Setting Specifications for a Biotech Therapeutic Product in the Quality by Design Paradigm - Manufacturing using meaningful, science-based specifications will ensure that we attain the optimal balance

ADVERTISEMENT

Setting Specifications for a Biotech Therapeutic Product in the Quality by Design Paradigm
Manufacturing using meaningful, science-based specifications will ensure that we attain the optimal balance between manufacturing flexibility and product safety.


BioPharm International
Volume 23, Issue 1

Examples of Setting Specifications


Figure 2. Ratio of the product quality and clinical design spaces for a hypothetical monoclonal antibody product. The quality attributes shown have been chosen from Table 1.
Figure 2 presents an illustration of the data presented in Table 1 with the ratio of the product and clinical design spaces plotted against the clinical lot number. A ratio of 1 would mean that the specification is the same as the variability in product quality seen in the clinic. It can be seen that product-related impurities such as percent purity by high performance size exclusion chromatography (HP SEC) and percent purity by ion exchange chromatography (IEC) are at ratios <2. In contrast, process related impurities such as HCP and DNA are at ratios >10. This reflects our knowledge about how a particular attribute affects the safety, efficacy, and consistency of the product. The less knowledge we have, the more we must depend on the clinical experience of the product to justify a specification.3

Establishing Specifications for Product-Related Quality Attributes


Figure 3. Illustration of clinical and product design spaces for a few chosen product related quality attributes from Table 1
Product-related quality attributes fall into two categories.2 The first is product-related variants, which include species such as deamidation that are related to the product and have potency, clearance, immunogenicity, and safety properties similar to the product. The second group covers product-related impurities such as aggregation, which differ in the above-mentioned properties from the product. Figure 3 illustrates the comparison between the clinical and product quality design spaces for two product-related impurities. It is seen that the product quality design space as defined by the specifications is only slightly broader than the clinical experience for percent purity by HP SEC (specification: ≥98%; clinical experience: 99.1–99.8%) and percent purity by IEC (specification: ≥95%; clinical experience: 97.5–100.0%). The broader product design space in these cases would still need to be justified by nonclinical studies evaluating the safety and efficacy of these impurities or by clinical and nonclinical studies related to these impurities with other platform molecules.


blog comments powered by Disqus

ADVERTISEMENT

ADVERTISEMENT

PDA Announces Technical Report on Drug Shortages
September 9, 2014
European Commission Approves RoACTEMRA for Treatment of RA
September 9, 2014
DPT Laboratories Acquires Media Pharmaceuticals' Lakewood Facilities
September 5, 2014
Merck KGaA Breaks Ground on Facility in China
September 5, 2014
FDA Releases Guidance Electronic Submission of Lot Distribution Reports
September 5, 2014
Author Guidelines
Source: BioPharm International,
Click here