DRAFT MEETING PACKAGE

docx

School

Northeastern University *

*We aren’t endorsed by this school

Course

6207

Subject

Medicine

Date

Dec 6, 2023

Type

docx

Pages

15

Uploaded by MinisterMagpie2727

Report
LYMPHOCURE Dear [FDA Reviewer], I'm writing to request approval of our New medication Application (NDA) for Lymphocure, an experimental medication for the treatment of relapsed or refractory Acute Lymphocytic Leukemia (ALL). Lymphocure is a new immunotherapy drug that uses the immune system's capacity to target cancer cells and trigger immune-mediated death. We think Lymphocure has the potential to be of great help to individuals with relapsed or refractory ALL, for whom therapy choices are restricted. Our preclinical studies show that Lymphocure can bind to CD19 and CD20 receptors on cancer cells and promote immune- mediated death. Lymphocure was demonstrated to be effective in lowering tumor burden in both xenograft and syngeneic ALL models in both in vitro and in vivo settings. A single-arm, multicenter phase II investigation in patients with relapsed or refractory ALL is included in our planned clinical trial design. The study's primary aim is objective response rate (ORR), with secondary objectives including duration of response, progression-free survival (PFS), overall survival (OS), and safety. This trial design, we feel, is appropriate for assessing the effectiveness and safety of Lymphocure in this patient group. We conducted thorough preclinical toxicity investigations in rats and nonhuman primates, demonstrating Lymphocure's safety and tolerability at dosages up to ten times the intended therapeutic dose. Mild to moderate alterations in hematology and clinical chemistry parameters, including temporary declines in white blood cell counts and elevations in liver enzymes, were the predominant toxicological results. We appreciate the opportunity to submit our research and discuss the development of Lymphocure with the FDA. We think Lymphocure represents a substantial development in the treatment of relapsed or refractory ALL, and we look forward to collaborating with the FDA to provide this critical medicine to patients in need. Sincerely, Hema Anantha Harshitha Nalam Rushikesh Reddy Nandireddy Sahithi Swarna Sahithi Puja Uppaluru Sai Ram Yadlapalli Boston, MA Agenda: DRAFT MEETING PACKAGE 1
LYMPHOCURE Lymphocure introduction and summary: Provide a brief review of the medicine and its intended application for the treatment of relapsed or refractory ALL. Discuss the patient population's unmet medical needs and the possible advantages of Lymphocure. Toxicology research and preclinical data: Examine the preclinical data and toxicity studies done in rats and nonhuman primates, including Lymphocure's mode of action and the drug's safety and tolerability profile. Provide a summary of the planned Lymphocure clinical trial design, including the patient population, study objectives, and statistical analysis strategy. Discussion of any available comparison data with licensed medications for the treatment of relapsed or refractory ALL. Questions for the FDA: Request comments and direction from the FDA on critical development concerns such as study design, patient selection criteria, and clinical outcomes. Specific inquiries may include: Are the proposed criteria for inclusion and exclusion suitable for the patient population? Is ORR alone sufficient to demonstrate efficacy, or should other endpoints be considered? Should the clinical study contain a comparison arm, and if yes, which comparator is best? Following steps: Discuss the future stages in the development of Lymphocure, such as the timing for submitting new data and the FDA approval procedure. Conclusion: Thank you for your time and insight, and please repeat the company's commitment to discovering safe and effective therapies for patients with relapsed ALL. Company: DRAFT MEETING PACKAGE 2
LYMPHOCURE XYZ Pharmaceuticals, a biopharmaceutical firm focused on creating novel medicines for cancer and other critical diseases, is developing Lymphocure. The firm was established in 2005 and is based in San Francisco, California. Background: Lymphocure is a new small molecule inhibitor of BTK, a crucial enzyme in the B-cell receptor signaling pathway involved in B-cell survival and proliferation. Lymphocure is intended to decrease the proliferation and survival of malignant B-cells in patients with relapsed or refractory ALL by inhibiting BTK. Preclinical investigations have shown that Lymphocure is highly selective for BTK and has substantial anticancer action in vitro and in vivo against ALL cell lines. Furthermore, Lymphocure demonstrated a positive safety profile in preclinical toxicological investigations in rats and nonhuman primates. Lymphocure is now being tested in a phase 1 clinical trial in patients with relapsed or refractory ALL, with early findings expected in the next 6-12 months. The trial's goal is to assess Lymphocure's safety, tolerability, and preliminary effectiveness as a single drug in this patient group. If the phase 1 study findings are positive, the business intends to launch a pivotal phase 2/3 trial to support regulatory approval of Lymphocure. Product Information DRAFT MEETING PACKAGE 3
Your preview ends here
Eager to read complete document? Join bartleby learn and gain access to the full version
  • Access to all documents
  • Unlimited textbook solutions
  • 24/7 expert homework help
LYMPHOCURE Lymphocure, as a fictitious medicine, has no comparison research with licensed drugs. Potential comparison studies, depending on the mechanism of action and current data on other CD19-targeted treatments, might include: Blinatumomab vs. Lymphocure: Blinatumomab is a CD19-targeted therapeutic licensed for the treatment of relapsed or refractory ALL. In patients with relapsed or refractory ALL, a comparison trial might compare the safety and effectiveness of Lymphocure vs Blinatumomab. Lymphocure combined with chemotherapy vs. chemotherapy alone: The current standard of treatment for ALL is chemotherapy, and some chemotherapy regimens include CD19-targeted medicines. In newly diagnosed patients with ALL, a comparison research might compare the safety and effectiveness of adding Lymphocure to conventional treatment vs chemotherapy alone. Lymphocure vs Hematopoietic stem cell transplantation (HSCT): HSCT is a potentially curative therapeutic option for certain ALL patients, but it is fraught with dangers and problems. A research comparing the safety and effectiveness of Lymphocure against HSCT in patients with relapsed or refractory ALL who are suitable for both therapies might be conducted. These are only a few examples of prospective Lymphocure comparative studies in the treatment of ALL. The particular design of comparison studies would be determined by the study aims, patient population, and resources available. Lymphocure's distinct traits as a fictitious medicine may be identified by its supposed attributes and mode of action. Lymphocure is distinguished by its new method of action, which employs a bispecific antibody to target CD19-positive cancer cells. This method of action differs from existing treatments for Acute Lymphocytic Leukemia (ALL), which mostly include chemotherapy and hematopoietic stem cell transplantation. Another distinguishing feature of Lymphocure is its ability to elicit long-lasting reactions with low harm. Although CD19-targeted treatments have shown encouraging outcomes in the treatment of ALL, they can cause serious adverse effects such as cytokine release syndrome and neurotoxicity. Lymphocure's dual specificity for CD19 and T-cell receptors has the potential to improve the efficacy and reduce the toxicity of CD19-targeted treatment. Lymphocure might be a beneficial therapy option for individuals with relapsed or refractory ALL if it can demonstrate safety and effectiveness in clinical studies. Lymphocure is a good contender for FDA clearance due to its novel mode of action and potential for low toxicity, assuming it passes all regulatory standards for safety and efficacy. Finally, the FDA will base its judgment on the totality of clinical trial data, including the drug's safety, effectiveness, and potential advantages above existing treatment choices. DRAFT MEETING PACKAGE 4
LYMPHOCURE Description: Lymphocure is a novel treatment for Acute Lymphocytic Leukemia (ALL), a kind of blood cancer that affects lymphocytes, which are white blood cells. The medication targets and destroys malignant lymphocytes while leaving healthy cells alone. Phase I Clinical Trial Study Design: The goal of this study was to assess the safety and maximum tolerated dosage of Lymphocure in individuals with ALL. Participants: ALL patients (n = 20) Intervention: To examine safety and acceptability, administer Lymphocure at three different dosages (10mg, 25mg, and 50mg). Outcome measurements include adverse events, vital signs, laboratory tests, and electrocardiograms. Clinical Trial in Phase II: The goal of this study is to determine the effectiveness and safety of Lymphocure in individuals with ALL. Patients with ALL (n=100) participated. Intervention: To test effectiveness and safety, administer Lymphocure at the optimum dosage determined in Phase I. Outcome measurements include efficacy evaluations such as overall response rate, progression-free survival, and overall survival, as well as safety assessments such as adverse events, vital signs, laboratory tests, and electrocardiograms. The goal of the Phase III clinical trial is to validate the effectiveness and safety of Lymphocure in a broader group of patients with ALL. Patients with ALL (n=500) took part in the study. Intervention: To establish effectiveness and safety, administer Lymphocure at the optimum dosage determined in Phase II. Outcome measurements include efficacy evaluations such as overall response rate, progression-free survival, and overall survival, as well as safety assessments such as adverse events, vital signs, laboratory tests, and electrocardiograms. DRAFT MEETING PACKAGE 5
LYMPHOCURE Regulatory Affairs Landscape: Preclinical studies: Animal models are used to assess the safety and efficacy of Lymphocure before human trials. Before Phase I trials may begin, data from these research is submitted to regulatory authorities for assessment and permission. Application for an Investigational New Drug (IND): Requested approval from regulatory authorities to undertake Phase I clinical studies in people. This application contains information on the research design and safety procedures, as well as data from preclinical trials. A phase I clinical trial was conducted to evaluate the safety and maximum tolerated dosage of Lymphocure in ALL patients. Before Phase II trials may begin, data from this trial is submitted to regulatory authorities for assessment and approval. Lymphocure effectiveness and safety were evaluated in a phase II clinical trial in individuals with ALL. Before Phase III trials may begin, data from this trial is submitted to regulatory authorities for assessment and approval. Phase III Clinical Trial: Conducted to establish Lymphocure's effectiveness and safety in a broader group of ALL patients. Before the medicine may be licensed for commercialization, the data from this study is submitted to regulatory authorities for assessment and approval. NDA stands for New Drug Application. Lymphocure has been submitted to regulatory authorities for commercial authorisation. This application contains information from preclinical and clinical studies, as well as manufacturing, labeling, and post-marketing surveillance plans. Post-marketing surveillance: Ongoing monitoring of Lymphocure's safety and efficacy after it has been approved for marketing. This involves tracking adverse occurrences and performing more research. DRAFT MEETING PACKAGE 6
Your preview ends here
Eager to read complete document? Join bartleby learn and gain access to the full version
  • Access to all documents
  • Unlimited textbook solutions
  • 24/7 expert homework help
LYMPHOCURE Mechanism of Action: Lymphocure is a targeted treatment that works by specifically attaching to and suppressing the expression of a particular protein called CD19 on the surface of malignant cells in patients with Acute Lymphocytic Leukemia (ALL). By inhibiting the function of CD19, Lymphocure causes the immune system to destroy malignant cells while protecting healthy ones. Adverse Reactions: Lymphocure, like other medicines, has the potential to induce negative effects. The following are the most common adverse effects documented in clinical trials: Reactions to infusion: Lymphocure is given intravenously and can induce fever, chills, headache, nausea, vomiting, and allergic reactions. These responses can be controlled by slowing down or stopping the infusion and delivering appropriate therapy. Neutropenia: Lymphocure may result in a reduction in the quantity of neutrophils, a kind of white blood cell that aids in the fight against infections. This increases the likelihood of bacterial infections, and patients may require antibiotics or antifungal medications to prevent or cure infections. Thrombocytopenia: Lymphocure may induce a drop in platelet count, which is required for blood coagulation. This increases the risk of bleeding, and patients may require platelet transfusions or other therapies to control their bleeding. Anemia: Lymphocure may result in a reduction in the quantity of red blood cells, resulting in anemia and weariness. To treat anemia, patients may require red blood cell transfusions. Lymphocure may cause the release of cytokines, which are immune system signaling molecules, resulting in cytokine release syndrome. Flu-like symptoms such as fever, exhaustion, muscular pains, and low blood pressure might result from this. Severe instances of cytokine release syndrome can be fatal and need immediate medical attention. Tumor lysis syndrome: Lymphocure may cause cancer cells to be rapidly destroyed, releasing huge quantities of potassium, phosphate, and other biological components into the circulation. This can lead to electrolyte imbalances, renal damage, and other problems. To avoid or manage tumor lysis syndrome, patients may require hydration, electrolyte replacement, and other therapy. It should be noted that not all patients may have these adverse effects, and the severity of side effects might vary from patient to patient. Patients using Lymphocure should be thoroughly watched for any evidence of adverse effects and should get any necessary supportive treatment. DRAFT MEETING PACKAGE 7
LYMPHOCURE Preclinical Data Lymphocure has been shown in preclinical experiments to attach to CD19 and CD20 receptors on cancer cells and promote immune-mediated death of these cells. Lymphocure was demonstrated to be effective in lowering tumor burden in both xenograft and syngeneic ALL models in both in vitro and in vivo settings. Data on safety and toxicity that is relevant Lymphocure was usually well-tolerated in toxicity investigations in rats and nonhuman primates at dosages up to ten times the suggested therapeutic dose. There were no reported treatment-related fatalities or serious side effects. Mild to moderate alterations in hematology and clinical chemistry parameters, including temporary declines in white blood cell counts and elevations in liver enzymes, were the predominant toxicological results. Furthermore, a repeat-dose toxicity investigation in cynomolgus monkeys revealed no indication of Lymphocure buildup following repeated dosage, as well as no detrimental effects on organ weights or histology. The maximum dose examined was judged to be the No Observed Adverse Effect Level (NOAEL). Preclinical study summary Overall, the preclinical studies suggest that Lymphocure might be developed as a feasible treatment option for patients with relapsed or refractory ALL. The safety and toxicology findings imply that the planned clinical dosage is well tolerated and that the medicine has a positive risk-benefit profile. DRAFT MEETING PACKAGE 8
LYMPHOCURE Proposed clinical trial design, endpoints, and safety monitoring plan A multicenter, open-label, single-arm, phase 2 research is proposed for Lymphocure in relapsed or refractory ALL. Up to 100 adult patients with relapsed or refractory ALL who have had at least two previous lines of treatment, including a CD19-targeted therapy and an anthracycline-based regimen, will be enrolled in the research. Lymphocure will be administered to patients as a single treatment at a dose of 200 mg twice day until disease progression, unacceptable toxicity, or withdrawal of consent occurs. Endpoints: The overall response rate (ORR) will be the primary outcome of the research, defined as the proportion of patients who achieve a complete response (CR), full response with incomplete blood count recovery (CRi), or partial response (PR) according to the 2017 updated IWG criteria for ALL. Duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety will be secondary goals. Safety Monitoring Plan: Clinical laboratory testing, physical examinations, and adverse event (AE) reporting will be used to monitor safety throughout the trial. Patients will be evaluated for adverse events (AEs) at each study visit and will be monitored for safety for 30 days after stopping Lymphocure. For the management of AEs, dosage reductions and interruptions will be permitted, and dose changes will be performed based on the severity and duration of the AEs. Phase II/III Studies: If the phase 2 study findings are encouraging, a critical phase 3 trial will be undertaken to support regulatory approval of Lymphocure for the treatment of relapsed or refractory ALL. The phase 3 trial will be a randomized, controlled trial comparing Lymphocure plus standard of care (SOC) versus SOC alone in patients with relapsed or refractory ALL who have previously undergone at least two lines of treatment, including a CD19-targeted therapy and an anthracycline-based regimen. The phase 3 study's primary goal will be progression-free survival (PFS), with secondary endpoints including overall survival (OS), overall response rate (ORR), and safety. The trial, which is planned to last 2-3 years, will enroll up to 300 individuals. DRAFT MEETING PACKAGE 9
Your preview ends here
Eager to read complete document? Join bartleby learn and gain access to the full version
  • Access to all documents
  • Unlimited textbook solutions
  • 24/7 expert homework help
LYMPHOCURE Proposed regulatory pathway and timeline for submission The FDA's fast approval program for the treatment of relapsed or refractory ALL is the planned regulatory approach for Lymphocure. Based on the results of the phase 2 trial, a New Drug Application (NDA) for Lymphocure will be submitted, followed by a confirmatory phase 3 study to support complete approval. The NDA is planned to be submitted about two years following the end of the phase two research. The NDA review process is estimated to take up to 12 months, followed by eventual FDA approval. The confirmatory phase 3 study is scheduled to begin soon after the NDA is submitted and continue throughout the review process. The conclusion of the phase 3 trial and eventual final approval is expected to take another 2-3 years. Potential for Accelerated Approval: Because of the unmet medical need for patients with relapsed or refractory ALL and the impressive preclinical and clinical results to date, the possibility for speedy approval of Lymphocure is strong. Lymphocure would be authorized faster if it was based on a surrogate objective, such as overall response rate (ORR), rather than a clinical endpoint, such as progression-free survival (PFS) or overall survival (OS). The ORR objective is predicted to be reached in the phase 2 research, and a confirmatory phase 3 study would be necessary to validate Lymphocure's therapeutic benefit. Furthermore, Lymphocure may be eligible for FDA breakthrough treatment designation and/or priority review, which would speed up the review process and perhaps lead to quicker approval. Overall, the regulatory approach and possibility for rapid approval for Lymphocure are encouraging, and we look forward to collaborating closely with the FDA throughout the submission and review process. DRAFT MEETING PACKAGE 10
LYMPHOCURE Proposed Risk Minimization Measures: Lymphocure is a powerful and targeted therapy for relapsed or refractory ALL, and it is critical that patients receive the necessary treatment and monitoring to reduce the potential hazards associated with its use. The risk-mitigation measures proposed include: Lymphocure will only be available through accredited speciality pharmacies that have been trained to handle and dispense the medicine correctly. Patient selection criteria: Patients must meet the study's inclusion and exclusion criteria to be considered suitable candidates for Lymphocure treatment. Patient monitoring: During and after treatment with Lymphocure, patients will be thoroughly followed for any adverse events, including laboratory testing and physical exams. Healthcare practitioners will be required to receive training on the proper use and administration of Lymphocure, as well as the management of potential adverse events. Risk communication: Patients and healthcare providers will be informed about the potential hazards of Lymphocure, such as cytokine release syndrome and neurological toxicities. Plans for Post-Marketing Pharmacovigilance: Post-marketing pharmacovigilance is crucial for identifying and managing any potential safety problems with Lymphocure. Post-marketing pharmacovigilance plans include: Adverse event reporting: Healthcare practitioners and patients will be encouraged to notify the FDA and the manufacturer of any adverse events connected with Lymphocure. Long-term outcomes will be tracked for patients treated with Lymphocure, including disease response, progression-free survival, and overall survival. Risk management plan: A risk management plan will be established and implemented to detect and address any potential safety risks linked with Lymphocure. Regular safety reviews will be done to monitor the safety of Lymphocure and identify any developing safety issues. Overall, the suggested risk-mitigation procedures and post-marketing pharmacovigilance plans for Lymphocure are intended to assure the drug's safe and effective usage in patients with relapsed or refractory ALL. DRAFT MEETING PACKAGE 11
LYMPHOCURE Questions for FDA Question: Based on the preliminary evidence, we believe Lymphocure has the potential to significantly assist patients with relapsed or refractory ALL. What extra data would the FDA advise us to collect in our phase II trial to support the possibility of speedy approval? Company position: We believe that the available preclinical data supports the potential for accelerated approval of Lymphocure. We are committed to working closely with the FDA to identify the most appropriate clinical trial endpoints and design to support this pathway. Question: A single-arm, multicenter phase II research is included in our suggested clinical trial design. Can you give me your thoughts on the trial design and sample size required to demonstrate efficacy and safety in this patient population? Company position: A single-arm, multicenter phase II research, we feel, is a reasonable design for assessing the effectiveness and safety of Lymphocure in patients with relapsed or refractory ALL. The trial was planned with key opinion leaders' input, and we believe it will give significant evidence to support the development of this essential therapeutic option. Question: We are thinking about making overall survival the primary objective of our phase III trial. Can you offer advice on using overall survival as a primary outcome in trials with relapsed or refractory ALL? Company position: We believe that overall survival is an adequate primary objective for our phase III research. We recognize the difficulties in showing a survival benefit in this patient population and are dedicated to conducting a comprehensive trial to assess the potential benefit of Lymphocure in these individuals. We look forward to addressing the use of overall survival as a main endpoint with the FDA, as well as investigating other alternative endpoints that may be appropriate. DRAFT MEETING PACKAGE 12
Your preview ends here
Eager to read complete document? Join bartleby learn and gain access to the full version
  • Access to all documents
  • Unlimited textbook solutions
  • 24/7 expert homework help
LYMPHOCURE List of specific questions and topics for discussion Can you provide guidance on the proposed clinical trial design and endpoints for Lymphocure? Are there any additional endpoints that should be considered for the trial? How do you recommend balancing the potential risks and benefits of Lymphocure in patients with relapsed or refractory ALL? What is the likelihood of accelerated approval for Lymphocure based on the available preclinical and clinical data? What is the FDA’s position on the proposed risk minimization measures for Lymphocure, including the restricted distribution, patient monitoring, and healthcare provider training requirements? Can you provide guidance on the plans for post-marketing pharmacovigilance for Lymphocure? Are there any additional safety monitoring measures that should be considered? Are there any potential drug interactions or contraindications that should be considered with Lymphocure? How do you recommend addressing the potential for cytokine release syndrome and neurological toxicities associated with Lymphocure? What is the FDA’s position on the proposed target product profile for Lymphocure, including the proposed patient population and treatment goals? Are there any additional studies or data that should be considered for Lymphocure prior to submission for FDA approval? What is the FDA’s timeline for review and approval of Lymphocure, and are there any potential challenges or obstacles that should be anticipated? Supporting documentation, including relevant scientific literature, regulatory guidance documents, and clinical trial protocols. DRAFT MEETING PACKAGE 13
LYMPHOCURE Here are some regulatory guidance documents and clinical trial procedures that may be useful in the development of the aforementioned drug: FDA Industry Guidance: Drugs and biologics: Expedited Programs for Serious Conditions: This guidance document discusses the expedited programs available for the development and licensing of medicines and biologics for critical or life-threatening illnesses such as acute lymphocytic leukemia. FDA Guidance for Industry: Developing Products for Treatment of Hematological Disorders Using Animal Models: This paper contains suggestions on the use of animal models in the development of medications for hematological disorders like leukemia. FDA Guidance for Industry: Clinical Trial Endpoints for Cancer Drug and Biologic Approval: This document contains information on the clinical trial endpoints that are acceptable for cancer drug and biologic approval, including those for acute lymphocytic leukemia. ClinicalTrials.gov This website includes thorough information on the required data items for clinical trial protocols, particularly those for interventional trials utilizing experimental medications. Common Terminology Criteria for Adverse Events (CTCAE) v5.0 from the National Cancer Institute: This website offers a standardized system for classifying the severity of adverse events in clinical trials, which can aid in the consistency of reporting and monitoring of safety data. International Clinical Trials Registry Platform (ICTRP) of the World Health Organization: This resource offers a searchable database of clinical trial protocols and outcomes from across the world, which can aid in the design and execution of clinical studies for the aforementioned medicine. These resources should be used in conjunction with the specific regulatory requirements and guidelines for the development of medications for acute lymphocytic leukemia. It is advised that regulatory specialists and/or FDA representatives be consulted for particular guidance on the development and approval of the aforementioned medicine. DRAFT MEETING PACKAGE 14
LYMPHOCURE References: 1. Pediatric drug development https://www.fda.gov/regulatory-information/search-fda-guidance-documents/pediatric-drug- development-under-pediatric-research-equity-act-and-best-pharmaceuticals-children-act 2. Patient-Focused Drug Development https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient- focused-drug-development-incorporating-clinical-outcome-assessments-endpoints-regulatory 3. Clinical Trial Considerations to Support Accelerated Approval of Oncology Therapeutics https://www.fda.gov/regulatory-information/search-fda-guidance-documents/clinical-trial- considerations-support-accelerated-approval-oncology-therapeutics 2. BESPONSA (inotuzumab ozogamicin) FDA Approval package https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761040Orig1s000TOC.cfm 6. BESPONSA (inotuzumab ozogamicin) Administrative documents https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761040Orig1s000AdminCorres.p df 7. BESPONSA (inotuzumab ozogamicin) Multidisciplinary document https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761040Orig1s000Multidiscipline R.pdf 8. BESPONSA (inotuzumab ozogamicin) Risk evaluation document https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761040Orig1s000RiskR.pdf 9. BESPONSA (inotuzumab ozogamicin) Chemistry review document https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761040Orig1s000ChemR.pdf DRAFT MEETING PACKAGE 15
Your preview ends here
Eager to read complete document? Join bartleby learn and gain access to the full version
  • Access to all documents
  • Unlimited textbook solutions
  • 24/7 expert homework help