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

Susan Haigney

The Center for Drug Evaluation and Research Ombudsman’s office released its 

 detailing the common questions and complaints received by the office in 2011. A total of 461 inquiries was received, an increase of 11% from 2010. The majority of inquiries, 60%, originated from industry, with consumers accounting for 23%, healthcare providers 7%, FDA employees 5%, and other 5%. 

The most common questions and complaints received by the office regarded 510(k) submissions, adverse events and safety issues, drug applications, appeals processes, disputes of FDA-483 notices, and problems with the new electronic drug-registration process. Policies and procedures were listed as the number one reason the office was contacted. 

The report cites a new trend in an increase in communications from small, emerging biotechnology and pharmaceutical companies, attributing the increase to smaller companies being less familiar with regulatory requirements and smaller companies having a financial need to resolve disputes quickly. Complaints about observations made on FDA-483s continued to be a trend from previous years.

The CDER Ombudsman is an independent public official that works to informally resolve questions, complaints, and comments the office receives from a variety of areas of the pharmaceutical industry, including advocacy groups, research institutions, consumers, healthcare providers, and FDA employees. 

Articles

The Center for Drug Evaluation and Research Ombudsman's office released its annual report detailing the common questions and complaints received by the office in 2011. A total of 461 inquiries was received, an increase of 11% from 2010. The majority of inquiries, 60%, originated from industry, with consumers accounting for 23%, healthcare providers 7%, FDA employees 5%, and other 5%.

CDER Ombudsman Releases Annual Report

On Apr. 27, 2012, FDA issued Warning Letters to 10 companies that manufacture and distribute dietary supplements that contain dimethylamylamine (DMAA). FDA cited the companies for marketing the supplements without submitting evidence that the products are safe.

Under the law, manufacturers of dietary ingredients are responsible for notifying FDA within 75 days of marketing their products with evidence that supplements containing new dietary ingredients are safe. "Before marketing products containing DMAA, manufacturers and distributors have a responsibility under the law to provide evidence of the safety of their products. They haven’t done that and that makes the products adulterated," said Daniel Fabricant, PhD, Director of FDA’s Dietary Supplement Program, in an FDA 

FDA warned the companies in the letters that because synthetically produced DMAA is not a dietary ingredient it is “not eligible to be used as an active ingredient in dietary supplements.” 

According to FDA, DMAA “is known to narrow the blood vessels and arteries, which can elevate blood pressure and may lead to cardiovascular events ranging from shortness of breath and tightening in the chest to heart attack.” Forty-two adverse event reports regarding products containing DMAA have been submitted to FDA. 

The companies have 15 business days to provide FDA with the steps they plan to take in response to the Warning Letters. The companies cited in the FDA press release are listed below:

FDA has issued Warning Letters to 10 companies that manufacture and distribute dietary supplements that contain dimethylamylamine. FDA cited the companies for marketing the supplements without submitting evidence that the products are safe.

FDA Issues Warning Letters to Ten Companies for Lack of Safety Evidence

FDA has detailed, in a new report, the agency’s objective to give postmarket drug-safety monitoring the same priority as premarket drug review. According to an FDA 

, the “strengthened and modernized postmarket drug program has resulted in a substantial improvement in…oversight of drugs once they reach the American public.” The report “

Advances in FDA’s Safety Program for Marketed Drugs

,” released on Apr. 21, 2012, gives an overview of FDA tools and capabilities used in the monitoring of postmarket drug safety. According to the report, drug-safety information is being communicated to the public faster than it has in the past, with the Center for Drug Evaluation and Research (CDER) issuing 68 drug-safety communications in 2011 compared to 39 in 2010.  

In 2004, CDER introduced the new drug-safety plan, which was enhanced by the Food and Drug Administration Amendments Act (FDAAA) of 2007. FDAAA authorized changes to the safety monitoring of postmarket drugs and gave FDA the authority to require postmarket studies of drug-safety concerns and drug-labeling changes.  

Since 2008, FDA’s postmarket monitoring program has required 65 safety-related labeling changes and has required manufacturers to implement risk evaluation and mitigation strategies. CDER has increased staff, established specific safety positions within new drug application divisions, and created the new Office of Biostatistics, which focuses on postmarket drug safety. FDA has also created drug-monitoring programs such as Safety First, Sentinel, and Safe Use. The Mini-Sentinel pilot project has enabled FDA to utilize access to electronic healthcare information nationwide.  

“Our oversight of the safety of marketed drugs has changed significantly over the past few years,” said Janet Woodcock, MD, director CDER, in the press release. “This report shows that the quality, accountability, and timeliness of postmarket drug safety decisions have been enhanced, and our public communication of this information is more effective.”  

FDA Seeks More Timely Drug Information Electronically

FDA highlights success of CDER's drug-monitoring program.

FDA Reports Improvement in Postmarket Drug Oversight

 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.

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.