Bioequivalence and Bioavailability Forum • FDC with ascorbic acid

qualityassurance
★

2024-07-23 10:08
(72 d 11:56 ago)

Posting: # 24087
Views: 1,547

FDC with ascorbic acid [Regulatives / Guidelines]

Dear Forum members,

In case FDC (two active ingredients) with ascorbic acid is not approved in Europe. However, FDC (two active ingredients) is approved. In case if we want to apply for FDC (two active ingredients) with ascorbic acid in Europe, is it needed to conduct any safety and efficacy study in patients or only BE study will be enough justifying that ascorbic acid is used as an excipient?

Regards,
QA

Ohlbe
★★★

France,
2024-07-23 11:55
(72 d 10:09 ago)

@ qualityassurance
Posting: # 24088
Views: 1,364

FDC with ascorbic acid

Post reply

Dear qualityassurance,

❝ In case FDC (two active ingredients) with ascorbic acid is not approved in Europe. However, FDC (two active ingredients) is approved. In case if we want to apply for FDC (two active ingredients) with ascorbic acid in Europe, is it needed to conduct any safety and efficacy study in patients or only BE study will be enough justifying that ascorbic acid is used as an excipient?

I am not sure that I fully understand what you are trying to achieve here.

If ascorbic acid is indeed only used as excipient (e.g. as antioxidant), and you are not intending to put it on the list of active substances: a BE study should be enough in module 5. You will have to justify the use of ascorbic acid in module 3, including the amount used, just like any other excipient.

If you're just trying to disguise ascorbic acid as an excipient to make your life easier, but the quantity is not consistent with that use (500 mg won't do), or if you try at the same time to mention it on the SmPC elsewhere than just the list of excipients: this won't do, and you will have to provide justifications in module 5. Difficult to say which without knowing what your two active ingredients are. Could be limited to bibliography (well-established use), could need to provide more.

—
Regards
Ohlbe

qualityassurance
★

2024-07-23 12:13
(72 d 09:51 ago)

@ Ohlbe
Posting: # 24089
Views: 1,333

FDC with ascorbic acid

Post reply

Dear Ohlbe,

❝ I am not sure that I fully understand what you are trying to achieve here.

We want to register anti cold product combining with ascorbic acid. FDC of anticold is already registered however FDC of anti cold with ascorbic acid is not registerd in EU.

❝ If ascorbic acid is indeed only used as excipient (e.g. as antioxidant).

Actually ascorbic acid in our formulation will have therapeutic effect. In this case only BE is suffice or safety and efficacy is needed in patients?

❝ Difficult to say which without knowing what your two active ingredients are

It is very known molecule used in cold and flu.

Regards,
QA

Helmut
★★★

Vienna, Austria,
2024-07-23 14:39
(72 d 07:25 ago)

@ qualityassurance
Posting: # 24090
Views: 1,328

Placebo?

Post reply

Hi qualityassurance,

❝ We want to register anti cold product combining with ascorbic acid.

❝ Actually ascorbic acid in our formulation will have therapeutic effect.

Don’t get me wrong but ascorbic acid in such a condition is not more than a placebo (except in pregnancy and for endurance athletes during a competition). Lots of publications, e.g., this one:*

Conclusion
While data do show a decreased severity and duration of colds when vitamin C is consumed at doses at or above 0.2 g/day, it is most reasonable for patients to obtain this from their diet, considering supplementation did not decrease the overall incidence of colds in the general population. Regular supplementation may have a place in special populations, specifically those under high physical stress and those with marginal vitamin C status.
Overall, while there is a wide variety of data available, there is a lack of consistency, and further study is necessary to provide clarity on the utility of vitamin C for therapeutic purposes. Given the low cost and relative safety of vitamin C supplementation, it is not unreasonable for patients experiencing cold symptoms to see for themselves if therapeutic vitamin C is beneficial, but they should know that the data behind its use are largely inconsistent. It appears the greatest potential for benefit of vitamin C in treating the common cold occurs when supplementation is initiated within 24 hours of symptom onset at high doses (~8 g daily) and when therapy is continued for at least 5 days.

IMHO, such a product is a mere marketing gimmick.

Bucher A, White N. Vitamin C in the Prevention and Treatment of the Common Cold. Am J Lifestyle Med. 2016; 10(3): 181–3. doi:10.1177/1559827616629092. Free Full text.

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Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

mittyri ★★ Russia, 2024-07-23 16:54 (72 d 05:10 ago) @ Helmut Posting: # 24091 Views: 1,291	Placebo? Post reply
	Hi Helmut! Just adding fuel in the fire (warning! will be downloaded): Aspirin + C forte 800 mg/480 mg Brausetabletten — Kind regards, Mittyri

Helmut
★★★

Vienna, Austria,
2024-07-24 13:16
(71 d 08:48 ago)

@ mittyri
Posting: # 24097
Views: 1,280

🇦🇹 AGES

Post reply

Hi Mittyri,

oh dear!

The presence of period, sequence, and treatment effects were evaluated.

Why the heck?

For AUC_0-t, a significant treatment effect was observed for ASA (p = 0.0221).

So what?

The lower and upper limit of the CI was below 100% …

A consequence of p < 0.05.

… but within the lower limit of the acceptance range of 80.00[%]

Again: So what?
Similar nonsense for SA.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

qualityassurance ★ 2024-07-24 13:37 (71 d 08:26 ago) @ Helmut Posting: # 24098 Views: 1,268	Placebo? Post reply
	Hello Helmut, ❝ IMHO, such a product is a mere marketing gimmick.❝ Thank you for your HO. Let the BD and marketing team take the call. Allow me to ask the same question. As a strategy to register this product in EU, what is your suggestion? Regards, QA

Helmut
★★★

Vienna, Austria,
2024-07-24 15:31
(71 d 06:32 ago)

@ qualityassurance
Posting: # 24099
Views: 1,219

Sorry – wrong addressee

Post reply

Hi QA,

❝ ❝ IMHO, such a product is a mere marketing gimmick.❝

❝ Thank you for your HO. Let the BD and marketing team take the call.

Sure. At the end of the day the ‘Guy in the Armani suit’ decides.

❝ Allow me to ask the same question. As a strategy to register this product in EU, what is your suggestion?

I’m not the best person to support something that I cannot scientifically defend.
To give you an example: I was once asked by an innovator to develop the concept for a modified (i.e., prolonged) release formulation of a drug with a half-life of > 48 hours, which is only administered chronically. Doesn’t make any sense – a clear case of evergreening. BE of MR is much more difficult than the one of IR.
Not my circus, not my monkeys. I refused.
🙈 🙉 🙊

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

mittyri
★★

Russia,
2024-07-24 18:01
(71 d 04:03 ago)

@ Helmut
Posting: # 24100
Views: 1,196

lucky

Post reply

Hi Helmut,

❝ To give you an example: I was once asked by an innovator to develop the concept for a modified (i.e., prolonged) release formulation of a drug with a half-life of > 48 hours, which is only administered chronically. Doesn’t make any sense – a clear case of evergreening. BE of MR is much more difficult than the one of IR.

❝ Not my circus, not my monkeys. I refused.

A man is lucky (and wise) if he can say 'no' to work proposal due to internal concerns!

—
Kind regards,
Mittyri