Outsourcing the development of controlled substance APIs

18th May 2020

Mike Gibson: Chief Technology Officer

The potential for controlled substance active pharmaceutical ingredients (APIs) to meet the needs of many clinical conditions including depression, post-traumatic stress disorder (PTSD), addiction and pain management, has fuelled a surge in development. It has also led to demands for safer and more robust processes in the manufacture of these compounds. For drug development companies that do not have the necessary expertise, capabilities, and infrastructure to manufacture these APIs in line with increasingly stringent regulatory requirements, outsourcing to contract development and manufacturing organisations (CDMOs) may present the most efficient route to gaining market approval.

The market for controlled substances

The negative perception of controlled substances fuelled by the opioid epidemic has, for many years, stigmatised their use, with many medical professionals believing their prescription does not reflect best clinical practice. This opinion led to several studies during the 1950s and 1960s being abandoned or not used to their full potential. Better understanding is now helping to change this, with studies currently exploring the therapeutic use of controlled drugs in greater depth.

Today, controlled substances are being considered for many products, including the treatment of attention deficit hyperactivity disorder (ADHD) and the increased exploration of their use in oncology. Valued at $64bn globally in 2018, the controlled substances market is expected to reach a CAGR of 7% between 2019-2027 [1].

Regulatory challenges

In 2013, The Controlled Drugs (Supervision of Management and Use) Regulations were published to ensure good governance concerning the safe management and use of controlled drugs. Despite these regulations bringing much needed clarity to development and manufacturing, only a limited number of companies can at present manufacture and formulate controlled substance APIs, mainly due to licensing issues. This has provoked much discussion in the industry as to whether the stringent legislation and control measures surrounding the use of controlled drugs are holding up progress and medical advancements in this area.

Manufacturing controlled substance APIs in the UK requires companies to adhere to specific measures established by the UK Home Office. These are often expensive to implement and demand a high-level of knowledge and expertise, leaving many developers falling short of the requirements. The necessary control measures vary depending on the substance classification attributed to a specific compound, with classification ranging from schedule I-V (I being regarded as the highest risk of abuse or harm and V being regarded as the lowest). Sterling had many of these controls in place before beginning to work with controlled substance APIs, but additional investment has been made to obtain the Schedule I license.

Value in outsourcing

Many smaller organisations will find value in outsourcing their controlled substance API requirements to a reputable CDMO. These providers not only have the required quality control measures, licenses, and comprehensive expertise in place, but will be highly adept in navigating the stringent regulatory requirements. Previous experience is critical in ensuring the compliant handling of APIs and accelerating products from development to commercialisation.

Working with CDMO can also be beneficial when entering stringently regulated markets such as the UK and US. These providers can assist developers in sidestepping import restrictions by manufacturing APIs in the required locations before shipping product to its destination.

Key considerations

CDMOs that offer flexible manufacturing capabilities and are proficient at working with small batch sizes will be best equipped to meet developers’ manufacturing requirements for the low dose APIs used in controlled substance products. They will also be able to offer thorough analytical sampling and stability samples.

A further key consideration is the transportation of controlled substance products. Specific licenses need to be obtained and careful measures put in place to thwart theft or loss.

Final thought

Having the infrastructure, processes and expertise in place to manufacture controlled substance APIs is enabling CDMOs to meet the growing demand for new molecules that make use of the medical value of these compounds in areas such as psychiatric disorders, pain management, and addiction treatment. The manufacturing of controlled substances requires increased diligence surrounding quality control, safety, and security. Outsourcing to a CDMO enables developers to take advantage of the necessary compliance procedures and comprehensive controls already being in place, while also benefitting from cost reductions and import/export assistance. Firms can also leverage their relationships with CDMOs to enter and develop a presence in tightly regulated markets such as the US and UK, rather than investing time, resources and capital into buying or redesigning existing facilities to meet challenging regulatory demands.

For more information, or to speak to a member of the Sterling team, please get in touch.


[1] https://www.marketresearchhub.com/pr/controlled-substance-market.html


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