CHAPTER 1 CONTROLLING REGULATORY COSTS 1
CHAPTER 2 CLEAR OPERATION DEFINITIONS OF REQUIREMENTS 11
CHAPTER 3 PREREGULATORY AUDITS 25
CHAPTER 4 QUALITY BY DESIGN 33
CHAPTER 5 OUTSOURCING 45
APPENDIX TO CHAPTER 5 51
CHAPTER 6 ELECTRONIC SUBMISSIONS 57
APPENDIX TO CHAPTER 6 63
CHAPTER 7 EMEA/FDA COORDINATION 81
APPENDIX TO CHAPTER 7 89
CHAPTER 8 MANAGING FDA INSPECTIONS 111
APPENDIX TO CHAPTER 8 119
CHAPTER 9 RISK ASSESSMENT 141
CHAPTER 10 CASES 161
CHAPTER 11 COST-CONTAINMENT ANALYSIS 203
CHAPTER 12 MANAGING REGULATION IN TIMES OF CHAOS 213
CHAPTER 13 INTERNATIONAL REGULATION 227
CHAPTER 14 COST-CONTAINED REGULATORY COMPLIANCE 259
CHAPTER 15 FUTURE 265
In difficult economic times, the first rule of management is to conserve financial resources. In good economic times, the same rule prevails. Cost containment means less borrowing, greater flexibility, and higher profits.
But to the pharmaceutical, medical device, and biologics industries, cost containment has a significance that transcends financial considerations. The altruistic goal of these health – care industries is to bring therapeutics, preventatives, and quality – of – life enhancements to the public. In the United States and much of the world, the major impairment to that access is cost: Regardless of need, expensive drugs, vaccines, and devices are less available to the people who need them.
There are a number of expense centers that need careful monitoring and close cost control: manufacturing, distribution, research, and so forth. Somewhere on the list — perhaps not at the top of the potential amount of savings but high on the opportunity for control — is the cost of regulation. The investment necessary to maintain top – level quality assurance and control, and to demonstrate that level to outside government (or industry) reviewers are not without need, but often may be layered in fat appropriate for trimming. There may well be areas in which quality can be achieved and demonstrated at lower costs without losing credibility or control.
This book identifi es eight proven strategies for containing the costs of regulatory compliance without sacrifi cing quality or safety. These are not techniques for fooling regulators, for shortcutting quality controls, or for risking public safety. Rather, these eight strategies address areas in which the pharmaceutical, biologics, and medical device industries have evolved approaches that add cost to the regulatory process without adding quality or safety. The strategies identify areas in which a lack of understanding or clarity of the letter and spirit of regulation has led to unnecessary and nonrequired industries standards that add nothing of value. Partially as a result of paranoia, partially because of FDA lack of clarity, and partially a result of evolutionary force ( “ most companies are testing 20 samples; let ’ s test 25 just to be safe ” ; “ they tested 25 at my old company; let ’ s use 30 as a standard to avoid problems … ” ), regulations seem to grow well beyond their original intent. While that growth seems harmless on the ground, it ultimately leads to reduced access for more and more patients — a cycle worth controlling.
The fi rst part of this book defi nes the eight cost – containment strategies. An introductory chapter (Chapter 1 ) provides the theoretical framework and introduces the eight strategies.
Chapter 2 describes a very successful strategy based upon the development and documentation of clear operational defi nitions of actual regulatory requirements, cutting that unnecessary fat described above. The “ Operational Defi nitions ” strategy tends to reduce overenthusiastic compliance that exceeds actual regulatory expectations.
Chapter 3 suggests that investing in an independent audit, conducted by either an in – house team or outside experts, will save signifi cant “ repair ” costs and will speed approval of related submissions. In many cases, the audit will actually replace all or part of an FDA visit, reducing lost response time and permitting more effective facility management.
Quality by Design (QbD) is an evolving FDA initiative for automating signifi – cant portions of the quality control process. Chapter 4 provides an explanation, and it discusses the ways in which an investment in a QbD system can result in signifi – cant regulatory savings.
Chapter 5 presents the concept of outsourcing as a short – term cost – containment strategy. When used effectively, outsourcing can help build internal expertise at the same time it reduces headcount and taps experience and expertise. Excessive outsourcing can, of course, result in long – term loss of effi ciency and control; the chapter suggests tactics for walking that fi ne line.
The wave trend toward electronic (rather than paper) submissions has been growing over the years, now reaching tsunami levels. Electronics submissions can save assembly time and expense, but more importantly can save review time and move a product more rapidly to market. Chapter 6 describes the process and the advantages.
Chapter 7 looks at the most common approach to submission of new products — NDAs, BLAs, and PMAs — to both the FDA and EMEA, and it suggests a simultaneous submission strategy as an alternative to sequential submissions that can save in both the assembly costs and the review times, carrying similar advantages to the electronic submission.
Coping with FDA visits — inspections and investigations — is a signifi cant cost sink. Chapter 8 provides a strategy for controlling those costs by assuming control of the FDA visit, replacing passivity with managerial responsibility. The fi nal strategy, Risk Assessment, is described in Chapter 9 . This strategy allows controlled investment in regulatory issues by providing a mechanism for determining what actions will make a real difference in theareas of FDA and QA responsibility and focus.
And how do these strategies work in the fi eld? Chapter 10 consists of a number of case studies, drawn from all three industries (medical device, biologics, and pharmaceuticals). In real situations (disguised for obvious reasons) the strategies have been tested over time, and the long – and short – term benefi ts have been estimated.
Chapter 11 summarizes the fi eld results, analyzes the results, and recommends which strategies are likely to be most successful for each industry and for a variety of circumstances. This chapter will provide the regulatory manager or executive with the information necessary to make and informed implementation decision. As a special topic analysis, Chapter 12 deals with tactics for coping with regulation in times of chaos, generally resulting from major changes in regulatory guidelines and from the transition period as those guidelines are defi ned . Chapter 13 reviews the international regulatory scene. While the USFDA and European EMEA tend to dominate, regulatory agencies in many other countries not only control product development and licencing within their boarders but also infl uence international agencies including the Organisation for Economic Co-operation and Development (OCED) and the World Health Organization (WHO). This chapter provides a clear model of those areas of infl uence.
Chapter 14 , guest written by scholar Ronald Fuqua, provides a summary of the theoretical base of cost-contained regulatory compliance, along with an applicational model for utilization of that theory to manage a pharmaceutical, biologics, or device organization. It bookends the introductory chapter, and provides a basis for the predictions and coming changes highlighted in the next chapter.
Chapter 15 , the last chapter, looks to the future, identifying (a) the major trends that are affecting the Food and Drug Administration today and tomorrow and (b) the impact of those trends on the eight strategies that are suggested.
Several of the cases described in Chapter 10 have been developed by friends and colleagues: my thanks to Carl A. Rockburne, Ronald Fuqua, and Arthur Spalding.