At AAPS San Antonio yesterday, experts in the field of inhalation, dermal and ocular drug formulation discussed whether FDCs were a feasible alternative to single API products and though there are limited drawbacks for manufacturers and patient, the answer was equivocally they were.
Head of Respiratory Product Development at Merck & Co. Brent Donovan told the room for an ICS/LABA (Inhaled corticosteroid/Long-Acting Beta-Agonists) asthma drug, the combination beat giving the patient individual APIs for both peak expiratory flow and quality of life studies, even when compared to increasing the dose of the individual APIs alone.
However, Donovan acknowledged that though such studies advocate the use of FDCs, combining two APIs together from a manufacturer’s angle is almost always more than twice the overall workload with additional effort and costs required to ensure the two compounds are complimentary.
David Marsh, a Research Investigator at Allergan, echoed Donovan’s views, though used ocular examples to highlight the case. Combinations, he said, had a number of advantages for the patient including a reduced prescription cost (as the patient is technically paying for one product rather than two), increased compliance, lower exposure to preservatives and improved efficacy.
He also argued the drugmaker can reduce manufacturing costs and, more importantly, can register an FDC as a new product extending the exclusivity of two APIs and even receiving a brand new patent.
Like Donovan, he did admit there are a number of drawbacks from the formulation perspective and the necessity to ensure the two APIs are complementary is challenged by differences in stability, toxicity and the chance of adverse effects.
Jean-Philippe Therrien from Stiefel – a GSK subsidiary – acknowledged there were these same issues for dermal combination products (DCPs), telling the room though his company had proven success in a number of two product DCPs, there was no formulation option for an attempted triple combination of BPO, Tazarotene and Clindamycin in cream form.
Regulatory Definitions, and What is a Prefilled Syringe?
A combination product, as the name suggests, involves two products being put together. However, from a regulatory perspective the US Food and Drug Administration (FDA), has four classifications for such drugs and, Marsh said, its European counterpart has similar:
Class I is for a combination of products where the components are physically, chemically or otherwise defined, and includes devices.
Class II, where the components are packaged together such as in prefilled syringes, which led to the question whether – with the proviso of Category I – a single API prefilled syringe is technically a combination product. According to Marsh the FDA regard these as FDCs and therefore they must undergo the same regulatory pathway for approval.
Class III is for a combination of an investigational product and an approved product, whilst Class IV is to define two investigational products