Ensuring bioequivalence
Most nations require generic drug manufacturers to prove that their formulation exhibits bioequivalence to the innovator product.
In the U.S., the FDA must approve generic drugs just as innovator drugs must be approved. The FDA requires the bioequivalence of the generic product to be between 80% and 125% of that of the innovator product.
This value range is part of a statistical calculation and does not mean that FDA lets generic drugs differ from the brand name counterpart by up to 25 percent.
FDA recently evaluated 2,070 human studies conducted between 1996 and 2007. These studies compared the absorption of brand name and generic drugs into a person’s body.
These studies were submitted to FDA to support approval of generics.
The average difference in absorption into the body between the generic and the brand name was 3.5 percent and is comparable to differences between two different batches of a brand drug
Bioequivalence, however, does not mean that generic drugs must be exactly the same (“pharmaceutical equivalent”) as their innovator product counterparts, as chemical differences may exist (different salt or ester – a “pharmaceutical alternative”).
A physician survey in the US found that only 17% of prescribing physicians correctly identified the USFDA's standards for bioequivalency of generic drugs.
A latest development to address this issue enables interested doctors and consumers to check generic drug interactions and outcomes detail to the specific drug and drug company.
The generic equivalent of name-brand warfarin has only been available under the trade name Coumadin in North America until recently.
Warfarin (either under the trade name or the generic equivalent) has a narrow therapeutic window and requires frequent blood tests to make sure patients do not have a subtherapeutic or a toxic level.
A study performed in the Canadian province of Ontario showed that replacing Coumadin with generic warfarin was considered safe.
In spite of the study, many physicians are not comfortable in allowing their patients to take the branded generic equivalent agents.
As such, in countries such as Australia where warfarin is prescribed under more than one brandname (Marevan in 1 mg, 3 mg, 5 mg respectively and Coumadin in 1 mg, 2 mg, 5 mg respectively, etc.), the pharmacist may not substitute brandnames.
In regards the specific example of Australia, this only occures if the Doctor has written the prescription out using a brandname & ticked the box on the prescription marked "Brand substitution not permitted".
If the doctor has left that box unticked on the prescription, then the pharmacist can make out the prescription using any equivalent brandname drug (that's available with the same active ingredient makeup in the same dosage with similar levels of sustained release) to the brandname drug the prescription is written out for, just as if the prescription was written out by the doctor using the certified name of the active ingredient/s in the 1st place rather than specifying a particular brandname for the same medication (for example "methadone 10mg" instead of "Physeptone 10mg").
U.S. generics approval process
Enacted in 1984, the U.S. Drug Price Competition and Patent Term Restoration Act, informally known as the “Hatch-Waxman Act”, standardized U.S. procedures for recognition of generic drugs.
An applicant files an Abbreviated New Drug Application (or “ANDA”) with the Food and Drug Administration (FDA) and seeks to demonstrate therapeutic equivalence to a specified, previously approved “reference listed drug”.
When an ANDA is approved, the FDA adds the drug to its Approved Drug Products list, also known as the http://www.fda.gov/cder/ob/ “Orange Book”, and annotates the list to show equivalence between the reference listed drug and the approved generic.
The FDA also recognizes drugs using the same ingredients with different bioavailability and divides them into therapeutic equivalence groups. For example, as of 2006, diltiazem hydrochloride had four equivalence groups all using the same active ingredient but considered equivalent only within a group.
On October 4, 2007, FDA launched the Generic Initiative for Value and Efficiency, or GIVE. The initiative will use existing resources to help FDA modernize and streamline the generic drug approval process.
GIVE aims to increase the number and variety of generic drug products available. Having more generic-drug options means more cost-savings to consumers, as generic drugs cost about 30 percent to 80 percent less than brand name drugs.
In the United States, generic drug substances are named through review and recommendation of the United States Adopted Names (USAN) Council.
Further Reading
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