Dose Consistency of Insulin Formulations

S

sreeranjini

#1
Hello,

I am working on an insulin delivery device. We came across a requirement for checking the consistency of the dose delivered from the device.
Is this a regulatiry requirement? If yes, what should be the test methodology or strategy of conducting this test.

Thanks
Sree
 
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v9991

Trusted Information Resource
#2
i am not into devices/insulin mfg but here's 1 reference from FDA,...
but here';s starting point,
"APDS control algorithms currently recommend periodic insulin dosing with frequencies ranging from 1-30 minutes. These frequent bolus doses are extremely small and ask the pump to perform accurately near the lowest doses available in the pump. In order to understand how well the APDS can deliver the recommended insulin or drug, bolus dose accuracy testing should be performed. This testing should evaluate the APDS using the most frequent dosing rate (i.e., the shortest time between dosing adjustments) and accuracy measurements should be tested using the minimum dose, maximum dose and incremental doses between the min and max. The testing of this system should mimic the conditions of the clinical study and the measurement technique should account for evaporation of small doses during the testing. Temperature should be controlled and reflect the use environment."
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm281706.htm

also refer...sec. E.1
FDA recommends completion of the following dose accuracy testing.
? Testing to demonstrate that the volume/weight of drug/biological product expelled through the injector is the same as the set dose
? Testing to ensure that multi-dose cartridge injectors satisfy the requirement
that each successive dose is the same as the first set dose
? Testing to ensure that dose settings/markings correlate with the volume of drug/biological product delivered

Because diluents may affect the drug/biological product and the injector, the above testing should ensure that the delivery volume meets the dose accuracy specification for the specific drug/biological product when reconstituted according to its approved or proposed labeling, as applicable.

We recommend, where appropriate, that injectors include a mechanism or feature that notifies the user that an incorrect dose has been delivered. Performance testing should include testing of such mechanism(s). Product labeling should also include information instructing the user on what action should be taken in the event of incorrect dosage.

http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM147095.pdf

hope this helps...
just in case if you have not already seen this...
 

Ajit Basrur

Staff member
Admin
#3
Homogeneity within a batch and consistency between batches are goals of Process Validation activities. Hence if you say that your process is validated, this becomes mandatory.
 
S

sreeranjini

#4
Homogeneity within a batch and consistency between batches are goals of Process Validation activities. Hence if you say that your process is validated, this becomes mandatory.
Dear Ajit,

We have already established consistency between different batches of the formulation. So I assume we have validated our process. Please correct me if I am wrong :).
My question was regarding the consistency of the doses delivered from the device. Whether it should be based on the volume or weight of the drug delivered or do we need to conduct any chemical analysis?

Thanks
Sree
 
S

sreeranjini

#5
Dear V9991,

Thank you for the valuable guidance considering you are not into this particular field. I have seen this guidance, but in this guidance, "• Testing to ensure that multi-dose cartridge injectors satisfy the requirement that each successive dose is the same as the first set dose" this line confused me. We are checking the accuracy of the dose delivered. But I wanted to know whether it has to be the drug product or the device that should be analysed here.

Thanks
Sree
 
Last edited by a moderator:
I

isoalchemist

#6
You should be looking at the device. You are really trying to show that the delivery is consistent if the vial is full, half full, or nearly empty and when you change vials it stays the same.

Weight or volume come down to whatever is easier and more accurate to measure since they are related by specific gravity.
 

v9991

Trusted Information Resource
#7
Re: Dose Consistency of Insulin Formulations ...

If you are not looking for specific methods & numbers ... let try to put my understanding forward......(typically what we do in validation procotols in similar context)

Protocol/study plan :-
a) identify the range of device characteristics (basically batch to batch variation of its accuracy, precision etc.,)
b) identify the range of product characteristics which device has to handle... ( different levels of pH, viscisity, assay, CU or any other relevant/specific parameter )
c) arrive at an test-method(sequence viz., device operating conditions, settings, ) and acceptance criteria (of accuracy and precision.... )

b) & c) are usually an extension(matrix) of product requirements and device performance capabilities.(as selected by you or as stated by vendor)

while execution/implementing the protocol ...
* first characterize the batch at the required levels as identified above
* execute the experiment.
* analyze the data.
*conclude (addressing the recommendations, / deviations etc)

hope this helps.


further,
We have already established consistency between different batches of the formulation. So I assume we have validated our process. Please correct me if I am wrong
yes, your formulation is consistent not the product/process!!!
for us product is formulation+device; hence consistency of formulation alone wouldn't really be complete w/o addressing rest of the part as well.!!!
 

Ajit Basrur

Staff member
Admin
#8
Dear Ajit,

We have already established consistency between different batches of the formulation. So I assume we have validated our process. Please correct me if I am wrong :).
My question was regarding the consistency of the doses delivered from the device. Whether it should be based on the volume or weight of the drug delivered or do we need to conduct any chemical analysis?

Thanks
Sree
You should comply per stated and labeled claim.
 
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