Anyone with experience in the pharmaceutical industry knows that the active pharmaceutical ingredients (APIs) in drug products are tested rigorously for safety and efficacy before reaching the market. Some may not be as familiar with the regulations for excipients, or inactive ingredients, in a drug product. Before any raw material can be used for manufacturing, it must meet the requirements outlined in the Code of Federal Regulations (CFR) chapter 211.84, which states that “each lot of components, drug product containers, and closures shall be withheld from use until the lot has been sampled, tested, or examined, as appropriate, and released for use by the quality control unit.”
Even minor issues with the API or a raw material could compromise the product’s integrity, leading to patient harm or expensive corrective actions such as recalls. Companies that perform drug product manufacturing and raw material testing, such as Singota, take this responsibility seriously. Robust quality assurance and quality control systems ensure that all materials meet the pre-defined requirements before being released for use.
There are a few reasons that raw materials may not meet the required specifications for pharmaceutical manufacturing. Raw material testing ensures that the supplier has provided the correct material, and it also confirms that the integrity of the material hasn’t been compromised during storage or shipment. In addition, raw material manufacturers may supply to multiple industries, and the manufacturer’s established specifications for the material may be less stringent than necessary for pharmaceutical manufacturing.
The best place to start researching for your raw material program is by referencing the United States Pharmacopeia (USP) or other body of federal guidelines for pharmaceutical manufacturing. Here you will find monographs for the most common raw materials used in the industry, and these monographs will clearly outline the accepted tests and specifications used to identify, quantify, and characterize the raw material. If the material does not have a monograph, key quality characteristics need to be identified and justified by the user, and appropriate tests and specifications need to be set for those characteristics.
Typical Identity tests include a variety of wet chemistry techniques, infrared absorption (IR) analysis, appearance testing, UV-Vis analysis, and thin-layer-chromatography testing, among other techniques.
Purity is generally assessed via robust separatory methods such as high-performance liquid chromatography (HPLC), capillary electrophoresis (CE), or gas chromatography-mass spectrometry (GC-MS).
The material and its impurities can be characterized using a multitude of techniques and instruments. These include but are not limited to: size exclusion chromatography (SEC), HPLC, wet chemistry, titrations, pH testing, Loss on Drying, UV-Vis, osmolality, and specifically tailored plate assays. For non-sterile materials, bioburden or other microbiology testing may need to occur to guarantee that biological matter is below an acceptable level. This is especially important if biological material could impact the API before sterilization of the drug product occurs.
In some cases, the full suite of monograph testing will be required for each lot of raw material. In other cases, some tests can be specially selected to ensure the materials meet only the necessary requirements. The specific language from CFR 211.84 states “at least one test shall be conducted to verify the identity of each component” and “each component shall be tested for conformity with all appropriate written specifications for purity, strength, and quality.”
For a Contract Development and Manufacturing Organization (CDMO) such as Singota, the testing program is discussed and developed in collaboration with the client. The testing program should ultimately be decided by the entity that plans to distribute and market the finished product, and the program should be well documented and justified for subsequent interactions with regulatory bodies.
In the next segment of this blog, Captisol® will be used as a specific example to illustrate the considerations that must be made when developing a raw material testing program for a product that will see global distribution.
If you have specific questions regarding raw material testing, raw materials management, or regulatory requirements for drug products, contact us at firstname.lastname@example.org, or visit our testing service page.