Scale process performance, product quality

During product development, measurements are established and specifications set to ensure polymer performance. At the plant scale, processes and product quality are monitored to ensure that the produced product meets specifications. Improved methods to monitor and control the reaction process variability, capture manufacturing efficiencies, and to produce a more consistent, higher quality product are continually being sought and implemented. 

Contrary to the commodity chemical business, the key to win in the specialty products market does not lie in squeezing out profits by means of economies of scale or process optimization. Rather, it lies in the ability for fast new product launches in order to capture the largest market share as soon as possible. Since superior product quality and performance is what really differentiates one specialty product from another, the product properties need to be adjusted as required by business needs. For example, the ability to manipulate functional chemicals in detergent products such as enzymes and zeolites, as well as backbone chemicals like surfactants, is often the key to success for both the detergent manufacturers and chemical suppliers [3], This trend has created an urgent need for an efficient and effective product and process development for these products. 

External resources may he needed if the incident investigation work exceeds site capahilities. These resources could include corporate personnel or experts from outside the company. (The team leader may also he external if the incident is major since the leader s independence sets the tone for the investigation.) Company business unit leaders should confer with the team leader to determine whether external assistance is recommended. Factors to consider include significant offsite consequences such as environmental impact or product quality concerns. A team of trained specialists should formally investigate any process incident that could significantly affect the business. At the lower end of the scale, if a near miss or minor incident occurs that has no potential for significant consequences, local supervision or front-line personnel normally may perform the investigation without outside assistance. 

Pharmaceutical development of a medicinal product must retain the drug s promising in vitro pharmacological activity and provide a predictable in vivo response. The marketed product must be stable, correctly packaged, labelled and easily administered, preferably by self-administration. The product must also be economical to manufacture on a large scale by a method that ensures product quality. In addition, development and eventual production processes must comply with the regulatory requirements of proposed market countries, and all development studies must be performed to acceptable levels of quality assurance. 

Tables 2 and 3 show an antibody purification process scale-up from laboratory scale (1 mL) to intermediate scale (500 mL) to large scale of 10-85 L column volumes, maintaining the column bed height constant. Product quality and biocontaminant levels were maintained throughout the scale-up, though operational flow rates were significantly changed, demonstrating the consistency of the overall purification process. Thorough analysis of each coliunn performance is essential in order to sustain the process robustness at different scales of operation.

IMPACT OF SCALE-UP ON PROCESS PERFORMANCE AND PRODUCT QUALITY... 

Hussain AS. A collaborative search for efficient methods for ensuring unchanged product quality and performance during scale-up of immediate release solid oral dosage forms. In Michael Levin ed. Pharmaceutical Process Scale-Up. Marcel Dekker, Drugs and the Pharmaceutical Sciences, Volume 118, 2002. 

During a validation process, the products and processes are subjected to testing at extreme conditions of in-process limits and their performance is evaluated against the acceptance criteria. The parameters of different pharmaceutical operations are varied and product properties are recorded and evaluated (Figure 3). When it is found that adjustment is required, necessary actions are taken in consultation with R D personnel. Generally, validation data of three production scale batches are compared to generate a high level of quality assurance. 

The preparation of any pharmaceutical product requires controls over the production operations to assure the end result is a product that meets the required quality attributes. The methods utilized for this control are supported by formalized validation studies in which proof of consistency is demonstrated by appropriately designed experiments. The definition of appropriate operating parameters is the primary objective of the development activities and is further confirmed during scale-up to commercial operations. The validation supports that the routine controls applied to the process are appropriate to assure product quality [36], This is typically accomplished in formalized validation activities in which expanded sampling/testing of the product materials is performed to substantiate their uniformity and suitability for use [30],... 

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