Given the risks highly potent active pharmaceutical ingredients (HPAPIs) present in cross-contamination and containment, it is important to consider manufacturing and handling approaches carefully. In fact, because of the demands of HPAPI manufacturing, many drug developers select a contract development and manufacturing organization (CDMO) partner to make the substance. The discussion below outlines some of the considerations for HPAPI manufacturing and, when appropriate, HPAPI CDMO selection.
With the significant infrastructure and capital investments required for effective HPAPI manufacturing, it is simply not feasible for many of the small and mid-size companies to make this extensive investment. In the suites alone, Alcami is investing approximately $7 million in 2017. Not to mention its investment in skilled personnel and procedural development. These levels of investment are not possible or prudent for many companies.Some of the larger pharmaceutical companies have chosen to invest in high-potency manufacturing facilities, but even they often outsource manufacturing in the earlier stages of development before potentially transferring production to their own facilities in later stages or for commercial manufacturing. In this way, high-potency development and manufacturing for big pharma is not unlike other outsourcing models in the industry.
Selecting an HPAPI CDMO Partner
For companies that decide to outsource HPAPI manufacturing, it is critically important to understand what goes into highly potent manufacturing and to ask the right questions. The following is a list of questions to ask when selecting an HPAPI CDMO partner:
- Does the facility or company have experience with HPAPIs?
- Does it have robust capabilities to prevent cross-contamination?
- Are contamination-control approaches engineering-based (technology, facility, equipment) or administrative-based (human-centric processes and procedures)? Engineering-controlled processes are far superior.
- Is the facility overly reliant on personal protection equipment (PPE) for containment and worker safety?
- Has the facility been specifically designed for HPAPI manufacturing?
- Can it do small-scale work and scale the product through the various stages of its lifecycle?
- Has industrial hygiene data been gathered to ensure the controls are actually performing at the expected levels?
- Does the facility have robust HPAPI regulatory compliance management and quality system programs?
Warning Signs of an Ineffective HPAPI CDMO Partner
- Poor retrofitting of existing laboratories to accommodate high-potency compounds – a recipe for disaster
- Overreliance on administrative processes and PPE rather than sophisticated engineering controls to manage containment
- Lack of expertise to appropriately evaluate the potency of a compound and the approaches needed to manage and handle it, like engineering controls
- Overemphasis on low-cost service offerings – you may be required to accept substantial risks in safety, contamination and supply chain
The Alcami Advantage– HPAPI Expertise
Alcami has built end-to-end service offerings that facilitate an integrated approach, from early-phase development through commercial manufacturing. This approach is embodied in our ProForm Select™ service offering, which integrates solid-state chemistry, process chemistry and formulation development to ensure clinical milestones are achieved and processes are stable.
We have applied this approach to the development and manufacturing of HPAPIs. Our state-of-the-art manufacturing facilities meet global regulatory requirements, cGMP compliance standards and are FDA inspected and approved. Our production, engineering and development teams focus on developing and executing a robust process control strategy to ensure right-first-time design and scale-up of your API synthesis.
Stay tuned for our next HPAPI post titled: 8 Characteristics of a State-of-the-Art HPAPI Facility