DID - May 13, 2009 Issue

Vol. 8 No. 93

FDA, Baxter Review Two Deaths in Hospital Patients on Heparin

Baxter International and the FDA are investigating two deaths and an adverse reaction in hospital patients given a heparin product made by Baxter, the company says.

The adverse events occurred at Beebe Medical Center in Lewes, Del., Baxter spokeswoman Erin Gardiner told DID. She said all three patients were receiving a heparin premix IV bag, which contains diluted heparin.

“It is early in the investigation,” Gardiner said Tuesday. “On Friday we were notified by Beebe Medical Center about three patient adverse events and that they thought our product, the heparin premix IV bag, could be associated with these events.”

Gardiner said the product is not the same as the Baxter heparin products with a contaminated active pharmaceutical ingredient from China’s Changzhou SPL that caused 81 deaths and resulted in a widespread recall last year (DID, April 22, 2008).

FDA spokeswoman Crystal Rice told DID, “FDA is aware of this incident and is actively investigating.” The agency is gathering more information about the adverse events, doing analytical testing of Baxter’s heparin and components, and examining adverse events in the agency’s database, she said. 

“FDA also is in regular contact with Baxter about its investigation,” Rice added. “Results of product testing to date by FDA and Baxter have not revealed any problems. As far as we can determine at this point, while we continue to investigate, this appears to be an isolated incident.”

Gardiner said, “We’re trying to understand what happened and if there’s any relationship with our product. We flew a medical team there Saturday, and they are taking samples.”

“All test results to date have shown no problem with the product. We have contacted multiple high-volume users, and no safety signal has been detected,” she added.

The incidents would be the only spontaneous adverse events reported for the premix IV bags. More than 14,000 of these bags are used each day — 5 million per year, Gardiner said. She added that the sourcing is different from that of the heparin products recalled last year, and they are manufactured at different Baxter facilities.

The active pharmaceutical ingredient is sourced from Pfizer and made in both China and the U.S. “We believe the lot all three patients received was North American-sourced,” Gardiner said. — Martin Berman-Gorvine


Texas Senate to Consider Physician Sunshine Bill on Gifts

A bill requiring the disclosure of gifts from drugmakers to physicians is headed for a floor vote in the Texas Legislature as early as Thursday.

Texas S.B. 553 passed the state Senate’s Health and Human Services Committee this week. The bill is similar to the Physician Payments Sunshine Act, sponsored in Congress by Sens. Chuck Grassley (R-Iowa) and Herb Kohl (D-Wis.), according to Graham Keever, a spokesman for state Sen. Royce West, who sponsored a third bill that has been superseded by S.B. 553.

The Physician Payments Sunshine Act, S. 301, would establish a nationwide standard for reporting payments to physicians and posting them online, all of which would be regulated by HHS (DID, Jan. 23). Keever said the Texas bill will not take effect unless the federal bill does not become law.

The Texas law requires that by Feb. 1 every year, manufacturers or repackagers of prescription drugs must submit to the Texas HHS “a report that discloses any gift, fee, payment, subsidy or other economic benefit received by a physician, physician’s office, hospital, nursing home, pharmacist, health benefit plan administrator or other person authorized by law to dispense or prescribe prescription drugs in this state in connection with detailing, promotional, or marketing activities of the manufacturer or repackager, directly or through its pharmaceutical marketers.” The Texas HHS is required to post the reports online by March 1.

Exceptions include:

  • Gifts worth less than $75;
  • Clinical trials payments;
  • Free samples of prescription drugs intended for distribution to patients;
  • Scholarships or other support for medical students, residents or fellows to attend professional educational, scientific or policy-making conferences; and
  • Grants to support such conferences.

The bill stipulates a $10,000 civil penalty for failure to comply. The text of the bill is available at www.legis.state.tx.us/tlodocs/81R/billtext/doc/SB00553I.doc. — Martin Berman-Gorvine


Drug Contract Manufacturer Gets FDA Warning Letter

The quality control unit for Mississippi-based Pharma Pac has insufficient control over its production operations and did not establish adequate in-process controls for manufacturing the motion sickness drug meclizine HCl, according to an FDA warning letter.

Pharma Pac also is cited for not applying an expiration date to the product and failing to have equipment to control humidity and other environmental factors during production, according to the warning letter dated April 27 and posted on the FDA’s website Tuesday.

The company’s facility in De Kalb, Miss., was inspected by the agency last summer. In Pharma Pac’s July 31, 2008, response to the inspector’s Form 483 observations, the company tells the agency it has discontinued production of meclizine, the FDA says.

“Be aware, however, it is your responsibility as a drug manufacturer to proactively assure all drug products manufactured in your facility, now or in the future, are manufactured in accordance with all” current good manufacturing practices, the agency tells the company.

Pharma Pac also was cited for producing unapproved prescription drugs that contain the following active ingredients:

  • Brompheniramine maleate;
  • Dextromethorphan hydrobromide;
  • Pseudoephedrine HCl USP;
  • Phenylephrine tannate; and
  • Chlorpheniramine tannate.

Inactive ingredients for the prescription drugs were not on finished product labels as required by regulation, and the products were not listed with the FDA, the letter says.

The company also makes an OTC skin lotion that was cited in the letter. Labeling for the product says it hydrates irritated skin, speeds healing and contains three vitamins, listing the positive effects from the vitamins.

The FDA says those statements “go beyond cosmetic claims,” making the lotion subject to the final monograph on OTC skin protectants. But the company’s healing lotion has a combination of ingredients that is not authorized under the monograph, the letter says.

Pharma Pac did not comment on the warning letter by press time. The letter is available at www.fda.gov/foi/warning_letters/s7185c.pdf. — Christopher Hollis


Merck Wins More Time to Appeal Vioxx Lawsuit in Canada

Canada’s Court of Appeal for Ontario gave Merck until May 21 to appeal the certification of a lawsuit over its recalled pain drug Vioxx.

The appellate court granted the deadline extension so the drugmaker would have enough time to appeal Justice Denise Bellamy’s decision last November to deny its appeal of a previous decision certifying the class action.

A recent court decision in a class action involving Vioxx (rofecoxib) in Saskatchewan — denying the lawsuit’s certification — led Merck to decide to file a second appeal in the Ontario case, the company says in court filings.

The Saskatchewan court found that the lawsuit in that case should not have been certified as a class action because the cases involved did not have an identifiable class or common issues — a point Merck asserts may also be true in the Ontario case.

Justice Paul Rouleau of the Ontario appellate court said the Saskatchewan decision significantly altered the Ontario case.

“It may well be that, as submitted by the moving parties, [Justice Bellamy] would have viewed the matter differently had the decision of the Saskatchewan Court of Appeal quashing the certification order been issued prior to her rendering her decision,” Rouleau says in his decision. “I am not, therefore, prepared to say that the proposed appeal is without merit.”

Rouleau’s decision allows Merck additional time to appeal the certification of the lawsuit in Ontario but does not alter its current certification.

The company plans to file an appeal by the May 21 deadline, Ronald Rodgers, a spokesman for Merck, told DID.

A copy of the Court of Appeal for Ontario’s decision can be found at www.ontariocourts.on.ca/decisions/2009/may/2009ONCA0393.pdf. — David Belian


AstraZeneca Adds Patent to Pulmicort Complaint Against Apotex

AstraZeneca has filed an amended complaint in a patent dispute with Apotex over Pulmicort Respules, a treatment for childhood asthma.

The revised complaint adds the ’834 patent to the ’603 and ’099 patents. All three expire in 2018 but have pediatric exclusivity extending to 2019, according to the Orange Book.

AstraZeneca’s filing in the case AstraZeneca LP and AstraZeneca AB v. Apotex, Inc. and Apotex Corp. comes a little more than a month after the FDA approved Apotex’s generic Pulmicort Respules (budesonide), prompting the brand-drug maker to file a sealed complaint in the U.S. District Court for the District of New Jersey.

Subsequently, AstraZeneca sought a temporary restraining order enjoining Apotex from selling its product. Judge Renee Marie Bumb granted the request April 16, according to an AstraZeneca statement (DID, April 20).

Last year, AstraZeneca settled with Teva Pharmaceutical Industries in a separate case involving Pulmicort Respules. Under the agreement, Teva will be allowed to sell its generic version of the drug through an exclusive licensing agreement starting Dec. 15 (DID, Nov. 26, 2008).

Pulmicort Respules is a maintenance asthma treatment indicated for use in children age 12 months to 8 years. Last year, the Pulmicort franchise had U.S. sales of about $982 million, AstraZeneca says in a statement. — Elizabeth Jones


GSK Gives Up Marketing, Distribution Rights in South Africa

GlaxoSmithKline (GSK) and Aspen Pharmacare Holdings have completed an agreement that will give Aspen control of the marketing and distribution rights for all of GSK’s drugs in South Africa.

The agreement, under which GSK will take a 16 percent stake in the South African drugmaker in exchange for relinquishing control of the products, is an attempt by GSK to “simplify its operations and divest certain products which can be more efficiently commercialized by other parties,” the company says in a statement Tuesday.

The companies will combine their operations in sub-Saharan Africa and will collaborate on the commercialization of their current and future products in the region. GSK will transfer marketing and distribution rights for all of its pharmaceutical products in South Africa to Aspen. The company also will give full control of eight specialist medicines and a manufacturing facility in Germany to Aspen.

The specialist medicines GSK will transfer to Aspen are Alkeran (melphalan), Kemadrin (procyclidine HCl), Lanvis (tioguanine), Leukeran (chlorambucil), Myleran (busulfan), Purinethol (mercaptopurine), Septrin (co-trimoxazole) and Trandate (labetalol HCl). Aspen will receive worldwide distribution rights for all of the drugs except Alkeran; GSK will maintain control of that treatment in the U.S. Combined sales of the products were about $81 million in 2008, GSK says. — David Belian


Repackager Initiates Recall of Caraco Heart Drug

A-S Medication Solutions, a drug-repackaging company based in Libertyville, Ill., is recalling all digoxin tablets manufactured by Caraco Pharmaceuticals and distributed before March 31.

The consumer-level recall is being undertaken because the digoxin tablets could vary in size and deliver a variable dose of the drug, A-S Medication Solutions says.

“Digoxin is a drug product used to treat heart failure and abnormal heart rhythms,” the company says in a statement. “It has a narrow therapeutic index and the existence of higher-than-labeled doses may pose a risk of digoxin toxicity in patients with renal failure.”

Digoxin toxicity can cause nausea, vomiting, dizziness, low blood pressure, cardiac instability, slow heart rate and even death, the company says.

Caraco originally initiated the recall nearly two months ago (DID, April 1). Last year, the facility that made the product received a warning letter for good manufacturing practice  violations (DID, Dec. 3, 2008). — Christopher Hollis

Customer Service: Kim Williams
(888) 838-5578 • +1 (703) 538-7600
Editorial: David Grant
(703) 538-7600
Ad Sales: Andrew McSherry
(703) 538-7643
Content Sales: Alka Desai
(703) 538-7669

300 N. Washington St., Suite 200 • Falls Church, VA 22046-3431
Phone: (888) 838-5578 • +1 (703) 538-7600 • Fax: +1 (703) 538-7676

Reporters: Martin Berman-Gorvine, Christopher Hollis, Elizabeth Jones, Nick Wills, David Belian

President: Cynthia Carter; Publisher: Matt Salt; Editorial Director: David Grant; Executive Editor: Theresa Barry

Copyright © 2009 by Washington Business Information Inc. All rights reserved. Drug Industry Daily (ISSN 1541-6607), an executive briefing on the regulation of pharmaceuticals, is published daily, 250 issues, for $1,495. Photocopying or reproducing in any form, including electronic or facsimile transmission, scanning or electronic storage is a violation of federal copyright law and is strictly prohibited without the publisher’s express written permission. Subscribers registered with the Copyright Clearance Center (CCC) may reproduce articles for internal use only. For more information, contact CCC at www.copyright.com or call (978) 750-8400. For site licenses for multiple users or to purchase multiple copies, contact Content Sales Manager Alka Desai at (703) 538-7669.