Examining High-Potency API Manufacturing - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

Examining High-Potency API Manufacturing
High-potency manufacturing of active pharmaceutical ingredients is a growing and specialized capability.


Pharmaceutical Technology
Volume 33, Issue 7, pp. 42-46


Patricia Van Arnum
High-potency active pharmaceutical ingredients (HPAPIs) are a niche but growing area for pharmaceutical manufacturers and contract manufacturing organizations (CMOs). Specialized considerations in facility design, equipment, operation, and process safety are needed to achieve the desired level of containment of the drug substance or finished-drug product. For drug-substance manufacturing, the HPAPI may be a small-molecule, biologic, or a hybrid of the two such as an antibody–drug conjugate, which links a cytotoxic small-molecule to a monoclonal antibody.

Assessing HPAPIs

The definition of an HPAPI varies depending on the literature, but generally is defined as (1):

  • A pharmacologically active ingredient or intermediate with biological activity at approximately 150 g/kg of body weight or below in humans (therapeutic daily dose at or below 10 mg)
  • An API or intermediate with an occupational exposure limit (OEL) at or below 10 g/m3 of air as an 8-h time-weighted average
  • A pharmacologically active ingredient or intermediate with high selectivity (i.e., ability to bind to specific receptors or inhibit specific enzymes) and/or with the potential to cause cancer, mutations, developmental effects, or reproductive toxicity at low doses
  • A novel compound of unknown potency and toxicity.


IMAGES COURTESY OF SAFC
The potency of HPAPIs is characterized by OELs in g/m3. The lower the value, the more potent the compound, and the greater the level of containment required (1). OELs and related criteria such as toxicity and carcinogenicity are used in determining the performance-based exposure control limits, which link compound toxicity and potency to procedures for safe-handling of HPAPIs (1). The industry generally uses two rating programs that categorize compounds based on performance-based exposure limits, a five-tiered system or a four-tiered system, which is similar to the one developed by SafeBridge Consultants (Mountain, View, CA) (1).

Facility design, equipment, engineering controls, and the proper operation of facilities and equipment are needed to achieve the desired level of containment in HPAPI manufacturing. Operator safety is also critical and involves the use of personal protection equipment, related training in handling HPAPIs, and implementation of safe-handling practices and current good manufacturing practices (CGMPs) to prevent operator exposure and contamination (1).


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
Which of the following business challenge poses the greatest threat to your company?
Building a sustainable pipeline of products
Attracting a skilled workforce
Obtaining/maintaining adequate financing
Regulatory compliance
Building a sustainable pipeline of products
30%
Attracting a skilled workforce
27%
Obtaining/maintaining adequate financing
14%
Regulatory compliance
30%
View Results
Eric Langer Outsourcing Outlook Eric LangerBiopharma Outsourcing Activities Update
Cynthia Challener, PhD Ingredients Insider Cynthia Challener, PhDAppropriate Process Design Critical for Commercial Manufacture of Highly Potent APIs
Jill Wechsler Regulatory Watch Jill Wechsler FDA and Manufacturers Seek a More Secure Drug Supply Chain
Sean Milmo European Regulatory WatcchSean MilmoQuality by Design?Bridging the Gap between Concept and Implementation
Medicare Payment Data Raises Questions About Drug Costs
FDA Wants You!
A New Strategy to Tackle Antibiotic Resistance
Drug-Diagnostic Development Stymied by Payer Concerns
Obama Administration Halts Attack on Medicare Drug Plans
Source: Pharmaceutical Technology,
Click here