unilife's products shows a weak business case , page-24

Karljasper ... re your question over 1 year or 3 years. It can be anything. The cliff notes to consider in answering your question.

New vs existing
If its a new generic than they will need to do submit an Abbreviated New Drug Application / ANDA.

Now the take away with ANDA vs NDA is because they are viewed as being similar in effect, dose etc as the established branded drug they do not have to go through the same animal and human clinical trials to prove the drug works and is safe.

Rather than timely and expensive clinical trials they need to be able to scientifically demonstrate that the drug has similar uptake in the bloodstream etc etc based around the assumption that if the drug works the same as the branded drug then showing the bioavailabilty/absorption in the blood then you are on your way

So part of the approval of the drug itself, irrespective of branded or generic is that you demonstrate the syringe or other selected primary container is capable of maintaining its microbial barrier integrity. Must also prove that the drug does not react with its contact parts in the primary container. And lastly the shelf life of the drug when stored in the primary container.

The exact words of the regulator are:

"Every proposed packaging system should be shown to be suitable for its intended use: it should adequately protect the dosage form; it should be compatible with the dosage form; and it should be composed of materials that are considered safe for use with the dosage form and the route of administration. If the packaging system has a performance feature in addition to containing the product, the assembled container closure system should be shown to function properly"

Now the beauty of being a branded drug and needing to do clinical trials etc is that during these trials you have been afforded the opportunity to check the drug/container for extended periods of time and even formally conduct stability trials in parallel.

SO stability trials are often mis-represented and understood. I think UNS have allowed the to be a crutch and reason for some delays

REMEMBER....drug companies want to get drugs on shelves for sale. They dont want to use 3+ batches for stability trials, sterility tests, filling validation etc and not derive any immediate sales from that drug's maufacture or wait whilst it sits in dark cool rooms in stability trials. Regulators recognise this but of course still need to hold manufacturers to account

Its all about risk assessment. A well trodden path is 6 months of data that include accelerated and long-term conditions. Accelerated can be high temp, humidity, light etc whilst long term is your normal storage conditions.

6 months....PROVEN. The thinking is that if you have 6 months data, then by the time the drug goes on sale....if any of your ongoing stability trials that can go for years if you are going for extended shelf life and expiry dates; afford the drug manufacturer a window where they can recall any unused drug IF they find that after 2 years that the drug may eg. degrade and become inactive.

Remember in cases it can take 18+ months for a drug to reach a customer... storage, distribution...sales. So 6 months data is pretty low risk as essentially it gives you room to do activities in parallel. Whilst you are undergoing regulatory approval you continue with stability trials and accumulating data etc

But typically you can get away with 6 months data if it has the desired window dressing with the application showing data from similar drugs, container systems etc etc...ie risk mitgation. The quality of Unilife' device master recrod is crtitical. I assume the absence of drugs in our products means that the "library" on info about drugs-Unifills is limited. The main opportunity for leveraging here is the microbial performance of the stoppers etc when stored long term

If your drug, which may be the case with some more complex biologics are seen as degrading than the durations and testing is more laborious. Don't expect that to be an issue with generics.


SO long winded...sorry, but this gets asked a bit and often mis-quoted.

So that is for a NEW generic. Hikma have a number of drugs to be migrated over to Unifill.In this case its not a regulatory submission for the drug, but simply a change in the primary container used.

I find it hard to believe 3 years, (is polite way to say BS) that a generic manufacture will take 3 years. 18 moths? Yep. Not 3 years.

To the FDA a change in syringe supplier s considered a "Major Change" to an approved drug as it has the potential to have an adverse effect on the identity, strength, quality, purity, or potency of the drug. SO HIKMA will need to submit a Prior Approval Supplement which is basically a heads up that they are changing syringe supplier, here is some data and then once signed off they are allowed to sell the drug in the new syringe.

It would be expected that this submission be accompanied with some stability data...6 months is reasonable.

The approval time for the Prior Approval Supplement can be up to 6 months from submission.

So you have the time to compile. The time for approval from submission. You can assume you proceed with ordering from your new supplier, filling etc on the assumption that the regulator will give you approval...but its a risk that they wont...most business will accept the risk and kick things off and not release product until approval is received.

So its easy to see how it can be 18 moths. You dont just have the regulatory steps either You need to find windows in your production schedule to make extra batches for filling validation, stability tests (usually 3 batches). Thats no easy task for a production group, especially when they cannt sell the product.

The above is typical to US and FDA but EMA, JP etc are all similar in expectations.

This perhaps spells out whey I have been so wary of the "great news" out of the business.

Ask yourself, would you go down this path without a supply agreement? Locking in conditions, volumes and price?

You could...but I would be laughed out of my building and black listed by management if I suggested we manufacture extra product, do stability trials, do regulatory submissions all without locking up a firm supply agreement on $$$$ and conditions of contract.

The rapid ramp up of Hikma and Sanofi....well the lack of news about increased capacity tells me that the past few years any stability trials were a bit mis-targeted.

Apologies for the rambling...too lazy to go over and proof read...hope it makes sense