The Fine Science of Manufacturing APIs for Injectables

Five Questions to Ask to Learn If your CDMO Is Up To the Task

Intravenous or intramuscular injection of drugs is becoming a fast and effective route to administration of life-saving treatments. Injectable drugs do not involve absorption in the digestive tract, which allows the medication to be absorbed more quickly. The three main routes are intradermal injection, subcutaneous injection (the fat layer) and intramuscular injection (into the muscle), each targeting a different skin layer.

Injectable drugs meet a clear need, yet, they must be produced according to the highest standards of quality, purity and sterility, since they enter directly into the blood stream. Also, many injectable drugs are used to treat patients who may already be immune compromised or have complex medical histories, so ensuring sterility and eliminating residual toxins is critical.

Quality can be compromised by inadequate manufacturing processes that don’t ensure sterility, or Active Pharmaceutical Ingredients (APIs) with high levels of impurities.

The importance of maintaining quality when manufacturing injectables has been put in the spotlight recently, with the millions of doses of COVID-19 vaccines that were removed because of contamination. 


Yet, in addition to these types of biologics, API manufacturers must rethink their approach to ensuring production quality across all projects. They need to establish standards of excellence and adhere to stringent compliance protocols, and be on top of quality issues before they even happen.

When selecting a Contract Development & Manufacturing Operations (CDMO) to produce APIs for injectable drugs, vetting their capabilities is more important than ever. Below are five questions to ask to make sure they’re up to the task.

  1. Do you maintain adherence to GMP? One of the key questions to ask is if the CDMO has ample current Good Manufacturing Practices (GMP) suites. Adhering to GMP means they have cleanrooms, which maintain extremely low levels of particulates, such as dust, airborne organisms or vaporized particles. The cleanliness is rated by the number of particles per cubic meter at a predetermined molecule measure. Our suites at Seqens CDMO NA have been validated to class 100,000. However, our annual recertification tests have shown our suites to be between 12,000-14,000 on an ongoing  basis.
  2. How much do you test the quality of the API? After an API is produced for an injectable, samples are sent out for microbiological testing where endotoxin tests are performed to make sure they don’t contain bacteria, such as salmonella, fungi or other residual bacteria. These tests are conducted by heating the samples in a petri dish to see if anything grows (since in organic chemistry those types of microbes cannot survive in organic media, they need water and oxygen and warm conditions). Outside microbiological testing can be expensive, but a good CDMO will consider the cost money well spent to ensure validated results.
  3. What are your cleaning protocols? A prerequisite for GMP manufacturing is the cleaning of equipment to meet a predetermined specification. This is established by assessing the toxicity and potency of the existing residues on potential human consumers of the next product to be manufactured by the same equipment. Cleaning procedures are based on the nature of the residues, the equipment design and the expected effectiveness of the procedure. Ask your CDMO about its procedures.
  4. How do you outfit the staff? You should inquire about the operating procedures that ensure that all staff in proximity to the API are free of contaminants. Everyone working on an injectable API project should be gowned from head to toe (in that order), wearing masks at all times.  Each person should wash and dry exposed body parts, such as face and hands, before putting on gloves and garments. In addition, all staff working in or near the GMP suite or handling the materials in any way should be free of any illness before coming to work.
  5. How do you handle impurities? It’s important to ask the CDMO which guidelines it uses to address chemical impurities. Many CDMOs follow the International Conference of Harmonization (ICH) guidelines, which provides a practical framework for identifying, categorizing and qualifying genotoxic impurities to limit potential carcinogenic risk.  According to the guidelines, when genotoxic impurities are identified, an appropriate control strategy leveraging process understanding and/or analytical controls should be developed to ensure that the mutagenic impurity is at or below the acceptable cancer risk level.

Injectable drugs provide the fastest route to drug delivery, but maintaining a sterile environment, eliminating impurities and maintaining quality become the prerequisite to their safety.  Before selecting a CDMO to work on your API for injectables, make sure they have what it takes to ensure a smooth pathway to FDA approval and ultimately safety for patients who rely on them

For more insights, check out: Whose Manufacturing Your Prized API?, How to Stem the Flow of Tainted Generic Drugs, or Coming Clean on Cleanroom Operations in GMP Manufacturing.