Postcommercialization activities

Postcommercialization activities

Commercialization of a drug product involves many different functions in addition to the research and development (R&D). Key commercializa-tion functions that intercept with R&D are marketing, finance, and man-ufacturing. The marketing function identifies the regions and countries where the drug product should be marketed, as well as the country of first approval, the competition in the same therapeutic category, and the desired product characteristics. Finance function provides input regarding cost-of-goods analyses and feasibility of a particular product and technology. The manufacturing function is responsible for day-to-day operations in repro-ducibly producing the drug product to meet market demand.

The postcommercialization involvement of R&D with a particular drug molecule focuses on three areas: manufacturing support, intellectual prop-erty, and life cycle management.

Manufacturing support

As the manufacturing operations produce multiple batches, they may face unforeseen problems that require R&D input and troubleshooting. These problems often come from changes in the input raw material properties (CMAs) or some drift in the process parameters (CPPs) and reflect as an impact on the quality attributes of the drug product (CQAs). Although the manufacturing personnel themselves usually address common problems, the ones that require additional research are usually brought to the inter-face with R&D. Additional development activities often result in the iden-tification or refinement of current CMAs or CPPs.

The regulatory bodies restrict postapproval changes to the drug sub-stances or drug products, or their manufacturing process. Thus, a sponsor of an NDA or a BLA is required to manufacture the drug product within the confines of what was filed at the time of seeking the approval. If a signif-icant change is required post approval, depending on the nature and extent of change and its impact on the drug product, the sponsor must seek the FDA’s approval before implementing this change in commercial operations.

Intellectual property

Intellectual property, in the form of patent rights, forms the cornerstone of ensuring profitability on commercialization of new medicines. This mecha-nism serves a significant social need of providing sufficient incentive to encourage individuals and organizations to invest in developing new medi-cines for unmet medical needs.

A new compound, when entering the development pipeline, is patented by the innovator company. A typical patent life consists of discovery and development of the compound through various stages of clinical trials. On commercialization, the patent provides exclusive marketing rights to the sponsor and allows the sponsor to recoup the cost of developing the drug. The commercial return on investment increases with time as the drug gains increasing acceptance. On expiration of the patent, the profits of the inno-vator company decline significantly due to generic competition and price reduction. Thus, an innovator company is under constant pressure to con-tinue the discovery and development of new medicines to replace the ones that would predictably expire at the end of their patent life.

In addition to pursuing new compounds, innovator companies also seek to extend patent life by filing additional patents that would provide signifi-cant value addition to the molecule. These fall in the category of life cycle management.

Life cycle management

Typical life cycle of an NCE/NME is several decades, with different stages that can generally be characterized as follows:

·           An NCE/NME is first conceptualized and synthesized during discov-ery. A patent that assigns the commercial rights of this compound to the sponsor is filed.

·           The compound is nurtured through different stages of clinical trials and commercialization, during which process it evolves into a drug product.

·           The drug product is commercialized, it gains widespread acceptance and use, and the sponsor is able to recoup the investment in the com-pound through exclusive commercialization for the duration of the patent life.

·           On expiration of the patent, several generic competitors enter the market, which significantly reduces the profitability of the sponsor in this compound. Market viability and lifetime of the compound then depend on market conditions such as the disease state, other mol-ecules or therapies available, and patients’ need.

The R&D efforts postcommercialization of an NCE or NME are targeted on improving the value proposition from the compound, with a goal of increasing patent life. These could include, for example:

·           Improving some aspect of the drug product that increases the value proposition, such as higher bioavailability or reduction in variability in drug absorption. For example, an improvement in the drug prod-uct, such as micronization of the drug, that overcomes the effect of food or gastric pH on oral absorption.

·           Different route of administration. For example, conversion of a previ-ously IV route of administration to subcutaneous route can lead to significant patient benefit, in terms of convenience, and the ability to self-administer the drug in an outpatient setting.

·           Combination of drug product with another compound that leads to synergism in therapy. For example, amoxicillin is often coadminis-tered with clavulanic acid, saxagliptin is coadministered with met-formin, and several antihypertensive drugs are coadministered in a single-dosage unit.

·           Introduction of drug–device combination products, such as insulin pens or pumps.

·           Increasing label claim to include coverage of additional disease states. For example, an oncology drug approved for a given indication can increase its market by seeking approval for additional indications if clinical studies are done to prove its efficacy.