Lyo Market Growth Depends on Regulations

There are stringent GMP guidelines for the manufacture of freeze-dryers. Because lyophilization equipment stabilizes drug molecules used for improving human health or animal health, it is necessary to follow the guidelines from various regulatory bodies like the Food & Drug Administration (FDA) and European Regulatory bodies. The growth of this market is very much dependent on these regulatory guidelines.

FDA Manufacturing Guidelines

• GLP/GMP compliance means having a validated designing, manufacturing, and testing facility for pharmaceutical and biopharmaceutical products. These guidelines contain the validation of the lyophilization process and equipment. As per these guidelines, the lyophilization equipment requires Performance Qualification.
• FDA governs all inspection guidelines for the lyophilization of drug products. The Lyophilization of Parenterals (7/93) is the guide for the lyophilization of parenterals. This references material for investigators and other FDA personnel.
• The Center for Biologics Evaluation and Research (CBER) of the FDA regulates freeze-dried biological products in its section pertaining to residual moisture, as published in Title 21 of the Code of Federal Regulations for Food and Drugs.

FDA Regulatory Considerations for Pharmaceutical Lyophilization

• Hold Time and Equipment Compatibility
• Fill Volume/Fill Volume Tolerances
• Product-specific Characterization/Development Studies
• Establishing the Critical Process Parameters
• Establishing the End Points for Primary and Secondary Drying
• Sampling Plan
• Critical Quality Attributes
• Scale-up
• Post-Approval Lifecycle Perspective

European Union Regulations

• The European Medicines Agency (EMA) coordinates inspections to verify compliance with these standards and plays a key role in harmonizing GMP activities at the European Union (EU) level.
• Any manufacturer of medicines intended for the EU market, no matter where in the world it is located, must comply with GMP.
• Annex 17: Real Time Release Testing and Parametric Release provides guidance for the interpretation of the principles and guidelines of good manufacturing practice (GMP) for medicinal products as laid down in Directive 2003/94/EC for medicinal products for human use and Directive 91/412/EEC for veterinary use.
• Process Analytical Technology (PAT)/RTRT (Real Time Release Testing, Annex 17 of the EU GMP Guide) systems for in-line process monitoring are used to control and determine critical processing parameters. PAT plays an important role in continuous lyophilization processes.
• In February 2020, the Directorate for Health and Food Safety of the European Commission published a second draft for the revision of Annex 1 of the EU GMP Guide. Chapter 8, “Production and Specific Technologies,” discusses approaches to the sterilization of products, equipment, and packaging components. The chapter now also discusses different technologies, such as lyophilization, form-fill-seal, and single-use systems (SUS), where specific requirements apply.

Partnering with a CDMO that understands the various lyophilization regulations will be essential in accelerating the development of complex drug candidates.