Life Science Compliance Update

April 20, 2017

FDA Under Pressure to Speed Up Generic Approvals


As has been reported, the FDA is under pressure to speed up approval of generic medicines. In response, the FDA released data indicating its actions on the approval of generic medication. However, as noted by NPR in one example consumers and lawmakers pushing for cheaper alternatives to the EpiPen and other high-priced medications are seeking answers about what they describe as a “stubborn” backlog.

FDA’s response

In Kathleen Uhl, MD’s presentation (Director, Office of Generic Drugs at CDER within FDA), she stated the agency is meeting all of its obligation under GDUFA and even going above and beyond its commitments. FDA states it is “building a modern, 21st Century generic drug program,” which is resulting in “significant and sustained increases in communications, actions & approvals.”

According to numbers from FY2016, FDA approved 190 generic drugs with tentative approval to 48. December 2016 was the highest number of approvals and tentative approvals in one month ever for the FDA at 99. CY2015 broke the record for the highest number ever in a year at over 700+.

To continue building the FDA’s operations, Uhl stressed an interested in foundational restructuring, the building of more internal FDA infrastructure, improvement of business processes, hiring and training more staff, a new IT platform, and improved communications. Regarding IT improvements, FDA says it improved communication and increased productivity—a direct result of its improved IT system for the generic drug program. This provides the agency with workload management and review management tools. They have assigned over 130,000 items in this new platform.

The presentation offers a lot of data which is worth reviewing. However, it also stresses there is “no filing backlog” and that filing is currently done in “real time” (31 days). The first step in review is filing. Something acceptable for filing means the application is sufficiently complete to permit substantive review. It does not mean it will be approved.

Industry response

As reported by Stat: “Overall, there’s some improvement,” said Robert Pollock, a former acting deputy director of the FDA Office of Generic Drugs, who now works at Lachman Consultants and advises drug makers on regulatory matters. “But the question is can it be sustained, and will there be progress beyond what we’ve seen.”

Stat explains that generic drug approval is getting more attention due to the national debate over drug costs. Generics now account for 88 percent of all prescriptions written in the United States, according to IMS health. As a result, FDA’s leadership has stressed its work on accelerating generic approvals. And as Stat notes, Adam Fein of Pembroke Consulting, who tracks pharmaceutical distribution, contends the increasing number of approvals is starting to temper the price hikes for generic drugs. But historically, the FDA has been unable to keep up with the pace of marketing applications filed by generic drug makers.


Regulatory Focus notes that the median time to market has fallen considerably as GDUFA has progressed. For the fastest 5% of ANDAs approved under GDUFA, the median approval time has gone from about 24 months in FY 2013 to less than 15 months in FY 2015. However, under the next iteration of GDUFA, which will take effect in FY2018, ANDA standard review time will likely be 10 months from submission and priority review would be eight months from submission.

This is compared to the 42- to 44-month average approval time before GDUFA was in place. However, ANDA submissions do continue to outpace approvals and criticism of the median approval times does seem warranted according to Regulatory Focus, when considering that it takes FDA only 10 months to review and approve much more complex new drug submissions.

February 15, 2016

US Continues to Face Drug Shortages

Once again we are facing national shortage of key drugs, including anesthetics, painkillers, antibiotics, and cancer treatments. We have written several times about previous drug shortages, all resulting in little to no beneficial long-term action.

The American Society of Health-System Pharmacists maintains a list of drug shortages, which is currently 150 drugs and therapeutics long. The 150 drugs are at inadequate supply levels for a multitude of reasons, ranging from manufacturing problems to federal safety crackdowns to drug makers abandoning low-profit drugs. While the shortages have long been public knowledge, what hasn't been in the public eye as much is the rationing that results from the shortages.

Why Does This Continue to Happen?

While there are a multitude of reasons behind the continuing saga of drug shortages, one such reason is that many drugs are made by only one manufacturer, so production or safety problems at just one plant can have huge ramifications. For any other company to begin making comparable drugs and getting them approved by regulators requires a magic equation of manufacturing capabilities and economic incentives.

Other reasons may include product quality concerns, difficulty in acquiring component parts or active pharmaceutical ingredients (API), increases in demand, and shipping delays, among many other things. Another reason is in the US there are Medicare Price Controls on generic injectable drugs under Medicare Part B.

Drug Rationing

Choices as to who receives the drugs that are in short supply have been made in different ways at different institutions, sometimes resulting in contradictory conclusions, murky ethical reasoning, and even medially questionable practices.

While some institutions have formal committees that include ethicists and patient representatives, other institutions rely on individual physicians, pharmacists, or even drug company executives, to decide which patient will receive the necessary drug.


The decisions made by hospitals, individual providers, and pharmacists have real consequences to the individuals who are not considered "better qualified" for the drug. For some shortages, the effects of rationing are immediate, such as increased pain or nausea, when the drugs that are typically used to control symptoms are withheld, or patients who have to undergo invasive surgery to control cancer when anti-tumor medicines are delayed.

Studies have associated alternative treatments during drug shortages like this with higher rates of medication errors, side effects, disease progression, and deaths. While many physicians say that many of the changes they make seem to do no harm, they acknowledge that no one is really tracking outcomes in patients who get a drug versus those who get a substitute or delayed treatment.

A study published last year in Anesthesia and Analgesia, a medical journal, surveyed patients at the Mayo Clinics in Arizona, Florida, and Canada about their preferences when it comes to drug shortages. The study found that most patients wanted to know about a drug shortage that might affect their care during elective surgery, even if there was only a minor difference in potential side effects. Many said they would even delay surgery, if they knew of a drug shortage that would affect them.

When the study was published, the journal published an accompanying editorial that urged healthcare professionals to disclose any drug shortages, and their implications. The editorial stated, "[p]atients want to know and they should know. There is no ethical ambiguity."

The Future

Surveys performed in 2012 and 2013 showed that 83% of healthcare professionals who regularly prescribed cancer drugs reported being unable to provide the preferred chemotherapy agent at least once during the previous six months. Being unable to provide the preferred chemotherapy agent led to forced "difficult decisions about which patients to exclude."

Dr. Peter Adamson, the Chair of the Children's Oncology Group, has assigned his organization to set priorities, saying, "[w]e've been forced into what we think is a highly unethical corner." The priority effort is being led by Dr. Yoram Unguru, a Baltimore oncologist, who recommends that the drugs be rationed based on the ability to save lives or years of life, including how curable the child's cancer is and the importance of the drug in improving chances.

The FDA has previously asked for comment on how to improve the continuing drug shortages, and Congress has previously taken a stab at fixing things their way. Neither approach has gotten anywhere, nor have any new ideas been populated by either branch of government.

We once again argue that we believe one of the reasons these drug shortage problems continue to happen is because the market does not sufficiently reward quality. Buyers – including hospitals and clinics – tend to consider generic products as perfect substitutes, giving manufacturers little room for differentiations. The FDA has previously acknowledged this, in a report written in part by Janet Woodcock, MD, the director of the Center for Drug Evaluation and Research at the Food and Drug Administration. In that report, Woodcock and other FDA officials argued that "the fundamental problem with injectable shortages is insufficient market reward for quality (including reliability of production) stemming from the buyers' inability to observe it." Such a situation gives manufacturers strong incentives to minimize quality system investments, especially when faced with other pressures, such as new production opportunities, aging facilities, and the economic downturn that has not fully rebounded. Until new incentives exist for manufacturers to improve quality, it is unlikely that drug makers will adequately address quality issues.

December 29, 2015

FDA DSCSA Implementation: Product Tracing Requirements for Dispensers – Compliance Policy (Revised)

The Drug Supply Chain Security Act (DSCSA) requires most of the entities along the drug supply chain--from manufacturers to wholesale distributors to dispensers (primarily pharmacies)--to comply with new requirements regarding product tracing. The intent of the law is to enhance the FDA's ability to protect consumers from exposure to drugs that may be counterfeit, stolen, contaminated, or otherwise harmful by improving detection and removal of potentially dangerous drugs from the drug supply chain to protect U.S. consumers. The development of the system will be phased in with new requirements over a 10-year period. The DSCSA mandates that the FDA develop standards, guidance documents, pilot programs, and conduct public meetings, in addition to other efforts, to support efficient and effective implementation.

Starting in 2015, manufacturers, wholesale distributors, dispensers, and repackagers are required to provide the subsequent purchaser of certain prescription drugs with product tracing information. The trading partners are to obtain product tracing information and maintain the applicable information for at least six years following the date of the transaction.

The FDA had previously issued a Compliance Policy on July 6, 2015, which stated that the FDA did not intend to take action until November 1, 2015, against dispensers that accepted ownership of product without receiving the product tracing information, or dispensers who did not capture and maintain the product tracing information as required by law. This essentially gave dispensers a "free pass" and a bit more time to get their procedures in compliance with the law.

With the November 1 deadline rapidly approaching, last week, the FDA issued a new guidance, DSCSA Implementation: Product Tracing Requirements for Dispensers – Compliance Policy (Revised). The new guidance "addresses the readiness of dispensers in the pharmaceutical distribution supply chain to comply with the provisions in section 582 of the Federal Food, Drug, and Cosmetic Act ... related to the exchange of transaction information, transaction history, and transaction statements (product tracing information)."

This most recent guidance announced that the FDA will extend the previously issued Compliance Policy grace period from November 1, 2015 to March 1, 2016 because some dispensers have expressed that they needed additional time to comply with the law. The FDA does not intend to take action against dispensers who, prior to March 1, 2016, accept ownership of a product without receiving the product tracing information, under section 582(d)(1)(A)(i) of the FD&C Act. This compliance policy, however, does not extend to the requirements under section 582(b)(1), (c)(1), and (e)(1) that other trading partners (manufacturers, wholesale distributors, and repackagers) provide product tracing information to dispensers.

This new compliance policy also does not extend to transactions in which dispensers must provide the subsequent owner with product tracing information, including transaction history, as required by section 582(d)(1)(A)(ii).

As a result of the FDA not taking action against most dispensers who accept ownership of a product without a transaction history, transaction information, and transaction statement, the FDA does not intend to take action against dispensers who do not maintain the product tracing information for a minimum of six years as required under section 582(d)(1)(A)(iii).

However, the grace period was extended by only four months and it is uncertain if the FDA will continue to extend the grace period. Therefore, if a dispenser has not received product tracing information prior to, or at the time it takes ownership of a product, the FDA recommends that the dispenser work with the previous owner to receive this information to ensure complete compliance with the law.

It is important to note that this guidance does not change the current requirements for manufacturers, wholesale distributors, nor repackagers. This guidance only affects dispensers who do not need to provide a subsequent owner with product tracing information. All other dispensers, or manufacturers, wholesale distributors, and repackagers are still required to obtain and maintain tracing information as required under the FD&C Act.


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