Purple Book Research Articles

Dynamics of biological markets with multiple biosimilar competitors in the United States

ABSTRACT Background The dynamics of biological markets with multiple biosimilar competitors in the United States are poorly understood. Moreover, due to confidentiality issues, the relationship between originator biologic net prices, rebates, and biosimilar entry is largely unexplored. Research design and methods We conducted a review of the Food Drug Administration (FDA) purple book and manufacturer websites to identify all originator biologics with multiple competitors and their characteristics. We leveraged a novel data source to examine originator biologic net prices and rebates over time and used descriptive statistics and interrupted time-series analyses to assess their relationship with biosimilar entry. Results By December 2022, only five originator biologics had three or more available biosimilar competitors. Mean time between biosimilar approval and biosimilar launch was 9 months (SD = 7.04 months). By third biosimilar competitor, entry net prices for originator biologics had decreased by 9.34% to 50.93%, while rebates had increased by 25.35% to 89.71%. Conclusions Very few originator biologics have multiple available biosimilar competitors. Barrier to biosimilar availability seems to be at the approval level as the time between approval and launch is relatively short. However, originator biologics respond quickly to biosimilar competition, mainly through an increase in rebates.

A Comprehensive Analysis of Biopharmaceutical Products Listed in the FDA's Purple Book.

Although biopharmaceuticals constitute around 10% of the drug landscape, eight of the ten top-selling products were biopharmaceuticals in 2023. This study did a comprehensive analysis of the FDA's Purple Book database. Firstly, our research uncovered market trends and provided insights into biologics distributions. According to the investigation, although biotechnology has advanced and legislative shifts have made the approval process faster, there are still challenges to overcome, such as molecular instability and formulation design. Moreover, our research comprehensively analyzed biological formulations, pointing out significant strategies regarding administration routes, dosage forms, product packaging, and excipients. In conjunction with biologics, the widespread integration of innovative delivery strategies will be implemented to confront the evolving challenges in healthcare and meet an expanding array of treatment needs.

Quantifying Challenges to Development of Generics and Biosimilars in Non-Hodgkin's Lymphoma Therapeutics: The Future of Low-Cost Alternatives from Monoclonal Antibodies to CAR-T

Background: There are numerous monotherapies and combination therapies available to treat Non-Hodgkin lymphoma's (NHL), however relatively few of these varied antineoplastics agents have commercially available, lower-cost generic forms in the United States. High cancer drug prices, in particular for socioeconomically vulnerable and underinsured patients, pose challenges to affordable cancer treatment in the United States. In 2017, FDA initiated the Drug Competition Action Plan (DCAP) that aimed to ensure timely market competition by enabling generic drug development, review, and approval, and streamlining regulatory complexities. This regulatory program was designed to limit so-called “gaming” recognized as a cause of delay to generic drug approvals, a phenomenon that has the further deleterious effect of extending brand monopolies beyond what Congress intended with Hatch-Waxman Amendments (1984) establishing modern generic drug regulatory processes. In 2018, FDA announced analogous Biosimilars Action Plan (BAP). However, to date the efficacy of these measures has not been comprehensively assessed in the NHL development landscape. Methods: A model was created by surveying the FDA Orange Book (drug approval database) and Purple Book (biologic product approval database) for initial approval of drugs/biologics with their initial generic/biosimilar approval. Approvals were classified by drug class and availability of generic/biosimilar for the innovator product with approval from 2002 to 2023 (Fig. 1) and t-test were used to determine significance. Results: Of small molecule drug NHL therapeutics approved in the last two decades, only 37% (19/52; Fig. 2) have available, lower-cost generics, with use in more than one indication and time on market both positively and significantly corresponding with availability of generics for the original innovator drug (P < 0.05). Notably, while generic drug approvals dropped during the 2020-2021 period (possibly due to impact of the COVID-19 pandemic), after 2017 implementation of DCAP more generics for common NHL antineoplastics were approved. Conversely, there are relatively few biologic drugs (total of 41 approvals; Fig. 2) with biosimilars, in part due to retained patents and exclusivity, and perhaps indicating a lack of efficacy in BAP among NHL antineoplastics therapies. For off-patent innovator monoclonal antibodies (mAbs), which make up the majority of these therapies, development of biosimilars is effectively blocked by secondary or “process-related” patents which effectively extend the period of non-competition for complex biologic therapies. It is expected that novel bispecific antibody (biAb) therapeutics and novel therapies, such as CD19 CAR-T will also have a delayed time to low-cost biosimilar availability following a similar trend. Conclusions: With drug price and ever-rising insurance and patient payments a critical area of public health, in particular in the United States, availability of lower cost generics and biosimilars is a critical issue for NHL patients. As we move into the maturation of gene therapies and CAR-T therapeutics, it merits consideration of that additional regulatory programs may be needed to incentivize the development of efficacious and lower cost biosimilars. However, it is critical that controlling competition be carefully balanced with investment in both biologic drug entity and process-related innovations among these relatively complex therapeutic entities.

Clinical Similarity of Biosimilars and Reference Drugs: A Comprehensive Review and New Hope for Public Health in a New Frontier.

Patents and exclusive rights on reference biologics contribute to the emergence of biosimilars. Regulatory bodies, such as the Food and Drug Administration (FDA), World Health Organization (WHO), and EMA (European Medicines Agency) for assessing clinical safety, effectiveness, and consequences between biosimilars and reference medications, have established guidelines. Since generic small molecules from reference can be easily swapped, biosimilars cannot be used interchangeably and may not always indicate interchangeability due to highly restrictive properties. It can be replaced with a reference without the healthcare provider's help under the interchangeability context. The purpose of our study is to analyze and compare evidence-based clinical safety, therapeutic potential, and importance (outcomes) of several biosimilars with their references along with clinical uses in chronic diseases. Through a comprehensive systemic literature review of more than 100 articles involving medicinally important drugs whose bio-similarity works optimally, safety-efficacy parameters have been analyzed. Analysis of biosimilar usage, approval, and safety-efficacy aspects are majorly focused upon herein in this review. From this systemic review, it can be stated that the majority of biosimilars are clinically and statistically equivalent to their originators. As biosimilars have good safety-efficacy aspects with lower prices, their utilization can be more encouraged, which was already done by the FDA with the establishment of a public online database entitled "Purple Book," which includes all information regarding biological drugs. To conclude, we suggest widespread use of high-grade biosimilars in clinical practice, maybe via changing, exchanging, or switching, with appropriate clinical monitoring and pharmacovigilance to improve patient accessibility to modern medicines, as it provides similar efficacy and safety parameters across all the accumulated clinical trials and studies.

Pharmacokinetic characterization, benefits and barriers of subcutaneous administration of monoclonal antibodies in oncology.

Therapeutic monoclonal antibodies in oncology are slowly becoming the dominant treatment option for many different cancer types. The main route of administration, infusion, requires extensive product preparations, patient hospitalization and close monitoring. Patient comfort improvement, staff workload reduction and cost savings dictated the development of subcutaneous formulations. The aim of this review is to present pharmacokinetic characteristics of subcutaneous products, discuss the differences between intravenous and subcutaneous routes and to point out the advantages as well as challenges of administration route shift from the formulation development and pharmacometric angle. Food and Drug administration's Purple book database and electronic medicines compendium were used to identify monoclonal antibodies in oncology approved as subcutaneous forms. Using keywords subcutaneous, monoclonal antibodies, pharmacokinetics, model, as well as specific drugs previously identified, both PubMed and ScienceDirect databases were researched. There are currently six approved subcutaneous onco-monoclonal antibodies on the market. For each of them, exposure to the drug was similar in relation to infusion, treatment effectiveness was the same, administration was well tolerated by the patients and costs of the medical service were reduced. Development of subcutaneous forms for existing and emerging new monoclonal antibodies for cancer treatment as well as shifting from administration via infusion should be encouraged due to patient preference, lower costs and overall lack of substantial differences in efficacy and safety between the two routes.

Modelling Waqf Performance and Governance for Public Universities in Malaysia

Islamic philanthropy in Malaysian education system has been well rooted in religion-based traditional educational institutions. Currently, Waqf and Endowment (WAE) grow rapidly at higher education institutions as an income generation and a long-term financial sustainability initiative. The initiative is as a result of budget cut by 20 percent for public universities since 2016 and 2017 but no raise in fee is allowed. This initiative is in line to recommendation in the University Transformation Programme (UniTP), Purple Book shift No 5, the Malaysia Education Blueprint 2015-2025 (Higher Education). Being a non-profit organization, the performance of WAE in Malaysian public universities is expected to be different as compared to commercial entities. The importance of having WAE performance measurement may include the economy, effectiveness and efficiency aspects of its activities towards the intended objectives. The method of the study is based on documents review on performance although the literatures on WAE performance measurement in higher education institution is still lacking. As such, the need to develop a holistic model that covers both aspect of performance measurement and good governance are required consistent with the vision of establishment of WAE to act as one of a perpetual financial source for universities. Hence, this research aimed to propose Waqf Performance Measurement and Governance Model used to evaluate WAE’s reliability and performance in Malaysian public universities. Future research is required to test and verify this model on the initial sample from waqf institutes in public universities. The expected finding of this study is this model can become as a main reference in measuring the performance of WAE in Malaysian public universities embedded with good governance principles, that could result the positive implications in strengthening the WAE’s credibility and stakeholder confidence for universities financial sustainability.

A brief guide to polymerization terminology (IUPAC Technical Report)

Abstract The use of self-consistent terminology to describe polymerizations is important for litigation, patents, research and education. Imprecision in these areas can be both costly and confusing. To address this situation the International Union of Pure and Applied Chemistry (IUPAC) has made recommendations, which are summarized below. In the version shown as the supplementary material, references and hyperlinks lead to source documents; screen tips contain definitions published in IUPAC recommendations. More details can also be found in the IUPAC Purple Book. This guide is one of a series on terminology and nomenclature. Refer to the supplementary material for the complete and interactive version of this brief guide.

ISU DAN CABARAN DANA WAKAF ILMU UITM CAWANGAN PERLIS

The establishment of waqf funds in institutions of higher learning is increasingly being developed by many public and private institutions of higher learning throughout the country. The phenomenon of the establishment of waqf funds has triggered great innovations in the development of waqf in the country. It is in line with the launch of the UniTP Purple Book Guidelines that has been enforced for use in October 2016 by the Ministry of Higher Education to develop their respective endowment management centers to generate income. In this regard, UiTM Perlis Branch took the initiative to establish the UiTM Perlis Knowledge Endowment Fund (DWIPs). Thus, this study examined the issues and challenges faced by DWIPs in helping the income generation of higher learnings institutions. This study used a qualitative method with a case study at UiTM Perlis Branch. The experience of the authors and fellow authors who led DWIPs from the beginning of the establishment to the present were analyzed and described descriptively and comparatively. The findings of the study found that there are four issues and challenges, which are lack of understanding and public awareness of waqf, management bureaucracy problems, lack of energy resources in the management of DWIPs as well as legal and financial barriers. The results of this study are intended to help spread awareness of DWIPs among the staff and gain attention from the university management. In relation to that, it can also increase the amount of knowledge endowment fund collection and benefit all UiTM Perlis Branch staff.

Recent Orange and Purple Book legislation suggests a need to bridge drug and biologic patent regimes.

Recent Orange and Purple Book legislation suggests a need to bridge drug and biologic patent regimes.

Countries Manufacturing Pharmaceuticals for the US Market: A 10-Year Analysis of Public Data

Concerns about strategic supplies and quality have increased the scrutiny of the countries where US pharmaceuticals are made. To examine the locations of manufacturers of brand name, biological, and generic drugs over 10 years. This longitudinal descriptive study used publicly available data from US government Web sites, including the Food and Drug Administration (FDA) Drug Establishments list, FDA National Drug Code Directory, FDA Orange Book, FDA Purple Book, and the National Institutes of Health DailyMed Drug Labels. These data were collected from 2011 to 2020. Brand name drug manufacturing in the United States and Europe decreased from 89% in 2011 to 79% in 2020. Biological manufacturing in the United States decreased, while that in Western European countries increased; 100% of biological manufacturing was done in the United States or Europe in 2011 and decreased to 93% by 2020. Generic manufacturing in India increased from 21% to 51%, while US manufacturing decreased from 52% to 35% from 2011 to 2020. These analyses were limited to publicly available data, and the results could be affected by the accuracy and completeness of the data. Brand name drugs and biologicals are primarily made in the United States and Europe. Generic drugs are increasingly made in India, but the United States remains a major supplier. If the country of origin for pharmaceuticals is important, these findings support supply chain concerns for generic drugs. We recommend that product containers and official labeling prominently include the manufacturer and location for active pharmaceutical ingredients and finished dosage forms.

Ocular adverse effects of therapeutic biologics.

Biological drugs, termed biologics, are medications that contain or are derived from a living organism (human, animal, or microorganism). With new biological agents being approved by the Food and Drug Administration (FDA) every year, clinicians need to know potential ocular adverse effects that are associated with these drugs. This review provides an overview of ocular adverse effects of biological medications used to treat both ophthalmic and non-ophthalmic diseases. We searched PubMed for relevant case reports, case series, reviews, and clinical trials reporting ocular adverse effects caused by biologics. This review was conducted in June 2021 and investigated the drugs listed in the most updated (April 2021) FDA Purple Book Database of Licensed Biological Products. This review focuses on monoclonal antibodies, interleukins, and receptor fusion proteins. We explore ocular side effects of 33 biological drugs, stating whether they are frequent, common, or rare.

FDA approves first interchangeable biosimilar insulin

In July 2021, FDA approved the first interchangeable biosimilar insulin product (Semglee–Viatris/Biocon Biologics, insulin glargine-yfgn), which can be substituted for its reference product (Lantus–Sanofi Aventis, insulin glargine) at the pharmacy level, depending on state pharmacy laws. Although FDA first approved Semglee in June 2020 to improve glycemic control in pediatric patients with type 1 diabetes and adults with type 1 or type 2 diabetes, this approval marks the first interchangeable biosimilar designation for insulin from the agency. “The approval of an interchangeable insulin glargine may offer cost savings to select patients, as biosimilars have, on average, launched with lower initial prices compared with their branded counterparts,” said Daphne Smith Marsh, PharmD, BC-ADM, CDCES, a clinical pharmacist in ambulatory pharmacy services at Mile Square Health Center in Chicago. However, she added there are several other considerations that health care practitioners must keep in mind. “Pharmacists should understand that Semglee can be substituted for Lantus without intervention of the prescriber, but currently cannot be interchanged with Basaglar–Lilly, another insulin glargine product on the market,” she said. “If patients previously receiving Lantus are given Semglee at the pharmacy, patient education is essential to avoid duplication of therapy, as some patients may not understand that they are the same type of medications and may continue to use both products once they get home.” Biologics are large, complex molecules that usually contain a mix of many slight variations of a protein that cannot be copied exactly. FDA does not approve a biosimilar product as interchangeable unless the company specifically seeks an interchangeable designation. The application includes additional data and information about the impact of switching or alternating between the biosimilar product and the reference product. According to FDA, a manufacturer of a proposed interchangeable product must show that the product is biosimilar to a reference product and that it can be expected to produce the same clinical result as the reference product in any given patient. Additionally, the manufacturer must also demonstrate that, for a product administered to a patient more than once, there is no additional risk or reduced efficacy if a patient switches back and forth between an interchangeable product and a reference product, compared to using the reference product without switching. FDA's “Purple Book” contains more information on biologics, biosimilars, and interchangeability, under the “Lists of Licensed Biological Products with Reference Product Exclusivity and Biosimilarity or Interchangeability Evaluations.” Also, APhA has created an FAQ document—available at pharmacist.com/Advocacy/Issues/Biosimilars—to help our members and their patients navigate the rapidly evolving biologic and biosimilar landscape. Pharmacists should consult their state pharmacy association to understand their specific state law for pharmacy-level substitution, since it can vary from one state to the other. For example, in most states, patients will need to be told they are getting an interchangeable biosimilar and pharmacists will not be allowed to make the switch if the prescribing physician has expressly indicated they are prescribing the reference product (e.g., Dispense as Written [DAW], Brand Medically Necessary). Smith Marsh said that patients receiving Semglee should understand that this is not a generic form of Lantus and that it works the same way as that medication. Patients should have a general understanding of what a biosimilar is and how these products are similar to their reference product. Patients should also be educated on all basic insulin counseling pearls, such as appropriate dosing, proper use of the multidose vials or pens, the correct way to discard any unused portions after 28 days, and potential adverse events (e.g., signs/symptoms of hypoglycemia, injection site reactions, edema, weight gain, etc.). Smith Marsh recommended that patients be encouraged to inform their prescribers of the switch.

Real-world trends in biosimilar prescribing among oncology providers, 2019-2021.

e18701 Background: The number of approved biosimilars in the United States has increased exponentially in recent years. Within the oncology market, there are currently 14 approved biosimilars, with 11 launched since the start of 2019. The emergence of new oncology biosimilars provides a tool for success in value-based care, and has the potential to lower costs to patients and providers and expand access to care. Methods: Analysis of biosimilar prescribing behavior was performed using 2020 prescription data (Wolters Kluwer, n = 130,836), sales data (IQVIA), and dosage data for patients taking bevacizumab, trastuzumab, rituximab, or an FDA-approved biosimilar for these products (FDA Purple Book), between 2019-2021 (ION Solutions, n = 69,884). Drugs not directly interchangeable with the bevacizumab, trastuzumab or rituximab reference products according to NCCN guidelines were excluded. Results: Biosimilar products are currently available for bevacizumab (2 biosimilars), rituximab (3 biosimilars), and trastuzumab (5 biosimilars). We found that in 2020, 8.2% of new prescriptions for any of these three reference products were for a biosimilar. An analysis of real-world drug administration data revealed that in the 3 months following the 2019 launch of trastuzumab’s first biosimilar (trastuzumab-anns), 7.3% of initiating line 1 patients were prescribed the biosimilar over the reference product. During the same period in 2020, when a total of 5 trastuzumab biosimilars were available, 80.5% of initiating line 1 trastuzumab patients began treatment on a biosimilar, suggesting rapid uptake by providers. However, this differed by product, with the initial uptake for the first rituximab biosimilar (rituximab-pvvr), at only 2.3%. Uptake also occurred within treatment lines, with 11.1% of all patients (bevacizumab: 11.3%, trastuzumab: 14.1%, rituximab: 7.9%) switching from a reference product to a biosimilar during treatment. Uptake was particularly rapid for trastuzumab biosimilars: among patients on trastuzumab at the time of its first biosimilar launch, 18.2% switched to trastuzumab-anns in the first 90 days post-launch. Biosimilars launched at significantly lower prices than their reference products, with cost per prescription at -42.0%, -29.9% and -89.5% relative to the reference product for trastuzumab, rituximab and bevacizumab, respectively. However, biosimilar launches had little impact on reference product pricing, with 2019-2020 year-over-year (YOY) differences in price per prescription close to the YOY averages in previous years (2015-2019) for all three reference products. Conclusions: We conclude that uptake of biosimilars among oncology providers between 2019-2020 was rapid, although the extent of biosimilar prescribing varied among products. Biosimilars offered greatly reduced costs to providers, although reference product prices remained stable despite increased biosimilar competition.

Regulatory Prototype for Biological Products in the United States

Biological products are used for the treatment of many disease, so the biological application submitted for the approval of products are also increasing. The progress of a biosimilarproduct is more difficult and expensive than a small molecule generic product. Biosimilars are not true generic drugs, but demonstrate a high degree of similarity to the reference biological product. In order to improve access to costly biological treatments, a biosimilar pathway in the US was established under the Biologics Price Competition and Innovation Act of 2009. The study highlighted the “Regulatory prospective for the registration of Biological products in US” and a brief description about the development, Manufacturing and approval process of biosimilar products. This article is also focused on the regulatory framework, Biological License Application, Purple book, and Pharmacovigilance of biological products.

Experience of the Globally Harmonized System’s Implementation at an Anatomy Laboratory

Anatomy laboratories and amphitheaters general practice requires constant chemical substances usage. Previous classification systems used in laboratories around the globe exposed wide margins of confusion, no symbology consensus and were open to interpretation, associated with occupational injuries, workplace related diseases and a lack of students and workers protection. For this reason, it was necessary to establish a universal, homogenized, technical and internationally recognized by scientific community system: the Globally Harmonized System of classification and labeling of chemical products (GHS).The GHS was proposed with the purpose of harmonizing the characteristics and data sheets of different substances, reagents and components. When projected by the UN, this system was standardized according to international protocols. Even the Intergovernmental Forum for Chemical Safety recommends that all countries implement the GHS as soon as possible, being one of the main reasons the fact that student’s misunderstanding of labeling of chemical substances can result in unsafe behavior that may cause accidents or disasters.Our aim is to describe and evaluate the main differences between the implementation of the GHS compared to previouslly used classification systems. A documentary analysis of United Nations purple book on the updated official report of the globally harmonized system was carried out, together with documents from previous organization systems.As a main finding, nine danger pictograms are set (previously eight), that harmonize criteria to avoid physical, health and/or environmental danger situations. For each sheet the use of specific danger pictograms, warning words, hazard instructions and precautionary statements is stablished. These sheets must be accompanied by a hazard communication paper that includes detailed information about identification, manufacturer, importer and/or supplier, classification, hazards, precautionary measures and emergency procedures, among others.The implementation of the GHS in an anatomy laboratory consists in four principles: checklist of hazardous materials in stock, labeling of hazardous materials, preparation of material safety datasheets with the format and the requirement of at least a 3‐h training course for eligible students and workers.The GHS implementation together with an easy divulgation of hazards and the Occupational Health and Safety requirement (BS OHSAS 18001) which is a framework that contains necessary policies, procedures and controls that helps workspaces achieve the best possible working conditions, aligned with internationally recognized best practices, leads to optimized human and environmental protection, besides constituting a guide system for those countries that lacked one, reducing the need to test chemical products and facilitating the trade of dangerous substances.Support or Funding InformationAnatomy Laboratory, Universidad de los Andes, School of Medicine.

Performance on the Initiatives Taken T oward Financial Sustainability of Public Universities in Malaysia

The initiative to reduce Public Universities (PUs) dependency on the Malaysian federal government grants for operation and development expenditure was highlighted in the Malaysian Education Blueprint (MEB) 2015-2025. In the MEB, PUs are expected to strengthen their income generation to achieve financial sustainability while staying focus on their core educational missions. The purpose of this study is to assess income enhancement initiatives carried out by PUs to achieve financial sustainability. The initiatives suggested in UniTP Purple Book to help PUs in their quest to be financially sustainable is used as the variables. This study found that the PUs in Malaysia have a clear objective towards achieving financial sustainability. However, their initiatives in enhancing income are limited, mostly on the routine tasks and activities with low financial risks.

Understanding the globally harmonized system of classification and Labeling of Chemicals-The Purple Book

Global Harmonized System (GHS), relating to hazard chemicals, is a process of making a regulation among countries uniform to the extent possible so as to benefit an industry to export its products to several countries with one communication system. On one side, the system is helpful to develop communication as labeling and material safety data sheets, and on the other side is helpful for the personnel in the chemical and pharmaceutical industry in using chemicals carefully, especially hazardous. Such international guidelines are believed to be the most reliable information so that the end user of hazard chemicals is confident enough in handling and using. The current article is a brief understanding of the guideline, an attempt, how the hazard chemicals are being classified, communicated as labels, symbols and material safety data sheets.

Monoclonal Antibodies and Fc-Fusion Proteins for Pediatric Use: Dosing, Immunogenicity, and Modeling and Simulation in Data Submitted to the US Food and Drug Administration.

The experience with the use of monoclonal antibodies and Fc‐fusion proteins (mAb/Fc) in the pediatric population is limited. The objective of this study is to review those factors impacting the clinical efficacy and product safety of mAb/Fc products in pediatric patients during drug development. We reviewed the list of biologic products in the US Food and Drug Administration's Purple Book as of March 2018 with a focus on mAb/Fc products that are indicated for use in both adults and pediatric patients. Of 68 mAb/Fc products in the Purple Book (excluding biosimilars), 20 products have approved indications in both adults and children. Thirteen products had concurrent approval for both adult and pediatric populations. The sample size of pediatric studies generally ranged from approximately 2% to 70% of the sample size of adult studies with the same indication. In general, pediatric dosing regimens were found to be more based on body weight and weight tiered than the regimens for adults. Modeling and simulation techniques comprised mainly population pharmacokinetic and pharmacodynamic models. A review of the immunogenicity incidence did not reveal any notable difference in the 5 products having data on both pediatric and adult patients. In conclusion, most of the mAb/Fc products have a different weight‐based dosing regimen for pediatric patients versus adults. An understanding of the comparative experience in drug development for mAb/Fc products between adult and pediatric patients coupled with the application of advanced modeling and simulation methods should assist future development of new mAb/Fc products for pediatric patients.

An Invasive Launch of Two Compendiums: Orange Book and Purple Book by FDA

This article particularly focuses on the Orange Book which is more formally known as the Approved Drug Products with Therapeutic Equivalence Evaluations and also on the Purple Book-more formally known as List of Licensed Biological Products with Exclusivity of Reference product and Biosimilarity or Interchangeability Evaluations. Major topics covered in this article include: the legislative background of the ‘Orange Book’, safety and effectiveness, Hatch-Waxman Act, Patents and exclusivity comparisons, (ANDA) Abbreviated New Drug Application Patent Certification process, Contents of the Orange Book, Therapeutic Equivalence Code, Electronic Orange Book and about the Upgrade of Orange Book. In addition to this it also reviews the FDA’s Purple Book in detail. Since the use of biological products ha exponentially increased over the last few decades new regulations for reducing the cost of the original Biological Products have been framed among which the Purple Book was also one such stride. These types of reference guide will assist the pharmacists to provide leadership to the public about the substitution of appropriate generic and Biologic equivalents to the reference product. Hence let’s plunge into the article for more interesting information.

A retrospective examination of the US Food and Drug Administration's clinical pharmacology reviews of oncology biologics for potential use of therapeutic drug monitoring.

BackgroundBiologics have gained traction for use in oncology, but have demonstrate clinical variability for efficacy and safety. Therapeutic drug monitoring (TDM) can benefit patients’ outcomes from a biologic therapy when the latter has a defined therapeutic window. A clinically relevant therapeutic window may exist for biologics with established exposure-response (E–R) relationships for efficacy and/or safety and a documented maximum tolerated dose (MTD). Additionally, the inter-individual variability (IIV) on the clearance (CL) parameter could determine risks for patients falling outside the proposed therapeutic window.Materials and methodsThe US Food and Drug Administration (FDA)-approved oncology biologics between 2005–2016 were reviewed via FDA “Purple Book” (FDA-repository for licensed biologics). Data were extracted from biologics’ pharmacokinetic models available on the clinical pharmacology reviews published on the FDA-Approved Drug Products website. Evaluated features for biologics with established E–R relationships for efficacy and/or safety and MTD include an IIV for the CL and various other covariates including demographic factors, disease factors, blood chemistry, or immunogenicity.ResultsFive therapies were identified with documented E–R relationships for both efficacy and safety including, Yervoy®(ipilimumab), Zaltrap® (ziv-aflibercept), Portrazza® (necitumumab), Adcetris® (brentuximab-vedotin), and Blincyto® (blinatumomab). The corresponding IIV on CL were: 34%, 33%, 29%, 47%, and 97%, respectively. Among the five therapies, only three had defined MTD including, brentuximab-vedotin, necitumumab, and blinatumomab.ConclusionOf the medications examined, blinatumomab was identified as the anticancer drug with the most available information for the establishment of TDM, and hence, may benefit through the use of TDM to optimize effectiveness and minimize patients’ toxicity. The approach used here may provide a generalizable framework to retrospectively identify anticancer biologics with high IIV that may benefit from TDM to improve patients’ clinical outcome.