4 Tips for Your Preclinical Development Plan

Are you or will you soon go through early drug development stage?

The preclinical development is a critical phase during which important feasibility, iterative testing, and drug safety data are collected.

It includes all the tasks required to advance a new drug candidate through manufacturing, formulation, pharmacology, pharmacokinetic and toxicology testing.

If you are looking for guidelines, or tips to implement a preclinical development stage, you should be interested in this article.

Know the typical timelines

You should know that the typical timeline for preclinical testing programs is around a year or so. The program is divided into different stages, each one reserved for certain tasks.

At first, from the in-house discovery to the candidate selection, about a month is the average time spent.

Then begins the analytical developments. It means that the biological analysis and chemistry of the compound are conducted to study its stability. This stage lasts until the candidate compound is tested in a clinical trial and even after. In fact, the objectives of the preclinical safety studies are to define pharmacological and toxicological effects not only prior to the initiation of human studies but also during clinical development.

The non-clinical toxicology study begins in parallel with analytical development. This stage enables to study the pharmacokinetics of the candidate. This stage lasts around 10 months and allows to determine all the data that are required to constitute the application for marketing:

• Mechanism of action.
• The rate of diffusion in the body.
• Distribution of the molecule in the tissues.
• Active doses.
• Mode of transformation and elimination by the organism.
• Compound becoming and environmental impact.
• Toxicity.

Then, the last stage before going to clinical trial is preparing the regulatory documentation. This, you can begin after the first four months and give yourself about 6 or 7 months to finish.

Understand the elements on which the preclinical plan will depend

The development of the plan relies on several elements :

• The product type and if it shares similarities with existing agents, from which you already have safety profiles.

• The indication in human, for which the candidate compound is proposed. The pathology (cancer, arthritis, etc…) impacts the plan.
• The duration and the route of administration of the product. If it is short term or chronic for example.
• If you have a certain target population, pregnant women, infants or elderly.
• If you use a compound under pattern consideration.

The study also adjusts specifically for the compound under development when choosing the animal species for the tests. The animal chosen should be sensitive to the compound for example. There is also a cost issue. When performing a study, with a single dose of a drug a day, using rats is half cost compared to using dogs.

And if you expect certain toxicity it can also guide you in choosing the dose range of pilot studies for example.

Be aware of the challenges

Some challenges are typical, some will be unexpected. But you can be sure to face challenges during your preclinical development plan.

The lack of certain resources such as money or expertise in product development is a real issue. You can overpass this by outsourcing part of the required analysis.

Make sure you have a precise clinical plan. When you don’t have a clear and defined vision of what should be done and when, your team will probably face misunderstandings, resulting in delays in the development of the drug. In preclinical studies are not designed, conducted and interpreted correctly, it adds considerable time and expenses to the program.

During the manufacturing stage, a lack of test article, problems in the formulation or scale-up issues can be a slowdown.

Even if the investors are in the heart of the matter, they can be a big pressure. Meeting the deadlines isn’t always easy. Make sure you communicate a lot with them. If they understand your plan and your status, they will not be surprised if you face unexpected delays. If they feel fully involved in the project as a regular part of your team, they can be very supportive…

The last but not the least is management. Make sure you have a complete overview of what is going on. You may use software to organize everything: from contract laboratories for the preclinical development and analytical stages to contract manufacturers for supplies of test articles, and consultants for regulatory affairs or even biostatistics analysis.

Write a compliant Clinical Trial Application in Europe

The purpose of a well prepared preclinical development plan is to lead to a compliant clinical trial application. The key elements of a European clinical trial application portfolio usually include several documents.

The Investigational Medicinal Product Dossier: it includes summaries on the quality, manufacture, and control of the product. Also, data from preclinical studies and from its clinical use. And an overall risk-benefit assessment, as well as critical analyzes of the data on the potential risks and benefits.

The Investigator’s Brochure: it is a summary of information about the candidate compound obtained during a drug trial. It is intended to provide the investigator with insights necessary for the management of the clinical trial. It stipulates the dose (of the study drug), the frequency of dosing interval, methods of administration and safety monitoring procedures.

The clinical trial protocol: It includes information such as the objectives of the trial; the proposed endpoint; the specificities of the population on which the trial is conducted (size, gender, age,…); the estimated duration of the trial; and other information of that kind.

To finish with, you will need to add the patient’s information leaflet and of course, the related informed consent form.

A successful preclinical development program resulting in a high-quality submission relies on several details :

• Get prepared to face the challenges you will have to go through.

• Understand that animal toxicology data impacts the clinical trial design and vice versa.
• Co-ordinate toxicology and manufacturing to ensure the high-quality product is available when it needs to be (with all the information about purity, stability, identity, and quality very well documented).
• Have a regulatory strategy, meaning that if you don’t have experience, you might want to outsource to a consultant for help.