Expired anti-biotics

[CharonY]

4 minutes ago, J.C.MacSwell said:

Not necessarily. It depends on the test protocol for the particular drug.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040264/

"Medication's potency gradually decreases starting from the moment of its manufacture."

While I'm not sure this is true in all cases it is certainly true generally.

(For balance and/or more context) It continues:

"This process is not in any way spontaneous after the expiry date.

Expired drugs have not necessarily lost their potency and efficacy. The expiration date is only an assurance that the labeled potency will last at least until that date. Ongoing research shows that stored under optimal conditions, many drugs retain 90% of their potency for at least five years after the labeled expiration date, and sometimes longer. Even 10 years after the expiration date many pharmaceuticals retain a significant amount of their original potency.²

Solid dosage forms, such as tablets and capsules, are most stable past their expiration date. Drugs that exist in solution or as a reconstituted suspension may not have the required potency if used when outdated."

Can you clarify what you attempt to argue here? If you read your posted article:

Quote

The expiration date is the final day that the manufacturer guarantees the full potency and safety of a medication. Drug expiration dates exist on most medication labels, including prescription, over-the-counter (OTC) and dietary (herbal) supplements.

That is what is being regulated and I have provided the regulatory requirements by the FDA. At this point it starts to look more like backpedalling of your original demand.

17 hours ago, J.C.MacSwell said:

Is this factually correct?

I'm going to go out on a limb and claim you can't provide a link that peak quality is required to be maintained to that point in time.

I suspect that you assume that drugs lose potency the moment they hit the shelf and as such, stability testing as I outlined initially cannot be happening. And that assumption might be intuitive, but after presumably reading the regulatory demands and the FDA interpretation of the regulations I would have assumed that this assumption should have been modified. Instead, this looks a bit like doubling down by selective quoting.

[J.C.MacSwell]

17 hours ago, J.C.MacSwell said:

Is this factually correct?

I'm going to go out on a limb and claim you can't provide a link that peak quality is required to be maintained to that point in time.

 

14 hours ago, CharonY said:

Of course I can...

Me backpedalling? I was simply trying to help you out, as you were more factually incorrect than wrong. If you had taken the chance to add context you could have simply been more accurate, but instead doubled down with a narrative that you felt justified your position.

Next time read what I posted and do less assuming.

[CharonY]

1 hour ago, J.C.MacSwell said:

 

Me backpedalling? I was simply trying to help you out, as you were more factually incorrect than wrong. If you had taken the chance to add context you could have simply been more accurate, but instead doubled down with a narrative that you felt justified your position.

Then kindly specify the point where I was factually incorrect. The issue is that you keep insinuating things but not specifying what you consider wrong and which context was missing. 

The only thing I can think of (with no help from your side) is that I said "no drop in quality" rather than "no significant drop in quality", which, as admittedly is a bit sloppy, though I assumed by now that most folks would know that in science lingo we do refer to statistical significance when we refer to differences.

If that is your point of contention, which, I repeat, you have yet to specify, I see it more it fairly hypocritical that you demand increasing precision from someone while apparently no putting much effort into being precise yourself. 

 

1 hour ago, J.C.MacSwell said:

Next time read what I posted and do less assuming.

Then how about being more precise in what you want to say. Your last post just adds to the confusion as, again, the selective quoting does not really change anything of the discussion and forces me to interpret what you intend to say.

So let me put some final effort in to help you understand where I see that you might have misinterpreted things:

  

2 hours ago, J.C.MacSwell said:

Not necessarily. It depends on the nature and test protocol for the particular drug.

It doesn't really- the guidelines are pretty firm on them meeting the stability requirements, unless there is a specific point you want to make that makes it relevant. For example they might require storage at high humidity or light for moisture or photosensitive drugs. Yet the same baseline has to be reached in terms of potency of the active ingredients. I have outlined that detains in the guidance document earlier, kindly refer to where you might disagree with them or how the quote you provided might supersede FDA regulations.

Or do you mean any other specific parameters (see, you do not specify that, so I have to start guessing again) that are unrelated to drug quality (especially for accelerated testing) ? What other test protocols are you referring to here? Again, in the document the parameters are listed. I should also add there are certain intricacies regarding the methods, especially HPLC (which is still standard in many areas) can have trouble separating active ingredient from degradation products (though LCMS takes care of that). But IIRC for many drugs batch testing is allowable within +/- 10% for most drugs, except when there is indication that therapeutic effects change within that range (but I have not been involved in production testing, so cannot say for sure).

 

2 hours ago, J.C.MacSwell said:

Medication's potency gradually decreases starting from the moment of its manufacture."

That is true, but as pointed out repeatedly, the manufacturer has to make sure that there is no (statistically significant) drop in potency or other relevant quality indicators used for the approval. If you read the first couple of paragraph in your article, you would have seen that. It occured to me that you might be unaware that batches also have (allowable) variations. I.e. the point is that stability should be comparable to batch variations.

 

2 hours ago, J.C.MacSwell said:

Expired drugs have not necessarily lost their potency and efficacy. The expiration date is only an assurance that the labeled potency will last at least until that date. Ongoing research shows that stored under optimal conditions, many drugs retain 90% of their potency for at least five years after the labeled expiration date, and sometimes longer. Even 10 years after the expiration date many pharmaceuticals retain a significant amount of their original potency.²

This is totally irrelevant as we have already discussed that the true shelf life might extend beyond the indicated shelf life. The issue is (in case you have forgotten) whether manufacturer arbitrarily decide on the self life and purposefully put a shorter in to make a profit.

I have pointed out that they cannot just decide on a date, rather have to do stability testing to ensure that during the indicated time period no loss of potency is observed. You keep insinuating that this is somehow incorrect, yet fail to point out what that is beyond providing quotes that do not appear to provide any additional context.

Telling me to read what you wrote and not misinterpreting it seems really  lazy at this point, I am afraid. It looks to me that you fundamentally misunderstand something but perhaps someone else can figure out what it is as I apparently am not able to interpret your writing the you want it to mean.

[J.C.MacSwell]

3 hours ago, CharonY said:

I have pointed out that they cannot just decide on a date, rather have to do stability testing to ensure that during the indicated time period no loss of potency is observed. You keep insinuating that this is somehow incorrect, yet fail to point out what that is beyond providing quotes that do not appear to provide any additional context.

 

Again. That is not a blanket requirement in any link you provided, or quoted.  Read and try to understand the wording.

If you can't get passed that what's the point of my going through your other requests based on what you think I might be insinuating?

Edited September 17 by J.C.MacSwell

[J.C.MacSwell]

Just as an aside, any general guideline that would require "no drop in potency" through the expiration date would, especially with regard to certain drugs, be of significant detriment to health care.

Edited September 18 by J.C.MacSwell

[CharonY]

5 hours ago, J.C.MacSwell said:

Again. That is not a blanket requirement in any link you provided, or quoted.  Read and try to understand the wording.

If you can't get passed that what's the point of my going through your other requests based on what you think I might be insinuating?

In that case I suggest your read up on the concept of significance in testing and revisit the references  I provided. Specifically the quote I provided outlines what is considered a significant change:

Quote

In general, significant change for a drug product is defined as one or more of the following (as
appropriate for the dosage form):
• A 5 percent change in assay from its initial value, or failure to meet the
acceptance criteria for potency when using biological or immunological
procedures
• Any degradation product’s exceeding its acceptance criterion
• Failure to meet the acceptance criteria for appearance, physical attributes, and
functionality test (e.g., color, phase separation, resuspendibility, caking, hardness,
dose delivery per actuation). However, some changes in physical attributes (e.g.,
softening of suppositories, melting of creams) may be expected under accelerated
conditions.
• Failure to meet the acceptance criterion for pH
• Failure to meet the acceptance criteria for dissolution for 12 dosage units

Or conversely it means, if those criteria are met, there is no significant difference within the product. I am not clear why this seems to keep tripping you up. Perhaps to clarify, and please answer really specific. If we test the product within its shelf life and do not see a significant change in all those criteria, how do you think does it affect potency?

I believe that might be the crux why you don't think that following the guidelines would result in the same potency as fresh products (i.e. within error margins).

(Just as a side note, there are some intricacies between potency and stability testing, but given that the very basics seem to be confounding, I doubt that this is what is meant and really is caused that many standards were developed on HPLCs).

 

 

4 hours ago, J.C.MacSwell said:

Just as an aside, any general guideline that would require "no drop in potency" through the expiration date would, especially with regard to certain drugs, be of significant detriment to health care.

Please provide a citation for that claim.

I will repeat another tidbit of information that you ignored, but which is important in this context (and which hopefully does not trip you up further. From what I recall, industry standards generally allow for variations of around 10% (though I assume there are exceptions, as noted). I do not have any regulatory documents for those (again, have never been involved in process control) but USP documents generally indicate expectations of 90-110% (USP documents are paywalled, but here is a doc referring to that). https://www.usp.org/sites/default/files/usp/document/FAQs/strength-stability-testing-compounded-preparations.pdf

Quote

USP has established that the acceptable
range of most compounded preparations is typically ±10%, or within the range of 90.0%–
110.0%.

However, there are drugs requiring more stringent requirements, when degradation rates are uneven, such as for a thyroid drug:

Quote

FDA is mandating that levothyroxine sodium drug products tighten their potency specifications to meet a 95 percent to 105 percent potency specification until their expiration date. The shelf life is the length of time a drug can be stored before it degrades to unacceptable levels. The 95 percent lower potency specification will ensure the drugs do not degrade by more than 5 percent of the labeled claim before their expiration date and the 105 percent upper specification is appropriate to address occasional analytical testing variability. Currently, these products are allowed a potency range of 90 to 110 percent.

Again, note that there are upper and lower boundaries, which conform to the preparation requirements and are extended to the shelf-life. In other words, you can think of the potency of any product as a bell curve, with boundaries at 90-110. Following all guidelines would ensure that all products, fresh or on the shelf within the expiration date would fall into the same range. Now, obviously if you take a fresh product and test it once and then half a year later, test the same package again, you might measure but you would only know because you are drawing from the same package. If you were provided with a anonymous samples (fresh and shelf product mixed) you wouldn't know as all should fall within that range.

Perhaps to shorten this overlong discussion, how about you simply find a regulatory document (or at least a paper that describes the regulation) that supports your claim that a lower potency than the accepted batch-to-batch variation during its shelf life is in fact acceptable (or at least contradicts the references I have provided)  and that having it otherwise would be detrimental to health care (your second claim).

 

 

 

[J.C.MacSwell]

@CharonY

No drop in potency =/= allowable drop. You can claim an allowable drop of 5 or 10% is insignificant, except as you state...when it is, but you can't claim an allowable drop is not a drop. 

Not allowing any drop during shelf life would make many drugs unaffordable. If you can't understand that that would be detrimental to health care I can't help you.

There is a reason with some drugs that the potency requirements are stricter at manufacture or release than at later times during their shelf life. Some degradation is expected, so time left to expiration date is a factor.

This is a simple concept but feel free to continue to gaslight the Hell out of it.

Edited September 18 by J.C.MacSwell

[CharonY]

Thanks for clarifying. This is a distinction without consequence as any drop has to be within the same tolerance as new productions. I suspected that this is the part that of your comment and I tried to explain by amending my statement that:

  

On 9/17/2024 at 8:19 AM, CharonY said:

I.e. the product is still virtually indistinguishable from fresh products. 

The point you are seemingly unclear about is that a) there are allowable variation in batch production  and b) the product also has to remain within this tolerance during its shelf life (as per the guidelines).

In other words if you take a random sample from the shelf and compare it to a fresh product the levels all fall within that limit and you would be unable to distinguish which is which. I.e. if you have a sample with 94% of its potency, it could be a degraded from originally 97% (which I think is what you think about) or it could be a new batch that started off with 94%. Assuming that I am not misunderstanding the guidelines somehow (and so far I am not seeing any information from your end that addresses it), it does mean that any medication pulled from a shelf has to work within the same tolerance as a freshly produced batch.

  

2 hours ago, J.C.MacSwell said:

Not allowing any drop during shelf life would make many drugs unaffordable. If you can't understand that that would be detrimental to health care I can't help you.

In other words, you ignore the issue of tolerances in manufacturing and then make things up from there, gotcha. Again, this is not how the analysis works. 

I will note that the  comment that started it was related to industrial guidelines regarding shelf life and while you were thinking about degradation within individual packages, I was thinking about the actual process (i.e. batch variation and stability testing) which fall under the guidelines. I have admitted that my initial language use was sloppy as I was taking the context under consideration without spelling it out, but again I have tried to provide context, which seemingly is continued to be ignored (and again, feel free to debunk them).

 

2 hours ago, J.C.MacSwell said:

There is a reason with some drugs that the potency requirements are stricter at manufacture or release than at later times during their shelf life. Some degradation is expected, so time left to expiration date is a factor.

OK that seems like a clear claim. Can you show me the guideline showing the differences in allowable limits and how they factor in the degradation in use. I have only done (blind) stability testing myself and was under the impression they were looking for the same tolerances. The only case I am aware of is tightening the tolerance for stability testing over manufacturing when degradation is faster than expected (the example I gave above for the thyroid medication was such a case). I.e. the stability values have to be tighter than the manufacturing tolerances, which seems to be the opposite to what you were stating.