Clinical Manufacturing – How It Works

The drug development process includes these five stages:

  1. Discovery and Development
  2. Preclinical Research
  3. Clinical Research
  4. Regulatory Agency Review
  5. Regulatory Agency Post-Market Safety Monitoring

Clinical research is the third stage of the drug development process and drugs that are being tested and researched in this stage of the process are not usually manufactured the same way or in the same facilities as drugs that are in commercial production.

In this article, we’ll discuss the basics of clinical manufacturing, including:

  • What Clinical Manufacturing is.
  • Current good manufacturing practice (cGMP) guidelines.
  • The difference between clinical manufacturing and commercial.
  • The benefits of specialty clinical trial manufacturing services.

What Is Clinical Manufacturing?

Clinical manufacturing, or clinical trial material manufacturing (CTM), is focused on producing drugs for use in clinical research. It can be done on a large scale or a smaller scale to allow greater flexibility.

The first step in clinical manufacturing is to create a plan and timeline to provide a roadmap of the development and clinical trial process. This timeline should be created before an investigational new drug file or investigational medicinal product dossier is formally submitted.

To ensure the integrity of clinical manufacturing, consistency is paramount. Following cGMP guidelines and having strict quality controls are key factors to achieving consistent clinical trial materials even as formulations and dosages are still in flux.

Implementing cGMP as early as possible in the development of a drug, not only helps protecting the safety of clinical trial participants, it also provides a foundation for a robust quality management system (QMS) for a gradual integration of processes.

Current Good Manufacturing Practice (cGMP) guidelines

In the development of a new drug, clinical project teams often have difficulties with when they should apply for current Good Manufacturing Practices (cGMP).

The cGMP guidelines are applied to most types of drugs in phase I and II development, including vaccine products, recombinant and non-recombinant therapeutic products, small molecule drugs, gene therapy and more. But you have to be careful because the cGMP guidelines apply for each type of drug are different.

GMP is a system for ensuring products are consistently produced and controlled according to quality standards. It is designed to minimize the risks involved in any pharmaceutical production that cannot be eliminated through testing the final product.

In this article we will focus on FDA guidelines and EMA guidelines.

FDA Regulations and Guidance

The FDA cGMP regulations for drugs are published in Title 21 of the US Code of Federal Regulations, Parts 210 and 211 (21 CFR 210/211), where drugs used for Phase I studies are exempts from compliance with 21 CFR 210/211; however, this does not exempt:

  • An investigational drug for use in a Phase I study once it is available for use in a Phase II or Phase III study.
  • A drug lawfully marketed as a monograph drug or by an FDA approved market application.

Additional guidance on cGMP for investigational drugs used in Phase I clinical trials is provided in FDA’s Guidance for Industry Current Good Manufacturing Practice for Phase 1 Investigational Drugs. According to 21 CFR 210.2(c) the cGMP regulations formally apply for drugs used in Phase II/III studies.

EMA Regulations and Guidance

The European Medicines Agency (EMA) coordinates inspections to verify compliance with these standards and plays a key role in harmonizing GMP activities at European Union (EU) level.

The Agency has a coordinating role for GMP inspections of manufacturing sites for medicines whose marketing authorization in the EU is submitted through the centralized procedure or as part of a referral procedure.

Any manufacturer of medicines intended for the EU market, no matter where in the world it is located, must comply with GMP. The GMP requires that medicines:

  • are of consistent high quality.
  • are appropriate for their intended use.
  • meet the requirements of the marketing authorization or clinical trial authorization.

vaccine vials


Three legal instruments lay down the principles and guidelines of GMP in the EU:

  • Regulation No. 1252/2014 and Directive 2003/94/EC, applying to active substances and medicines for human use;
  • Directive 91/412/EEC applying to medicines for veterinary use.

In addition, Directive 2001/83/EC and Directive 2001/82/EC lay down related provisions.

Related Read: Quality By Design in Biologic Drug Development

Clinical Manufacturing and Commercial: What’s the Difference?

The difference between clinical manufacturing and commercial is that clinical manufacturing needs to be nimble.

While, commercial drug manufacturing involves batches that are identical where formulations and dosages are already set, clinical trial manufacturing may call for each batch being made differently and the flexibility is primordial.

One common obstacle for clinical trial materials is the coordination of supply chains. Sometimes the components are supplied from different sites and even different continents. This may not seem like a challenge, but when a biologic is part of this kit, it means that through each step of the process, the drug must be stored at the proper temperature and protected against contamination and compromise.

Related to this, shipments must also be carefully monitored. Variations in temperature and environment can be catastrophic, when sensitive drugs are involved, rendering drugs for clinical trials ineffective and impacting the results of clinical research. Because clinical trial materials aren’t delivered directly to patients, the products must be stored at trial sites and kept in proper conditions until they are ready to use.

Finally, quality assurance is more difficult with clinical trial materials. As we have mentioned before, commercial manufacturing produces batches of drugs are identical to each other; QA personnel have familiarity with the drugs, packaging, and manufacturing process than they do with clinical trial materials, which are manufactured in smaller batches that have much more variability.

Benefits of Specialized Clinical Trial Manufacturing Services

Utilizing the services of a specialtized CDMO like 53Biologics can help pharmaceutical companies expedite the clinical trial process and get their drugs to market sooner. Specialized CDMOs bring knowledge on cGMP guidelines and lay the foundation for a smooth transition from clinical trial manufacturing services to scaling up for the market.

In addition, 53Biologics offers a rapid process development service that involves partnering with discovery-stage pharmaceutical companies to provide lab-scale suitable for pre-clinical testing. And when it’s time to move onto the next stage of development, we provide trial formulations that are suitable for animal studies, toxicology studies, and cGMP clinical trial materials for phase I research.

More than 98% of proteins in our hands have improved their production and/or recovery yields.

Learn More About Clinical Manufacturing

If you plan on using a specialized CDMO for your clinical trial supplies manufacturing, consider 53Biologics. Our knowledge and experience in biologics make us the ideal choice for clinical trial manufacturing. Contact Us today to get started.

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