Custom Conjugation Services for ProDrugs Based on Potent APIs and Controlled Substances

Cedarburg Hauser has the expertise and experience to take your innovative prodrug discovery work and conjugation technology to a larger scale for preclinical research and clinical trials through our custom development services.

The therapeutic benefits of prodrugs have been studied and utilized for years. However, there is now a growing trend of scientists utilizing them more than ever to significantly improve the pharmacokinetic profiles of the drugs they are developing as well as their overall efficiency and physicochemical properties.

Developing prodrugs based on controlled substances as well as potent and cytotoxic drugs takes special experience and expertise

The term “Prodrug” was introduced by Adrian Albert in the 1950’s, and many such molecules have been made, tested, and successfully marketed. The idea is that although a drug molecule may have an optimum design for effectiveness at the cellular level, it may also have serious drawbacks in terms of poor solubility, poor bioavailabilty, and formulation problems.

Other modifications to the active molecule may help target the desired organ, such as the brain, increase oral activity, minimize gastroenteric side-effects, etc. In many cases the Prodrug has little intrinsic bioactivity, and its usefulness is only revealed after a biotransformation in the patient. This is an especially important strategy when the drug itself is potent or cytotoxic.

There are several important qualifications and requirements that a CRO/CMO must have if they are going to help you develop your potent, cytotoxic or controlled substance prodrug:

1. EXPERIENCE WITH POTENT & CONTROLLED SUBSTANCES
   Experience not only working with potent and controlled substances, but also experience with conjugating linkers to them as well.
2. EXPERIENCE WITH MODIFYING EXISTING APIs BEFORE CONJUGATING THEM
   It’s not always as easy as just conjugating a linker to an existing potent or cytotoxic drug to develop the new prodrug. Many times the drug or an advanced intermediate must be chemically modified before you can conjugate a linker to it, so that it produces the desired effect.
3. TECHNICAL EXPERTISE WITH GMP MANUFACTURING SPECIFICALLY FOR POTENT & CONTROLLED SUBSTANCES
   In addition to the usual GMP issues, potent drugs and controlled substances require additional layers of operating procedures, such as environmental containment issues, worker exposure limits, and equipment cleaning validation to extremely low levels. Controlled substances also require the experienced management of secure storage areas, meticulous documentation of inventory and disposal, and additional worker training and monitoring.
4. EXPERIENCE HANDLING POTENT & CONTROLLED SUBSTANCES
   There are special handling requirements for potent and controlled substances, not only in the manufacturing facility, but how they are received, transferred, packaged and shipped. Furthermore, the same concerns discussed above for the manufacture of potent and controlled substances apply to their handling and use in the laboratory during the research phase of your project. Careful inventory control is also necessary to ensure all material is accounted for, and safe disposal is documented; special laboratory equipment must be used, properly isolated and cleaned; and all laboratory workers must be trained and be aware of the hazards.
5. PERMITS AND QUOTAS
   The CRO must have all the appropriate permits and quotas to work with and produce potent, controlled substances. If the CRO does not have the appropriate permits and quotas to work with and produce your controlled substance, they cannot legally help you. If you choose a CRO without them you will risk potential delays to your timeline, extra costs to your budget and failure.

Because Cedarburg Hauser Pharmaceuticals has extensive experience developing, producing and handling potent APIs and controlled substances, we have also been successful in helping several of our clients develop and scale their prodrugs based on those compounds. We have experience with modifying the API synthesis to efficiently accommodate the conjugation steps under cGMP conditions.

If you are developing a prodrug based on a potent drug or controlled substance, you can feel very comfortable working with Cedarburg Hauser as your CRO/CMO for its development, scale-up and production throughout the phases of preclinical and clinical studies. We’d love to talk with you about your project. Feel free to contact us any time.

Cedarburg Hauser is highly experienced in successfully developing, optimizing and scaling processes, routes, and analytical methods for a variety of prodrug types, such as:

• Small Molecule Drug Conjugates (SMDC) such as cytotoxics and controlled substances
• Peptide Conjugates
• Small and Large Molecule Polymer Conjugates

Cedarburg Hauser offers the following conjugation services:

PROCESS DEVELOPMENT, OPTIMIZATION & SCALE-UP OF API AND DRUG CONJUGATES
Many of our clients approach us with MedChem or early development routes that need to be optimized to be more realistic, practical and safe for the next phases of development. Our scientists will use their experience and expertise with potent and controlled substances to recommend alternatives that will create the most efficient process for your prodrug, improving your yields, quality, costs and timeline.

ANALYTICAL METHOD DEVELOPMENT, OPTIMIZATION & SCALE-UP FOR API AND DRUG CONJUGATES
We also offer you a comprehensive suite of analytical services to ensure your potent or cytotoxic prodrug meets the levels of purity and stability you require throughout the various stages of your drug development project. Cedarburg Hauser Pharmaceuticals’ analytical method development processes are managed by our experienced, in-house analytical chemists.

cGMP & NON-GMP MANUFACTURING OF API AND DRUG CONJUGATES
We have GMP isolation suites for non-GMP R&D projects, GMP kilo-labs for early phase development projects, and GMP plant capacity for late stage and commercial APIs. We have glass-lined reactors ranging from 30-500 gallons and a variety of auxiliary equipment for your project.

PERMITS & QUOTAS FOR POTENT, CONTROLLED SUBSTANCES
Cedarburg Hauser has permits and quotas to legally work with, develop, manufacture and ship potent, Schedule 1-5 controlled substances. With our strong history of regulatory compliance and our positive relationships with the FDA and DEA, Cedarburg Hauser can also help you smoothly navigate your potent, cytotoxic or controlled substance prodrug to market and/or prepare it for licensing.

HANDLING & SHIPPING HAZARDOUS GOODS & CONTROLLED SUBSTANCES
Cedarburg Hauser can ship hazardous goods and controlled substances wherever in the world it is permissible. We manage the complete process of assembling the appropriate permits and documentation that are required, packaging your product according to domestic and/or international legal and customs requirements, and shipping it in the most efficient and cost effective way possible to meet your needs.