This infographic describes the drug development process leading up to phase 1 clinical trials. These are steps that companies must perform for each drug they are trying to get into the clinic. While many recognize how difficult it is to discover a drug, a significant portion of the costs and challenges of getting a drug into the market actually lies in the manufacturing process.
Many people are very familiar with drugs that come in the form of a tablet or capsule. They don’t think much about it, but there’s a lot that goes into deciding why and how drugs are prepared for human intake. Dosage form, such as a tablet or capsule, affects whether a drug gets to the right place or not, and how quickly. The following describes key steps in the drug development process.
The first step of the drug development process is called pre-formulation development. Before we even think about what physical form would be best to package the drug, we have to understand the drug’s physical and chemical properties. This knowledge guides us on decisions, such as the kinds of excipients to use and the type of dosage form that is most appropriate to produce high bioavailability, or how the majority of the administered drug gets into the systemic circulation of the patient.
From the pre-formulation work, we move into pilot formulation development stage, in which we create a pilot batch of the drug product. This batch is used to conduct pharmacokinetic, pharmacology and toxicology studies in animals. Though the pilot batch can be used for in vivo animal testing, it still needs work before it can be given to humans in a clinical trial.
After creating and testing the pilot batch of a drug (as part of the drug product formulation development stage) and getting approval from the FDA, the next step is manufacturing clinical supplies for a clinical trial. This manufacturing occurs under current good manufacturing practices (cGMP) that are determined by the FDA. This ensures that the product is of the highest quality before being administered to humans.
In order to obtain the highest manufacturing quality, specific methods of testing a drug must be developed. IRISYS has a group of analytical chemists and quality control scientists who develop methods for determining the quality of a drug product. Quality is defined by how much drug is present in a dosage form, and how much of the drug is released in several in vitro conditions. These data guide how quality during manufacturing can be controlled. The methods that we develop have to be assessed in a way that ensures that the methods themselves are of high quality. This level of stringency allows for determining how much drug is present, and also evaluating specific measurements that are uniquely required for each drug product.
While manufacturing clinical supplies, we have to be sure that the product is stable and doesn’t lose its properties over time. The required shelf-life period varies for each drug but should last at least the length of the clinical trial. These properties will dictate the product’s expiration dates.
Stability studies can be time-consuming but our experience allows us to perform many tests in parallel while maintaining quality. This saves time for our customers who are waiting for results.
Once we have developed the drug product and our QC group has verified that it is stable, we then package and label the clinical supplies. They are then shipped to the site where the phase 1 clinical trial will be performed.
Beyond manufacturing and testing for quality, IRISYS helps with regulatory work that is required before a drug is permitted to enter a phase 1 clinical trial. This includes participating in the pre-IND meeting. An “IND” is an investigational new drug application that is required to be approved by the FDA in order to conduct human clinical trials. In the pre-IND meeting, we discuss aspects of a drug product with the FDA and what our customer plans to do along the development pathway. The FDA gives feedback about whether the customer is going in the proper direction, and also outlines how to proceed once the IND is approved for clinical trials in humans. The pre-IND meeting is extremely important for getting the IND approved. At IRISYS, we always recommend that clients go through a pre-IND meeting, because it’s a very cost-effective way to help lay out the entire drug development process and to get the FDA’s input for a higher chance of approval.
The pre-IND meeting can be done at any point before you file the IND; it depends on the product.
For most drug products that we routinely produce, such as small molecules that are similar to previous drugs, we all have a very good idea of what nonclinical or preclinical studies have to be included in the IND. In these cases, the pre-IND meeting can occur after you have data on the drug in terms of safety, toxicology, and pharmacology.
However, there are instances the pre-IND meeting should take place earlier, because you can gain clarity on best practices for your drug. The FDA gives valuable advice about what to do in terms of toxicology studies, safety studies, and manufacturing. This saves you from wasting money because you went in the wrong direction. The timing of the pre-IND meeting is a case-by-case basis. The point is to avoid spending a lot of money down the wrong path only to have the FDA tell you, “Yes, you’ve done a lot, but the studies we really wanted are these other ones.”
Once the pre-IND meeting is completed and you have ideas from the FDA about how to go forward, you can submit the IND application. The submission must now be done electronically. IRISYS helps with the submission through what’s called an “electronic Common Technical Document,” or eCTD. When the IND, which is a very big document containing all your studies is submitted, the FDA has 30 days to review it. They then inform you that it’s okay to proceed with your phase 1 proposed clinical trial, or that you must go back and do additional studies.
Because of the pre-IND meetings, the FDA has an idea of the number of submissions that may be coming in. Ideally, the FDA should spend more than one month on each IND, but this time period is a long-standing protocol. The FDA maintains enough staff members to work within a 30-day response time. Also, experienced FDA reviewers have seen a lot of different submissions, so they know what to look for each type of drug. They can quickly decide the level of risk in allowing the company to go forward. If they are unsure of the data that you submitted, or unsure of the clinical trial proposed, they can always put a hold on the process. They will send you a letter asking questions or for additional information, which extends the 30-day review window until they are satisfied with your answers.
This is a summary of the drug development process up to phase 1 clinical trials. Later, we’ll discuss the other phases of drug development and what IRISYS can do to bring your drug development program to a successful conclusion.
Don’t hesitate to contact us for advice on developing your drug and getting it through the IND approval process. Our experience will save you time and money. Our team is ready to make your goals a reality. We know what are best practices for each type of drug, so you can have peace of mind that your efforts are cost-effective. Contact us today!