Capitalising pharmaceutical opportunities: why early-stage regulatory expertise is crucial by Kushal Vyas, ELC Group
Kushal Vyas, ELC Group
Competition in the pharmaceutical business is increasing. Companies are under pressure to invent new molecules and reprogram their existing molecules owing to major patent cliff. The generics business for conventional dosage form is becoming crowded with multiple new entrants, leading to an increased focus on high technology products, biosimilars and 505b2/hybrid products.
Given these highly competitive markets, incremental innovation patents can be very helpful to brand companies by extending the product lifecycle.
Examples of key incremental innovation patents include protections of: Salts; polymorphs; crystal habit; particle size; purity/impurity; dosage forms; dosage strengths; shapes; method of treatment; dosage regimen; drug interactions; REMS issues; distribution system for controlled drug substances and so on
There have been court proceedings for patent infringement surrounding these issues, which has affected generic entry in some cases. Involving regulatory experts – along with intellectual property agents – at an early stage and during development, can be helpful in identifying key inventive concepts and securing protection of such critical inventions.
Generics, on the other hand are typically focused on innovative design-around to overcome product lifecycle extension strategies. Major barriers to generic entry are: Regulatory exclusivities, such as new active substance, new use, orphan drugs, pediatric studies, new combination, new dosage forms and so on; patent extensions related to delay in regulatory approval; patent linkage; patents covering basic molecule and incremental innovations and in some instances, trademarks, designs and utility models
Among these barriers, the patents covering incremental innovation listed above are more important from a design-around perspective. Additionally, increased competition and stricter regulatory guidelines have compelled generics to perform common multi-country formulation development complying with their respective regulatory authorities. Multi-country development is also important due to the difference in expiration of critical blocking patents, so that early return-on-investment can be expected from the countries with early patent expiry. In view of these issues, understanding the viability of design-around strategies and their acceptance by regulatory authorities is of prime importance. These lucrative design-around strategies, in some cases, require expensive development and clinical studies planning. For example, change of a patent-protected salt will allow early generic entry; however, due to relatively higher investment, its regulatory feasibility needs to be ascertained at a very early stage. Another example is related to purity patents, where a legally possible design-around strategy could be to use less pure API (compared to its claimed value in the patent), however these impurity value are still within justifiable broadened regulatory limits. These strategies can help in early launch of design-around products versus waiting for a 20-year patent term to expire.
Related similar issues are: Feasibility/acceptance of skinny labelling by regulatory authorities; change in dosage form, its shapes, inactive ingredients etc; BA/BE queries related to morphology/PSD; interchangeability and sameness requirement related to parenteral & other dosage forms
These issues are more complex and significant with high technology and biosimilar products due to the grant of patents on various aspects of products and relatively less advanced regulatory guidelines for such products. Therefore, anticipating and identifying a solution for these design-around queries will lead to a high probability of successful, viable products.
Both brand and generic companies can gain a competitive advantage from proactively designed strategies by involving highly skilled regulatory experts, who can visualize and resolve complex scientific and legal issues by convincing regulatory authorities beyond the general guidelines. Strategising at aa early stage – and during the development stage – can deliver better product life cycle management and differentiate generic companies by early generic entry, offering increased business certainty in a fiercely competitive and crowded market.