Name a combination product which is currently on the market such as a drug releasing stent.
Specify the primary mode of action and department you believe that the device should be under(CDER, CBER, CDRH). Explain.
Based on your selection, layout the regulatory process which would need to be done for that medical device to be marketed.
An example of a combination product is a cell seeded scaffold, which is used to repair tissue damages. I believe that this product falls under the CBER regulation because it is designed to be therapeutic and aid in damaged tissue, which requires clinical testing before it can be used. The regulatory processes that needs to be done according to the CBER regulation is that it must follow the IND, (Phase 1,2,3) or Pivotal Trials, and BLA.
Combination product of investigation: Epinephrine auto-injector (injection pen)
This device is intended to inject epinephrine directly into the patient’s body during an allergic reaction for most rapid response time. Epinephrine causes the body to delay/ stop anaphylaxis caused by the initial allergen, exercise, or other trigger therefore potentially saving the patient’s life. The delivery vessel is the needle; however, the primary method of action (PMOA) of this device is the drug epinephrine which causes CDER to be the lead agency. Lastly, the submission pathway most applicable for this combination device would be a New Drug Application (NDA) or an appropriate filling of a 505(b)2.
https://www.meddeviceonline.com/doc/how-to-determine-a-combination-product-s-primary-mode-of-action-pmoa-0001
https://www.drugs.com/epipen-auto-injector.html
Immunostimulating hydrogels are a combination product. Hydrogels depending on the peptide structure are chemically synthesized through peptide synthesis. Designer hydrogels can have small growth factors or biologics attached to the peptide strand that then forms into a hydrogel.
The hydrogel studied here acts a drug delivery vehicle that can transport chemical drugs or biologics to a designated site. The primary mode of action for this device is to deliver a sustained release of drug to the transdermal layer. This product would fall under the CBER regulations because the product is a biologic that aids in transdermal drug delivery. This product will require both in-vitro and in-vivo testing as well as clinical trial process to determine the safety and efficacy on animal and human models.
An example of a combination product: Bone morphogenetic proteins (BMPs) are a class of proteins that induce bone formation. New technology in orthopedic repair combines BMPs with a carrier matrix to create a combination product that, when implanted in a bony defect, initiates bone formation (osteoinduction) and provides local containment and cell adhesion (osteoconduction).
Example :FDA approved INFUSE bone graft, which contains a recombinant human bone morphogenetic protein (rhBMP-2),which consists of:Recombinant human bone morphogenetic protein (rhBMP-2); absorbable collagen sponge; sterile water.
Applications submitted:Separate applications submitted to CDRH and CDER: 510(k) (controller), NDA (patch)
Manufacturer: Vyteris
https://www.fda.gov/downloads/combinationproducts/meetingsconferencesworkshops/ucm116740.pdf
Combination product: Insulin glargine pen injector
The pen injector is intended to deliver long-acting insulin used to tread adults with type 2 diabetes and adults and pediatric patients (children 6 years and older) with type 1 diabetes for control of high blood sugar. The PMOA is assigned to the insulin glargine and most recently been filed with CDER following 505(b)(2) application. No insulin glargine products are currently licensed under the Public Health Service Act, so there is no "reference product" for a proposed biosimilar product.
https://www.biosimilarsresourcecenter.org/faq/biosimilar-insulin-available/
Transdermal patch is a combination product which is used to deliver drugs through skin. Currently around 17 drug molecules are approved by FDA for transdermal delivery. The patch has micro needles which will deliver the drug through the skin. The application pathway for this would be submitting application at CDER under NDA/ANDA because the the drug constitues the PMOA. It should undergo invitro testing to determine the safety and action of the drug.
Band-aids with Neosporin bandages (the band-aids that come with the Neosporin already applied) are a combination product. It's primary mode is it protects your wound and also helps treat it. This would be under the CDRH because it is first a medical device and it would be class 1. The regulatory pathway would be like the one outlined on slide 31. The pathway in chronological order is RFD and then 510(k). Its a combination product so it would need an RFD but its also a class 1 device under the CDRH so a 510(k) would be needed.
Another combination product on the market is a catheter with antimicrobial coating. They are used to lower the risk of catheter colonization and infection. The Foley catheter, for example is describe as "flexible tubular device that is inserted through the urethra and used to pass fluids to or from the urinary tract." These type of devices are classified as Class II and I think they should be regulated under CDRH. Changes to the device should be made in line with 21 CFR 807.87 and significant changes may require 510k submission. The FDA also may require additional information such as a rationale for the modification, any bench, animal, clinical, functional, in vitro, and/or any other testing data to support marketing claims. Significant changes to the antimicrobial agent that is used on the catheter is the subject of an approved new drug application NDA as per CDER guidance.
Antimicrobial wound dressings is consider a combination product, it is mainly used to cover partial and full-thickness wounds the wounds and it also help to reduce the risk of infection. I think it will be consider as CDRH and it does required RFD because it delivers a drug and 510(k)only because it is consider as class 1. And Bio-compatibility tests has to be done as required by ISO 10993.
[1] https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=878.4018
A collagen coated vascular prosthesis is considered a combination product. The product is used as a vascular graft and considered non-porous by coating it with a layer of collagen, taken from young calf skin. These grafts were implemented in the thoracic aorta and did not require special preparation time before implementation. I believe this type of product should be under the regulation of CDER since the product is made from a nonhuman resource. This product specifically will deal with human implementation and create an easy procedure that does not require special care for its use. It was able to suture easily and did not bleed. The bovine collagen was also reabsorbed completely in 90 days and replaced with native tissue. The tissue did not create any other issues in the body. The regulatory pathway should definitely fall under the CDER and undergo animal testing before it can be released into the market for its use.
combination product: Vosevi. It is use for treatment of adults with chronic hepatitis C virus (HCV) genotypes 1–6 without cirrhosis or with mild cirrhosis. It's department is under Biologics Regulation, CBER. And requires Premarket Approval Application (PMA). A CBER -> IND, (Phase 1,2,3) or Pivotal Trials, BLA
Reference:
A medical device that I can’t speak to much on because of IP is considered a combination product. It’s a diagnostic device which can accurately read small concentrations in the pico-scale. The device can use blood and or urine to detect let’s say tuberculosis. First the primary mode of action is to test concentration of blood of whatever agent in it against a standard. The department most suitable for this device will be CBER ( Center for Biologic Evaluation and Research). The pathway has several possibilities. Will have to do a BLA (Biologics License Application) . The biological product or diagnostic device is used in blood testing. It has to demonstrate Drug GMP compliance and/or Device QSR. It may go to Panel. The approval may be more heavily focuses on manufacturing facilities and issues. The regulatory path way is -> IND, (Phase 1,2,3) o pivotal Trials, BLA as stated before. However since this diagnostic is not new it can be considered a Class 1.
Combination product: metered dose inhalers, MDIs
An MDI is made up of a pressurized canister containing a drug substance and possibly excipients formulated with a propellant. The formulation is aerosolized through a valve fitted with an actuator (mouthpiece). Per FDA regulation, MDIs are considered drug-device combination products. The primary mode of action, PMOA, is the drug component, hence it falls under the Center for Drug Evaluation and Research (CDER). It has recently been filed with CDER following 505(b)(2) application.
There are lot of combination product in the market today, especially combination device with drugs.
One of the combination device which was recently created by Bayer's Healthcare in September 2015 is the "Electronic Autoinjector" indicated as a treatment for relapsing-remitting multiple sclerosis (RRMS) to deliver their drug Betaseron. According to Bayer “all a patient will have to do is prepare the Betaseron syringes provided in the medication pack and use BETACONNECT for a more convenient and effective delivery”, that allows patient to select the speed and depth of injections as well.
BETACONNECT will also feature an app to upload data to a smartphone or computer. The app is used to set reminder alerts for the next injection, with a calendar of all injections that have been scheduled, recorded, or missed. This injection history can be emailed directly to the patient or physician, so it is an added feature that benefits the patient and allows oversight by the healthcare provider. (Reference: FDA Approves BETACONNECT Autoinjector for BETASERON Delivery; Anna Tan, In News. As accessed at www.multiplesclerosisnewstoday.com on November 1, 2016.)
According to the FDA, to determine what department this device falls under, the primary mode of action will be considered.
But looking at the BetaConnect device, is it possible that this device could fall under Multiple Marketing Applications like Center for Drug Evaluation & Research (CDER), Center for Devices & Radiological Health (CDRH) and Software as a Medical Device (SaMD)?
