Developing Drug / Device Combination Products
: Concept to Commissioning
Dr. Atul Sardana
Chairman
Alfa Corpuscles Pvt. Ltd., New Delhi |
Definition of Drug/ Device Combination
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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.
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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.
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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.
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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 user-loaded prefilled cartridge
- Liquid medication with dosedispenser |
• 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
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A Device may require a drug to
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Improve its Safety especially over long term implantation or when being placed
in pathological conditions or challenging environments within the body.
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To augment the function of the device by providing synergy
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To enhance the efficacy of the device by suitably modifying the local or
systemic conditions
To reduce device associated co-morbidities and complications.
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A Drug may need a Device in order to :
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Ensure or regulate proper dosing
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To provide a constant rate of drug elution and sustained release
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To monitor drug release and concentration levels as in a loop feedback
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Improve patient compliance
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To ease administration and make self administration possible.
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To enhance the shelf life of the drug
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To reduce filling and administration losses and drug contamination
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To improve drug safety
Classification of Drug/ Device Combination
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“Single Entity” or “Integral” product comprises of two or more different
regulated components (drug/device) that are physically, chemically, or otherwise
combined or mixed.
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“Co-packaged” or “Kitted” unit in a single package comprising of drug(s)
and device(s).
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“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.
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To provide targeted drug delivery
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2.Design Development Design
development of a drug device combination needs in depth understanding and
critical analysis of the following :
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Understanding
the drug device Interphase with the body
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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.
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Leachable
interaction with the body and the drug
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Extractable
interaction with the body and the drug
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Additives and
Coatings to be used on the device and their interactions with the drug.
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Barrier
Properties of the Material and effects of oxygen, moisture and other gases
on the drug.
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Stability
Testing of Drugs in the drug device combination
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The effect on
drug(s) on Polymer(s) properties and function
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DMPK (Drug
Metabolism and Phamacokinetics) Study
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Shelf life
study and accelerated ageing of the drug device combination
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Method of
sterilization to be used for the combination with respect to drug
stability.
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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.
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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.
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The Current Challenges faced During the Development and Marketing of Drug /
Device Combination can be summarized as below :
1.During Manufacturing of the Drug Device combination the following
challenges may be encountered
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Large Scale Manufacturing
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Device Filling in Aseptic Lines with Drugs
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Replication of the Drug Impregnation / Coating process on commercial scale
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Combipack Development
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Integration of Automation
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From Production to Filling/ Coating
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Validation Protocols to be used
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Clinical Trials requirements for Novel Devices
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Packaging Requirements (Intermediate and Final)
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Filling Lines
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Sterility of Ready to Fill Systems in Aseptic Lines
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Labeling for Regulators and Users
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Choice of Sterilization Methods
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Standardization of Exchange of Data amongst Device and Drug Manufacturers
2. Affixing Responsibility
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Post Market Clinical Feedback
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Post Market Surveillance
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Vigilance and Incident Reporting
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Complaints
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Corrective and Preventive Actions
3. Classification of Drug/Device combinations in the currently prevailing law
in India.
4. Regulatory Approvals
5. Legal and Intellectual Property Right Issues amongst the parties involved in
collaborative development (drug manufacturer and device manufacturer) |