3. Pharmaceutical Development:
It is recommended to use an internationally harmonized structure when submitting a dossier for obtaining a marketing authorization. This section therefore follows the ICH-CTD structure according to ICH M4 (8).
The text of the M4Q (CTD-Q) guideline (9) is reproduced
verbatim in this document in italic text, with minor modifications
to accommodate WHO terminology and to include certain
changes to the text that would be appropriate for multisource
pharmaceutical products, notably:
■ Drug substance is replaced with active pharmaceutical
ingredient or API;
■ Drug product is replaced with finished pharmaceutical product
or FPP;
■ Application is replaced with product dossier or PD;
■ Combination product is replaced with fixed-dose combination
or FDC;
■ Clinical batches is replaced with comparative bioavailability or
biowaiver batches.
Following the italic text of the M4Q (CTD-Q) guideline (9),
additional guidance by WHO is added in normal type to enable it to
be easily distinguishable from the ICH text. This additional text is
included to further clarify WHO’s expectations and requirements.
This approach is intended to facilitate the identification and origin
of the text in the document (i.e. whether from ICH or WHO).
In section 3.2.P.2 below, reference may be made to CTD sections
that are not discussed in this document. This is done to guide
the manufacturer in completing the PD according to national or
regional requirements.
3.2.P.2 The Pharmaceutical development section should contain information on the development studies conducted to establish that the dosage form, the formulation, manufacturing process, container-closure system, microbiological attributes and usage instructions are appropriate for the purpose specified in the product dossier. The studies described here are distinguished from routine control tests conducted according to specifications. Additionally, this section should identify and describe the formulation and process attributes (critical parameters) that can influence batch reproducibility, product performance and FPP quality. Supportive data and results from specific studies or published literature can be included within or attached to the Pharmaceutical development section. Additional supportive data can be referenced to the relevant nonclinical or clinical sections of the product dossier.
Pharmaceutical development information usually includes, at a minimum:
■ The definition of the QTPP as it relates to quality, safety and efficacy,
considering, for example, the route of administration, dosage form,
bioavailability, strength and stability;
■ Identification of the potential CQAs of the FPP so as to adequately
control product characteristics that could have an impact on quality;
■ Discussion of the potential CQAs of the API(s), excipients and
container-closure system(s) including the selection of the type, grade
and amount necessary to deliver the product of the desired quality;
■ Discussion of the selection criteria for the manufacturing process
and the control strategy required to manufacture commercial lots
meeting the QTPP in a consistent manner.
These features should be discussed as part of the product development, using the principles of risk management over the entire life-cycle of the product (ICH Q8 (10)). The information gained through the predevelopment activities may already have disclosed some of these features and could form an integral part of pharmaceutical development.
For a discussion of additional pharmaceutical development issues specific to the development of FDCs, reference can be made to WHO Technical Report Series, No. 929, Annex 5, section 6.3.2 (6).
Reference documents for pharmaceutical development include ICH guidelines Q6A, Q8, Q9 and Q10 (2, 10–12).
Pharmaceutical Development of multi source (generic) Finished Pharmaceutical Products - points to consider, (Annex 3, WHO Technical Report Series 970, 2012)
