Back in March, the NY Times published an article claiming that we lose $3 billion dollars each year because of the cancer drug that are wasted. The article was inspired by a paper from Memorial Sloan Kettering Cancer Center which came up with the daunting $3 billion number. The crux of the argument is that drug companies sell their products in packages that leave physicians no choice but to throw out the “extra” drug that remains after a dose is administered. If drug companies simply sold their products in more convenient sizes, we could reduce this waste and recoup some of that $3 billion.
Going even further than that, Peter Bach, one of the authors of the paper, infers that drug companies are intentionally doing this to boost their profits! That’s quite an accusation.
The leftover drug still has to be paid for, even when discarded, making it possible for drug companies to artificially increase the amount of drug they sell per treated patient by increasing the amount in each single dose vial relative to the typically required dose. – Peter Bach
In reality, reducing the wastage of drugs would have no impact whatsoever on the price of drugs. And more importantly, if drug manufacturers followed Peter’s advice and came up with more vial sizes to reduce waste, that would be going against FDA guidance and likely result in an increase of mis-dosing of cancer drugs.
It is true that cancer drugs are wasted. In fact, it’s practically unavoidable for certain drugs that are dosed based on body-weight. Since patients come in all shapes and sizes, you would need an infinite number of vial sizes in order to make sure no wastage occurred. But the question is, would reducing wastage reduce drug prices?
The answer to the question is no. Drug companies determine price independent of packaging or vial size. Let’s look at a hypothetical drug, Product A. If Product A is 10% better than a drug on the market, you might chose to price it at a 10% premium (yes, it’s more complex than that, but bear with me). If the competing drug is $1000/month, you would then price Product A at $1100/month. Keep in mind you haven’t even thought about your packaging or dosing at this point. Pretty straightforward so far.
Let’s look at a couple of extreme examples to see how you might price Product A under different vial size scenarios: (1) only one large vial size is produced and (2) 5 smaller vial sizes are produced. How would each one be priced?
Option 1: One large vial (200 mg)
This vial would be large enough so that any patient would require only one vial. The math is easy on this one, just price the vial for an average patient ($1100/month). Yes, for smaller patients, most of the vial would be thrown away, but every single patient would cost $1100/month.
Option 2: Five smaller vials (1 mg, 5 mg, 10 mg, 25 mg, 50 mg)
Since there are so many more vial sizes, there will be a lot less wastage in this scenario. Before we look at costs, lets do some math so we have the numbers we need.
If the average patient should cost $1100/month the the price per mg is $11/mg ($1100/month for average patient who take 100 mg per month).
If an average patient weights 70 kg and is taking 100 mg per month, the dose is 1.4 mg/kg.
Looking at the costs across three different patient types:
Small patient (50 kg) – they need 70 mg per month (1 x 50mg and 2 x 10mg vials), so they cost $770
Average patient (70 kg) – they need 100 mg per month (2 x 50mg vials), so they cost $1100/month
Large patient (90 kg) – they need 129 mg per month (2 x 50mg, 1 x 25mg and 4 x 1mg vials, $1414/month
What do you end up with if you average costs across all patients? A cost of $1100/month. Nothing has changed except you wasted a lot less of the drug and the large patient’s physician or nurse needs to gather up 7 vials in 3 different sizes and make sure there are no mistakes!
Now you might be saying “but you’re not wasting as much drug! Isn’t that a positive thing?” Yes, reducing waste would reduce manufacturing costs, so yes, it is a positive thing in isolation. But what if we look at the big picture?
First off, raw material costs are a very small part of the cost for most pharmaceuticals. The cost of goods sold (COGS) for most drugs is less than 10% of the price and often only a few percent. However, if you chose to create more vial sizes, that has additional expense as well. You have more vials to manufacturer, more validation studies to do, etc. Overall, the cost of having more vials might be more than the savings on raw materials!
However, the most important reason to limit the number of vial sizes is patient safety, as show in the “large patient” example above. That’s why the FDA prefers fewer rather than more vial sizes. If you go in for a chemotherapy session, do you know if the pharmacist grabbed the right vial? You do if there is only one size available. Fewer vial sizes means less of an opportunity for dosing mistakes.
In conclusion, the paper published by Memorial Sloan Kettering has good intentions, but missed out on the bigger picture. Reducing drug waste would likely result in no cost savings whatsoever and an increase in medical errors.
It seems like the debate over the cost of patented drugs never ends: patients complain about the ever increasing prices and the drug companies complain about the high costs of R&D. However, one question you rarely see asked is how much does it really cost to make that one dose of a new drug? How much of the price is profit?
Now keep in mind when I say profit I really mean contribution margin. Contribution margin is price minus the variable cost of producing a single unit and ignores the fixed costs which in the case of a new drug includes the cost of R&D, marketing and the equipment used to manufacture the drug, just to name a few. It’s called a contribution margin because it’s the part of the revenue that contributes to paying for the fixed costs. A good example of a contribution margin comes from the entertainment industry: once you’ve shot a film, paid the actors, edited the film and put it on a DVD, what is the cost of producing another copy of the DVD compared to the price it’s sold for?
In the world of pharmaceutical manufacturing, the variable cost of producing a unit of drug can vary a great deal. Relatively simple drugs, like aspirin, can be very cheap to manufacture, while the complex biological drugs, like Herceptin, can be relatively expensive to manufacture. And the costs don’t stop there. What patients typically refer to as a “drug”, is known as a “drug product”, that is the tablet or injection that patients receive. Before a drug is made into a tablet or injection, it’s known as API (active pharmaceutical ingredient) and is typically a powder of some sort. Since you can’t just give a patient a bottle of powder to take, you need to turn into into a drug product first and that can be either inexpensive (making a tablet) or very expensive (making an inhaler for an asthma medication).
BG-12 (Dimethyl fumarate)
OK, so now that we have all of the industry jargon out of the way, let’s look at an actual example using (very) rough numbers. Biogen Idec has a new drug in clinical trial for multiple sclerosis known as BG-12. BG-12 is very unique in that it is an incredibly simple and inexpensive drug. BG-12 is dimethyl fumarate, a chemical that is manufactured on a huge scale in ton quantities. To give you an example, here is a Chinese chemical supplier who is offering dimethyl fumarate for sale for $1 – $50 per metric ton, but you have to buy at least 2 tonnes and if you need a lot, they can supply up to 2000 metric tons per year. Supply is obviously not an issue here.
If BG-12 is approved by the FDA, patients with multiple sclerosis would receive 240 mg of the drug 2 or 3 times a day (based on clinical trial data). Using rough approximations, let’s calculate how much it would cost to treat one MS patient for a year using BG-12.
Cost of dimethyl fumarate: $25/ton (let’s choose the average cost)
Dose of BG-12 per day: 750 mg (let’s go with the high dose)
Total dose of BG-12 per patient per year: 750 mg * 365 days = 274 g
Total cost of BG-12 per patient per year: $25 * (274g /1,000,000 g) = $0.007
Based on the commodity price of dimethyl fumarate, it would cost less than 1 cent to treat an MS patient with BG-12 for one year. Of course you need to turn the dimethyl fumarate into tablets and put them in a bottle, so let’s assume all those added costs are $0.05/tablet. I honestly have no idea how much it actually costs to make tablets on an industrial scale, but it can’t be much considering you can buy a bottle of 100 generic Tylenol tablets at Target for about $3 or $0.03/tablet all in. However, we’ll estimate on the high side and say $0.05/tablet. If we add in the cost of the dimethyl fumarate ($0.007/tablet) and round up, we get $0.06/tablet or $65.70 to treat an MS patient for a year with BG-12. Not very expensive!
Now we know the variable cost to produce a year’s treatment of BG-12, but how much will it sell for? Well, BG-12 looks like it will be a very effective drug without a lot of side-effects, so Biogen certainly isn’t going to price it less than treatments that are currently on the market. If we take a look at this article from Pharmalot, we can see that the annual cost to treat an MS patient with current drugs ranges from approximately $36,000 to $48,000 per year. Let’s assume that Biogen will match the highest price therapy (Gilenya).
Contribution margin = revenue – variable cost
= $48,000 – $67.50
= $47,932.50 or a 99.85% contribution margin
Now before you start screaming about greedy pharmaceutical companies, remember, this is just the contribution margin. Current estimates put the cost of developing a new drug somewhere between $500M and $2B dollars. Biogen will have to treat a large number of patients for many years to recoup their development costs and begin making a profit on BG-12 (for example: treating 1000 patients with BG-12 for 5 years would pay off $1B in development costs). This is why it’s estimated that only 1 in 3 drugs that hit the market actually make a profit for the company; you may have an incredible contribution margin on a drug, but if all of the margin goes into paying off the fixed costs that went into development, you may end up not making any profit at all.
The other lesson from this exercise is now you can see why the cost of generic drugs is so low. A generic pharmaceutical company incurs only a fraction of development costs that an R&D-based company does and thus can charge a much lower price (typically 80-90% lower), receive a much smaller contribution margin and still make a profit.
Update: After some delay, the FDA has promised to make a decision on BG-12 (brand name: Tecfidera) on March 28th, 2013.