Critical review and appraisal of published clinical literature: useful skill in biotechnology product development.

Critical review of published literature may be necessary during several stages of biotechnology product development. The reviewer should develop a standardized method for reviewing and comparing published papers on a given topic and should be aware of common errors found in published papers.

Using nanotechnology to improve the characteristics of antineoplastic drugs: improved characteristics of nab-paclitaxel compared with solvent-based paclitaxel.

Nanotechnology refers to the use of very small pieces of matter, typically < or =200 nm in diameter. Nanoparticle albumin-bound (nab) paclitaxel, a soluble form of the cytotoxin paclitaxel that has demonstrated utility in the setting of cancer chemotherapy, is produced by nab technology using the protein albumin. nab-Paclitaxel targets tumors, enhances tumor penetration by the novel mechanism of albumin receptor-mediated (gp60) endothelial transcytosis, and avoids the use of surfactants and solvents such as Cremophor and Tween. nab-Paclitaxel minimizes the toxicities associated with Cremophor and eliminates the need for premedication for hypersensitivity reactions caused by Cremophor. The albumin coating that surrounds the active drug assists in the transport of the nanoparticles to the interior of the tumor cell that preferentially takes in albumin as a nutrient through the gp60 pathway. In nonclinical studies, nab-paclitaxel achieved higher intratumoral concentrations compared with solvent-based paclitaxel and increased the bioavailability of paclitaxel by eliminating the entrapment of paclitaxel in the plasma. Compared with solvent-based paclitaxel, at equitoxic doses, the nab-paclitaxel produced more complete regressions, longer time to recurrence, longer doubling times, and prolonged survival. nab-Paclitaxel has been shown to have superior efficacy compared with solvent-based paclitaxel without the need for premedication in clinical trials of patients with advanced solid tumors. nab-Paclitaxel has been effective in patients for whom previous chemotherapy has not been helpful. nab Technology has the potential to be applied to other insoluble drugs.

Clinical trial registries and clinical trial result posting: new paradigm for medical writers.

Clinical trial registries and posting of clinical trial results have recently become standard procedures for drug development. Several groups, including journal editors and professional trade organizations have called for legislation or have mandated terms or both for the public disclosure of current trials and the results of the clinical trials within a short timeframe after the trial has ended.

Medical writing departments in biopharma companies: how to establish a department.

Medical writers have important roles in preparing the documentation for approval for marketing of new products, writing manuscripts for publication, and other nonclinical, clinical, and promotional materials. Medical writing departments can be organized in different ways to accommodate the needs of the company. When organizing a new department or when determining metric for an existing department, it is important to understand what medical writers in the biopharma industry do, how they are recruited and trained, and how metrics are developed.

A prospective, non-randomised phase 1-2 trial of VACOP-B with filgrastim support for HIV-related non-Hodgkin's lymphoma.

Non-Hodgkin's lymphoma (NHL) remains an important complication of associated HIV infection despite advances in antiretroviral therapy (ART), and the optimum chemotherapy regimen for this disease remains to be defined. A dose-escalation trial was performed to determine the maximum tolerated doses of etoposide and doxorubicin as part of the 12-week VACOP-B regimen, supported by filgrastim (r-metHuG-CSF). Patients with aggressive histology HIV-related NHL who were previously untreated with chemotherapy, and who had no active opportunistic infection were eligible for the study. Chemotherapy consisted of cyclophosphamide 350 mg/m2, vincristine 2 mg, bleomycin 10 U/m2; and prednisone 100 mg q2 days x 12 weeks, with increasing doses of doxorubicin 25-50 mg/m2 and etoposide 25-50 mg/m2 intravenously and 50-100 mg/m2 orally. Central nervous system prophylaxis (intrathecal cytarabine 50 mg x 4 doses), antifungal, and Pneumocystis carinii prophylaxis were used, and filgrastim was administered to prevent neutropenic complications. One dose level was expanded to permit the concomitant use of ART. Endpoints were determination of maximum tolerated dose of doxorubicin and etoposide, treatment tolerability, and survival. Forty-seven patients were enrolled, most with diffuse large-cell or immunoblastic NHL. Protocol-defined maximum tolerated dose was not reached and the limits of dose-limiting toxicity were not exceeded, even in patients receiving ART. Thirty-two cycles (4.9%) were delayed >6 days because of toxicity; 30 patients (64%) completed all 12 weeks of treatment. After completion of therapy, 14 patients had a complete response (30%), and 4 had a partial response (8%). Median time to progression was 9 months. At 42 months, progression-free survival was 25% and overall survival was 28%.

Drug-induced and antibody-mediated pure red cell aplasia: a review of literature and current knowledge.

Anti-erythropoietin (EPO)-induced pure red cell aplasia (PRCA) is an uncommon, potentially life-threatening condition in which the bone marrow stops manufacturing red blood cells. In the past few years, reports of drug-induced, anti-EPO antibody-mediated PRCA have increased substantially, with most cases attributed to the use of one erythropoiesis-stimulating protein, Eprex. A literature review was undertaken to document the reports of drug-induced PRCA, with all drugs and drug regimens. The sudden increase in reports of antibody-mediated PRCA is discussed.

Using the biologic license application or new drug application as a basis for the common technical document.

With the introduction of the common technical document (CTD), many writers in the biotech and pharmaceutical industries are now required to submit dossiers in this format. The format of the CTD is not extremely difficult from the familiar documents of the Biologic License Application (BLA) or New Drug Application (NDA). The CTD can be mapped to existing areas of the BLA or NDA. The components of the CTD are discussed and references to the current guidance worldwide are provided to assist the writer.

Guidelines and policies for medical writers in the biotech industry: an update on the controversy.

Papers reporting the results of clinical trials written by medical writers employed by the biotech and pharmaceutical industries have been criticized for possible bias in presentation and failure to adhere to authorship guidelines. Several groups have attempted to address the concerns of journal editors, academics, regulators, and the general public by issuing guidelines and policies for the preparation of such material.

Production of high-quality marketing applications: strategies for biotechnology companies working with contract research organizations.

Many biotechnology and pharmaceutical companies use clinical research organizations (CROs) to assist in the writing and preparation of clinical documents intended for submission to health authorities. Start-up companies often require the expertise of a CRO to prepare their first regulatory documents. Larger or more experienced companies often require CRO staff to assist at times of multiple simultaneous submissions. The timely production of high-quality new drug marketing applications requires close collaborations between the drug company and the CRO. The views of both CRO and industry in ensuring best practices are discussed.

Review of current authorship guidelines and the controversy regarding publication of clinical trial data.

Publication of clinical trial data is the final step in the scientific method and an important method by which pharmaceutical and biotechnology companies, i.e., drug sponsors, disseminate information about their products. Because of the nature of large, multicenter trials, multiple investigators from many institutions may be considered as authors of these papers. Controversy concerning the rights of academic institutions and the rights of drug sponsors has been widely debated. This chapter summarizes the controversy and the current policies.

The development of supportive-care agents for patients with cancer.

As the population ages, a dramatic increase in the number of cases of cancer is expected and the need for supportive-care agents, those used to ameliorate some of the side effects of cancer or its treatment, becomes more urgent. At present, supportive-care products are available and new agents are being developed with novel mechanisms of action or modifications of existing agents that improve performance. Because of the urgent need for such products, efficient development is required to deliver useful products to patients as rapidly as possible. This chapter uses actual examples to illustrate the stages of drug development, phase I through phase 3.

Darbepoetin alfa: a new approach to the treatment of chemotherapy-induced anaemia.

Chemotherapy-induced anaemia has important consequences on the quality of life and social function of cancer patients. The finding of erythropoietin (EPO) deficiency in these patients led to the therapeutic development of erythropoietic proteins. Darbepoetin alfa (Aranesp), Amgen Inc, Thousand Oaks, California), a new erythropoietic growth factor, has eight more sialic acids than epoetin alfa. The increased sialic acid content confers a three-fold longer half-life and allows the drug to be administered less frequently than epoetin alfa. Darbepoetin alfa affects the same early haematopoietic cells as epoetin alfa and the endogenous hormone EPO. Preclinical pharmacokinetic studies suggest that the intrinsic pharmacological properties of darbepoetin alfa are comparable to those of epoetin alfa, but that the increased sialic acid content allows for less-frequent administration with superior performance. Darbepoetin alfa has been shown to have safe clinical efficacy in a variety of tumour settings and with several types of chemotherapy.