our company has recently developed a monoclonal antibody for the treatment of cancer. The antibody is called Ziblofril and within the company, we have currently completed the preclinical testing. During the preclinical testing stages, the first different monoclonal antibodies were tested using cell-based high throughput assays to identify potential drugs which prevent the growth of cancer. Following this, the discovery of these compounds, pre-clinical testing involving further testing in cell lines was conducted. Then testing in animal models to confirm the findings occurred. Several different animal cancer models were used to verify the findings of Ziblofril. In addition, this pre-clinical testing includes characterizations to determine if the drug of interest is toxic and the effectiveness of the compound. It establishes the dosing information and the specific toxicity of the drug (Brodniewicz & Grynkiewicz, 2010).

Following this testing, the third step is that of clinical research. In order for a drug to be tested in humans, there must be strong preclinical evidence. While preclinical information can provide insight into the safety of the drug it does not determine specifically how the drug will react in the human body. It is for this reason that there are four different phases of clinical trials. During Phase 1 clinical trials, the purpose is to determine the safety and dosage of the drug of interest. In this phase, only around 20 to 100 healthy individuals are tested and testing lasts for only a couple months (Umscheid, Margolis, & Grossman, 2011). If the drug passes phase 1 clinical trials it then enters phase 2 clinical trials. Here, the purpose of this phase is to establish the efficacy of the drugs in patients with cancer and to determine if there are any potential side effects. In general, a couple hundred people with cancer would be used to test Ziblofril. Here the testing could last anywhere from around several months to several years (Evans, 2010).

If the drug is deemed effective with minimal side effects, it would then enter phase 3 clinical trials. The drug has previously been shown to be effective, but only in a small number of patients with cancer. Therefore, the purpose of this phase is to determine the efficacy of the drug in a larger number of patients to see if the findings are repeatable. In addition, with a larger patient set, the goal is to also monitor for the occurrence of adverse reactions or side effects, which may not have shown up in a smaller sample group. Therefore, for this phase usually, a couple thousand individuals that have the condition are tested. In general testing in this phase can last for a couple of years. Because of the longer duration of the study, rare side-effects are more likely to occur. It is in this phase where the majority of the safety information for the drug of interest is determined (Akhondzadeh, 2016).

Finally, if the drug continues to display efficacy and has minimal/no adverse reactions it moves to the final phase of clinical testing, phase 4. Phase 4 testing only occurs after a drug has received FDA approval. The drug has now been approved for use in humans and this phase is designed to monitor the efficacy and safety of the drug during the post-marketing stage. In general, several thousand patients are tested in this phase, and it can last for many years. Because of the long duration of this phase, it can help to identify any rare side-effects that may not have been identified in phase 3. It is possible for drugs which have been approved to later have their approval revoked, based on the results of this phase of testing (Suvarna, 2010).

Throughout the process, there are several points where interactions with the FDA are necessary. The first occurs after preclinical testing where an investigational new drug (IND) application is submitted for approval. While there can be meetings with the FDA before this application, this application is the first step to starting clinical testing in humans. Throughout the clinical testing phase, there are meetings are reports required which determine if the drug moves to the next phase. After completion of phase 3 trails, a full application is then submitted for approval to the FDA (FDA, 2015). Under the Prescription Drug Act (PDUFA) fees must be paid to the FDA and must be paid prior to approval of the drug by the FDA. However, if a drug is granted Orphan Drug status, and is going to be used to treat a rare disease, then no application fee is required to be paid (FDA, 2018b). If the drug is granted breakthrough status, meaning that it a novel therapy for a severe disease for which no highly effective treatment exists, then the FDA will expedite the review and development process of the drug. This means that the drug will go through an accelerated approval process (FDA, 2018a).

In the case of development of Ziblofril, there are several sections of the Code of Federal Regulations (21 CFR) which are applicable. In particular, section 601.2 states that monoclonal antibody products for in vivo use require a biologics license application (FDA, 2017). In addition according to section 316, which pertains to orphan drugs, then an antibody must be considered to have a sameness in order to obtain the orphan drug status (FDA, 2016). Overall, when it comes to the development of new drugs, there are many different steps and regulations involved. As such a full understanding of all steps of the process is necessary to ensure the smooth transition of the drug through all stages of the process.