Microbiota restoration therapy (MRT) compositions and methods of manufacture
Microbiota restoration therapy (MRT) compositions (e.g., oral MRT compositions) and methods for manufacturing MRT compositions are disclosed. An example method for manufacturing an MRT composition may include collecting a stool sample, purifying the stool sample to form a purified sample, stabilizing the purified sample to form a stabilized sample, converting the stabilized sample to a solid, adding one or more additives and/or excipients to the solid to form a treatment composition, and encapsulating the treatment composition.
1. A method for manufacturing an oral microbiota restoration therapy (MRT) composition, the method comprising:
manufacturing a drug substance, the drug substance comprising fecal-derived microbiota and a cryoprotectant;
wherein the cryoprotectant includes polyethylene glycol;
adding a diluent to the drug substance;
mixing the drug substance and diluent to form a mixture;
centrifuging the mixture to form an intermediate material;
lyophilizing the intermediate material to form one or more lyophilized pellets;
mechanically processing the one or more lyophilized pellets to form a processed drug material; and
encapsulating the processed drug material in one or more capsules.
2. The method of claim 1 , further comprising filtering the mixture, wherein filtering the mixture comprises filtering the mixture to obtain a sample having particles in the range of 50 to 70 micrometers (μm).
3. The method of claim 1 , wherein centrifuging the mixture comprises centrifuging the mixture at a rate such that the centrifugal force is in the range of about 8-12,000 g for in the range of 15 to 45 minutes.
4. The method of claim 1 , wherein lyophilizing the intermediate material comprises:
mixing the intermediate material with a lyophilization excipient to form a lyophilization intermediate;
placing the lyophilization intermediate into a plate having one or more wells;
lowering a temperature of the lyophilization intermediate to a temperature in the range of −40 to −45° C.;
applying a vacuum to the lyophilization intermediate and raising the temperature of the lyophilization intermediate to approximately 0° C.;
initializing a secondary drying step and raising the temperature of the lyophilization intermediate to approximately 25° C.; and
releasing the vacuum; and
removing the one or more lyophilized pellets from the plate.
5. The method of claim 4 , wherein the lyophilization excipient comprises PEG 3350, glycerin, trehalose, and sucrose.
6. The method of claim 4 , wherein the lyophilization excipient comprises polyvinylpyrrolidone and trehalose.
7. The method of claim 1 , wherein the one or more capsules comprise hypromellose capsule.
8. The method of claim 1 , further comprising banding the capsules with a banding material comprising hypromellose, an anionic copolymer based on methacrylic acid and methyl methacrylate, hypromellose phthalate, hypromellose acetate succinate, or combinations thereof.
9. The method of claim 1 , further comprising packaging the one or more capsules into packets in individual dosage quantities and wherein the packets comprises metallized polyester/polyethylene bonded film.
10. The method of claim 9 , further comprising placing the packets into one or more child-resistant containers.
11. The method of claim 1 , wherein centrifuging the mixture includes a pre-spin process and a secondary centrifugation process.