China registration QC testing for NDA

Registration Testing

· When registration testing is needed:

· NDA of NCE/NBE

· Post-approval CMC changes: case by case, there is no clear guidance from HA. Very high potential for most major CMC changes and/or changes related with TM update.

· Two options to initiate local QC testing for NDA:

· Pre-NDA registration testing: applicant can choose to initiate QC testing before submission of NDA dossier to HA. The prerequisite is completion of commercial-scale process validation, finalization of submission dossiers (especially the TM), and readiness of samples, RS, and other materials.

· Normal NDA registration testing is after NDA submission, after dossier is accepted HA will issue notification of QC testing

· Registration testing for post-approval variations may be initiated:

· When HA issue notification of QC testing after the acceptance of submission dossier.

· HA may also request QC testing during technical review.

Registration Sample Requirement

· Remaining shelf-life

· When submit samples to HA lab, remaining SL shall be generally not less than 2 registration inspection cycles. If the sample testing and specification verification are performed at the same time, it should be no less than 180 working days; if only the sample testing is performed, it should be no less than 120 working days

· When apply for import license at provincial HA, remaining SL of not less than 12 month is required.

· Considering the timing for shipping, customs clearance, testing document review by HA, the remaining SL for samples when CPO place order in BOE, will be longer the above requirement, usually >12 month.

· Number of batches

Chemical drug:

· in most cases, only FP is needed. 3 batches per strength FP.

· DS sample will be needed if we register DS in China.

Biologics:

· DS & FP needed for NDA.

· For variations, if not change related with DS, only FP is needed.

· Generally requires 3 consecutive batches for DS & FP. If different FP strengths are in same formulation and only differ in filling volume, then 3 batch of the largest strength and 1 batch of other smaller strengths may be acceptable

· Sample amount

· The quantity of samples in each batch is 3 times the quantity required for full test of the specification (referred to as 3-time quantity. If to verify some items, the quantity of samples in each batch is 3 times the quantity required for relevant test items). The quantity required for the full test generally is the sum of the number of minimal packages of samples required for separate test of all test items.

· Sometimes need site support to aliquot biologic DS into smaller vials (e.g. 0.5-1.0ml/vial).

1. Sample Packaging

· Pack size: should be commercial packaging, same as the proposed/approved in China

· Label presentation:

o contents of label must be consistent with the corresponding contents of the data.

o The contents of label shall conform to the relevant provisions of label and insert of NMPA. Samples without formal label must be affixed with temporary label. The contents of label shall include: Name, batch number, strength, manufacturer, expiry date and storage conditions.

o MAH information on label should be same as China MAH (to be confirmed)