True Confession spoken to the only people who deserve it

The BBQ Pit
1

Dear SDMB readers,

This is a very personal rant. I have no real plans on swearing. You will find no creative insults here. But there is nothing to debate, I am not asking any questions, and I don’t want your opinion, so there is nowhere else to place this.

I share this with you all because I respect you.

I am neither a theist nor an atheist. I am not an agnostic. I really am a Discordian. Do not ask me if that is a joke; if you know anything about Discordianism you should know enough that a straight answer can never come to such a question. Similarly, do not ask me if the teachings of Discordianism are a joke.

I am not straight or gay. It is a stretch of the imagination to call me bisexual.

I am not a conservative, nor am I a liberal. Moderation finds no home in me.

I do not believe that everything is mind, and I do not believe that everything is matter. All propositions that begin with “Everything is…” are nonsensical, including this sentence. That is paradoxical, but it is not meant to be witty or insightful.

I do not reject labels. I do not reject generalizations. I do not endorse stereotypes, but I find them impossible to do without. In reading this you may form a generalization or three about me, which are welcome to do. Language demands universals; anyone who rejects them rejects their own mode of speech, and that paradox, too, is not meant to be witty or insightful.

…

Two things have happened to me today which, throught the context of Discordianism, are linked. One might be tempted to cry “synchronicity”, but there are good folks on this board that would reject anything said afterwards, so I shall not do so; should anyone else feel compelled to make such an analysis, I will not be offended.

The first thing is my introduction with the FDA’s 21CFR Part 11 regulations for work on data integrity and electronic signatures. My initial introduction-- a prequel, if you will-- to this was several weeks ago. My impression was that it was simply a means of storing data gathered during drug studies to ensure that no one was tampering with it. My gut reaction was philosophical skepticism; that is, I knew such a hope was impossible. While I do not consider myself to be a startling example of the species, I do have the audacity to feel that beauracracy itself is the worst way to handle integrity of anything. Paperwork is something beauracrats use to cover philosophical mistakes. As Ayn Rand has mentioned, one can avoid reality, but one cannot avoid the consequences of avoiding reality. While this applies to beauracrats, it also applies to me (it applies to everyone, and yes this is paradoxical given previous statements; please don’t think you are being witty by pointing that out).

Today was my real introduction to 21CFR11 compliance. It was four 1000+page books. The cost of this testing was over $300,000 US. The point of this was so that the beauracrats we are required to have in our company can guarantee the beauracrats in other companies that everything is cool. It does not, and cannot, serve any other purpose.

The intention was to solve the rather sticky problem of scientists tampering with data. This is not a small issue. Constrained by time and budgets (which is not a flaw of the capitalist system but is inherent in all realities where resources are finite, though if it occurred to you to think it was a flaw of capitalist resource allocation then I suppose this comment wouldn’t phase your partisanship anyway, so I waste precious time in typing them), scientists will often creatively interpret or arrange data to give the answer needed.

This, clearly, could not be accepted. And you’ll have to trust me that it was enough of a problem that it got the beauracratic engine turning over, gasping for oxygen to combust fuel.

You see, the average armchair philosopher like myself, unbound by things like religion or politics, can tell at a glance when a thing is impossible. Also not being restricted by a zen-like notion of avoiding labels, I am not ashamed to say so.

This regulation will stifle growth. Period. Anyone who has worked with it or is about to will see that instantly. I cannot stare at four binders that size for an instrument that simply reads spectral data and say with a straight face that it is a good thing we have this. If watches needed to comply with this no one could tell time. I know there are some people involved with 21CFR on this board, and they will surely chime in to agree with me, quibble, or outright deny my claim.

So be it. Specrometers are not complicated devices, and collecting data from them is a somewhat simple task. That we are required to create such a heavy set of papers to explain this strikes me as absurd by inspection.

This weekend I will have the opportunity to read over the regulation itself. I plan to write a very long letter to the FDA about this. Nevertheless, I feel compelled to share this with you, my internet friends and (possibly) enemies (though if I have any here, I am not aware of it).

The second event that sparked this is the current “issue” about atheism, the PoA, and such commentary. When I first sat back to think about the pledge some time ago (actually, it was in boot camp, but that isn’t really relevant), it struck me in a similar manner: patently absurd by inspection. There is no way to interpret the pledge without practicing state religion, and I mean that in the Big Brother sense, not that the state is actually endorsing a religion.

That is what those words mean. That is how we would use those words.

I am ashamed to be a human when I hear someone complain that I (or someone else) shouldn’t complain about being subjected to the pledge on a regular, ritualistic basis. Ritual and repetition is the basis for all learning; it is not sufficient, but it is necessary. You did not learn your native language from a dictionary or some other tome, you learned it through use, being subjected to others using it, and repetion of this.

The so-called “social contract”, the notion of proper conduct in contextual situations, are also not learned from books (though they could be). They are learned from being subjected to it. There is no arguing about this. You wear clothes because that is what you do, not because it is illegal to walk around naked.

Being subjected to the pledge, even if not required to speak it, is being subjected to state religion, to the religion of the state.

Red Skelton’s little quip on the pledge is amusing for its prima facie ignorance. It specifically details exactly what the words mean and then proceeds to comment that it would be a shame if it were banned!

Greek sophists could not compete with such doublethink. Lawyers, bound by language itself, would be at a loss to fight such bologna. The only way to combat the tar-baby that is the praise of the state is to laugh at it for all its absurdity, the same way I plan to laugh at the 21CFR. It is beyond self-contradictory (like my claim that all propositions that begin with “all propositions” are false).

The pledge only makes semantic and contextual sense in the realm of state religion. It should be held in contempt or be outright vilified in all other situations. It is worship of a false idol. It replaces gods. It makes unsupportable labels. It demands impossible requirements. It requires a lack of inquisitiveness. It stifles thought. There is no question about a literal interpretation, and anyone who tries to pull the old “figurative interpetation” schtick on me will get a swift internet :smack:. The time and manner which we are subjected to the pledge does not afford even the brightest person access to the critical facilities necessary to command a figurative interpretation, and even if it were, it would still be impossible.

This is my assertion. I hope it offends someone, because that is why I type it. I like people agreeing with me, and it warms my heart to receive the occassional email complimenting my statement of opinion/interpretation/etc from these boards. But it would not please me for anyone to agree with this (it wouldn’t disappoint me, either, before anyone thinks that). It would please me only if everyone agreed with it.

I take offense to the notion that I must comply with 21CFR in order to put out an instrument. I take offense to the notion that I must learn and (should I have any children) teach my kids about religion so that they might “understand” what is going on out there.

Religion and patriotism have become tar-babies. They are now butting heads with beauracracy. This, in my slippery slope estimation, spells doom for compelling and interesting freedom of thought, opinion, and action.

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For clarity’s sake, the initial impetus for 21CFR was simply a means of electronic submission of information to the FDA. But the reason they had to make it so blasted complicated was because of the data integrity issue. Hope that didn’t mess anyone up.

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C2 by '92

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21CFR Part 11 is huge.

It is cumbersome.

It is entirely achievable.

Pharmas and the companys the contract to, and support, them must jump through hoops, and document the hell out of everything in pursuit of Part 11 (henceforth refered to as ERES: Electronic Records/Electronic Signatures).

Why…?

Because Ethical Pharmaceuticals (read: Prescription Drugs) must be verified efficatious and reasonably non-hazardous to human life, and in order to do that, the data reviewed by the FDA must be of highest quality and highest confidence (else we have an ImClone / Erbitux - style disaster). In order to speed review, increase commonality in submission format, and reduce overhead, the FDA is going towards Electronic Submission,and the Pahrmas are using electronic document and data management. Electronic records are more easily manipulated, making them more vulnerable to adulteration for motives numerous. They are also more susceptable to inadvertant modification due to bugs and flaws. Therefore, these records must be protected and verified as closely as possible within the practical bounds of feasibility.

Hence, ERES.

The Pharmas have their hands pretty well wrapped around ERES. They’ve been following proceedures that lend towards ERES for decades. It’s called Validated software and processes. There are large numbers of firms that sepeciallize in helping pharmas meet validation, and the pharmas have internal resources that are highly expert in this area. To ensure that the pharmas, bio-science companies, Contract Research Organizations, Consulting firms, software makers, and all the rest meet requirements, the FDA has AUDITORS.

I put AUDITERS in allcaps becasue these people are scary. They’re good. They have the power to shut-down a drug line or even take more drastic measures, if they feel it necessary, and they’re willing to use it. I’ve seen an auditor thumb through a stack of code print-out, and stop on the one place where the code wasn’t commented. They’re that good.

It is fear of the AUDITOR, and the FDA, that ensures that Validation efforts are followed through, and it is detailed process that makes damn sure the results are as expected.

People are fallible, sometimes lazy, sometimes worse, but Validated Process covers the gaps, and catches the mistakes, and Validated Software ensures the data remains intact and correct from entry to submission. You need both.

I work in the regulatory affairs department of a major pharma. Before that, I consulted to Pharmas, life science, and healthcare. Validation and ERES are a pain in the arse, but they work, and progress goes forward. ERES does not hinder progress for companies that are willing to meet it head on. It’s only when a company tries to avoid the requirements that trouble starts.Yes, ERES is slow, and it’s requirements are heavy, but they are there to ensure that the data that shows a drug is safe and efficatious is actually the data that is suppposed to be there.

ERES is to prevent a company from hiding a Thalidomide.

If you want to play in the drug market in the US, you have to be willing to prove that your data is accurate, appropriate, and untampered with. Its part of the cost to ensure that drugs are reasonably safe. That is also part of the reason that drugs are fairly expensive… The review and testing process is deliberately long and involved to ensure that as much data as possible is available before submitting, and that follow-up data is constantly provided after submission.

New drugs and biologics get developed and submitted all the time, and ERES has NOT stopped that.

I understand that ERES can be a rude shock to a company or a person that’s not used to doing things in a highly rigorous, controlled, and documented fashion, but that’s what you’ve got to do, if you want to play a part in developing chemicals and biologics that people are going to put into their bodies.

Deal with it.

Don’t expect too much from your letter to the FDA: They also must follow the law, and 21CFR Part11 is law.

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Writing over 4000 pages of information about collecting spectral data is not efficient, does not guarantee safety, doesn’t eliminate overhead, drive down cost, or speed development in any hypothetical world, nevermind this one. When all is said and done, the same work must be done to bring a drug to market, coupled with all the extra work and documentation for compliance. This, in no reality, can be said to be quicker or cheaper. Whoever has convinced you otherwise is lying. Paperwork is not what takes so long to bring a drug to market. Drug development is not done in ten minutes and then followed by 4 years and 11.99 months of paperwork.

My job has become 1000 times more complicated because some incompetent can’t be trusted to submit real data. I cannot accept this without complaint. If that is a terrible inconvenience for you, you’ll just have to deal with it.

That last sentence was meant to be witty and insightful.

Regards,
erl

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[sub]and I wasn’t expecting much… I’d be surprised if I even got a form letter that had anything to do with the regs. :)[/sub]

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erislover I feel your pain.

Now, how about some gucamole?

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Oh, Encinitas, don’t tease me like that. My taste buds haven’t been the same since. :slight_smile:

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erislover, I don’t expect you to enjoy it. It’s a monumental pain. However, in a world filled with fallible, and sometimes mendacious, people, this is the only way to prove that, in the end, all data is as it is supposed to be. This is an “Absolute Minimization Of Risk” effort, and it will be intrusive. Indeed, while I have no doubt that you’re fully caring, carefull, and competant, how are you going to prove that to an FDA reviewer, 10, 18 months, or even years down the road…? Should they simply take your word on it…? Your employers word…? Even if you are then working somewhere else…? Or have (God Forbid) passed away…? This are just a tiny sample of the contingencies the FDA must account for.

You think this is bad…? Try doing the verification from the Pharma’s end and processing it purely on paper: You ain’t seen nothing yet!

Sure, ERES slows you way the hell down, and yet, it will speed the process for the CRO, Pharma, and FDA. Why…? Because they will not need to come back and check again. You, by complying with ERES, provide to the contracting organization the assurance that your data is sound and unadulterated (assuming you’ve followed GLP). The Pharma and/or CRO, by complying with ERES, provides the assurance to the FDA that all the accumulated non-clinical and clinical data is unadulterated, and then the FDA has only to review the submission.

The final proof…? Submission review time is averaging a year from final submission, sometimes even as little as six months, and despite massive increases in quantities of data, and numbers of studies, review time has not increased! This is not all, or even mostly, due to ERES, but Part11 is a significant part of the mix that allows timely review to continue despite the increased load of material.

I realize that you can’t see the big picture from where you sit, and that you have a steep learning curve ahead of you, and I’m sorry about that, but it the FDA does not have the resources to make the kinds of exceptions that you seem to want them to make… They don’t have the resources to inspect, examine, hear appeals, deal with people trying to slip through the cracks, and deal with all the myriad administrative issues that will be raised if they go into the business of making exceptions.

That would require an agency vastly more huge and bloated than we already face. That would be slow (even if your little part is easier)! Finally, even if they did have the resources, there is no lawful mechanism for permitting the exception you want. ERES is not intended to make life easy for you, it’s to ensure that the material available for review is of the highest confidence, allowing the agency to review with a minimum of QA and audit, because QA is built into every step.

And, in the end, like or not, it’s the law. Deal with it, as I have to.
In short, welcome to the club.

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This is a major hijack, but is the statement “everything is” internally self consistent?

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I wouldn’t say it is inconsistent or not, but it can’t be descriptive. How would “Everything is X” say anything more than “Everything is”?

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There are 3 sorts of societies.

(Actually there are a great deal more and furthermore I am not an anthropologist. But this is the Pit, so I’ll continue.)

In the first, everybody knows everybody. This society is what humans are best adapted to, since it reflects the conditions of their ancestral environment. Group size ranges from 30 to 500, with a strong bias towards the lower end of the range. Murder is rampant. Reputation matters; insulting someone is an extremely serious act, since a reputation for weakness can have mortal consequences.

In the second society, everybody knows somebody who knows somebody who knows anybody that matters. The remainder are nobody. Reputation still matters, but institutions partly displace relationships. Anonymous markets are possible, although caveat emptor is extremely important: you don’t make a serious purchase from somebody unless you know them at least indirectly. Merchant societies in ancient India, Arabia come under this heading, as does guild-dominated medieval Europe and even Victorian England. In some variants, respect for virtuous living has it’s mirror image in acceptance of hypocrisy. Society #1 is considered to be barbaric by the virtuous.

In the third society, you no longer need to know your contractual associates personally, as you are protected by a web of laws and regulations. Such is life in contemporary developed countries. The risk of unexpected mortality plummets, though that does little to curb feelings of anxiety. Celebrity replaces virtue. In this land of big brother there is a greater potential for anonymity and privacy as a much smaller group of neighbors feels obliged to monitor your behavior or character.

This creates some interesting paradoxes as technology drives the costs of inflicting mayhem on the body politic downwards. But that’s for another thread.

Society #2 is considered prudish by the sophisticated members of society #3.

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From the context of this thread, Tranq, go fuck yourself. I most assuredly will “deal with it”. This post is part of that effort, but your blind-obediance-legal-lapdog diatrabe isn’t making it any easier to accept the conclusion that comapnies with billions of dollars are forcing me and mine to make up for their mistakes and problems and there is piss-all I can do about it.

Maybe Yossarian didn’t live after all.

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erislover, you are being a bit closeminded and egocentric about this whole regultion thing aren’t you? Granted I know nothing about this law other than what you and tranquilis have told me about it, but I think I have the gist.

Take a step back from yourself and your situation. This law seems to have been enacted to enforce a code of ethics amongst scientists. While I am sure that no scientist who is dedicated to his field and his own accuracy would alter his research to hurry a drug onto the market, there are those who are not so concerned with the results of thier research. There are CEOs out there who would very much like to start making money from a drug before it is fully tested and verified.

That being said: Get over it. I’m real sorry that you have to do some extra work. I am not sorry that some new drug is going to do it’s job and not produce Thalidimide babies because it was untested.

In closing, get the fuck over yourself. You are not the most important person in this equation. That would be the consumer. Face facts buddy. The law was enacted for a reason.

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I pledge allegiance to the flag of the United States of America, and to the republic for which it stands, one nation, indivisible, with liberty and justice for all.

Fuck you!

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More salient advice: “Get over it”. This is truly grand! “Gee, erl, we know that you are basically being punished for other people’s problems, but get over it! The rest of the public gets safer drugs! You should be happy you’ve been chosen to serve a billion-dollar industry, and have you and yours bear the costs yourself.”

Shall I be digging my own grave, too? Would that suit you? I’d hate to be a burden on anyone.

Why do I doubt that?

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Because you have a finely tuned nose for sarcasm I hope. :smack:

So your solution is to get rid of the rules and give everyone really shitty drugs backed by research that is possibly slipshod? Is that a real answer?

Were you just trying to blow off steam, or are you seriously complaining about having to meet the necessary standards to protect the public from money hungry drug corporations? If it is the former please let us know because you sound silly otherwise.

If it is the latter, then you can go fuck yourself with the regulation book. You want to sound erudite and then belie that with your petulant complaining. “I don’ wanna do that much work!”

Wah, Wah. Shut the fuck up.

Good God man.

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Because you have a finely tuned nose for sarcasm I hope. :smack:

So your solution is to get rid of the rules and give everyone really shitty drugs backed by research that is possibly slipshod? Is that a real answer?

Were you just trying to blow off steam, or are you seriously complaining about having to meet the necessary standards to protect the public from money hungry drug corporations? If it is the former please let us know because you sound silly otherwise.

If it is the latter, then you can go fuck yourself with the regulation book. You want to sound erudite and then belie that with your petulant complaining. “I don’ wanna do that much work!”

Wah, Wah. Shut the fuck up.

Good God man.

19

Heck no! My solution is to have the companies that are the source of the problem be the solution to it. I can document a spectrometer 8 ways to Sunday and it isn’t going to change the operation of the instrument.

“Necessary” is the word in question, in my estimation. I had a long talk with my boss about my concerns for the regulation, and he did not disagree with me.

For example: we have an instrument for sale. End-user cost is approximately $22K US. I’ll let you guesstimate what the raw cost comes out to be. In order to document this, the cost will be between $50K and 300K (strongly leaned toward the 300K side, for the record).

How does anyone bring this product to market? We are in a bad spot. The demand for this instrument is there, but not in the quantity which would allow us to profit from it to cover such expenditures as 21CFR11 demands. So what do we do? Two options: sell the instrument without compliance and lose business, or eat profits. Raising the price significantly in order to recuperate development costs is almost out of the question. The instrument just isn’t worth that much, even if it comes with a 4000 page book. The alternative to this method makes experiments three times as long. However, factoring in higher costs of an instrument versus higher labor costs on experiments that aren’t run all the time (but are no less necessary) leads one to a not-so-cheery conclusion.

I’ll let you decide how that helps the world.

Yes, I am trying to blow of steam. But there is no “just” to it. Following this regulation requires extensive documentation all along the development process. And I do mean extensive. Funny thing about development, though, is that it is a rather seat-of-the-pants operation. Procedures change, better methods are discovered or developed. It is simple to say that “this is what you should have been doing all along.” It also requires little thought. Management theory, to my understanding, has never quite figured out how to impliment formalism without stifling creativity and progress. Formalism tends to create factories, and research goes by the wayside. When the costs of research increase, and the expected payoff is the same (or less), then the drive to research is running on low-octane fuel.

But, hey, I must just be a lazy fuck.

20

Despite spiralling trial sizes, the ever increasing need to document the living shit out of every process to avoid lawsuits (and if your company is going the CRO route, it WILL be either named or subpeaned, sooner or later), and all the other difficulties, submission review time is actually trending downward. Slowly so, sure, but when you consider that it’s doing so against the current, so to speak, I have to fairly impresssed.

I’m not blind in my support of this law, I’ve got a sense of misson. I have three projects under development right now, and they would all be easier if I could toss Part 11. But I willingly deal with Part 11 requirements. Why? Because it means that the next time the FDA has to question my work, I show them my validation paperwork, and they go away again, that easy. I won’t have to deal with a lengthy, distracting audit, buring my time, resources, and interfering with my job.

Validate once, properly, and it’s done. Maintain the code, the proceses, and it’s easy once you’ve gotten it done. It’s only the start-up that it’s a bitch.

you’d be better served dumping your energy into the learning curve that whining about it. You’re now sounding like a little kid that doesn’t want to take her medicine. You may as well take it and be done, your crying about it isn’t geting it done any quicker.