Deal includes provisions on global harmonizationThe Food and Drug Administration reform legislation signed into law Nov. 21 by President Clinton could have a dramatic effect on the ability of manufacturers to more efficiently bring new products to
Deal includes provisions on global harmonization
The Food and Drug Administration reform legislation signed into law Nov. 21 by President Clinton could have a dramatic effect on the ability of manufacturers to more efficiently bring new products to market. The legislation, entitled the Food and Drug Administration Modernization Act of 1997, promises to enhance the agency's development and review process, particularly for imaging equipment and pharmaceuticals.
Congressional mandates to the FDA promise to reduce time delays for new products by streamlining the review process; relaxing restrictions on the dissemination of information for applications that are not strictly covered in FDA labeling; and encouraging the agency to make greater use of national and international standards.
The radiology industry is especially well positioned to benefit from the new law, which is scheduled to go into effect Feb. 19, because virtually all imaging products are either Class I or Class II devices, which seldom require clinical studies. Devices that require clinical data are exempt from the relaxed rules.
"We came out big winners," said Robert Britain, vice president of medical products at the National Electrical Manufacturers Association (NEMA). "Our equipment is perfect for this setup."
Nuclear medicine may benefit most, due to two provisions that directly address its technologies: PET imaging and radiopharmaceuticals in general. Section 121 of the act relieves the nuclear medicine community of a burden under which it had chafed for several years: the FDA's regulation of PET radioisotopes. The FDA reform legislation removes the FDA as a direct overseer of this market and orders the agency to apply the standards and official monographs of the U.S. Pharmacopoeia in regulating PET radiopharmaceuticals.
"The major problem is that the FDA really didn't know how to go about the approval process," said Dr. William Strauss, section chief of nuclear medicine at Stanford Medical Center and president of the Society of Nuclear Medicine.
The new law will resolve this dilemma, directing the agency to develop procedures and requirements that take account of the special characteristics of PET radiopharmaceuticals, as well as the special techniques and processes used to produce them. The one catch is time: The FDA has up to four years to establish these requirements.
The nuclear medicine community is grateful for any progress, and there is more in Section 122, which promises to relax FDA requirements even further across all radiopharmaceuticals. This section directs the agency to propose regulations for governing the approval of these agents that take into account their special nature.
"The thought is that radiopharmaceuticals might be treated a bit differently than conventional drugs, which are typically used in multidose situations," Strauss said. "Radiopharmaceuticals usually involve a single administration or at most three or four administrations over a period of months or years."
The same might be said about contrast agents in other modalities, and Strauss believes the new regulations regarding radiopharmaceuticals might eventually be applied to the review of imaging agents used in x-ray, ultrasound, nuclear medicine, and MR. Yet, even before reaching that point, the developers of contrast media stand to gain from this legislation. Under the new law, drug and device companies will have the right to obtain in writing from FDA officials the details of how necessary clinical data should be gathered and, after submitting an application to the FDA, what deficiencies-if any-are holding up clearance or approval.
The most apparent weaknesses in the past relationship between the FDA and industry have been found in the review of contrast agents. Notable examples are the reviews of two agents submitted by Advanced Magnetics of Cambridge, MA. The MR liver agent I.V. Feridex and MR gastrointestinal medium Gastromark were both ensnared in the FDA review process, said Jerome Goldstein, president and CEO of the company. Although he is hopeful that the changes now written into law will enhance the review process, Goldstein is cautious.
"You just don't know until you see it implemented and see how these (new requirements) are applied in practice," Goldstein said.
Another benefit that might be derived from the new law is that the FDA will no longer be able to hold 510(k) applications hostage to other issues it may have with the company making the submission. In the past, the agency has occasionally delayed applications until outstanding problems were remedied, such as a manufacturing site that fails to comply with good manufacturing practices (GMPs) requirements. In the future, the FDA will have to show that a serious risk to human health is involved before imposing any such delay.
Manufacturers will also have more flexibility in the way they present information about their products. Previously, manufacturers had to be careful to provide information only about applications that had been explicitly cleared or approved by the FDA, when describing a commercially available product. Providing any other such information was considered to be an illegal activity-marketing the product for "off-label" uses-unless the information requested was not solicited by the vendor. Under the new law, companies will be able to distribute information about applications if they intend to apply to the FDA for extended labeling.
"This provision is absolutely astounding," said Robert Sheridan, vice president for marketing submissions at the consulting firm of C.L. McIntosh in Rockville, MD. "It essentially puts off-label uses on the label."
Also noteworthy is the widening availability of third party review. Imaging systems that do not require supporting clinical data to conduct the 510(k) assessment qualify for review by third-party groups that have been certified by the FDA to conduct such assessments. While the FDA will have the final word on whether a device is cleared, any applications passing through third-party review, which will be done according to FDA criteria, should be very close to final clearance. Therefore, manufacturers can speed up the review of their devices, depending on the availability of a certified third party and the willingness of the company to pay for this review. But before that can happen, the FDA must issue a guidance for the review of specific types of devices and then certify third parties to review those devices.
The greatest benefits of the reform legislation, however, may still be years in the future. The act specifically states that the FDA "recognize all or part of an appropriate standard established by a nationally or internationally recognized standard development organization for which a person may submit a declaration of conformity in order to meet a premarket submission requirement or other requirement under this Act to which such standard is applicable."
This reform of the FDA signifies an important milestone in the attempt to harmonize U.S. regulations with those of other nations around the world, according to NEMA vice president Britain. The FDA and U.S. medical device companies have been working for several years on developing Mutual Recognition Agreements with governments representing key global markets, including Europe and Asia. These agreements are slowly drawing the regulatory schemes of the various nations closer together. If regulatory review is eventually based on commonly accepted standards, as is the goal of these agreements, devices cleared in one part of the world might be only a formality away from commercialization in markets globally.
"We could be in a very good position for using international standards as a basis for most 510(k)s," Britain said. "If your product meets the standard that all other products meet, then by definition your product would be equivalent."