Susan Haigney is lead editor of Pharmaceutical Technology and Pharmaceutical Technology Europe.

Susan Haigney

 published on FDA’s website on March 15, 2012, Janet Woodcock, M.D., director of the Center for Drug Evaluation and Research, outlined the current status and future plans for FDA’s 

, an electronic drug-safety tracking system established as part of the FDA Amendments Act of 2007. 

Woodcock’s presentation outlined Mini-Sentinel, a pilot project developed to inform and facilitate development of the Sentinel System for monitoring the safety of FDA-regulated medical products. Collaborators in Mini-Sentinel include data and academic partners that provide access to healthcare data and ongoing scientific, technical, methodological, and organizational expertise. 

Mini-Sentinel includes a coordinating center that can access automated healthcare data systems to develop and evaluation scientific methodologies that might be used in the fully operational Sentinel System. The pilot program would also provide FDA with the opportunity to investigate safety issues in existing data systems. 

The presentation also featured an update on other plans in development, including a framework to refine safety signals in “near real time” and plans to incorporate registries and other data sources to match nonpersonally identifiable data. 

Also featured in the presentation was the Observational Medical Outcomes Partnership (OMOP) project, which includes an active surveillance community and a research experiment to test various methods for detecting associations between drugs and medical outcomes and characterizing datasets and investigation of the impact of multiple “parameter settings” for each method.

Future plans for the Sentinel Initiative include expansion of data sources through Mini-Sentinel, continued research, and ongoing data utilization. FDA envisions a public-private partnership that would “allow other parties to participate in research and studies using Sentinel infrastructure.” FDA also hopes for a future national secondary use data resource for research, according to the presentation.

The Sentinel Initiative was established to create a postmarket risk identification and analysis system to link and analyze safety data from multiple sources, including federal health-related electronic data and private-sector electronic health data. By linking the data, FDA hopes to identify and evaluate safety issues “in near real time.” The Initiative will also give FDA access to longer-term data and expand access to advents not normally reported to FDA.

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In a presentation published on FDA's website on Mar. 15, 2012, Janet Woodcock, director of CDER, outlined the current status and future plans for FDA's Sentinel Initiative, an electronic drug safety tracking system established as part of the FDA Amendments Act of 2007.

FDA Updates Sentinel Initiative Status

On Feb. 21, 2012, FDA announced steps the agency plans to take to increase the declining supply of certain cancer drugs. These steps came in response to President Obama’s Oct. 31, 2011 

FDA announced a temporary importation of the chemotherapeutic drug Lipodox (doxorubicin hydrochloride liposome injection) in response to the shortage of Doxil (doxorubicin hydrochloride), used in the treatment of ovarian cancer and AIDS-related Kaposi’s sarcoma and multiple myeloma. FDA expects the importation of this replacement drug to end the shortage and meet patient need within weeks.

Supply of methotrexate is also in decline. FDA, seeking to increase supply, approved a preservative-free formulation of methotrexate manufactured by APP Pharmaceuticals, a subsidiary of Fresenius Kabi Pharmaceuticals Holding, Inc. FDA expedited the review of the drug maker’s application to ensure the supply of the cancer drug. The drug is expected to become available in March. The agency has also engaged many firms to assist in maintaining supply. Hospira expedited the release of additional supplies, resulting in 31,000 vials of new product, and Mylan and Sandoz Pharmaceuticals have increased production. Methotrexate is used to treat a variety of cancers as well as other diseases.

 detailing requirements for mandatory and voluntary notifications to the agency of potential problems that could disrupt the drug supply.

, that the President’s Executive Order and 

 have increased awareness of the importance of early notification and that awareness has “resulted in a sixfold increase in voluntary notifications by industry of potential shortages. In 2011, there were a total of 195 drug shortages prevented. Since the Executive Order, FDA has prevented 114 drug shortages.”

“A drug shortage can be a frightening prospect for patients and President Obama made it clear that preventing these shortages from happening is a top priority of his administration,” said FDA Commissioner Margaret A. Hamburg, M.D., in the press release. “Through the collaborative work of FDA, industry, and other stakeholders, patients and families waiting for these products or anxious about their availability should now be able to get the medication they need.”

On Feb. 21, 2012, FDA announced steps the agency plans to take to increase the declining supply of certain cancer drugs. These steps came in response to President Obama's Oct. 31, 2011 Executive Order.

FDA Takes Proactive Steps to Prevent Cancer Drug Shortages

On Feb. 17, 2012, McNeil Consumer Healthcare, a division of McNeil-PPC, a subsidiary of Johnson & Johnson, voluntarily recalled approximately 574,000 bottles of its over-the-counter pain reliever and fever-reducer Infants’ Tylenol Oral Suspension, 1 oz. Grape. The voluntary recall was initiated after consumers complained of having difficulty using the SimpleMeasure dosing system.

The SimpleMeasure dosing system used for Infants’ Tylenol includes a dosing syringe that is inserted into a flow restrictor at the top of the bottle to measure dosage. Complaints were received from some consumers that the flow restrictor was pushed into the bottle when the syringe was inserted.

, that the voluntary recall was at the wholesale and retail level for seven lots distributed nationwide in the United States and that no adverse events have been reported. McNeil states that consumers may continue to use the product “provided that the flow restrictor at the top of the bottle remains in place,” but cautions consumers to not use the product if the flow restrictor is pushed into the bottle.

The specific lot numbers recalled were BIL0U00, BIL0V00, BIL3500, BJL2D00, BJL2E00, BJL2T00, BJL2U00, UPC Code 300450122308. Consumers can request a refund from McNeil by visiting 

On Feb. 17, 2012, McNeil Consumer Healthcare, a division of McNeil-PPC, a subsidiary of Johnson & Johnson, voluntarily recalled approximately 574,000 bottles of its OTC pain reliever and fever reducer Infants' Tylenol Oral Suspension, 1 oz. Grape. The voluntary recall was initiated after consumers complained of having difficulty using the SimpleMeasure dosing system.

McNeil Voluntarily Recalls Infants' Tylenol Oral Suspension Product

President Barack Obama released his budget proposal for fiscal year 2013. Included in the proposed budget is a $654-million increase in FDA funding, for a total FDA budget request of $4.49 billion. 

The proposed budget also includes $1.97 billion in user fees, including $583 million in proposed new user fees. The budget request includes “inflationary increases for FDA user fee programs, as authorized by law.”

“The resources in this budget will allow FDA to perform its fundamental public health responsibilities in new and more efficient ways. Our budget also supports industry efforts to innovate and bring new products to market that will benefit American patients and consumers and strengthen our economy,” states FDA Commissioner Margaret A. Hamburg, in the 

Included in the proposed FDA budget is an additional $363 million earmarked for projects that protect patients, including addressing and detecting risks from products manufactured in China. “The budget contains new resources to increase FDA’s capacity to detect and address risks in products and ingredients manufactured in China before they result in harm to Americans,” states Hamburg.

The proposed FY 2013 budget sustains the current level of staffing and activities for the Medical Countermeasures Initiative, which is designed to meet national security and public health requirements for medical countermeasures (MCM) readiness. FDA will continue to partner with industry and academia to shorten MCM development timelines and improve success rates.

Health and Human Services Deputy Secretary Bill Corr, in a 

, states the proposed Health and Human Services budget “continues to support President Obama’s historic push to stamp out waste, fraud, and abuse in our health care system…and our budget helps reduce the deficit by $366 billion over 10 years, almost all of which comes from reforms to Medicare and Medicaid.”

PhRMA expressed concerns about the President’s proposed budget and the changes to Medicare in a 

, “Medicare Part D is working well for seniors. Due to competition, costs continue to be far below initial projections. We should not disrupt this successful program.”

PhRMA also responded to the budget’s handling of data protection, biosimilars, and patents. “We are also troubled by the President’s proposal to reduce data protection for innovative biologic medicines, which is critically important to the development of cutting-edge medicines so needed by patients… The biosimilars provision of the health care reform law-the only provision in the law to garner strong bipartisan support-achieves an essential balance. It provides appropriate incentives to support future medical advances. It supports high-value jobs that are critical to our nation’s economic recovery. And, it provides savings by creating the first pathway for federal regulators to approve biosimilars.”

“Similarly, patent settlements are a vital aspect of a patent owner’s ability to protect intellectual property. Restricting such settlements, which already are subject to review by the Federal Trade Commission and the Department of Justice, could discourage pro-consumer settlements, which often bring generics to market years before patent expiration. Without settlements, costly litigation could keep these generics from being available to patients for years.”

President Barack Obama released his budget proposal for fiscal year 2013. Included in the proposed budget is a $654-million increase in FDA funding, for a total FDA budget request of $4.49 billion.

White House's 2013 Budget Includes FDA Increases

On Jan. 13, 2012, FDA announced it had completed, and transmitted to Congress, its recommendations for three user fee programs including the fifth authorization of the Prescription Drug User Fee Act (PDUFA) and programs for human generic drugs and biosimilar biological products.

FDA modeled the proposed user fee programs on the PDUFA created by Congress in 1992. Commissioner Margaret A. Hamburg, PhD, stated in a FDA 

 that the PDUFA has “ensured a predictable, consistent, and streamlined premarket program for prescription drugs.” Under the programs, the pharmaceutical industry helps to fund a portion of FDA’s drug review activities by paying fees. In return, FDA agrees to process applications in a particular timeframe as well as other performance goals.

Commissioner Hamburg stated, “At a time of greater budgetary constraint, user fees provide a critical way for leveraging appropriated dollars, ensuring that FDA has the resources needed to conduct reviews in a timely fashion.” With the recommended programs, FDA would be able to continue to conduct timely reviews of critical prescription drugs, provide communication with small and emerging companies, promote the use of electronic data, and advance drug development for rare diseases.

The generic-drug market has been growing and applications for new generic drugs have been on the rise. FDA stated in the press release that the proposed Generic Drug User Fee program would ensure that the agency had the necessary funding to process new generic drug applications. The proposal includes review timeframes that would reduce the review backlog and provides a “commitment to achieve parity between surveillance inspections of foreign and domestic establishments by the 2017 fiscal year.”

FDA intends for fees included in the Biosimilar and Interchangeable Products User Fee program to generate revenue in the near-term and support development-phase meetings with sponsors. FDA stated that the proposed biosimilar program would spur competition in the biologic drug market by allowing companies to develop alternative products. According to FDA, a biosimilar is “a biological product that is highly similar to a US-licensed reference biological product notwithstanding minor differences in clinically inactive components, and for which there are no clinically meaningful differences between the biologic product and the reference product in terms of safety, purity, and potency of the product.”

On Jan. 13, 2012, FDA announced it had completed, and transmitted to Congress, its recommendations for three user fee programs including the fifth authorization of the Prescription Drug User Fee Act and programs for human generic drugs and biosimilar biological products.

FDA Recommends Three Drug User Fee Programs

On Dec. 29, 2011, FDA approved the TIRF REMS Access Program, a single-shared risk evaluation and mitigation strategy (REMS) for transmucosal immediate-release fentanyl (TIRF) products, narcotic pain medicines used by cancer patients to manage pain. The TIRF REMS program is intended to ease the burden on the healthcare system by allowing prescribers and pharmacies to enroll into one new single system instead of several different systems.

“This TIRF REMS will ensure safe use and access to these drugs for patients who need them,” said Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research in a 

. FDA hopes to limit the risk of misuse, overdose, abuse, and complications related to TIRF medicines, which include the brand names Abstral, Actiq, Fentora, Lazanda, and Onsolis. The program will ensure that TIRF drugs are prescribed and dispensed only to appropriate patients and will prevent inappropriate conversion between fentanyl products.

Prescribers, patients, and pharmacies will begin using the program beginning in March 2012, but until then the current individual REMS programs will continue to be used. Those already enrolled in established individual REMS for TIRF products will automatically be transitioned to the shared program. Patients who receive TIRF medicines in inpatient situations (e.g., hospitals and hospices) will not be required to enroll in the program, nor will the doctors that prescribe TIRF drugs in inpatient situations. However, patients receiving the medicines on an outpatient basis are required to be enrolled.

Safety Concerns and Shortages Challenge Pharma

On Dec. 29, 2011, FDA approved the TIRF REMS Access Program, which is intended to ease the burden on the healthcare system by allowing prescribers and pharmacies to enroll into one new single system instead of several different systems.