"Choosing the Right Regulatory Career" looks at the wide range of opportunities available to those interested in the regulatory profession.
The 21 authors, all experienced regulatory professionals, discuss the role of the regulatory professional in a variety of settings including large and small prescription drug companies, generic pharmaceutical companies, medical device and IVD manufacturers, Institutional Review Boards and consultancies, as well as specialties such as CMC, regulatory intelligence, promotional regulatory and medical writing.
The experienced authors also reflect on the paths they took into the regulatory profession.
The following is excerpted from Choosing the Right Regulatory Career, copyright © 2011 Regulatory Affairs Professionals Society.
Chapter 17. Your Career as a Biopharmaceutical Regulatory Writer
One option for a career in regulatory affairs is becoming a regulatory writer in the biopharmaceutical industry. This profession is acknowledged as meaningful and challenging, and regulatory writers are recognized as vital to the industry. Regulatory writers are employed in biotechnology, pharmaceutical and medical device companies, as well as contract research organizations (CROs), and can be full‑time staff members or consultants to all of the above. This chapter describes the work of a regulatory writer in the field of drug research. It explains the fundamental knowledge required to perform the work and the specialized knowledge needed for success. Its focus is on submission of drug applications in the US.
What do Regulatory Writers Write?
Regulatory writers in the biopharmaceutical industry create documents, such as protocols and data summaries, for submission to regulatory agencies in support of drug development. Specifically, they create documents compliant with the requirements of the Common Technical Document (CTD), a set of specifications governing applications in support of new medicinal products. The CTD was developed by the International Conference on Harmonisation (ICH). Consisting of representatives from three regions,-the US, the EU and Japan-ICH develops common standards and practices related to the process of drug development and registration. Such practices are intended to "reduce or obviate the need to duplicate the testing carried out during the research and development of new medicines." ICH developed the CTD in order to decrease the time and resources needed to compile and review a drug application as well as to simplify the exchange of information among regulatory authorities.1 The CTD, particularly now that is usually submitted electronically (an "eCTD"), has become the raison d'être for regulatory writers.
Who Are Regulatory Writers?
Regulatory writers come from a variety of backgrounds. Currently, no clearly defined degree or certification is required for someone to be hired as a regulatory writer. However, almost all those employed in the industry hold at least a bachelor's degree; very often, they have an advanced degree, such as a master's or doctorate, or a professional degree such as an RN, JD, MD or PharmD. While many regulatory writers have scientific backgrounds, a significant number with liberal arts training are highly successful regulatory writers. Regardless of their education and background, successful regulatory writers understand the process of drug development and are thoroughly conversant with the CTD structure and guidelines.
The Fundamentals-Understanding Drug Development and the CTD
Drug Development in a Nutshell
A regulatory writer needs to understand enough about drug development to determine which documents need to be written. The decision to create a particular document is based upon the drug's stage of development and the region of the world in which that document will be submitted. The goal of research in the biopharmaceutical industry is to bring to market a product that fulfills an unmet medical need. A pharmaceutical or biotechnology company that sponsors the development of a drug (the sponsor) must determine whether that drug will be a viable medicinal therapy. That is, the sponsor must find out whether that drug is effective in a certain indication (disease or condition, such as asthma or obesity) and whether the benefits of that drug outweigh its risks-often called adverse effects. The sponsor first tests the drug in vitro-"in glass"- and then in vivo-in animals, usually mice, rats, dogs, rabbits and sometimes monkeys and other primates. If data from these investigations are encouraging, a US sponsor submits an application known as an Investigational New Drug Application (IND) to FDA. Technically, the IND is a formal request to ship the drug across state lines; in fact, the IND is a petition to test the drug in human subjects. After review of the application, FDA will authorize studies of the drug in human subjects if it believes that participation in these studies does not expose subjects to unreasonable risks. An independent ethics committee also reviews the clinical study protocol associated with the IND for the same reason. In the US, this group is called aninstitutional review board(IRB); in Europe and many other regions of the world, it is known as an ethics committee (EC).
Investigations of a new drug intended for use in human subjects consist of three phases of clinical trials. If data from these trials are encouraging, a US sponsor submits a formal application, known as a New Drug Application (NDA), to FDA asking that the drug be approved for marketing and sales. If the drug is a vaccine or a blood product, the sponsor submits a Biological License Application (BLA). If, after review, FDA deems the drug to be effective and safe when used as directed, it will approve the drug for marketing. Very likely, it will require the sponsor to conduct more studies in human subjects in order to determine how the drug affects large segments of the population.
Submitting a drug application such as an IND, NDA or BLA (also known as the "dossier," the "filing" and the "submission") is a mandatory process for any sponsor who wants to sell and market a drug in the US. The application must be based on the CTD described earlier. The process of compiling a CTD-compliant application is time consuming and labor intensive. More often than not, the scientists and clinicians who have worked to develop a drug do not have the time, resources or skills to write the individual documents contained in any of these applications. Thus, the stage is set for the regulatory writer. A writer who understands the regulations governing both drug development and the CTD-the basis of the IND, NDA or BLA-and who has the skills and dedication necessary to create these documents becomes an invaluable partner to those in the field of drug development.
The CTD in a Nutshell
The CTD consists of five sections, referred to as modules. The five modules are described below, along with some of the documents required for each. (Note on nomenclature: Writers who write documents for Modules 3 and 4 are often called technical writers. Those who write documents for Module 5 are often called medical writers. Both types of writers are properly called regulatory writers.)
Module 1: Regional Administrative Information
This module is not considered part of the CTD proper because it contains regional documents, many of an administrative nature, that are not "common" to all regions (the US, the EU or Japan). Rather, the documents in this module are specific to the region in which the drug is being submitted. Because regulatory writers are often involved in creating documents contained in this module, some key Module 1 documents are listed below:
- general investigational plan
- risk management plans
- product label (often called the "package insert")
- Investigator's Brochure (This document is prepared for the investigator who conducts a clinical trial. It presents current nonclinical and clinical data about the drug under investigation as well as a description of the drug's active and inactive ingredients.)
Module 2: Summaries
This module consists of high-level summaries of information found in Modules 3, 4 and 5. Documents contained in Module 2 include:
- quality overall summary, which includes subsections for materials, validations, analytical procedures and stability
- nonclinical overview, which provides conclusions about nonclinical investigations
- nonclinical summaries-both written and tabulated-of in vitro studies and in vivo pharmacodynamic, pharmacokinetic, toxicology and immunologic studies in animals
- clinical overview, which provides conclusions about clinical investigations and includes an analysis of the risks and benefits of the drug to human subjects
- clinical summaries-both written and tabulated-of bioanalytical methods and of pharmacokinetic, pharmacodynamic, immunologic, efficacy and safety studies in human subjects
Module 3: Quality
This module contains the chemistry, manufacturing and controls (CMC) information. It consists of reports (and associated study protocols and protocol amendments) conducted to characterize the pharmaceutical nature of the drug and ensure its purity (quality).
Module 4: Safety
This module contains reports, associated study protocols and protocol amendments for in vitro studies and in vivo studies-pharmacokinetic, pharmacodynamic, toxicologic and immunologic-of the drug in animals.
Module 5: Efficacy
This module contains reports, associated study protocols and protocol amendments for studies of the drug in human subjects. Included in this section are the reports of pharmacokinetic, pharmacodynamic, toxicologic and immunologic studies as well as the following types of studies:
- Phase 1, 2 and 3 clinical studies, which include narrative summaries detailing how the drug has affected individual patients
- Integrated Summary of Safety (ISS) and Integrated Summary of Efficacy (ISE)-although these documents are entitled "summaries," they actually contain analyses of pooled data; thus, they differ from the nonclinical and clinical summaries found in Module 2
- Postmarket reports
Other Required Skills and How to Acquire Them
Listed below are additional areas of knowledge as well as specific skill sets that can play a role in a successful career in regulatory writing. If the list appears daunting, be encouraged by the fact that successful and seasoned regulatory writers are mere mortals who have managed to learn these subjects.
Learn the relevant regional, national and local regulations governing drug development. If you are writing documents in support of drugs that will be tested and/or filed for marketing in the US, become familiar with the following parts of volume 21 of the Code of Federal Regulations (21 CFR):
- 11: Electronic submissions and signatures
- 50: Specifications for protection of human subjects in clinical trials
- 56: Specifications for institutional review boards that oversee clinical trials
- 58: Description of good laboratory practices for nonclinical studies associated with clinical trials
- 312: Requirements for an investigational new drug
- 314: Requirements for applications for approval and marketing of a new drug
Be aware of four key ICH guidelines regarding the conduct and reporting of a clinical trial:
- Clinical Data Safety Management: Definitions and Standards for Expedited Reporting E2A
- Structure and Content of Clinical Study Reports E3
- Guideline for Good Clinical Practice E6
- General Considerations for Clinical Trials E8
Become familiar with four key ICH guidelines regarding the CTD as well as the overall CTD table of contents:
- Organization of the Common Technical Document for the Registration of Pharmaceuticals for Human Use M4
- The Common Technical Document for the Registration of Pharmaceuticals for Human Use: Quality-M4Q(R1) Quality Overall Summary of Module 2; Module 3: Quality
- The Common Technical Document for the Registration of Pharmaceuticals for Human Use: Safety-M4S(R2) Nonclinical Overview and Nonclinical Summaries of Module 2; Organization of Module 4
- The Common Technical Document for the Registration of Pharmaceuticals for Human Use: Efficacy-M4E(R1) Clinical Overview and Clinical Summary of Module 2; Module 5: Clinical Study Reports
Understand the principles embodied in the US Health Insurance Portability and Accountability Act (HIPAA) and the Declaration of Helsinki. The former ensures the privacy of data related to healthcare. The latter is the declaration of the World Medical Association regarding ethical conduct of research in human subjects. Cornerstone principles of this declaration are the right of individuals to self-determination and to make informed decisions. This declaration is considered by many to be morally binding.
Data and How to Work With Them
Learn basic principles of the following:
- data entry
- data interpretation
- coding of adverse events and drugs via specialized dictionaries such as the Medical Dictionary for Regulatory Activities (MedDRA) and the World Health Organization (WHO) drug dictionary
Drug Characterization and Mechanism of Action
Learn the basics of the following:
- chemistry, manufacture and control of the drug, including the drug substance and the final drug product
- pharmacology of the drug, including its pharmacokinetics and pharmacodynamics (that is, what the body does to the drug and what the drug does to the body)
Principles and Practices of Clinical Trials
Be conversant with the following:
- protocol design, both nonclinical and clinical, including the logistics of the proposed trials
- safety reporting, including the reporting of serious adverse events
- creation of the final study report for a clinical trial
- basic clinical laboratory tests and interpretation of chest X-rays and electrocardiograms (ECGs)
Diseases and Conditions
Gain a working knowledge of the following for the drug on which you are writing:
- etiology of the targeted indication (disease or condition, such as asthma, multiple sclerosis, diabetes, obesity and infections caused by Gram‑negative or Gram-positive pathogens resistant to current antibiotics)
- current treatments for the indication or condition and reasons why the drug may fulfill an unmet medical need
- immunologic responses of the body to the drug in healthy individual and individuals with the proposed condition for treatment
Care and Feeding of Documents
FDA strongly encourages electronic submission of CTD-based drug applications (eCTDs), whether INDs, NDAs or BLAs. Electronic submissions enable all documents contained in the application to be linked electronically to one another by means of an XML backbone-the technological core of the CTD. Linking allows reviewers to conduct online reviews of the application and facilitates traceability of information and data. Therefore, it is necessary for the regulatory writer to understand electronic documents and to have a command of the following:
- basic and advanced computing skills with the following programs and formats:
- Microsoft Word, including the Styles feature
- Microsoft PowerPoint, Microsoft Excel and Adobe Acrobat
- Creation and format of tables (in Microsoft Word), figures (in Prism or other graphing software) and study schemas (in Microsoft Visio or other software)
- use of templates, including links within and between documents
- preparation of a document for linking to an XML backbone
- methods of archiving and referencing documents
Art and Craft of Writing
Be skilled in the following:
- basic writing, including a firm command of organization, syntax, grammar, punctuation and logical development of information
- document style
- standard style guides such as the AMA Manual of Style, 10th edition and the Chicago Manual of Style
- in-house style of the sponsor for whom you write-usually a combination of one of the manuals mentioned above and sponsor idiosyncrasies
Be knowledgeable about the following:
- The business of your business-how the drug you are writing about fits into the worldwide market of drug products
- The politics and goals of the of the organization in which you are working
- Basic business skills-project management, estimating time and costs for projects, writing contracts
- Procedures for reviewing and signing off documents
How Do I Learn all This?
You learn by a combination of the following: doing; absorbing the counsel of a willing mentor (see below on what a mentor is and how to find one); taking courses in the field; and independent reading and research. You also create a development plan so you can assess and then fill in the gaps in your knowledge.
Just Do It!
The best way to learn is by doing. Given an assignment, plunge in-intelligently. Look for an approved example of the document you are assigned to write as well as any regulations, both draft and final, governing the creation of that document. Then perform a bit of reverse engineering. For example, if you are assigned to write a clinical study report (CSR), obtain the ICH E3 Guidelines (mentioned above), the study protocol, tables, listings, figures and in-house style guide. Then examine the report section by section and figure out how the writer of the approved document created that document.
Find the right mentor, and life can be close to blissful. In Homer's Odyssey, Mentor was the wise and trusted counselor of Telemachus, son of Odysseus. Athena, goddess of wisdom, sometimes assumed the guise of Mentor in order to counsel Telemachus. Your mentor will probably not be Athena or come to you unasked. But you can ask a person inside or outside your organization to mentor you. That person should be well versed in some aspect of drug development-possibly a regulatory writer, clinical research associate (CRA), biostatistician, regulatory affairs associate or research scientist. That person should also be willing and able to share the benefit of his or her experience with you and, if appropriate, provide you with constructive feedback about your work. The mentoring relationship entails a commitment of time and energy on the part of both individuals. Honor it by heeding the advice of your mentor, asking your mentor for feedback about your work (if appropriate) and preparing thoughtful questions about issues related to daily tasks, corporate policies and regulations governing drug development.
Industry-sponsored courses that describe the processes and regulations associated with drug development abound. The Drug Information Association (DIA), Regulatory Affairs Professionals Society (RAPS) and American Medical Writers Association (AMWA) offer coursework leading to certification in many aspects of drug development. AMWA also offers courses that teach individuals how to write for a scientific and regulatory audience. The Pharmaceutical Education Research Institute (PERI) sponsors courses explaining the biological basis of specific indications and optimal ways to conduct clinical trials with drugs targeting that indication.
University-sponsored courses also exist. The University of Chicago and the University of the Sciences in Philadelphia sponsor programs that lead to certification in medical writing; the latter also offers a master's degree program in medical writing.
Independent Reading: Print and Online
Many resources exist that will enable you to further your training in regulatory writing on your own. Some of these are listed below. Many of the books in print are issued with CDs or allow access to an online version of the material:
Style and Formatting Guides
- AMA Manual of Style, 10th edition
- Scientific Style and Format: The CSE Manual for Authors, Editors, and Publisher, 7th edition
- Microsoft Word for Medical and Technical Writers by Peter G. Aitken and Maxine M. Okazaki
Guides to Regulatory Writing
- Targeted Regulatory Writing Techniques: Clinical Documents for Drugs and Biologics by Linda Fossati Wood and MaryAnn Foote
- The Merck Manual (physician and home editions)
- Pharmacokinetics Made Easy by Donald J. Birkett
- Medical Abbreviations: 30,000 Conveniences at the Expense of Communication and Safety, 14th edition byNeil M. Davis
- A Manual of Laboratory & Diagnostic Tests by Frances Talaska Fischbach
- How to Report Statistics in Medicine, 2nd edition by Thomas A. Lang and Michelle Secic
- Fundamentals of US Regulatory Affairs, 6th edition
- Stedman's Medical Dictionary
- Mosby's 2010 Nursing Drug Reference byLinda Skidmore-Roth.
- Guide to Clinical Trials by Bert Spilker
Magazines and Journals
- Applied Clinical Trials (trade journal)
- DIA publications, especially DIA Today
Anything else I need to know?
There are two more fundamentals for success in this area.
You must get along with people and work as part of a team. A regulatory writer does not work alone. To create clearly written documents that comply with the regulations, contain accurate statements about the data they present and are internally consistent, you must interact successfully with other people. For instance, you will need to obtain data and other information from people in all parts of the organization you work in; work with others to craft interpretations of the data (often called "messages"); circulate documents for review; address and adjudicate comments from colleagues; and finalize documents for publication in electronic format. After a review of one of your documents, you may have to re-conceptualize it completely and rewrite it from the ground up. Your success in these areas depends upon your ability and willingness to subordinate your ego when necessary and to assert yourself when appropriate. If doing this does not come naturally to you, many courses sponsored under the catch-all terms "leadership" and "management" can teach you how to work and play with your colleagues. Interpersonal skills are serious skills and their lack can compromise your career as a regulatory writer.
You must continue training-and have a development plan. That is, you must continually reassess your skill sets and knowledge base, identify gaps that can impede your ability to function as a regulatory writer and figure out how to plug those gaps. The world of drug development is never static, and in this fast-paced environment, you must, to quote Carl Sagan, "learn how to learn."
Your work as a regulatory writer helps bring medicines that potentially improve quality of life, alleviate suffering and cure disease to the people who need them. As a regulatory writer, you will work with the brightest and the best of research and clinical scientists to accurately and meticulously report research results in a manner that facilitates review by a regulatory agency. To succeed in this career, you must understand the basics of drug development, the regulations that govern this process, and the rationale and structure of the CTD. Above all, you must get along with people, work as part of a team and constantly reassess the skills needed to write the documents you are asked to write. Drug development, including the rules and procedures that govern it, is here to stay. And so are regulatory writers.
- US Food and Drug Administration (FDA), Center for Drug Evaluation and Research, Guidance for Industry M4: Organization of the CTD).