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

Susan Haigney

On Mar. 19, 2009, IMS, the leading provider of market research for the pharmaceutical and healthcare industries, reported that annual sales of prescriptions in the US grew 1.3% from $287.6 billion in 2007 to $291.5 billion in 2008. According to IMS, sales growth was slower in 2008 than in previous years. 

IMS cited higher demand for generic drugs, a reduced number of new products, and low consumer demand because of the economic downturn as reasons for the slow growth.

Sales for approximately half of the top grossing pharmaceutical companies were down from 2007. The two top moneymakers, Pfizer (New York) and GlaxosmithKline (London), were millions of dollars down from their 2007 sales.  Companies that saw a rise in sales included Astrazeneca (London), Hoffman-LaRoche (Paris), Lilly (Indianapolis), and Teva Pharmaceutical Industries (Jerusalem). 

Antipsychotic drugs were the most sold in overall sales through both retail and non-retail channels with lipid regulators, proton pump inhibitors, and seizure disorder medications following closely behind on the list of top selling drugs in 2008. Lipid regulators, antidepressants, ACE inhibitors, and beta-blockers were among the most widely dispensed prescriptions in 2008.

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On March 19, 2009, IMS, the leading provider of market research for the pharmaceutical and healthcare industries, reported that annual sales of prescriptions in the US grew 1.3% from 287.6 billion in 2007 to 291.5 billion in 2008.

Growth of US Prescription Sales Slow in 2008

On Mar. 2, 2009, President  Obama nominated Kansas Governor Kathleen Sebelius as his new Secretary of Health and Human Services (HHS). Sebelius, who has served as governor of Kansas since 2003, was Kansas’ Insurance Commissioner from 1994-2002. Sebelius, a Democrat governor in a predominately Republican state, is expected to help facilitate bipartisan healthcare reform. “As Secretary of Health and Human Services, Sebelius will work with Democrats and Republicans alike to cut costs, expand access, and improve the quality of healthcare for all Americans,” a White House 

 states. Her nomination awaits Senate approval.

President Obama also appointed Nancy-Ann DeParle Counselor to the President and Director of the White House Office for Health Reform. DeParle was previously commissioner of Tennessee’s Department of Human Services. According to the White House press release, DeParle handled budget matters for federal healthcare programs during the Clinton administration and managed Medicare and Medicaid.

Obama stated in the release that, “Healthcare reform that reduces costs while expanding coverage is no longer just a dream we hope to achieve-it’s a necessity we have to achieve. And today, I am proud to announce key members of my team who will be critical to that effort: Kansas Governor Kathleen Sebelius for my Secretary of Health and Human Services and Nancy-Ann DeParle as Director of the White House Office for Health Reform.”

President Obama nominated Kansas Governor Kathleen Sebelius as his new Secretary of Health and Human Services (HHS).

Governor Kathleen Sebelius Nominated for Secretary of HHS

The US Food and Drug Administration has stated its considerations in regard to the three draft annexes to the International Conference on Harmonization’s Q4B document "Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions." The draft annexes were published in late 2008 and resulted from the Q4B processes for uniformity of dosage units, dissolution tests, and sterility tests.

The draft annexes state that the pharmacopoeial texts for each individual processes (i.e., dosage units, dissolution tests, and sterility tests) from the United States Pharmacopeia, Japanese Pharmacopoeia, and the European Pharmacopoeia can be considered interchangeable. FDA, however, “might request that a company demonstrate that the chosen method is acceptable and suitable for a specific material or product, irrespective of the origin of the method.”

In regard to uniformity of dosage units, FDA states in draft Q4B Annex 6 that it “finds unsuitable for regulatory purposes  

not more than (NMT) 2% relative standard deviation (RSD)

 exception to the 25 mg/25% threshold. Accordingly, for those items below the 25 mg/25% threshold, testing by content uniformity should be performed.”

FDA comments on Annex 7, addressing dissolution tests, state “An appropriately rigorous mechanical calibration method (such as ASTM International’s ASTM E2503-07, Standard Practice for Qualification of Basket and Paddle Dissolution Apparatus, or the procedures for Mechanical Qualification of Dissolution Apparatus 1 and 2, DPA-LOP.002, on the FDA website), when properly executed, will satisfy the current good manufacturing practice (CGMP) requirement for dissolution apparatus calibration under 211.160(b)(4) of Title 21 of the Code of Federal Regulations.”

The draft annexes can be downloaded here:

Uniformity of Dosage UnitsGeneral Chapter

The US Food and Drug Administration stated its considerations in regards to the three draft annexes to the International Conference on Harmonization's Q4B document.

FDA Comments on ICH Q4B Draft Annexes

-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:

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.