- Legislative Background
Under section 314 of the NCVIA, FDA was required to determine whether the warnings, use instructions and precautionary information for certain enumerated childhood vaccines were adequate to warn health care providers of the nature and extent of the risks posed by such vaccines. The NCVIA limited this requirement to childhood vaccines listed in the Vaccine Injury Table (VIT) established in section 2114 of the PHS Act.6 If FDA determined that any such warnings, use instructions or precautionary information were inadequate, then manufacturers were required to revise and reissue such warnings, use instructions or precautionary information as expeditiously as practical.
On June 13, 1988, the Secretary delegated authority to implement section 314 of the NCVIA to the Assistant Secretary for Health (ASH).7 On September 16, 1988, the ASH delegated authority to implement section 314 of the NCVIA to the Commissioner of Food and Drugs.8 On April 1, 1993, FDA delegated to the Center for Biologics Evaluation and Research authority to implement section 314 of the NCVIA.9
- FDA'S Process for Conducting the NCVIA Labeling Review
FDA conducted its review of vaccine labeling under section 314 of the NCVIA through a process that involved extensive opportunities for public comment on childhood vaccine labeling. By applying existing drug labeling regulations (e.g., 21 CFR 201.56 and 201.57), current labeling as supplied by the manufacturer, as well as a survey of medical practitioners, FDA created draft Summaries of Important Information (SII) for each applicable vaccine listed in section 2114's Vaccine Injury Table (VIT) and distributed them to the appropriate manufacturers on March 3, 1992.
On July 31, 1992, FDA announced the creation of a public docket and scheduled a public meeting to seek comments on manufacturers' and FDA's proposed revisions to the package inserts, which had been made available for public examination.10 At that time, FDA also made available the respective vaccines' most recently approved package inserts, manufacturers' proposed revised drafts of package inserts, as well as FDA's comments on the inserts. FDA established time frames for completion of its review and response to public comments.11 Subsequently, FDA reviewed each manufacturers' proposed labeling changes, and, after considering the public record, approved labeling changes for the listed childhood vaccines, thus determining the revised labeling to be adequate to warn health care providers of the nature and extent of the risks posed by such vaccines.
Throughout its review process, FDA consulted the Advisory Commission on Childhood Vaccines (ACCV) to assess the warnings, use instructions and precautionary information issued for applicable childhood vaccines. The NCVIA mandated creation of the ACCV to provide expert advice to the Secretary about, among other things, the implementation of the statute. The ACCV also makes recommendations regarding changes to the VIT and surveys Federal, State and local information regarding childhood vaccine associated injuries.12 FDA representatives attended ACCV meetings and briefed the ACCV on the labeling review.
- Preparation of Summaries of Important Information
As discussed above, FDA prepared an SII for each vaccine listed in the VIT to serve as a guide to manufacturers when revising package inserts. Creation of the SIIs also facilitated harmonization of package inserts for similar vaccines produced by different manufacturers. In the SIIs, FDA recommended the location and content of specific package insert sections and subsections and in several instances, suggested precise wording.13
On March 3, 1992, FDA sent to the respective childhood vaccine manufacturers copies of the draft SIIs for each vaccine listed in the VIT. FDA notified manufacturers of the workshop planned for September 18, 1992, and requested them to submit to FDA suggested revisions of draft SIIs. FDA presented revised draft SIIs for public review prior to the workshop and acceptepted comments filed to Docket No. 91N-0494.14 The docket included the following: (1) package inserts most recently approved by FDA; (2) manufacturers' draft package inserts with FDA's comments, if revisions were still pending as of July 1992; or (3) the most recently approved package inserts and FDA's comments, if revised drafts had not been received by July 1992; and (4) copies of the SIIs.
As the basis for these draft SIIs, FDA used the labeling requirements listed under 21 CFR 201.56 and 201.57, the Advisory Committee on Immunization Practices' (ACIP) "Recommendations & Reports," and approved package inserts. FDA also referred to reports prepared by the Panel on the Review of Bacterial Vaccines and Toxoids15 and the Panel on the Review of Viral Vaccines and Rickettsia,16 epidemiological information from MMWR, literature references, and summaries from VAERS.
- Public Participation
As noted previously, FDA took into account the views of several public panels during the review of childhood labeling. The Panel on the Review of Bacterial Vaccines and Toxoids and the Panel on the Review of Viral and Rickettsial Vaccines conducted separate reviews regarding the safety, efficacy, and labeling of bacterial vaccines, toxoids with standards of potency, antitoxins, and immune globulins; and viral and rickettsial vaccines, respectively. Each panel's review resulted in a proposed order that was published in the Federal Register. Both panels' reports recommended that information in the package insert be presented in a clear, unambiguous and accurate manner. The panels also reviewed FDA's requirements for package inserts and suggested the types of information that should be included. FDA considered the recommendations of both panels and incorporated many of them into the relevant SIIs.
At the September 1992 public workshop, FDA described its labeling review process and presented the reviews it had conducted for each childhood vaccine pursuant to section 314 of the NCVIA. Several groups presented comments, including: Government agencies such as the National Institutes of Health and the CDC; advisory bodies (including ACIP, ACCV, the American Academy of Pediatrics, and the National Vaccine Advisory Committee), and the Vaccine and Related Biological Products Advisory Committee; manufacturers; and interested members of the public. FDA considered these presentations and submissions made during the workshop, comments submitted to the Docket, as well as direct correspondence from manufacturers and other interested members of the public. FDA reviewed the revised labeling of the childhood vaccines enumerated in the VIT and determined that the labeling, as revised, contained adequate warnings.
