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Bringing any new drug to the market is a challenging and complicated process. But if that drug is a controlled substance, the challenges multiply. The development and manufacturing processes are even more heavily regulated, requiring adherence to the strict standards set by state, federal and international agencies. Whether the manufacture is carried out in-house or outsourced to a CDMO, legal and regulatory requirements must be met in their entirety. A range of practices, procedures and protocols are needed in order to stay compliant.
Meeting strict regulatory expectations
In the US, controlled substances are under the oversight of the Drug Enforcement Administration per the Controlled Substances Act (CSA) of 1970. The agency’s main aim is twofold: allowing controlled substances to be produced to meet legitimate medical needs and preventing their diversion for illicit purposes. For Schedule 1 and Schedule 2 drugs, the DEA issues quotas based on specific drug codes, and grants permission to manufacturing quota based on their assessment of the market need. The Siegfried Acceleration Hub, for example, has a manufacturing registration that encompasses 71 different drug codes across two US-based manufacturing sites. These quotas have an important purpose: they ensure production aligns with legitimate medical needs to conduct clinical trials or supply to the market while preventing excessive amounts being manufactured or products being stockpiled.
A number of established procedures, in combination with detailed information about our customers’, and by extension their patients medical needs, helps ensure compliance with all relevant laws and regulations and the prevention of stockpiling. For example, we have set up a chain of custody that allows us to account for the volume of controlled substances we have on site and ensure we have the appropriate DEA quotas for these. Each employee must pass a thorough background check and screening to confirm they meet the legal requirements to work with controlled substances. We work closely with our customers to understand the nature of their clinical trials including dose, dose frequency, additional material needed for testing, stability, and regulatory retains in order to ensure adequate material can be justifiably manufactured.
Building compliance into every process
Another critical aspect of compliance involves compiling – and maintaining – precise documentation. Batch production records and testing records must be meticulously written if they are to abide by all controlled substance laws and all material is accounted for down to the milligram. This ensures transparency and accountability throughout the manufacturing process and provides the clear trail of compliance required by the regulatory agencies.
Securing materials and facilities
The storage of controlled substances must also be secure. We have a multi-million-dollar DEA-inspected and approved vault systems that are tested regularly to maintain its certification. We have also installed high-tech biometric, physical, and surveillance systems to prevent unauthorized access to controlled substances on site.
Applying controls from early development onward
The legal and regulatory requirements apply to any compound considered a controlled substance under the CSA, not just those that have been commercialized. This is regardless of where on the compound is in the clinical lifecycle, starting in preclinical. Strict standard operating procedures are essential to ensure every step is executed with both precision and compliance.
In any pharma manufacturing facility, there is no substitute for a team of highly trained manufacturing staff who are well versed in compliance with cGMP protocols. But, of course, maintaining compliance with both FDA and DEA requirements adds a further layer of complexity to manufacturing operations, even if that takes place in an R&D laboratory.
Supporting global supply chains
Even more complexity arises if the controlled substances are to be shipped overseas. This is where an experienced provider will impart invaluable guidance, and assistance in working with the equivalent of the DEA in every country they are being shipped to. Each of these organizations, unsurprisingly, has its own processes for importing and issuing the appropriate permits needed to compliantly import.
The International Narcotics Control Board (INCB) was created in 1968 under the Single Convention on Narcotic Drugs of 1961 to govern the implementation of United Nations international drug control conventions. The INCB manages the legitimate trade of medical drugs and prevents the diversion of chemical precursors into illicit global markets. INCB dispenses quotas for the legitimate medical needs for certain drugs controlled and monitored under international treaties. A knowledgeable manufacturer working in a global market will work with customers to determine the needs for each export destination, and also with individual countries’ health authorities or other governing bodies to obtain export permits.
Choosing the right CDMO partner for controlled substances
At the Siegfried Acceleration Hub, we understand all the complexities, laws and regulations involved in the manufacture of controlled substances. Whether it’s managing quotas, navigating international regulations or securing permits, the team is ready to provide guidance and assistance at every step.
If you are interested in learning more about Siegfried and its capabilities, contact us:
