Lyophilized products

Kits. Kits for the preparation of radiopharmaceuticals are a convenient solution to synthesis of products containing short-Hved radionucHdes (eg, In, I, Tc) bound to a nonradio active moiety. The labeling step is performed either at a commercial radiopharmacy, or within the institutional nuclear medicine laboratory. The kits are usually stored as a frozen solution or lyophilized product. The material of interest is then metered out into kit dosages. The kit vials are thawed or reconstituted and mixed with the appropriate radionucHde. 

Vials - Reconstitute the peginterferon alfa-2b lyophilized product with only 0.7... 

Dosage form Ceredase is a sterile solution for injection, supplied in 5ml bottles containing alglucerase 80 units/ml. Cerezyme is supplied as a sterile lyophilized product for injection. Each vial contains imiglucerase 212 or 424 units. Amost all patients with Gaucher s disease use Cerezyme for enzyme replacement therapy. Ceredase is only available in limited supplies for the treatment of patients who do not tolerate Cerezyme. 

Process Flow, Variables, and Responses Lyophilized Products... 

Step 6. Lyophilized products are then visually inspected according to the... 

Lyophilization simulation simulation of all filling and handling procedures required for processing lyophilized product. Media fills... 

Media fill protocol and manufacturing direction were established and approved per SOPs to simulate process for lyophilized product. 

Area clearance procedure for parenterals QA inspector responsibilities in injectable area Particulate matter in injectables, DSP criteria Visual inspection of lyophilized products parenterals... 

SUBJECT Visual Inspection of Lyophilized Product Parenterals... 

Attachment No. 1700.50(A) Issued date mm/dd/yyyy Revision no. VISUAL INSPECTION OF LYOPHILIZED PRODUCT Product name Batch no. Code no. Batch size Sample size Lyophilized Cake ... 

The hlling operation of lyophilized products shall be accomplished in 24 hours as follows ... 

Lyophilizer media fills will consist of a simulation of all filling and handling procedures that would be required when processing a lyophilized product, such as steam sterilization of lyophilizer 12 hours (minimum) before loading the first tray of media, introduction of the vials into the lyophilizer, holding vacuum for a minimum of 24 hours, and subsequent releasing of vacuum and activation of the stoppering mechanism. 

In cases of freeze-dried (lyophilized) products, reconstitute with the appropriate volume of sterile nonpyrogenic WEI before pooling the samples. 

In addition to the product specifications other attributes peculiar to lyophilized products should be verified. These may include uniformity of cake, cake color, cake height, reconstitution time, moisture content (if not a product specification), and short-term (accelerated) and long-term stability. 

As part of the preformulation activities, investigations include physiochemical character, purity, solubility, stability, and optimal pH studies. In preparation for clinical studies, potential product formulations considering route of administration and solution stability are also studied. Unique to dosage form development studies for lyophilized products, thermal analysis of the drug substance and product formulations are also necessary. Data generated during this phase of product development is useful for future development activities, along with validation. 

Figure 2 A cake that is uniform in appearance, texture, and color, occupying the original volume of the liquid fill epitomizes a pharmaceutical elegance for a lyophilized product. 

The defined range suitable for acceptable stability may approach the variability of the moisture determination method or may be as great as a few percent. For example, many lyophilized products with the USP have a finished product residual moisture specification of less than 2% of dry weight. Other products, such as amphotericin B, have a residual moisture limit of 8.0% [31]. Whether the allowable residual moisture specification is small or large, a range of acceptable residual moisture needs to be identified and correlated to suitable long-term stability. 

Scheaffer, G., Sum, L., Trappier, E. Techniques in demonstrating batch uniformity for lyophilized products. Presented at the Annual Meeting of the PDA, Boston, Nov. (1995). 

Fakes, M.G., Dali, M.V., Haby,Th.A., Morris, K.R., Varia, S.A., Serajuddin, A.T.M. Moisture sorption behavior of selected bulking agents used in lyophilized products. PDAJ. Pharm. 

Ethanol (about 60 ml) is added to the above lyophilized product (1.2 g) of N-(l,3-dihydroxy-2-propyl)valiol amine, and the mixture is warmed for 30 minutes in a hot water bath (the bath temperature 90-95°C), followed by leaving on standing in a refiegerator. The resultant crystalline substance is recovered by filtration, washed with ethanol and then dried in a desiccator under reduced pressure. Yield of 0.95 g. MP 162-163°C. [a]D25 = +26.2° (c = 1, H20). 

Stability of biopharmaceutical compounds should also be determined under conditions that mimic their normal usage. For instance, the stability of reconstituted lyophilized products should be assessed with respect to time and temperature and, if applicable, light and mechanical stimuli. Likewise, the stability of a compound included in implantable devices and controlled-release microsphere formulations should be determined over the course of its required use, under conditions which mimic the heat, moisture, light, and enzymatic physiological conditions to which it... 

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