# An Adequate Pharmaceutical Quality System for Personalized Preparation
## 6 Quality = Homogeneity/Heterogeneity  
Industrially manufactured medicine and personalized preparations present substantial differences throughout their life cycle, which means that their pharmaceutical quality system cannot be the same. Industrially manufactured medicine needs to duplicate exact copies of a product that meets a series of quality parameters, such that the concept of industrial quality can be equated to that of homogeneity, both in processes and in the end product. Figure 2: Ishikawa diagram with the categorization of the possible root causes that contribute to noncompliance with specifications in the adequate concentration or dosage of active pharmaceutical ingredients (APIs). The main difference found between industrially-manufactured and magistral medicines in the description of the ICH preparation objectives (see above) is the association of the idea of homogeneity as a sign of quality, described literally as \"the reduction of variability\" in objective three. An industrially manufactured medicine is designed and controlled throughout its life cycle, and the definition of quality production for these medicines is associated with the idea that millions of \"identical copies\" of the design are produced in the manufacturing laboratory. Both the manufacturing processes and the quality controls performed on these medicines aim to demonstrate their homogeneity and consider any deviation from the standard pattern as non-compliant. In laboratories where personalized preparations are produced, the compounding pharmacist must deal with the design and life cycle of a multitude of different products--as many, in fact, as there are patients and pathologies. Hence, it is not feasible to work with the concept of quality = homogeneity, rather it must be shown that quality can coexist with a certain degree of heterogeneity. This entails design, management, and quality control systems of its own that are different from that of industrially manufactured medicines. The heterogeneity of a personalized preparation is an intrinsic quality of that preparation and does not imply a lack of quality. If a medicine is not standardized, it does not mean that the product in question is not a quality product. It means that we must guarantee its quality through a management system appropriate to this heterogeneity, i.e., through mastery and control of the processes used in its manufacture. The compounding of personalized preparations should be governed by quality by design, as per ICH8 [53]. This would allow regulatory authorities to consider modifications within the design space as changes that have no impact on the degree of quality of the products compounded. These design modifications make it possible to achieve the objective of personalized preparations, i.e., adapting to a patient and a specific pathology without affecting medicine quality, and substantiating the idea of quality in heterogeneity. It would be fitting for this approach to be taken into account in the latest version of RD 175/2001 that is currently being drafted. To this effect, the Quality Tested Product Profile (QTPP) is established within each test undertaken by PACMI, defining dosage form, route of administration, dosage and characteristics of APIs, conditioning, and quality criteria. The main objective of the PACMI study within each proficiency test is to identify critical variables, Critical Quality Attributes (CQA), and Critical Process Parameters (CPP). In addition to identifying them, their acceptable ranges should be determined. Let us see some examples for the purposes of clarity. The critical quality attribute (CQA) of a personalized preparation containing very little active ingredient would mean that that amount of active ingredient is within concentration limits in the preparation of \(\pm\)10%, or within the range of 90.0-110% of its declared theoretical concentration. One critical process parameter (CPP) could be the variability of factors that may affect the weighing process and have an impact on the defined CQA.