Angie Drakulich was editorial director of Pharmaceutical Technology.

Angie Drakulich

The US Food and Drug Administration will hold a public hearing Oct. 2, 2008, to obtain input regarding over-the-counter (OTC) cough and cold drugs marketed for pediatric use. The hearing comes after more than a year of concerning reports on these nonprescription drugs and their safety and efficacy for children under age 6. 

FDA is developing a proposed rule to revise the pediatric labeling contained in the Final Monograph for Cough, Cold, Allergy, Bronchodilator, and Anti-asthmatic Drug Products for Over-the-Counter Human Use, according to the agency announcement. The hearing is meant to provide FDA with input about certain scientific, regulatory, and product use issues as it proceeds with the rulemaking and reviews new drug applications (NDAs) for related drug ingredients.

To provide background, in March 2007, a group of pediatric healthcare practitioners petitioned FDA to amend the OTC drug monograph in 21 

 part 341 so that the labeling for antitussive, expectorant, nasal decongestant, antihistamine, and combination cough and cold products would not be used for children under age 6 because the products have not been found to be safe or effective in that age group. In addition, according to FDA’s hearing announcement, the 2007 petition asked FDA to notify manufacturers of products whose labeling either uses such terms as "infant" or "baby," or displays images of children under age 6, that such marketing is not supported by scientific evidence and that manufacturers will be subject to enforcement action.

FDA convened a joint meeting of the Nonprescription Drugs Advisory Committee and the Pediatric Advisory Committee in October 2007 to discuss the safety and efficacy of these OTC cough and cold products. The 22-person committee was “nearly unanimous in agreeing that new studies were necessary because extrapolation of efficacy data for the common cold indication from adults to children was not acceptable for children less than 2 years old or for children 2 years to less than 12 years.” The committee also voted 13 to 9 to recommend that pediatric cough and cold drugs should not be used for children under 6 years of age while rulemaking proceeded, and voted 15 to 7 to recommend that the products could, continue to be sold for use in children ages 6 to under 12 while new studies are conducted.

Wyeth, Prestige Brands, Johnson & Johnson, and Novartis did voluntarily withdraw related medications for children under age 2 last October.

In January of this year, FDA issued a Public Health Advisory recommending that these drugs not be used to treat infants and children under 2 because serious and potentially life-threatening side effects can occur. The advisory also indicated that FDA had not yet completed its review of the safety of these medicines in children aged 2 to 11; the agency committed to completing the review as quickly as possible.

Since that time, FDA has been reviewing available data concerning the use of cough and cold medications in children and, ultimately, noted that children under age 4 are more likely to experience non-allergic adverse events than older children. However, given that 1 in 10

children uses one or more cough and cold products during a given week with exposure being highest among 2 to 5 year olds, and high in children under 2.4 years old, according to a recent report, the agency has noted that serious adverse events are relatively rare given the extensive use of the drug products.

However, according to the public hearing announcement, FDA is interested in obtaining public comment on these issues, including: What types of studies should be conducted to assess effectiveness and/or safety, and to determine appropriate dosing of cough and cold ingredients in the pediatric population?  What is the most appropriate method for determining pediatric doses? Can measurement errors in dosing be reduced using more standardized measuring devices or alternative dosage forms?

The hearing will be held from 8 am to 5 pm, Oct. 2, at the Sheraton Washington
 North Hotel, 4095 Powder Mill Rd., Beltsville, MD 20705. Comments and written registration can be submitted to: Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852, or online, at 

. Registrations are due Sept. 15; comments are due Dec. 2.

Drug Makers Voluntarily Recall OTC Infant Cough and Cold Medications

FDA Committees Recommend Ban on Cough and Cold Medications for Young Children

FDA Recommends No Cough and Cold OTCs for Children Under Two

Articles

The US Food and Drug Administration will hold a public hearing Oct. 2, 2008, to obtain input regarding over-the-counter (OTC) cough and cold drugs marketed for pediatric use.

Public Comment on Cough and Cold Meds for Kids

It’s no secret that industry pipelines are thin at the moment. But what about innovations in pharmaceutical science? Are companies keeping up with the times to develop new ways of testing, delivering, formulating, analyzing, or manufacturing drugs? 

 would like to hear from you. In fact, we launched a call for nominations for the 

2008 Innovations in Pharma Science Awards

 earlier this summer. The awards will honor achievements in the pharmaceutical sciences, specifically in these five areas:

But the deadline for nominations is here. Check out 

 to nominate your company's work in one of five areas by next week. The winners will be announced in the December issue.

The deadline for nominations for the Innovations in Pharma Science Awards is here. Check out http://pharmtech.com/Innovations to nominate your company's work in one of five areas by next week

Time is Running out for Innovation Awards

The US Food and Drug Administration may soon ask doctors to undergo special training to be able to prescribe powerful narcotics, Dr. Bob Rappaport told 

 last week. Rappaport, director of FDA’s Anesthesia, Analgesia and Rheumatology Products division, said the agency is considering recommending additional education for doctors in early 2009, as FDA doesn’t have the authority to require such training-that authority rests in the hands of state medical boards. 

More attention is being paid to this controversial issue as reports of improper use of painkillers have increased in recent months, despite FDA alerts. The drugs under concern include methadone, fentanyl, and some forms of oxycodone.

FDA issued a second safety warning on the Fentanyl skin patch, which contains opioid fentanyl, in December 2007 after continuing to receive reports of deaths and life-threatening side effects. Doctors have inappropriately prescribed the patch, whose directions need to be followed exactly to avoid overdose, and patents have incorrectly used it, according a Dec. 21 FDA release. 

Methadone, another opium-based drug, has been implicated in more than twice as many deaths as heroin and is close to overreaching deaths related to OxyContin and Vicodin, reports 

. This drug, in particular, has been associated with drug abusers. The number of methadone prescriptions went up 700% between 1998 and 2006, and yet, reports the 

, too few doctors understand how patients differ in their responses to the drug.

Currently, doctors only need to be licensed and registered with the Drug Enforcement Administration to be able to prescribe narcotic drugs, but pain experts are calling for increased education even though it may limit the number of doctors prescribing such medications, according to 

 that FDA may also ask drugmakers to develop programs to monitor how narcotics are prescribed.

 of the May 2008 Joint Meeting of FDA’s Anesthetic and Life Support Drugs Advisory Committee, and the Drug Safety & Risk Management Advisory Committee, addressing fentanyl.


Doctors and Narcotics–More Training, Please

The US Food and Drug Administration may soon ask doctors to undergo special training to be able to prescribe powerful narcotics, Dr. Bob Rappaport told The New York Times last week. Rappaport, director of FDA's Anesthesia, Analgesia and Rheumatology Products division, said the agency is considering recommending additional education for doctors in early 2009.

Misuse of Narcotics May Call for Additional Doctor Training

The US Food and Drug Administration issued a new draft guidance for public comment on sterile manufacturing. Titled 

Submission of Documentation in Applications for Parametric Release of Human and Veterinary Drug Products Terminally Sterilized by Moist Heat Processes

, the guidance provides recommendations on what to include in a new drug application (NDA), abbreviated new drug application (ANDA), new animal drug application (NADA), abbreviated new animal drug application (ANADA), biologics license application (BLA), or supplement or other postmarketing report regarding parametric release for sterile products terminally sterilized by moist heat.

Currently, FDA requires that sterile products meet certain sterility requirements before release to the market. According to the draft guidance, the requirements for batch release are most often fulfilled with a sterility test of finished units drawn from the batch. 

is defined as a sterility assurance release program where demonstrated control of the sterilization process enables a company to use defined critical process controls, in lieu of the sterility test, to fulfill the intent of 21 

With this strategy, market release of terminally sterilized products can be based on meeting the defined sterilization parameters rather than  performing an approved sterility test. “Meeting the requirements of the parametric release process,” according to the draft guidance, “can provide greater assurance that a batch meets the sterility requirement than can be achieved with a sterility test of finished units drawn from the batch.”

The guidance may apply to products sterilized by other terminal sterilization processes such as radiation sterilization, which may be suitable for parametric release. 

Comments on the draft guidance are due Oct. 6. Read the 

The US Food and Drug Administration issued a new draft guidance for public comment on sterile manufacturing.

Sterile Manufacturing Draft Guidance Provides Application Information

-Next week, the US Food and Drug Administration’s communications with pharmaceutical companies will change. Under new regulations that govern the drug approval process, FDA’s Center for Drug Evaluation and Research (CDER) will no longer issue “approvable” or “not approvable” letters when a drug application is not approved, according to an FDA release. Instead, CDER will issue a “complete response” letter at the end of the review period to let a drug company know of the agency’s decision on the application. The change takes effect August 11.

 “These new regulations will help the FDA adopt a more consistent and neutral way of conveying information to a company when we cannot approve a drug application in its present form,” said CDER Director Janet Woodcock in the release. “Thorough and timely review of drug applications is a priority of the FDA, and these new processes will make our communications with sponsors of applications more consistent.”

A “complete response” letter will let a pharmaceutical company know that the review period for its submitted drug is complete but that the application is not yet ready for approval. The letter will describe specific deficiencies and, when possible, outline ways the company might improve the application to make it approval-ready.

When assessing new drug applications, FDA currently responds with one of the following: an “approval” letter, meaning the drug has met agency standards for safety and efficacy and the drug can be marketed for sale in the United States; an “approvable” letter, which generally indicates that the drug can probably be approved at a later date provided that the applicant provides certain additional information or makes specified changes (such as to labeling); or a “not approvable” letter, meaning the application has deficiencies generally requiring the submission of substantial additional data before the application can be approved.

 “Complete response” letters are currently used to respond to companies that submit biologic license applications. The new regulations will make the process for drugs and biologics consistent.

Next week, the US Food and Drug Administration's communications with pharmaceutical companies will change, and the agency will begin issuing complete response letters in place of approvable letters.

FDA's Complete Responses Commence

-The US Food and Drug Administration released its user fee rates for fiscal year (FY) 2009 last Friday. The new fees take effect Oct. 1, 2008, and remain in effect through Sept. 30, 2009.

FDA derives its authority to issue user fees from the Federal Food, Drug, and Cosmetic Act, and the Prescription Drug User Fee Amendments of 2007 (PDUFA IV). Below is a list of the new fees:

Application fees requiring clinical data:      $1,247,200

Application fees not requiring clinical data:      $623,600

FDA estimates that there will be 25 establishment fee waivers in FY 2008 and probably another 10 in FY 2009 tied to orphan drugs per the Food and Drug Administration Amendments Act of 2007. The agency estimates there will be approximately 70 waivers, including exemptions tied to orphan drugs, for product fees in FY 2009 as there were in FY 2008.

The total fee revenue amount for FY 2009 is $510,665,000, including $35 million for drug safety compared with FY 2008 drug-safety fees of $25 million. 

The new fee information is detailed in the Aug. 1 

The US Food and Drug Administration released its user fee rates for fiscal year 2009 last Friday.