Warning Letter For Violating Safety Rules: Fill & Download for Free

The office of prescription drug promotion (OPDP), the division of the FDA that regulates what can be used in advertisements and marketing materials for FDA-approved drugs, has guidelines that require it.The guidance is typically boiled down to what’s known as the “fair balance rule.” That is, anything (and that includes statements, words, visuals, time spent in a TV commercial, area of a journal ad) that talk about what benefits a drug can confer, has to be equally balanced with information talking about the potential risks of using the drug.OPDP has three cardinal rules that all ads need to follow (there are others as well, but these are the big ones):Going beyond the approved indication - that is, any suggestion that the drug does something in addition to the specific use that the FDA has approved it for. So for example, if a drug were approved to treat metastatic lung cancer after patients had already failed one systemic regimen, anything that made it look like it was a drug that could be given as soon as cancer was diagnosed as being metastatic would be in violation of this rule, since it’s beyond the indicated treatmentOverstatement of efficacy - the FDA-approved prescribing information includes details from all “pivotal studies” (that is, clinical trials used to gain approvals) in section 14. This is where the different efficacy measures used in the trials are described, as well as their results. So for example, if a drug used to treat pain showed a 40% reduction in patient-reported pain scale, vs a placebo of 20% - but this was shown on a bar graph where the entire y-axis scale only went up to 40%, it could fall afoul of this rule (though OPDP has been somewhat inconsistent in this particular issue) because it would look like the pain reduction scale went to 100% instead of just 40%Minimization of risk - this is probably the most important rule. Anything that suggests that a drug is safer than the clinical data actually support, either through omission of safety data or showing it in a way that makes it look less severe than it actually is, violates this rule. This is where the fair balance rule gets applied. So for example, if I have a page with a 35 point font header saying “In a clinical study, X drug reduced inflammation due to arthritis by up to 34%” and then lower on the page, in 22 point font, I have a headline saying “22% of patients experienced a grade 2 or lower adverse event” that could technically be in violation of the rule, since I’m showing visually that the efficacy overpowers the safety, and hence the piece is misleading because the efficacy claim isn’t fairly balanced with the safety claimWhat you see in TV ads is application of the fair balance rule. Even those first 5 seconds where all you see is grandma and grandpa walking down the beach with their golden retriever, even if there’s no accompanying voiceover or text on screen, is considered by OPDP to be an efficacy claim because it suggests that someone taking the drug can partake in that activity. So all those safety warnings you hear later on are to balance out that “efficacy” portion of the ad, and failure to be sufficiently comprehensive or balanced in their presentation or length could result in a warning letter or fine to the manufacturer from OPDP.

All marketing and sales materials produced by a pharmaceutical company to promote an FDA-approved drug or device are subject to oversight by the office of prescription drug promotion (OPDP), an arm of the FDA.OPDP has three cardinal sins that it tries to stop:Going beyond an approved indication. Every drug has a specific “indication” that outlines which patients are eligible for it and under what circumstances. This is based on the clinical trial data that’s included in the submission package from the company for approval. Any attempt to make it appear as if the drug can be used to treat something for which it is not approved (like, for example, a drug approved to treat Follicular Lymphoma after failing chemotherapy trying to make it seem like it can be used as a first-line treatment, or a drug approved for treating people with Type 2 Diabetes making it seem like it’s also appropriate for treating people with Type 1 Diabetes) will fall afoul of this rule and potentially get the company in trouble.Overstatement of efficacy. Section 14 of every drug’s prescribing information outlines the demonstrated effectiveness of that product in treating people within its approved indication. Any sleight-of-hand that makes it seem like the drug is more effective than it actually is can get the company in trouble. For example:This figure is taken from the Eliquis website and shows the reduction in stroke or systemic embolism of Eliquis compared to the generic warfarin. There’s a 21% relative risk reduction, but see the scale on the chart? I’m sure they would have loved to just showed the chart between 1 and 2% event rates per year, so the difference would be really stark between the two. But they more conservatively showed in a much longer scale, so as not to seem like the efficacy was being overstated.Minimization of risk. This is really what the question is getting at. OPDP does not look at all kindly on anything that might make it seem like the risks associated with using the drug are less than they actually are based on the clinical data. One common way to do this is through the use of what’s called “fair balance” while discussing the drug. That is, there’s a rough guideline that for any content talking about what the drug can do to treat a patient, an equivalent amount of content talking about the potential safety risks of the drug also needs to be included. Hence the long voiceovers at the end of pharmaceutical ads listing safety concerns. Pharma companies (obviously) don’t include these because they want to, but because OPDP requires it as safety information that “balances” out the prior discussion of efficacy. It’s pretty obvious here:As you can see, just about exactly at the 45 second mark (halfway through the ad) it stops talking about how the drug works or how it can help patients, and starts getting into adverse reactions and contraindications. That’s fair balance. OPDP probably takes this more seriously than anything else. If you do anything to suggest that your drug is safer than it actually is, they will not be pleased, and can levy large fines as a result.More often than not though, OPDP will simply issue what’s called a “warning letter” that goes to the manufacturer and tells them they need to change what’s in the promotional material or risk being fined. This can be expensive for the company since they’ll have to pull that material from the market and recreate it (or abandon it and lose the money they invested in it).Of course, this applies to marketing materials, but there’s also quite a lot of in-person drug promotion from sales reps, and the company isn’t able to exert as much control over them since you can’t physically restrain people from saying things that OPDP wouldn’t like. This is harder to find out but OPDP also doesn’t like it very much. Drug companies will create fairly strict rep training materials that severely discourage this sort of behavior (and provide them some measure of legal distance if a sales rep “goes rogue” and starts violating established guidelines to promote their drug.)To answer the larger question - yes, of course drug companies don’t want you to focus on any potentially dangerous effects of their drugs and would prefer that you only think about the benefit those drugs can bring. But it comes down to a question of their risk tolerance in doing so. OPDP has limited resources and can’t review everything that a drug company does in promoting their products, so the company has to ask itself “is the potential fine from the FDA if we get caught worth the potential gain in prescription sales if we don’t?”Usually the answer is no, but of course there’s always going to be some bad apples. What companies will do is try to come as close to the line as possible in terms of being OK with OPDP rules but still being as effective from a promotional perspective as they can be.Colloquially, at least, there’s some thought that companies that often fall afoul of OPDP rules have a harder time getting their drugs approved or getting beneficial label language that will help them promote their drugs. I haven’t done a formal analysis to see whether that’s actually the case, but many companies believe it to be, and so will do what they can to maintain as positive a relationship as possible with the FDA.

Pharmaceutical industry plays a vital role in the in the healthy life in modern society. It is addressing so many issues that are related to human health. The industry is not only providing the medicines, but also became a crucial part in the new global economy.Manufacturing of medicines was industrialized in the 20th century with the advancement of chemical engineering. Organic chemical synthesis stood as a backbone of the industry. Scientist successfully implemented isolation and purification technologies to produce individual organic compounds with high quality.The bulk drug is a substance which is used in the manufacture of the pharmaceutical product, i.e., medicinal drug product such as tablets, ointments and syrups. This is also called as "Active Pharmaceutical Ingredient (API)" or "Drug Substance".Manufacture of Bulk Drugs is a critical one and at the same time, it is expensive. It requires a lot of resources and technical knowledge. Developing a consistent process to manufacture a specific drug is not that much easy as we think. Meeting required quality while maintaining safety measures is a major challenge to the bulk drug industry.An active pharmaceutical ingredient (API) is a substance which is used in the preparation of a drug product. API andexcipients (inert materials) together form a drug product which is used for the treatment of diseases in human beings. The API is also called as a drug substance.The pharmaceutical industry is directly controlled by the Governments. Every country has its own country-specific regulations and Health Ministries. WHO governs the industry at an international level.Every country has its own Pharmacopoeia. The following are some examples.1. WHO - International Pharmacopoeia2. USA - United States Pharmacopeia (USP)3. India - Indian Pharmacopoeia (IP)4. European Union - The European Pharmacopoeia (Ph. Eur.)5. Japan - Japanese Pharmacopoeia (JP)6. China - Chinese Pharmacopoeia (CP)7. United Kingdom - The British Pharmacopoeia (BP)Implementation of Good Manufacturing Practices (GMP) is mandatory in the manufacturing plants. Transparency and data integrity must be maintained at any cost. Violation of these rules may lead to severe consequences as per the law laid in their country. The majority of drugs are exported to the USA, as it is a profitable market. US FDA is taking strict measures against the violations of Drugs law.You might have heard about the warning letters from US FDA for some companies in recent years. This is the result of GMP violations. The companies cannot do any business in the countries from where they received warning letters. Because public health is the topmost priority for the governments in any country. Ultimately, this leads to, business losses and sometimes imprisonment also.The pharmaceutical industry is manufacturing many of the active pharmaceutical ingredients(APIs) of the pharmaceutical drugs by organic synthesis method.Organic synthesis starts with simple compounds. The "starting material" is the one which begins the reaction, i.e., the very first compoundThe length of the process may be from two steps to 50 steps long or higher, based on the target molecule's complex structure. The reaction starts sequentially from the first step to the final step until the target molecule's structure is achieved. In between, an "intermediate" forms at each step.Once the process of organic synthesis is finalized, R&D chemist prepares the target molecule in small quantities in a laboratory. If everything goes well and the target molecule forms with the expected quality and yield, then it goes for the commercial scale in the plant.Learn the pharmaceutical scince and it gives immense pleasure.