Method for the production of freeze-dried pellets comprising factor VIII

Patent metadata

Field	Value
Publication number	US-10407489-B2
Application number	US-201615775730-A
Country	US
Kind code	B2
Filing date	Nov 4, 2016
Priority date	Nov 12, 2015
Publication date	Sep 10, 2019
Grant date	Sep 10, 2019

Abstract

A method for the production of freeze-dried pellets comprising factor VIII comprises the steps of: a) freezing droplets of a solution comprising factor VIII to form pellets; b) freeze-drying the pellets; wherein in step a) the droplets are formed by means of droplet formation of the solution comprising factor VIII into a cooling tower which has a temperature-controllable inner wall surface and an interior temperature below the freezing temperature of the solution and wherein in step b) the pellets are freeze-dried in a rotating receptacle which is housed inside a vacuum chamber.

First claim

The invention claimed is:

1. A method for the production of freeze-dried pellets comprising factor VIII, the method comprising the steps of:
a) freezing droplets of a solution comprising factor VIII to form pellets; and
b) freeze-drying the pellets to produce freeze-dried pellets comprising factor VIII,
wherein the droplets in step a) are formed by droplet formation, wherein the solution comprising factor VIII is sprayed into a cooling tower comprising a temperature-controllable inner wall surface and an interior temperature below a freezing temperature of the solution, and
wherein in step b) the pellets are freeze-dried in a rotating receptacle, wherein the rotating receptacle is housed inside a vacuum chamber.

2. The method of claim 1 , further comprising
c) storing and homogenizing the freeze-dried pellets comprising factor VIII;
d) assaying the freeze-dried pellets comprising factor VIII while they are being stored and homogenized; and
e) loading the freeze-dried pellets comprising factor VIII into containers.

3. The method of claim 1 , wherein freezing droplets of a solution comprising factor VIII to form pellets comprises passing the solution comprising factor VIII through frequency-assisted nozzles.

4. The method of claim 3 , wherein an oscillating frequency of the frequency-assisted nozzles is ≥1000 Hz and ≤2000 Hz.

5. The method of claim 1 , wherein the inner wall surface of the cooling tower comprises a temperature of ≤−120° C.

6. The method of claim 1 , wherein the inner wall surface of the cooling tower is cooled by passing a coolant through one or more pipes, wherein the one or more pipes are in thermal contact with the inner surface.

7. The method of claim 2 ,
wherein factor VIII of the freeze-dried pellets comprising factor VIII comprises a target dosage,
wherein assaying the freeze-dried pellets comprising factor VIII while they are being stored and homogenized comprises determining an active content of factor VIII in the freeze-dried pellets comprising factor VIII, and
wherein loading the freeze-dried pellets comprising factor VIII into containers comprises loading an amount of freeze-dried pellets comprising factor VIII into the containers such that a dosage of factor VIII in the amount of freeze-dried pellets comprising factor VIII equals or exceeds the target dosage by ≤25%.

8. The method of claim 1 , wherein the pellets of step a) comprise a maximum of the particle size distribution d50 of ≥200 μm to ≤1500 μm.

9. The method of claim 1 , wherein the solution comprising factor VIII in step a) comprises a content of dissolved solids of ≥8 weight-% and ≤12 weight-%.

10. The method of claim 1 , wherein 1 gram of the solution comprising factor VIII in step a) comprises the following composition, the balance being water for injection:

Factor VIII
≥99 IU to ≤101 IU

Sucrose
≥68 mg to ≤72 mg

Histidine
≥2 mg to ≤4 mg

Glycine
≥23 mg to ≤26 mg

NaCl
≥1 mg to ≤3 mg

CaCl 2
≥0.2 mg to ≤0.4 mg

Polysorbate 80
≥0.07 mg to ≤0.1 mg.

Assignees

• Bayer Pharma AG

Inventors

• Olbrich Carsten
• Plitzko Matthias
• Luy Bernhard
• Schneid Stefan Christian

Classifications

• A61P7/04

  Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents · CPC title

• F26B11/04

  rotating about a horizontal or slightly-inclined axis {(F26B11/022, F26B11/024, F26B11/026, F26B11/028 take precedence)} · CPC title

• F26B11/049

  with provisions for working under increased or reduced pressure, with or without heating · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A61K38/37

  Factors VIII · CPC title