Clinical Supply Chain: Audio Transcript Slide 1: Welcome to the Clinical Supply Chain Course. The upcoming lessons will help you become familiar with

Transcription

1 Clinical Supply Chain: Audio Transcript Slide 1: Welcome to the Clinical Supply Chain Course. The upcoming lessons will help you become familiar with the dynamics involved in the pharmaceutical Clinical Supply Chain and the skills required for a career in the industry. To begin this course, click the NEXT button below. Slide 2: This course introduces clinical colleagues to the responsibilities and skills involved in working in the Clinical Supply Chain (CSC). Slide 3: By the end of this course, you will be able to identify the types and phases of clinical trials and ways in which the clinical supply chain fits into the clinical trial. You will be able to define clinical terms, such as First Patient In, First Patient Dosed. Become familiar with the importance of enrollment forecasting and CSC s role in managing inventory. Recognize key skills required for a successful career in clinical trial supply. Slide 4: The course is divided into three lessons. Lesson one is an overview of clinical trials. Lesson two provides information that will help you to understand the importance of enrollment forecasting and CSC s role in managing inventory. Lesson three offers examples of the skills and behaviors required for a successful career in clinical trial supply. Slide 5: Lesson one, an overview of clinical trials. Slide 5.1:The goal of a pharmaceutical company is to create products that improve people s lives, and are safe and effective. To ensure this goal is reached, clinical trials, which are also known as clinical studies, are conducted. The Clinical Supply Chain helps provide products so that the company is able to conduct successful trials. Slide 5.2: Lesson one covers trial types, trial design, the role of Clinical Supply Chain in a clinical trial, clinical trial terms, and critical CSC milestones. Slide 5.3: So let s think about this. We re describing a process but that s impersonal. On one side of the process, are people who are working very hard to improve other people s lives. They re in this industry to create products that can really make a difference for somebody else. They also want to make sure that

2 what they create is safe. They want to know that what they make actually improves the lives of others. Slide5.4: On the other side of the process are people who need, sometimes desperately, products that will improve their lives. For some, unfortunately, it s life or death. They need to know what they are taking is safe and effective. Slide 5.5: Between those who create the products on one side and those who need them on the other, there is the clinical trial system. Safety and effectiveness drive this system. Now within the clinical trial system, there s a Clinical Supply Chain. It s built to ensure that the right product is in the right place for the right person when it needs to be. A lot of thought and effort has been made to ensure this vital link. Fulfilling one s responsibilities in the Clinical Supply Chain should be a conscientious effort one that should be taken seriously. Imagine having a grandparent who is enrolled in a clinical trial. As a family member, you would want to be assured that the right product was available when it's needed. It s more than merely a job. People s well-being and even their lives are at stake. Slide5.6: To ensure the efficacy of investigational medicine and the safety of trial subjects whom the drug will treat, clinical trials are classified into different phases. Each trial phase has specific requirements and goals. Slide5.6.1: We begin with preclinical trials. These trials involve the testing of experimental drugs in the test tube or in animals. This phase occurs before trials in humans may be carried out. Slide 5.6.2: Phase I trials are initial studies designed to determine the metabolism and pharmacologic action of drugs in humans. Phase one also helps determine the side effects associated with increasing doses and gives an insight into early evidence of effectiveness. A phase one trial may or may not include healthy participants or subjects. Slide 5.6.3: Phase II trials are controlled clinical studies conducted to evaluate the effectiveness of the drug for a particular indication or indications in subjects with the disease or condition under trial. Phase two trials are also conducted to determine the common short term side effects and risks. Slide 5.6.4: Phase III trials are expanded controlled and uncontrolled studies. They are performed after the preliminary evidence suggests the effectiveness of the

3 drug has been obtained. The intent of conducting phase three trials is to gather additional information to evaluate the overall benefit-risk relationship of the drug and provide an adequate basis for physician labeling. Slide5.6.5: Phase IV trials are post-marketing studies to delineate additional information, including the drugs risks, benefits, and optimal use. Slide 5.6.6: Compassionate use trials are also known as expanded access trials. In a compassionate use trial, a company sponsoring a drug in the late stages of drug development, such as phase three clinical trials, can offer expanded access programs for subjects who are not able to enroll in a clinical trial. Subjects who don t qualify for either clinical trials or expanded access programs, if one exists, may be able to get the unapproved new drug by applying for single subject access. Slide 5.6.7: The Investigator-Initiated trial is a study in which the sponsor is a physical person such as a physician, a nurse, or another health professional. An investigator initiated study may also be sponsored by a not-for-profit organization, which could be a governmental body such as the National Institutes of Health, a public institution like a hospital, a university, or a trust, or a research organization. Slide5.7: So let s test what you ve learned. Please match the description of the trial to the appropriate trial phase. Slide5.8: Before a clinical trial can begin, various roles in the pharma organization draft a trial design so that key activities that meet regulatory and policy requirements can be performed effectively and on time. Trial design is performed through the partnership with the Clinical Supply Chain and other functional areas within a sponsor organization such as a global clinical operations team. Slide 5.8.1: Some considerations for trial design include: in which countries will the clinical trial be conducted, how many sites per country are needed, how many subjects will be at each site per month per country. Part of the trial design also includes figuring out how many depots or distribution centers are needed. Is one depot needed in the US or are several needed around the world? Where will they be located? Determining how many subjects will be required for the trial contributes to creating an enrollment forecast and the enrollment rate on a

4 month to month basis. This helps to determine the quantity of the drug that needs to be manufactured for, and managed during, the trial. Slide 5.9: Most clinical trials are randomized or controlled. Randomization is the process of assigning trial subjects or control groups to a treatment group using an element of chance to determine the assignment in order to reduce bias. Slide 5.9.1: A single blind trial is a trial in which one of the categories of individuals remains unaware of the intervention assignments throughout the trial. The categories of individuals are the participants who are the subjects, or patients, that are being treated, the investigators the healthcare providers, or the assessors those collecting the outcome data. A double blind trial is one in which all three categories of individuals remain unaware of the intervention assignments throughout the trial period. An open label trial is one in which everyone involved knows who has received which interventions throughout the trial. Slide 5.9.2: It is essential for the Clinical Supply Chain to always be mindful to maintain the blind. This means the Clinical Supply Chain must be cautious while communicating with blinded individuals so as to not create any bias within the trial. Slide 5.10: The goal of a pharmaceutical company is to create products that improve people s lives, and are safe and effective. To support this purpose, clinical trials are conducted. The Clinical Supply Chain, or CSC, is charged with ensuring that adequate inventory of the supplies are provided to treat subjects enrolled in the clinical trial. Specifically, this is having the correct medication, in the correct quantity, at every site so that subject treatment is safe and uninterrupted. Slide The contrast between a clinical and commercial supply chain is the relationship to the subject. In a Clinical Supply Chain, subjects and their well-being are the primary focus of your efforts - the daily decisions made that can directly affect trial subjects. By contract, in a commercial supply chain your performance is primarily measured by inventory turns and costs. Slide : Another difference is that the Clinical Supply Chain does not provide an unending supply of product. The products that the Clinical Supply Chain are

5 charged with supplying to their trial subjects are specialized, rare, and take time to produce. They are expensive to safely manufacture, package, ship, and store. Having the product available where it is needed, when it is needed is critical. Slide : Keeping the investigational sites sufficiently stocked is the most important factor in keeping the subjects enrolled in a trial. Why? Consider the following. Subjects cannot start the clinical trial or remain enrolled in the trial if the investigational medication is not available. The products that sponsor companies are creating for their trials are so unique that some subjects may have no other treatment options. Slide : Some subjects travel from remote locations to participate in a trial; others may not be able to get healthcare anywhere else in their home country or in their region. When a subject drops out of a trial, the sponsor company and the industry overall lose valuable data which could ve contributed to the advancement of treatment. More significantly, losing a subject from the enrollment the trial means the investigational medication offers no chance of helping them. Pursuing unmet medical needs is even more important and more rewarding when trial results are positive. Slide : Another primary goal of the Clinical Supply Chain in a trial is to reduce waste, or scrap. Scrap can be defined as any leftover or unused materials of the conduct of a clinical trial. This is a challenge as trial materials are often overproduced at the start of a trial. Overproduction occurs because the sponsor might not have accurate information regarding how many subjects or patients will be enrolled in the trial and/or to ensure that the trial sites do not stock out, leaving subjects without trial medication. Without an accurate enrollment forecast, trial sites could stock out, or run out of product, which would leave subjects without trial medication. To avoid this, the CSC will often overproduce prior to the trial start date. The act of balancing drug production and consumption of trial drug supply against the trial enrollment, while preventing waste, is the primary challenge of the CSC. Slide 5.11: To support the goals of the CSC, an understanding of the following terms is required. Click each term to view its definition. Slide 5.12: It is of utmost importance to be aware of these critical supply chain milestones, and communicate any risk associated with them so you can ensure

6 that the appropriate drug is provided at the right time throughout the study. Click each milestone in the timeline to learn more. Slide 5.13: You just learned that a new country will be added to your trial. At any point before LPI, this could occur. Should this happen in your trial, what are the factors you need to consider? Select all that apply and click the Submit button. Slide 5.14: In this lesson, you learned that among the goals of a pharmaceutical company is to create products that improve people s lives, are safe and are effective. The Clinical Supply Chain helps provide investigational medication to clinical trial sites to conduct successful trials. You were introduced to important trial-related terminology and that there are different types of clinical trials. The goal of the Clinical Supply Chain process is having the correct medication, in the correct quantity, at every site, so that subject treatment is safe and uninterrupted. This is done in part by monitoring data that include important milestones during a trial. Slide 6.1: In this lesson, we will explore the importance of enrollment forecasting and CSC s role in managing inventory throughout the following phases of supplying a clinical trial: planning, manufacturing, packaging and labeling, storage and distribution and close out. Slide 6.2: Planning for the supply of a clinical trial begins the supply chain process, but planning is also iterative and occurs throughout the life of a trial. Having the investigational medication available, where and when it s needed, is the ultimate goal of all of this planning. Investigational medicine is precious, unique and hard to replace. If product is not available at a trial site there isn t a replacement. Investigational medications are also expensive; some can cost $1,000 per dose or more. Consequently, there are substantial costs associated with inaccurate forecasting. Slide 6.2.1: Having insufficient supply presents the risks of trial subjects dropping out of the trial. The value of the lost data is hard to measure. Insufficient supply can also result in delayed trial timelines and impact market authorization approvals, which have substantial impact on the sponsor s revenues.. The greater loss is realized when subjects may have benefitted from the trial treatment, but it is not available. Having too much investigational medicine presents the risk of

7 incurring the cost of manufacturing, transporting, and storing unused inventory. It also presents the possibility of not having this drug available for other trials. Costs are also incurred from the destruction of scrap. Slide 6.2.2: Therefore, data-driven decisions must be made when supplying a clinical trial. Very small trials can be forecasted manually. For larger more complex trials, demand estimates should be performed using more sophisticated simulation tools. Open communication is key to the success of a trial. Asking questions, cultivating partnerships, and setting expectations is essential to making critical decisions, not only in forecasting, but also other risks. The clinical supply chain needs to communicate openly with partners regarding all known risks (for example, risks due to product quality problems, such as over enrollment or equipment failure.) Slide 6.2.3: This open communication also allows all involved to proactively make preparations for unexpected circumstances during the trial. If Mother Nature delivers conditions that cause an unexpected delay in the supply of a trial drug how will you accommodate for that in a trial supply plan? Slide 6.3: Included in the end to end Clinical Supply Chain are the manufacturing process steps of Active Pharmaceutical Ingredient, or API manufacturing and drug product manufacturing. API manufacturing is the process step by which the Active Pharmaceutical Ingredient which is biologically active, is produced. Drug product manufacturing is the process in which the active ingredient is converted into the format used for the final dispensing dose. Slide 6.3.1: Molecules used as active substances can be divided into two classes: small and large molecules. They differ not only in size, but also in how they were made, how they behave, their mode of action in the body, and their suitability for certain drug forms. Small molecules are chemically active substances that can be processed into ingestion tablets or capsules. Small molecules are typically stored at room temperature or in ambient conditions. Large molecules, or biologics, are a class of drugs based on protein that have a therapeutic effect. Biologics are administered by injection or infusion and are typically required to be stored in refrigerated or frozen conditions. Slide 6.4: Packaging and labeling is a complex process that can take time to complete. Trial medication and kits can be manufactured in one location, then

8 packed and labeled in another location, which very well may be all the way around the world. Every clinical trial has a unique packaging design with specific trial labels including text- and country-specific panels and a kit designed to ensure subject compliance to the clinical protocol. Slide 6.4.1: All manufacturing, packaging and labeling must follow local and global regulations (such as regulatory or GxP), and industry guidance for example ICH and EMEA, and governmental (FDA). Country-specific and local health authority standards all need to be considered, and in many trials it s critical for clinical packaging and labeling to "protect the blind". This means that everything has to look identical. This includes the labels, cartons, pills, or vials. Even slight variations are unacceptable as they can introduce bias at the investigational site. Slide 6.5: Investigational medication is very often packed and labeled in one location and stored in another. Maintaining the integrity of the trial depends on supplying effective product and the efficacy of many API s can be compromised when exposed to certain temperatures. To accommodate the temperature sensitivity of investigational medication, there are multiple types of storage condition requirements, ambient or room temperature, refrigerated, frozen or deep frozen. Slide 6.5.1: Some factors that need to be considered when storing and shipping investigational medication include: Was the proper temperature maintained during shipping and storage? Are you sure that no tampering occurred to the product? Also, you will need to account for the special requirements for the handling of narcotics that are in place in many countries. Slide 6.5.2: Release of the investigational medication from the storage location, or the depot, to trial site also needs to be considered. Depots are a local storage and distribution locations established to accommodate trial site areas regionally. Depots may also be set up to supply harder-to-reach trial sites, or locations that have strict requirements with long lead times which can be as many as three months in some countries. Slide 6.5.3: Time also needs to be allotted for country release. In order to release trial kits from a depot, to an investigational site quality release must be

9 performed. Quality release is a review conducted by quality and regulatory personnel that ensures the investigational medication complies with all local and global regulations for good manufacturing practice, or GMP. Some countries have specific release requirements (for example, there may be a limit on expiration dates that is different than other parts of the world). Slide 6.6: Leading up to close out, clinical trial database lock involves the closing of a database after all clinical trial data has been gathered and reviewed, all queries have been resolved, and all issues have been addressed. It s essential that you can prove that the database cannot be altered in any way. Clinical trial database lock is a critical milestone when the trial becomes unblinded so that information can be more freely shared between blinded and unblended personnel. Slide 6.6.1: Close out is a significant step in the supply process as your work can be audited after a trial has ended. It s essential to ensure that you can demonstrate that the trial was managed properly and all investigational medication inventory is accounted for, from manufacturing to subject to destruction. Close out involves not only the destruction of trial materials, but also the reconciliation of your inventory and the lock of the trial database. Attention to detail is critical to make sure each kit is accounted for whether the product was administered, damaged, destroyed, or returned to the sponsor. Slide 6.7: Based on what you have learned to this point in the course, let's see how you would handle the following scenarios. Slide 6.8: In this lesson, you learned that planning is not only performed before a trial begins, but planning is also an iterative practice through all supply phases of the supply chain. Planning considers both known and unknown risk that may occur. Attention to detail and open communication among both sponsor and vendor trial teams throughout the trial is essential to success in the CSC. Slide 7.1: This lesson will cover a review of skills required for a career in clinical trial supply, including project management, communication skills, versatility, and resourcefulness. Slide 7.2: Managing scope, timing, quality, and budget is the crux of project management, and these skills will serve you well in your support of the Clinical

10 Supply Chain. As the previous lesson indicated, being able to "recognize icebergs," or risks ahead of time, is a major factor in making good decisions in the dynamic Clinical Supply Chain. Identifying subtle changes in your data or in the process is key when trying to recognize risk. Slide 7.2.1: The ability to manage timelines, restrictions, and variables in the supply process is also required. Local regulations and requirements are varied, and understanding how to incorporate the appropriate regulatory and company policy requirements into your process to serve a global clinical trial is also needed. For example, managing the timelines involved in applying for a license to conduct a trial in a foreign country is a dynamic process. Application guidelines and rules may vary from country to country and lead time and rules may change from one year to the next. Slide 7.2.2: There are easy to work with countries where you may be able to get a drug to a subject in two days. There are also more challenging countries in which it could take several months to accomplish the same task. In awareness of the complexity of the manufacturing process is also needed. A penchant for investigation and problem solving will serve you well in the CSC. Slide 7.3: Effective communication skills are required for personnel throughout the supply chain. This includes building trust openly and honestly; setting realistic expectations among trial colleagues; tailoring communication for different audiences such as internal business partners, vendors and clinicians at an investigational site; clearly communicating risk, and building excellent working relationships. In person communication supports this, and should be your primary means of communication whenever possible. This can be challenging in a global environment where you may need to rely on video chat via the internet. Slide 7.4: CSC is not an easy job; it can be stressful. The job focuses on identifying and managing risk, adapting to change, and building strong relationships that can help you manage the complexity of a trial. If you thrive on challenges and unpredictability, a position in the Clinical Supply Chain is a job for you. Slide 7.4.1: As mentioned in the previous lesson, there are many environmental factors that can come into play during a trial. Some that are out of our control entirely, such as production issues and Mother Nature. For example, in the United States, Hurricane Sandy recently closed roads and businesses on the east

11 coast for weeks. And, in 2010, the Volcanic Ash eruption in Iceland in 2010 halted international flights for six days over Europe. Slide 7.4.2: Close attention to trial demand changes is essential. CSC exists to try and manage what goes wrong anticipating, mitigating, and managing risk to keep investigational risk sites sufficiently supplied and trial subjects safe. This can be challenging since the demand for investigational medication is not always stable, shelf life is short, and enrollment forecasts are not exact. Slide 7.4.3: Many of your colleagues in the clinical supply chain will be from different cultures so an awareness of, and respect for, different cultural standards is required. This includes taking into consideration the various time zones in which your colleagues are located when scheduling meetings. Included in multicultural awareness is the careful selected use of communication that is needed when working with colleagues in other countries whose primary language is not the same as yours. Avoiding the use of slang and regional colloquialisms is always recommended. Slide 7.4.4: A successful CSC employee must be resourceful, persistent, and assertive. Becoming and remaining aware of your options for gaining the information you need to do your job is needed. Being able to independently seek out information, resources, and personnel is very helpful. And exhibiting a dedication to supporting your team and colleagues will benefit you and your efforts in the Clinical Supply Chain. A personable and dependable employee is a valuable one in the Clinical Supply Chain. Building and maintaining relationships by following through on your commitments, asking for help when you need it, and acknowledging your mistakes will allow you to build trust with your colleagues Slide 7.5: The goal of a pharmaceutical company is to create products that improve people s lives, are safe, and are effective. The Clinical Supply Chain helps to provide product to clinical sites so that the company is able to conduct successful trials. In this activity, you will learn about the different skills needed to be successful in the Clinical Supply Chain role. Slide 7.5.1: There is an industry shift occurring that is pushing the CSC to more efficient planning in order to save costs while not compromising quality and reliability. This exercise helps us think through some of these shifts.

12 Slide 7.5.2: Read each of the following statements and indicate which are True and which are False. Slide 7.6: Developing excellent working relationships is critical to your success in the Clinical Supply Chain organization. Learning how to negotiate to resolve conflicts, and how to build trust, will ensure successful relationships. Negotiation is key to resolving issues. Negotiation is defined as a discussion between two or more disputants who are trying to work out a solution to their problem. Different negotiation styles can be used depending on the situation. Click on the bubbles in the image to learn more. Slide 7.6.2: Trust generates mutual respect among coworkers. When you extend trust to a colleague, it signifies that you have confidence in them and their abilities. Honest communication and open ended questions encourage the sharing of information. The more information you have, the better equipped you are to satisfy the needs of all involved. Taking your goals and the goal of your colleague into consideration will open the floor for discussion and it will build trust. Trust is the foundation of effective communication and collaboration in the workplace. If coworkers feel that they cannot trust each other, they spend more time looking out for themselves and less time being productive. With a lack of trust comes a reduction of collaboration. With a diminished sense of working together towards shared goals, colleagues can eventually develop feelings of isolation that they are on their own. A lack of trust makes everyone s job more difficult. Slide 7.6.3: Read the following questions and indicate which build trust and which erode trust. Slide 7.6.4: A question that requests concrete information, not just a yes or no response, might make for a more relaxed conversation. Can you tell me more about your request? A question that implies or infers something that is not actually stated may seem judgmental, even if it s well intentioned. If you can t handle this, who can I contact? If during a business conversation your colleague said, do I need to go to your manager with this? How would you feel? Probably undermined. A question that requests not only a definitive response, but also the feeling or opinion of your coworker, can indicate that you value their input. Based on your experience, do you think this will work? A question that recaps the information you have is a great vehicle for indicating to your coworker that you

13 are listening to them, or that you have done some research. Given the size of your team, your budget, and the timing of the request, will this be sufficient? Slide 7.7: In this lesson, you learned that there are many valuable skills that are needed for a successful career in the Clinical Supply Chain. These include, but are not limited to, project management, communication skills, attention to detail, versatility, resourcefulness, and persistence. Slide 8: Before we end this course, let s review some key points covered in this course. Lesson one provided an overview of the types and phases of clinical trials and let you know how the Clinical Supply Chain fits into a clinical trial. Lesson two defined important terms you will encounter in the Clinical Supply Chain and stressed the importance of enrollment forecasting and the CSC s role in managing inventory. Lesson three presented the key skills and competencies required for a successful career in clinical trial supply. Slide 9: Congratulations, you have completed the clinical supply overview course. Now you should be able to: Identify the types and phases of clinical trials and how the clinical supply chain fits into a clinical trial Define clinical trial terms such as First Patient In and First Patient Dosed Understand the importance of enrollment forecasting and CSC s role in managing inventory, and Recognize key skills required for a successful career in clinical trial supply. Auto-navigate to final slide (not shown in the menu): Thanks for attending. To exit the course click the end button at the top right of the interface.