ESTABLISHMENT OF QUALITY SPECIFICATIONS AND MANUFACTURING PROCESS FOR THE CANDIDATE SIXTH NATIONAL REFERENCE STANDARD FOR WHOLE-CELL PERTUSSIS VACCINE

Abstract

The RP5 National Reference Standard for whole-cell pertussis (wP) vaccine (66 IU/vial) has been used for vaccine potency testing since 1999, but the remaining stock is expected to be sufficient for only the next 1–2 years. There is an urgent need to produce a new whole-cell pertussis reference vaccine batch to replace RP5. This study aimed to establish quality specifications, optimize the production process, and produce a candidate RP6 National Reference Standard for whole-cell pertussis vaccine. Two pertussis bulk suspension batches, PM 0125-TN (200 IOU/ml; potency, 46.73 IU/ml) and PM 0126-TN (280 IOU/ml; potency, 86.43 IU/ml), were selected for pilot lyophilization of three formulations, with 200 vials per batch. All three pilot batches met the specified requirements for appearance, sterility, residual moisture, and mass uniformity, with mean potencies of 25.33, 34.60, and 48.05 IU/ml, respectively.  Among the three batches, only CT3, formulated at 180 IOU/ml using the PM 0126-TN pertussis bulk suspension, met the specified potency requirement of ≥40 IU/ml. Therefore, the CT3 formulation was selected for the production of one candidate reference standard batch, RP6-DT, approximately 2,000 vials. Quality evaluation showed that RP6-DT met the established quality specifications, with a potency of 58.42 IU/ml. In conclusion, the study established quality specifications for the national whole-cell pertussis vaccine reference standard, selected an appropriate bulk formulation, and successfully produced a candidate reference vaccine batch that met the established specifications and could proceed to further calibration for establishment as the national reference standard.