Chapter 22: Pharmaceutical Industry and Regulatory Agency Drug Information

After completing this chapter, the reader will be able to

• Design an organization chart for a pharmaceutical company.

• Discuss opportunities for health care professionals (HPs) within the pharmaceutical industry.

• Describe how HPs are regulated in the pharmaceutical industry.

• Determine acceptable interactions between pharmaceutical companies and practitioners.

• List the components of a standard response and personalized letter.

• Explain the importance of collecting adverse event information.

• Identify pharmaceutical industry–associated organizations.

• Recommend methods for communicating safety information to consumers.

• Describe the role of the Division of Drug Information (DDI) at the Food and Drug Administration (FDA).

• List the main differences between the DDI and a typical drug information center.

• Illustrate the different types of drug information services provided by the FDA.

• Identify factors that guide selection of a specific FDA-sponsored resource or Web site.

• Discuss student and professional opportunities within the FDA.

1. Pharmaceutical companies' scientific or medical divisions are staffed with highly trained health care professionals (HPs) working in a multitude of specialized fields.

2. Medical information specialists respond to inquiries, provide training, and draft materials for a variety of internal and external audiences.

3. Pharmaceutical companies are regulated both externally by the FDA and internally by standard operating procedures (SOPs).

4. The FDA's draft Guidance for Industry “Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices” describes the FDA's current thinking about how manufacturers and distributors of prescription human drug products can respond to unsolicited requests for information about unapproved indications (off-label information) related to their FDA-approved or cleared products.

5. Unsolicited requests are those initiated by persons or entities that are completely independent of the relevant firm.

6. The FDA considers requests for off-label information that are prompted in any way by a manufacturer or its representatives to be solicited.

7. Interactions between pharmaceutical companies and HPs are defined, but not regulated, by a code of conduct established by the Pharmaceutical Research and Manufacturers of America (PhRMA) through the revised version of the Code on Interactions with Health Care Professionals.

8. Clinical response letters are written correspondence that contains company-approved content in response to an unsolicited request for medical information.

9. Patient variability, clinician experience, and previously unaddressed questions require personalized responses that cannot be fulfilled with a standard response letter.

10. Adverse drug experiences, or adverse events, are required to be reported to the FDA by pharmaceutical companies.

11. The mission of the FDA is to protect “the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation's food supply, cosmetics, and products that emit radiation.”

12. Timely communication of important drug safety information provides HPs, patients, consumers, and other interested persons with access to the most current information concerning the potential risks and benefits of a marketed drug, helping them to make more informed treatment choices.

13. The FDA uses various tools and methods to communicate drug safety information to the public.

14. The mission of the Division of Drug Information (DDI) is to optimize the Center for Drug Evaluation and Research's (CDER) educational and communication efforts to the global community. The DDI supports the FDA's mission to promote and protect public health.

15. The DDI has built effective internal and external interactions to provide timely, accurate, and useful information through both traditional and social media channels.

16. In addition to dedicated drug safety communication (DSC) channels, the DDI has several proactive and innovative tools to communicate information about human drug products to the public.

17. The FDA offers many opportunities for health professional students. One of the most popular programs is the FDA Pharmacy Student Experiential Program. Student opportunities are also available within the United States Public Health Service (USPHS) Commissioned Corps.

There are many roles available to health care professionals (HPs) within the pharmaceutical industry and regulatory agencies focused on public health. In industry, these roles span medical education, publications, marketing, medical information, and more. In public health agencies, the roles are usually separate functions supporting the organizational mission statement and generally pertain to protecting the health of all Americans and providing essential human services, especially for those who are least able to help themselves. Job titles and descriptions may vary slightly from company to company or agency to agency, but the importance of HPs within each area is constant across organizations.

Throughout this chapter the reader will become familiar with the organization of a pharmaceutical company, professional mentoring relationships, industry's regulated interactions with outside HPs, fulfillment of a medical information request and responses to unsolicited inquiries, the many roles and career paths available to HPs in industry, and the importance and requirements of adverse event reporting and postmarketing surveillance. Information surrounding the role of medical information within a regulatory agency, specifically the Food and Drug Administration (FDA), will then be presented. At the end, the reader should have a general knowledge of the roles and responsibilities of HPs employed in the pharmaceutical industry and FDA, the expectations practitioners receiving medical information from a pharmaceutical company or regulatory agency may have, and how to pursue opportunities and careers within the pharmaceutical industry or a regulatory agency with a public health mission.

❶ Pharmaceutical companies' scientific or medical divisions are staffed with highly trained HPs working in a multitude of specialized fields (see Figure 22–1).¹ The following section will highlight specific opportunities within the pharmaceutical industry for HPs.

CUSTOMER RESPONSE CENTER

Customer response center representatives are the first-line response team for unsolicited requests∗ for medical information. HPs in this setting are well trained for customer response center representative positions. Customer response center HPs are faced with a variety of responsibilities as the first line of communication with patients and providers. Responsibilities include capturing adverse events (AEs) that are reported and triaging nonmedical and medical information requests (MIRs). Customer response center HPs are provided with a variety of tools, including, but not limited to, product labeling (or package inserts), response letters, question and answer (Q&A) documents, and clinical topic overviews, typically drafted by peers in the medical information division to assist in answering unsolicited requests for product information. A guidance document, published by the FDA, regarding responding to unsolicited requests, also offers industry the FDA's current thinking on this topic.² Customer response center staff use product labeling, response letters, and literature searches to assist them in responding to MIRs. HPs serving in this capacity must have excellent verbal communication skills and are highly trained in effectively searching for information. Some MIRs may require additional research or analysis resulting in the customer response center HPs escalating the inquiry to a medical information specialist for further investigation.

MEDICAL INFORMATION

❷ Medical information specialists respond to inquiries, provide training, and draft materials for a variety of internal and external audiences. Medical information specialists are HPs who respond to unsolicited MIRs, write and update response letters, conduct scientific analysis of medical literature topics, review promotional materials, develop Academy of Managed Care Pharmacy (AMCP)-formatted dossiers for formulary consideration, and train company staff (e.g., sales force, peers, account managers, and others [see Figure 22–2]).^3,4

Medical information specialists also respond to MIRs that are escalated to them by customer response center representatives. Escalation, or the transfer of MIRs, occur frequently when the customer response center representatives do not have the resources necessary to formulate a response. Frequently, escalations involve questions about off-label use. This will be discussed later in the section entitled Regulation of Health Care Professionals in Industry. Medical information specialists may have access to additional resources, such as comprehensive reports from clinical trials, information provided to study investigators, marketing materials, posters and abstracts, and contacts in other departments, which makes them invaluable resources for analyzing and synthesizing information.

MEDICAL SCIENCE LIAISONS

Medical science liaisons (MSLs) originated as a highly specialized customer response center representative. An MSL supports, and is supported by, the scientific affairs and medical information team. MSLs have a close working relationship with key opinion leaders and are expected to engage in clinical conversations ranging from broad clinical guidelines to patient-specific care (Table 22–1).⁵ MSLs are expected to attend national meetings and provide comprehensive clinical presentations. MSLs may focus on one product or therapeutic area, so there may be overlapping MSLs working for the same company in one location, supporting different products and specialty areas, or vice versa, there may be one MSL in a remote location responsible for multiple products and therapeutic areas.

OUTCOMES RESEARCH

Outcomes research specialists are known in some companies as field-based outcomes liaisons or FBOLs. This position is similar to that of an MSL, except the focus of FBOLs may be to demonstrate the value of a product to managed care organizations, pharmacy benefit managers (PBMs), or other HPs in similar decision-making roles through the generation of outcomes data. Outcomes data typically provides studies focused on identifying, measuring, and evaluating the end result of a health care service or treatment. For example, a company that is marketing an antiplatelet medication might request that their FBOLs demonstrate to customers the value of the product through quality-life years gained or may request that the FBOLs create a risk stratification tool (e.g., stratification of risk for patients with cardiovascular disease) to assist clinicians in determining appropriate therapy options for their patients.

MEDICAL EDUCATION

HPs in medical education evaluate funding requests for continuing medical education (CME), continuing education (CE), and other programs submitted by qualified organizations. Grants are reviewed by medical education to ensure the program outlined in the grant addresses specific needs of clinicians in clinical practice and is consistent with the company's educational goals and objectives for a specific therapeutic area.¹ CME and CE programs must meet standards set by the corresponding accrediting body for the audience and should follow guidance documents published by the FDA.^6,7

MEDICAL AFFAIRS

Medical affairs HPs typically oversee phase IV clinical trial programs and may also be involved with preclinical studies through phase IV or postmarketing studies. These HPs are primarily conducting research on marketed pharmaceuticals in areas of high therapeutic demands or information need. Medical affairs HPs play a key role in shaping the direction of future clinical development including where to focus resources on specific disease states, what drug candidates to support in human clinical studies, and what marketed drugs to develop with new indications or to study through the investigator-initiated study process. In addition, medical affairs staff is involved in a variety of tasks with peers in medical information, marketing, and with key opinion leaders in the field. These tasks include reviewing promotional and marketing materials, supporting phase IV clinical trial sites and maintaining communication with trial investigators, reviewing product labeling, formulary dossiers, training materials for promotional and education purposes, and developing and presenting original research in the form of posters, abstracts, and manuscripts. Medical affairs HPs are responsible for reviewing these materials for accuracy of medical information and to ensure that the final products (e.g., promotional materials, package inserts) are unbiased, fair balanced, and not misleading.¹

MARKETING

HPs in the marketing division of a pharmaceutical company are responsible for developing the branded messages for a product. See Chapter 23 for further information on pharmaceutical marketing. The tag lines and main selling points seen in journal advertisements, on Web pages, and on printed materials are created by the marketing division. It is important for HPs in marketing to understand the clinical practice environment of their peers so they can provide useful, valuable tools and materials. Marketing drafts a plethora of promotional materials from journal and television advertisements to functional educational tools such as dose conversion guides. All of these materials are then reviewed by peers in medical information and medical affairs, and other internal business partners in regulatory and legal.¹

PUBLICATIONS

The team of HPs in the publications department has the important task of ensuring the appropriate information reaches the appropriate audience. For example, a company coming to market with a new blood pressure medication would want its publications department to create a plan that would publish trial data (preclinical through post hoc and review data) concurrently with major meetings of prescribers treating blood pressure. The publications department ensures that reprints of posters, abstracts, and manuscripts are readily available for dissemination to HPs in the field. HPs in this department are also responsible for reviewing the final content of publications and drafting comments if necessary, often through a partnered review process with medical affairs and medical information, to make certain accurate information is available for practitioners in clinical practice.¹

As outlined in this section, HPs have many varied opportunities within the industry. Each of the functions described previously abide by a set of rules and regulations. Understanding and complying with these rules and regulations help ensure the success of industry-employed HPs.

❸ Pharmaceutical companies are regulated both externally by the FDA and internally by standard operating procedures (SOPs).^8,9 To help internal staff understand the regulations governing their department's duties and establish an efficient methodological approach to the business, SOPs are developed internally by the company.^2,3 While practitioners in clinical practice may not be governed by the same regulations as industry, having a basic understanding of company's regulations will help align the external clinicians' expectations with what can be provided by internal industry HPs.

CODE OF FEDERAL REGULATIONS

The Code of Federal Regulations (CFR) Title 21 regulates the United States (U.S.) pharmaceutical industry throughout the life cycle of a product, from before the investigational new drug application (pre-IND) through phase IV clinical trials, including postmarketing data collection.^6,7,10–14 HPs working for a U.S. pharmaceutical company must achieve a thorough understanding of these regulations to ensure compliance with the regulations that pertain to their daily duties.

FDA GUIDANCE DOCUMENTS

FDA guidance documents represent the FDA's current thinking on a topic. Guidance documents do not create or confer any rights for or on any person and do not operate to bind the FDA or public. Guidance documents are very useful because they expand upon the regulations. ❹ The FDA's draft Guidance for Industry, “Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices,” describes the FDA's current thinking about how manufacturers and distributors of prescription human drug products can respond to unsolicited requests for information about unapproved indications (off-label information) related to their FDA-approved or cleared products. An important portion of this guidance document for pharmaceutical companies is the discussion of unsolicited requests that are encountered through emerging electronic media. First though, several important definitions are provided with examples.

UNSOLICITED REQUESTS

❺ Unsolicited requests are those initiated by persons or entities that are completely independent of the relevant firm. (This may include many HPs, health care organizations, members of the academic community, and formulary committees, as well as consumers such as patients and caregivers.) Requests that are prompted in any way by a manufacturer or its representatives are not unsolicited requests.

Two Types of Unsolicited Requests

Nonpublic unsolicited requests

A nonpublic unsolicited request is an unsolicited request that is directed privately to a firm using a one-on-one communication approach. For example: An individual calls or e-mails the medical information staff at a firm seeking information about an off-label use. In this case, neither the request nor the response would be visible to the public.

Public unsolicited requests

A public unsolicited request is an unsolicited request made in a public form, whether directed to a firm specifically or to a forum at large. For example: During a live presentation, an individual asks a question, directed to a firm's representative but heard by other attendees, regarding off-label use of a specific product. This request is a public request. Similarly, a response by the firm that is conveyed to the same audience as the original question would be considered a public response. Another example is if an individual posts a question about off-label use of a specific product on a firm-controlled Web site (or a third-party discussion forum), that is visible to a broad audience. The request could be directed to a firm specifically or posed to users of a discussion forum at large. This request is a public online request. Similarly, a response by the firm that is visible to the same audience as the original question would be considered a public online response.

SOLICITED REQUESTS

❻ The FDA considers requests for off-label information that are prompted in any way by a manufacturer or its representatives to be solicited. Such solicited requests may be considered evidence of a firm's intent that a drug be used for a use other than that specifically approved by the FDA. For example, if a firm announces results of a study via a microblogging service (e.g., Twitter) and suggests that an off-label use of its product is safe and effective, any comments and requests received as a result of the original message about the off-label use would be considered solicited requests.

The FDA has long taken the position that firms can respond to unsolicited requests for information about FDA-regulated medical products by providing truthful, balanced, nonmisleading, and nonpromotional scientific or medical information that is responsive to the specific request, even if responding to the request requires a firm to provide information on unapproved indications or conditions of use.

STANDARD OPERATING PROCEDURES

SOPs provide additional guidance to employees, supplementing regulations from federal and state government agencies. SOPs allow a company to digest federal regulations, making them applicable to employees and their everyday job functions.¹⁵ The pharmaceutical industry employs HPs and lawyers in regulatory affairs to ensure SOPs are up-to-date and provide employees proper guidance for complying with all applicable regulations.

HPs within the pharmaceutical industry hold themselves to a high standard when it comes to providing accurate, concise, and timely information. ❼ Interactions between pharmaceutical companies and HPs are defined, but not regulated, by a code of conduct established by Pharmaceutical Research and Manufacturers of America (PhRMA) through the revised version of the Code on Interactions with Health Care Professionals.¹⁶ The prior edition, from 2002, addressed primarily products being marketed and activities prior to the launch of a medication. The updated version released in January 2009 includes more specific guidance regarding the interactions between pharmaceutical industry representatives and HPs. The goal of these regulations is to provide transparency to HPs and patients alike as to the motives and channels through which industry conducts business with external customers and business partners.¹⁷

HPs and patients may contact a pharmaceutical company with questions regarding a medication when an answer is not readily available. A typical process for responding to these questions is described in Figure 22–3.

RESPONSE LETTERS

❽ Clinical response letters are written correspondence in response to unsolicited requests for medical information. The use of evidence-based medicine in response letters allows consumers and HPs to be confident they are receiving fair-balanced, unbiased, and not misleading information.¹⁸ Response letters are usually created according to a template for consistency (see Table 22–2) and drafted in anticipation of, or in response to, frequently asked questions.¹⁰ Solvay Pharmaceuticals determined that prior to the launch of a product, response letters took four to 8 hours each to create. The time spent by Solvay's staff to create a response letter following launch significantly increased, taking 4 to 7 days to create. This was directly related to the increased workload and the continuous arrival of new MIRs.¹⁹ Once a product is available on the market, the number and complexity of MIRs is likely to increase. This increases HP's total workload and, therefore, increases the time it takes to complete individual tasks, such as creating response letters. Because of this, the time to create a response letter and respond to an MIR may differ from Solvay's results.

Pharmaceutical companies' response letters are created from source documents in response to frequently asked questions and are peer reviewed internally.²⁰ Standard response letters developed by companies may be either proactive or reactive. For example, if the evening news reports that a marketed drug, similar to Drug A^® causes yellow stripes to appear on patients' skin, the company that makes the competitor to Drug A^® should react immediately by developing a response letter to address questions from HPs and patients on this adverse event (i.e., reactive). In another example, the sponsor of Drug A^®, may wish to proactively develop a response letter in anticipation that the likelihood of experiencing yellow stripes with Drug A will be frequently asked, based on the report of this reaction with the competing similar drug. Using the example above, the company that manufacturers Drug A^® may need more than 1 day to prepare a complete, concise response and, thus, in the meantime may tell customers they are currently researching the issue in question. When this response is provided, the requestor should expect a complete response to be delivered in a timely manner (see Appendix 22–1 for an example of a response letter).

UNIQUE RESPONSES FOR NONFREQUENTLY ASKED QUESTIONS

❾ Patient variability, clinician experience, and previously unaddressed questions require personalized responses that cannot be fulfilled with a standard response letter. HPs in the customer response center and medical information department then use their literature search and evaluation skills to determine if relevant information has been published or is available through internal company data (also known as data on file) that addresses the inquiry.²⁰ If no information is found, the requestor is contacted with the results and a statement that the company cannot provide any information. If relevant publications are found, a response is drafted that includes the citations or reprints (when copyright allows) of the information and this is provided to the requestor along with a verbal conversation (if possible) to discuss the findings and applicability to the requestor's situation.²² Requestors expect their inquiry to be addressed in a timely manner and often prefer a verbal answer, allowing for a peer-to-peer discussion and the option to request written information.²³ All MIRs are valuable and provide timely information to the company regarding the current state of their product in clinical practice. MIRs are typically compiled and analyzed periodically to identify trends and patterns. These trends are published internally in the form of periodic reports; this may signal to a company that a response letter is needed on a particular topic that is reported frequently, identify new educational gaps, or lead to the development of new product formulations. Periodic reports may alternatively signal to a company that previous “hot topics,” or frequently asked questions, are no longer of interest to practitioners in clinical practice; often times identifying new areas of interest that practitioners need to have addressed.

FDA approval of a medication does not denote complete safety of the product. It is important to keep in mind that any medicine capable of curing or treating a disease may also have the potential for serious adverse events. An adverse drug experience is defined by the CFR Title 21, Section 314.80—Postmarketing reporting of adverse drug experiences as, “Any adverse event associated with the use of a drug in humans, whether or not considered drug related, including the following: an adverse event occurring in the course of the use of a drug product in professional practice; an adverse event occurring from drug overdose whether accidental or intentional; an adverse event occurring from drug abuse; an adverse event occurring from drug withdrawal; and any failure of expected pharmacological action.”²⁴ ❿ Adverse drug experiences, or adverse events, are required to be reported to the FDA by pharmaceutical companies. It is the charge of the pharmaceutical company to monitor these risks once the drug is on the market, also known as the postmarketing phase of the drug's life cycle.^24,25

Pharmaceutical companies learn of adverse events in a variety of ways, including postmarketing trials, publications, customer calls, physician reports, social media sites, blogs, and in some cases, even by being in close proximity to a personal conversation. The reporting process may vary from company to company so long as the information required by the FDA is reported with each adverse event through completion of FDA Form 3500A. FDA Form 3500A differs from voluntary FDA Form 3500 and FDA Form 3500B, which are intended for HPs and consumers, respectively. FDA Form 3500A requests such information as patient demographics, medication identifiers, and a description of the adverse event.²⁶

Pharmaceutical companies are dynamic entities that are constantly evolving. In today's media it is possible to stay up-to-date with new information from industry including drug approvals, publications, and presentations, as well as safety alerts and labeling changes. The Drug Information Association (DIA) and other industry-associated organizations (see Table 22–3) are resources for pharmaceutical company information. HPs in clinical practice should familiarize themselves with these reliable sources for industry news so that they can share current industry information with their patients and other clinicians.

The Department of Health and Human Services (HHS) is the U.S. government's principal Agency for protecting the health of all Americans and providing essential human services, especially for those who are least able to help themselves. HHS is headed by the Secretary who is the chief managing officer for the HHS family of agencies, including 11 operating divisions, 10 regional offices, as well as the Office of the Secretary.^11,27Table 22–4 describes each agency and office and provides the mission statement for each. This illustrates how HHS programmatic areas each have their own goals and objectives. The composition of each agency or office under HHS varies. Ultimately, a common theme can be applied to these agencies. HHS creates agencies to address specific areas of public health. Each organization is further divided into groups depending on the roles and responsibilities assigned to the agency. These agencies are further divided into centers supporting the role assigned to the agencies. In the United States, there is a center or office available to provide some regulatory guidance on most, if not all, areas of public health.

MISSION OF A FEDERAL AGENCY IN THE DEPARTMENT OF HEALTH AND HUMAN SERVICES

⓫ The mission of the FDA is to protect “the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation's food supply, cosmetics, and products that emit radiation.”¹² The FDA consists of nine centers and offices. Figure 22–4 shows the FDA's organization chart. The Center for Drug Evaluation and Research (CDER) is of particular interest to pharmacists and other HPs because of the Center's responsibility for ensuring that drug products are of high quality, and are safe and effective for their intended use.²⁴ CDER provides the public with access to accurate, science-based information needed to evaluate the risks and benefits of human drugs and strives to provide easily retrievable information about human drugs through the FDA Web site, www.fda.gov.

COMMUNICATION OF DRUG SAFETY INFORMATION

⓬ Timely communication of important drug safety information provides HPs, patients, consumers, and other interested persons with access to the most current information concerning the potential risks and benefits of a marketed drug, helping them to make more informed treatment choices.²⁸ The FDA's safety assessment of medicines does not diminish after drugs are approved for marketing.¹⁵ Although the premarket phase of study is very intensive, much work still remains to monitor approved drugs over time. Once a drug is approved and marketed, the FDA often gains additional information as the drug is used and studied in broader and more diverse populations. Such information helps provide a better picture of a drug's benefits, risks, and enables FDA to give HPs and patients the latest information on potential or newly identified risks, and strengthens FDA's ability to safeguard patients against unacceptable risks.

SAFETY COMMUNICATION TOOLS

The FDA has created effective and ongoing relationships with a wide array of trade and professional associations, patient advocacy and consumer groups, safety organizations, media, and other entities. When drug safety issues arise, the FDA contacts these groups and works with them to communicate the safety issue to their constituencies. ⓭ The FDA uses various tools and methods to communicate drug safety information to the public. Important tools used in this effort include, but are not limited to, FDA-approved prescribing information (i.e., drug labeling) and a postmarket communication tool called a Drug Safety Communication (DSC), along with other important tools and methods used to communicate drug safety information to the public.

LABELING UPDATES

The drug labeling, or written material that accompanies drug products, is the most complete single source of information on the drug. A change to the drug label may have tangible benefit in expanding the education of risks, benefits, and optimal usage of marketed drugs.

Over time, new information often emerges about a product, such as:

• Side effects

• Dosing

• New indications

This new information is added by the manufacturer to the drug's label so consumers and HPs have all the information necessary for safe and effective use of the drug. All changes to a drug's label must be approved by the FDA. The manufacturer sends proposed changes to the FDA for review and, revision if necessary.

Risk Evaluation and Mitigation Strategies

The creation of Risk Evaluation and Mitigation Strategies (REMS) is one of the many methods of communicating safety information to patients and practitioners beyond the traditional labeling.¹³ REMS were enacted on September 27, 2007, as part of the FDA Amendments Act (FDAAA). A REMS provides information regarding the risks of a specific medication in an effort to ensure the benefits will outweigh the risks for a potential patient, mitigating the likelihood of a negative outcome with the product's use. Following the enactment of FDAAA, REMS programs may be requested by the FDA for a particular drug as part of the NDA process. A REMS may also be submitted voluntarily as part of the NDA prior to receiving a request from the FDA. Finally, a REMS may be requested by the FDA after a drug receives approval. (See Figure 22–5.) General REMS program requirements are outlined by the FDA, subject to the FDA's approval, and enforceable through penalties.¹³

Prior to the codification of REMS, risk minimization action plans (RiskMAPs) were established. RiskMAPs are safety plans that are designed to achieve prespecified goals and objectives¹⁷ to minimize known safety risks of a medication while concomitantly maintaining the benefits. RiskMAPs can employ one or more tools to achieve its set goals and objectives (see Table 22–5 for more detail). Some drug and biological products that previously were approved and/or licensed with RiskMAPs are now deemed to have a REMS.²⁹

Medication Guides and Patient Package Inserts

Medication Guides and patient package inserts (PPI) are other examples of safety measures required by the FDA prior to 2007.^10,13 Medication Guides are paper handouts issued with certain prescription medications to address safety concerns specific to that drug or drug class in an effort to reduce adverse events.³⁰ All Medication Guides are subject to the requirements of 21 CFR 208, which means for HPs that the medication guide must be provided directly to the patient or their agent when the drug product is dispensed, unless an exemption applies.²¹ Alternatively, PPIs are required to be issued with oral contraceptive products to satisfy the requirement that patients using these products are fully informed of all the potential risks and benefits.¹¹ Manufacturers of oral contraceptives may request informal guidance from the FDA to help them create a PPI.

Drug Safety Communications

A Drug Safety Communication (DSC) is a specific tool used by the FDA to communicate to the public important information about safety issues, including emerging safety information, about marketed drugs.²⁰ DSCs are standardized electronic communications posted on the FDA Web site. Written clearly, DSCs are targeted to both HPs and patients. DSCs generally communicate the following information:

• A summary of the safety issue and the nature of the risk being communicated

• The established benefit or benefits of the drug being discussed

• Recommended actions for HPs and patients, when appropriate

• A summary of the data reviewed or being reviewed by the FDA

The DSC is the FDA's primary safety communication tool for important postmarket drug safety issues. In the past, safety communications were issued by the FDA in a variety of formats. They were issued under different titles and targeted to different audiences. Safety communications have been issued under the titles Early Communications about Ongoing Safety Reviews, Public Health Advisory, Patient Information Sheet, Healthcare Professional Sheet, and Alerts on Patient Information and Healthcare Professional Sheets. In early 2010, the FDA began using a single communication tool—the Drug Safety Communication.

It is important to note that while a DSC communicates important safety issues about marketed drugs, it is not a crisis communication document. If a drug product is defective or tainted, or poses some other form of immediate danger, the FDA uses other communication tools, such as Public Health Alerts, press releases, stakeholder calls, and media briefings, to inform the public rapidly.

The focal point at the FDA for public inquiries related to human drugs is the Division of Drug Information (DDI). ⓮ The mission of the DDI is to optimize CDER's educational and communication efforts to our global community. The DDI supports the FDA's mission to promote and protect public health.³¹ The DDI is staffed with a team of pharmacists and other HPs. They provide expert advice and guidance on a broad range of CDER activities. This requires the DDI's staff to have an extensive knowledge of human drug products and the regulations guiding drug development and marketing. The role of the DDI is unique from hospital and academic-based drug information centers because it serves the general public domestically and internationally through direct contact via phone, letter, and e-mail. The DDI also works internally to support the center by collaborating with experts throughout the center to effectively communicate important and emerging topics.

The division has several unique characteristics that differentiate it from a more traditional drug information centers. First, the DDI has a unique visitor (customer) makeup. Visitors include the United States and international regulated industry, consumers, HPs, insurance companies, academia, law enforcement, attorneys, and other government agencies. The majority of requests received from U.S. visitors are from consumers, followed by industry and HPs. Industry and small businesses make up most of international requests.

It is not uncommon for the DDI to prepare responses for a wide variety of requestors (Table 22–6). The preponderance of the information used by the DDI to answer drug information queries comes directly from the FDA's Web site. The DDI's staff are highly trained experts in drug information and retrieval. In fact, DDI's drug information specialists are able to answer most inquiries without further consult by using their knowledge of FDA's available public resources. Sometimes, an inquiry cannot be addressed using readily available information. In that case, the DDI's specialists work with subject matter experts across the center to find information suitable to answer the inquiry.

DDI SERVES CDER AND PUBLIC HEALTH

Drug information services provided by the DDI fit generally into one of three categories: correspondence, dissemination, and other (Table 22–7). Correspondence represents a majority of direct contact provided by the DDI. In an average month, the DDI responds to 2000 e-mails, 6000 telephone calls, and over 100 letters. The most common inquiries are related to regulatory issues, such as the drug review and approval process (Table 22–8). Many times the same question will be asked in a different way by a different requestor. For example, a consumer might call FDA asking for more information about a DSC. The same question might be addressed by an HP wanting to know the impact on clinical practice and possible labeling changes.

FDA DRUG INFORMATION RESOURCES

⓯ The DDI has built effective internal and external interactions to provide timely, accurate, and useful information through both traditional and social media channels.Table 22–9 lists commonly used FDA Web sites and the intended purpose of each page. In order to select the most appropriate FDA sponsored resource/Web site, practitioners should have a basic understanding of what Web sites are available and what information is provided. Table 22–9 provides a brief overview of these Web sites. Practitioners are strongly encouraged to visit and explore these Web sites to become familiar with what is offered.

⓰ In addition to dedicated DSC channels, the DDI has several proactive and innovative tools to communicate information about human drug products to the public. Information is disseminated through DDI's listservs, RSS feeds, CDERLearn continuing education (CE) programs, videos, Twitter, radio, and audio podcasts. All of these examples represent new ways to promote the safe and effective use of human drug products.

CDER Small Business and Industry Assistance

Most DI centers would not have a component that serves industry, which is a unique characteristic of this federal DI center. The DDI is the home of CDER's Industry and Small Business Assistance Program and interacts with regulated industry by assisting domestic and international industry seeking timely and accurate information relating to development and regulation of human drug products. SBIA outreach activities include a series of online Webinars and live workshops held around the United States. Inquiries are received, triaged to subject matter experts if necessary, and responses are coordinated from the CDERSBIA@fda.hhs.gov e-mail account. Additional key elements of the industry assistance program are monthly Webinars and CDERLearn CE programs. These are methods by which the FDA educates specific audiences about the safe use of medicine, drug regulatory process, vital role HPs play to assist FDA in fulfilling its duties, and many other important issues with the added benefit of CE credit for pharmacists, physicians, and nurses, many of whom work in industry.

CDER TRADE PRESS

An additional team within the DDI, the CDER Trade Press team, provides members of the trade press with accurate and timely information regarding CDER policies, programs, and initiatives. In addition to facilitating interactions between trade press and FDA subject matter experts, CDER Trade Press also alerts FDA leadership and staff to relevant FDA coverage in the trade media. Relationships with members of the trade press are fostered, and maintained by this unique team of practitioners. The CDER Trade Press team provides general and ongoing assistance to the FDA's Field Office Public Affairs Specialists (PASes) and Public Affairs Liaisons (PALs).

SOCIAL MEDIA OUTREACH

The DDI uses social media to reach audiences that prefer to receive the latest drug information in a variety of media formats. The DDI tweets the latest drug information and may be followed on Twitter @FDA_Drug_Info. FDA Drug Info Rounds is a series of training videos for practicing clinical and community pharmacists written and casted by DDI pharmacists. These videos may be viewed on the FDA's Web site and YouTube. Audio podcasts are broadcast in conjunction with the release of each new DSC. If interested, a person may find and subscribe to the FDA's Drug Safety Podcasts on iTunes and the FDA's Web site RSS feed.

GLOBAL ALLIANCE OF DRUG INFORMATION SPECIALISTS (GADIS)

DDI networks with fellow drug information specialists around the world through the Global Alliance of Drug Information Specialists (GADIS). GADIS advances public health by promoting partnerships among drug information pharmacists in academia, hospitals, and federal government. GADIS establishes a community among DI specialists to support collaborative strategies, a forum for the exchange of evidence-based best practices, and an opportunity to gain insights and feedback from peers to support collaborative strategies on critical trends and transformations for addressing FDA regulatory actions. GADIS offers online Webinars with speakers from within the FDA, and external experts on topics such as the implementation of REMS programs. GADIS also provides a monthly News & Notes service to its members. GADIS News & Notes highlights important FDA information to drug information specialists that occurred over the prior calendar month.

There are several opportunities for both current and future HPs within the FDA.

FOR THE STUDENT

⓱ The FDA offers many opportunities for health professional students. One of the most popular programs is the FDA Pharmacy Student Experiential Program.³²Student opportunities are also available within the United States Public Health Service (USPHS) Commissioned Corps.¹³ The experiential program provides an opportunity for students to gain experience working in various divisions within the FDA. Depending on where the student is placed, he or she will have the chance to learn about the FDA's multidisciplinary processes for addressing public health issues involving drugs, biologics, or medical devices. Pharmacy students who complete the FDA Pharmacy Student Experiential Program gain unique experience in regulatory affairs, which proves beneficial to their future careers.

The Commissioned Corps created the Commissioned Corps Officer Student Training and Extern Program (COSTEP) for students studying in the health professions field. There are two programs: the Junior COSTEP and Senior COSTEP. Students in selected health fields can apply to the Junior COSTEP program if they have completed at least one to 2 years of their professional program. The Junior COSTEP program takes place during school breaks and most assignments last anywhere from 1 to 4 months. There is no obligation to commit or work for the Commissioned Corps after graduation as this opportunity is focused on allowing students to experience the program before joining. One major benefit for those students enrolled in the COSTEP programs is the diverse opportunities available after completion of the program. Some have gone on to provide clinical services in the Indian Health Service, work in labs at the National Institutes of Health, provide care to patients in the Bureau of Prisons, or join agencies within the FDA or Centers for Disease Control, just to name a few. For those students who wish to find out more information or apply, they are encouraged to visit the U.S. Public Health Service Web site at http://www.usphs.gov/student/.

FOR THE PHARMACY GRADUATE

Postgraduate opportunities for students are also available with the FDA. One opportunity is the Regulatory Pharmaceutical Fellowship.¹⁴ The purpose of this fellowship is to develop candidates with advanced experience in the medical and regulatory aspects of drug information dissemination, drug safety, or drug marketing and advertising. The program exposes fellows to three areas of regulatory pharmaceutical experience: FDA, academia, and pharmaceutical industry.

Only a few of the potential opportunities for health professional students are described in this chapter. There are several opportunities for students interested in regulatory affairs beyond what is described here, and students are encouraged to research and contact those programs directly for further information.

FOR THE PROFESSIONAL

Due to new legislation, CDER has an ongoing need to recruit qualified HPs in order to carry on the mission of the FDA. HPs have several opportunities to serve either as civil service or join the U.S. Commissioned Corps. Physicians are needed to help evaluate submitted clinical trial data of new drugs for safety and efficacy. Pharmacists are needed for a variety of duties including reviewing, evaluating, and recommending approval (or nonapproval) of new and generic drugs. Scientists evaluate the technical portions of applications such as INDs and NDAs. Mathematical statisticians and computer specialists are hired for statistical and technical support of human drug product reviews. Consumer safety officers are vital to managing and monitoring regulatory teams in certain divisions. The consumer safety officer is sometimes referred to as a project manager or division liaison and often these roles are filled with biologists, chemists, pharmacists, nurses, physicians, engineers, and others. The team of HPs working at the FDA is diverse and so are the opportunities to help fulfill the mission of assuring the quality, safety, and efficacy of drugs available to the American public.

Pharmaceutical companies and regulatory agencies provide many services to and have many opportunities for HPs. Pharmaceutical companies' scientific or medical divisions are filled with highly trained HPs working in a variety of specialized fields in order to provide medical information and support for various brands marketed by the company. Efforts are currently ongoing to make the pharmaceutical industry more transparent in the way they conduct the business of drug development and product marketing. Regulatory agencies are also focusing on ways to be more transparent, and monitor and improve the communication of the benefit/risk equation to the general public. The DDI offers traditional and social media channels to those seeking regulatory drug information. Most pharmaceutical companies have detailed and structured processes for responding to clinician's questions. The DDI uses effective internal and external interactions to provide timely, accurate, and useful responses to individual inquiries. An informed HP is a professional who is aware of the valuable information available from industry and FDA, can effectively communicate safety and risk information, and dedicates their career to positively impacting public health.