Resources

Advanced Therapy Medicinal Products (ATMPs)

2013. Guideline on the risk-based approach according to annex I, part IV of Directive 2001/83/EC applied to Advanced therapy medicinal products. European Medicines Agency. London, UK.

2012. Reflection paper on clinical aspects related to tissue engineered products. European Medicines Agency. London, UK.

2012. Reflection paper on classification of Advanced Therapy Medicinal Products. European Medicines Agency. London, UK.

2011. CHMP/CAT position statement on Creutzfeldt-Jakob disease and advanced therapy medicinal products. European Medicines Agency. London, UK.

2010. Reflection paper on stem cell-based medicinal products. European Medicines Agency. London, UK.

2010. Reflection paper on in-vitro cultured chondrocyte containing products for cartilage repair of the knee. European Medicines Agency. London, UK.

2009. COMMISSION DIRECTIVE 2009/120/EC  amending Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use as regards advanced therapy medicinal products. European Medicines Agency. London, UK.

2009. COMMISSION REGULATION (EC) No 668/2009 implementing Regulation (EC) No 1394/2007  Evaluation and certification of quality and non-clinical data relating to advanced therapy medicinal products developed by micro, small and medium-sized enterprises. European Medicines Agency. London, UK.

2007. Draft Guideline on Human Cell-Based Medicinal Products. European Medicines Agency. London, UK.

2007. REGULATION (EC) No 1394/2007 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004. European Medicines Agency. London, UK.

2006. Draft Guideline on Potency Testing of Cell Based Immunotherapy Medicinal Products for the Treatment of Cancer. European Medicines Agency. London, UK.

2004. Directive 2004/23/EC of the European Parliament and of the Council of 31 March 2004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells. European Medicines Agency. London, UK.

FDA Cell Therapy Guidance

February 2019. Food and Drug Administration.  Expedited Programs for Regenerative Medicine Therapies for Serious Conditions; Guidance for Industry.  U.S. Department of Health and Human Services, Rockville, Maryland.

February 2019. Food and Drug Administration.  Evaluation of Devices Used with Regenerative Medicine Advanced Therapies; Guidance for Industry. U.S. Department of Health and Human Services, Rockville, Maryland.

July 2018. Food and Drug Administration. Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs); Draft Guidance for Industry. U.S. Department of Health and Human Services, Rockville, Maryland.

July 2018. Food and Drug Administration. Long Term Follow-up After Administration of Human Gene Therapy Products; Draft Guidance for Industry. U.S. Department of Health and Human Services, Rockville, Maryland.

July 2018. Food and Drug Administration. Testing of Retroviral Vector-Based Human Gene Therapy Products for Replication Competent Retrovirus During Product Manufacture and Patient Follow-up; Draft Guidance for Industry. U.S. Department of Health and Human Services, Rockville, Maryland.

July 2018. Food and Drug Administration. Human Gene Therapy for Hemophilia; Draft Guidance for Industry. U.S. Department of Health and Human Services, Rockville, Maryland.

July 2018. Food and Drug Administration.  Human Gene Therapy for Rare Diseases; Draft Guidance for Industry.  U.S. Department of Health and Human Services, Rockville, Maryland.

July 2018. Food and Drug Administration. Human Gene Therapy for Retinal Disorders; Draft Guidance for Industry. U.S. Department of Health and Human Services, Rockville, Maryland.

December 2017. Food and Drug Administration. Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use; Guidance for Industry and Food and Drug Administration Staff. U.S. Department of Health and Human Services, Rockville, Maryland.

November 2017. Food and Drug Administration.  Same Surgical Procedure Exception under 21 CFR 1271.15(b): Questions and Answers Regarding the Scope of the Exception; Guidance for Industry. U.S. Department of Health and Human Services, Rockville, Maryland.

September 2017. Food and Drug Administration. Deviation Reporting for Human Cells, Tissues, and Cellular and Tissue-Based Products Regulated Solely Under Section 361 of the Public Health Service Act and 21 CFR Part 1271; Guidance for Industry. U.S. Department of Health and Human Services, Rockville, Maryland.

September 2016. Food and Drug Administration. Recommendations for Microbial Vectors Used for Gene Therapy; Guidance for Industry. U.S. Department of Health and Human Services, Rockville, Maryland.

August 2015. Food and Drug Administration. Design and Analysis of Shedding Studies for Virus or Bacteria-Based Gene Therapy and Oncolytic Products; Guidance for Industry. U.S. Department of Health and Human Services, Rockville, Maryland.

December 2015. Food and Drug Administration.  Draft  Guidance for Industry: Deviation Reporting for Human Cells, Tissues, and Cellular and Tissue-Based Products Regulated Solely Under Section 361 of the Public Health Service Act and 21 CFR Part 1271. U.S. Department of Health and Human Services, Rockville, Maryland.

August 2015. Food and Drug Administration. Guidance for Industry: Design and Analysis of Shedding Studies for Virus or Bacteria-Based Gene Therapy and Oncolytic Products. U.S. Department of Health and Human Services, Rockville, Maryland.

June 2015. Food and Drug Administration. Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products. U.S. Department of Health and Human Services, Rockville, Maryland.

December 2014. Food and Drug Administration. Draft Guidance for Industry: Minimal Manipulation of Human Cells, Tissues, and Cellular and Tissue-Based Products. U.S. Department of Health and Human Services, Rockville, Maryland.

December 2014. Food and Drug Administration. Draft Guidance for Industry: Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) from Adipose Tissue: Regulatory Considerations. U.S. Department of Health and Human Services, Rockville, Maryland.

October 2014. Food and Drug Administration. Draft Guidance for Industry: Same Surgical Procedure Exception under 21 CFR 1271.15(b): Questions and Answers Regarding the Scope of the Exception. U.S. Department of Health and Human Services, Rockville, Maryland.

June 2014. Food and Drug Administration. Draft Guidance for Industry: Determining the Need for and Content of Environmental Assessments for Gene Therapies, Vectored Vaccines, and Related Recombinant Viral or Microbial Products. U.S. Department of Health and Human Services, Rockville, Maryland.

March 2014. Food and Drug Administration. Guidance for Industry: Biologics License Applications for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic and Immunologic Reconstitution in Patients with Disorders Affecting the Hematopoietic System. U.S. Department of Health and Human Services, Rockville, Maryland.

March 2014. Food and Drug Administration. Guidance for Industry and FDA Staff: Investigational New Drug Applications for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic and Immunologic Reconstitution in Patients with Disorders Affecting the Hematopoietic System. U.S. Department of Health and Human Services, Rockville, Maryland.

November 2013. Food and Drug Administration. Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy Products. U.S. Department of Health and Human Services, Rockville, Maryland.

December 2011. Food and Drug Administration. Guidance for Industry: Preparation of IDEs and INDs for Products Intended to Repair or Replace Knee Cartilage. U.S. Department of Health and Human Services, Rockville, Maryland.

October 2011. Food and Drug Administration. Guidance for Industry: Clinical Considerations for Therapeutic Cancer Vaccines. U.S. Department of Health and Human Services, Rockville, Maryland.

June 2011. Food and Drug Administration. Guidance for Industry and FDA Staff: Investigational New Drug Applications (INDs) for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic Reconstitution for Specified Indications. U.S. Department of Health and Human Services, Rockville, Maryland.

January 2011. Food and Drug Administration. Guidance for Industry: Potency Tests for Cellular and Gene Therapy Products. U.S. Department of Health and Human Services, Rockville, Maryland.

October 2010. Food and Drug Administration. Guidance for Industry: Cellular Therapy for Cardiac Disease. U.S. Department of Health and Human Services, Rockville, Maryland.

October 2009. Food and Drug Administration. Guidance for Industry: Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic Reconstitution for Specified Indications. U.S. Department of Health and Human Services, Rockville, Maryland.

 September 2009. Food and Drug Administration. Guidance for Industry: Considerations for Allogeneic Pancreatic Islet Cell Products. U.S. Department of Health and Human Services, Rockville, Maryland.

April 2008. Food and Drug Administration. Guidance for FDA Reviewers and Sponsors: Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs). U.S. Department of Health and Human Services, Rockville, Maryland.

August 2007. Food and Drug Administration. Guidance for Industry: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps). U.S. Department of Health and Human Services, Rockville, Maryland.

March 1998. Food and Drug Administration. Guidance for Industry: Guidance for Human Somatic Cell Therapy and Gene Therapy. U.S. Department of Health and Human Services, Rockville, Maryland.

Food and Drug Administration. Blood Guidance Documents. U.S. Department of Health and Human Services, Rockville, Maryland.

Good Manufacturing Practices

• 2013. Therapeutic Goods Administration.  Australian Code of Good Manufacturing Practice for Human Blood and Blood Components, Human Tissue and Human Cellular Therapy Products. Australia.
• 2012. Federal Register. Food and Drug Administration. Amendments to Sterility Test Requirements for Biological Products Final Rule. 21 CFR Parts 600, 610, and 680 [Docket No. FDA–2011–N–0080]. 77(86): 26162-26175.
• 2012. European Commission. EU guidelines to good manufacturing practice, Annex 2. Manufacture of Biological active substances and Medicinal Products for Human Use. EudraLex, European Union: Brusselles, Belgium.
• 2010. European Commission. EU guidelines to good manufacturing practice, Annex 14. Manufacture of Medicinal Products Derived from Human Blood or Plasma. EudraLex, European Union: Brusselles, Belgium.
• 2008. European Commission. EU guidelines to good manufacturing practice, Annex 1. Manufacture of sterile medicinal products (corrected version). EudraLex, European Union: Brusselles, Belgium.
• 2004. Food and Drug Administration. Guidance for Industry: Sterile drug products produced by aseptic processing -Current good manufacturing practice. U.S. Department of Health and Human Services, Rockville, Maryland.
• 2004. Food and Drug Administration. Final report for pharmaceutical cGMPs for the 21st Century – A risk-based approach. U.S. Department of Health and Human Services, Rockville, Maryland.
• 2000. International Conference on Harmonization. Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients – Q7. Geneva, Switzerland.

ICH Guidelines

Pharmacopoeias Q4B

• 2010. International Conference on Harmonization. Sterility Test General Chapter Q4B Annex 8(R1). Geneva, Switzerland.
• 2012. International Conference on Harmonization. Bacterial Endotoxins Test General Chapter Q4B Annex 14. Geneva, Switzerland.

 Quality of Biotechnology Products Q5A – Q5E

• 1999. International Conference on Harmonization. Quality of Biotechnology Products: Viral Safety Evaluation of Biotechnology Products Derived From Cell Lines of Human or Animal Origin Q5A(R1). Geneva, Switzerland.
• 1995. International Conference on Harmonization. Analysis of the Expression Construct Cells Used for Production of r-DNA Derived Protein Products Q5B. Geneva, Switzerland.
• 1995. International Conference on Harmonization. Stability Testing of Biotechnological / Biological Products Q5C. Geneva, Switzerland.
• 1997. International Conference on Harmonization. Derivation and Characterization of Cell Substrates Used for Production of Biotechnological/Biological Products Q5D. Geneva, Switzerland.
• 2004. International Conference on Harmonization. Comparability of Biotechnological / Biological Products Subject to Changes in Their Manufacturing Process. Geneva, Switzerland.

Specifications Q6B

• 1999. International Conference on Harmonization. Specifications: Test Procedures and Acceptance Criteria for Biotechnological / Biological Products Q6B. Geneva, Switzerland.

Pharmacopeial References

• United States Pharmacopeia, General Informational Chapter <71>. Sterility Tests. Rockville. MD.
• United States Pharmacopeia, General Informational Chapter <85>. Bacterial Endotoxins Test. Rockville. MD.
• United States Pharmacopeia, General Informational Chapter <788>. Particulate Matter in Injections. Rockville, MD.
• United States Pharmacopeia, General Informational Chapter <1046>. Cell and Gene Therapy, Rockville. MD.
• United States Pharmacopeia, General Informational Chapter <1043>. Ancillary Materials Used in the Manufacturing of Cell Therapy Products. Rockville. MD.
• United States Pharmacopeia, General Informational Chapter <1223. Validation of Alternative Microbiological Methods. Rockville. MD.
• European Pharmacopeia 2.6.1. Sterility.
• European Pharmacopeia 2.6.27. Microbiological Control of Cellular Products.
• European Pharmacopeia 5.1.6. Alternative Methods for Control of Microbiological Quality.

TGA Australian Guidance

2014. Therapeutic Goods Administration. Australian Regulatory Guidelines for Biologicals: Appendix 4 Guidance on TGO 88 – Standards for donor selection, testing and minimising infectious disease transmission via therapeutic goods that are human blood and blood components, human tissues and human cellular therapy products. Australia.

2013. Therapeutic Goods Administration. Therapeutic Goods Order No. 88  Standards for donor selection, testing, and minimising infectious disease transmission via therapeutic goods that are human blood and blood components, human tissues and human cellular therapy products. Australia.

2013. Australian Code of Good Manufacturing Practice for human blood and blood components, human tissues and human cellular therapy products 2013. Australia.

2011. Therapeutic Goods Administration. Australian Regulatory Guidelines for Biologicals Part 1 – Introduction to the Australian Regulatory Guidelines for Biologicals. Australia.

2011. Therapeutic Goods Administration. Australian Regulatory Guidelines for Biologicals Part 2 – Regulatory lifecycle for biologicals that are included on the Australian Register for Therapeutic Goods. Australia.

2011. Therapeutic Goods Administration. Australian Regulatory Guidelines for Biologicals Part 3 – Access to unapproved biologicals. Australia.

2008.  Therapeutic Goods Administration. Guideline for the Preparation of Technical Master Files for Blood, Blood Components and Haematopoietic Progenitor Cells Third edition. Australia.

Tissue Guidance

• 2013. Food and Drug Administration. Draft Guidance for Industry: Use of Donor Screening Tests to Test Donors of Human Cells, Tissues and Cellular and Tissue-Based Products (HCT/Ps) for Infection with Treponema pallidum (Syphilis). U.S. Department of Health and Human Services, Rockville, Maryland.
• 2013. Food and Drug Administration. Draft Guidance for Industry: Use of Nucleic Acid Tests to Reduce the Risk of Transmission of West Nile Virus from Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps). U.S. Department of Health and Human Services, Rockville, Maryland.
• 2011. Food and Drug Administration. Guidance for Industry: Current Good Tissue Practice (cGTP) and Additional Requirements for Manufacturers of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps). U.S. Department of Health and Human Services, Rockville, Maryland.
• 2011. Food and Drug Administration. Guidance for Industry: Class II Special Controls Guidance Document: Cord Blood Processing System and Storage Container. U.S. Department of Health and Human Services, Rockville, Maryland.
• 2009. Food and Drug Administration. Draft Guidance for Industry: Use of Seriological Tests to Reduce the Risk of Transmission of Trypanosoma cruzi Infection in Whole Blood and Blood Components for Transfusion and Human Cells, Tissues, and Cellular and Tissue-Based Products. U.S. Department of Health and Human Services, Rockville, Maryland.
• 2008. Food and Drug Administration. Draft Guidance for Industry: Use of Nucleic Acid Tests to Reduce the Risk of Transmission of West Nile Virus from Donors of Whole Blood and Blood Components Intended for Transfusion and Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps). U.S. Department of Health and Human Services, Rockville, Maryland.
• 2008. Food and Drug Administration. Guidance for Industry: Certain Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) Recovered from Donors Who Were Tested for Communicable Diseases Using Pooled Specimens or Diagnostics Tests. U.S. Department of Health and Human Services, Rockville, Maryland.
• 2007. Food and Drug Administration. Guidance for Industry: Regulation of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) Small Entity Compliance Guide. U.S. Department of Health and Human Services, Rockville, Maryland.
• 2007. Food and Drug Administration. Guidance for Industry: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products. U.S. Department of Health and Human Services, Rockville, Maryland.
• 2007. Food and Drug Administration. Guidance for Industry: Current Good Tissue Practice (CGTPs) and Additional Requirements for Manufacturers of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps). U.S. Department of Health and Human Services, Rockville, Maryland.
• 2007. Food and Drug Administration. Draft Guidance for Industry: Minimally Manipulated, Unrelated, Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic Reconstitution in Patients with Hematological Malignancies. U.S. Department of Health and Human Services, Rockville, Maryland.
• 2006. Food and Drug Administration. Guidance for Industry and FDA Staff: Minimal Manipulation of Structural Tissue Jurisdictional Update. U.S. Department of Health and Human Services, Rockville, Maryland.
• 2006. Food and Drug Administration. Guidance for Industry: Compliance with 21 CFR Part 1271.150(c)(1) – Manufacturing Arrangements. U.S. Department of Health and Human Services, Rockville, Maryland.
• 2005. Food and Drug Administration. Guidance for Industry: MedWatch Form FDA 3500A: Mandatory Reporting of Adverse Reactions Related to Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps). U.S. Department of Health and Human Services, Rockville, Maryland.
• 2004. Food and Drug Administration. Guidance for Industry: Recommendations for Obtaining a Labeling Claim for Communicable Disease Donor Screening Tests Using Cadaveric Blood Specimens from Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps). U.S. Department of Health and Human Services, Rockville, Maryland.
• 2002. Food and Drug Administration. Guidance for Industry: Validation of Procedures for Processing of Human Tissues Intended for Transplantation. U.S. Department of Health and Human Services, Rockville, Maryland.
• 2000. Food and Drug Administration. Guidance for Industry: Availability of Licensed Donor Screening Tests Labeled for Use with Cadaveric Blood Specimens. U.S. Department of Health and Human Services, Rockville, Maryland.
• 1997. Food and Drug Administration. Guidance for Industry: Screening and Testing of Donors of Human Tissue Intended for Transplantation. U.S. Department of Health and Human Services, Rockville, Maryland.