PdAsS

Eor high value food packaging appHcations, minimal migration of contaminants into food products is critical. Currently the PDA requirement is a maximum 0.5 parts per biUion (ppb) of noncarcinogenic compounds by dietary exposure (22). 

Available as both film and sheet unless otherwise noted. All materials are available in PDA grades except for CTA, PVP, and PL EX = extrusion CL = calendering REG = regeneration CAST = casting BO = biaxial orientation. 

The Food Chemicals Codex. The Food Chemicals Codex is developed by the Committee on Pood Chemicals Codex, which is a part of the Pood and Nutrition Board, Institute of Medicine, National Academy of Sciences, under a contract with the U.S. PDA. The Committee has the responsibihty for the development and revision of the PCC. To meet this responsibiUty, the Committee also contacts manufacturers, trade associations, and other knowledgeable parties to obtain comments and criticisms of monographs proposed by the committee. Broader pubHc input is sought by pubhcation, by the PDA in the FederalFegister, of current committee activity regarding new and revised monographs proposed for inclusion in the PCC. 

K. R. ErvaU and R. Murray, Lvaluation of Commercially Nvailahk Laser Frotective Lyewear, HEW Publication (PDA) 79-8086, U.S. Dept, of Health, Education, and Welfare, Bureau of Radiological Health, RockviUe, Md., 1979 R. L. Elder, Science 182, 1080 (1973). 

The anainoacridines, tacrine (19) and its 1-hydroxy metaboUte, velnacrine (20), are reversible inhibitors of AChE. Tacrine was synthesi2ed in the 1940s and has been used clinically for the treatment of myasthenia gravis and tardive dyskinesia (115). Placebo-controUed studies have indicated modest efficacy of tacrine to treat AD dementia (122,123) and in 1993 the dmg was recommended for approval by the PDA under the trade name Cognex. Tacrine (19) has been shown to interact with sites other than AChE, such as potassium channels (124) and muscarinic receptors. However, these interactions are comparatively weak and are not thought to contribute to the biological activity of the dmg at therapeutic levels (115). 

In addition, many grades of paper and paperboard are used in direct or indirect contact with foods. Thus, many mills only use paper chemicals that have been cleared for use by the U.S. Pood and Dmg Administration (PDA) (3), so that it is not necessary to segregate machine broke (off-grade paper and edge clippings that are reclaimed for their fiber value) and white water. Most of the chemicals discussed in this article are approved by the PDA for use in paper and paperboard that are intended for appHcations in food processing and packaging. However, there are various restrictions on both the specific functional uses and amounts of paper chemical additives which can be used, so the PDA status should be confirmed by the suppHer before use. 

Pubhc concerns about pesticides in the diet of infants and children resulted in an expert committee convened by the U.S. National Academy of Sciences which devoted four years to the review of all available data. A consensus report was issued in 1993 (80). A number of recommendations for further work to more precisely define what constitutes the diet of infants and children were made. No risk could be estimated. The residue data reviewed by the panel were mainly from monitoring studies conducted by the PDA using multiresidue methods to analyze fresh produce and market basket samples collected from various geographic areas (81,82). These and other rehable scientific studies have demonstrated that relatively few food samples contain detectable residues. Most residues are far below estabhshed tolerances which are set above the maximum residue found in treated raw agricultural... 

The pharmacist or physician can report any problems experienced with dmg products and medical devices. In cases where the PDA and/or manufacturer finds that a marketed product constitutes an actual or potential threat to the safety and welfare of the pubhc, that product must be withdrawn from the marketplace, ie, recalled. Several classes of recalls exist, depending on the relative danger that the product exhibits. C/ass I dmgs pose a serious health threat and may require withdrawal at the consumer level C/ass II dmgs pose a possible or potential health problem that usually means withdrawal at the pharmacy or wholesaler levels and C/ass III dmgs may present a remote hazard to health and safety. 

In 1966 the PDA utilized the services of the National Academy of Sciences—National Research Council (NAS—NRC) to estabhsh the relative therapeutic efficacies of prescription dmgs marketed between 1938 and 1962. Those products that were found to meet safety and efficacy requirements were allowed to stay on the market. Suitable changes were required for other products for compliance, ie, formulation or label changes, additional data... 

Health and Safety Factors. Animal-feeding studies of DMPPO itself have shown it to be nontoxic on ingestion. The solvents, catalyst, and monomers that are used to prepare the polymers, however, should be handled with caution. Eor example, for the preparation of DMPPO, the amines used as part of the catalyst are flammable toxic on ingestion, absorption, and inhalation and are also severe skin and respiratory irritants (see Amines). Toluene, a solvent for DMPPO, is not a highly toxic material in inhalation testing the TLV (71) is set at 375 mg/m, and the lowest toxic concentration is reported to be 100—200 ppm (72). Toxicity of 2,6-dimethylphenol is typical of alkylphenols (qv), eg, for mice, the acute dermal toxicity is LD q, 4000 mg/kg, whereas the acute oral toxicity is LD q, 980 mg/kg (73). The Noryl blends of DMPPO and polystyrene have PDA approval for reuse food apphcations. 

Polyalurninum chloride products used in the treatment of potable (drinking) water must be approved by the National Sanitation Eoundation (NSE). NSE certification has superseded EPA approval. Aluminum chlorohydrate for topical use as an antiperspirant is regulated by PDA. 

Post-amendment devices ate automatically classified as Class III devices. However, a post-amendment device can be brought to market under the 510(k) process, if the PDA determines that the device is "substantially equivalent" to a preamendment device. If the post-amendment device is identical to a preamendment device, it is substantially equivalent. Then the 510(k) is accepted by the PDA and the post-amendment device is placed in the same class as the preamendment device to which it is substantially equivalent. Pot example, a wound dressing identical to a preamendment Class I wound dressing would be found substantially equivalent to the preamendment wound dressing and classified in Class I. 

Other offices within ODER may become involved in the review process via consults. Eor example, the Office of Epidemiology and Biostatistics analyzes statistical data, the Office of Research Resources provides bioavailabiHty reviews, and the Office of Compliance determines from the results of inspections whether the firms meet EDA s Current Good Manufacturing Practice (cGMP) regulations. Advisory committees composed of independent experts are often asked to meet and further analyze the data. Often they also advise as to what additional data and information may be needed. After PDA s review is completed, PDA issues either a Summary Basis of Approval (SBA) for the dmg or a recommendation against approval. If approved, PDA releases the SBA and a summary of the safety and effectiveness data to the general pubHc. 

Regulating dmg quaHty is a federal concern that is reflected beyond the approval process. PDA has implemented extensive regulations to ensure that dmg products that are produced and marketed, as well as thek chemical constituents, continue to meet high standards of quaHty, purity, and safety, and have the identity and strength accurately represented. 

Another distinct class of dmgs are those requiring a prescription or a written order from a physician or health professional. Congress authorized PDA to determine whether a dmg should be a prescription dmg. Typically prescription dmgs are those that (/) have habit-forming characteristics (2) requke a physician s supervision, because of toxic or other harmful effects, methods of use, or coUateral measures necessary for use or (J) are limited to prescription use under an NDA. 

Unless otherwise exempt, a firm must submit a premarket notification, also called a 510(k), to the PDA 90 days before it intends to market a device for the first time (17). The 510(k) submission must contain sufficient information to show that the device in question is substantially equivalent to a legally marketed device for a particular intended use. This notification is also required for a product when there is a change or modification to a product that may significantly affect the safety or effectiveness of the device, or when there is a significant change or modification to the intended use of the device. 

Class III devices, unless they are substantially equivalent to a device already marketed without a PMA appHcation, require formal PDA approval through the PMA process before initial sale. The PMA process is comparable to the new dmg approval process (18). In both cases, safety and effectiveness data must be reviewed by PDA prior to marketing. An approved PMA appHcation acts like a private Hcense granted to the appHcant to market a particular device. Other firms seeking to market the same type of device for the same use must also have an approved PMA. 

PMA requirements differ between preamendment and post-amendment devices. Preamendment devices are those in commercial distribution before May 28, 1976 post-amendment devices are those first commercially distributed after the date. Class III post-amendment devices that are not substantially equivalent to preamendment Class III devices are considered new devices. Manufacturers of such devices are required to obtain PMA appHcation approval before marketing these. If the post-amendment device is substantially equivalent to a preamendment device and PDA has not initiated a regulatory process specifically requiring the submission of a PMA for the device category, a 510(k) submission can be made. 

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