The Top 66 Aseptic Processing Regulations | IVT

Aseptic processing during the manufacturer of pharmaceuticals, medical devices, and combination products is coming under increasing scrutiny over the last few years. From 2004 to 2010, three quarters of drug product recalls involved sterile drug products, and of these sterile product recalls, approximately 80% were due to lack of sterility assurance. The manufacturing of sterile drug products has consistently remained challenging, and industry is always seeking ways to improve and remain compliant with global regulations.

In March, 2014, IVT hosted the "Advances in Aseptic Processing conference," where participants were updated on regulatory expectations and had the opportunity to benchmark with peers. Taken from these presentations, below is a list of international regulations and guidance for aseptic processing. Knowledge of these requirements and resources will guarantee compliance with international regulatory agencies and lean, efficient aseptic processing

US Food and Drug Administration

  1. Guidance for Industry Sterile Drug Products Produced by Aseptic Processing, read it here.
  2. Code of Federal Regulations Title 21 Part 211 (Specifically, 211.113, 211.42, 211.67, 211.63, 211.167, 211.165, 211.192, 211.194, 211.22, 211.25, 211.28, 211.65, 211.103, 211.84, 211.46, 211.166, 211.13), read it here.
  3. Code of Federal Regulations Title 21 Part 820 (Specifically, 820.30), read it here.
  4. Code of Federal Regulations Title 21 Part 606, read it here.
  5. Code of Federal Regulations Title 21 Part 177, read it here.
  6. Guide to Inspections Validation of Cleaning Processes, read it here.
  7. Compliance Program Guidance Manual, Sterile Drug Process Inspections Program, Chapter 56-Drug Quality Assurance, read it here.
  8. Process Validation: General Principles and Practice, read it here.
  9. Technical Considerations for Pen, Jet, and Related Injectors Intended for Use with Drugs and Biological Products, read it here.
  10. Glass Syringes for Delivering Drug and Biological Products: Technical Information to Supplement International Organization for Standardization (ISO) Standard 11040-4, read it here.
  11. Submissions for Postapproval Modifications to a Combination Product Approved Under a BLA, NDA, or PMA, read it here.
  12. Classification of Products as Drugs and Devices and Additional Product Classification Issues, read it here.
  13. Interpretation of the Term "Chemical Action" in the Definition of Device Under Section 201(h) of the Federal Food, Drug, and Cosmetic Act, read it here.
  14. How to Write a Request for Designation (RFD), read it here.
  15. Proposed Rule: Current Good Manufacturing Practice Requirements for Combination Products (74 Fed. Reg. 48,423), read it here.
  16. New Contrast Imaging Indication Considerations for Devices and Approved Drug and Biological Products, read it here.
  17. Devices Used to Process Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps), read it here.
  18. Minimal Manipulation of Structural Tissue (Jurisdictional Update), read it here.
  19. Early Development Considerations for Innovative Combination Products, read it here.
  20. Application User Fees for Combination Products, read it here.
  21. Current Good Manufacturing Practice for Combination Products (Draft Guidance), read it here.
  22. Submission and Resolution of Formal Disputes Regarding the Timeliness of Premarket Review of a Combination Product, read it here.
  23. Guidance for Industry: Manufacturing, Processing, or Holding APIs, read it here.
  24. ORA: ORA-Lab.5.3; Facilities and Environmental Conditions, read it here.

International Conference for Harmonisation

  1. ICH Q10, Pharmaceutical Quality System, read it here.
  2. ICH Q8, Pharmaceutical Development, read it here.
  3. ICH Q9, Quality Risk Management, read it here.

Medicines and Healthcare Products Regulatory Agency

  1. Rules and Guidance for Pharmaceutical Manufacturers and Distributors 2014 - the 'Orange Guide', read it here.

European Union

  1. EudraLex - Volume 4 Good manufacturing practice, Annex 1 (specifically, Annex 1.4, 1.42, 1.55, 1.3, 1.36, 1.54, 1.55, 1.61, 1.56), read it here.
  2. EudraLex - Volume 4 Good manufacturing practice, Annex 5.37, read it here.

United States Pharmacopeia

  1. USP <1116> Microbiological control and monitoring of aseptic processing environments.
  2. USP 36-NF 31, read it here.
  3. USP <71>, Sterility Tests.
  4. USP <87>, Biological Reactivity Test, In Vitro.
  5. USP <88>, Biological Reactivity Test, In Vivo.

International Organization for Standardization

  1. ISO 14644, Cleanrooms and associated controlled environments, read it here.
  2. ISO 9000: Quality Management, read it here.
  3. ISO 19011:2011, Guidelines for auditing management systems, read it here.
  4. ISO 1901:2008, Quality management systems -- Requirements.
  5. ISO 9004:2009, Managing for the sustained success of an organization -- A quality management approach, read it here.
  6. ISO 11040, Prefilled syringes, read it here.
  7. ISO 14644-2:2000, Clean rooms and associated controlled environments: Part 2, read it here.
  8. ISO 11137, Sterilization of health care products -- Radiation, read it here.
  9. ISO 11135, Sterilization of health care products -- Ethylene oxide, read it here.
  10. ISO 17665, Sterilization of health care products -- Moist heat, read it here.
  11. ISO 20857, Sterilization of health care products -- Dry heat -- Requirements for the development, validation and routine control of a sterilization process for medical devices, read it here.

Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme

  1. Guide to Good Practices for the Preparation of Medicinal Products in Healthcare Establishments, read it here.
  2. Recommendation on the Validation of Aseptic Processes, read it here.
  3. Isolators Used for Aseptic Processing and Sterility Testing, read it here.
  4. Guide to Good Manufacturing Practice for Medicinal Products PE 009-10 (Part I).

World Health Organization

  1.  Good Manufacturing Practices for Sterile Pharmaceutical Products, read it here.

Parenteral Drug Association

  1. I. Kaesler, G. Haake, H. Hennig, A. Rosenhagen, T. H. Meltzer, and M. W. Jornitz, "The Importance of Accurate Microorganism Identification in Microbial Challenge Tests of Membrane Filters—Part I," PDA Journal of Pharmaceutical Science and Technology 65, 92-99, March/April 2011, read it here.
  2. G. Haake, I. Kaesler-Neumann, H. Hennig, T. H. Meltzer, and M. W. Jornitz, "The Importance of Accurate Microorganism Identification in Microbial Challenge Tests of Membrane Filters. Part II. The Comparison of Hydrogenophaga pseudoflava ATTC 33668 and Curvibacter sp. ATCC 700892 by Microbial Challenge Tests with Membrane Filters," PDA Journal of Pharmaceutical Science and Technology 66, 346-353, July/Aug 2012, read it here.
  3. "Validation of Moist Heat Sterilization Processes," PDA Technical Report 1, read it here.
  4. "Moist Heat Sterilizer Systems Design, Commissioning, Operation, Qualification, and Maintenance," PDA Technical Report 48, read it here.
  5. "Fundamentals of an Environmental Monitoring Program," PDA Technical Report 13, read it here.
  6. "Sterilizing Filtration of Liquids," PDA Technical Report 26, read it here.
  7. K. Mignot, “Key Factors for Validating a Disposable System” PDA Letter, October 2013.
  8. I. Kaesler, G. Haake, H. Hennig, A. Rosenhagen, T.H. Meltzer, M.W. Jornitz, “The Importance of Accurate Microorganism Identification in Microbial Challenge Tests of Membrane Filters-Part I & Part II” PDA Journal of Pharmaceutical Technology 65 (2), 92–9, 2011 and 66 (4), 346–53, 2012, read them here and here.


  1. A. Bhatia, “HVAC Design for Cleanroom Facilities”, read it here.
  2. J. Boehm, “Single-Use Connections Enable Advancements in Aseptic Processing," BioProcess International 8 (4), 32–35, April 2010, read it here.
  3. M.A. Petrich, “Design and deployment Strategy for Single-Use Components and Assemblies,” American Pharmaceutical Review, December 2013, read it here.
  4. M. Trotter, “Adoption of Single-Use Disposable Technology in Biopharma Industries – Manufacturing, Economic and regulatory Issues to Consider,” American Pharmaceutical Review, March 2012, read it here.
  5. J. Boehm, "Improving Flexibility and Saving Money for Biopharmaceutical Manufacturers,” BioProcess International, April 2010.
  6. E. Jenness and V. Gupta, “Implementing a Single-Use Solution for Fill-Finish Manufacturing Operations,” BioProcess International, May 2011, read it here.
  7. J.D. Vogel, “The Maturation of Single-Use Applications,” BioProcess International 10 (5), 10–18, May 2012, read it here.
  8. Collected pieces from Rizwan Sharnez, read them here.
  9. Collected pieces from the Journal of Validation Technology and the Journal of GXP Compliance, "The Aseptic Core," read them here.

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