Approval Of Biologics Research Articles

Trends in FDA drug approvals over last 2 decades: An observational study.

Introduction:The discovery of novel drugs is critical for pharmaceutical research and development as well as for patient treatment. Repurposing existing drugs that may have anticipated effects as potential candidate is one way to meet this important goal. Systematic investigation and comprehensive analysis of approved drugs could provide valuable insights into trends in the discovery and may contribute to further discovery of newer drugs systematically. Food and drug administration (FDA's) Center for Drug Evaluation and Research (CDER) every year summarizes novel drugs, some of which are truly innovative and help in advancing clinical care. This study was conducted to find a trend in drug approvals by FDA in the last 2 decades. Awareness of these new drugs amongst the primary care physicians is also crucial as they have been prescribing these agents in the past.Methodology:In this cross-sectional study, we collected, surveyed, and analyzed drugs approved by U.S. Food and Drug Administration (USFDA) from the year 2000 till 2017 identified from ClinicalTrials.gov and online database of FDA. Drugs approved every year were assessed for total number, class of drug, indication, and category of approval. Type of accelerated regulatory pathways and reasons for speedy approvals every year were also studied. Microsoft Office Excel 2007 was used for tabulation and analysis.Results:Total 209 were approved from 2000 to 2008. Out of these 9.09% were indicated for cardiovascular disorders and 12.91% for neurological disorders. Antibiotics (5.26%) and antivirals (5.74%) were least contributed, whereas anticancer drugs (11.96%) and biologics (7.17%) approval remained constant. Whereas, out of three hundred and two drugs approved during 2009--2017, 5.29% were for cardiovascular disorders, 9.93% for neurological disorders. Antibiotics (5.29%) and antivirals (5.96%) were least in number, whereas anticancer drugs (17.54%) and biologics (15.56%) approval took a steep rise in these years. Also, a wide variation in the number and category of approval was observed over a period of years. The use of fast track, accelerated approval, and priority review programs have also been steadily increasing since 2000.Conclusion:There has been a steady rate of introduction of new drugs by CDER over the last two decades. Expedited approval of anticancer and biologics is seen as recent trend in drug development. Relatively, slow progress in approval of drugs for neurological disorders (depression, psychosis, multiple sclerosis, etc.) and lifestyle diseases like obesity, atherosclerosis, diabetes, etc., were seen. These findings reflect more emphasis being laid down in research for anticancer drugs and biologics.

Characteristics of patients with rheumatoid arthritis undergoing primary total joint replacement: A 14-year trend analysis (2004–2017)

Objectives: To examine time trends in the characteristics of patients with rheumatoid arthritis (RA) undergoing primary total joint replacement (TJR).Methods: Biologics were approved in Japan for use in patients with RA in July 2003. A total of 403 large joints in 282 patients who underwent TJR at our institute between 1 January 2004 and 31 December 2017 were retrospectively examined.Results: A significant decreasing trend was observed in the number of TJRs performed from 2004 to 2017 (p = 0.013). No significant trend was observed in time from RA onset to TJR (p = 0.294). Age at RA onset (p = 0.034) showed a significant increasing trend, and serum C-reactive protein (CRP) levels showed a significant decreasing trend (p < 0.001). Negative CRP (defined as ≤0.3 mg/dl; partial regression coefficient (B) = 2.44, p = 0.016) was independently associated with time from RA onset to TJR as well as age at RA onset and juxta-articular osteophyte formation.Conclusion: The number of TJRs decreased since the approval of biologics in Japan, and changes were observed in the characteristics of patients with RA undergoing TJR. Negative CRP was an independent factor associated with longer time from RA onset to TJR.

Variations in patient-reported outcome (PRO) collection and reporting in novel FDA approved anticancer therapies.

e18202 Background: Patient-reported outcomes (PROs) are increasingly valued as a key tool in patient-focused treatment decisions. However, a lack of standardization leads to significant variability in PRO collection and reporting in ground-breaking clinical trials of novel agents. We sought to characterize the mechanisms of assessment and variability by which PROs are reported for newly approved anti-cancer therapies. Methods: We reviewed the U.S. Food and Drug Administration (FDA) approvals between 2011 and 2017 for anti-cancer new molecular entities (NMEs) and new biologic approvals (BLAs). For each therapy, the pivotal clinical trial leading to FDA approval was identified using the national clinical trial (NCT) number and assessed for inclusion of PROs. A separate PubMed search was conducted to evaluate for PRO publication distinct from the original trial based on national clinical trial registry number. Results: From 2011 to 2017, the FDA approved 66 NMEs/BLAs based on 74 clinical trials for cancer treatment. Of the 74 clinical trial publications, 21 (28%) of the trials published PRO data in their original clinical publication, 18 (24%) published a separate PRO analysis, and 35 (47%) did not publish PRO data in either format. Among the 32 clinical trials (43%) that listed PROs as pre-specified outcomes, 72% published PROs (23/32). The separate PRO analyses (N = 18) were published considerably later following FDA approval (mean 605 days) than the original clinical trials (mean 20 days, N = 74, P &lt; 0.001). Conclusions: As cancer treatment options expand, therapy decisions become increasingly nuanced. PROs assist decision-making by providing detailed information on important aspects of quality of life and tolerability. Our research has identified a significant lag in the publication of companion studies of PRO data associated with pivotal clinical trials, representing a meaningful gap in information critical to patients and oncologists in the process of making informed decisions.

Toll-like receptor-induced cytokines as immunotherapeutic targets in cancers and autoimmune diseases.

Immune cells of the myeloid and lymphoid lineages express Toll-like receptors (TLRs) to recognize pathogenic components or cellular debris and activate the immune system through the secretion of cytokines. Cytokines are signaling molecules that are structurally and functionally distinct from one another, although their secretion profiles and signaling cascades often overlap. This situation gives rise to pleiotropic cell-to-cell communication pathways essential for protection from infections as well as cancers. Nonetheless, deregulated signaling can have detrimental effects on the host, in the form of inflammatory or autoimmune diseases. Because cytokines are associated with numerous autoimmune and cancerous conditions, therapeutic strategies to modulate these molecules or their biological responses have been immensely beneficial over the years. There are still challenges in the regulation of cytokine function in patients, even in those who take approved biological therapeutics. In this review, our purpose is to discuss the differential expression patterns of TLR-regulated cytokines and their cell type specificity that is associated with cancers and immune-system-related diseases. In addition, we highlight key structural features and molecular recognition of cytokines by receptors; these data have facilitated the development and approval of several biologics for the treatment of autoimmune diseases and cancers.

The Case for Disclosure of Biologics Manufacturing Information.

Ten years after the enactment of the Biologics Price Competition and Innovation Act (BPCIA), competition in biologics markets remains scant and far from sufficient for lowering prices of biologics to the level of 80-90% price drops seen in generic drug markets. This reality is not a result of one or two cardinal reasons, but many. If lowering the price of biologics is the goal and competition is the means by which we seek to achieve that goal, then there does not seem to be a quick fix to address all of the many impediments to competition that plague biologics markets. Yet, certain changes to how the Food and Drug Administration (FDA) evaluates and approves biologics may go a long way toward the creation of meaningful competition in biologics markets. One such change would be making original biologics' manufacturing information available to follow-on manufacturers. As recognized by several commentators, access to biologics manufacturing information is key to increasing competition in biologics markets. Without access to such information, making follow-on biologics is difficult and expensive, if not outright impossible. This is expected to be especially true for the highly anticipated class of interchangeable biologics, none of which has been approved by the FDA to date. Yet, it has long been the position of the brand-name pharmaceutical industry (Industry) that biologics manufacturing information is proprietary and, thus, may not be shared. Congress has subscribed to the Industry's position, prohibiting the FDA from disclosing regulatory filings submitted by developers of original biologics, including manufacturing information, to third parties. That prohibition not only undermines competition in biologics markets, but is also wasteful, potentially unethical, and poses unnecessary risks to the health and safety of patients. This article makes the case for FDA sharing of original biologics manufacturing information with follow-on biologics developers. It is informed by the similar legal and commercial circumstances in the area of pesticides and the regulatory regime established by Congress in the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), which is administered by the Environmental Protection Agency (EPA). The article reviews the FIFRA regime, including its upholding as constitutional by the United States Supreme Court, and then examines its applicability to the area of biologics. The article concludes with a proposal for a similar regime to be incorporated into the pathway for approval of follow-on biologics as a means of increasing competition in biologics markets.

Biosimilars in India; Current Status and Future Perspectives.

Many key biologics are scheduled to lose their patent by the year 2020, which will provide the opportunity to other biopharmaceutical companies to develop the similar biologics. Biosimilar or similar biologic used has increased in the recent year following the approval of the first biosimilar in early 2000. India is one of the leading manufacturers of similar biologics. India has developed a new guideline in 2012 for the pre- and post-marketing approval of similar biologics.

Data Exclusivities in the Age of Big Data, Biologics, and Plurilaterals

The past decade has seen many new developments impacting the intellectual property system. The introduction of big data analytics has transformed the fields of biotechnology and bioinformatics while ushering in major advances in drug development, clinical practices, and medical financing. The arrival of biologics and personalized medicines has also revolutionized the healthcare and pharmaceutical industries. In addition, the emergence of bilateral, regional, and plurilateral trade agreements have raised serious, and at times difficult, questions concerning the evolution of domestic and international intellectual property standards. One topic linking all three developments together concerns the establishment of international standards to protect clinical trial data that have been submitted to regulatory authorities for the marketing approval of pharmaceutical products. During the negotiations for the Trans-Pacific Partnership (TPP), for example, the protection of clinical trial data submitted for the marketing approval of biologics was highly contentious. Although the United States’ withdrawal in January 2017 has since placed the TPP Agreement and its data exclusivity provisions for pharmaceuticals and biologics on life support, the debate on the protection of clinical trial data will continue and will emerge in future bilateral, regional, and plurilateral trade negotiations, including the renegotiations on the North American Free Trade Agreement (NAFTA). Part I of this Article reviews the protection of clinical trial data under Article 39.3 of the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS Agreement) of the World Trade Organization (WTO). Even though the provision covers both pharmaceutical and agricultural chemical products, this Article focuses only on the former. Part II examines the additional protection clinical trial data have received through TRIPS-plus bilateral, regional, and plurilateral trade agreements. Part III outlines five specific recommendations to help advance the debate on such protection in the age of big data, biologics, and plurilateral trade agreements.

Novel Therapies and Treatment Strategies for Patients with Inflammatory Bowel Disease.

This article reviews current treatment options and strategies and provides an update on the status of drug development programs of new therapeutic agents for inflammatory bowel diseases (IBD). In the past two decades, tumor necrosis factor antagonist therapy has given clinicians better treatment options. However, not all patients respond to induction therapy with these agents, and of those initially responding, up to 40% ultimately lose response due to suboptimal drug exposure (e.g., caused by immunogenicity), side effects, or other poorly characterized mechanisms. Recently, additional therapies, such as vedolizumab, an integrin blocker that prevents T cell trafficking to the gut, and ustekinumab, an antibody blocking the common p40 subunit of interleukin (IL)-12 and 23, were introduced to the market. In addition, other agents including novel anti-trafficking therapies (e.g., anti-β7 and sphingosine-1-phosphate receptor modulators), antibodies against p19 (unique to IL-23), and small molecules including Janus kinase inhibitors are under investigation in phase II and III trials. Furthermore, the management of IBD has evolved from targeting control of symptoms to suppression of mucosal inflammation. This shift in thinking has been accompanied by the early use of highly effective therapy in poor prognosis patients, accelerated treatment escalation and utilization of a treat to target paradigm approach, and adoption of therapeutic drug monitoring. The treatment landscape for IBD is rapidly evolving with the recent approval of novel biologics as well as several other agents in late phase of clinical development. Moreover, we have started to use agents more intelligently with a focus on risk stratification and early use of highly effective therapy in high-risk patients, treat to target using patient-reported outcomes (PROs), biomarkers, endoscopy, and therapeutic drug monitoring.

Proposal for the development of biologics in pediatric rheumatology.

In order to assess the development, approval and early introduction into clinical practice of biologics in the pediatric field, we herein describe the current status of the development to approval of biologics as anti-rheumatic agents for children in Japan, discuss the present problems and provide a proposal for the future. It has become apparent that the duration of the review period required for the preparation of clinical trials and Pharmaceuticals and Medical Devices Agency approval is clearly reduced compared with the past. Thus, it was speculated that a rate-limiting step in the process from development to approval was the duration of clinical trials from start to end. Hence, we focused on thefollowing key words with regard to promotion of the development of biologics and their early practical use: "registry", "centralization", and "global cooperation", all of which are related to the reduction of duration of a clinical trial. In conclusion, to reduce the duration of a clinical trial, it is essential to complete a world-scale registry system by developing the registry system established by the Pediatric Rheumatology Association of Japan. The next step is then to carefully plan to participate in the international network using the world-scale registry system, and develop global cooperative trials in which we can ensure a sufficient number of entries from Japan.

Drug delivery to melanoma brain metastases: Can current challenges lead to new opportunities?

Melanoma has a high propensity to metastasize to the brain, and patients with melanoma brain metastases (MBM) have an extremely poor prognosis. The recent approval of several molecularly-targeted agents (e.g., BRAF, MEK inhibitors) and biologics (anti-CTLA-4, anti-PD-1 and anti-PD-L1 antibodies) has brought new hope to patients suffering from this formerly untreatable and lethal disease. Importantly, there have been recent reports of success in some clinical studies examining the efficacy of both targeted agents and immunotherapies that show similar response rates in both brain metastases and extracranial disease. While these studies are encouraging, there remains significant room for improvement in the treatment of MBM, given the lack of durable response and the development of resistance to current therapies. Critical questions remain regarding mechanisms that lead to this lack of durable response and development of resistance, and how those mechanisms may differ in systemic sites versus brain metastases. One issue that may not be fully appreciated is that the delivery of several small molecule molecularly-targeted therapies to the brain is often restricted due to active efflux at the blood-brain barrier (BBB) interface. Inadequate local drug concentrations may be partially responsible for the development of unique patterns of resistance at metastatic sites in the brain. It is clear that there can be local, heterogeneous BBB breakdown in MBM, as exemplified by contrast-enhancement on T1-weighted MR imaging. However, it is possible that the successful treatment of MBM with small molecule targeted therapies will depend, in part, on the ability of these therapies to penetrate an intact BBB and reach the protected micro-metastases (so called “sub-clinical” disease) that escape early detection by contrast-enhanced MRI, as well as regions of tumor within MRI-detectable metastases that may have a less compromised BBB. The emergence of resistance in MBM may be related to several diverse, yet interrelated, factors including the distinct microenvironment of the brain and inadequate brain penetration of targeted therapies to specific regions of tumor. The tumor microenvironment has been ascribed to play a key role in steering the course of disease progression, by dictating changes in expression of tumor drivers and resistance-related signaling mechanisms. Therefore, a key issue to consider is how changes in drug delivery, and hence local drug concentrations within a metastatic microenvironment, will influence the development of resistance. Herein we discuss our perspective on several critical questions that focus on many aspects relevant to the treatment of melanoma brain metastases; the answers to which may lead to important advances in the treatment of this devastating disease.

Challenges in the delivery of therapies to melanoma brain metastases.

Brain metastases are a major cause of morbidity and mortality in patients with advanced melanoma. Recent approval of several molecularly-targeted agents and biologics has brought hope to patients with this previously untreatable disease. However, patients with symptomatic melanoma brain metastases have often been excluded from pivotal clinical trials. This may be in part attributed to the fact that several of the approved small molecule molecularly-targeted agents are substrates for active efflux at the blood-brain barrier, limiting their effective delivery to brain metastases. We believe that successful treatment of melanoma brain metastases will depend on the ability of these agents to traverse the blood-brain barrier and reach micrometastases that are often not clinically detectable. Moreover, overcoming the emergence of a unique pattern of resistance, possibly through adequate delivery of combination targeted therapies in brain metastases will be important in achieving a durable response. These concepts, and the current challenges in the delivery of new treatments to melanoma brain metastases, are discussed in this review.

Working with the U.S. Food and Drug Administration to obtain approval of products under the Animal Rule.

While the development of medical products and approval by the U.S. Food and Drug Administration (FDA) is well known, the development of countermeasures against exposure to toxic levels of radiation, chemicals, and infectious agents requires special consideration, and there has been, to date, little experience in working with the FDA to obtain approval of these products. The FDA has published a regulation entitled "Approval of Biological Products when Human Efficacy Studies are not Ethical or Feasible." This regulation, known simply as the "Animal Rule," was designed to permit approval or licensing of drugs and biologics when efficacy studies in humans are not ethical or feasible. To date, 12 products have been approved under the Animal Rule. It is highly recommended that sponsors of products that are to be developed under the Animal Rule meet with the FDA and other government entities early in the development process to ensure that the efficacy and safety studies that are planned will meet the FDA's requirements for approval of the product.

The use of 'Omics technology to rationally improve industrial mammalian cell line performance.

Biologics represent an increasingly important class of therapeutics, with 7 of the 10 top selling drugs from 2013 being in this class. Furthermore, health authority approval of biologics in the immuno-oncology space is expected to transform treatment of patients with debilitating and deadly diseases. The growing importance of biologics in the healthcare field has also resulted in the recent approvals of several biosimilars. These recent developments, combined with pressure to provide treatments at lower costs to payers, are resulting in increasing need for the industry to quickly and efficiently develop high yielding, robust processes for the manufacture of biologics with the ability to control quality attributes within narrow distributions. Achieving this level of manufacturing efficiency and the ability to design processes capable of regulating growth, death and other cellular pathways through manipulation of media, feeding strategies, and other process parameters will undoubtedly be facilitated through systems biology tools generated in academic and public research communities. Here we discuss the intersection of systems biology, 'Omics technologies, and mammalian bioprocess sciences. Specifically, we address how these methods in conjunction with traditional monitoring techniques represent a unique opportunity to better characterize and understand host cell culture state, shift from an empirical to rational approach to process development and optimization of bioreactor cultivation processes. We summarize the following six key areas: (i) research applied to parental, non-recombinant cell lines; (ii) systems level datasets generated with recombinant cell lines; (iii) datasets linking phenotypic traits to relevant biomarkers; (iv) data depositories and bioinformatics tools; (v) in silico model development, and (vi) examples where these approaches have been used to rationally improve cellular processes. We critically assess relevant and state of the art research being conducted in academic, government and industrial laboratories. Furthermore, we apply our expertise in bioprocess to define a potential model for integration of these systems biology approaches into biologics development.

Regulatory Review of Abbreviated Biologics Regulations in ICH Countries

Biobetters are new biological entities, that are related to approved biologics by target or action, but they are intentionally altered to improve disposition, safety, efficacy, or manufacturing attributes. Due to the growing need for lower cost better versions of biological medicines, the markets for biobetters are rising. Regulatory authorities of many countries have precise technical standards and legal pathway for approval of synthetic drugs. The objective of the article is to view the different approaches taken by the ICH countries in regulating biobetters; strictly, there are no specific guidelines for biobetters but biosimilar guidelines are adopted. In March 2010, United States (US) passed the Biologics Price Competition and Innovation Act; but Europe had biologics approval process since 2005, while Japan since 2009. In US, it requires to provide clinical data of the drug for multiple years; same as provided by the innovator drug whereas in Europe it is not required to do so, but safety and efficacy data is required. The critical issue in biological with reference to small molecules (drugs), might be to influence doctors, other healthcare professionals and patients that biobetters have sufficient similarity to risk compared to existing biologics. A full preclinical package may be required unless to prove the differences between the biobetters and the innovator products are petite. Keywords: Follow-on biologics, Biobetters, Pathway, Similarity, Preclinical, Safety and efficacy.

10 No Difference in Ulcerative Colitis Colectomy Rate in Pre and Post Biologic Era

Background: Approximately 35% of patients with ulcerative colitis (UC) will require surgery some time during the course of their disease. However, this past decade has seen major changes in the medical management of UC with FDA-approval of anti tumor necrosis factor alpha (Anti-TNF), for moderate to severe UC. Anti-TNF has demonstrated beneficial impact on the short-term colectomy rates in patients with UC. However, limited data are available regarding the long-term efficacy. The aim of this study was to determine the trends in the rate of colectomy in pre and post biologics era in hospitalized patients with UC. Methods: Nationwide Inpatient Sample (NIS), maintained by the Healthcare Cost and Utilization Project of the Agency for Healthcare Quality and Research, is the largest all-payer inpatient hospitalization database in the US. Hospitalizations from prior to the approval of biologics for ulcerative colitis (the pre-biologic era (1998-2005) and for post-biologic period from 2006-2011 were used. Our study included all patients hospitalized for primary diagnosis of Ulcerative Colitis (ICD-9-CM 556.x) and secondary diagnosis of UC related comorbidities and procedures. Surgeries were classified as elective if the admission was coded as being elective, the source of admission was not the emergency room and surgery occurred on day 0 or 1 of hospitalization. It was defined as emergent if the patient was admitted from the emergency room, the admission was characterized as emergent, and the procedure was performed within 0, 1 day of admission. A previously published risk score was used to adjust for severity of ulcerative colitis hospitalization. Results: A total of 399,579 admissions with primary diagnosis of UC and 38,505 (10%) colectomies were recorded during this period. 212,951 (53%) were females and average age was 46 years. Descriptive data of the group are shown in table 1. There was no difference in colectomy rate in pre and post biologic periods (figures 1). Females, whites and teaching hospital had significantly high rates of colectomies (table 1). Rate of colectomy is significantly increased up to age 70 with lowest rate among the age-group 10-20 yrs (p <.0001). Conclusions: No difference in colectomy rate in UC was noted in post and pre biologic era. Females, whites and admission to teaching hospital are predictors of colectomy. Multivariate logistic regression on colectomy

11 Inhibition of KRAS Activation Ameliorates Pre-Cancerous Metaplastic Conversion in the Mouse Stomach

Background: Approximately 35% of patients with ulcerative colitis (UC) will require surgery some time during the course of their disease. However, this past decade has seen major changes in the medical management of UC with FDA-approval of anti tumor necrosis factor alpha (Anti-TNF), for moderate to severe UC. Anti-TNF has demonstrated beneficial impact on the short-term colectomy rates in patients with UC. However, limited data are available regarding the long-term efficacy. The aim of this study was to determine the trends in the rate of colectomy in pre and post biologics era in hospitalized patients with UC. Methods: Nationwide Inpatient Sample (NIS), maintained by the Healthcare Cost and Utilization Project of the Agency for Healthcare Quality and Research, is the largest all-payer inpatient hospitalization database in the US. Hospitalizations from prior to the approval of biologics for ulcerative colitis (the pre-biologic era (1998-2005) and for post-biologic period from 2006-2011 were used. Our study included all patients hospitalized for primary diagnosis of Ulcerative Colitis (ICD-9-CM 556.x) and secondary diagnosis of UC related comorbidities and procedures. Surgeries were classified as elective if the admission was coded as being elective, the source of admission was not the emergency room and surgery occurred on day 0 or 1 of hospitalization. It was defined as emergent if the patient was admitted from the emergency room, the admission was characterized as emergent, and the procedure was performed within 0, 1 day of admission. A previously published risk score was used to adjust for severity of ulcerative colitis hospitalization. Results: A total of 399,579 admissions with primary diagnosis of UC and 38,505 (10%) colectomies were recorded during this period. 212,951 (53%) were females and average age was 46 years. Descriptive data of the group are shown in table 1. There was no difference in colectomy rate in pre and post biologic periods (figures 1). Females, whites and teaching hospital had significantly high rates of colectomies (table 1). Rate of colectomy is significantly increased up to age 70 with lowest rate among the age-group 10-20 yrs (p <.0001). Conclusions: No difference in colectomy rate in UC was noted in post and pre biologic era. Females, whites and admission to teaching hospital are predictors of colectomy. Multivariate logistic regression on colectomy

Two Decades of Publishing Excellence in Pharmaceutical Biotechnology

Recombinant biological products have revolutionized modern medicine by providing both remarkably effective vaccines to prevent disease and therapeutic drugs to treat a wide variety of unmet medical needs. Since the early 1980s, dozens of new therapeutic protein drugs and macromolecular vaccines have been commercialized, which have benefitted millions of patients worldwide. The pharmaceutical development of these biological products presented many scientific and technical challenges, some of which continue today with newer candidates including recombinant protein-based vaccines with novel adjuvants, peptide and RNA-based drugs, and stem cellular therapies. Compared with small molecule drugs, the characterization, stabilization, formulation, and delivery of biomolecules share common hurdles as well as unique challenges. This area of drug development research has been referred to as “pharmaceutical biotechnology”, in recognition of the critical role that recombinant DNA technology plays in the design and production of most of these biological products. Current research focus areas in this field include (i) determination of structural integrity of the primary sequence, post-translational modifications, and higher-order three dimensional shapes, (ii) assessment of physicochemical degradation pathways and their effects on biological activity and potency, (iii) formulation design and development to optimize stability and delivery, (iv) evaluating and optimizing process development steps including lyophilization and fill-finish, (v) analytical method development and applications of new instruments and data visualization tools, (vi) design and development of drug delivery approaches, and (vii) studies of biological effects including pharmacokinetics, pharmacodynamics, and adverse immunogenicity. During the early days of pharmaceutical biotechnology research, there were numerous scientific challenges because the analytical characterization approaches needed for development of recombinant biological molecules in “real world” pharmaceutical dosage forms were essentially unknown. Furthermore, understanding critical drug product manufacturing issues (e.g., stability of biological compounds during processing, storage, and shipping as well as reproducibility of fill-finish production technologies) and behavior during and after patient administration was often achieved by “on-the-job” training. Fortunately, the pioneers in the field regularly presented research at key conferences and started publishing early in pharmaceutical sciences journals such as Journal of Pharmaceutical Sciences. Recognizing this critically important new field, the then Editor of the journal, Professor Bill Higuchi, instituted a new “pharmaceutical biotechnology” category for research papers. This insightful move was coupled with an equally wise decision to recruit Dr. C. Russell Middaugh as the new Associate Editor for the new research category. As will be detailed below, under Dr. Middaugh’s diligent and expert guidance, pharmaceutical biotechnology papers have grown in number, scope, and impact over the past 20 years, and these days, the Journal of Pharmaceutical Sciences is viewed by scientific leaders in the field as the “go to” place for publication of the most important results and descriptions of innovations in pharmaceutical biotechnology.

Progress of biological agents on psoriatic arthritis.

Psoriatic arthritis (PsA) is an inflammatory arthritis, characterized by mild arthralgia to severe joint deformities. Long term management of these diseases with nonsteroidal anti-inflammatory drugs (NSAIDs) and diseasemodifying antirheumatic drugs (DMARDs) is limited due to lack of efficacy and potential organ toxicity. Recently, the approval of injectable biologics, such as T cell inhibitors and TNF-α antagonist, has changed the treatment of moderateto- severe psoriasis and PsA. Unlike NSAIDs and DMARDs, TNF-α antagonists not only provide unambiguous benefits for the skin and joints, but also prevent the progression of structural damage in peripheral joints. Biological agents in the treatment of PsA have broad prospects. More and more biological agents are being developed for the treatment of PsA. In the current review, we will discuss the progress of biological agents on PsA.

More than skin-deep: the many dimensions of the psoriatic disease.

Psoriasis is among the most common skin diseases, exhibiting a wide spectrum of clinical manifestations. Joint involvement in the form of psoriatic arthritis is readily recognised, but both frequency and severity of this manifestation have long been underestimated. More recently, additional important diseases have been found to be associated with psoriasis, including the metabolic syndrome (or components thereof), cardiovascular diseases, lymphoma, and anxiety/depression. In the past, psoriasis treatment aimed at suppressing acute rashes. Current concepts regard psoriasis as a chronic systemic inflammatory condition and cardiovascular risk factor. In the light of this concept, long-term disease control through systemic maintenance therapy is increasingly recommended by experts. This approach became feasible with the approval of numerous biologics for the treatment of psoriasis. But to really address all medical needs of psoriasis patients, a truly interdisciplinary, comprehensive management approach is needed. Several national societies have already published algorithms to ensure that this need will be implemented in the daily practice of dermatologists and nondermatologists alike.

Patents vs. Statutory Exclusivities in Biological Pharmaceuticals - Do We Really Need Both?

On March 23, 2010, President Obama signed into law the Biologics Price Competition and Innovation Act (BPCIA) as part of the Patient Protection and Affordable Care Act (also known as the Healthcare Bill). BPCIA sets up a framework for the approval of generic biologics and provides for up to 12.5 years of market exclusivity for FDA approved bio-pharmaceutical products. The exclusivity is intended to run in parallel and in addition to any patents that may apply to such approved bio-pharmaceutical products, which would also grant the developers of these products monopolies in the underlying technologies on which such bio-pharmaceutical products are based. This seeming “double dipping” raises questions regarding the need and justification, if any, for such parallel, double protection of this particular class of biological products. This article seeks to address these questions. Analyzing the fundamentals and underlying assumptions of the legal regimes of patents and statutory exclusivities, this article examines their applicability to the context of bio-pharmaceuticals. Based on the conclusions reached, this article then further examines the proposition that statutory exclusivity regimes could become a blueprint for “patentless” areas of technology, replacing the traditional patent regime with a new class of incentives to invent and invest in the development of new technology.