Are Generic Drugs Dangerous?

A Tough Pill to Swallow

As a physician, I was always taught that generic drugs were a great option - in fact, usually preferred, if available. Big pharma inflates brand name drug prices, taking advantage of ill individuals.

Generic versions are said to be biologically equivalent to the brand name medication and allow for a huge cost savings for patients and insurance companies alike.  It cannot be argued that quite often, generic medications are literally life saving. 
 
This is what pharmacy and medical students are told during their education process. It is also what the FDA states on its website: “A generic drug is identical–or bioequivalent–to a brand name drug in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use. Although generic drugs are chemically identical to their branded counterparts, they are typically sold at substantial discounts from the branded price.”
 
So shouldn't we always choose generic over brand name? The answer isn't so clear.  

Medical school is much akin to military boot-camp.  What doesn't kill you makes you stronger and you best fall in line or get run over. Certain patterns of learning are steadily engrained into brains over years and years.  

I believe this style is necessary in order to train physicians to recognize life threatening symptom patterns in patients, although this style also comes with a downside: creating medical soldiers who do not question safety from the top down.  In this case, the government and the FDA.  

Gulp.

When this member asked about the safety of generic drugs, I felt a bit like I was about to embark on a conspiracy theory, best left to jaded medical minds.  But I also had a nagging feeling that I needed to look under the hood, even though I was not fully prepared for what I would find.  
 
If you want to take a look under that hood, read on...

Bottle of Lies

Investigative journalist,  Katherine Eban, recently published a book entitled "Bottle of Lies", which documents the concern surrounding the safety and purity of overseas generic pharmaceuticals. You can hear interviews with her in the two following links.... I highly recommend a listen.  

https://www.npr.org/sections/health-shots/2019/05/16/723545864/the-generic-drugs-youre-taking-may-not-be-as-safe-or-effective-as-you-think

and
 
https://www.democracynow.org/2019/5/20/bottle_of_lies_how_poor_fda


Generic Pharmaceuticals
 

  • The generic pharmaceutical industry brings in $93 billion dollars per year

  • 80% of active ingredients in all US drugs are made overseas

  • 40% of all finished drugs in the US are manufactured in India

  • 90% of all US drugs are generic forms


Brand name pharmaceuticals are protected by many layers of patents and when the time comes to allow generic versions, the brand name companies don’t simply hand over the formula wrapped in a big red bow. 

Generics are technically very challenging to create. They need to be reverse engineered; deconstructed and then reconstructed in a laboratory. This includes the not just the active ingredients, but all chemical constituents, the time-release formulations, and in the end, they need to be “bio-equivalent”. 
 
The FDA’s definition of bioequivalence is surprisingly broad: The active ingredient’s maximum blood concentration must not fall more than 20% below or 25% above that of the brand name. This equates to a potential range of 45% in total. The additional ingredients, known as excipients, can be different and are often of lower quality. 
 

The Hatch-Waxman Act 

In the 1980s, the Hatch-Waxman Act allowed generics to be pushed to manufacturing sooner. Looser guidelines of this act gave companies an incentive to file ASAP, because companies who are first to file receive 6 months of exclusivity on the market, and can sell at approximately 80% of the brand name price; all without the rigorous testing given to those filing as a brand name.
 
Eban notes that as of 2005, most of the generic medicines being sold in the U.S. are manufactured overseas, mostly in India and China (this is both due to looser environmental regulations and for manufacturing savings). The U.S. Food and Drug Administration states that it holds foreign plants to the same standards as U.S. drug-makers.
 
But is this true? 


Logistics

In the US, FDA inspectors show up to pharmaceutical manufacturing plants unannounced and stay as long as they want. Overseas, the FDA announces their travel plans ahead of time. Overseas manufacturing plants “host” the FDA, often arranging for accommodation and travel logistics for US FDA inspectors. This allows time for strategic staging and false documentation.  

"These plants know that [the FDA inspectors are] coming," Eban says. "I discovered [some overseas drug companies] would actually ... alter documents, shred them, invent them, in some cases even steaming them overnight to make them look old."


Bringing it Home 

The concern about impurities and safety is higher for people on maintenance medications who take these drugs day in and day out. If the drugs have toxic impurities, these impurities can build up in the liver (which filters everything taken by mouth). Often, patients are totally unaware, or they may suffer from unrecognized side effects before realizing they were switched to a different generic or they were switched from a brand name to a generic.

Eban advises consumers to research generic manufacturers and look up any problems that regulators have found.

With 2 autoimmune diseases myself, I decided to do a bit of sleuthing.  I grabbed a recently filled generic medication and looked up the manufacturer: Mylan. Specifically, I looked into "FDA Warning Letters, Mylan".  

Exhibit A: A warning letter written to Mylan in November of 2018: 
https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/mylan-laboratories-limited-nashik-fdf-517906-04032017

Some highlights of this letter here: 

  • "1. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192)."

  • "2. Your firm failed to establish an adequate quality control unit with the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated (21 CFR 211.22(a))."

  • "Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture."

  • "If you are considering an action that is likely to lead to a disruption in the supply of drugs produced at your facility, FDA requests that you contact CDER’s Drug Shortages Staff immediately, at drugshortages@fda.hhs.gov, so that FDA can work with you on the most effective way to bring your operations into compliance with the law. Contacting the Drug Shortages Staff also allows you to meet any obligations you may have to report discontinuances or interruptions in your drug manufacture under 21 U.S.C. 356C(b) and allows FDA to consider, as soon as possible, what actions, if any, may be needed to avoid shortages and protect the health of patients who depend on your products."


Thyroid Connection

Do you know the number 1 most commonly prescribed pharmaceutical in the US? It's neither a blood pressure medication, nor a high cholesterol medication. It's levothyroxine, the generic thyroid medication used to treat low thyroid function.  And it's one that needs to be taken day in and day out.   

If you take thyroid medicine, you may have been made aware of a recent national shortage. This had medical facilities in a panic of sorts, calling every pharmacy in town to order the largest possible quantity for patients.

I have to assume with this type of pressure on manufacturers, along with huge financial obligations, shortcuts might be tempting. Was the recent shortage due to multiple FDA violations and subsequent reduced production, or were shortcuts taken to supply the demand?   

Even with the FDA at the helm of the ship, responsible for patient safety, there are always gaps in the midst of storms, whether intentional or unintentional.

In private practice, I have seen an upswing in unexplainable side effects and seemingly erratic laboratory values, not to mention poor hypothyroid symptom management. Medications that once kept patients stable for most of their lives seem to be wavering in efficacy. I may never have proof of generic impurities or contamination, but when it smells like a rat, it's probably a rat.  


Override 

Here lies another issue.  Even when generic pharmaceuticals cause unwanted effects and fall short in therapeutic efficacy, consumers may find they are not allowed by their health plan to switch to alternatives, because of cost.

There are times when, as an overseeing physician, I can tell the pharmacy NOT to fill the generic form of a medication, but not always.  

Pharmacists are often encouraged to offer patients the generic form of medications whenever possible, and insurance companies can also override my medical advice on brand name, or at least, refuse to cover the brand name cost.

At times, with stacks of paperwork, and late nights free of compensation, I can win an argument with the insurance company.  Sometimes, the patient ends up agreeing to pay out of pocket and at other times, both the patient and I give up, exhausted of resources.  


A Breathe of Fresh Air

This is where I have found compounding pharmacies to be invaluable. 

Pharmacy compounding is the art and science of preparing personalized medications specifically formulated for an individual. Compounded medications are “made from scratch.” Individual ingredients are mixed together in the exact strength and dosage form required by the patient. This method allows the compounding pharmacist to work with the patient and the prescriber to customize a medication to meet the patient’s specific needs.

Myth:

  • Compounded medications are not regulated because they are not subject to FDA regulation.


Myth Buster:

  • Compounded medications are not regulated by the FDA because they are governed at a state level, not federal, and always have been.  

  • Standards set by the United States Pharmacopeia (USP) are used in compounding.

  • Compounding pharmacies are required to prove their products contents, and in fact, are often held to more strict manufacturing guidelines than the large pharmaceutical companies. 

  • Accredited pharmacies follow standards set by The Pharmacy Compounding Accreditation Board (PCAB).


However, the majority of health insurance companies do not cover compounded medications at this point in time. The FDA also seems to be set on threatening the existence of compounding pharmacies, which is another subject for another day. 
 

Knowledge as Power

I leave you with knowledge as power.  We may not always want to face the issues at hand, and it may seem disheartening, but trust your gut. If you feel that odd symptoms occurred around a medication refill or a change from brand to generic form, speak to your physician; they are not always aware of just how often these issues arise.
 

Further References: 
http://fortune.com/2013/01/10/are-generics-really-the-same-as-branded-drugs/
 
https://www.peoplespharmacy.com/2011/04/11/why-pharmacists-are-wrong-about-generic-drugs/