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

Susan Haigney

On July 9, 2012, Congress passed the Generic Drug User Fee Act (GDUFA) in an effort to get generic drugs to market in a timely manner. The Act authorizes the collection of user fees from generic-drug manufacturing companies for the first time in the industry’s history. 

As a result of a growing generic drug market, applications for new products have increased, causing a backlog of pending applications. The user fees collected by the generic drug industry will provide FDA with the funds it needs to process new drug applications and meet review deadlines established under the law. 

between FDA and representatives of the generic drug industry, the Act builds on the Prescription Drug User Fee Act program, which has streamlined the premarket program. According to FDA’s

, GDUFA “will enhance global supply chain safety by requiring that generic drug facilities and sites around the world use a self-identification process to include the source of all materials used in the manufacturing of generic drugs.”  

Articles

On July 9, 2012, Congress passed the Generic Drug User Fee Act in an effort to expedite the process of bringing generic drugs to market. The Act authorizes the collection of user fees from generic-drug manufacturing companies for the first time in the industry's history.

Congress Passes Generic Drug Act

 on the labeling of OTC products that contain acetaminophen. The draft guidance would give manufacturers an alternative option to properly clarify the risk of liver damage in OTC acetaminophen-containing products.

The current guidelines require manufacturers of OTC products that contain acetaminophen to include a specific warning on the label that exceeding the maximum daily amount of acetaminophen could cause liver damage. The current language refers to the product’s maximum dosage in terms of dosage units or total amount of tablets in a 24-hour period. 

The new draft guidance would give manufacturers the option of stating the maximum daily dosage as 4000 mg. The new language states: “Liver Warning: This product contains acetaminophen. Sever liver damage may occur if you take more than 4000 mg of acetaminophen in 24 hours; with other drugs containing acetaminophen; 3 or more alcoholic drinks every day while using this product.”

According to the draft guidance, FDA “believes that this alternative language should eliminate the potential confusion…and help ensure appropriate dosing of OTC acetaminophen-containing products, while also informing consumers that using more than the currently proposed maximum daily dose of 4000 mg of acetaminophen may result in severe liver damage.”

FDA has issued a draft guidance on the labeling of OTC products that contain acetaminophen. The draft guidance would give manufacturers an alternative option to properly clarify the risk of liver damage in OTC acetaminophen-containing products.

FDA Issues Draft Guidance on OTC Products that Contain Acetaminophen

FDA has updated its website to include the latest 

 issued to pharmaceutical companies by the Office of Prescription Drug Promotion and the Center for Drug Evaluation and Research (CDER). 

Improper training and a lack of written procedures were among some of the citation trends. Deviations from cGMP in the manufacture of APIs cited by CDER include:

Failure to use dedicated production areas when performing operations with beta-lactam products.

Failure to have laboratory records that include complete data derived from all tests conducted to ensure compliance with established specifications and standards.

Failure to ensure laboratory instrumentation for assuring the quality of APIs is calibrated according to written procedures and an established schedule.

Failure to have a written procedure to investigate out-of-specification results.

Failure to ensure batch production records are prepared for each API and include complete information relating to the production and control of each batch.

Failure of quality unit to review and approve all appropriate quality related documents.

Failure of your quality unit to establish written procedures.

Failure to validate those operations critical to the quality and purity of the API.

Violations in regulations for finished pharmaceuticals include:

Not thoroughly investigating the failure of a batch to meet its specifications whether or not the batch has already been distributed.

Not establishing the reliability of the supplier’s analyses through appropriate validation of the supplier’s test results at appropriate intervals.

Not establishing scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that drug products conform to appropriate standards of identity, strength, quality, and purity.

Not establishing or following appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile.

Warning Letters issued by the Office of Prescription Drug Promotion in 2012 cite drug manufacturing companies for overstating efficacy of products, misbranding, presenting misleading information, making unsubstantiated claims, and omitting risk information from advertising materials in a variety of media outlets. 

A complete list of FDA-issued Warning Letters can be found at 

FDA has updated its website to include the latest Warning Letters issued to pharmaceutical companies by the Office of Prescription Drug Promotion and the Center for Drug Evaluation and Research.

FDA Updates List of Warning Letters

The European Medicines Agency’s Committee for Orphan Medicinal Products (COMP) made recommendations for nine orphan drug designations during its June 2012 meeting. Included in COMP’s recommendations were four designation applications for rare forms of lipodystrophy.

The COMP meeting also confirmed Vertex Pharmaceuticals's Kalydeco (ivacaftor) for orphan designation. The confirmation follows the recommendation made by EMA’s Committee for Medicinal Products for Human Use (CHMP). Based on CHMP requirements, COMP confirmed that “Kalydeco continues to fulfill the orphan designation criteria.” COMP will publish the review of Kalydeco’s orphan designation after the European public assessment report for the drug is published. 

COMP’s recommendations will be sent to the European Commission for adoption. Sponsors will have access to certain

 during development once the orphan designation is granted.

A full list of COMP’s recommendations can be found in COMP’s monthly 

The European Medicines Agency's Committee for Orphan Medicinal Products made recommendations for nine orphan drug designations during its June 2012 meeting. Included in COMP's recommendations were four designation applications for rare forms of lipodystrophy.

EMA Makes Orphan Drug Recommendations

The National Institutes of Health (NIH) have gained the participation of Abbott, Bristol-Myers Squibb, GlaxoSmithKline, Janssen Pharmaceutical Research & Development, and Sanofi in their effort to advance new therapeutic research. 

In May 2102, NIH’s National Center for Advancing Translational Sciences (NCATS) launched the 

Discovering New Therapeutic Uses for Existing Molecules Program

. The program is a collaboration between NIH and industry to match researchers with compounds that have already cleared the development process to test for new therapeutic uses. Participating companies will provide compounds and data determined to meet specific NIH eligibility criteria. Compound preliminary information is available on the NCATS 

"Each company participating in this innovative collaboration has made substantial research and development investments to advance these compounds to the point where they can be used in clinical studies," states Kathy L. Hudson, NCATS acting deputy director, in a NIH press release. "If researchers funded through this effort can demonstrate new uses for the compounds, they could significantly reduce the amount of time it takes to get a treatment to patients in need."

NCATS plans to provide up to $20 million in fiscal year 2013 to fund cooperative research grants. The NIH press release states that researchers who meet specific milestones will “conduct preclinical validation and clinical feasibility studies in the first stage, and proof-of-concept clinical trials in the second stage, to test whether one of the compounds may be effective against a previously unexplored disease target.” 

Pfizer, AstraZeneca, and Eli Lilly have already signed on to the program.

The National Institutes of Health have gained the participation of Abbott, Bristol-Myers Squibb, GlaxoSmithKline, Janssen Pharmaceutical Research & Development, and Sanofi in their effort to advance new therapeutic research.

NIH Initiative Gains Five New Companies

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.

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."