A | Production process/manufacturer |
A1 | Are all biosimilars approved in Europe produced under GMP conditions? |
A2 | Is the exact production site of API and final product always known to EMA? |
A3 | Have all production facilities of API and final product been checked by EMA or other authorities? |
A4 | Are all recalls reported to EMA? |
A5 | Is the manufacturer experienced in the production of biopharmaceuticals? |
A6 | Which national authorities are responsible for inspecting the manufacturing site? |
A7 | How long has the biopharmaceutical been on the market? |
A8 | How extensive is the clinical experience with each individual biosimilar? Expressed as the number of patient-days worldwide |
A9 | Does the manufacturer guarantee active information about major changes of the manufacturing process? |
A10 | Is the reference medicinal product authorised in the European Community? |
A11 | How has it been validated that the production of the API and final product is always performed under the same conditions? |
A12 | Has EMA checked quality control systems of the producers of API and final product? |
A13 | Are data concerning batch reproducibility (inter-batch and intra-batch variability) available at EMA before and after approval? |
A14 | Are specifications of quality control of the marketing authorisation holder (MAH)/manufacturer known to EMA and assessed by EMA? |
A15 | Is it taken into consideration whether materials of animal origin or potentially allergenic materials are used during the production or formulation? |
A16 | Does EMA take into consideration where clinical studies were performed or is only the quality of the study an item of discussion? |
A17 | How is batch consistency ensured by the manufacturer and/or by third party? |
B | Product specifications |
B1 | Are there any differences in isoform pattern in comparison to the reference product or other biosimilars? |
B2 | Are there any differences in drug formulation and administration in comparison to the reference product or other biosimilars? |
B3 | What is the number of registered indications for the biopharmaceutical/biosimilar? |
C | Reliability of supply |
C1 | Does the supplier reliably guarantee the supply of the biosimilar over a long time period? |
D | Good handling practice |
D1 | Is the biosimiliar delivered according to good storage (GSP) and distribution practice (GDP)? |
E | Clinical efficacy |
E1 | Is the clinical development programme consistent with the current regulatory requirement? |
E2 | Which clinical trials in which patient populations with which designs, endpoints and results were performed? |
E3 | Are there different results in comparison to the reference product? |
F | Clinical safety and tolerability |
F1 | Which (serious and mild) adverse events and in which frequency were they reported in clinical trials with the biopharmaceutical? |
F2 | Are there any contraindications, precautions or warnings which are different compared with the reference product? |
F3 | Is immunogenicity, as far as known, caused by a homogeneous type of antibody or is there a high intra-individual or inter-individual variability? Is there a difference between biosimilar products regarding drug antibody homogenicity? |
F4 | Are there differences in the incidence and severity of drug interactions |
F5 | Are there differences in the incidence of local reactions? |
G | Pharmacovigilance |
G1 | Does the MAH have a 24 h phone number equipped with adequate personnel to report adverse events? |
G2 | How is pharmacovigilance controlled? |
EMA, European Medicines Agency; GMP, good manufacturing practice.