Quantified by input
Revised May 2005
This document was developed in order to provide guidance on the appropriate criteria for permitting quantification by input as an alternative to performing an assay for the content of an active ingredient(s) in a complementary medicine during batch release testing.
Quantified by input (pdf,101kb)
Guidance development
Following acknowledgment of the need to provide guidance on this issue, a draft document was prepared by the Australian Regulatory Guidelines for Complementary Medicines (ARGCM) Consultation Group with input from the TGA. The draft document was made available for public comment and circulated to the industry associations requesting comment on behalf of their members.
The ARGCM Consultation Group reviewed the comments received from industry and amended the document to reflect necessary changes.
In August 2004, the guidance document was updated to include additional information for sponsors in regard to implementing the requirements for 'Quantified by Input'.
This revised version (May 2005) incorporates guidance for sponsors in regard to the use of validated limit tests.
'Quantified by Input'
The issue of use of the term 'Quantified by Input' on certificates of analysis has been raised by the TGA's Manufacturer Assessment Section (MAS) (formerly the GMP Audit and Licensing Section (GMPALS)) and referred to the Office of Complementary Medicines (OCM) for consideration. In addition, complementary medicine manufacturers have requested clarification over the requirement to assay certain ingredients in complementary medicines. These matters raise questions as to what are the circumstances under which the practice of 'quantified by input' is appropriate and what terminology should be used on certificates of analysis where this practice has been applied?
To ensure compliance with batch release specifications it is best practice to assay all batches of all finished products for the content of active ingredient(s). However, the TGA realises that this may be difficult with some complementary medicines. In recognition of this, the attached document sets out the conditions where manufacturers may not be required to perform an assay on an active ingredient (or a component in the active ingredient) in complementary medicine products.
Scope
This guidance does not extend to medicines other than complementary medicines nor is it applicable to other medicines containing a complementary medicine component.
Implementation
To allow sufficient time for manufacturers to change their recording systems, the implementation of the principles outlined in this guidance document will be phased in over a two-year period commencing on 1 January 2004. An additional one-year phase-in period will be allowed for the development of justifications for not assaying active ingredients in finished products.
Manufacturers who wish to quantify an active ingredient(s) in a finished product using 'quantified by input' are expected, as of 1 January 2004, to begin the development of a justification for not assaying the ingredient(s) in the finished product. They should not wait until the end of the phase-in period (1 January 2007) before developing a justification for not performing an assay. Consistent with the principles and guidance in this document and irrespective of the phase in period, some active ingredient testing must be performed on each batch of the finished product where a quantitative claim is made on the label. That is, there must be sufficient testing to provide assurance that the product is of intended quality (see Flow Chart).
The TGA acknowledges that justification, validation and implementation of an alternative procedure may take some time. Provided a manufacturer can demonstrate progress in developing a justification for using 'quantified by input' to a MAS auditor, or in a response to request from the TGA as part of its post-market surveillance program, then this would be considered an acceptable interim measure for not performing an assay. This approach would be particularly applicable for manufacturers with an extensive product range. Documentation should be available showing a schedule for introducing 'quantified by input' together with progress against the schedule.
In justifying the use of 'quantified by input' and for not undertaking an assay, the issue of what is a reasonable attempt at performing an assay is difficult to judge with objectivity. It may often be a subjective judgement as to whether the justification for not assaying is sufficient. Such cases will be resolved through discussion between the manufacturer and the TGA.