Cobert's Manual Of Drug Safety And Pharmacovigilance (Third Edition). William Gregory
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The FDA has multiple “clients” to which it must answer: the Secretary of Health and Human Services (in the President’s cabinet), the Congress (which provides funding and oversight), the American public, activist groups (consumer groups, lobbies, etc.), the media (press, TV, Internet, blogs, etc.), the pharmaceutical industry, other healthcare players, and, indirectly, foreign health agencies.
Pharmaceutical companies also have multiple clients but some are different: the stockholders (owners) of the company, the Securities and Exchange Commission, the American public, activist groups, the media, licensing partners, academic collaborators, trade groups, the FDA, and, for multinational companies, other health agencies, insurance companies and other payers, and foreign media.
The FDA’s fundamental viewpoint and raison d’être differ from those of pharmaceutical corporations. The FDA’s prime concern is protecting the American public (and animals). They are, in theory, not concerned with the viability or profitability of corporations or market share, whereas companies, again in theory, have a primary fiduciary goal of increasing shareholder value. Obviously, a company would not want to increase its stock price at the expense of the public health. But, in practice, decisions on what is good or bad for public health are almost never black and white. Rather, they are the subject of debate on the risks and benefits that usually fall somewhere in the gray area between the extremes. Nevertheless, it is in the interest of the public health for the public and healthcare community to have access to medical products when needed; all stakeholders should strive to ensure that the benefits of these products outweigh their risks.
Other factors come into play. In general, salaries and bonuses, particularly for professionals, are often better in private sector companies than in the FDA or academia. However, benefits, pensions, and retirement packages are often better in government service. Private sector companies tend to have more resources (people, computers, parking spaces, etc.) than government agencies.
As with other federal agencies, there is often a steady flow of personnel leaving the Agency to go to the private sector and, with the FDA, occasionally vice versa. This is generally viewed as a good phenomenon because it allows government workers to understand the functions and pressures in private industry and for private industry personnel to understand how government agencies function. Others feel this is a bad concept as it binds the regulators and the regulated too closely together and influences the actions of regulators who may want to get a job in industry after leaving the Agency. Many people enter the industry or the FDA from academia, often just after finishing training (in medicine, pharmacy, nursing, pharmacology, toxicology, statistics, IT, etc.) and, thus, the “first job” provides basic training that is essential for success in either industry or the government.
There is a continuing debate, which varies in intensity and persistence over time, on whether the FDA works too slowly (“drug approval lag”) or too quickly (“releasing dangerous drugs onto the market without adequate evaluation”) and whether there are too many regulations (“the biopharmaceutical industry is one of the most regulated or over-regulated industries in the United States”).
Most pharmaceutical companies live with a low-level dread of the FDA and other health agencies coming into their safety departments (or other departments) to do an inspection (unannounced as a rule when done by the FDA). The inspection may be routine, done periodically (often every 1 to 2 years) or “for cause” (wherein the FDA has a suspicion that all is not right). The inspection may last from a few days to months if major issues are found. The FDA may go to sites outside the United States, if appropriate. Conversely, the EMA and other agencies abroad inspect in the United States. However, most companies now understand that building quality management systems is now obligatory, not just in safety, but throughout the organization. They also realize that periodic audits (including self-audits) and governmental inspections are now part of the norm and “a cost of doing business”. Such inspections not only provide markers for compliance, but also serve to promote trust in medical products and the regulatory system.
There has been much controversy after the withdrawal of Vioxx and other products from the US market as well as contaminated products (e.g., heparin) for safety reasons. Some (both from within the FDA and from the outside) have accused the FDA of not sufficiently protecting the American public from “dangerous” drugs, food, and other products. There have been accusations of too rapid approval of drugs, insufficient analysis of data submitted to the FDA, companies’ not submitting complete or sufficient data to the FDA, and other charges. Similar controversies have been seen with other regulatory agencies in regard to financial regulation, air transport safety, and so forth. The PDUFA, FDAAA, and other changes are a result of these controversies. More will come.
Drug Safety Inspections
The FDA has an extensive role in doing drug safety and PV inspections. This is covered in a subsequent chapter in this manual.
Frequently Asked Questions
Q: Is there too close a relationship between the FDA and the pharmaceutical industry?
A: The answer depends on whom you ask. The FDA would (most probably) say that they are not compromised by maintaining correct and formal communications with the industry. Indeed, close communication promotes an understanding of regulatory expectations as well as practical challenges. The industry supplies FDA with much of the post-marketing safety data and nearly all of the pre-marketing safety data. There must be communication between the industry and the Agency to clarify ambiguous points, get further information on critical cases, and so forth. The FDA also encourages (and legislation even requires in some cases) meetings with the industry during the development of regulation and guidance. The FDA also regularly tracks drug development and meets with sponsors to discuss progress and next steps with investigational drugs (in the IND phases) and in post-marketing situations where safety issues arise. It is a professional-to-professional exchange of information to ensure the safety of the American public.
The industry would say that its influence on the FDA is slight. Companies go out of their way to be sure the FDA gets what it needs (and wants) and companies often submit more than regulations require to be sure that the FDA gets what it wants and that the companies are not accused of hiding or under submitting data. The industry often (privately) believes that the FDA is rather tough and tends to not give the industry a fair shake or a level playing field. Some feel the FDA treats big pharma differently from small pharma or start-up companies, cutting the latter a little more slack and giving them more “hand-holding”.
There has been speculation that the substantial PDUFA fees provided by industry for scientific assessment of new data by FDA “guarantee” new product approval, i.e., payment for a positive opinion. For example, in 2017 the fee for review of an application with clinical data was $2,038,100. Of course, integrity and objectivity of FDA reviewers is not adversely influenced by payments to the Agency (not to individuals) for operational expenses that improve efficiency of the drug review process.
Others claim that there is too much interchange of personnel between the FDA and industry, wherein some people start their careers or spend some time at the FDA and then move on to work for pharma companies, or vice versa, carrying with them their contacts and inner knowledge (which often becomes outmoded quickly) of the other. Some feel that this may influence a person’s actions in the company or FDA since his or her next job may be for the “other side”.
The consumer groups and activists believe that the FDA is indeed in bed with the industry and point to the various “fiascos” in safety that have