Complex drug products are the dosage forms with complex active pharmaceutical ingredient (API), complex formulations, complex routes of administration, complex drug-device combination, complex physicochemical testing or any other product where complexity or uncertainty concerning the approval pathway. Complex drug products have been broadened to include dosage forms for one reason or another present an atypical challenge in either drug formulation development, manufacturing or administration.
Biologics exemplify one category of complex drugs, but there are also non biological complex drug products including sterile products (extended-release injectables), transdermals, metered dose inhalers and nanomedicines including emulsions, liposomes, polymeric microspheres iron-carbohydrate complexes, etc. In considering the above, complex drug products encompass a wide range of technologies including solubilization & bioavailability enhancement techniques and various pharmaceutical formulations containing controlled substances or highly potent active pharmaceutical ingredients (APIs). Nanotechnology provides a growing number of innovator-driven complex drug products.
Controlled substances such as opioids have high potential for addiction and it also requires strict documentation and interaction with the DEA. However, many of these controlled substance active pharmaceutical ingredients (API) are essential for treating conditions such as PTSD, addiction, depression, acute pain or CNS disorders.The controlled substance drug formulation is a type of complex drug product since controlled drugs come with increased risk profiles and require extra paperwork and enhanced containment.
Producing controlled substances drug formulation is really no different than producing them for other pharmaceutical formulations. All require cGMP facilities, equipment, expertise, and other infrastructure, but they can be more costly to produce and require extra control in terms of quality, authorizations, licenses, quotas, and levels of security. The mentioned attributes add extra layers of complexity both scientific and regulatory in controlled substance manufacturing & development.
Additionally, all facilities and personnel are subject to additional audits from the DEA to maintain licenses for the controlled substance manufacturing and packaging.Monitoring methods for the controlled substances must then be established, and actual handling of the controlled drugs may require specialized PPE and equipment, an isolator that separates the compound from the greater environment.
Employees involved in the controlled substance manufacturing and development are also subjected to regular scrutiny from the DEA, who can audit a facility and its operations at any point to maintain licenses for the drug product development of controlled substances along with their manufacture, storage and distribution.
Quality assurance is particularly important, and controlled substance drug product manufacturers must follow established and validated methods of preparation.
Contract development and manufacturing organizations (CDMOs) that may have experience and expertise in complex drug product development including controlled drug formulation development may offer controlled drug handling services, formulation services and controlled release drug formulation development services. In addition, these organizations may provide pre-formulation services, formulation development services for clinical trial materials which can ultimately accelerate drug development process from early phase development to clinical development and commercialization.