The Importance Of Reward Management Business Essay

The Importance Of Reward Management Business Essay Reward management in a business organisation is basically the way in which that particular business forms and implements strategies and policies to reward the employees to a fair standard and in accordance with how the organisation values them. Reward management in a business organisation usually consists of the business analysing and controlling the employees remuneration and all of the other benefits for the employees. The main aim of reward management in a business organisation is to reward the employees fairly for the work that they have completed. The main reason reward management exists in business organisations is to motivate the employees in that particular organisation to work hard and try their best to achieve the goals which are set out by the business. Reward management in business organisations not only consist of financial rewards such as pay but they also consist of non-financial rewards such as employee recognition, employee training/development and increased job responsibility. Reward management in a business organisation deals with the design, implementation and maintenance of reward practices that are geared towards the improvement of the business organisations performance. The Importance of Reward Management The elements of reward management within a business organisation are all the things that they use to attract potential employees into their business which includes salary, bonuses, incentive pay, benefits and employee growth opportunities such as professional development and training opportunities. Having a reward management system in place provides the business with many advantages, especially in small to medium size organisations where the managers must have a good relationship with the employees. Reward programmes have proved to be very successful in motivating employees and in turn increase the performance of the organisation as a whole. Below are some of the reasons why a reward system is important: Mutually beneficial- A reward system is beneficial not only to the employee but also to the organisation. The employee will feel more motivated to work harder.by having a reward system in place the employee will feel more committed to their work and their productivity will increase. An increase in productivity will then benefit the organisation. Therefore a reward system is mutually beneficial to the employee and the organisation. Motivation-A reward system will motivate employees by reaching targets and organisational goals in exchange for rewards. A reward system is great at motivating employees but they will also be motivated to prove themselves to the organisation. Absenteeism-A reward system will reduce absenteeism in the organisation. Employees like being rewarded for a job well done and if there is a reward system in place, employees will be less likely to be ringing in sick and not showing up for work. Also by having a reward system in place the employees will be clearer about the targets and goals of the organisation as they will be rewarded when reach certain targets. So by having a reward system as an incentive they will be less likely to be absent from work. Loyalty-A reward system will increase the employees loyalty to the organisation. By a reward system being in place the employee feels valued by the organisation and knows that their opinion matters. If an employee is happy with the reward system, they are more likely to appreciate work place and remain loyal to the organisation Morale-Having a reward system in place providing employees with incentives and recognition will boost their morale. By encouraging employees to meet goals and targets it gives them clear focus and purpose which will their morale. By the employees morale being boosted this will increase the morale of the entire organisation. This is all down to a reward system in the organisation. Teamwork- The reward system will increase the teamwork spirit in the organisation. The reward system will promote teamwork to the employees. The employees will work together as part of a team to achieve their targets in return for rewards. Teamwork within the organisation will help increase efficiency and create a happier workplace. This is another reason why reward systems are important in business organisations. Types of Reward Systems There are several ways to classify rewards; the three most common types are as follows: Intrinsic Rewards Vs Extrinsic Rewards- Intrinsic rewards are the personal satisfaction you get from the job itself eg having pride in your work, having a feeling of accomplishment or being part of a team. If an employee experiences feelings of achievement or personal growth from the job, this would be labelled as an intrinsic reward. Extrinsic rewards would include money, promotions and other benefits. Extrinsic rewards are external to the job and come from an outside source, usually management. If an employee receives a salary increase or a promotion, this would be labelled as an extrinsic reward. Financial Rewards Vs Non-Financial Rewards- Financial rewards are those that will enhance the employees financial well-being directly eg bonus, increase in wages and profit sharing schemes. Non-financial rewards do not enhance the employees financial position directly but make the job more attractive. Some of the Non-financial rewards that a business organisation offer might include-an attractive pension scheme, access to private medical care, help with long-term sickness, crà ¨che facilities, counselling services, staff restaurant etc. Performance-Based Rewards Vs Membership-Based Rewards- The rewards that a business organisation gives to their employees can be based on either their performance or membership criteria. Performance-based rewards are exemplified by the use of commissions, piecework pay plans, incentive schemes, group bonuses, merit pay or other forms of pay for performance plans. Membership-based rewards would include cost of living increases, benefits and salary increase, seniority or time in rank, credentials or future potential. Case Study Tom Warner owned a plumbing, heating and air-conditioning business in Montgomery County,Maryland. In the early 1990s, he faced a major problem. His main customers were commercial property management businesses and they wanted to cut costs. In order to do this; these commercial property management businesses decided to end their contract with Tom Warner and hire their own handymen. Tom Warner didnt want to lay off any of his 250-person workforce. He decided to reconstruct his workforce into territories. He assigned each worker their own territory and told them to operate their territory as if they were running their own business. He put each area director through training in sales techniques, budgeting, negotiating, cost estimating and how to handle customer complaints. Warner believed that if he had technically superb, friendly, and ambitious employees, they could successfully operate like small-town handymen, even though they would be part of a large organisation. Tom Warners programme proved to be very successful. The area directors developed a strong sense of pride and ownership in their territories. Each employee was able to schedule their own work, handle their own equipment, develop their own estimates and advertising campaigns. These were the rewards that each employee desired. Tom Warners programed increased the employees wages. A typical employee working for Warner before he introduced the programme was earning $60,000.In the first year of the programme that employee was earning $100,000.In the second year he was earning $125,000. From a reward point of view, Warners employees are extremely happy and Tom Warners business grew by more than 200 per cent in 24 months. Literary Review According to the book Human Resource Management in Ireland 3rd edition by Patrick Gunnigle, Noreen Heraty and Michael j. Morley: Schuler (1995) outlines a number of core objectives that a business organisation should have in relation to the reward package that they offer. Schuler states that in order for a business organisations reward package to be successful it must meet the following objectives: It should attract potential employees- along with the organisations human resource plan and recruitment and selection techniques the reward package should make potential employees want to work there. The reward package including its mix of pay, incentives and benefits should serve to attract suitable potential employees. It should assist in retaining good employees- the reward package must be perceived internally by the employees as fair and equitable and it should be perceived externally as competitive. Internally the employees should feel happy with the reward package and they should know that in comparison to other businesses it is a very competitive reward package so they wont want to leave and seek employment elsewhere. It should motivate employees- the reward package should help and assist motivating employees to work harder. By linking rewards to performance it should motivate employees to work harder as there is an incentive element. It should contribute to human resource and strategic business plans- the reward package should create a rewarding and supportive climate to work in and therefore it should be perceived as an attractive place to work. This will benefit the business as it will be attracting the best applicants. Reward management in business organisations is extremely important as the reward package helps to attract employees, retain employees and influence performance and behaviour at work. According to the book People Management and Development; Human Resource Management at Work by Mick Marchington and Adrian Wilkinson: Lawler (1984) feels that a reward system within the business organisation can influence a number of HR processes and practices, which then have a direct impact on the organisations performance as a whole. Influence recruitment and retention: Lawler states that any business organisations that have a reward system in place will attract and retain the most people. If better performers are rewarded more highly than poor performers. This also will have an effect on recruitment and retention, so performance-based systems are more likely to attract high-performers. For Example: If a business organisation rewards their employees with high wages, they will attract more applicants which will allow the business more of a choice over selection and hiring decisions. This hopefully will reduce labour turnover in the organisation. Influence Motivation: Employees see that by having a reward system in place, it puts an importance on various activities and tasks. Reward systems therefore have a motivational impact on the employees. However the management must integrate the reward system with the behaviour they expect from the employees. Influence Corporate Culture: The way in which the employees are rewarded will have a huge influence on the corporate culture of the organisation. For example: If a business organisation has a reward system in place that provides benefits for long-serving staff, this will likely shape the existing culture into one where loyalty is seen as central to the business organisations ideology. In contrast, if a business organisation has a reward system in place that rewards the employees for innovative behaviour and ideas, this is more likely to shape the businesses corporate culture into one where creativity and innovation is important. Cost as an influence: Cost is a huge factor and influence in the reward system. Some business organisations may not be able to afford to set up and maintain the reward system; it may be too costly for them. On the other hand, some business organisations may not want to waste the money on a reward system. This may demotivate the employees as they will think that not worth it and this will have a direct impact on their performance in the organisation which in turn will in turn have a direct impact on the organisations performance as a whole. According to the book Human resource management in Ireland 4th edition by Patrick Gunnigle, Noreen Heraty and Michael j. Morley: Lawler (1977) highlights that in order for reward management to be successful the reward system needs to have the essential characteristics: Reward level- In order for reward management to be successful, the reward package must satisfy the employees basic needs for survival, security and self-development. Individuality- Along with satisfying the employees basic needs, the reward system should be flexible enough to meet the employees varying individual needs. Internal equity- The rewards must be seen as fair when compared to others in the business. The criteria and reasons for the allocation of rewards to employees should be equitable and clear to everyone in the organisation .The reason behind the allocation of rewards to employees should be communicated and accepted by all parties. The rewards should be applied consistently throughout the organisation. External equity- The rewards must be seen as fair when compared to those offered for comparable work outside the organisation. Trust- In order for reward management to be successful in the organisation, the management and the employees must believe in the reward system 100 per cent. The employees must believe and accept that will receive rewards when they meet the relevant criteria. The management should trust that the employees will perform at a high standard and the best to their ability in return for rewards. According to Lawler (1977) in order for a business organisation to be successful in reward management, he believes that a reward system must have the characteristics listed above. According to the book Human resource management 6th edition by De Cenzo and Robbins: Armstrong and Murlis (1998) offer some broad distinctions between the main types of reward system: Gain Sharing Schemes-the pay of a group of workers is linked to improvements in internal company productivity. Employee Stock Ownership Schemes (ESOPs)-The business organisation offers company stock (at a lower rate than normal) to certain employees. Profit-Sharing Schemes-The business organisation gives a certain percentage of the end of year profits to the employees. Skill-Based Pay Schemes-The business organisation rewards the employees with pay on the basis of job-related skills or competencies. Individual Incentive Schemes-The business organisation rewards the employees for reaching or exceeding specific established performance criteria. Piece- rate schemes are the most obvious form of individual performance related rewards. Group Incentive Schemes-The business organisation rewards groups of employees with the same principles they use on individual schemes. Used most commonly when group work or team work is present in the business organisation. Conclusion To conclude I am going to give a brief run through the topics I have covered throughout this report. I defined and explained the meaning of what reward management is and how organisations manage rewards in organisations. I then went on to discuss the importance of reward management within organisations, by doing this I pointed out the advantages of having reward systems in an organisation. These benefits included mutually beneficial, increases motivation, improves morale, increases the employees loyalty to the organisation, improves teamwork and reduces absenteeism. I looked at commonly used reward schemes. I looked at a case study about Tom Warner was forced to reward his employees with a huge amount of responsibility; however it had an extremely successful outcome for him. I then looked at the main aims that every reward system should have; attract potential employees, assist in retaining good employees, motivate employees, contribute to human resource and strategic business plans. I explained the direct impact a reward system can have on the organisation as a whole ie influence o n performance, influence on motivation, influence on the corporate culture. I looked at and explained the essential characteristics a reward system must have in order to be effective. This is important for management when designing their reward system. They should look at and evaluate their current reward system and make sure it possesses the right characteristics. I then differentiated between the most common types of reward schemes according to research I found on Armstrong and Murlis point of view on reward systems.

Honour & Shame Essay

One Sunday morning I was driving my children back from their regular soccer game. It was a warm summer day, sun shining ever so brightly, making the uneven town picturesque. As I drove along in my Holden with rigid brown seats and the windscreen wipers that didn’t work, I looked over to my sixteen year old daughter sitting next to menodding and shaking her head rhythmically to, in her words, ‘legendary’ music band One Direction. An image of Asreen flashed through my mind†¦ †¦Ã¢â‚¬Å"Kiran?† the voice on my mobile phone was barely more than a whisper. â€Å"Kiran? Is that you?† .The train ride back home was a typical for Friday eveningIt was very busy Friday evening train ride back from work, â€Å"Are you able to speak up a little?† I asked, raising my own voice overagainst loud chatterschatters from fellow passengers and rattling noise from the train. â€Å"I found your number in Indus Age, My – † the line went suddenly went dead. Indus Age is a local monthly newspaper. iIt has largest circulation to Indian and South East Asian community in the country. I was interviewed a week ago concerning about my plight with honour based violence. After two years of lengthy legal proceeding over evidence of injury which included tampered medical records I managed to get a divorce. I was sure that such crimeshonour based violence against women was prevalent and practiced behind closed doors, after my divorce I wanted to assist other women in similar situation and have my phone number published in the newspaper. I thought I lost her but then, few minutes later, she was back. â€Å"Sorry I had to hang up I thought someone was coming. My parents are forcing me to marry a 35 year old man who I don’t even know. I am a prisoner in my own house. I can’t take it any longer. I need help.† She stopped for breath. â€Å"Please help me,† she said in a trembling voice. She sounded frantic; it seemed that she was at the mercy of her family. I didn’t know who I was talking to but I knew I had to help. I spoke quickly, â€Å"Can you get out? There are all sorts of help available if you can get out.† I knew from my own experience that if a girl has made up her mind to run she usually finds a way to do it. This woman could be anywhere in the country but she was desperate and I had to reassure her. â€Å"There is help for you,.† I said. â€Å"There are women refuge houses, people to support. I would support you. You’ll be okay.† â€Å"But how†¦Wait, that’s Dad. He’s coming. I have to go† Her phone went dead. I felt anxiousiety, my pulse shot up as I tried as best I could to get on with my daily household choresroutine and parental responsibilities. Later in thethat evening while I was preparing dinner my phone rang again. I tried hard to understand but couldn’t make out anything except the gasping sound panting. I turned off my range-hood and enquired, â€Å"Hello?† â€Å"It’s me, Asreen,† she spoke, her voice penetrating as if she was right next to me. â€Å"I did it, I ran away† â€Å"Where are you?† â€Å"Redfern.† â€Å"Asreen, you have to call the police. DailDial 000† I had put my phone on speaker as I washed my hands. â€Å"No, I don’t want police. My family will never see me again. My community will disown me,† she said claimed almost hysterical. I could imagine why Asreen didn’t want police to be involved. She was in a state of fear and frustration. Her parents who loved her dearly until very recently changed overnight and now consider family’s honour more important than that of their daughter’s well-being and happiness. â€Å"Meet me at Redfern railway station in 45 minutes,.† I said cleaning up my kitchen. â€Å"Please don’t be late,.† she hung up. I called on my children and explained them that I need to go out on an emergency. I drove as fast as I could past the motorway speeding up to maximum limit. I reached Redfern at 8 p.m. it was crowded, people pushing one another to get ahead in line. Few country trains hurried past while the intercity trains stopped at the platform for passengerss dark and deserted. I walked across the automatic ticket machine to find myself staring at a tall slim woman leaning against the closed door humming what I could understand a very popular song. from Justin Beiber. She looked no more than sixteen dressed in a traditional outfit her head was covered in a veil. I caught her eye and she smiled and then waved at me. â€Å"Kiran,† she said enthusiastically. â€Å"Yes.† I walked closer I could see her eyes swollen lips dried smeared make up over her face. I offered her a bottle of water and walked with her to my car. No one spoke, the two minute walk felt like an eternity. Breaking the silence she spoke softly, â€Å"Thank – thank you Kiran. You saved my life. I read your story and only after I spoke to you I found courage to leave my house.† I didn’t know what to say, I was in a state of shock. I felt rage I could barely focus on my driving I wanted to say something. Asreen continued, â€Å"There were bolts on all doors and someone from the family was always home. I didn’t know how to get out. And if I did, where would I go?† We talked about family, food, school, fashion and many other issues on our way back. We talked as if we were best friends and had known each other for many years. I introduced Asreen to my children Maya and Vicky and offered her rice and lamb curry for dinner. It was close to midnight she looked very tired and fell asleep as soon as she sat on the lounge. I imagined her situation; it was her mother who arranged her marriage. She grew up knowing that one day the subject of her marriage would come up but didn’t expect it when she was sixteen. She was one of the smartest girls in her school; she wanted to become a psychiatrist. One day when her parents woke her up and told her that she was going to get engaged Asreen said bluntly, â€Å"But I don’t want to.† For the next few days I enquired at women’s refuge centre, department of community services, legal aid and other community based organisations. What followed was another court proceeding lasting more than 12 weeks. I became Asreen’s foster parent while she continued her education. Later that year Asreen and I started Honour to help other women from South East Asian family facing honour based violenceI sat next to her contemplating on the events of the day. I wanted to help Asreen and reach out to other women in similar situations confronting criticism and oppression from inside their communities and often close family members for not being obedient to the traditional rules set by men for thousands of years. â€Å"Are you alright?† Asreen said waking up suddenly. I realised that I accidentally dropped my glass on the wooden floor breaking it into pieces. â€Å"Why can’t I live like any other sixteen year old girls? Why can’t I have boy-friends like girls from my school?† she cried while cleaning up broken pieces of glass. It was close to two, I was so exhausted I could barely feel any strength in my legs. I could hear Asreen’s voice slowly fading away. With my eyes closed I tried to seek explanation for such acts against own daughter. The issue of status of women is always in question in a patriarchal society. For thousands of years people from Indian sub-continent had considered daughter a painful burden, a potential source of shame to her father. Family is vital principal group and marriage hallowed as sacred. Women are deprived of their freedom and those who rebel or go against the norms faces threat the people of the community so much so that they are even killed for honour. †¦perhaps this comes out as it makes it like a newspaper article, not a narrative. †¦ As we arrived home I hugged my daughter tightly and said with tears running down my cheeks, â€Å"I love you.† The time frame here doesn;’t work, you’ve already taken the story on years but now go back to the present†¦

Treatment of Solid Tumors including Metastatic Breast Cancer - Free Essay Example

Sample details Pages: 9 Words: 2828 Downloads: 5 Date added: 2019/02/06 Category Medicine Essay Level High school Topics: Breast Cancer Essay Did you like this example? Citizen Petition Reconsider Issuance of RMAT Designation for Therapeutic Armed Activated T Lymphocytes Treatment of Solid Tumors including Metastatic Breast Cancer The undersigned submits this petition under to request the Commissioner of Food and Drugs to reconsider issuing a Regenerative Medicine Advanced Therapy (RMAT) designation to autologous T-lymphocyte therapies for patients with malignant advanced stage solid tumors, specifically stage IV metastatic breast cancer, on the basis that it can meet an unmet medical need as substantiated by new clinical trial evidence resulting from trial involving OKT3 x Herceptin Armed Activated T Cells, Low Dose IL-2, and GM-CSF, as relevant to section 506(g) of the Federal Food, Drug, and Cosmetic Act (FDC Act), as added by section 3033 of the 21st Century Cures Act (Cures Act). A. Action Requested The Expedited Programs for Regenerative Medicine Therapies for Serious Conditions Draft Guidance for Industry states that in order for an investigational drug to receive a Regenerative Medicine Advanced Therapy (RMAT) designation it must fulfill the following criteria1:. Don’t waste time! Our writers will create an original "Treatment of Solid Tumors including Metastatic Breast Cancer" essay for you Create order It meets the definition of regenerative medicine therapy (see section I of [draft guidance] document) It is intended to treat, modify, reverse or cure a serious condition; and Preliminary clinical evidence indicates that the regenerative medicine therapy has the potential to address unmet medical needs for such condition The Expedited Programs for Regenerative Medicine Therapies for Serious Conditions Draft Guidance for Industry states that the definition of regenerative medicine therapy is1: †¢ Cell therapies, therapeutic tissue engineering products, human cell, and tissue products, and combination products using any such therapies or product And Gene therapies, including genetically modified cells, that lead to a durable modification of cells or tissues may meet the definition of a regenerative medicine therapy. In said draft guidance, unmet medical need is defined as: †¢ An unmet medical need is a condition whose treatment or diagnosis is not addressed adequately by available therapy. An unmet medical need includes an immediate need for a defined population (i.e., to treat a serious condition with no or limited treatment) or a longer-term need for society (e.g., to address the development of resistance to antibacterial drugs). We, the undersigned, petition the Commissioner of Food and Drugs to reconsider issuing an RMAT designation to autologous T-Lymphocyte therapies for solid tumors, and we offer new clinical trial data from the trial named Treatment of Stage IV Breast Cancer With OKT3 x Herceptin Armed Activated T Cells, Low Dose IL-2, And GM-CSF (NCT00027807) as clinical evidence that indicates the potential to meet an unmet medical need thereby fulfilling the requirement â€Å"that the regenerative medicine therapy has the potential to address unmet medical needs for such condition† listed in The Expedited Programs for Regenerative Medicine Therapies for Serious Conditions Draft Guidance for Industry.1 B. Statement of Grounds Cancer is the second leading cause of death in the United States, with breast cancer following lung cancer as cancers with the highest mortality rates. While there have been a number of cancer therapies found to either treat or cure early-stage cancers, late-stage solid t umors tend to elude these therapies, and as a result, there are very few therapies that can attempt to treat them. Breast cancer is a disease that affects 1 out of 8 women, with 10% of all cases eventually metastasizing 5 years after the patient has received therapy for it.2,3 Many patients receive a form of therapy for breast cancer that may involve surgery with adjuvant chemotherapy, or even in the case of high-risk breast cancer high-dose chemotherapy with a stem cell transplant. Unfortunately, relapse rates after these therapies remain high, and often times the cancer has metastasized at that point. 55-87% of women who have primary breast cancer with 10 or more axillary lymph nodes relapse within 5 years of when they were diagnosed. 4 Stage IV metastatic breast cancer represents an unmet medical need, as it is not being met by current treatments or therapies. Additionally, there is research that indicates that combination therapies would work in a more effective manner against metastatic breast cancer than a single therapy.4 Some of the therapies that are currently being considered in clinical trials involve chimeric T cells, others are looking at armed activated T cells (aATC), and others are considering antibodies.3,4 The trial in question that we are using as the basis for our petition analyzes the combination immunotherapy consisting of HER2Bi armed activated T cell infusions, IL-2, and GM-CSF.3,4 The HER2Bi or BsAb consists of two monoclonal antibodies that were heteroconjugated and used to arm the T cells. These two monoclonal antibodies were Trastuzumab (Herceptin, Genentech) and an anti-CD3 (OKT3, Centocor, Ortho-Biotech) that were prepared under Current Good Manufacturing Practice (cGMP) regulations as enforced by the Food and Drugs Administration.5 Trastuzumab or the brand name Herceptin has been approved for use in the treatment of breast cancers that overexpress the HER2/neu receptor, which is a tyrosine kinase transmembrane epidermal growth factor receptor family member.3 The HER2/neu receptor is overexpressed in many breast, ovarian, gastric, lung, prostate and oral cancers. This overexpression of HER2/neu makes it an ideal therapeutic target. 3,4 Moreover, women with HER2- cancers have fewer therapeutic options, but the trial demonstrated a positive result in those patients as well, which further supports the claim that this therapy can fulfill an unmet need for a serious condition. The OKT3 or anti-CD3 antibody targets the CD3 T cell receptor. Together they form the HER2 Bispecific antibody (HER2Bi), which is engineered to direct cytotoxicity at tumor cells that overexpress the HER2/neu receptor. In this trial, they combined the HER2Bi with Interleukin-2 and the granulocyte macrophage colony-stimulating factor (GM-CSF). Interleukin-2 is a cytokine produced by leukocytes, which increases the growth and activity of other T lymphocytes and B-lymphocytes, as well as affecting the development of the immune system. GM-CSF is another cytokine that helps create additional white blood cells specifically granulocytes, macrophages, and cells that become platelets.3 The primary endpoints of the trial were to determine the safety and maximum tolerated dose. The highest dose that was administered consisted of 20 x 10^9 aATC, and the maximum tolerated dose level was not reached, nor were there any dose-limiting toxicities observed at this dosage level. The secondary endpoints of the study were assessments of response rates: complete response (CR), stable disease (SD), partial response (PR), and no evidence of disease (NED), time to progression (TTP), and overall survival (OS). TTP and OS were measured from the date of enrollment in the trial.3 The study consisted of 23 women with stage IV metastatic breast cancer, of both HER2+ and HER2- patients, in a traditional 3+3 dose escalation design. One patient in the study died from digoxin toxicity related congestive heart failure, and the autopsy of the patient did not show any myocardial T cell infiltrates. The remaining 22 patients were evaluated at 14.5 weeks. Results showed 59.1% (13/22) of patients had SD or better (NED, PR, or SD) and 40.9% (9/22) of patients had PD. The overall survival rate of the 22 evaluable patients was 36.2 months. Within the overall survival rate, the breakdown was an overall survival rate of 57.4 months for HER2+ and 27.4 months for HER2-. The results of t his study showed that there were no major negative side effects associated with this aATC therapy. There were no cytokine storms, which has been a problematic side effect in past T-cell therapies, but there were however what the researchers designated cytokine flurries.3 And while a number of patients had to have their aATC washed to reduce side effects, not a single patient had to have their dose lowered. The main side effects observed were grade 3 chills and grade 3 headaches. The incidence of chills was 8.6%, 20.8%, and 43.1% at dose levels 1, 2, and 3, respectively. The incidence of headaches was 3.1%, 8.3%, and 19.6% at dose levels, 1, 2, and 3. Two patients were hospitalized to manage other side effects that included nausea, hypotension, vomiting, and dehydration, but after the successful resolution of these side effects they resumed the trial and continued to receive the infusions of the aATCs. In this trial, the innate cytotoxicity of T cells was redirected by the formation of the aATC (can be prepared with either CD4+ or CD8+,). Normal patients and cancer patients who rec eived this combination therapy of aATC with HER2Bi combined with IL-2 and GM-CSF both exhibited specific cytotoxicity towards target cells, and the cytotoxicity increased as the dosage amount of the aATC increased. 4 The cytotoxicity persisted for more than 54 hours towards the target cells, and other cytokines including IFN-?, TNF- ?, and GM-CSF were induced when the tumor antigen was bound to the aATC.4 This capability of the aATC to induce IFN-? when it binds to a tumor antigen may be clinically beneficial, as other studies have already shown in preclinical and clinical studies that cytotoxic T cells produce IFN-? and that IFN-? is tumoricidal.6,7 Another advantage of this particular therapy is that it does not require large quantities of HER2Bi unlike other infusional therapies that do require large doses of bispecific antibodies. In fact, billions of armed activated T cells can be armed with just milligrams of the HER2Bi antibody. The aATCs proved to be cytotoxic even towards breast cancers that had a low expression level of HER2 receptors, such as the MCF-7 breast cancer cell line. 4 The SK-BR-3 cell line, which has higher levels of HER2 receptors, had even more susceptibility to cytotoxic effects from the aATC, causing greater amounts of tumor cells to be lysed.4 This indicates that even a small amount of the combination of the anti-CD3 and anti-HER2 antibodies that are used to arm activated T cells can mediate high levels of cytotoxicity that is directed at tumor cells. Even when the levels of the tumor antigen expression is low as in the case of the MCF-7 cell line, and are able to mediate cytotoxicity in vivo for many days after infusion of the aATCs.4 The fact that that the maximum tolerated dose was not reached, that there were no dose-limiting toxicities, nor was there any evidence of a life-threatening cytokine storm, and all other side effects were relatively mild and successfully resolved supports the idea that multiple infusions of aATC in combination with IL-2 and GM-CSF were both safe and technically feasible. The results of this study showed that combining antibody targeting and T cell-mediated killing could greatly augment cytotoxicity that can be directed towards cancer cells and provides a rationale to develop new nontoxic immunological approaches that can eradicate any residual tumor cells. 4 Ultimately the researchers have concluded that multiple intravenous infusions of the HER2Bi aATC are feasible, and most of them would go to the lungs and then migrate to, and settle, in the spleen, bone marrow, and liver. This is advantageous because many breast cancers metastasize to these locations, which would make the targeting of these metastases by the aATC easier. The authors of this study had intended on moving forward with a Phase II trial, and the results supported the rationale for moving forward. However, this trial ultimately did not move forward to a Phase II trial, but it did provide the rationale for further clinical trials on similar immunotherapies. A separate trial studied the HER2Bi armed activated T cells in HER2+ colorectal cancer, both in vitro and in vivo. The aATC exhibited increased cytotoxicity against HER2+ tumor cells, and showed significant suppression of colorectal carcinoma cells in comparison to unarmed ATC. Similar to the above-mentioned breast can cer trial, researchers were able to reach these results by using a very low dose of HER2Bi, which eliminated previously seen side effects of Herceptin which included cardiotoxicity that manifested as left ventricular dysfunction and heart failure in a different research project. 8 Much like the trial conducted on metastatic breast cancer, the data in this trial also showed that aATC induced IFN-? secretion levels that were higher than those induced by unarmed ATC, As such the researchers of this trial concluded that â€Å"HER2Bi?armed ATCs with anti?tumor effects may provide a promising immunotherapy for colorectal carcinoma for the future†.9 Another Phase I trial examined the HER2Bi aATC in metastatic castrate-resistant prostate cancer. They also found an increased level of IFN-? as well as no dose-limiting toxicities that were associated with this immunotherapy. 3 out of 7 patients in this trial showed a decrease in their prostate-specific antigen (PSA) and pain levels. The results of this trial provided strong rationale to continue onto a Phase II trial.10 Furthermore, there is another trial in progress that is also researching HER2Bi armed activated T cells combined with pembrolizumab, which blocks the PD-1 pathway, in patients with metastatic bre ast cancer. The trial (NCT03272334), sponsored by the University of Virginia is currently recruiting patients, but we look forward to seeing if it reaches its primary endpoints, which are evaluating the side effects and best dose for this treatment without reaching any dose-limiting toxicities. 11 While we need to keep a watchful eye on more severe side effects such as the possibility of life-threatening cytokine storms in future trials, the fact that the trial on metastatic breast cancer only had cytokine flurries is an encouraging sign. Novel immunotherapies including T-cell therapies are making headway as therapeutics for solid tumors and is a field that holds great promise because it can boost patients preexisting tumors responses, in a nontoxic manner, specifically in tumors that have no current successful therapy options.12 We would request that the Commissioner of Food and Drugs reconsider issuing an RMAT designation to autologous T-Lymphocyte therapies for solid tumors based on the preclinical trial data as covered above from the trial Treatment of Stage IV Breast Cancer With OKT3 x Herceptin Armed Activated T Cells, Low Dose IL-2, And GM-CSF (NCT00027807). We feel that this data, along with the fact that metastatic breast cancer is a serious condition that has very few therapies available to treat, and as such is an unmet medical need, fulfills all the requirements of an RMAT designation which are listed as: It meets the definition of regenerative medicine therapy (see section I of [draft guidance] document) It is intended to treat, modify, reverse or cure a serious condition; and Preliminary clinical evidence indicates that the regenerative medicine therapy has the potential to address unmet medical needs for such condition C. Environmental Impact The petitioner hereby states that the action requested in this petition will have no environmental impact and that, therefore, an environmental assessment is not required under 21 CFR 25.30. D. Economic Impact Not applicable; this section has not been requested by the Commissioner. E. Certification The undersigned certifies, that, to the best knowledge and belief of the undersigned, this petition includes all information and views on which the petition relies, and that it includes representative data and information known to the petitioner which are unfavorable to the petition. References 1. Food and Drug Administration. (2017, November). Expedited Programs for Regenerative Medicine Therapies for Serious Conditions Draft Guidance for Industry. Retrieved December 11, 2018, from https://www.fda.gov/downloads/biologicsbloodvaccines/guidancecomplianceregulatoryinformation/guidances/cellularandgenetherapy/ucm585414.pdf 2. American Cancer Society. (n.d.). How Common Is Breast Cancer? Retrieved from https://www.cancer.org/cancer/breast-cancer/about/how-common-is-breast-cancer.html 3. Lum, L. G., Thakur, A., Al-Kadhimi, Z., Colvin, G. A., Cummings, F. J., Legare, R. D., . . . Rathore, R. (2015). Targeted T-cell Therapy in Stage IV Breast Cancer: A Phase I Clinical Trial. Clinical Cancer Research, 21(10), 2305-2314. doi:10.1158/1078-0432.ccr-14-2280 4. Sen, M., Wankowski, D. M., Garlie, N. K., Siebenlist, R. E., Epps, D. V., Lefever, A. V., Lum, L. G. (2001). Use of Anti-CD3 Ãâ€" Anti-HER2/neu Bispecific Antibody for Redirecting Cytotoxicity of Activated T Cells Toward HER2/ neu Tumors. Journal of Hematotherapy Stem Cell Research, 10(2), 247-260. doi:10.1089/15258160151134944 5. Center for Drug Evaluation and Research. (n.d.). Manufacturing Facts About the Current Good Manufacturing Practices (CGMPs). Retrieved from https://www.fda.gov/drugs/developmentapprovalprocess/manufacturing/ucm169105.htm 6. Ogawa M, W-G Yu, K Umehara, M Iwasaki, R Wijesuriya, T Tsujimura, T Kubo, H Fujiwara and T Hamaoka. (1998). Multiple roles of interferon-gamma in the mediation of interleukin 12-induced tumor regression. Cancer Res 58: 2426–2432. 7. Quian J-H, JA Titus, SM Andrew, D Mezzanzanica, MA Garrido, JR Wunderlich and DM Segal. (1991). Human peripheral blood lymphocytes targeted with bispecific anti- bodies release cytokines that are essential for inhibiting tumor growth. J Immunol 146:3250–3256. 8. Babar, T., Blomberg, C., Hoffner, E., Yan, X. (2014). Anti-HER2 Cancer Therapy and Cardiotoxicity. Current Pharmaceutical Design,20(30), 4911-4919. doi:10 .2174/1381612820666140604145037 9. Han, H., Ma, J., Zhang, K., Li, W., Liu, C., Zhang, Y., . . . Gao, B. (2014). Bispecific anti-CD3 x anti-HER2 antibody mediates T cell cytolytic activity to HER2-positive colorectal cancer in vitro and in vivo. International Journal of Oncology,45(6), 2446-2454. doi:10.3892/ijo.2014.2663 10. Vaishampayan, U., Thakur, A., Rathore, R., Kouttab, N., Lum, L. G. (2015). Phase I Study of Anti-CD3 x Anti-Her2 Bispecific Antibody in Metastatic Castrate Resistant Prostate Cancer Patients. Prostate Cancer,2015, 1-10. doi:10.1155/2015/285193 11. ClinicalTrials.gov. National Library of Medicine (U.S.). (n.d.). Her2-BATS and Pembrolizumab in Metastatic Breast Cancer (Breast-47)r. Retrieved from https://clinicaltrials.gov/ct2/show/NCT03272334 12. Melton, C. (2018, November 28). Novel T-Cell Therapies Make Inroads Into Solid Tumors. Retrieved December 17, 2018, from https://www.onclive.com/publications/oncology-live/2018/vol-19-no-22/novel-tcell-therapies-make-i nroads-into-solid-tumors?p=1

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