US Food and Drug Administration (FDA) Commissioner Scott Gottlieb outlined new efforts by the agency to increase access of samples of branded drugs needed by generic-drug developers for testing. Its measures include increasing transparency and reforming elements of the REMS (Risk Evaluation and Mitigation Strategy) system.

 “At the FDA, we’re taking steps across a broad range of areas to improve new and generic drug competition as a way to improve access and affordability,” Gottlieb said in a May 17, 2018 agency statement. “Among these efforts, we’re especially focused on addressing tactics we sometimes hear of branded companies pursuing as a way to forestall expected generic entry. One such abuse that I’ve spoken about often is a practice by brand companies to create obstacles for generic developers in purchasing samples of their brand drugs.”

He explained that access to drug samples arise as generic-drug developers need samples of the brand drug to develop their generic product and/or to conduct testing to show that their product is bioequivalent to the brand drug for FDA approval. A generic-drug developer generally needs 1,500 to 5,000 units of the brand drug to perform what are often relatively straightforward studies for FDA approval, according to information from the FDA. “Without these samples, generic-drug makers may not be able to develop generic alternatives. Yet, the FDA has heard that some brand companies will adopt tactics to make it hard for the generic companies to purchase these brand drugs at a fair value and in the open marketplace,” he said in the May 17 statement. “The FDA is taking new steps to address this issue.

To increase transparency, the FDA has now published a list of companies that have potentially been blocking access to the samples of their branded products. It is also publishing a list of the inquiries it has received from generic-drug developers which report having trouble accessing testing samples. Gottlieb said that the agency will continue to update this list periodically. The information being disclosed includes the brand drug company, the drug product, and the number of inquiries the agency has received.

The FDA is addressing limitations on distribution of samples through a Risk Evaluation and Mitigation Strategy (REMS), a program that the FDA implements for certain drugs to manage a known or potential serious risk associated with a medicine and to enable patients to have continued access to such medicines by managing their safe use. “We have heard that some drug makers have either refused to sell samples of products with REMS with Elements to Assure Safe Use (ETASU) impacting distribution to potential generic competitors or have imposed conditions on the sale of such samples that generic companies find hard or impossible to comply with,” said Gottleib in the statement. “In other cases, we understand that brand companies have placed restrictions in their commercial contracts or agreements with prescription drug distributors, wholesalers, or specialty pharmacies that limit the ability of these intermediaries in the drug supply chain to sell samples to generic drug developers for testing.”

Gottlieb said the FDA has received more than 150 inquiries from generic-drug developers seeking assistance in obtaining samples from brand companies and is taking several steps to address these issues. “First, the FDA will determine whether these products have in place a REMS program with ETASU that may impact distribution, which has been cited as a reason to refuse to provide samples. In many cases, we find that there’s no such REMS program in place,” Gottlieb said in his statement. “In these cases, the FDA informs the generic-drug developer that there are no FDA-required restrictions on the distribution of the drug that would impede obtaining samples. We’re also notifying the Federal Trade Commission (FTC) — the agency responsible for addressing anticompetitive business practices — about these inquiries. We also encourage the generic-drug developers to raise these cases with the FTC if they believe that anticompetitive conduct has taken place.”

To facilitate the transfer of samples in cases where there is an existing REMS program with ETASU for the brand drug that impacts distribution, the FDA has a voluntary process through which generic companies can submit their bioequivalence testing protocols to the agency, and it will evaluate these protocols to ensure that the companies’ plan for testing the product contains safety protections comparable to the brand product’s REMS program. “Assuming that the generic-drug developers’ plans include appropriate protections, then the generic drug developers can request that the FDA send a letter to the brand company stating that the REMS program does not mean the brand drug maker can’t sell [its] product to generic-drug developers for comparative testing,” said Gottlieb.

To date, the FDA has issued 21 of these notifications, called Safety Determination Letters. The agency is also specifying companies of products that have been the subject of a Safety Determination Letter from the FDA clarify that there are no REMS-related reasons why samples of their product can’t be provided to generic-drug developers.

Source: FDA