Quality risk management in pharmaceutical development

Abstract

The objective of ICH Q8, Q9 and Q10 documents is application of systemic and science based approach to formulation development for building quality into product. There is always some uncertainty in new product development. Good risk management practice is essential for success of new product development in decreasing this uncertainty. In quality by design paradigm, the product performance properties relevant to the patient are predefined in target product profile (TPP). Together with prior knowledge and experience, TPP helps in identification of critical quality attributes (CQA's). Initial risk assessment which identifies risks to these CQA's provides impetus for product development. Product and process are designed to gain knowledge about these risks, devise strategies to eliminate or mitigate these risks and meet objectives set in TPP. By laying more emphasis on high risk events the protection level of patient is increased. The process being scientifically driven improves the transparency and reliability of the manufacturer. The focus on risk to the patient together with flexible development approach saves invaluable resources, increases confidence on quality and reduces compliance risk. The knowledge acquired in analysing risks to CQA's permits construction of meaningful design space. Within the boundaries of the design space, variation in critical material characteristics and process parameters must be managed in order to yield a product having the desired characteristics. Specifications based on product and process understanding are established such that product will meet the specifications if tested. In this way, the product is amenable to real time release, since specifications only confirm quality but they do not serve as a means of effective process control.

7.3 Process Characterization for Upstream and Downstream Process Development

“…Reducing the number of CQAs during product characterization studies becomes a major challenge, especially considering potential immunogenicity of a quality attribute. Product risk assessments are often performed early in the development cycle and reevaluated and refined throughout the development lifecycle as more data becomes available [1,22,24,25,27]. Potential CQAs during development are confirmed as being truly critical based on suitable product data; however, in some cases criticality may never be fully elucidated.…”

“…Since the initial list of potential process parameters Brought to you by | New York University Bobst Library Technical Services Authenticated Download Date | 7/6/15 12:03 PM can be quite large, this risk assessment is used to prioritize and reduce the number of process parameters to be studied [19,24]. The application of this risk assessment is virtually the same as the first variation, except the potential impact of process parameter on CQA or process performance is evaluated instead of the impact of quality attributes on safety and efficacy of drug product.…”

Risk assessment of supply chain for pharmaceutical excipients with AHP-fuzzy comprehensive evaluation

“…It consists of the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards 16 (Figure 1). …”

“…16:7301 r 11 ¼ 0:4450, r 12 ¼ 0:5550, r 13 ¼ 0:000, r 14 ¼ 0:0000 P 21 ¼ 9:7778, P 22 ¼ 1:7143, P 23 ¼ 0:0000, P 24 ¼ 0:0000, P 2 ¼ 11:4921 r 21 ¼ 0:8508, r 22 ¼ 0:1492, r 23 ¼ 0:0000, r 24 ¼ 0:0000 P 31 ¼ 6:3333, P 32 ¼ 9:5714, P 33 ¼ 1:6000, P 34 ¼ 0:0000,P 3 ¼ 17:5047 r 31 ¼ 0:3618, r 32 ¼ 0:5468, r 33 ¼ 0:0914, r 34 ¼ 0:0000 P 41 ¼ 0:7778, P 42 ¼ 8:1429, P 43 ¼ 8:0000, P 44 ¼ 071 ¼ 9:4449, P 72 ¼ 4:2852, P 73 ¼ 0:0000, P 74 ¼ 0:0000, P 7 ¼ 13:7301 r 71 ¼ 0:6879, r 72 ¼ 0:3121, r 73 ¼ 0:0000, r 74 ¼ 0:0000 P 81 ¼ 8:4444, P 82 ¼ 8:4286, P 83 ¼ 0:0000, P 84 ¼ 0:0000, P 8 ¼ 16:8730 r 81 ¼ 0:5005, r 82 ¼ 0:4995, r 83 ¼ 0:0000, r 84 ¼ 0:0000 P 91 ¼ 9:2222, P 92 ¼ 6:0000, P 93 ¼ 0:0000, P 94 ¼ 0:0000, P 9 ¼ 15:2222 r 91 ¼ 0:6058, r 92 ¼ 0:3942, r 93 ¼ 0:0000, r 94 ¼ 0:0000 P 101 ¼ 8:4444, P 102 ¼ 9:1429, P 103 ¼ 0:0000, P 104 ¼ 0:0000, P 10 ¼ 17:5873 r 101 ¼ 0:4801, r 102 ¼ 0:5199, r 103 ¼ 0:0000, r 104 ¼ 0:0000 P 111 ¼ 8:2222, P 112 ¼ 9:4286, P 113 ¼ 0:0000, P 114 ¼ 0:0000, P 11 ¼ 17:6508 r 111 ¼ 0:4658, r 112 ¼ 0:5342, r 113 ¼ 0:0000, r 114 ¼ 0:0000 P 121 ¼ 4:6667, P 122 ¼ 9:4286, P 123 ¼ 3:2000, P 124 ¼ 0:0000, P 12 ¼ 17:2953 r 121 ¼ 0:2698, r 122 ¼ 0:5452, r 123 ¼ 0:1850, r 124 ¼ 0:0000 P 131 ¼ 9:7778, P 132 ¼ 1:7143, P 133 ¼ 0:0000, P 134 ¼ 0:0000, P 13 ¼ 11:4921 r 131 ¼ 0:8508, r 132 ¼ 0:1492, r 133 ¼ 0:0000, r 134 ¼ 0:0000 P 141 ¼ 8:8889, P 142 ¼ 7:8571, P 143 ¼ 0:0000, P 144 ¼ 0:0000, P 14 ¼ 16:7460 r 141 ¼ 0:5308, r 142 ¼ 0:4692, r 143 ¼ 0:0000, r 144 ¼ 0:0000 P 151 ¼ 0:0000, P 152 ¼ 7:7143, P 153 ¼ 9:2000, P 154 ¼ 0:0000, P 15 ¼ 16:9143 r 151 ¼ 0:0000, r 152 ¼ 0:4561, r 153 ¼ 0:5439, r 154 ¼ 0:0000 P 161 ¼ 0:0000, P 162 ¼ 3:5714, P 163 ¼ 8:8000, P 164 ¼ 3:6667, P 16 ¼ 10:8095 r 161 ¼ 0:0000, r 162 ¼ 0:3304, r 163 ¼ 0:3304, r 164 ¼ 0…”

The DEVELOPMENT OF A VALIDATED STABILITY INDICATING LC-MS METHOD FOR THE DETERMINATION OF TENOFOVIR DISOPROXIL FUMARATE USING QUALITY BY DESIGN APPROACH

“…Further, risk evaluation compares the estimated risk variables to the defined criterion qualitatively or quantitatively [32].…”