Single-Source vs Multi-Source Drugs: What Patients Need to Know About Cost, Effectiveness, and Choices

When you pick up a prescription, you might not realize you’re choosing between two very different kinds of medicine. One is made by just one company. The other? Made by many. That difference can save you hundreds of dollars a month-or cost you more than you expect.

What Exactly Is a Single-Source Drug?

A single-source drug is a medication made by only one manufacturer. Usually, that’s the original brand-name company, and no generic version is allowed yet. This happens because the drug is still under patent protection or has some kind of exclusivity from the FDA. Think of drugs like Humira before 2023, or newer cancer treatments. These aren’t just expensive-they’re often the only option.

These drugs carry an ‘N’ code in the Medi-Span system, which pharmacies and insurers use to track drug availability. Because there’s no competition, the manufacturer sets the price with little pushback. In 2023, the average list price for a single-source drug was over $900 per month, with rebates to insurers matching that increase almost dollar-for-dollar. But here’s the catch: those rebates rarely lower your out-of-pocket cost. You still pay the full price at the pharmacy unless your plan has special coverage.

Patients on single-source drugs are more likely to skip doses because of cost. A 2022 Kaiser Family Foundation survey found that 41% of people taking these drugs skipped or cut pills to save money. That’s compared to just 22% for multi-source drugs. If you’re on one of these, ask your pharmacist: Is there a generic coming? Could I switch to something similar?

What Are Multi-Source Drugs-and Why Do They Matter?

Multi-source drugs are the opposite. They’re available as both the brand-name version and multiple generic versions from different manufacturers. These drugs have an ‘O’ or ‘Y’ code in Medi-Span. They’re everywhere. In fact, 86% of all prescriptions filled in the U.S. are for multi-source drugs, even though they make up only about 23% of total drug spending.

Why? Because generics are cheaper. The FDA requires them to have the same active ingredient, strength, dosage form, and route of administration as the brand. They also must prove they work the same way in your body-bioequivalence. That means the amount of drug in your bloodstream falls within 80-125% of the brand’s levels. That’s not a loophole. That’s science.

But here’s what patients don’t always realize: even though generics are required to be identical, some people notice differences. A 2023 Drugs.com review showed 68% of negative feedback on generic drugs cited ‘inconsistent effectiveness’ between different manufacturers. That doesn’t mean the FDA got it wrong. It means your body might react slightly differently to fillers, coatings, or manufacturing processes-even if the active ingredient is exactly the same.

Price Differences: It’s Not Just About the Label

The biggest difference between single-source and multi-source drugs? Price. A 2023 study showed the average monthly cost for a single-source drug was $587. For a multi-source drug? Just $132. That’s more than 75% cheaper.

But here’s where it gets tricky. The price you see on the shelf isn’t always the price your insurer pays. Insurers use something called Maximum Allowable Cost (MAC) to set what they’ll reimburse for generics. MAC is usually 50-60% lower than the brand’s Average Wholesale Price (AWP). So if your plan uses MAC pricing, you might pay $5 for a generic, even if the pharmacy paid $15 for it.

Single-source drugs don’t have MAC pricing. They’re priced based on list price, rebates, and complex contracts between drugmakers and pharmacy benefit managers (PBMs). That’s why you might see the same drug priced at $400 at one pharmacy and $550 at another. The price isn’t fixed. It’s negotiated behind the scenes.

Therapeutic Equivalence: What the FDA Really Says

The FDA doesn’t just approve generics and call it a day. They rate them using a two-letter code in the Orange Book. If a drug has an ‘A’ code, it means the FDA considers it therapeutically equivalent to the brand. That’s the gold standard. You can switch between any ‘A’-rated generics without worry.

But some generics get a ‘B’ code. That means they’re pharmaceutically equivalent but the FDA hasn’t confirmed therapeutic equivalence. These are rare, and usually involve complex delivery systems like inhalers or injectables. You won’t see ‘B’ codes on everyday pills like lisinopril or metformin.

Patients often get confused when their pharmacy switches them from one generic brand to another. You might get a blue pill one month, a white one the next. That’s normal. It’s because PBMs switch suppliers to get the lowest MAC price. The FDA says it shouldn’t matter. But some patients report side effects or changes in how well the drug works. If you notice something different, tell your pharmacist. Ask if the manufacturer changed. You might be able to stick with the one that works best for you.

How Insurance and PBMs Control Your Choices

Your insurance plan doesn’t just cover drugs. It controls which ones you can get-and at what price. Most plans put single-source drugs on higher tiers, meaning higher copays or coinsurance. They often require you to try the generic first (called step therapy). If you’re prescribed a single-source drug, your doctor might need to file a prior authorization just to get it approved.

Even worse, some plans will drop coverage for the brand-name version entirely once a generic is available. That’s called ‘brand exclusion.’ So even if you’ve been on the brand for years, your insurer might force you to switch.

And then there’s the ‘single-source generic’ loophole. Sometimes, a brand-name company will release its own generic version-called an authorized generic. It’s the same drug, same factory, same packaging, just without the brand name. It’s cheaper than the brand, but not as cheap as other generics. And because it’s the only generic available for a while, it acts like a single-source drug. That’s how some companies keep profits high even after patent expiry.

What You Can Do Right Now

You don’t have to guess how this system works. Here’s what to do:

1. Ask your pharmacist if your drug is single-source or multi-source. They can check the Medi-Span code or look up the Orange Book.
2. Check your copay. If you’re paying over $100 a month for a common medication, ask if a generic exists.
3. Request the manufacturer if your generic switches. If you feel different after a switch, ask for the same brand again.
4. Use the FDA’s website (fda.gov/generics) to learn how generics are approved. They have simple tools to compare brand and generic versions.
5. Call your insurer and ask about MAC pricing. Find out what your plan pays for your drug. That number might surprise you.

Don’t assume your doctor knows the pricing system. Most don’t. But you can be your own advocate. Ask questions. Demand clarity. And don’t accept high costs just because ‘that’s how it’s always been.’

What’s Changing in 2025?

The FDA is speeding up generic approvals under GDUFA III. By 2025, they aim to approve generics in under 10 months. That means more single-source drugs will become multi-source faster. Drugs like insulin, certain blood thinners, and newer antidepressants are expected to lose exclusivity soon.

The Inflation Reduction Act also introduced a new penalty for drugmakers who raise prices faster than inflation-especially for single-source drugs. That’s starting to pressure companies to lower list prices or face paying back billions to Medicare.

But the real shift is in patient awareness. More people are asking: ‘Why am I paying $500 for this when someone else pays $15?’ That’s changing the game. And it’s giving you more power than ever before.