At the November 2020 WG2 Meeting the form was discussed.
Clarification of Billing Unit Standard
Request:
JELMYTO is supplied as a carton (kit) containing two inner NDCs that are mixed together prior to administration:
-Two 40 mg (each) single-dose vials of mitomycin supplied as a sterile, lyophilized cake or powder. (NDC 72493-0101-40)
-One 20 mL single-dose vial of sterile hydrogel supplied as a sterile, clear, colorless gel to be used as a vehicle for reconstitution. (NDC 72493-0102-20)
As there are multiple items in the JELMYTO package, this is considered a kit, and the outer NDC, 72493‐0103‐03, JELMYTO, is the only commercially available product. JELMYTO is intended to be dispensed as a complete carton as described in the Instructions for Pharmacy (IFP) and Prescribing Information (PI).
Why Needed:
Currently the Package Size is listed as “2” and should be listed as “1” for the carton NDC
Outcome Anticipated:
Update the carton Package Size to “1” for the JELMYTO carton NDC (72493-0103-03).
Task Group Discussion (7/28/20):
- Notes from prior task group discussion on June 16, 2020 on this product:
- Nothing on label to make it a kit
- Each vial has a BU = EA; there are 2 vials of mitomycin
- Reconstitute mitomycin with hydrogel
- The gel is a diluent and a delivery vehicle
- Agreement for 2 EA per 5.1, 5.1.2, and excluding the diluent per 5.5.1 of BUS
- A representative from the manufacturer provided the following information:
- There are 2 inner NDCs and 1 outer NDC. The two inner NDCs are not for individual sale and they will not be separated or split from the carton.
- The hydrogel is not really a diluent. It is a core product. It cannot be purchased separately.
- It is highly unlikely medical personnel will try to reconstitute the mitomycin with another solution.
- The Instructions for Pharmacy state “Must be Reconstituted with Sterile Hydrogel Before Use”
- Patients prescribed this product are enrolled in a hub and the product is only provided through the hub. There is a specific tracking number for a specific patient to be used on a specific day. It is not a product sitting on a pharmacy shelf.
- It is administered by a urologist through a catheter as part of a procedure. The carton is only opened to mix and administer to a single patient.
- If for a single patient, why are their two vials of mitomycin instead of a single vial?
- Manufacturer will check for the answer.
- In light of the special properties of the hydrogel which make it more of an active ingredient than a diluent, there is a case for qualifying this product as a kit and the package size could be 1 each.
- There would be two distinct items with different billing units qualifying it as a kit.
- However, we want to be sure we aren’t opening ourselves to a re-adjudication of other products with
- It was noted there is some confusion in the marketplace as to the package size. CMS is listing as 1 each.
- The task group can reach out to our CMS contact
- Although we want to minimize discrepancies, we want to make sure we don’t create a bigger problem with legacy products.
- The task group agreed to table a final determination.
- Need to research existing products. What is the best way to accomplish?
- Recommendation to the manufacturer: For future products, either label the hydrogel as an active ingredient or add an alcohol wipe to the carton to qualify for kit designation per the Billing Unit Standard.
Task Group Discussion (8/25/20):
- Representatives from UroGen gave a presentation about their product, JELMYTO, focusing on the hydrogel and how it plays an active clinical role in the mechanism for JELMYTO and is not just a diluent.
- It releases over an extended period of time for longer absorption of mitomycin.
- PI says it forms a semisolid gel which dissolves releasing mitomycin for up to 4-6 hours.
- The hydrogel has its own NDC.
- FDA typically will not assign a NDC to something that is not clinically relevant. An inactive ingredient would be given a UPC.
- However, sterile water in kits for reconstitution have NDCs
- It was noted this product needs to be mixed in a clinical setting by someone with certification and administered to the patient within 8 hours. It is unique to the patient and ordered through a hub. The mixing process is pretty extensive.
- An outstanding question from the initial review of the QUIC form was why there are 2 vials instead of 1 vial of mitomycin. It was determined it was better to use two 40 mg vials than an 80 mg vial.
- Since the sterile hydrogel plays an active role in the mechanism for JELMYTO, Alisha recommended this be 1 each because of 2 different billing units (hydrogel (ML) and mitomycin (EA) which is in alignment with the BUS.
- Six compendia representatives agreed based on today’s presentation however 2 expressed concern about the impact on other products this package assignment will have.
- Worried other manufacturers could or can say their diluent can play an active role. The task group doesn’t want to have to make clinical decisions.
- It was suggested we treat this an exception and draft a FAQ. It is causing disruption, billing issues, misunderstanding and possibly impact to patient safety.
- Another option was suggested was to not have an exception but clearly state in the QUIC form that the hydrogel is needed for sustained release of the mitomycin and is part of the dosage form.
- There was a recommendation for the co-leads and WG2 co-chairs have a separate discussion on the topic.
- Will also have to coordinate changing the package size from 2 to 1; this impacts more than the compendia listing.
- Some files only update monthly. October 1 was suggested but do not want a final decision on the date until we know how we are handling this product.
- We will confirm our approach and select a date on the call on 9/8.
Task Group Discussion (9/23/20):
- Concerns with creating an exception for this product
- Unless the diluent is actually listed as an active product, it is not a separate entity. It doesn’t fit the definition of a kit.
- Because components of a product have separate NDCs do not constitute a kit (or 1 EA).
- What section of BUS do we cite for providing a billing unit that is different than what this looks like on the surface (2 EA).
- There may be other products already on the market similar to this where we gave it a 2 EA.
- The presentation slides from UroGen and the product package insert, provide clinical justification to consider the Hydrogel as a key clinical component to the absorption and release of Mitomycin in the kidney, pelvis and calyces.
- The Hydrogel is a liquid at near freezing temperatures and turns to a solid when exposed to body temperature and acts as a depot releasing mitomycin over a 4-6 hour time period. This process allows for longer absorption and greater clinical benefit. This would not occur without the hydrogel.
- The Hydrogel doesn’t simply dilute or buffer.
- From the PI:
- Section 11 (Description)
- Hydrogel is clear, purple LIQUID when frozen and turns to a SOLID when instilled and at body temperature.
- Jelmyto admixture requires certification. The mitomycin is mixed with Hydrogel, the hydrogel/mitomycin mixture turns to a solid after instillation into the bladder.
- Normal urine flow would eliminate the mitomycin, whereas the hydrogel acts as a depot and releases the mitomycin into the kidney, pelvis and calyces over a 4-6 hour time period allowing for longer absorption and greater clinical benefit.
- Section 12.3 (Pharmacokinetics)
The systemic exposure of mitomycin following instillation of up to 60 mg of mitomycin as JELMYTO into the pyelocalyceal system was evaluated pre-instillation and hourly for up to six hours postinstillation in six patients. The concentrations of mitomycin in plasma were variable and ranged from 2.43 to 12.80 ng/mL over the course of treatment; the mean Cmax was 6.24 ng/mL, which is estimated to be less than 1% of the expected Cmax after intravenous administration.
Following instillation into the pyelocalyceal system, JELMYTO forms a semisolid gel which dissolves from normal kidney urine flow releasing mitomycin for up to 4 to 6 hours. Mitomycin is eliminated unchanged in the urine. Systemically absorbed mitomycin is rapidly cleared from the serum and approximately 10% is excreted unchanged in the urine.
Mitomycin is metabolized primarily in the liver, but metabolism occurs in other tissues as well. It is believed that the rate of clearance is inversely proportional to the maximal serum concentration because of saturation of the degradative pathways.
- Could support an exception as it is a unique type of product. It doesn’t fit where we would usually fit it within the BUS.
- What was perceived to be diluent (hydrogel) and discounted is actually a clinical component as the product won’t work without it.
- This puts the product in a different categorization and an exception is not needed.
- Two different billing units for two different clinical components is a kit (1 EA) per BUS 5.5.1.
- Those on the call agreed to a package size of 1 EA per BUS 5.5.1.
- The compendia have it as 2 EA currently, so a change has to be coordinated.
- Is October 1st achievable?
- WK would have to announce this week in order to do it for 10/1
- Cerner cannot accommodate until mid-month (10/15)
- Scriptpro can do 10/1
- FDB can do 10/1
- Elsevier can do 10/1
- IBM is missing from call – confirm off-line (post-call they said it can be in daily and weekly deliverables by 10/1 (majority of their clients) but not the monthly file for 10/1 as the data has already been pulled. It will be available on 11/1.)
- NCPDP Now article for this week if possible
WG Discussion (11/04/20):
A motion was made and seconded to classify the BU=Each (kit) for a quantity of 1 per Section 5.5.1 of the Billing Unit Standard. The motion carried.