Filling of vials

Vials used in a filling operation are fed into the system automatically by a conveyor from a vial sterilizer or manually from trays that have been 

Powder fills are made by aseptically transferring the sterile bulk powder from its containers into the hopper of the filling machine. The transfer is usually done from a container that is mechanically positioned over the hopper with a solid aseptic connection to the hopper. 

The type of filling machine to be used is best determined from trial runs of various supplier machines. All filling lines and equipment should be designed to prevent contamination by people and particulate matter. A typical vial filling operation is shown in Fig. 5. More recent designs incorporate barrier technology to accomplish this objective.  

Once a vial has been filled with powder, it is stoppered and transported out of the sterile area, and is capped. The current regulatory trend is to perform the capping operation in a sterile area using sterilized caps. After capping, vials are usually visually inspected, labeled, and packaged. 

A liquid fill operation is delivered to a pump throu lines that have been sterilized in place or sterilized and assembled aseptically. 

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After sterile filtration of the formulated therapeutic and aseptic filling of vials, lyophilization is performed. Containing no added preservatives, the finished product is a sterile, non-pyrogenic, lyophilized preparation of concentrated rFVIII for intravenous use. An overview of basic rAHF-PFM processing is depicted in Fig. 3.4. 

Procedure. Samples are collected in 40-mL vials with screw-caps lined with a Teflon septum. Fill the vial to overflowing, ensuring that there are no air bubbles. Add a reducing agent of ascorbic acid (25 mg/40 mL) to quench the further production of trihalomethanes, and seal the vial. Store samples at 4 °C, and analyze within 14 days. 

For the analyses given in Table 1, samples were contained in special polyethylene vials specifically designed to fit the Kaman Nuclear dual-axis rotator assembly. These vials are 4,5cm long and 1.0cm o.d. with an internal volume of 2.3cu cm. When filled, a vial contains approx 0,5g of NC and 2.3g of TNT or HMX. 

P 53] Before operation, a start-up time of about 10 min was applied to stabilize pressure in the chip micro reactor ([R 6]) [20]. As a result, a stable flow pattern was achieved. The reactant solutions were filled into vials. Slugs from the reactant solutions were introduced sequentially into the micro chip reactor with the autosampler and propelled through the chip with methanol as driving solvent. The flow rates were set to 1 pi min The slug volume was reduced to 2.5 pi. 

In freeze-drying, a solution is filled into vials, a special slotted stopper is partially inserted into the neck of the vial (Fig. 3), and trays of filled vials are transferred to the freeze-dryer. The solution is frozen by circulation of a fluid, such as silicone oil, at a temperature in the range of — 35 to about — 45°C through internal channels in the shelf assembly. When the product has solidified sufficiently, the pressure in the freeze-dry chamber is reduced to a pressure less that the vapor pressure of ice at the temperature of the product, and heat is applied to the... 

A laminar flow enclosure provides a means for environmental control of a confined area for aseptic use. Laminar flow units utilize HEPA filters, with the uniform movement of air along parallel lines. The air movement may be in a horizontal or vertical direction and may involve a confined area, such as a workbench, or an entire room. Laminar flow modules are suspended above filling lines, vial- and stopper-washing equipment, and other processes to provide an aseptic and particulate-free environment. 

Figure 5 Temperature profile in primary drying of dobutamine HCl-mannitol (1 1), 53 mg solids/mL, 10 mL fill volume. Vials are 5304 molded glass vials (8.3 cm2 cross-sectional area) which are placed in a flat aluminum tray. The heat flux is 42 cal/(cm2 hr), and the chamber pressure is 0.1 torr. (From Ref. 5.)...

TMA measurements have been helpful in explaining the breakage of vials during the warming of frozen solutions of mannitol and other stereoisomers [1.125]. For example, above -25 °C mannitol expands 30 times more than standard type 1 flint glass. Depending on the filling volume and the concentration, 10-40 % of the vials break when filled with 3 % mannitol solution. 

Fig. 2.2. Automatic filling of a product to be freeze dried in vials, which are cooled by LN2. In the installation the following steps are carried out with a speed of up to 9000 vials per hour Precooling of the vials down to -180 °C, filling of the vials, shock freezing of the product, placing the stoppers on the vials (photograph Groninger Co. GmbH, D-7180 Crailsheim).

The function of 7 ice = f (pc) depends on the design of the plant, quality of the product, type and number of vials, filling height and shelf temperature. With these data, constant, Tice has been found very reproducible during four different runs each with 400 vials filled with 2000 cm3 10 % saccharose solution, operation pressure (pc) controlled at 0.15 mbar ... 

Figure 1.4 is the cooling curve of vials filled with a solution of 4 % solid content and 27 mm filling height. From curve, the vf can be estimated ... 

Step 8 Use separate set of vials filled with background electrolyte for the separation run. It is, however, important to determine the maximum number of runs that can be performed using one set of run vials. This will be discussed further in the durability section. 

The probability of detection of nonsterility in a media fill = 1 - (1 - x)", where x = acceptable contamination rate and n = the number of vials filled, ft should be the same as a normal production run, but not less than 3000 units. 

Number of vials filled - Number of damaged vials The acceptable percentage of contamination is <0.1%... 

Inspection room no. inspection of filled containers (vials... 

The (provide vial size) vial used for the filling of (product name) USP and the media fill run study are the same in dimension and in conformity to glass container requirements as dehned by USP <66l> and EP3.2.1. The stoppers are made up of bromobutyle-based robber formulation, conform to EP 3.2.9 (type I closure), ISO 8871, Current USP, JPXII, and are sterilizable Tyvek bags. The aluminum flip-cap seals used meet the PDA regulation 21 CFR 177.1520 (c) (1.16). 

Within a type of vial, the minimum and maximum vial size must be tested for each neck finish size. Within a size of vial, the maximum fill for that vial size is considered worst case, due to its having the smallest headspace. 

The sterile solutions are filled in different sizes of vials and lyophilized in freeze dryer under aseptic conditions. For this purpose, all operations and conditions were validated according to the approved protocols. To ensure sterility during aseptic processing, the frequency was established to revalidate all sterilization cycles by one-heat penetration/distribution study and microbial challenge test using B. stearothermophilus strip. 

The sterile solutions are filled in different sizes of vials and ampoules. One dosage form is lyophilized injection and filled in A-ml vials. To ensure the sterility during the aseptic processing, it was decided to revalidate the A-ml vials sterilization/depyrogenation cycle once in a year by one heat penetration study and endotoxin challenge test. 

When filling of the ampoules starts in the area, QAI will be informed. He will check the area/equipment clearance and then check the dose of the filled ampoules (by weight and volume), length of the ampoules, and sealing and also check that ampoules/vials are free from particles. See SOP (provide number). When the dose of the filled ampoules is found satisfactory, QAI will give release for filling... 

The number and size of vials and ampoules filled as well as the size of closure used... 

Examine the activities occurring during the filling of the vials in the tray where the positive vial was found. 

The machine run at a speed lower than routine production Fill volume of approximately 50% of vial capacity... 

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