Strategies to Facilitating Accelerated Drug Development

Accelerated Drug Developmentis an approach where FDA expedites the approval process and give the final approval in less time as compared to drugs in traditional approval. The program is implemented for medicines that are critical for the treatment of serious conditions that have previously been not developed.

An important element in accelerated drug approvals are surrogate markers, used to correlate outcomes of a drug. The FDA uses surrogate markers to ensure the efficacy of the developed drug before giving approval under accelerated drug approval.

However, even after giving accelerated approval based on surrogate markers, clinical studies are necessary to correlate the results with clinical outcomes. If at this stage, the drug fails to prove its clinical benefit, the FDA can withdraw approval of that drug.

The contrary to the accelerated drug development is full approval that follows all steps i.e. discovery & development, preclinical research, clinical research, FDA Drug review and FDA post-market drug safety monitoring, and could take more than six months for final approval.

What are the FDA guidelines regarding the Accelerated Approval?

The current and relevant FDA guideline is “Guidance for Industry Expedited Programs for Serious Conditions – Drugs and Biologics”. In it, the FDA describes many forms of expedited approval programs, including the Accelerated Approval.

The current applicable guidance is finalized in May of 2014. However, FDA has issued draft guidance on this subject, which is distributed for comments and feedback.

What is the meaning of the term “serious condition”, and what type of drug fulfils these criteria?

Serious Condition

The major aim of accelerated approval is to speed up the availability of therapies for serious conditions as soon it is established that the drug’s therapeutic effects are sufficient, without digging deep into the complexity of clinical trials.

But what justifies the definition of a serious condition? The FDA has also provided the answer to that.

According to the FDA guideline and in its section III – A (1), a serious diseases or condition is a medical condition

· That impacts day–to–day functioning.

· A persistent or recurrent condition, that is not irreversible

· If left untreated, it will progress from a less severe to a more serious condition based on factors such as day-to-day functioning and survival.

Drug characteristics for treating serious conditions

According to this guideline, the drug for the treatment of serious conditions must possess the following characteristics

· The drug intended for the diagnostics or treatment must have improved outcomes for the patients or end users.

· The drug must be able to prevent or mitigate side effects related to a serious treatment. For example. Infection in patients undergoing immunosuppressive therapy

· a drug intended for diminishing or avoiding serious adverse effects related to available therapy targeting serious illness, such as less cardiotoxic than available cancer therapy

· a drug for preventing a serious condition or to reduce the likelihood of progression to a more serious condition

Strategies to facilitating Accelerated Drug Development

Let’s discuss some strategies to facilitate accelerated drug development

Using the latest Technology to support accelerated drug development

Latest technologies, such as Artificial Intelligence – AI and Machine Learning ML, can be used to replicate and create experimental data, which is critical in the development of pharma drug products. One downside of traditional experimentation is that it requires time and effort to support the under-developed drug. And for the drugs under the accelerated program, time is critical and traditional experimentation cannot be implemented.

AI and ML can create experimental data models for studying the effect of the drug under consideration. They can design the target drug substance model without practically and physically making them. Additionally, they can also be used to predict the outcome and side effects related to a particular drug product.

High-throughput screening

High-throughput screening - HTS is a method where a compound that targets specific diseases is identified. The capabilities of HTS can be used in accelerated drug development to screen large groups of compounds practically.

The main advantage of HTS is that it helps drug developers follow a realistic path with specific conditions that facilitate accelerated drug development. It can simplify the developmental process.

Computational Methods

Computational methods utilize computer models and simulations to predict drug compound and can also be used to optimize molecules.

In this method, a complex algorithm is used to pinpoint drug compounds for drug developmental purposes.  This, in turn, saves the researcher’s time and money for using on sourcing, arranging and analyzing large amounts of data. This is also beneficial as compared to the traditional approach, which usually occurs on trial & error basis.

Real World Data

Real-world data indicate the patient health status collected from different sources, such as electronic health records, medical claims data and many other data sources, that resides outside traditional clinical trials. RWD can be used to gain insight into a specific drug on a certain population and disease.

RWD enables accelerated drug development by enhancing clinical trials by helping to identify populations that have either more chances of benefitting or not benefitting. It could be more beneficial for instances where rare drug products are being developed and specified patient population is not easily available.

It can also be used with simulation modes to test a drug instead of on real patients.

Adaptive Trials

Adaptive trials can be used to change product parameters, without wasting for end results. It enables researchers to timely identify any deviation in desired results during developmental process, and act accordingly.

Decentralized Trials

Clinical trials pose many challenges, such as excessive travelling, dependency on geographical location and adherence to culture for the participants.

These factors, and many more alike, create delay in completing their trials, and affect the drug availability to patients

 To cater for this problem, the concept of Decentralized trial has been introduced. It uses digital and innovative solutions to complement the physical presence of both participants and researchers in a single location.

Technologies such as telemedicine and apps collect patient-specific data. At the same time, drugs and materials can be directly delivered to the patient’s location.

For the benefit and methods mentioned above, decentralized trials can be used to accelerate drug development by preventing and avoiding hindrances, such as the unavailability of participants and logistical burdens in traditional clinical studies. Additional advantages include improved patient participation, real-time data, cost-effectiveness and flexible design.

Some features of current FDA guidelines regarding Accelerated Approval

Let’s discuss some features of FDA guidelines regarding accelerated drug development

· The FDA may allow accelerated approval for products that are serious or life-threatening depending on the surrogate endpoint likely to predict clinical benefit that is likely to benefit, taking into account the severity, rarity, or prevalence of the condition and lack of alternate treatments.

· Drugs following an accelerated approval path and post-market conformity trials are required to verify the therapeutic effect on IMM.

· An accelerated development path is used for treating a disease that takes more time to progress in its stages, development and effect. For this purpose, a longer period is required to measure the clinical benefit. Examples include a variety of cancers and HIV disease, where the therapeutic effect on tumour growth and viral load can be assessed rapidly.

· Accelerated approval is also helpful in acute disease cases that require very large studies to demonstrate the clinical benefit of the drug. This is due to the reason that the clinical event under evaluation occurs rarely. For example, in cases where the effect on surrogate endpoint could be shown in a smaller number of patients  and requires a larger study to show the impact on clinical outcome

· Sponsors should contact the agency early regarding the potential eligibility of the drug to follow the accelerated approval path, proposed surrogate endpoints, intermediate clinical endpoints, clinical trial designs, and confirmatory trials. The sponsor must also prepare itself for other aspects of drug development, such as manufacturing.

· The following is the qualifying criteria.

o A serious condition, as described earlier in this article

o The drug has a meaningful advantage over available therapies or lack of alternate treatments.

o If the drug offers more added clinical value, as compared to the existing and significant number of patients who respond differently to the new drug developed

o An endpoint that demonstrates clinical benefit

· Two types of endpoints can be used as a basis for accelerated approval.

o Surrogate endpoints that can likely predict clinical benefit

o A clinical endpoint that directly measures the theopoetic effect of a drug or how a patient feels

· Drugs under accelerated approval must meet the same statutory standards for safety and effectiveness for drugs granted under traditional approval.

· Conditions for accelerated approval

o Applicant must submit during the pre-approval review period copies of promotional material, promotional labelling, and advertisement within 120 days of following market approval.

o Post-marketing conformity trials for the verification of clinical trials must be conducted promptly.

· Withdrawal of Accelerated Approval – The FDA may withdraw approval of a drug approved under an accelerated approval program due to reasons such as

o Trial to verify the predicted clinical benefit fails

o Sufficient evidence has been established product is not safe or effective.

o Failure to perform post-approval trial with due diligence.

o False or misleading promotional material of the product

o If the FDA determines the above factors, or like, the agency may ask the applicant to request withdraw application. After receiving the application, the applicant has 15 days to file a request for a hearing in written form. If not, the applicant will lose the opportunity of hearing.