USP Standards for Ancillary Materials

Transcription

1 Quality Standards for Medicines, Supplements, and Food Ingredients throughout the World USP Standards for Ancillary Materials 8 th Annual Somatic Cell Therapy Symposium September Fouad Atouf, Ph.D. Scientist, Biologics and Biotechnology

2 USP Mission... To improve the health of people around the world through public standards and related programs that help ensure the quality and safety of medicines and foods.

3 An 1820 USP Monograph Roger L. Williams, M.D. EVP-CEO

4 United States Pharmacopeia (USP) Independent Standard Setting Organization Established in 1820 by Medical Community Recipes for Pharmacist Permanent Legal Recognition in late 1800 s via State Laws Permanent National Recognition in 1906 via Pure Food and Drugs Act Food, Drug and Cosmetic Act in 1938 Created FDA & Mandated Enforcement of USP

5 Official Recognition The U.S. Federal Food, Drug, and Cosmetics Act designates the USP NF as the official compendia for drugs marketed in the United States. A drug product in the U.S. market must conform to the standards in USP NF to avoid possible charges of adulteration and misbranding.

6 Documentary vs. Physical Standards Documentary Standards Physical Reference Standards

7 Documentary Standards: Monographs vs. General Chapters Monographs Products-specific Requirements for the product to meet General Chapters with number <1000 Enforceable by FDA or other regulatory authority Test methods chapters Methods referenced in product monographs General Chapters with number >1000 Interpretive and intended to be informational Used as a guidance

8 Standards Setting Approach: A Collaborative Process Review by Expert Committee Publication in PF Public Comments 90 days Review by USP Staff liaison Reprinting in PF USP Expert Committee Review Documentary Standards Development. Initiated by Industry, Regulators, USP Staff and Expert Committees Approval Approval by -Council of Experts- -Board of Trustees- Monograph Becomes official and Published in USP-NF

9 Biologics and Biotechnology at USP USP Develop Standards for Drugs Biologics Blood and Blood products Cell, Gene, and Tissue Therapies Proteins and Polysaccharides Vaccines Excipients Dietary supplements Food and Food ingredients

10 USP CGT EC Members and USP staff Members William E. Tente, M.S., Chair Darin J. Weber, Ph.D., Vice-Chair Scott R. Burger, M.D. Nancy H. Collins, Ph.D. Maria A. Croyle, Ph.D. Gary C. du Moulin, Ph.D. Joseph F. Gallelli, Ph.D. Beth M. Hutchins, Ph.D. Deepak Jain, Ph.D. Ann A. Jakubowski, M.D., Ph.D. Nicole C. Provost, Ph.D. Elizabeth J. Read, M.D. Anthony A.G. Ridgway, Ph.D. USP Staff Fouad Atouf, Ph.D. Tina Morris, Ph.D.

11 Biologics and Biotechnology (B&B) Standards at USP Procurement/ Source Material Equipment Operator/ Technologist Process Materials B&B Products Cell, Gene and Tissue Therapies Environment/ Clean Rooms Selection Devices Raw Materials Ancillary Materials

12 Ancillary Materials (AMs) Biological and Biochemical substances that are used to manufacture cell therapy, gene therapy or tissue-engineered products or therapeutics derived from cell culture (i.e. vaccines, proteins) but are not intended to be in final product. Include raw materials, processing and purification aids or agents used during manufacture. Ancillary Material requirements are intended to help standardize these items. Protein A Fetal Bovine Serum Trypsin DNA Nuclease Transferrin Interleukin-4

13 Ancillary Materials Standards: Development Strategy <1043> Ancillary Materials for Cell-, Gene-, and Tissue-Engineered Products Official Chapter Ancillary Material Requirements- Specific Products Under Development Ancillary Material Reference Standards

14 <1043> Ancillary Materials - Official Chapter Quality of ancillary material can affect stability, safety, potency and purity of medicinal products Validation of manufacturing processes to ensure removal of ancillary materials from final products Residual testing is important as residual ancillary material may trigger immune reaction Development of qualification programs for AMs used in cell manufacturing Risk-based classification of AMs

15 <1043> Ancillary Materials Qualification Programs Identification Selection Suitability of use Characterization Vendor qualification QA/QC data

16 Qualification Programs (Cont d) Identification Source material Concentration of use Tests for identification Manufacturing steps Selection Early phase of development Microbiological BSE/TSE risk assessment

17 Qualification Programs (Cont d) Suitability of use Evaluate the risk associated with transmission of diseases, when using human or animal-derived AMs Material traceability Risk can be reduced by using a quantitative or semiquantitative risk-assessment tool (e.g. FMEA) Characterization Level of testing is based on the risk assessment profile Specifications to be established for each AM used in manufacturing, to ensure quality of the product Acceptance criteria should be based on pre-clinical studies and early clinical studies

18 Qualification Programs (Cont d) Vendor qualification Vendor should be qualified early during development Audit of vendors should include their GMP and testing program for AM Vendors should be familiar with principles of validation QA/QC data Qualification program need to comply with cgmps and should be monitored by QA/QC unit QA/QC data to include: Inspection and release of AM prior to use in manufacturing, vendor auditing, certificate of analysis, stability testing

19 Risk-based Classification of Ancillary Materials (AMs) USP chapter <1043> lists four(4) risk-based categories, with examples for each category The tables are provided only as a guide Other criteria for risk assessment are the amount and stage of use during manufacturing as part of a risk assessment strategy (not addressed in the tables of chapter <1043>)

20 Risk-based Classification of Ancillary Materials (AMs) Four categories of ancillary materials: Tier 1 Low-Risk, Highly Qualified Materials with Intended Use as Therapeutic Drug or Biologic, Medical Device, or Implantable Material Tier 2 Low-Risk, Well Characterized Materials with Intended Use as AMs, Produced in Compliance with GMPs Tier 3 Moderate-Risk Materials Not Intended for Use as AMs (frequently produced for in vitro diagnostic use or reagent grade materials) Tier 4 High-Risk Materials, Materials not Produced in Compliance with cgmps and materials not intended to be used in cell manufacturing

21 Ancillary Materials Current Chapters Requirements for specific ancillary material products will be included in chapters <130> Protein A Quality Attributes (official) <1024> Bovine Serum (PF) <90> Fetal Bovine Serum- Quality Attributes (Draft) <92> Cytokines & Growth Factors, in cell manufacturing (Draft) These Chapters can specify reference standards that to demonstrate compliance to compendial tests Reference standards may also be qualified for use as markers and calibration standards for residual testing

22 Conclusions The qualification programs described in <1043>, and the risk-based categories are provided as a guide Qualification programs need to be developed on case by case basis for a specific material to be used in a specific application Specifications and acceptance criteria should be established for each AM used in manufacturing, to ensure quality of the product Reference materials associated with chapters and monographs can be used to demonstrate compliance with the requirements The USP Cell, Gene, and Tissue Therapies Expert Committee is considering a revision of chapter <1043> Your feedback is appreciated (send comments to fa@usp.org)

23 Quality Standards for Medicines, Supplements, and Food Ingredients throughout the World