When manufacturing a healthcare product, controlling the quality of the raw materials used (for example, the excipients or the components that make up your product) is as important as controlling the quality of your active pharmaceutical ingredients and your finished product. Managing your raw materials as part of your quality system will help to ensure that your finished healthcare product meets its quality attributes. It is wise to initiate such a system at the outset of product development and build it into the product design.1 Having this in place will help steer appropriate selection of the raw materials used.
Selecting the right raw materials for healthcare products
Key considerations when selecting the raw materials2,3 include:
- Is there enough information to support the safety of the material selected (as well as its by-product[s])? For example, is the raw material commonly used in the regulated industry (that is, is it “generally recognized as safe” [GRAS] material)? Is it known to have toxicological concerns (for example, carcinogenetic potential)?
- Would the raw material lead to any pharmaceutical response or is it considered an inert substance? For pharmaceutical products, does it raise questions about interaction with your drug substance? For medical devices, does it change your product from a medical device to a combination product (which would lead to different regulatory requirements and pathways)? If yes, is there a different agent that could help you avoid a more difficult pathway?
- Is the supply of this material limited? If so, can it be replaced with another raw material? If not, it is critical to ensure the supply of this material (have a contract with the supplier or identify an alternate supplier) so that no shortages affect the manufacture of your healthcare product during clinical or commercialization phases.
- Is the material compatible with your finished product? For instance, in pharmaceutical products, the excipients can comprise more than 90% of a product’s weight. Therefore, evaluate the compatibility of the ingredients that may contribute to the quality (for example, hardness, dissolution rate) of the dosage form.
- Is the ingredient available as a pharmacopeial grade or medical grade? If it is, does it meet the requirements in the targeted jurisdiction? If not, can it be substituted by another ingredient?
In summary, the quality, safety and efficacy of the healthcare product should be scientifically evaluated to ensure the right materials are selected.
Ensuring the right quality of raw material
Once the product design is finalized, implement a robust supplier management program to assure and control the quality of the raw ingredients.2 In general, base this program on general Good Manufacturing Practices (GMP). Some aspects may include:
- Reviewing the supplier history, including any relevant information on their manufacturing reliability
- Determining the reliability of results reported on Certificates of Analysis (a document issued by a supplier to certify the quality and purity of each product lot)
- Assessing the quality of raw materials through routine testing
- Performing a supplier audit, if required
- Considering information obtained via ongoing communication with suppliers
In summary, know the supply chain of the raw material for your product. Identify and mitigate risks throughout the supply chain and document the measures you take to secure it.2
Consider cooking as an analogy
One of the fundamental principles of good cuisine is the use of high-quality ingredients. Even if you have a great recipe with the steps, ingredients, and cooking methods and conditions clearly stated, the dish will not turn out quite right, or even safely, if the ingredients used are not what they purport to be and if they are not fresh (that is, not expired) and clean (that is, not contaminated with chemicals or microbes). The span of ingredients can include the main ingredient (say, chicken) as well as all the spices. Sometimes just changing the brand (that is, changing the supplier) of an ingredient may be enough to affect the “quality,” or taste, of the food. Similarly, the quality of the raw materials selected to manufacture your healthcare product could significantly affect the quality, safety and efficacy of your product; hence the need for tight controls.
The information presented in these articles is intended to outline the general processes, principles and concepts of the healthcare product development lifecycle. Since regulatory requirements are ever-changing, it is current only as of the date of publication and not intended to provide detailed instructions for product development. Every healthcare product is unique and therefore so is its associated product development lifecycle. Specific advice should be sought from a qualified healthcare or other appropriate professional.
Published: October 17, 2012
- Gonzales, L. (2004). Chapter 14. Raw material contamination control. In K.L. Williams (Ed.) Microbial contamination control in parenteral manufacturing. Informa Healthcare.
- Holtz, F. & Sehat, N. (2011, September). A Supplier’s Role in Ensuring and Improving Excipient Quality. Pharmaceutical Technology, 35, 36-38. Retrieved September 24, 2012, from PharmTech.com: http://www.pharmtech.com/pharmtech/article/articleDetail.jsp?id=738388.
- Ansel, H.C., Popovich, N.C. & Allen, L.V. Jr. (1995). Chapter 4. Dosage form design: General considerations, pharmaceutical ingredients, and current good manufacturing practice. In Pharmaceutical dosage forms and drug delivery systems (6th ed.). Baltimore: A Waverly Company.