nobody
nothing

2015-05-12 12:01
(3243 d 07:33 ago)

Posting: # 14788
Views: 4,453
 

 FDA - Biowaiver Class III [Regulatives / Guidelines]


Kindest regards, nobody
Helmut
★★★
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Vienna, Austria,
2015-05-12 14:27
(3243 d 05:07 ago)

@ nobody
Posting: # 14791
Views: 3,806
 

 FDA - Biowaiver Class III

Hi nobody,

❝ Is this new?


Yep. Samaya notified us last week. :thumb up:
The FDA proudly announced the revision at the “Global Bioequivalence Harmonisation Initiative” (March 2015, Amsterdam). Harmonized with their own product-specific recommendations and to a good part with EMA’s. Doubtful whether Japan will ever board the ship.

❝ ...class III biowaivers for FDA---

  • ƒ 90% ⇒ 85%
  • pH 7.5 ⇒ 6.8
  • Fixed Dose Combinations
If you want to explore further differences: The August 2000 guidance here.

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nobody
nothing

2015-05-12 15:14
(3243 d 04:20 ago)

@ Helmut
Posting: # 14792
Views: 3,986
 

 FDA - Biowaiver Class III

❝ ❝ Is this new?


❝ Yep. ...


Or better, Nope? :-D

Sorry for the double posting (little busy lately, not following all threads), maybe we can merge the threads or somefink like that?

The 2000 guideline I have here, on papyrus, as we had it in ancient times ;-)


Edit: Moving/merging of threads/posts is not implemented in the current version of the Forum’s scripts (on the to-do-list for ages). Too lazy to fiddle around in the MySQL-DB. [Helmut]

Kindest regards, nobody
jag009
★★★

NJ,
2015-05-14 18:31
(3241 d 01:03 ago)

@ Helmut
Posting: # 14820
Views: 3,674
 

 FDA - Biowaiver Class III

❝ Yep. Samaya notified us last week. :thumb up:


And the Test and Ref need to be super fast in dissolution time. 15 mins... for Class 3

For Class 1 they only ask for within 30mins...

John
Helmut
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Vienna, Austria,
2015-05-14 20:51
(3240 d 22:43 ago)

@ jag009
Posting: # 14822
Views: 3,636
 

 FDA - Biowaiver Class III

Hi John,

❝ And the Test and Ref need to be super fast in dissolution time. 15 mins... for Class 3

❝ For Class 1 they only ask for within 30mins...


Harmonized with EMA’s requirements in the BE-GL, Appendix III, Section II.

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luvblooms
★★  

India,
2015-05-15 09:31
(3240 d 10:03 ago)

@ nobody
Posting: # 14823
Views: 3,691
 

 OT: Reality vs Guidance

Hi John and HS

What baffles me the most is

a) There is no clarity on the triplicate Solubility data generation whether it need to be generated on one lot of API or on data of different/all the lots of API used in different batches of formulation (This is one of the most frequently asked Question on all the products which are filled through bio waiver approach and I will surely generate all the data in advance to keep them handy in case of a query)

b) Highest strength or highest dose??? Between line 135-139 guidance says that “ A drug substance should be classified as highly soluble 135 when the highest strength is soluble in < 250 mL of aqueous media over the pH range of 1-6.8. In other words, the maximum dose divided by 250 should be greater than or equal to the lowest solubility observed over the entire pH range of 1-6.8 of 1-6.8.” There could be a difference in highest strength and highest dose; example Capecitabine. Highest strength is 500 mg but highest dose is much higher at 1250 mg/m² orally twice daily. So in such conditions what to be used?

c) In case one have to take the body surface area for highest dose calculation for Cancer medicines or medicines which are dosed as per the body surface, what should be the standard body surface area to be taken to show the solubility?
BSA details as per Wikipedia

Child of 2 years--> 0.5 m²
9 years--> 1.07 m²
10 years--> 1.14 m²
12–13 years--> 1.33 m²
Women--> 1.6 m²
Men--> 1.9 m²
There was an average BSA of 1.73 m2 for 3,000 cancer patients from 1990 to 1998 in a European Organisation for Research and Treatment of Cancer (EORTC) database. During 2005 there was an average BSA of 1.79 m2 for 3,613 adult cancer patients in the UK. Among them the average BSA for men was 1.91 m2 and for women was 1.71 m2.
As per the label of Xeloda dose should be

SURFACE AREA (M²)->TOTAL DAILY DOSE* (MG)
≤ 1.25------> 3000
1.26-1.37------> 3300
1.38-1.51------> 3600
1.52-1.65------> 4000
1.66-1.77------> 4300
1.78-1.91------> 4600
1.92-2.05------> 5000
2.06-2.17------> 5300
≥ 2.18------> 5600

Now what should be the dose used for Solubility study?
a) 2800 mg (derived from BSA of 2.18?
b) 2300 mg (based on normal published BSA of cancer patients?

There are many more crude thoughts on the guidance but it will take some time to formulate them in questions. ;-)

~A happy Soul~
nobody
nothing

2015-05-15 12:34
(3240 d 07:00 ago)

@ luvblooms
Posting: # 14824
Views: 3,598
 

 OT: Reality vs Guidance

❝ What baffles me the most is


❝ a) ...of different/all the lots of API used in different batches of formulation...


Use common sense: All relevant batches should be studied, IMHO

❝ b) Highest strength or highest dose??? ...


Again: Common sense, only the WORST CASE, i.e. absolute highest therapeutic dose thinkable makes sense. If there is a "switch" from high to low solubility within the therapeutic dose range, might be interesting to the authority...

❝ c) In case one have to take the body surface area for highest dose calculation ...


See b)

;-)

Kindest regards, nobody
luvblooms
★★  

India,
2015-05-15 14:09
(3240 d 05:25 ago)

@ nobody
Posting: # 14826
Views: 3,553
 

 OT: Reality vs Guidance

Hi Nobody

❝ Use common sense: All relevant batches should be studied, IMHO


Using coomen sense I mentioned that but I have a bit different run in with FDA on couple of products
a) in one of our filing they didn't ask for data of any other lot of API
b) In recent submission they asked for all the data

❝ ❝ b) Highest strength or highest dose??? ...


❝ Again: Common sense, only the WORST CASE, i.e. absolute highest therapeutic dose thinkable makes sense. If there is a "switch" from high to low solubility within the therapeutic dose range, might be interesting to the authority...


Totally agreed to your point. But common sense also tells me that may be BSA of 2.18 will not be the right BSA for cancer patient. So does using the "absolute highest therapeutic dose thinkable" really make sense?
If so why to cut it off at 5600 mg? Why not even higher?

❝ ❝ c) In case one have to take the body surface area for highest dose calculation ...


Again the same augument!
A recent study showed that in a total of 3613 patients receiving chemotherapy for head and neck, ovarian, lung, upper GI/pancreas, breast or colorectal cancers were included, The overall mean BSA was 1.79 m2 (95% CI 1.78–1.80) with a mean BSA for men of 1.91 m2 (1.90–1.92) and 1.71 m2 (1.70–1.72) for women. So why to use BSA of 2.18?

In past we had the some arguments with FDA on the dose calculation using BSA and after long discussion FDA finally agreed on calculations based on BSA of 1.78-1.91 m2.

So better to get clarity on the stupid questions that one have :-D

~A happy Soul~
nobody
nothing

2015-05-15 18:40
(3240 d 00:54 ago)

@ luvblooms
Posting: # 14835
Views: 3,539
 

 OT: Reality vs Guidance

Hi Luvbloom


❝ Using coomen sense I mentioned that but I have a bit different run in with FDA on couple of products

❝ a) in one of our filing they didn't ask for data of any other lot of API

❝ b) In recent submission they asked for all the data


Learning curve ;-)

❝ ❝ ❝ b) Highest strength or highest dose??? ...

❝ Totally agreed to your point. But common sense also tells me that may be BSA of 2.18 will not be the right BSA for cancer patient. So does using the "absolute highest therapeutic dose thinkable" really make sense?

❝ If so why to cut it off at 5600 mg? Why not even higher?


I don't get the the point here, sorry :-) For a biowaiver the absolute highest dose makes sense to me. Only if you can show that e.g. 99% of patients receive "highly soluble" doses and only 1% is on "low solubility" dose in practice this would matter. IMHO ;-)

❝ ❝ ❝ c) In case one have to take the body surface area for highest dose calculation ...


❝ Again the same augument!


So why to use BSA of 2.18?

I never mentioned that figure ;-)

❝ In past we had the some arguments with FDA on the dose calculation using BSA and after long discussion FDA finally agreed on calculations based on BSA of 1.78-1.91 m2.


Sounds good! Go ahead!

If you want clarity write some comment to include the "dosing based on bodyweight" thing into the guidance with some sound suggestions (based on clinical practice) and see what happenz. You will never know before you start... :-D

Happy weekend!

Kindest regards, nobody
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