Methods of Manufacturing Biological Therapies

A method of developing a manufacturing process for a biological therapy, the method comprising:

• detecting a level of a molecular attribute of the biological therapy in a formulation at one or more timepoints under storage conditions;
• determining a rate of change of the molecular attribute under the storage conditions;
• obtaining data on safety and/or efficacy of the biological therapy in subjects that have received an administration of the biological therapy;
• estimating a level of molecular attribute exposure received by the subjects at the time of said administration, based on (i) the rate of change of the molecular attribute during storage of the biological therapy in the formulation and (ii) a duration that the biological therapy in the formulation was under the storage conditions prior to said administration;
• determining a presence or absence of a correlation between the estimated level of molecular attribute exposure and the safety and/or efficacy data of the biological therapy;
• and
• (a) if the correlation is absent, establishing the manufacturing process to produce levels of the molecular attribute at or below a specified permissible level based on the estimated level of molecular attribute exposure;
• or
• (b) if the correlation is present, establishing the manufacturing process to produce levels of the molecular attribute at or below a specified a maximum permissible level of the molecular attribute based on the highest level of the molecular attribute that is not associated with adverse events and/or inhibition of efficacy of the biological therapy.

A method of assessing a clinical impact of a molecular attribute of a biological therapy, the method comprising:

• detecting a level of a molecular attribute of the biological therapy in a formulation at one or more timepoints under storage conditions;
• determining a rate of change of the molecular attribute under the storage conditions;
• obtaining data on safety and/or efficacy of the biological therapy in subjects that have received an administration of the biological therapy;
• estimating a level of molecular attribute exposure received by the subjects at the time of said administration, based on (i) the rate of change of the molecular attribute during storage of the biological therapy in the formulation and (ii) a duration that the biological therapy in the formulation was under the storage conditions prior to said administration;
• determining a presence or absence of a correlation between the estimated molecular attribute exposure and the safety and/or efficacy of the biological therapy;
• and
• if (a) the correlation is absent, determining that the molecular attribute impacts neither clinical safety nor efficacy of the biological therapy;
• or
• if (b) the correlation is present, determining that the molecular attribute impacts safety and/or efficacy of the biological therapy.