Regulatory Open Forum

Hi Ryan.

This is always a fun question to answer (I do a lot of career fairs for people from middle school through college) and is always one that gets a lot of conversations going.  Before I go on, let me make it clear that I am in an area of regulatory that is rather different from many (possibly most) of the regular contributors that I see on the responses here at RAPS Exchange - I work in cosmetics and OTC products and have been in that world for my entire 30 years (so far) of a career.  But here are a few that I generally have had some interesting (and sometimes hysterically funny) conversations over during my career:

1. "Aren't all registrations the same?  I mean you're just telling the government about the product we want to sell - doesn't one simple file cover everything we need?"  Well, in some ways in the world of (A)NDAs and PMAs some of that might be true on the surface - but even in these worlds where the major global markets are moving further and further towards similarity and recognition of standards/expectations/formats/etc. the fact is that even in these areas there is really not necessarily a true "single document" that doesn't need to be amended or supplemented with further information for different countries.  In the OTC market there really isn't even the potential for even a single label because the US (and sometimes Canada) recognize some products (sunscreens, acne, etc.) as drug products while the rest of the world generally regulates these products as cosmetics which means that the use of the US label could be considered unacceptable in the rest of the world - oh, and that doesn't even consider the fact that even though Canada and the US consider these products as drugs the two countries have just enough differences in their labeling as to make it impossible to even use a single label for the US and Canada!
2. "We committed to the market that the product would be on shelf by XX/XXXX and we have to hit that commitment.  What is taking so long for us to receive final clearance of the product?"  What often causes this is simply government review times or even something as mundane as getting a document showing that your production facility complies with GMPs or has been audited in the past X years or even just getting a free sales certificate (equivalent to a certificate to foreign governments from FDA) for the countries in question.  But trying to explain this simple issue to some of my commercial sales colleagues has proven to cause significant amounts of graying of the hair I have remaining on top of my head (or in really bad cases significant loss of that limited amount of hair due to pulling it out in frustration!).
3. "When will we be able to move forward with this project?  You've had the information for a week - why isn't your assessment done and the ingredient listing released to us yet?"  For anyone who has ever worked in these areas they will almost always tell you that the point where all the "other delays" that have occurred in a project are expected to be made up it comes at the point where regulatory issues the ingredient listing for inclusion on the label.  I have even had situations where the ingredient list process was provided with 3-4 weeks in the project timelines but where the project has already fallen 3 months behind and the expectation was that regulatory would be able to issue an ingredient listing within the same day that the formulas were finalized at 5:30pm local time.  Not only is that unreasonable but it is also begging for disaster and significant costs when an issue is noted in the artwork after providing the ingredient list with errors.  That doesn't even get to the idea of whether there are any ingredients that are being used for the first time in any of the products that we have already produced - because almost every product launch has at least a few of these "trending" ingredients.  So in those situations, unless the information is readily available at the time the final formula is approved we need to gather that information from any of several different sources.  Then consider that the product requires registration in multiple jurisdictions so the ingredient list needs to consider all of them to get the information correct.  Or the fact that the US laws have changed and are continuing to evolve since the passage of the Modernization of Cosmetic Regulations Act (MoCRA) back in December 2022.  

These are just a few of the fun ones that I have had to explain or re-explain or "OTC explain" (you know - the explanation of the issues down to the level of a 6th grade reading level) or whatever else to get people in the organization to understand what the issues are and how they can significantly impact costs, timelines, plans, etc.

Hi Ryan.

This is always a fun question to answer (I do a lot of career fairs for people from middle school through college) and is always one that gets a lot of conversations going.  Before I go on, let me make it clear that I am in an area of regulatory that is rather different from many (possibly most) of the regular contributors that I see on the responses here at RAPS Exchange - I work in cosmetics and OTC products and have been in that world for my entire 30 years (so far) of a career.  But here are a few that I generally have had some interesting (and sometimes hysterically funny) conversations over during my career:

1. "Aren't all registrations the same?  I mean you're just telling the government about the product we want to sell - doesn't one simple file cover everything we need?"  Well, in some ways in the world of (A)NDAs and PMAs some of that might be true on the surface - but even in these worlds where the major global markets are moving further and further towards similarity and recognition of standards/expectations/formats/etc. the fact is that even in these areas there is really not necessarily a true "single document" that doesn't need to be amended or supplemented with further information for different countries.  In the OTC market there really isn't even the potential for even a single label because the US (and sometimes Canada) recognize some products (sunscreens, acne, etc.) as drug products while the rest of the world generally regulates these products as cosmetics which means that the use of the US label could be considered unacceptable in the rest of the world - oh, and that doesn't even consider the fact that even though Canada and the US consider these products as drugs the two countries have just enough differences in their labeling as to make it impossible to even use a single label for the US and Canada!
2. "We committed to the market that the product would be on shelf by XX/XXXX and we have to hit that commitment.  What is taking so long for us to receive final clearance of the product?"  What often causes this is simply government review times or even something as mundane as getting a document showing that your production facility complies with GMPs or has been audited in the past X years or even just getting a free sales certificate (equivalent to a certificate to foreign governments from FDA) for the countries in question.  But trying to explain this simple issue to some of my commercial sales colleagues has proven to cause significant amounts of graying of the hair I have remaining on top of my head (or in really bad cases significant loss of that limited amount of hair due to pulling it out in frustration!).
3. "When will we be able to move forward with this project?  You've had the information for a week - why isn't your assessment done and the ingredient listing released to us yet?"  For anyone who has ever worked in these areas they will almost always tell you that the point where all the "other delays" that have occurred in a project are expected to be made up it comes at the point where regulatory issues the ingredient listing for inclusion on the label.  I have even had situations where the ingredient list process was provided with 3-4 weeks in the project timelines but where the project has already fallen 3 months behind and the expectation was that regulatory would be able to issue an ingredient listing within the same day that the formulas were finalized at 5:30pm local time.  Not only is that unreasonable but it is also begging for disaster and significant costs when an issue is noted in the artwork after providing the ingredient list with errors.  That doesn't even get to the idea of whether there are any ingredients that are being used for the first time in any of the products that we have already produced - because almost every product launch has at least a few of these "trending" ingredients.  So in those situations, unless the information is readily available at the time the final formula is approved we need to gather that information from any of several different sources.  Then consider that the product requires registration in multiple jurisdictions so the ingredient list needs to consider all of them to get the information correct.  Or the fact that the US laws have changed and are continuing to evolve since the passage of the Modernization of Cosmetic Regulations Act (MoCRA) back in December 2022.  

These are just a few of the fun ones that I have had to explain or re-explain or "OTC explain" (you know - the explanation of the issues down to the level of a 6th grade reading level) or whatever else to get people in the organization to understand what the issues are and how they can significantly impact costs, timelines, plans, etc.

My personal "favorite" is "The stability (or validation, or fill-in-the-blank) schedule shows the last pull date as 15 June, so we will submit by 20 June." Over the years I have spent many hours explaining to executive management that there is a great deal of work to be done between the date the final data is obtained and the time it is ready for submission.

One of my biggest issues (I mainly work with small/virtual biotech companies) is teaching clients to use the correct terms for various activities. The most frequently misused and misunderstood is "validation", followed by qualification, verification, and specification. I recently spent two weeks re-writing a client-drafted pre-IND meeting request that asked if FDA would "validate the IND", if FDA would "approve the 'specifications'", and if FDA would "approve the starting material". 

There is also significant difficulty understanding what constitutes comparability, and why it requires more analyses for late-phase changes; why accelerated stability will not support shelf-life by itself; why compliance audits should be performed in advance of contracting a vendor/CMO; and why the FDA does not care how expensive a required activity is to do; and why clinical trials cannot be started prior to filing an IND. 

I like to think of it as job security (on days when it doesn't make me chew my toes).