Regulatory Focus™ > News Articles > GPhA Questions Legality of FDA Guidance on Physical Attributes of Generic Drugs

GPhA Questions Legality of FDA Guidance on Physical Attributes of Generic Drugs

Posted 14 September 2015 | By Zachary Brennan 

GPhA Questions Legality of FDA Guidance on Physical Attributes of Generic Drugs

The Generic Pharmaceutical Association (GPhA) is raising a number of concerns, among them the legality, of the US Food and Drug Administration's (FDA) recently issued final guidance on the size, shape and other physical attributes of generic drugs.


Since at least 2013, FDA has called on generic drug companies via draft guidance to gauge the physical differences -- including size, shape, smell, weight and surface area – and try to make generics as physically similar, or even the same, as their reference products.

Of particular issue in the past was the scoring of tablets, which some contended had to be identical between reference listed products and their generic versions. Some companies used the issue of identical scoring to delay market entry for generics, though FDA later cracked down on that practice.

FDA has also said patient compliance could be an issue, as the size or shape of a tablet could influence whether a patient decides to ingest it. In 2014, FDA said it would conduct a survey of pharmacists and patients to find out more information on adherence to drug regimens and whether a shift in a generic's physical attributes – particularly color -- has any impact on adherence.

"Studies indicate that patients are more likely to stop taking their generic medications when they experience a change in their drugs' physical appearances, leading to harmful clinical and public health consequences as well as increased health care costs from avoidable morbidity and mortality," FDA explained.


But in a letter from GPhA to FDA late last month, the association says that the final guidance on the physical attributes issued in June "imposes arbitrary requirements even in the absence of known safety issues."

GPhA references the Drug Price Competition and Patent Term Restoration Act of 1984 (better known as the Hatch Waxman Amendment), noting Congress took particular care to ensure generics and their reference-listed drug (RLD) would have the same active ingredient, bioequivalence and labelling.

"Where Congress permitted generic drugs to vary from the RLD, e.g., in manufacturing methods and in formulation, Congress provided for FDA to ensure that the generic drugs are safe and efficacious. Hatch Waxman specifically states that FDA may not require more than what is required to satisfy those statutory requirements," GPha says.

"Hence there is no provision in Hatch Waxman allowing FDA to deny the approval of an ANDA [abbreviated new drug application] based on differences in physical attributes between a generic product and the RLD. The premise of the guidance, that generic drugs must mimic the reference listed drug in size and shape, has no basis in law," GPhA added.

In addition, the association says that unless the FDA action on the physical attributes of a generic drug "represents a scientifically supported safety and/or efficacy concern," then any such action "exceeds the FDA's statutory mandate."

De Facto Requirement

In some cases, GPhA says, generic manufacturers have to produce a tablet or capsule that is larger than the RLD, or a different formulation, because of patent protections.

"A generic version of a product that differs from the size and/or shape recommendations set forth in the guidance does not automatically raise safety issues," GPhA says.

The association also takes issue with the fact that FDA appears to have been using this draft guidance as a "de facto regulatory requirement" and some of its member companies report that "Controlled Correspondence inquiries have not been subject to any scientific evaluation, rather are rejected regardless of the level of deviation from the guidance.

"When the generic product dimensions differ from the RLD, the proposed size and/or shape should be evaluated on a case by case basis to assess actual risks," GPhA says.

The group also says that the guidance creates a new life cycle management tool for new drug application (NDA) sponsors "to stifle and delay access" to generics because of this "inflexible criteria that are not necessarily applicable to a proposed deviation in size and/or shape."

Other specific issues on the size requirements, and whether ANDAs received and pending prior to the issuance of the final guidance will be held to the new requirements of this guidance, are also included in the letter.

GPhA Letter

Categories: Regulatory News

Regulatory Focus newsletters

All the biggest regulatory news and happenings.