Manufacturing

Developing Drug / Device Combination Products : Concept to Commissioning

 

Dr. Atul Sardana, Chairman, Alfa Corpuscles Pvt. Ltd., New Delhi

Definition of Drug/ Device Combination • A Drug Device combination is a product comprising of active pharmaceutical ingredient(s) and a medical device that are physically or chemically combined to produce a single product. • Such combination products are emerging as innovative medical products due to their contribution in advancing medical care and are thus expected have an impact in the coming years. • These offer several advantages including reduced adverse/side effects, improved patient compliance, controlled release of drugs and targeted drug delivery, overall reduction in healthcare expenses and augmented performance.

Classification of Drug/ Device Combination

• “Single Entity” or “Integral” product comprises of two or more different regulated components (drug/device) that are physically, chemically, or otherwise combined or mixed.
• “Co-packaged” or “Kitted” unit in a single package comprising of drug(s) and device(s).
• “Cross-Labelled” comprise of drug(s) or device(s) packaged separately that according to its  investigational plan or proposed labelling is intended for use only with another individually and where both are required to achieve the intended use, indication, or effect.

 

Examples of Drug/ Device Combinations
“Single Entity” or “Integral” • Prefilled Drug Delivery Systems - Prefilled syringes - Prefilled autoinjectors - Prefilled pen injectors - Prefilled on-body delivery systems - Dry-powder inhalers - Metered dose inhalers - Prefilled nasal sprayers - Transdermal patches - Oral Vaccine Delivery Devices	• Medicated Devices - Drug-coated stents - Drug-coated catheters - Drug-coated pacemaker leads - Antimicrobial surgical scrubs - Antimicrobial wound dressings - Antimicrobial Sutures - Drug impregnated surgical mesh - Antibiotic bone cements - Spermicidal condoms	Examples of Drug/ Device Combination “Co-packaged” or “Kitted” • Convenience kits - Surgical trays with anaesthetic and/or surgical scrub - Vial and syringe packs - Injector pen with userloaded prefilled cartridge - Liquid medication with dose- dispenser	• Other - Collagen sponge with bone morphogenic protein “Cross-Labelled” • Companion diagnostics • Photodynamic therapy (laser activated drug) • Contrast agent and diagnostic imaging • Iontophoretic delivery systems

The Development of Drug/ Device Combination entails the following steps :

1. Unmet Need Identification

• A Device may require a drug to
• Improve its Safety especially over long term implantation or when being placed in pathological conditions or challenging environments within the body.
• To augment the function of the device by providing synergy
• To enhance the efficacy of the device by suitably modifying the local or systemic conditions
• To reduce device associated co-morbidities and complications.
• A Drug may need a Device in order to :
• Ensure or regulate proper dosing
• To provide a constant rate of drug elution and sustained release
• To monitor drug release and concentration levels as in a loop feedback
• Improve patient compliance
• To ease administration and make self administration possible.
• To enhance the shelf life of the drug
• To reduce filling and administration losses and drug contamination
• To improve drug safety
• To provide targeted drug delivery

2. Design Development

Design development of a drug device combination needs in depth understanding and critical analysis of the following :

• Understanding the drug device Interphase with the body
• Understanding the interactions between the drug and the device throughout the product life cycle

Raw Material Selection for the device is based on the following criterion that need to be evaluated in all phases of the product development and use.

• Leachable interaction with the body and the drug
• Extractable interaction with the body and the drug
• Additives and Coatings to be used on the device and their interactions with the drug.
• Barrier Properties of the Material and effects of oxygen, moisture and other gases on the drug.
• Stability Testing of Drugs in the drug device combination
• The effect on drug(s) on Polymer(s) properties and function
• DMPK (Drug Metabolism and Phamacokinetics) Study
• Shelf life study and accelerated ageing of the drug device combination
• Method of sterilization to be used for the combination with respect to drug stability.
• Prototyping challenges for drug device combination usually preclude 3D printing as the combination needs to be tested with actual polymer proposed. Though it may be used for mechanical and dimensional validation.
• A thorough understanding by the devices manufacturer is required with regards to the drug filling lines and due consideration should be given to the environmental challenges of the aseptic conditions to be maintained.