Supplemental files

Supplemental files (review aids) are any data set needed by the reviewer for additional analysis purposes that cannot be readily extracted from the PDF report or additional information in electronic format that would enhance the reviewer s understanding or facilitate presentation of the data. 

Some data submitters were concerned about whether the supplemental files would be archived along with the data, and whether the supplemental files would be subject to Freedom of Information Act (FOIA) requests. OPP expects to maintain the CD provided as the electronic data submission, and archive the supplemental files on CD along with the rest of the electronic data submission. However, the official archive format at the present time is paper, and the supplemental files duplicate material in the paper submission. Supplemental files may be released upon FOIA requests after the first registration for the pesticide active ingredient, subject to the requirements of FIFRA 10(g), which include an affirmation statement from the requestor and a notice to the data owner, and exclude any FIFRA CBI. 

OPP scientists evaluated PDF submissions and supplemental files. For a pilot electronic data submission, OPP discussed the content of supplemental files with the registrant interested in providing an electronic data submission and worked on the data fields of interest for several toxicology studies. OPP evaluated SAS-XPORT (SAS Transport) files as a neutral file format for data tables. Two programs were evaluated by OPP DBMA Copy and Stat Transfer, which will transfer the data from the SAS-XPORT format into a format usable by the reviewer. 

OPP scientists are identifying the data elements (or fields) of interest for each study type where the reviewers felt that supplemental files would be useful, are identifying other information for each study type, which would be useful to have as electronic files, and are developing guidance for submission of supplemental files. This guidance is not ready to be published, but the scientists will work with the data submitters to ensure that the supplemental files for the particular study will be useful to the science reviewers. Even when guidance becomes available, OPP intends to be fiexible about the format of the supplemental files and will modify the guidance as needed. 

CIBA Vision Corp (2000). Visudyne supplemental filing granted priority review by FDA. Press Release, 29 August. 

Beilstein File. Beilstein first went on-line on STN International in December 1988 with information on 350,000 compounds, and several months later it was also on Dialog. Beilstein Online now comprises data on five million compounds. The organic substance records contain the critically reviewed and evaluated documents from the beilstein Handbook of Organic Chemist main volume and supplements 1—5, which cover the chemical Hterature from 1779 through 1979. These evaluated data are indicated as Handbook Data in the notes of Hterature references. The Beilstein Eile also contains organic substance records for unreviewed excerpts from the primary Hterature from 1980 to 1991. 

The Chinese patent file with its abstracts can be used to supplement WPI, which at this writing has only tides for Chinese patents. JAPIO provides abstracts based ia particular oa pateat claims, and can help to clarify uncertainties with Japanese abstracts from Derwent and/or CA. PATOLIS, ia Japanese, is a unique source of Japanese legal status information (37). EPIDOS staff carry out PATOLIS searches on request for those with sufficient need to search the PATOLIS database, software is available to enable those who cannot read Japanese to extract key data. 

This requirement supplements that for records to be readily retrievable but in addition implies a further requirement for security of records. After addressing the filing and storage requirements, you need to ensure that the records are accessible to those who will need to use them. This applies not only to current records but to those in the archive and any insurance copies you may have stored away. A balance has to be attained... 

Calcium is contraindicated in patients with hypercalcemia or ventricular fibrillation and in patients taking digitalis. Calcium is used cautiously in patients with cardiac disease. Hypercalcemia may occur when calcium is administered with the thiazide diuretics. When calcium is administered with atenolol there is a decrease in Hie effect of atenolol, possibly resulting in decreased beta blockade. There is an increased risk of digitalis toxicity when digitalis preparations are administered with calcium. The clinical effect of verapamil may be decreased when the drug is administered with calcium. Concurrent ingestion of spinach or cereal may decrease file absorption of calcium supplements. 

Short monograph concerning mass spectrometry. Full description of technique shown clearly, supplemented by numerous figures. Moreover, a MALDI tutorial in PDF file can be found on this site. 

Fluorine thermochemistry itself has not been previously reviewed, but has tended to be included in more general reviews and reports, or in data compilations (141,123,151). The most comprehensive literature survey, covering the years 1949-1961 (9), supplements the N.B.S Circular and Notes (203). (N.B.S. Technical Notes 270-3 to 270-7 issued from 1969-1973 were unfortunately published without literature references.) Subsequent work was conveniently traced from annual issues of the Bulletin of Chemical Thermodynamics, and from 1977 to 1979 (May) by accessing the Chemical Abstracts data files. Experimental aspects of fluorine thermochemistry are included in two rather dated volumes (214), and only general detail will be given in this review. 

It is not required to have prior FDA approval to use an alternative method to a compendial test. According to 21 CFR 314.70 Supplements and Other Changes to an Approved Application, the addition or deletion of an alternative analytical method does not require prior approval and may be filed in the Annual Product Report. However, the equivalency of the alternative method needs to be documented... 

In 1992, a New Drug Application for taxol was filed by BMS. The FDA approved taxol for the treatment of refractory ovarian cancer 6 months after filing. In December 1992, the FDA approved taxol for marketing. It had been 30 years since the first collection of Pacific yew for testing at the Research Triangle Institute. In 1993, taxol was marketed by BMS. In 1994, a supplemental FDA approval was issued for taxol in treatment of metastatic breast cancer. 

Particular attention is appropriately paid immediately following a system failure or problem. There is concern that improperly close files may result in corruption of existing data, or in misaUocation of newly entered data. Most automated laboratory equipment and systems have built-in operational checks and tests to guard against problems. This requirement calls for confirmation of the existence or IQ/OQ features and for the creation of supplemental checks when automated diagnostics are inadequate or absent. 

Filing documentation—A prior approval supplement with all data including the accelerated stability data is required. This change should also be documented in the annual report along with the long-term stability data. 

Filing documentation—Prior approval supplement including accelerated stability data plus an annual report showing longterm stability data. 

Filing documentation—A supplement should be hied showing the changes being effected. Long-term stability test data should be included in the annual report. 

Filing documentation required—Changes being effected should be identihed in a supplement. Long-term stability data are reported in the annual report. 

Filing documentation—Prior approval supplement with justification for change long-term stability data must be reported in the annual report. 

Filing documentation—A prior approval supplement must be filed with justification for the change. Long-term stability data should be submitted in the annual report. 

The law abolishes the long-standing prohibition on dissemination by manufacturers of information about unapproved uses of drugs and medical devices. The act allows a firm to disseminate peer-reviewed journal articles about an ojf-label indication of its product, provided the company commits itself to file, within a specified timeframe, a supplemental application based on appropriate research to establish the safety and effectiveness of the unapproved use.3... 

For an approved application (NDA, ANDA, or BLA), a change to a container closure system, to a component of the container closure system, to a material of construction for a component, or to a process involving one of the above must be reported to the application. The filing requirements are specified under 21 CFR 314.70 (supplements and other changes to an approved application) for an NDA or ANDA, and under 21 CFR 601.12 (changes to an approved application) for a BLA. 

In the event of a change in the DMF, the holder of a DMF must notify the holder of each application supported by the DMF (21 CFR 314.420(c)). Notice should be provided well before the change is implemented to allow the applicant or sponsor enough time to file a supplement or an amendment to the affected application. 

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