Author: Site Editor Publish Time: 2026-11-13 Origin: Site
CDE Issues Q3 Characterization Guideline for Topically Acting Chemical Generics
On September 30, 2026, the Center for Drug Evaluation (CDE) of China's National Medical Products Administration published the Technical Guideline for the Study of Physicochemical and Structural (Q3) Characteristics of Locally Acting Chemical Generic Drug Products (Notice No. 45 of 2026). It took effect on publication and applies to ointments, creams and gels for topical or transdermal use that act locally — products whose Q3 attributes can shift how the drug is released and how far it penetrates the skin. The guideline sets out ten study areas, rules for choosing batches and sample sizes, and principles for setting evaluation standards.
The scope is narrow and specific: chemical generic products for cutaneous or transdermal administration that act at or near the site of application, in the form of ointments, creams and gels. Products with a complex multiphase structure are the main concern, because their physicochemical and structural properties influence drug release, skin permeation and overall product performance.
The guideline describes itself as a set of scientific recommendations rather than a fixed protocol. Applicability is decided case by case, according to the drug substance and the dosage form — which places the selection of studies on the applicant, not on a template.
Q3 refers to the physicochemical and structural properties of the product. Ten areas are named, each with its own methods and expectations:
Appearance — color, clarity or opacity, texture and odor, documented by visual inspection and high-resolution images; appearance is the first signal of precipitation or phase separation.
Phase state — high-resolution microscopy at several magnifications, with detailed sample preparation records, including the dissolution state of the active ingredient.
Particulate structure — particle size distribution, crystal habit and, in multiphase systems, droplet size distribution; emulsion type is confirmed by dye testing or conductivity.
Polymorph of the active ingredient — required where the active ingredient or other particles are suspended, and controlled where necessary.
Density — air entrained during manufacture changes density and therefore dose accuracy.
pH — for water-containing formulations, with the buffer system composition stated in the formula.
Oil phase — for ointments with 70% w/w or more oil phase, such as petrolatum, the components and their relative proportions must be characterized.
Rheology — a complete flow curve across the relevant shear rate range, identification of low- and high-shear plateaus, yield stress where flow is plastic, and viscoelastic data (G′, G″, tan delta) plus thixotropy and creep.
Water activity and drying rate — evaporation or drying rate for water or alcohol systems; water activity where water content is below 50% w/w; neat oil-based ointments may be exempt.
Deformation-related properties — where a different container or closure system is used, the effect of dispensing, such as extrusion, on Q3 attributes across the shelf life.
Figure 1. The ten attributes named in the guideline — a menu, not a checklist.
The list is a menu, not a checklist. The guideline asks applicants to assess the product and the dosage form first, then decide which studies are needed — and to justify the ones left out.
Batch count and sample size are not fixed numbers. They should be set from the variability of the reference product and from the company's own data, and must be sufficient to be representative. In practice, this rewards applicants who characterize the reference product early rather than assuming a nominal value.
Methods must be fully validated, and the dossier should show the development and selection process as well as the validation data — a requirement that catches teams who validate a method without documenting why that method was chosen. Comparison against the reference product, supported by stability data, is the basis for characterizing Q3 attributes. Where differences exist, they must be explained and supported with evidence that quality, safety and efficacy are unaffected.
Figure 2. The sequence the guideline implies: characterize, select, compare, justify.
What this means for partners
The guideline moves quality research on topical generics from composition toward microstructure and performance. Two products can match on Q1 and Q2 and still differ in how they release and penetrate — which is exactly the failure mode this guideline is designed to surface.
For development programs, the practical consequence is sequencing. Q3 work belongs in formulation screening and process development, where microscopy, rheology and phase behavior can still change the formula. Assembled at filing, the same data becomes a description of whatever was already made, and any difference from the reference product turns into a justification problem.
Three capabilities decide how smoothly a program moves: imaging and rheology capacity, method validation depth, and access to enough reference product batches to establish a real variability range. Bestcomm will continue to track CDE technical guidelines and review practice, and will apply these expectations in its formulation development and regulatory work with partners.
Which products does the guideline apply to?
Chemical generic products that act locally after cutaneous or transdermal administration, in ointment, cream or gel form. It does not cover topical solutions or products that act systemically.
How is Q3 different from Q1 and Q2?
Q1 and Q2 describe what is in the formula — the same ingredients, in the same amounts. Q3 describes the physical and structural state of the finished product: how the phases are arranged, how the particles are sized, how the material flows. Two products can be Q1 and Q2 identical and still differ in Q3.
How many batches are required?
No number is prescribed. The guideline requires a scientifically justified batch count and sample size, based on reference product variability and the applicant's own data.
Is the guideline legally binding?
It is a technical guideline issued as a CDE notice, not a regulation. It sets out the current review expectations, and applicability is assessed case by case.
For topical generics, the hardest part of development has never been making a product that looks right. It is demonstrating that the product behaves like the reference — batch after batch, through the shelf life. The guideline gives that argument a common structure, and it raises the cost of leaving Q3 work until the end.
Source: Center for Drug Evaluation, NMPA, Technical Guideline for the Study of Physicochemical and Structural (Q3) Characteristics of Locally Acting Chemical Generic Drug Products, Notice No. 45 of 2026, published September 30, 2026.
