LOADING APPARATUS FOR A FREEZE DRYER FIELD OF THE INVENTION

The invention relates to loading apparatus for loading of containers into freeze dryer that are not set up for automated loading.

BACKGROUND OF THE INVENTION

Lyophilization or freeze drying is a process in which water is removed from a product after it is frozen and placed under a vacuum, allowing the ice to change directly from solid to vapor without passing through a liquid phase. The lyophilization process generally includes the following steps:

• dissolving the drug and excipients in a suitable solvent, generally water for injection (WFI)

• sterilizing the bulk solution by passing it through a 0.22 micron bacteria- retentive filter

• receiving into individual sterile containers _, and partially stoppering the containers under aseptic conditions

• transporting the partially stoppered containers to the lyophilizer and loading into the chamber under aseptic conditions

• freezing the solution by placing the partially stoppered containers on or pre- freezing in another chamber

• applying a vacuum to the chamber and heating the shelves in order to evaporate the water from the frozen state

It is important to note that filled containers that are transported and loaded into lyophilizer are partially stoppered and highly susceptible to contamination. Utmost care is therefore required during the transfer process of the filled containers to the lyophilizer. The Good manufacturing requirements indicate that the transfer and handling should take place under primary barriers, such as the laminar flow hoods under which the containers were filled. In a small or medium manufacturing unit, it is possible that the transport of containers to lyophilizer is done manually. Since the containers are not completely sealed and are partially stoppered, there is always a great concern of potential contamination. In order to overcome these problems, manufacturers may develop a laminar flow cart to transport the containers from the receiving line to lyophilizer or may build altogether new facility where the receiving line is located close to lyophilizer. Also, the manufacturer may provide a primary barrier extending from the receiving line to lyophilizer.

Some loading methods are known to involve the use a single frame to cover the entire freeze dryer shelf. The loading apparatus carrying such a single frame would be large in size as well as heavy and may not be usable in existing facilities which may be having narrow corridors. In some methods, the loading apparatus uses plurality of frames arranged in multiple rows and columns, where the frames may be transported individually or one row at a time. Transferring one row at a time may be, once again, not feasible due to the narrow size of corridors. So also, transferring single frames require the loading apparatus to be positioned precisely at the receiving and loading locations, for which the prior art suggests additional installations to be done in the manufacturing facility or to the freeze dryer. In a pre-existing, operational manufacturing unit, such changes are not at all feasible. So also, the alterations may be very expensive as well as time -consuming.

Attempts to tackle this situation have been documented in patent documents, for example, in United States patent numbers US 5, 129, 162A and US 5,649,800A. In United States Patent Number 5, 129, 162, the patent discloses that the containers are placed on a table top of a transfer table and, the transfer table is brought into proximity with the placement surface in a chamber of a freeze-drying apparatus with the help of some elements such as guide rails or abutment locations to be installed on the freeze dryer, to facilitate the alignment. Thus, in order to make use of such loading apparatus, additional modifications to the freeze dryer may be needed in order to make such loading apparatus operable. Such an additional alteration or modification to the freeze dryer may be expensive and time consuming, especially in a pre-existing manufacturing facility which is operational. Also some times such modifications to the freeze dryer may not be even possible. The prior art reviews further provides automated loading apparatus. Suitable apparatus are sometimes permanently installed in the vicinity of the freeze dryer subsequently transfer the containers o the shelf such as described in United States patent application publications numbers US20060016094A1 and US20090241362A1. In order to make the loading and unloading process more amenable to automation, newer freeze dryers are constructed to have shelves whose height can be adjusted so that loading and unloading can take place at a constant height. The layout of the manufacturing facility is designed so that conveyors may be installed to transport individual containers from the receiving area to the freeze dryer. The use of conveyors may be a concern since the container stoppers are not sealed and the transfer on conveyer may cause tipping and spillage.

Thus, there remains a need of loading apparatus that can fit into the pre-existing manufacturing facility and which do not require such alterations or installations. In addition, Installation of conveyers in a pre-existing facility typically involves considerable modification to the facility and thus renders such methods difficult and expensive to implement. Further, older designs of freeze dryers may not allow loading to be accomplished at a fixed height, which further adds complexity of installing conveyors. Alternatively, containers may be transported in frames. Several containers are placed on a supporting flat surface with a frame surrounding them, so that the collection of containers can be moved as a contiguous entity. The supporting surface is then carried to the freeze dryer, where the frame, with all the containers it encloses, is pushed on to the shelf.

Thus, there is a need of a semi-automatic loading apparatus where the design allows it to be used to load freeze dryers of different makes without the need to make any alterations to the freeze dryer design or to the facility or both. In pre-existing manufacturing units it is always desirable not to alter or modify the facility. The present invention precisely provides solution to this problem. The loading apparatus of the present invention is compact, light and easy to maneuver around the manufacturing area and permit the loading operation to be carried out without the need for sophisticated automation and is compatible for loading various makes of freeze dryers without the need to make any significant alterations or installations in the freeze dryer or to the manufacturing facility. OBJECT OF THE INVENTION

it is the object of the present invention to provide a loading apparatus that is compact, light and easy to maneuver in the manufacturing area and simple in design without the need for sophisticated automation,

Further it is the object of the invention to provide a loading apparatus that can be immediately deployed in existing facilities where receiving area may be located remotely to the freeze dryer or it may be difficult to install conveyors or the facility may have narrow corridors or different designs of freeze dryers with varying loading heights.

Further it is the object of the invention to provide a loading apparatus to eliminate direct human handling of the containers and maintain a sterile environment at all times during the loading process.

Also, there lies a need to develop a loading apparatus that can be flexible for various versions or makes of a freeze dryer without the requirement of any modification to the freeze dryer

It is another important object of the invention to provide a Class 100 area to the partially stoppered containers while being transferred from the receiving station to the freeze dryer.

SUMMARY OF THE PRESENT INVENTION

The present invention may be summarized as follows:

(A) A loading apparatus to load the containers to a freeze dryer, said apparatus comprising transfer table (1) attached to a table holder (2) wherein, the table holder (2) is moveably attached to the carriage (12) of the loading apparatus and wherein the transfer table (1) has a transfer edge (4) free to move in accordance with Figure 3b and the transfer holder (2) is operable to selectively move in a lateral (L), vertical (V) and depth (D) directions in relation to the carriage (12) of the loading apparatus. (B) A loading apparatus as described in (A) wherein transfer table (1) is fixed to table holder (2) on one side and free on the freeze dryer side.

(C) A loading apparatus as described in (B) wherein the transfer table (1) is fixed to the table holder (2) by means of one or more bolts (3).

(D) A loading apparatus as described in (A) wherein the table holder (2) is initially positioned such that the transfer edge (4) is above the freeze dryer shelf forming a small overlap (O) and subsequently a downward motion imparted to the table holder (2) causing the transfer edge (4) to bear against the surface of the freeze dryer shelf (9)

(E) A loading apparatus as described in (B) wherein surface of the transfer table (1) is held at an incline in relation to the surface of the freeze dryer shelf.

(F) A loading apparatus as described in (A) wherein the table holder (2) is initially positioned such that the transfer edge (4) is below the table of the receiving station (6) forming a small overlap (O) and subsequently an upward motion imparted to the table holder (2) causing the transfer edge (4) to bear against the surface of the table of receiving station (6).

(G) A loading apparatus as described in (A) wherein the table holder (2) can be moved in a lateral direction (L) in relation to the carriage (12) of the loading apparatus by mechanical means.

(H) A loading apparatus as described in (A) wherein the table holder (2) can be moved in a lateral direction (L) in relation to the carriage (12) of the loading apparatus by electric means.

(I) A loading apparatus as described in (A) wherein a laminar air flow unit is attached such that the containers are under laminar flow at all the time during the loading process. (J) A loading apparatus as described in (A) wherein the transfer table (1) is joint-less. (K) A loading apparatus as described in (J) wherein the transfer edge (4) bears upon the surface of the freeze dryer shelf and the surface of the transfer table (1) is at a small incline to facilitate smooth transfer across the transfer edge (4).

(L) A loading apparatus as described in (A) wherein the carriage (12) of the loading apparatus includes stoppers or abutment locations (15) by virtue of which the position and distance of the carriage (12) of the loading apparatus from the reference plane can be set by bringing the carriage (12) of the loading apparatus into contact with the reference plane through the abutment locations.

(M) A loading apparatus described in (L) wherein the stoppers or abutment locations ( 15) can be attached to the reference surface by magnetic means.

(N) A loading apparatus described in (A) wherein pulling fingers engage and disengages the frame of containers to a slider bar (16) attached to the apparatus in order to pull the frame onto the transfer table (1) from a table of the receiving station (6) that holds a Preformatted frame of containers.

BRIEF DESCRITION OF THE FIGURES

Figure 1 : Describes one of the embodiments of the present invention showing motions of the table holder (2) relative to the carriage (12) of the loading apparatus and adjustment direction of the stoppers or abutment locations on the carriage ( 12) of the loading apparatus.

Figure 2: Shows motions of the slider bar (16) and a set of pulling fingers relative to the table holder (2).

Figure 3: Shows several views of the transfer table (1) and its attachment with the table holder (2). Also shown is the free movement of the transfer edge (4) allowable by the configuration.

Figure 4a: Shows use of stoppers or abutment locations ( 15) to position the carriage ( 12) of the loading apparatus at a desired position and distance with a reference surface at the freeze dryer ( 19).

Figure 4b: Shows use of stoppers or abutment locations (15) to position the carriage ( 12) of the loading apparatus at a desired position and distance with a reference surface at the table of receiving station (6).

Figure 5a: Shows the configuration of the transfer table (1) and table holder (2) at the time of loading a frame of containers to a freeze dryer shelf (9).

Figure 5b: Shows the configuration of the transfer table (1) and table holder (2) at the time of receiving a frame of containers from the table of receiving station (6).

Figure 5c: Shows an alternative configuration of the transfer table and table holder at the time of receiving a frame of containers from the table of receiving station (6). Figure 6: Shows the use of the lateral motion (L) in order to precisely position the transfer table (1) along the length of the freeze dryer shelf (9) before pushing the frame.

DETAILED DESCRITION OF THE FIGURES

Figure 1 shows the loading apparatus according to one of the embodiments of the present invention. It comprises a carriage (12) with castors (13) located underneath, so that it is free to be maneuvered on the floor in all directions. A table holder (2) is moveably attached to the carriage (12) of the loading apparatus so that the transfer edge (4) of the transfer table (1) is on the front end of the carriage (12) of the loading apparatus. The table holder (2) can be selectively actuated to move relative to the carriage (12) of the loading apparatus in three directions, viz. vertical (V) direction, depth (D) direction in a horizontal plane along the front-rear axis of the carriage, and lateral (L) direction, also in a horizontal plane, but along the length of the transfer edge (4). A hand wheel (14) is used to effect the lateral motion (L). A slider bar (16) is moveably attached to the table holder (2) so that it slides in the direction shown. A pusher (10) is attached to the slider bar (16). Pulling fingers (1 1) may be pivoted on to the pusher (10). The carriage (12) of the loading apparatus has stoppers or abutment locations (15) attached to the front end, such that the length (DR) of each stopper is adjustable.

Figure 2 shows an embodiment of the loading apparatus of the present invention. A slider bar (16) is moveably attached to the table holder (2) so that it slides in the direction shown. A pusher (10) is attached to the slider bar (16). Pulling fingers (1 1) may be pivoted on to the pusher (10).

Figure 3 shows a transfer table (1) moveably attached to the table holder (2). In one embodiment as shown in Figure 3c and Figure 3a, one side of the transfer table (1) is fixed to a table holder (2) by means of one or more bolts (3). The transfer edge (4) is free to move as shown in Figure 3b and Figure 3e, to the extent permitted by the flexibility of the transfer table (1). The underside of the transfer edge (4) can thus become exactly coplanar to any substantially coplanar surface that the transfer table (1) is lowered on to. Since, the edges of the freeze dryer shelves are located some distance behind the front face of the freeze dryer, the table holder (2) is fully extended in the depth direction (D) in order to bring the transfer edge (4) in proximity with the freeze dryer shelf (9). Referring to Figure 4a, the length of the stoppers or abutment locations (15) is set so that the transfer edge (4) has the desired overlap (O) on the freeze dryer shelf (9) when the stoppers or abutment locations (15) bear on a reference surface (19) on the freeze dryer. The carriage (12) of the loading apparatus is positioned at the receiving station in the same manner, but with the table holder (2) in the retracted position. Fig 4b shows the configuration at the table of the receiving station (6). The vertical motion (V) of the table holder (2) of the loading apparatus (please see Figure 1) places the transfer edge (4) at the appropriate height relative to the freeze dryer shelf (9) or to the table of the receiving station (6).

Figure 5a illustrates the operation of loading the shelf of freeze dryer (9) from loading apparatus. The table holder (2) is initially positioned such that the transfer edge (4) is above the freeze dryer shelf forming a small overlap (O) on it. In addition, the surface of the transfer table (1) is held at an incline in relation to the surface of the freeze dryer shelf (9). Subsequently a downward vertical motion is imparted to the table holder (2), causing the transfer edge (4) to bear against the surface of the freeze dryer shelf (9), thus bringing the two in alignment. Proximity sensors or micro-switches (5) (Figure 3b and Figure 3e) attached to the table holder (2) detect the loss of contact with the transfer table (1), and therefore, co-planarity of the two surfaces. This input stops further downward motion of the table holder (2). A pusher (10) then slides along the transfer table (1) to push the frame onto the freeze dryer shelf.

Figure 5b illustrates the operation where the containers are received from the receiving station on to the transfer table (1) of the loading apparatus.

The table holder (2) is initially positioned such that transfer edge (4) is below the table of the receiving station (6) forming a small overlap (O) and subsequently an upward vertical motion in imparted to the table holder (2), causing the transfer edge (4) to bear against the surface of the table of receiving station (6). The vertical motion is stopped when proximity sensors or micro-switches attached beneath the table of receiving station (6) indicate loss of contact, and therefore, co-planarity of the underside of the edge of the receiving table (6) and the surface of the transfer table (1). This input stops further upward motion of the table holder (2). A pusher (7) which slides along the table of receiving station (6) pushes the frame onto the transfer table (1). Figure 5c shows an alternative embodiment of the present invention which does not have a pusher (7) at the receiving station, Rather it includes a pulling mechanism, which comprises of pulling fingers (1 1) pivoted onto the pusher (10). The pusher (10) on the transfer table (1) is kept in extended position. After alignment has taken place, the pulling fingers (1 1) are engaged in the frame. The pusher (10) is then retracted to pull the frame onto the transfer table (1).

Figure 6 shows the use of mechanical means such as a hand wheel (14) in order to place the transfer table (1) at the exact desired position along the width of the freeze dryer shelf (9). During the process of loading, the carriage (12) of the loading apparatus is first maneuvered approximately to the correct lateral position in front of the freeze dryer. The table holder (2) is so contrived that rotation of the hand wheel (14) causes the table holder (2) to move in the lateral direction (L). This actuation is used to precisely position the frame to be transferred (21), adjacent to a previously loaded frame (20). This feature allows the lateral positioning of the frame quickly and easily without the need for any locators attached to the freeze dryer or elsewhere in the manufacturing facility.

DETAILED DESCRIPTION OF THE PRESENT INVENTION

The term 'Class 100 area' (ISO 5) means the air in immediate proximity of the exposed sterilized containers/closures and filling/closing operations would be of appropriate particle quality when it has a per-cubic-meter particle count of no more than 3250 in a size range of 0.5 μπι and larger when counted at representative locations normally not more than 1 foot away from the work site, within the airflow, and during filing/closing operations. This level of air cleanliness is also known as Class 100 (ISO 5).

The present invention provides a loading apparatus to load the containers to a freeze dryer, said apparatus comprising transfer table (1) attached to a table holder (2) wherein, the table holder (2) is moveably attached to the carriage (12) of the loading apparatus and wherein the transfer table (1) has a transfer edge (4) free to move as in Figure 3e and the transfer holder (2) is operable to move in a lateral (L), vertical (V) and depth (D) directions in relation to the carriage (12) of the loading apparatus. In one embodiment, the lateral direction (L) in relation to the carriage (12) of the loading apparatus can be achieved by mechanical means. Alternatively, the lateral direction (L) can be achieved by electric means. This lateral movement of the transfer holder of the loading apparatus allows minimum human intervention while loading the freeze dryer with the partially stoppered containers. This is a very remarkable advantage since it is known that in a clean room environment, human presence is a major source for contaminating particles.

The loading apparatus according to one of the embodiments of the present invention comprises a carriage (12) with castors (13) located underneath, so that it is free to be maneuvered in all directions. A table holder (2) is moveably attached to the carriage (12) of the loading apparatus so that the transfer edge (4) of the transfer table (1) is on the front end of the carriage (12) of the loading apparatus. The table holder (2) can be selectively actuated to move relative to the carriage (12) of the loading apparatus in three directions, viz. vertical (V) direction, depth (D) direction in a horizontal plane along the front-rear axis of the carriage, and lateral (L) direction, also in a horizontal plane, but along the length of the transfer edge (4). A hand wheel (14) is used to effect the lateral motion (L). A slider bar (16) is moveably attached to the table holder (2) so that it slides in the direction shown. A pusher (10) is attached to the slider bar (16). Pulling fingers (11) may be pivoted on to the pusher (10). The carriage (12) of the loading apparatus has stoppers or abutment locations (15) attached to the front end, such that the length (DR) of each stopper is adjustable. The desired position and distance of the carriage (12) of the loading apparatus from a vertical reference surface can be achieved quickly and easily by maneuvering the carriage (12) of the loading apparatus to the reference surface on the freeze dryer or the table of receiving station (6) and bearing the stoppers or abutment locations (15) on it (see Figure 4). The stoppers or abutment locations (15) may be constructed to have a controllable magnetic property, and the reference surfaces may have ferro-magnetic properties or vice versa, so that the carriage ( 12) of the loading apparatus is secured in position when the magnetic property is activated. The apparatus can be constructed so that the range of vertical motion (V) allows the apparatus to be used with the desired receiving stations and freeze dryers.

In one embodiment as shown in Figure 3c and Figure 3a, one side of the transfer table (1) is fixed to a table holder (2) by means of one or more bolts (3). The transfer edge (4) is free to move as shown in Figure 3b and Figure 3e, to the extent permitted by the flexibility of the transfer table (1). This design allows the underside of the transfer edge (4) to become exactly coplanar to the freeze dryer shelf even if there are small alignment differences between the table holder (2) and freeze dryer shelves. This feature also allows the same loading apparatus to be used for different types of freeze dryers. This design has an additional advantage that, no modifications or attachments are required on the freeze dryer shelf in order to correctly align the transfer table (1) to it. In order to compensate for the small step over which the containers have to slide over, the surface of the transfer table is held at an incline that facilitates smooth transfer across the transfer edge (4). This enables a jerk-free transfer of the containers over the transfer edge (4).

In one preferred embodiment of the present invention, a slider bar (16) is moveably attached to the table holder (2) so that it slides in the direction shown. A pusher (10) is attached to the slider bar (16). Pulling fingers (1 1) may be pivoted on to the pusher (10). which engages and disengages the frame of containers to a slider bar (16) attached to the apparatus in order to pull the frame onto the transfer table (1 ) from a table of the receiving station (6) that holds a preformatted frame of containers. The transfer table (1) is constructed so that it can be easily removed and reattached to the table holder (2). Similarly, the pusher (10) and pulling fingers (11) can be easily removed and reattached to the slider bar (16). This serves a twofold purpose, firstly, since these parts come into direct contact with the containers, ease of removal and reattachment allows for easy sterilization. Secondly, if a frame of different size has to be handled, then only these two parts need to be replaced. This embodiment is described in the description of Figure 5c which shows a pulling mechanism such as pulling fingers (11) pivoted onto the pusher (10). In this embodiment, the pusher (10) on the transfer table (1) is kept in extended position. After alignment has taken place, the pulling fingers (11) are engaged in the frame. The pusher (10) is then retracted to pull the frame onto the transfer table (1). Alternatively, a ferromagnetic material may be embedded at the rear side of the frame so that a controllable magnetic property of the pusher (10) can be used as pulling mechanism.

In one embodiment, the loading apparatus of the present invention includes a laminar air flow unit (17) such that the containers are under coverage at all times during loading process. The apparatus can have onboard rechargeable energy sources, such as batteries or air reservoirs, eliminating the need for an umbilical for power supply. In one particular embodiment, the transfer table (1) is characterized in that it is joint-less and has a transfer edge (4) over which the containers move. During transfer, said transfer edge is made coplanar with the surface of a freeze dryer shelf (9) by bearing the transfer edge (4) onto the surface of the freeze dryer shelf (9), while holding the surface of transfer table (1) at an incline in relation to the surface of the freeze dryer shelf (9).

Said loading apparatus can be freely moved in all directions on a level surface. Its weight and dimensions are such that it can be easily maneuvered manually in narrow corridors, without the need of tracks or any guiding installations. Said loading apparatus comprises a laminar air flow unit and at least one rechargeable energy source to run the laminar air flow unit and provide motive power for all movements imparted to the frame of containers,

Although the invention has been described in terms of particular embodiments and applications, one of ordinary skill in the art, in light of this teaching, can generate additional embodiments and modifications without departing from the spirit of or exceeding the scope of the claimed invention, it should be emphasized that the above- described embodiments of the present invention, particularly any "preferred" embodiments, are merely possible examples of the invention of implementations, merely set forth for a clear understanding of the principles of the invention. Accordingly, it is to be understood that the drawings and descriptions herein are proffered by way of example to facilitate comprehension of the invention and should not be construed to limit the scope thereof.