The Food and Drug Administration (FDA) regulates the ways in which modern drugs are produced, marketed and prescribed. However, the federal laws that affect this approval process weren't always in place.
Did you know that some drugs have largely been immune to these regulations for decades?
Thanks to a loophole know as the “Grandfather Clause”, many older drugs have been legally marketed and dispensed for years without receiving official FDA approval.
This clause recently changed as part of a federal safety overhaul, and many marketed unapproved drugs are now under renewed scrutiny.
If you're a health care provider or patient, this clause and its recent changes may affect your medication options.
Exceptions to FDA Approval
You already know that the FDA requires rigorous and specific tests to prove a new drug's effectiveness, and that even after approval, drugs cannot be advertised or used without adhering to specific requirements. For example, drug companies must market drugs only for their proven, intended uses, and they must also provide fair warnings about possible side effects.
However, these requirements weren't as strict until the FDA implemented its evidence-based approval system in 1938 where for the first time drugs had to be proven to be safe, then amended again to prove effectiveness in 1962.
In the meantime, thousands of drugs were prescribed and sold commercially without undergoing these strict tests, and the “Grandfather Clause” was added in 1962 in order to accommodate these drugs.
Under the clause, unapproved drugs that were considered safe before 1962 may remain on the market, as long as their packaging and chemical makeup don't change at all.
Ophthalmologists frequently work with at least two of these unapproved drugs.
Tetracaine, a topical eye anesthetic, is available by prescription but never passed modern FDA tests of effectiveness. Topical fluorescein sodium products are also available but unapproved.
Both drugs still have side effects and application requirements, but ultimately they're not subject to the same scrutiny as new drugs, at least for now anyways.
Changes to the Grandfather Clause
The FDA eventually realized that these restrictions were too loose, and that some companies were taking advantage of them. For example, companies claimed certain drugs qualified while continuing to tweak the formulas.
The clause also allowed new manufacturers to make drugs with very similar makeups to older drugs, allowing them to be "grandfathered in".
In 2006, the FDA began an "unapproved drugs initiative". If one company receives approval on a drug that was formerly "grandfathered in", it means the drug is now subject to FDA approval. Any competing manufacturers must discontinue their product and file a generic approval if they want to sell the product again and wait on average 36 months for approval.
The following common ophthalmology products were marketed unapproved drugs under the Grandfather Clause but in recent years received their first FDA approval.
Unfortunately, as these updates put the manufacturing process on hold for some companies, some manufacturers have increasing control over the market.
As their competitors undergo around a three-year waiting period, approved pharmaceutical companies have full control over the market for these official formulas. They can raise prices freely, leading some ophthalmologists to seek alternatives.
Some practices haves sourced replicated drugs that are compounded from compounding pharmacy in order to try to cut costs. Compounded drugs are drugs that are chemical combinations that produce similar results to existing pharmaceuticals, but they're often produced in non-commercial settings that aren't subject to the same sterility requirements and approval methods.
Recent recalls have highlighted the negative reactions that can happen when "replacement" compounds are produced in non-sterile environments.
If you work with a drug that was originally "grandfathered in" but has recently been FDA approved, your options may be limited by shortages or bans.
It's important to do your research before seeking an alternative. It may be wiser to use the more expensive approved brand-name drug, than to put your patients at risk during the wait period.