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Dissolution profile comparision-Pharmaceutical industry

Hello Team,

Good day

Recently during close contact with Pharma customers in India, one of the customers from Sandoz/ Novartis (his name is: Karthik, Parsa <parsa.karthik@sandoz.com>) is asking about his wish list which been posted in our community last year :

Options for the calculation of the following for dissolution profile comparison(requirement of regulatory agencies)

a. F2

b. bootstrap F2

c.Multivariate model-dependent

d. Multivariate model-independent

Besides the request posted, we received more and more similar requests, asking for the Pharmacokinetics, Bioequivalence Test, dissolution comparison function in JMP.

As you may aware most of those Pharma companies in India are tablet manufacturers, like SUN Pharma, Lupin...

even though I'm not from the Pharma industry background, but from a business point of view, we understand this is one of the key buying points for Health and life science industry worldwide, how eager they would love to see that feature available in JMP (or can be in JMP PRO)

If we already have this feature in JMP16 EA, that's great!

if not, Hope we can consider adding this feature in JMP16, much appreciated

Status: Delivered

Comments

Yes, I agree that features like this should be included and I have voted for it. There are other ICH guidelines that could be directly incorporated as well like other Pharmacokinetic methods (non-compartmental) that relate to bioavailability, non-linear stability, other degradation profiles/modeling typically used in not only manufacturing (CMC) but also in the R&D groups when a drug is being developed.

I come from the R&D part so that is where my main expertise but I am familiar with many of the CMC requests given the years I have interacted with pharma. I know Byron Wingard worked in Pharma in the manufacturing side for many years and has a lot of experience as well (I would consider him, Don McCormack and Andrea Coombs the CMC experts).

-- from Chris Kirchberg

We have encountered such needs from time to time, especially for generic drug customers, the most recent one was a Chuchu‘s customer in Nanjing

--- from Alex Xu

We witnessed it together during our meetings with various Indian Pharma customers for the said request. It will surely bring in convincing values for JMP adoption in Pharma industry.

-- from ZhaoBin

I am so glad that you are using this channel to voice the need for Pharmacokinetics Bioequivalence. There was huge need for BE in China 2-3 years ago.

One key element that missed in JMP is non compartment analysis (NCA). JMP already can do one and two compartment analysis that is more complex than NCA.

- from Bao WenJun

chuchuchen

My customer Nanjing Baisheng also hope they could do Pharmacokinetics, Bioequivalence research in JMP recently.

mia_stephens

@PIN, this has been added to this open request: http://sww.sas.com/defects/java/iDefects/WebClient.html?defectid=S1570317

I'm chandramouli a new hire, from pharma background.

Yes including a dissolution feature which would address the basic need of pharma CMC. Especially the calculation of F1 (difference) & F2 (similarity) factors and its associated features would be a welcome addition.
Also as you have correctly observed the non compartmental analysis (NCA) toolbox is also a missing feature - (although there might be workaround for this in the curve fitting toolbox, it is not a sufficient solution as many of the required pharmacokinetic parameters are not computed).
What is your take on the Bioequivalence? as this feature has been always a part of the SAS workflow. Usually the dataset gotten from the Bioanalytical lab is processed in a NCA software (usually Certara Pheonix WINNONLIN(R)) and saved as a SAS *.xpt file for the SAS workflow; as FDA mandates the submission of this data in the SAS XPT format during the ANDA eCTD filing, and as you are aware a USFDA mandated script for BE computation. Although there are some popular apps in the industry like WINNONLIN, NONMEM, PKANALIX, STATA offers this feature out of the box, but regulatory tenability is suspect.

mia_stephens

Hi Chandramouli, welcome to JMP!

Thank you for your comments and questions.

1. We're currently researching feature requests for dissolution - thank you for confirming the importance of the calculations.
2. Noncompartmental pharmacokinetic curve fitting is also something that we are currently researching.
3. For Bioequivalence, you can request equivalence testing in Distribution and Fit Y by X. Additional functionality has been added in JMP 17.

Let's discuss further offline.

@Mark_Bailey, FYI

Chandramouli_R

Hi Team,

Pertinent to this thread we had an enquiry from a prospective customer considering JMP Prakash Muthudoss of ONCOGEN an oncology start-up in KL, MY.

He enquired if JMP had the capability of doing IVIVC (Invitro Invivo Correlation) - a predictive mathematical correlation technique of modeling the likely invivo behavior of certain drugs (which are highly soluble and permeable drugs) based on its invitro dissolution behaviour.

He further explained that he looked for it since he is trying to develop a cheaper generic version of an oncology drug by understanding the dissolution pattern.

This is a high-stake area in pharma since if IVIVC is proven mathematically a Biowaiver can be obtained - thereby avoiding costly human trials.

IVIVC is a hot area in pharma computing and analytics and a well designed and easy implementation of it (a la JMP) can bring a lot value to the customer. Every company that is into generics development will look for this feature since every company wants to avoid expensive bioequivalence trials by claiming Biowaiver for which IVIVC is the key.

Hence it a ripe and opportune moment that JMP should be having dissolution capabilities and gradually increasing its capabilities in this space. In this juncture inclusion of the following basic dissolution capabilities (gradually) will be good start:

Comparing formulations in development to ensure Dissolution profile similarity- F1 Difference & F2 similarity factor and depiction of f2 similarity region as a hyper spheroid.
Dissolution modeling based on:
1. Similarity factor (f2) – Model independent
2. Multivariate Statistical Distance (MSD) – Model independent, Parametric curves to describe dissolution profiles - Model-dependent (add -in exits for this)
Computing dissolution profile models describing in vitro release profiles over a time scale, Fitting dissolution release data points to one of the following models:

Higuchi
Korsmeyer-Peppas
Quadratic
Hixson-Crowell
Exponential
Probit
Logistic
Weibull
Gompertz

and , In Vitro–In Vivo (IVIVC) Correlations - Characterizing the link between in vitro release and clinical outcome and can result in huge savings in biowaivers in certain BCS drug classes.

If JMP attains this capabilities we can position it as a complete tool for pharma having robust capabilities in QbD and CMC and can compete traditionally strong case tools in pharma namely, Pheonix Certara Winonlin 8.3 (separate toolbox), SimulationsPlus Gastroplus 9.8 (IVIVCPlus a separate toolbox), SimulationsPlus DDDPlus (standalone), Excel, Excel macro & VBA, DDSolver (open source freeware) R Project (open source freeware).

If we can have this done, then we can have the attention of major generics companies like - Pfizer, Teva, Mylan, Sandoz, Fresenius, Sun, Mallinckrodt, Lupin, DRL and the likes of it.

@PIN @mia_stephens @markbailey

Audrey_Shull

Hi all, it looks like this item has been implemented in JMP 17. Wanted to let the interested parties know. JMP 17 will be shipping in the fall, so you can let your customers know about this feature, or you could even ask those who might be in the Early Adopter program to take a look at it in the next EA which is EA7. EA7 is the first EA where it will be available.

This item is now being tracked in Jira here: https://rndjira.sas.com/browse/JMP-10034.

SamGardner

This is in development, planned for v17, can we relabel this to In Development?

SamGardner

Much of this will be in JMP 17!