Educating Groups Influencing Generic Drug Use

Target audience: healthcare professionals, providers
Format: electronic newsletter
Content to cover: generic drug safety and efficacy, effectiveness, access and cost

Safety and efficacy
Generic drugs are important options that allow greater access to healthcare for all Americans. They are
the same as brand-name drugs in dosage form, safety, strength, route of administration, quality,
performance characteristics, and intended use.
All generic drugs approved by the U.S. Food and Drug Administration (FDA) through abbreviated new
drug applications (ANDAs) have the same high quality, strength, purity, and stability as brand-name
drugs. Also, the generic manufacturing, testing, and packaging sites must pass the same quality
standards as those of brand-name drugs.
As part of the ANDA, the generic drug manufacturer must prove its drug is bioequivalent to the brandname drug. This means that the generic drug must deliver the same amount of active ingredient(s) into
a patient's bloodstream or other target action site in the same amount of time as the brand-name drug.
Through review of bioequivalence data, the FDA ensures that the generic product performs the same as
its reference brand-name product. This standard applies to all generic drugs, whether immediate- or
modified-release.
Healthcare providers can search therapeutic equivalence codes for generic drugs in the Approved Drug
Products with Therapeutic Equivalence Evaluations (commonly known as the Orange Book). Recently,
the Orange Book 2.0 mobile app, which provides fast and easy searching of the Orange Book, became
available free of charge at Apple and Android app stores. Additionally, availability (manufacturer,
approval date, and strength) of generic drugs can be searched in the Drugs.com Generic Drug Database.

Effectiveness
A systematic review and meta-analysis published in 2008 evaluated the results of 38 published clinical
studies that compared cardiovascular generic drugs to their brand-name counterparts. There was no
evidence that brand-name cardiovascular drugs worked any better than generic cardiovascular drugs.1
An updated systematic review and meta-analysis published in 2016 further strengthens the evidence for
clinical equivalence between brand-name and generic cardiovascular drugs.2
However, although recent evidence has supported generic substitution for drugs with narrow
therapeutic index (such as some antiepileptics,3 immunosuppressants,4 and psychotropic drugs5), it
remains controversial in medical practice. Changes in patients’ clinical status during a switch to a generic
substitute can be related to psychological, interactional, physiological, and pharmacological factors that
may or may not be related to the change to a generic drug. For example, patients have expressed
concerns that the lower cost of generics is associated with reduced medication quality.6 This perception
may contribute to adherence barriers in regimens using generic alternatives.

Communication
Patients who report talking to their healthcare providers about generic substitution are more likely to fill
generic medications than those who do not have a discussion with their providers.7 Therefore, effective
communication between patients and healthcare providers regarding generic drugs and generic
substitution plays a critical role in optimizing patient outcomes.

Access and cost
The Office of Generic Drugs (OGD) in the U.S. FDA’s Center for Drug Evaluation and Research (CDER)
continues to provide access to cost-saving generic drugs. In 2016, OGD approved 630 abbreviated new
drug applications (ANDAs) and tentatively approved 183—the highest number of generic drug approvals
and tentative approvals in the history of the generic drug program (OGD Annual Report for 2016). FDAapproved generic drugs account for 89% of prescriptions dispensed in the United States (IMS Institute
for Healthcare Informatics). On average, the cost of a generic drug is 80% to 85% lower than the brandname product. Use of generic drugs has saved the U.S. healthcare system almost $1.7 trillion in the past
10 years, leading to cost savings for consumers.8
OGD has published more than 1,500 product-specific guidance documents related to developing generic
drugs, which are posted on the FDA’s website. These guidelines are intended to help generic drug
manufacturers develop and evaluate their generic drugs in a scientifically sound way. The public can also
access available educational resources regarding generic drugs such as brochures, posters, and
audio/multimedia presentations on the FDA’s website.

Pricing Resources for Generic and Brand-name Drugs
Micromedex 2.0®
Available from
Truven Health Analytics®
Cost
Individual subscription or
Institutional subscription
Access
Web
Mobile app
Price location
Red Book® tab
Searchable by
Product name
Active ingredient
Price source
Red Book®
Price type
Average wholesale price (AWP)
Prices by
Generic or brand
Strength
Package- and unit-quantity
Dosage form
Manufacturer
National Drug Identifier Code (NDC)

Epocrates®
athenahealth
Free
Web
Mobile app
Manufacturer/Pricing section
Product name
Active ingredient
GoodRx.com
Approximate retail price
Generic or brand
Strength
Select quantities
Dosage form

References
1.
2.
3.
4.
5.
6.
7.
8.

Kesselheim AS, Misono AS, Lee JL, et al. Clinical equivalence of generic and brand-name drugs
used in cardiovascular disease: a systematic review and meta-analysis. Jama.
2008;300(21):2514-2526.
Manzoli L, Flacco ME, Boccia S, et al. Generic versus brand-name drugs used in cardiovascular
diseases. European journal of epidemiology. 2016;31(4):351-368.
Yamada M, Welty TE. Generic substitution of antiepileptic drugs: a systematic review of
prospective and retrospective studies. The Annals of pharmacotherapy. 2011;45(11):1406-1415.
Ensor CR, Trofe-Clark J, Gabardi S, McDevitt-Potter LM, Shullo MA. Generic maintenance
immunosuppression in solid organ transplant recipients. Pharmacotherapy. 2011;31(11):11111129.
Carbon M, Correll CU. Rational use of generic psychotropic drugs. CNS drugs. 2013;27(5):353365.
Colgan S, Faasse K, Martin LR, Stephens MH, Grey A, Petrie KJ. Perceptions of generic
medication in the general population, doctors and pharmacists: a systematic review. BMJ Open.
2015;5(12):e008915.
Shrank WH, Cox ER, Fischer MA, Mehta J, Choudhry NK. Patients' perceptions of generic
medications. Health Aff (Millwood). 2009;28(2):546-556.
Association for Accessible Medicines. Generic Drug Access and Savings in the U.S. 2017;
http://accessiblemeds.org/sites/default/files/2017-06/2017-AAM-Access-Savings-Report-2017web2.pdf.

Target audience: formulary managers, policymakers, large purchasers
Format: electronic newsletter
Content to cover: FDA generic drug approval process, bioequivalence, effectiveness, access and cost

FDA generic drug approval process
Each year, the U.S. Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research
(CDER) approves a wide range of generic drug products submitted through abbreviated new drug
applications (ANDAs). The ANDA process does not require the generic drug manufacturer to repeat
costly animal and clinical research on ingredients or dosage forms already approved for safety and
efficacy with brand-name products. Rather, to gain FDA approval, a generic drug must:
•

•
•
•

Be pharmaceutically equivalent to the brand-name drug, which means it must:
o Contain the same active ingredients as the brand-name drug (inactive ingredients may
vary)
o Be identical in strength, dosage form, and route of administration as the brand-name
drug
o Have the same indications for use as the brand-name drug
Be bioequivalent to the brand-name drug (more details below)
Meet the same batch requirements for identity, strength, purity, and quality as the brand-name
drug
Be manufactured under the FDA’s same strict Good Manufacturing Practice Regulations
required for brand-name drugs

Bioequivalence
To obtain an ANDA approval, the generic drug manufacturer must prove its drug is bioequivalent to the
brand-name drug. This means that the generic drug must deliver the same amount of active
ingredient(s) into a patient's bloodstream or other target action site in the same amount of time as the
brand-name drug. Through review of bioequivalence data, the FDA ensures that the generic product
performs the same as its reference brand-name product. This standard applies to all generic drugs,
whether immediate- or modified-release.
Generic and brand-name drug products are considered to be therapeutically equivalent only if they are
pharmaceutically equivalent products with demonstrated bioequivalence. The coding system for
therapeutic equivalence evaluations is a two-letter system. Multisource drugs are coded with a first
letter as follows: (1) A: Drug products that the FDA considers to be therapeutically equivalent to other
pharmaceutically equivalent products; and (2) B: Drug products that the FDA does not consider to be
therapeutically equivalent to other pharmaceutically equivalent products at this time. The second letter
provides additional information on the basis of the FDA's evaluations. For example, “AB” indicates a
drug product for which actual or potential bioequivalence problems have been resolved with adequate
in vivo and/or in vitro evidence supporting bioequivalence.
1

Healthcare providers can search therapeutic equivalence codes for generic drugs in the Approved Drug
Products with Therapeutic Equivalence Evaluations (commonly known as the Orange Book). Recently,
the Orange Book 2.0 mobile app, which provides fast and easy searching of the Orange Book, became
available free of charge at Apple and Android app stores. Additionally, the availability (manufacturer,
approval date, and strength) of generic drugs can be searched in the Drugs.com Generic Drug Database.

Effectiveness
A systematic review and meta-analysis published in 2008 evaluated the results of 38 published clinical
studies that compared cardiovascular generic drugs to their brand-name counterparts. There was no
evidence that brand-name cardiovascular drugs worked any better than generic cardiovascular drugs.1
An updated systematic review and meta-analysis published in 2016 further strengthens the evidence for
clinical equivalence between brand-name and generic cardiovascular drugs.2
However, although recent evidence has supported generic substitution for drugs with narrow
therapeutic index (such as some antiepileptics,3 immunosuppressants,4 and psychotropic drugs5), it
remains controversial in medical practice. Changes in patients’ clinical status during a switch to a generic
substitute can be related to psychological, interactional, physiological, and pharmacological factors that
may or may not be related to the change to a generic drug. For example, patients have expressed
concerns that the lower cost of generics is associated with reduced medication quality.6 This perception
may contribute to adherence barriers in regimens using generic alternatives.

Access and cost
The Office of Generic Drugs (OGD) in the U.S. FDA’s CDER continues to provide access to cost-saving
generic drugs. In 2016, OGD approved 630 abbreviated new drug applications (ANDAs) and tentatively
approved 183—the highest number of generic drug approvals and tentative approvals in the history of
the generic drug program (OGD Annual Report for 2016). FDA-approved generic drugs account for 89%
of prescriptions dispensed in the United States (IMS Institute for Healthcare Informatics). On average,
the cost of a generic drug is 80% to 85% lower than the brand-name product. Use of generic drugs has
saved the U.S. healthcare system almost $1.7 trillion in the past 10 years, leading to cost savings for
consumers.7
OGD has published more than 1,500 product-specific guidance documents related to developing generic
drugs, which are posted on the FDA’s website. These guidelines are intended to help generic drug
manufacturers develop and evaluate their generic drugs in a scientifically sound way. The public can also
access available educational resources regarding generic drugs such as brochures, posters, and
audio/multimedia presentations on the FDA’s website.

2

Pricing Resources for Generic and Brand-name Drugs
Micromedex 2.0®
Available from
Truven Health Analytics®
Cost
Individual subscription or
Institutional subscription
Access
Web
Mobile app
Price location
Red Book® tab
Searchable by
Product name
Active ingredient
Price source
Red Book®
Price type
Average wholesale price (AWP)
Prices by
Generic or brand
Strength
Package- and unit-quantity
Dosage form
Manufacturer
National Drug Identifier Code (NDC)

Epocrates®
athenahealth
Free
Web
Mobile app
Manufacturer/Pricing section
Product name
Active ingredient
GoodRx.com
Approximate retail price
Generic or brand
Strength
Select quantities
Dosage form

References
1.
2.
3.
4.
5.
6.
7.

Kesselheim AS, Misono AS, Lee JL, et al. Clinical equivalence of generic and brand-name drugs
used in cardiovascular disease: a systematic review and meta-analysis. Jama.
2008;300(21):2514-2526.
Manzoli L, Flacco ME, Boccia S, et al. Generic versus brand-name drugs used in cardiovascular
diseases. European journal of epidemiology. 2016;31(4):351-368.
Yamada M, Welty TE. Generic substitution of antiepileptic drugs: a systematic review of
prospective and retrospective studies. The Annals of pharmacotherapy. 2011;45(11):1406-1415.
Ensor CR, Trofe-Clark J, Gabardi S, McDevitt-Potter LM, Shullo MA. Generic maintenance
immunosuppression in solid organ transplant recipients. Pharmacotherapy. 2011;31(11):11111129.
Carbon M, Correll CU. Rational use of generic psychotropic drugs. CNS drugs. 2013;27(5):353365.
Colgan S, Faasse K, Martin LR, Stephens MH, Grey A, Petrie KJ. Perceptions of generic
medication in the general population, doctors and pharmacists: a systematic review. BMJ Open.
2015;5(12):e008915.
Association for Accessible Medicines. Generic Drug Access and Savings in the U.S. 2017;
http://accessiblemeds.org/sites/default/files/2017-06/2017-AAM-Access-Savings-Report-2017web2.pdf

3