This week’s lecture introduced us to the different branches of the FDA that new products in development get assigned. The branches in question are the Center for Devices and Radiological Health (CDRH), Center for Drug Evaluation and Research (CDER), and the Center for Biologics Evaluation and Research (CBER). We also learned about combination products and depending on the product’s primary mode of action (PMOA) which branch it will be assigned to, which could be difficult in some cases where any of the three branches could technically apply. I’m sure we all have seen products and thought of which branch it was assigned to, only to find it was actually classified into another. So give an example of a combination product that is on the market or in development that you’ve seen somewhere, used, or just heard of and justify why which particular branch was assigned to it. Maybe also add in other details like what class it was assigned (1, 2, or 3) and other details
Example:
Polymethylmethacrylate (PMMA) bone cement with antibiotics
Class 2 Classification with 510(k)
Branch: CDER
The bone cement primary is used in implant fixation. It acts a void filler that creates a tight space which holds implants against the bone and acts as a plaster. Even though it has antibiotics on it, the PMOA is to act as a plaster to anchor together artificial joints to the bone.
Links:
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPCD/classification.cfm?ID=4525
https://www.fda.gov/MedicalDevices/ucm072795.htm#intro
I have had the opportunity over the last 10 years to work with Drug-Eluting Coronary stents. These stents are delivered by a catheter, used to prop open the coronary artery and are coated with a drug that is absorbed into the surrounding tissue. The primary mode of action (PMOA) is to open the coronary artery. The secondary mode of action (drug) is to prevent inflammation and restenosis. The review is assigned to CDRH due to the PMOA being a device. These devices are generally classified as a Class III device and require a PMA.
This one might be a layup but a pretty common one would be a first aid kit. They have aspririn and antibiotic cream that would go through CDER which are probably class 2 with 510k. The bandages and gauze would go through the CDHR and be a class 1 device.
Going in line with the example in the question, there are different coating on implants used to stimulate specific responses. For example the Hydroxyapatite coating on a titanium implant to convert fibrous tissue to bone around loaded implant. The implant itself would have to go through the CDRH and probably be a class 1 device as there are already an abundance of titanium implants, and the specialized coating could be considered a class 2 as it has special and unique health benefiting aspects, though not as extreme as a class 3 device.
Link: http://bjj.boneandjoint.org.uk/content/jbjsbr/75-B/2/270.full.pdf
Using a similar but different example, birth control implants are also combination products. The implant is a tiny, thin rod about the size of a matchstick. A doctor inserts the implant under the skin of the user’s upper arm. It releases the hormone progestin to stop the user from getting pregnant. In this case the implant is made of ethylene vinylacetate copolymer and serves as a reservoir for controlled release of progestin. The PMOA is attributed to the drug so review would be done primarily by CDER.
The Ellipta inhaler is considered to be a combination product in the same sense that a pre-filled syringe is. The Ellipta inhaler contains a drug that is combined with a device to facilitate the drug's delivery, regardless of whether the device is packaged separately from the active drug. This would classify as a Class I 510(k) exempt device that would register with an NDA under CDER. The Ellipta inhaler uses a dry powder for the administration of inhaled medication aimed at treating asthma and COPD, therefore the primary mode of action would be a metabolic reaction, thereby classifying the product as a drug. The FDA branch that the Ellipta inhaler falls under doesn't really come into question, but rather the classification of the inhaler itself in that although it is an everyday item that is easy to use (such as a band-aid, a tongue depressor, or another Class I product), the active drug directly affects the user's respiratory system. This indicates that any defect in the product's manufacturing can result in grave adverse effects, such as processing the inhaler with a drug concentration that is either too high or too low, or it may just have a defective trigger.
The medical device classification system in the U.S. has been considered to be somewhat outdated in the sense that the more medical devices being commercialized, the more broad these devices are in terms of their classification. The EU for example diverged their Class II devices into Class IIa & IIb. Both IIa and IIb devices carry medium risk and are classified under special controls, meaning that a IIa device can be held at slightly higher standards than a U.S. Class I device by methods such as implementing additional labeling requirements, more rigorous performance testing, post-market surveillance, or anything that further validates the inhaler as a medical device. Does this imply that the U.S. needs to alter its classification standards in response to the growing market for medical devices? Have there ever been any projects that folded as a result of the FDA informing the project company that their product is actually a higher classification than the company expected?
Grant, Andrew C et al. “The ELLIPTA® Dry Powder Inhaler: Design, Functionality, In Vitro Dosing Performance and Critical Task Compliance by Patients and Caregivers” Journal of aerosol medicine and pulmonary drug delivery vol. 28,6 (2015): 474-85.
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=874.5220
