Guide to Validation - Drugs and Supporting Activities

You may use larger samples with justification. Sampling locations: Sampling locations should enable full assessment of the blender and include potential problem areas (e.g. dead spots). Sampling method: Sample thieves remain widely used and can - in many cases - present acceptable results. However, they do have drawbacks because they cause bed disturbance so sampling errors are possible. Evaluate the reliability of sampling as part of the analytical method development. Testing requirements: Determine the number of replicate samples to be analyzed from each location. Testing more than one replicate sample has the benefit of helping to determine whether you have location to location variation or within location variation. Regardless of how many samples are taken, each sample should be tested separately. Combining doses as a make your own pills composite for a single analytical determination is not appropriate. Acceptance criteria: Pre-establish acceptance criteria and base it on a statistical analysis. Health Canada recommends that you consider innovative approaches to assessing the adequacy of mixing of powder blends.

1. This phase involves developing and optimizing a manufacturing process that consistently produces product meeting the required Quality Target Product Profile (QTPP). Quality target product profile (QTPP): A prospective summary of the quality characteristics of a drug product that ideally will be achieved to ensure the desired quality, taking into account safety and efficacy of the drug product. Critical quality attribute (CQA): A physical, chemical, biological or microbiological property or characteristic that should be within an approved limit, range or distribution to ensure the desired product quality. Critical process parameter (CPP): A process parameter whose variability has an impact on a critical quality attribute and therefore should be monitored or controlled to ensure the process produces the desired quality. Definitions are from ICH Q8(R2): Pharmaceutical Development. 2. The QTPP is normally defined at the beginning of Phase 1 as it represents the objective of the development process. It should be referenced throughout the product lifecycle and may need to be revisited as product and process understanding improve.

You can choose either a peristaltic or mechanical pump. Alternatively, you may also opt for special pumps depending on the type of material you are granulating. In case you need an efficient and excellent dispersion of binder solution, you can opt for pressure pot. It ensures fast and high-pressure delivery of the granulation solution. Again, the position of the spraying nozzle may vary depending on the design of the high shear granulation machine. However, it is mostly above the material you want to granulate. The complexity and design of the control system will also depend on the design, configuration and control software in the wet granulation machine. This can be in the form of a touchscreen HMI. It has various indicator lamps, while coordinating and controlling various operations of the machines. At the moment, quite a number high shear granulator manufacturers use the PLC control systems. As a matter of fact, it is common to find manufacturers varying the design and components of high shear granulation machines.

The aim here is to develop an efficient and reliable machine. Again, it is important to remember that, these are just a few parts and components of high shear granulation machines. This machine is an assembly of hundreds of small parts/components. To know every section of the machine, please download or request for an installation manual from your granulation machine manufacturer. In section 1, I did mention some critical aspects of the wet granulation process. In this section, I will explore how we can achieve every stage in that process. Let’s go right to the working principle of high shear granulation machine. Depending on the design of the high shear wet granulation machine, it will automatically fill the container with the material. So, by pressing buttons or functions, the material will automatically flow into the container. This process is automated such that, once it reaches a certain level, it will automatically stop. As the material fills the system, it will displace the air that was initially resent in the granulation bowl.

Qualification activities should consider all stages in the lifecycle approach from initial development of the user requirement specifications through to the end of use of the equipment, facility, utility or system. 2. Qualification of facilities, utilities and equipment generally includes the following: 1. Verifying that the proposed design of facilities, systems and equipment is suitable for the intended purpose. 2. Verifying proper manufacture and installation in accordance with approved drawings and specifications. 3. Ensuring that clear information is available to install, operate and maintain the facility/utility/equipment. Examples of this include manuals, drawings and standard operating procedures. 4. Ensuring that requirements are met for proper ongoing operation of the unit/facility (e.g. calibration, preventative maintenance and training). 5. Ensuring operation in accordance with the manner in which the system was designed including process and procedural requirements. The qualification effort should clearly demonstrate that the equipment/systems are operating in a manner that meets requirements as outlined in the user and functional requirement specifications. Operating ranges and/or worst case conditions should be challenged.