This article was originally published on 27.1.2016 and has now been updated with new information.
A growing number of pharmaceutical products contain highly potent active pharmaceutical ingredients (HP APIs) – molecules that are proven to be effective at much smaller dosage levels than traditional APIs, usually at mg scale and below.
The HP APIs are classified based on their toxicity, pharmacological potency and occupational exposure limits (OELs).
During the last decade, the demand for HP APIs has rapidly increased, mainly because of advantages in clinical pharmacology and oncology research. The overall HP API market is predicted to grow at approximately 10% per year, with about 25% of drugs already on the market today formulated with HP APIs.
The largest percentage of HP APIs is intended for the treatment of cancer: it was estimated that there are nearly 290 small-molecule targeted therapies currently under development against cancer.
These APIs are frequently characterized by complex structures requiring multi-step processes or semi-synthesis, often involving more than 10 synthetic steps.
The development and production of highly potent compounds, in fact must be achieved in a manner that protects researcher, operators and the environment from exposure to the HPAPIs and, in multi-product facilities, minimizes any risk for cross-contamination when switching from one product to another.
Expertise in synthetic organic chemistry, process development and optimization, purification capabilities, and highly sensitive analytical instrumentation and techniques, are to be performed under conditions that minimize the exposure to dangerous material.
Highly potent API development and manufacturing require specialized approaches in facility design, equipment selection and manufacturing processes to achieve desired levels of high level containment.
High Potency Manufacturing
At Teva api, our long tradition of highly potent product manufacturing dates back to the 1980s.
Initially, the focus at our HP sites was on steroids and steroidal hormones; subsequently, we added APIs that can be used in oncolytic drugs, muscle relaxants (anesthesia), immunomodulating drugs and drugs for pulmonary diseases (e.g., COPD and asthma) and HPAPI for Antibody-drug conjugates (ADCs).
Placing patient health as a top priority, Teva api prevents any risk of cross contamination with chemical entities active at the µg (microgram) level by operating four dedicated production lines based on our four areas of focus.
Today Teva api operates several HP sites. Teva asset includes specialized HP API R&D labs, pilot and finally launch and commercial scale production facilities.
In addition to fulfilling industry needs for injectable and respiratory drugs, Teva api also has implemented lyophilization (freeze-drying) and micronization processes at commercial scale.
At Teva api division, HP API are produced using combination of synthetic organic chemistry expertise, fermentation, natural product extraction, flow and continuous production technology and include API products such as: Tobramycin, Betamethasone valerate, Diflorasone diacetate, Paclitaxel, Fluticasone Furoate, Tacrolimus, Cisatracurium, and more.