There are six generics per branded oral product. Guess how many for Long-Acting Injectables (‘LAI’s)?- Less than 1 per branded product!

The scarcity of generic alternatives for LAIs is not sufficient to create price competition and offer options to patients. There is a clear opportunity for improvement in policy and regulations and innovative methods to enable generic entry for LAIs.

Several life-saving medicines are too costly. Millions of patients can benefit from pharmaceutical innovation only through generic products due to cost reasons. Lack of generics is a national crisis. In an era of increasing chronic diseases, medication adherence is a major challenge. At times even for a single medication, multiple doses need to be administered daily. One of the key alternatives is long-acting injectables (‘LAI’s).Long-acting injectables are pharmaceutical formulations that release drugs slowly and do not have to be administered frequently. They are complex to design, produce and manufacture. For many large, complicated molecules, the preferred formulation is that of an injectable or an implant.

There are mainly three types of ‘LAI’s.

1. Oil-based injectable solutions
2. Suspensions (Suspensions of active pharmaceutical ingredients without a carrier and Microparticles)
3. Implants

‘LAI’s have the edge over other formulations because they aid patient compliance, which helps with medication adherence.

In severe psychotic disorders and schizophrenia, ‘LAI’s prove to be a better choice, as they show stable blood levels while minimizing the need for repetitive dosing. Patients fear disease relapse; ‘LAI’s reduce this risk. The main challenge in the field of research for ‘LAI’s is to develop generic versions. They are therapeutically equivalent medications, meaning the patients can experience equal therapeutic outcomes to their existing marketed brand-name counterparts. Generic drugs are made after the expiry of the marketed patent of the original drug. The generic medicines cost less than their marketed brand-name counterparts because of lower R&D expenses than innovators. The generic manufacturers do not need to repeat clinical trials that were required for the branded drug.

If multiple generic companies are allowed to market the same product, it creates competition in the market and further lowers prices for patients.

Long-acting injectables are complex drug products, and most ‘LAI’s require a full clinical program to get approval and follow the 505(b)(2) NDA pathway with few following 505(j) ANDA pathway While generic ‘LAI will further help improve compliance with lower drug prices, bringing generic LAIs to market is complex. The main challenges in the development of generic ‘LAI’S include:

1. Ensuring equivalent therapeutic response due to continuous exposure

2. Maintaining continuous exposure for a set duration.

3. Ensuring controlled lot-lot variability of product performance characteristics such as rate of drug release.

Unfortunately, the current regulatory pathway for complex generic ‘LAI’s is slow and not efficient as show below using publicly available data from FDA.

LAI insights from FDA data using Vivpro’s RIA:

We sought to compare the availability of generic alternatives for medicines approved from 1/1/2001 through 12/31/2010 and for products marked as reference listed drugs (RLD). To improve the comparison, we removed discontinued and over-the-counter (OTC) products.

A total of 514 RLD products were identified. The following table provides an average number of generics approved by route of administration. This table excludes routes of administration for which there are less than five total products in a category.

It is evident from the table that the development of generic alternatives for complex products and long-acting products is challenging. For products approved for oral administration, there are on average six generic products compared to 1.3 for intramuscular, 0.9 for Transdermal, and 0.22 for subcutaneous administration. As most LAI’s will be intramuscular or subcutaneous products, it is clear that there is an average of 1 or fewer generic alternatives for LAIs.

The scarcity of generic alternatives for LAIs is not sufficient to create price competition and offer options to patients. There is a clear opportunity for improvement in policy and regulations and innovative methods to enable generic entry for LAIs.

Lead Author: Anoushka Gangal, Vivpro Corp