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

Susan Haigney

The United States Pharmacopeia (USP) has stated that references to General Chapter <911> “Viscosity” will be changed to General Chapter <911> “Viscosity—Capillary Viscometer Methods,” <912> “Rotational Rheometer Methods,” or <913> “Rolling Ball Viscometer Method.” Seventy monographs will be affected. 

The changes reflect a modernized General Chapter <911> and two new proposed General Chapters <912> and <913> published in 

(5) in 2011 and approved by the General Chapters—Physical Analysis Expert Committee. 

The changes will become official Dec. 1, 2012, and will be reflected in the Second Supplement to 

 of impacted monographs can be found on the USP website.

Articles

The United States Pharmacopeia has stated that references to General Chapter <911> "Viscosity" will be changed to General Chapter <911> "Viscosity-Capillary Viscometer Methods," <912> "Rotational Rheometer Methods," or <913> "Rolling Ball Viscometer Method."

USP Issues Change to Viscosity Reference in Monographs

The Parenteral Drug Association has released a revision of 

Parametric Release of Pharmaceuticals and Medical Device Products Terminally

The revised report, originally published in 1999, provides current best practices of the sterile product release method and emphasizes the use of science-based approaches when developing a parametric release program for “pharmaceutical and medical device products terminally sterilized by moist heat.”

The original TR 30 outlined a sterility assurance release program that utilized effective control, monitoring, and documentation of a validated sterile product manufacturing process dependent on achievement of critical operational parameters instead of end product sterility testing.   A group of international industry scientists, microbiologists, and engineers participated in the revision of TR 30.

 PDA members can access TR 30 for free until June 15, 2012.

PDA Revises Technical Report on Sterilized Products

The Parenteral Drug Association (PDA) has released 

 on the detection and mitigation of 2,4,6-tribromoanisole (TBA) and 2,4,6-trichloroanisole (TCA) taints and odors in pharmaceutical and healthcare products. 

 (TR 55) provides information on the origin of TBA and TCA odors and taints, analytical methods developed, and risk-management strategies. The report highlights the uses of 2,4,6-tribromophenol (TBP) and 2,4,6-trichlorophenol (TCP); the role of fungal halophenol methylation that generates TBA and TCA haloanisole taints; and sensory and physiochemical properties of TBP, TCP, TBA, and TCA. The report also gives case examples of recalls, the root causes behind those recalls, and remedial actions taken. 

From 2009 to 2011, companies in the pharmaceutical and consumer healthcare industries experienced product recalls due to the risk of product exposure to the TBA taint from tribromophenol-treated wood pallets. TR 55 offers “guidance on signal detection from adverse event and/or product quality complaints and resulting recalls, toxicology and safety, analytical method development and use, supply chain controls, risk analysis and mitigation.” 


PDA members can access TR 55 for free until May 31, 2012.

The Parenteral Drug Association has released guidance on the detection and mitigation of 2,4,6-tribromoanisole and 2,4,6-trichloroanisole taints and odors in pharmaceutical and healthcare products.

PDA Releases Technical Report on TBA and TCA Odors and Taints

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. 

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.