定性和定量（qualitatively and quantitatively，Q1 and Q2），是FDA对不同标准所采取的归类模式。定性标准一般可以用“是”“否”来判定，而定量标准一般为物理广度量，检验时需测出数值，建立接受标准。我们试举两例：
（1）“产品中有无某辅料”是定性问题；要求某辅料落在原研浓度正负5%的范围内，则是定量问题；
（2）“产品是否变色”是定性问题；针对产品颜色，建立经验证的特异性液相方法，并给出峰面积区间，则是定量问题。
参考 FDA Guidance Controlled Correspondence Related to Generic Drug Development 2014 (Draft)；
Lachman CONSULTANTS - Bob Pollock先生 2015-05-21
编译：识林-葳 2015-05-24
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For Q1 and Q2 Determinations, OGD Nixes “The Price is Right” Process!
There are certain products that must be Q1 (qualitatively) and Q2 (quantitatively) the same, in terms of active and inactive ingredients, in order to avoid having to conduct in vivo pharmacokinetic or bioequivalence studies with clinical endpoints. The Office of Generic Drugs (OGD) has historically permitted firms to submit proposed formulations for certain product types (e.g., ophthalmic products, some topical products, and some other solution products) for pre-review, during which OGD would evaluate the formulation to determine if it was indeed Q1 and Q2. If the proposed formulation submitted was not Q1 and Q2, OGD would inform the firm of which individual components of the formulation were either too high or too low. This process was lovingly known by the industry as the “Price is Right” process for formulation acceptability, referring to the iconic television game show.
We have heard from multiple sources that OGD will no longer provide directional guidance on which of the individual components are either too high or too low. OGD will apparently now only tell you that you hit the mark on all ingredients, or you have failed. From industry’s perspective, this is really a step back and may also have the potential for causing significantly more work for many more rounds of formulation reviews for the same product by OGD.
Why would the OGD make such a change in a program that has worked well for a number of years? We can only postulate that perhaps an innovator complained to the FDA that, by playing the “Price is Right” with the formulation review, the Agency was actually helping firms to zero in on their confidential formulation. Perhaps there are other reasons, but, in thinking about this issue, that is the only plausible explanation that makes any sense.
Many of the types of products that must be Q1 and Q2 have multiple ingredients, many of which are at relatively low levels and/or may be very difficult to accurately measure using reverse engineering. With some ingredients existing at levels that may be in the 0.005% level, trying to hit the mark for Q1 and Q2 may be very difficult, since the definition of Q1 and Q2 requires that the difference from the reference listed drug by no more than +/- 5% for each ingredient. Therefore, the lower the level of the ingredient in the product, the harder it is to hit the mark. Couple this requirement in a product that may have 3-8 different inactive ingredients, the chance of hitting the Q1/Q2 requirement is difficult at best, and, without any hint as to which ingredient misses the mark, and in which direction (high or low), the process for getting it right becomes extremely difficult, if not impossible for complex formulations.
This policy change, which, to my knowledge, has not yet been communicated publically to the industry in general, will significantly adversely impact generic firms that have pending controlled correspondence asking for Q1/Q2 determinations, as well as firms that will be seeking advice on this issue in the future. Hopefully, FDA will make public by issuing some kind of document that outlines the reason for its change to this long-standing policy.
