These long-acting products drastically increase compliance, improve patient outcomes, and provide additional economic opportunities for their sponsors, but they are considered complex drug products due to the following: As an example, long-acting depot injections have been developed for indications ranging from anti-virals to CNS indications to contraception. In addition, intellectual property can be gained or circumvented using this approach. These approaches can greatly improve convenience, economics, and even efficacy. This route of approval has become increasingly popular over the last decade and usually involves innovative dosage forms or drug delivery methods that are considered complex. More 505(b)(2) Products: In 2017, there were 63 drug product approvals that used the 505(b)(2) regulatory pathway-an all-time high.As a result, these products must be injected and require sterile processing, which adds to the complexity of manufacturing. For large molecules, bioavailability (oral) concerns are often accompanied by stability and microbial contamination issues. For example, a typical BCS Class II small molecule’s oral bioavailability can usually be substantially increased by reducing particle size. Various complex approaches can address this issue. For small molecules, this is usually related to bioavailability – the API is not soluble and/or has low permeability.
Challenging new APIs: Newer therapeutics are frequently not amenable to simple approaches, such as traditional solid oral dosage forms.Injectable products such as suspensions, emulsions, and depots can create complex formulation and manufacturing challenges. So what has led to this increase in complex drug products? Generally speaking, there are two main drivers: Complex processing challenges include, among others, aseptic manufacturing, the inclusion of highly potent compounds, milling/particle engineering, spray drying, extrusion, and microfluidization. Product technology examples in this sector include nanoparticles, drug-eluting systems/devices, liposomes, polymeric microparticles, and so forth. While complex products are gaining popularity and there are hundreds of advanced delivery platforms in development, only a handful of technologies are of practical use at this time. Other products where complexity or uncertainty concerning the approval pathway or possible alternative approach would benefit from early scientific engagement.Complex drug-device combination products (e.g., auto-injectors).Products with complex active ingredients (e.g., peptides, polymeric compounds, complex mixtures of ) complex formulations (e.g., liposomes, colloids) complex routes of delivery (e.g., locally acting drugs, complex ophthalmological products and otic dosage forms that are formulated as suspensions, emulsions, or gels) or complex dosage forms (e.g., implantables, transdermals, metered dose inhalers, extended-release injectables.In fact, complex drug products have become so prevalent that the FDA has defined them with the following categories: And with this trend, the definition of complex drug products has been broadened to include dosage forms that for one reason or another present an atypical challenge in either manufacturing and/or administration. However, with the rise of insoluble APIs, biologics, and 505(b)2 applications, complex dosage forms are quickly becoming the norm. In the past, “complex” drug products simply referred to uncommon products that weren’t your typical tablet. Implantable Drug Delivery Systems and Combination Products.Stability Indicating Method Development.Analytical Method Development and Validation.Solubility & Bioavailability Enhancement.
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