Manufacturing pharmaceuticals is a process that requires a great deal of science and experimentation. Several factors such as price, product quality, delivery time, and the reputation of the manufacturer can all affect the final outcome. The limits of the market demand, the manufacturing process, materials used and delivery conditions all influence the performance of the final product.
Most pharmaceutical companies have internal processes that help them select the material to be used in their manufacturing process. The pharmaceutical industry has a strict selection procedure, which is mainly based on drug potency and suitability. Generally speaking, the selection process is quite complicated and time-consuming.
Material selection is a key component in pharmaceutical manufacturing, and it needs to be carried out on an ongoing basis.
Material selection is a key component in pharmaceutical manufacturing, and it needs to be carried out on an ongoing basis. Knowledge and understanding of the effects of physical variability on finished product is the key. Product failure as a result of product variability is important. Quality raw material procurement is a necessary component in the entire production process of a pharmaceutical product. With the reduction in prices of raw material components and the increase in competition, it may be getting harder to distinguish quality raw material in a cost effective way. To cope with this, we need to work closely with our suppliers to find the best possible compromise.
Cost influence on material selection
Pharmaceutical companies have a choice when it comes to selecting their raw materials: follow their suppliers’ recommendations or choose from what is available. However, there are times when the industry has to select materials that aren’t available from their usual suppliers. The latter situation is more common in some industries than others.
There is a movement to reduce costs in manufacturing industry processes, however, this often leads to the quality of product being compromised, through using different materials or manufacturing in another country. The problem is that different sources of raw materials have different properties, so a compromise by using lower grades can lead to failure caused by impurities. Yet, there is a need for less expensive products and process as this would be an attractive option for consumers and the market as a whole. In order to increase the quality and safety of (e.g.) pharmaceuticals there are several key areas where quality can be improved including product design, material choice, actual design and properties achieved (the science) and process control (the art).
Quality control of the raw materials – a company must comply with the tightest limits, whether listed in the pharmacopoeia or included in the product registration, to ensure compliance globally. Source: Why Pharmacopoeia Compliance Is Difficult–An End-to-End Compendial Framework.
The top compromises that are made in the material selection process
Materials selection challenges
- Natural variability (e.g., physical characteristics)
- Processing variability (e.g., process inconsistencies)
Control and management of variability
- Process and Equipment Selection – maintenance and calibration
- Reducing the Effects of Processing Variability – process understanding, rationale, procedures and training
- Minimizing the Effects of Natural Material Variability – strict control on sourcing and monitoring of material with special attention to physical tests.
- Understanding Process Parameters – introduction of value-added in-process controls, standard operating instructions & procedures, training, re-training.
- Controlling and Measuring the Effects of Processing Variability – the “Voice of Process” is a unique feature that distinguishes a good manufacturing process from a bad one.
- Controlling and Measuring Material Variability – strict control on sourcing and compliance with the standard and additional test specific to the raw material, compendial specification (USP, Ph. Eur. etc.).
A holistic approach to quality management practices, in which the potential for variation introduced at each stage of the product life cycle is scrutinized at the design, process, and control levels, must be employed.
The top 3 areas with potential to reduce the impact of compromise in material selection
Material selection is the most important activity in the manufacturing industry. The following list is not all-inclusive and may help.
1: Understanding physical variability
Poor understanding of physical variability has a negative impact on product quality, which can eventually lead to product recalls and other serious issues.
Physical properties are one of the most important aspects of the quality of a pharmaceutical product because they are directly related to the pharmaceutical’s safety and effectiveness.
From a quality perspective, the physical properties should ideally be completely consistent across all batches of the same product. Unfortunately, physical properties often exhibit large variations between batches arising from various sources, including but not limited to differences in raw materials, manufacturing process, and storage conditions. Common examples include: magnesium stearate, stearic acid (batch-to-batch variability from the same source and physical changes during transportation).
The variability in the chemical properties of materials is an easy find. However, we need to be able to determine if changes (variation) in level and ranges throughout production are present and their impact on quality of the finished product.
2: Material selection and testing methods
Testing must be carried out on all materials according to strict requirements. Sampling technique itself can introduce variability of laboratory results and should be given due attention.
Companies use their own approach when it comes to the manufacturing process of new or updated pharmaceutical products. They prefer to use materials in which they can have confidence due to their generally high quality and suitability for the technical requirements of the process.
Local suppliers, manufacturers belonging to a particular company or selecting non-qualified suppliers from a large number of candidates may compromise the quality process during the product development.
Testing must be carried out on all materials according to strict requirements and criteria, in order to identify the most critical ones for manufacturing and performance.
As new products are developed, the challenges of testing become greater as the potential quality risks decrease due to better knowledge of the product mechanism, better understanding of the product response to storage, aging, and other process factors, and a greater number of samples to be analyzed by different laboratories. Quality control requires much stricter monitoring.
3: Consulting with others – Process Owners
Consultation must be conducted with all involved parties to clarify any possible issues before material selection is made.
Materials not selected by process operators or who possess knowledge and understanding of the effects of physical variability on finished product consistency, and therefore selection based on those effects is no longer a viable method of manufacturing.
For sustainable business, our industry constantly requires us to make compromises in the material selection process. On one hand, we need to meet the required standards of the regulatory bodies to make sure our products are safe, on the other hand, we also need to keep our costs down.
With the reduction in prices of raw material components and the increase in competition, it may be getting harder to distinguish quality raw material in a cost effective way. To cope with this, we need to work closely with our suppliers to find the best possible compromise.
Local suppliers, manufacturers belonging to a particular company, and preferred suppliers need to be thoroughly examined before material selection is made. Testing must be carried out on all materials according to strict requirements. Consultation must be conducted with all involved parties to clarify any possible issues before material selection is made.
Bonus topic: Quality Tools in Lean Manufacturing*
Lean manufacturing is a manufacturing philosophy and practice which seeks to achieve high-quality products and improved customer satisfaction by reducing waste, over-production, and unnecessary inventory.
Lean manufacturing is a way of thinking and working. It can be used to improve an organization’s efficiency and performance in many areas: suppliers, sales, production, and inventory. Lean activity ultimately translates into cost savings and making businesses profitable. Lean manufacturing tools are the tools used in Lean Manufacturing. The tools are often used in manufacturing to improve performance of processes.
*Bonus topics are selected based on our readers’ interest. You can read more in the future.
Disclaimer: The views and opinions expressed on PharmaRead are those of the authors and do not necessarily reflect the official policy or position of any agency or organization. PharmaRead articles are provided for information only with focus on global health, pharmacy practice, and healthcare systems in Low- and Middle-income Countries (LMICs). Readers should seek expert opinion for use, implementation or application of this knowledge based on their individual circumstances.