Generics – Frequently Asked Questions

What is a generic drug?

A generic drug is identical — or bioequivalent — to a brand name (innovator) drug in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use.

What do I need to know to distinguish between generics?

Medications have two names – the brand name which is the name decided upon by the drug company and the generic name which describes the main ingredient in the drug. The brand name is usually written in larger print than the generic name. Some generic drugs may only show the name of the inactive ingredient, others will have a brand name and some will bear the drug company’s name as the brand name. Apart from that, the drug manufacturer’s name is separately written in the jar/packaging. Generic drugs may differ in shape, size, color, flavoring due to the inactive ingredients used. The inactive ingredients are considered safe by the FDA and should not affect the effectivity of the drug. However, some people may have sensitivity to them and should always check. The generics may also differ in packaging and expiration date. Ask your pharmacist if the generic substitution is a therapeutic equivalent to the innovator drug.

How are generic drugs approved?

Drug companies must submit an abbreviated new drug application (ANDA) for approval to market a generic product when the patent protection for the innovator drug expires. The ANDA process does not require the drug sponsor to repeat costly animal and clinical research on ingredients or dosage forms already approved for safety and effectiveness.

What standards should a generic manufacturer must meet to get approval?

The generic drug must:

• contain the same active ingredients as the innovator drug (inactive ingredients may vary)
• be identical in strength, dosage form, and route of administration
• have the same use indications
• be bioequivalent
• meet the same batch requirements for identity, strength, purity, and quality
• be manufactured under the same strict standards of FDA’s good manufacturing practice regulations required for innovator products

What is an active ingredient?

The active ingredient is the chemical that has the desired biological effect. A drug may contain several ingredients but the active ingredient is the one that has an active effect in the body and should be the same for the generic version of an innovator drug.

Are there differences between generic and innovator (brand name) drug?

Generic drugs may vary in inactive ingredients like salts, excipients (color, flavor, and preservatives); manufacturing process, product name, and packaging; shape and size; and expiration date.

When the inactive ingredients differ significantly in their safety and/or efficacy profiles, the generic manufacturer has to submit to the FDA further proof of efficacy and safety.

Inactive ingredients are usually harmless substances that do not affect the body. They are used to provide bulk so that a tablet is large enough to handle, to keep a tablet from crumbling before it reaches its end user, and to help a tablet dissolve in the stomach or intestine for absorption and provide a pleasant taste and color. However, some inactive ingredients can cause unusual and sometimes severe allergic reactions in a few people. Ask your pharmacist for the drug package insert or use a searchable database like DailyMed to find out the inactive ingredients in your generic medication.

What does bioequivalent means?

Two related drugs are bioequivalent if they show comparable or no clinically significant difference in their bioavailability and similar times to achieve peak blood concentrations.

Bioequivalence studies are a surrogate marker for clinical effectiveness and safety data as it would be impractical and deemed unethical to repeat clinical studies for generic products.

One way to demonstrate bioequivalence is to measure the time it takes for the generic drug to reach the bloodstream in 24 to 36 healthy volunteers.  This gives them the rate of absorption (bioavailability) of the generic drug, which is then compared to that of the innovator drug.  The generic version must deliver the same amount of active ingredients into a patient’s bloodstream in the same amount of time as the innovator drug (bioequivalence).

It is important to note that bioequivalence studies are also performed for innovator drug manufacturers in some situations such as: between early and late clinical trial formulations or between the formulations used in clinical trials and the product to be marketed for new medicines; and when changes in formulation have occurred after an innovator product has been approved, for example a change in one or more excipients (inactive ingredients).

What is the accepted bioequivalence method and criteria?

In bioequivalence studies, participants are separated into two groups. The study is performed in two stages: In the first stage, Group A is given a generic drug and Group B is given the brand-name of the drug. Blood samples are collected at different points in time to assess the bioavailability of the drug in both groups of participants.

The following are measured to assess bioavailability:

• Maximum concentration of the drug in the plasma (C_max)
• Time it takes to achieve the maximum concentration (T_max)
• Extent of drug absorption based on plasma concentration and time (AUC)

At the second stage of the study, the group that received the generic drug in stage one is given the brand-name drug, and the group that was given the brand-name drug is given the generic drug. The bioavailability of the drug in the two groups is assessed in the same way as stage one. Each stage is separated by a washout period.

The bioavailability of the brand-name drug is then compared to that of the generic drug in each individual. When these comparisons show a relatively similar extent of both absorption and maximum drug concentration, bioequivalence is achieved and the generic drug is shown to be as safe and effective as the brand-name drug.

A generic drug must pass the following criteria: 90 percent confidence intervals of 80-125 percent AUC and C_max after log transformation.

This does not mean that drug concentrations can vary by 45 percent between the brand-name and the generic drug. This simply means that the allowable statistical total error is 10% (±5% from upper and lower limit after the 80 – 125% for AUC and C_max are log transformed). The true difference between brand and generic, as far as bioequivalence is concerned, is less than 5% and is not considered to be clinically significant for the vast majority of drugs. Most generics approved today are in the range of 3-4% difference in absorption.

What is bioavailability?

Bioavailability is a measurement of the extent and rate of the therapeutically active medicine that reaches the systemic circulation and is therefore available for absorption at the site of action. For example:

Drug A given orally has a bioavailability of 70%. This means that for every 100mg of the drug administered, 70 mg of it is absorbed unchanged. Reasons contributing to this could be that there is incomplete absorption in the GI tract or that 30% the drug was metabolized before it reaches the systemic circulation (e.g. first pass effect in the liver – most orally administered drugs are metabolized by the liver before entering the systemic circulation)

Are generics safe and effective as the innovator drug?

All generic medicines in the United States are approved by the Food and Drug Administration (FDA) and have been shown to be bioequivalent to the innovator drug according to standards. This means that any differences in bioavailability between generic and innovator drug are not clinically significant.

It is accepted that if plasma concentrations of the active ingredient of the generic and innovator medicines are the same, then their concentration at the site of action and therefore their safety and effectiveness will be the same.

Why are generic drugs cheaper?

Although generic drugs are chemically identical to their branded counterparts, they are typically sold at substantial discounts from the branded price.  Drug research is long and costly, and patent protection gives brand-name manufacturers at least 20 years to recover those costs—costs that generic manufacturers do not have.

What does patent-protected mean?

New drugs, like other new products, are developed under patent protection which lasts for a varied amount of time. The patent protects the investment in the drug’s development by giving the company the sole right to sell the drug while the patent is in effect. When patents or other periods of exclusivity expire, manufacturers can apply to the FDA to sell generic versions.

Is there a generic equivalent for my brand-name drug?

For outside the U.S., please check with the equivalent drug authority in your country.

To find out if there is a generic equivalent for your brand-name drug in the United States, use Drugs@FDA, a catalog of FDA-approved drug products, as well as drug labeling.

You can also search for generic equivalents by using the Electronic Orange Book. Search by proprietary “brand” name,” then search again by using the active ingredient name. If other manufacturers are listed besides the “brand name” manufacturer when searching by the “active ingredient,” they are the generic product manufacturers.

Since there is a lag time after generic products are approved and they appear in the Electronic Orange Book,  you should also consult the most recent monthly approvals for First Generics.

How will I know how other patients are doing on generic imatinib?

The Life Raft Group Patient Registry has been collecting patient data for over 15 years, from which we are able to identify common side effects, successful treatment patterns, and other resources to share with the public. We plan to continue to collect information as patients start generic imatinib, and share key information with our community as presented. Synonymously, patients can share their stories on the Life Raft Group ListServ, a patient-based forum utilized to share patient stores, and experiences as they navigate GIST.

How can I find out more about generic imatinib?

Currently, we are pursuing efforts to gain more patient education to share with our population. We will also be coordinating a webinar in the coming months to disseminate more verified information.

Why would my doctor choose the generic option rather than the brand name drug?

Doctors may prescribe the generic imatinib rather than the brand Gleevec in order to account for the patient’s financial or insurance restrictions. We advise patients to talk with their physicians regarding this option, to determine what might be the best plan for treatment.

Cost and Insurance Coverage

Will Medicare only pay for Generic?

Medicare guidelines state that when a drug is available in both generic and brand-name forms, some Medicare Prescription Drug Plans have pharmacists fill the prescription with the generic drug, even if the doctor wrote the prescription for the brand-name drug. In some cases, a doctor can indicate that the brand-name drug is medically necessary and that a generic cannot be substituted.

Some Medicare Prescription Drug plans have specific rules to cover these exceptions; contact your plan for more information. (http://www.ehealthmedicare.com/medicare-part-d-prescription/generic-drugs/)

Medicare Part D uses private plans to provide coverage for prescription drugs to beneficiaries, including senior citizens and certain people with disabilities. The federal government doesn’t set the amounts that plans pay for prescription drugs. Instead, plans directly negotiate payment rates with pharmacies and rebates from drug manufacturers as part of the competitive bidding process. Such competition provides incentives for plans to control their costs.

Federal laws require pharmacists to tell beneficiaries if a generic substitute is available. In most states, however, the pharmacist must get your consent, or at least inform you, when a generic drug is being substituted. If you prefer the brand-name drug even when your doctor prescribes its generic equivalent, you may be able to buy the brand-name drug and pay a higher copayment.

What if my drug isn’t covered or I think it should be on a different tier?

If your drug isn’t covered by your plan, you have the right to appeal. It is important to know the reason for the coverage denial so you know which step to take next. For instance, you have rights if your drug isn’t on the plan’s formulary, requires prior authorization, you’d like the drug covered on a lower tier, etc. You will likely need information from your doctor to request a coverage exception  or appeal a coverage denial detailed here.

What do I need to know about Medicare drug coverage (Part D) when choosing between brands versus generics?

If you are a Medicare patient, you have the option to join a Medicare Prescription Drug Plan (Part D).

To get Medicare drug coverage, you must join a plan through an insurance company or other private company approved by Medicare. There are two ways to get Medicare drug coverage¹:

1. Medicare Prescription Drug Plan (Part D) – These plans (also called “PDPs”) add drug coverage to Medicare.
2. Medicare Advantage Plan (Part C) (MA-PDs) – This plan acts like an HMO or PPO or other Medicare health plan (like Medicare Cost Plans, Medicare Private Fee-for-Service (PFFS) Plans, or Medicare Medical Savings Account (MSA) Plans) that offers prescription drug coverage. You can get Medicare Parts A and B and D through these plans.

If your Medicare Advantage Plan (Part C) includes prescription drug coverage and you join a Medicare Prescription Drug Plan (Part D), you’ll be disenrolled from your Medicare Advantage Plan and return to Original Medicare.

The Medicare drug plan incorporates the following payments throughout the year:

• Premium
• Yearly Deductible
• Copayments or coinsurance
• Costs in the coverage gap
• Costs if you get Extra Help
• Costs if you pay a late enrollment penalty

The Medicare Part D Standard Design has 4 phases. Deductible (may not apply), Initial Coverage, Coverage Gap (donut hole), and Catastrophic Coverage. Medicare beneficiaries that get Extra Help, also known as Low-Income Subsidy, to help pay the costs of their Part D plan and medication, do not have to pay higher prices out-of-pocket in the donut hole.

If your plan has a deductible, then every year you must pay a deductible (Up to $360 in 2016) for your prescriptions before your Medicare Prescription Drug Plan begins to pays its share of your covered drugs^3,4.

After you have paid the deductible, the next phase is the Initial Coverage phase and includes the amount you pay for each of your prescriptions with either a copayment or coinsurance (depending on a person’s selected plan). Some PDPs have different tiers of copayments or coinsurance. One should check that Gleevec and generic imatinib are available and on which tier of Medicare Part D because it impacts the price.

The next phase is the donut hole or the coverage gap. Patients may enter donut hole as early as the first prescription. In 2016, once you and your plan have spent $3,310 on covered drugs, you’re in the donut hole.^5,6 When in the donut hole, the patient is responsible for paying a higher percentage of the cost of prescriptions until they are through the donut hole.

When in donut hole, the patient is responsible for paying 45% of the cost of the branded therapy versus 58% of the generic therapy.

This donut hole exists until the steps with the Affordable Care Act are fully implemented which will in fact eliminate the donut hole altogether by 2020.

The last phase is Catastrophic coverage. Once the patient’s out-of-pocket medication payments plus their 50% brand name drug discount reaches $7,062.50 in 2016, they enter this last phase. At this point, the patient is responsible for greater of 5% of the costs or $2.95 for generic or $7.40 for brand (or non-preferred) drugs⁷.

The National Council on Aging has great resources to help you navigate this process.

One should note that most Part D plans are not standard plans. This means calculating TrOOP (True Out of Pocket) costs during the initial deductible and Initial Coverage Phase varies by plan. You can enter your medications for an estimate of the costs on the Medicare Plan Finder at www.medicare.gov. If you would like help sorting through your Part D choices or to see if you can get help paying some of the costs, the following are good resources of information:

1. Extra Help (click the ‘Do I qualify’ question to see the limits) to pay Part D costs based on your income and assets.
2. Medicare Savings Programs can help pay Medicare Part B premiums and other costs based on income and assets.
3. The NCOA BenefitsCheckUp tool helps you see if you qualify for programs to help with some of your costs. Set aside 20-40 minutes to complete the check up because you must complete it once you start vs. saving and returning to the site.
4. The State Health Insurance Assistance Program (SHIP) is a great source for free, unbiased help with Medicare and these programs. State contact information is available here shiptacenter.org.

To learn more information about Medicare, please visit www.medicare.gov.

1. https://www.medicare.gov/sign-up-change-plans/get-drug-coverage/get-drug-coverage.html

2. https://www.medicare.gov/part-d/costs/part-d-costs.html

3. https://www.medicare.gov/part-d/costs/deductible/drug-plan-deductibles.html

4. This amount may change each year.

5.  https://www.medicare.gov/part-d/costs/coverage-gap/part-d-coverage-gap.html

6.  This amount may change each year.

7. https://www.medicare.gov/part-d/costs/catastrophic-coverage/drug-plan-catastrophic-coverage.html

Will my private insurance still cover Gleevec when the generic becomes available even if the doctor prescribes Gleevec?

The doctor can prescribe the brand name drug Gleevec to patients and note to the pharmacy to “dispense as written” or “DAW.” However, if a patients insurance carrier does not cover the brand name, the doctor will be consulted by the pharmacy regarding the option to switch to the brand name.

State “Dispense as Written” Laws vary state by state. Please refer to: http://beta.aan.com/globals/axon/assets/4698.pdf to learn more information regarding your state policies and brand name requests.

To prevent substitution of your preferred brand name drug to its generic drug equivalent, please refer to the How to Prevent Substitution Guide.

Will my private insurance cover branded Gleevec or generic imatinib?

It is a complex process to make an informed decision about the right insurance plan for you.

Here is a list of questions you may want to consider when reviewing an insurance plan:

• Are the medications covered under the formulary?
• Are there restrictions on brand versus generic medications?
• What are the potential out of pocket costs?
• Are there benefit caps? This means that after a plan pays a certain amount for the year, it will not cover certain medications.
• Does the plan have an out of pocket max for prescription drugs in order to ensure the patient does not max out the prescription co-pay card?

Please note that Novartis has a free benefit investigation program in which a patient and provider can request Novartis to do a benefits investigation of private and publicly insured programs on their behalf. Novartis can help patients monitor potential changes to their insurance which may include annual benefit updates, employment changes, etc.

Is there co-pay assistance for branded Gleevec for privately insured patients?

Patients who have private insurance may be eligible for the Novartis $10 co-pay card for a 30-day supply of Gleevec. Please visit www.Gleevec.com or speak with a representative at 1-866-GLEEVEC (453-3832) to register for the co-pay card.

There are eligibility requirements for this assistance. As of this date, the co-pay card will cover up to $10,630/month for a 30-day supply and up to $30,000 per year that a patient is required to pay out of pocket for the drug (These numbers are not based on the true cost of the drug but based on patient out-of-pocket expenses). Examples:

Scenario 1: If a patient’s co-pay is $200/month, the co-pay card will kick in and the patient only has to pay $10/month.

Scenario 2: If the patient has a deductible of $12,000 to pay upfront, then the copay card will assist up to the $10,630 for that month; therefore, the patient pays $1,380 ($10 plus $1,370). Any remaining co-payments or co-insurance must be under $10,630 per month or less than $30,000 out of pocket expenses per year in order to qualify for the co-pay card to assist.

Most patients fit within these parameters and are encouraged to contact Novartis to apply. Please note that the co-pay card is not valid for cash-paying patients, Medicare, Medicaid, or any other federal or state program. The Program runs until 12/31/2016. Please see the Patient Assistance Programs page for more details.

Side Effects

What should I expect for side effects?

Currently, we are only familiar with the side effects associated with the brand name Gleevec. Since the generic imatinib contains the same active ingredients, it is likely that patients may experience similar ones. As with all side effects, they will vary patient to patient. It will be important to monitor these side effects and discuss treatment options with your physician.

The FDA monitors adverse events reports for all drugs including generic drugs in an effort to evaluate safety of drugs after approval. Reports are monitored and investigated, when appropriate. The investigations may lead to changes in how a product (brand name and generic counterparts) is used or manufactured.

Will generic imatinib respond the same way as brand name Gleevec when combined with over-the-counter drugs?

Response may vary case-by-case. As recommended, talk with your doctor before starting any over-the-counter drugs, so that an informed and educated decision could be made with specific attention to your individual health. Additionally, the website: http://www.epocrates.com/ can help give feedback regarding drug interaction. However, as previously stated, any decision to use drugs concomitantly should be first conferred with your physician.

Manufacturers

Will Novartis be manufacturing the generic?

Sun Pharmaceuticals was the first manufacturer for generics with a 180-day marketing exclusivity. Teva Pharmaceutical Industries Ltd. and Apotex Pharmaceuticals have announced they will be producing the generic Imatinib starting in August 2016, and we expect more manufacturers to follow in the coming year.  For list of generics available worldwide, please go to the Generics List page.

Availability

Will the Generic be regularly available in pharmacies?

The generic form should be accessible in most pharmacies, especially those that already provide the brand-name Gleevec.

What if I want to stay on the brand-name Gleevec?

You and your doctor may discuss the option to stay on Gleevec rather than switching to Imatinib based on your clinical information. For the full listing of the dispense as written laws, please go to the How to Prevent Substitution Guide.

Next Steps

Read About Other Treatments

How to Prevent Substitutions Guide

Generics Resources