Reconstitution shelf life

Water-borne adhesives are preferred because of restrictions on the use of solvents. Low viscosity prepolymers are emulsified in water, followed by chain extension with water-soluble glycols or diamines. As cross-linker PMDI can be used, which has a shelf life of 5 to 6 h in water. Water-borne polyurethane coatings are used for vacuum forming of PVC sheeting to ABS shells in automotive interior door panels, for the lamination of ABS/PVC film to treated polypropylene foam for use in automotive instmment panels, as metal primers for steering wheels, in flexible packaging lamination, as shoe sole adhesive, and as tie coats for polyurethane-coated fabrics. PMDI is also used as a binder for reconstituted wood products and as a foundry core binder. 

Figure 13.5 Outline of the production strategy of CEA-SCAN. The antibody-producing hybridoma cell line was originally obtained by standard methods of hybridoma generation. Spleen-derived murine B-lymphocytes were fused with murine myeloma calls. The resulting stable hybridomas were screened for the production of anti-CEA monoclonals. The clone chosen produces an IgG anti-CEA antibody. Note that the finished product outlined above is not radiolabelled. The freeze-dried antibody preparation (which has a shelf life of 2 years at 2-8 °C) is reconstituted immediately prior to its medical use. The reconstituting solution contains 99mTc, and is formulated to facilitate direct conjugation of the radiolabel to the antibody fragment...

Shelf life (when necessary after reconstitution or opening the container for the first time)... 

Two of the more recent such approvals are that of Ovitrelle and Luveris. Ovitrelle is the trade name given by Serono to its recombinant hCG-based product. The producer is an engineered CHO cell line that has been co-transfected with the genes coding for both the hCG a- and P-subunits. Downstream processing entails a combination of several chromatographic and ultrafiltration steps and the final product is presented in freeze-dried form. Each vial of product contains 285 fig of active substance (hCG) and the product has been assigned a 2 year shelf-life. It is reconstituted with water for injections (WFI) immediately before use. 

Buffer Maintain pH of formulation through product shelf life Maintain pH of formulation during lyophilization and upon reconstitution... 

There is also a market for reconstituted fruit juice made from concentrate and not further processed but maintained, during its short shelf life, by refrigeration. 

For the mAb in this comparison, the initial product is from an early cell line that is formulated as a liquid, stored frozen, and administered by IV injection. This is sufficient for initial safety, PK/PD, and pharmacologic activity assessments in phase 1 but is not an acceptable product profile for commercialization. To be competitive in the intended clinical indication, the product needs to be stored as a lyophilized powder (to increase shelf life and concentration), to be reconstituted and injected SC as needed. The acceptable volume for SC injection dictates a much more concentrated formulation. 

Drug Product Stability. A description of the stability protocols and results supporting the product s stability (expiration date and storage condition) should be provided. Stability data supporting the proposed shelf-life of reconstituted drug products and for all labeled dilutions also should be included. The stability protocol provided should include the following ... 

The lyophilized drug nanosuspensions can be transferred to a hnal dry oral dosage form such as tablets or reconstituted prior to administration. Drug nanosuspensions can be directly used as parenteral products. A shelf life of up to three years was shown for selected nanosuspensions. Sterilization can be achieved by aseptic processing of previously sterilized components, membrane filtration for particles sufficiently small or for drugs that can withstand it, steam sterilization, or y-irradiation. 

Lyophilization stoppers can be a source of volatiles that may contaminate the product during lyophilization or during its shelf life. Pikal and Lans [5] found that paraffin wax-like materials and sulfur from stoppers were a source of haziness in reconstituted antibiotics and that lower pressures during lyophilization exacerbated the problem. Further research determined that unsaturated and aromatic hydrocarbons from halobutyl stoppers were mainly responsible for the formation of the haze [6]. The amount of haziness caused by volatiles varies greatly with the type of stopper used [7]. The investigators [6] showed that Teflon-coated stoppers produced the least amount of haze. However, the data on most of the stoppers tested were not quantitative. Coated stoppers are considerably more expensive and may not seal with the vial well if the coating surface is on the upper flange of the vial [8]. 

Note for Guidance on Maximum Shelf-life for Sterile Products for Human Use After First Opening or Following Reconstitution CPMP, July 1998. 

Sodium ampicillin is approved for i.v. or i.m. administration to humans and horses. These formulations have a very short shelf-life after reconstitution. The human approved formulation come in a variety of presentations that are more convenient for use in different sizes of horses. The trihydrate salts of amoxicillin and ampicillin are available for i.m. administration to cattle. 

Oprelvekin is supplied us a lyophili/ed powder for recon-.stitution. Excipients include glycine and phosphate buffer components. The powder has a shelf life of 24 months. It should be stored at 2 to 8°C. If it is frozen, thaw it before reconstitution. 

Change in shelf life after reconstitution. Conditions to be met the studies must show that the reconstituted product continues to comply with the... 

Shelf-life - as packaged for sale, after reconstitution (if applicable), after first opening of packaging container... 

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