PART III: Nonclinical Documents
Ref. PART III: NONCLINICAL DOCUMENT of the ASEAN Common Technical Dossier (ACTD)
Primary purpose of this part of ACTD:
- To provide a comprehensive, factual synopsis of the nonclinical data. This section should provide an opportunity to discuss the toxicological evaluation and the significance of any issues that arise.
- Provide a simple list of all pre-clinical studies that were sponsored by the applicant in support of use in clinical trials in humans, or for significant changes to manufacture or use. Include in the list any important conclusions. For preclinical studies performed after initial licensure, indicate the reasons for these studies. Any other particularly relevant reports regarding safety aspects, whether or not generated by the applicant, should be provided.
- Therefore, the interpretation of the data, the clinical relevance of the findings, cross-linking with the quality aspects of the pharmaceutical, and the implications of the nonclinical findings for the safe use of the pharmaceutical (i.e. as applicable to labelling) should be addressed in this part.
- For new vaccine products, preclinical safety tests should always be part of the testing programme, even though it is recognised that full testing may not be necessary to the extend requested for conventional medicinal products. However, in the case of combined vaccines containing known antigens, preclinical toxicity testing may not always be necessary. Immunogenicity testing is still required. Attention should be paid to additives including adjuvants, preservatives and excipients.
- The following toxicity tests need to be taken into account:
- Single dose toxicity
- Repeated dose toxicity
- Embryo/ foetal and perinatal toxicity (if intended for use in women of child bearing age or during pregnancy)
- Pharmacodynamics
- Primary pharmacodynamic studies with respect to the ‘antigen-protective response’ should be carried out in a relevant species. The endpoint in these kind of studies should preferably be the protection against a challenge from the pathogenic organism where the animal model reflecting the infections in humans.
- Secondary Pharmacodynamic (Safety pharmacology): The potential for undesirable pharmacological activities e.g on the circulatory and respiratory systems should be considered for new vaccine and investigated in appropriate animal models.
- Pharmacokinetics
- Pharmacokinetic studies are usually not required for vaccines. However, such studies might be applicable when new delivery systems are employed or when the vaccine contains novel adjuvants or excipients. The need for pharmacokinetic studies and their design should be considered on a case by case basis.
- Local tolerance
- As vaccine will in most cases be administered intramuscularly, subcutaneously or intracutaneously, local tolerance should be evaluated, using formulation intended for clinical use.
Please refer:
Please provide the full nonclinical study reports.
Please refer:
