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

Susan Haigney

-In a letter to Acting Comptroller General Gene Dodaro dated Nov. 19, 2008, Congressman Joe Barton (R-TX) requested that the US Government Accountability Office (GAO) review the US Food and Drug Administration’s handling of the highly publicized tainted-heparin scare that occurred in 2007 and 2008. Congressman Barton is a ranking member of the US House of Representatives Committee on Energy and Commerce.

Concerns raised by Barton include whether FDA thoroughly investigated the heparin situation and whether the agency has been completely forthcoming with its findings. Barton cites potential discrepancies in information provided by FDA in regards to three reported patient deaths. Barton suggests in the letter to GAO that statements made in the press by FDA that heparin was linked to the deaths of three patients potentially contradict information provided by FDA to Barton. “FDA classified the cause of death from heparin as only ‘possible’ in two of those cases, and ‘unassessable’ in the third case,” Barton states. According to Barton’s letter, Baxter Healthcare Corporation (Deerfield, IL), the manufacturer of the heparin in question, performed its own investigation into the deaths and concluded that the three deaths were unlikely to be a result of heparin use.

Also in question is FDA’s potential lack of follow-up investigations, including interviewing clinical staff and the failure to use medical reporting databases other than the FDA’s Adverse Events Reporting System. In the Nov. 19 letter, Barton states his concern that FDA may not have thoroughly investigated reported deaths because the agency “did not follow up to interview clinical staff or Baxter for further details about each of these cases. In addition, FDA told Minority Committee staff the agency did not access other [adverse drug reaction] databases…”  

The letter states that Barton believes FDA may not have made certain information regarding the investigation public and that conflicting information makes it unclear if heparin made by American Pharmaceutical Partners (APP, Schaumburg, IL) is safe. “Out of the 16 allergic reaction heparin death reports received by FDA with lot numbers, the only case in which FDA determined that the cause of death from heparin infusion was ‘probable’ involved a heparin drug made by American Pharmaceutical Partners,” Barton states. 

The congressman expresses his concern that the heparin situation may indicate that FDA has not improved its drug safety system as it promised to do in 2007 hearings before the Subcommittee on Health and the Subcommittee on Oversight and Investigations. “The apparent gaps in FDA assessment and public communication about the cause(s) of heparin deaths raise questions about whether these FDA changes have actually resulted in real improvement in drug safety oversight,” states Barton in his letter to GAO. Barton hopes “GAO’s review will determine the strengths and weaknesses in FDA’s response to the heparin drug safety problem, and will make recommendations on what FDA could do better in dealing real-time with an emerging drug safety problem in the future.”

 Early in 2008, FDA investigated reported adverse drug affects associated with the use of the blood thinner heparin. In March 2008, FDA found the contaminant over-sulfated chondroitin sulfate in the active pharmaceutical ingredient produced by a Chinese manufacturer for Baxter.

For additional information on the heparin contamination, visit:

Articles

In a letter to Acting Comptroller General Gene Dodaro dated November 19, 2008, Congressman Joe Barton (R-Texas) requested that the US Government Accountability Office (GAO) review the US Food and Drug Administration's handling of the highly-publicized, tainted heparin scare that occurred in 2007 and 2008.

Congressman Questions FDA's Heparin Investigation

-In an effort to clarify its policy on the use and creation of genetically engineered (GE) animals, the US Food and Drug Administration released the draft guidance 

The Regulation of Genetically Engineered Animals Containing Heritable rDNA Constructs

 on Sept. 18, 2008. The guidance also outlines requirements and recommendations already existing in regards to GE animals and products derived from GE animals. 

GE animals are animals whose DNA has been manipulated with a recombinant DNA (rDNA) construct to bring about new or specific traits. These animals are used to create pharmaceuticals, serve as models for human diseases, and produce consumer products.  According to FDA, rDNA constructs meet the definition of a new animal drug under the Food, Drug, and Cosmetic Act (FD&C Act), which classifies “articles (other than food) intended to affect the structure or any function of the body of man or other animals” as drugs.  

“Genetically engineered animals hold great promise for improving human medicine, agriculture, the environment, and the production of new materials, and  FDA has long been involved in the scientific evaluation. Our guidance provides a framework for both GE animals and products made from them to reach the market,” stated deputy commission for policy Randall Lutter, PhD, in a press release.

The guidance indicates areas in which FDA will be coordinating with other federal agencies in the US Department of Agriculture and the Environment Protection Agency to develop policies in regard to GE animals. Specific questions addressed in the guidance include FDA’s enforcement entitlements, current regulations, and product development processes. The guidance also outlines the responsibilities for meeting environmental assessment under the National Environmental Policy Act for those applying for an animal drug application.  The draft guidance is limited to heritable rDNA constructs. Nonheritable constructs may be addressed in a future guidance.

Public comment on the draft guidance is open until November 18, 2008. A copy of the guidance can be downloaded 

In an effort to clarify its policy on the use and creation of genetically engineered animals (GE animals), the US Food and Drug Administration released the draft guidance "The Regulation of Genetically Engineered Animals Containing Heritable rDNA Constructs" on September 18.

FDA Outlines Rules on Genetically Engineered Animals

The US Food and Drug Administration has issued two warning letters to Ranbaxy Laboratories  (Gurgaon, Haryana, India), one of the largest suppliers of generic drugs imported to the US, expressing what the agency believes is a deviation from US current good manufacturing practice (CGMP) requirements at two of the company’s manufacturing facilities in India: Dewas and Paonta Sahib. Some areas of concern expressed in the warning letters included inadequate batch production and control records, inadequate failure investigations, inadequate written records of cleaning and use of equipment, and inadequate review procedures.

FDA stated in a press release that Ranbaxy has been informed that FDA will deny any new drug applications or abbreviated new drug applications that list either of the two plants as a manufacturer until the company resolves the CGMP deficiencies. 

FDA also issued an Import Alert for generic drugs produced by the two plants. The alert allows US officials at the US border to detain any imported active pharmaceutical ingredients (API) or finished drug products that were manufactured at the Ranbaxy facilities. While the alert affects more than 30 generic drugs, FDA stated it believed other drug suppliers could meet market demand and patients should continue to take their medications.

FDA stated in a press release that these actions “are proactive measures that the FDA is taking in order to assure that all drugs that reach the American public are manufactured according to CGMP requirements.” FDA also stated that it did not believe that Ranbaxy has yet shipped any defective products and that products produced at other Ranbaxy’s plants are not affected.

In a press release issued on Sept. 17, 2008, Ranbaxy stated that “the company has just received the warning letters that FDA has issued and has not had the opportunity to review those concerns that FDA has determined are unresolved. Once it has an opportunity to review the issues, the company looks forward to continuing to cooperate with FDA to resolve the remaining issues.”  Ranbaxy also expressed its disappointment by stating that “the company has responded to each concern FDA has raised during the past two years and had thought that progress was being made. We are, however, pleased that FDA’s testing and review led the agency to conclude that there is no reason to question the safety or effectiveness of Ranbaxy’s drugs.”

The US Food and Drug Administration has issued two warning letters to Ranbaxy Laboratories.

FDA Issues Warning Letters and Import Alert on Ranbaxy Laboratories

-The US Food and Drug Administration has updated its draft bioequivalence recommendations for several products, and added 66 new draft product-specific guidelines since October 2007. The drug products for which updated draft product-specific bioequivalence recommendations are available include: risedronate sodium, fosinopril sodium/hydrochlorothiazide, fluoxetine HCI/olanzapine, erlotinib HCI, and morphine sulfate.

In 2007, FDA announced in its draft guidance for industry, “

Bioequivalence Recommendations for Specific Products

,” that the agency was providing product-specific bioequivalence recommendations on its website to solicit public consideration and recommendations. The online process is intended to support drug manufacturers with abbreviated new drug applications. 

 for the announcement of the new recommendations and 

 for the updated bioequivalence recommendations list.  

The US Food and Drug Administration has updated its draft bioequivalence recommendations for several products, and added 66 new draft product-specific guidelines since October 2007.

FDA Updates Bioequivalence Guidelines

-The California Senate passed SB 1096 on May 29, voting to amend the state’s Confidentiality of Medical Information Act to allow pharmacies to provide third parties with patient information for the purpose of mailing prescription refill reminders and drug information directly to patients. The bill now moves to the California Assembly.

California’s Confidentiality of Medical Information Act prohibits health care providers and health service plans from sharing or selling patient information for marketing or other purposes without the patient’s authorization. SB 1096 would amend that Act to “allow a pharmacy to mail specified written communications to a patient, without the patient’s authorization under specified conditions.” The conditions limit information to prescription label language of only doctor-prescribed medication with instructions to contact a physician if the patient has questions. The mailed communications are prohibited from mentioning other products or medications that have not been prescribed by the patient’s doctor. Medications involved are limited to certain diseases listed in the bill. 

The state senate rejected an earlier version of SB 1096 because it did not give patients a clear enough way to opt out of the program. The bill was revised to include a provision that the pharmacy offer patients the ability to opt out of receiving mailed information at the time the patient picks up their medications. Patients would also have a phone number to call or a Website to visit to stop receiving mailings at a later date.

Supporters of SB 1096, introduced by California State Senator Ron Calderon, suggest that written, mailed information would encourage proper use of prescribed medication. A 

California Senate Health Committee Analysis of the bill

  notes a 2007 study released by the National Council of Patient Information and Education that estimated that only half of patients take their prescribed medication. Another study from the 

 showed that reminding patients to take their medication had positive results. Supporters suggest that improper use of prescribed medication results in millions of dollars in Medicaid costs and drug-related hospitalizations.

However, opponents of the bill, like the Consumer Federation of California (CFC), insist the bill violates patient privacy and may interfere with the doctor-patient relationship. In a letter posted on 

, the CFC stated that the bill “is a significant intervention by drug companies into the physician-patient relationship. We believe a patient’s doctor is the best source for informing a patient about how to manage his or her health condition.” The CFC believes that such mailings might confuse certain patients, especially senior citizens, if they receive contradictory information from what they have been told by their doctor. “This kind of direct interference in the doctor-patient relationship is potentially dangerous to patient health.” According to the CFC, the company sponsoring the legislation, Adheris Inc, may directly benefit from the bill. Passage of the bill could possibly invalidate a 2004 lawsuit filed against Adheris for mailing personalized letters from pharmacies to patients, according to the CFC.

The California Senate passed SB 1096 on May 29, voting to amend the state?s Confidentiality of Medical Information Act to allow pharmacies to provide third parties with patient information for the purpose of mailing prescription refill reminders and drug information directly to patients.

California Senate Passes Bill That Would Amend the State Confidentiality of Medical Information Act

The devastating May 12 earthquake that struck the Wen Chuan Sichuan province of China left tens of thousands dead, homes and businesses destroyed, and survivors without basic human needs such as shelter, food, and medicines. The quake also had a significant impact on the local industries of the region. Pharmaceutical companies located within the affected areas are assessing possible damage to facilities and loss of personnel. And in response to the area’s need for medical supplies, pharma companies inside and outside of China are offering help to the people left devastated by the disaster by providing drugs and medical devices. 

The majority of pharmaceutical plants located in the region have not yet reported any significant structural damage or loss of personnel because of the quake. 

, Inc (Xi’an, China), a developer and producer of plant extracts and pharmaceutical raw materials, announced that there was no damage to their facilities and workers have returned to the operation. “We are terribly saddened by the loss of life and property in the Sichuan Earthquake. While we are happy to report that neither our employees nor our facilities suffered any harm, Huifeng is prepared to provide support to the victims of this terrible disaster,” company CEO Jing’An Wang stated in a company press release. American Oriental Bioengineering also reported no significant impact. “Our thoughts are with the many victims of China’s earthquake and we are thankful to report that none of our staff was hurt in the tragic events. Our manufacturing, production, and overall operations were not impacted by the earthquake and we do not anticipate any damage-related impact to our sales in the second quarter,” stated Tony Lui, chairman and CEO, in a company press release.

However, not every pharmaceutical company came away unaffected. 

, located in Shenzhen, announced on May 14 that the quake damaged the water piping system in its Guiyang facility. The damage compromised the production of the osteoporosis drug Xianling Gubao (XLGB), and the company temporarily halted production.  Xiaochun Wang, Tongjitang’s chief executive office, stated in a company press release, “We are committed to the highest quality levels of production. Currently, we are working diligently to make sure that production will be resumed as soon as conditions allow.”

 has reported that pharmacies in the area have been destroyed, leaving a shortage of medicines. The pharmaceutical industry has responded to the devastation with donations of cash and supplies from nearly all pharmaceutical companies, big and small, across the globe and from companies inside China. According to Interfax China, 

 has donated $3.57 million in drugs and medical devices that include ventilators, electrocardiogram monitors, and IV infusion kits. 

 (Hainan) announced on May 16 that it donated over $280,000 of antibiotics, antivirus, and anti-cold products to the relief effort. 

 (Tustin, CA), donated more than $70,000 in products to the 

. Donations continue to arrive to relief organizations in the region from companies and individuals around the world.

The devastating May 12 earthquake that struck the Wen Chuan Sichuan province of China left tens of thousands dead, homes and businesses destroyed, and survivors without basic human needs such as shelter, food, and medicines. The quake also had a significant impact on the local industries of the region. Pharmaceutical companies located within the affected areas are assessing possible damage to facilities and loss of personnel.