R&D of Biological Products. Rochapon Wacharotayankun, Ph.D., R.Ph.

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1 R&D of Biological Products Rochapon Wacharotayankun, Ph.D., R.Ph.

2 Topic Biological products research and development Process development Product development Novel antigens and Novel excipients Quality and Biological products R&D Rochapon W. 2

3 Preamble New vaccines and biotherapeutics are being developed to get better ones for human use Development of new vaccine/ biotherapeutics is costly and complex; Mio US$/ 8-18 years Development requires expertise, multiple technologies, manufacturing facilities, clinical trials, sophisticated scale up processes Product and process variability, complex, biosafety concern Rochapon W. 3

4 Stages of Drug Development and Relevant Quality Practices Stage 1a DISCOVERY PER SE Stage 1b TRANSITIONAL RESEARCH Stage 1C NON- REGULATED NON- CLINICAL RESEARCH Stage 1 BASIC BIO- MEDICAL RESEARCH Stage 2 NON- CLINICAL SAFETY GLP Stage 3 CLINICAL GCP Stage 4 MARKETING Pharmacovigilance GCP NON-REGULATED RESEARCH MANUFACTURING GMP Rochapon W. 4

5 Drug Discovery Rochapon W. 5

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8 Not only Antigen matters Antigen Vector Adjuvant Other excipients Delivery system Accelerating next-generation vaccine development.recent advances in vaccine discovery and immune monitoring will enable new human immunology based clinical research studies to address major gaps in knowledge of vaccine-induced human immune responses and thereby accelerate development of next-generation vaccines. Rochapon W. 8

9 Novel.New.. New antigen New use/ application New delivery system New dose New route of administration New process New excipient (adjuvant, immunomodulatory, stabilizer, etc.) Rochapon W. 9

10 Novel antigen New antigen being used for the first time in human vaccine Newly discovered antigen New genetically engineered antigen Similar antigen to previous one but originated from different organism Rochapon W. 10

11 Excipient the constituents of a pharmaceutical form that are not the active substance. According to their function, these constituents can be classified as technological, applicatory, stabilizing or biopharmaceutical excipients. In general, excipients are used for following purposes: Stabilizer Bioavailability, or patient acceptability Preservative Buffer Enhance any other attribute of the overall safety and effectiveness of the drug delivery system during storage and use (e.g. Adjuvant, Immunomodulator) Rochapon W. 11 Vaccine excipients

12 Novel excipient (1/3) A novel excipient is an excipient which is being used for the first time in a drug product, or by a new route of administration. It may be a new chemical entity or a well established one which has not yet been used for human administration and/or for a particular human administration pathway in the EU and/or outside the EU. Rochapon W. 12

13 Novel excipient (2/3) If no precedence of use in drug product, then the material is to be considered a new excipient and a toxicological assessment should be made to demonstrate the safety of the material in the intended pharmaceutical application at the specified use level. The USP-NF Excipient Biological Safety Evaluation Guidelines provides guidance on conducting a safety assessment of a novel excipient. In the U.S., the FDA has also issued guidance on nonclinical studies for new excipients. Rochapon W. 13

14 Novel excipient (3/3) full details of manufacture, characterization, and controls, with cross references to supporting safety data (nonclinical and/or clinical) should be provided according to the drug substance format. a dossier should be established containing the same data as required for new active substances: Rochapon W. 14

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20 DNA, RNA removal* Chrom atogra phy* UF/DF* Filtration DNA, RNA removal** Chrom atogra phy** UF/DF** Filtration Rochapon W. 20

21 Stages of Drug Development and Relevant Quality Practices Stage 1a DISCOVERY PER SE Stage 1b TRANSITIONAL RESEARCH Stage 1C NON- REGULATED NON- CLINICAL RESEARCH Stage 1 BASIC BIO- MEDICAL RESEARCH Stage 2 NON- CLINICAL SAFETY GLP Stage 3 CLINICAL GCP Stage 4 MARKETING Pharmacovigilan ce GCP NON-REGULATED RESEARCH MANUFACTURING GMP Rochapon W. 21

22 ICH Q10 PQS Product Life Cycle Stage Goals Pharmaceutical development Lab. Studies, Clinical studies, DS development, formulation, method development QPBR/GLP/ GMP Investigational products GCP, GCLP Technology transfer of product/ process/ knowledge between / within sites GDP GEP Commercial manufacturing Production, QC, Lot Release, Storage & Distribution GMP Product discontinuation Document retention, sample retention, Continued product assessment and reporting PQS elements for continual improvement of process performance and product quality Enablers Management Responsibilities Process performance & Product Quality Monitoring System Corrective / Preventive Action (CAPA) System Change Management System Management Review Knowledge Management Quality Risk Management Rochapon W. 22

23 Lifecycle Approach : from R&D through clinical trials to commercial scale process validation should not be viewed as a one-time event but rather as an activity that spans the product lifecycle linking process development, validation of commercial manufacturing process, and its maintenance during routine commercial production Life cycle approach Product and Process development Validation of commercial Mfg Maintenance during routine commercial production Rochapon W. R&D Clinical trial Phase I, II, III Submission Commercial 23

24 Conclusion Research and Development of new vaccine/ biotherapeutics is complex, costly, risky and time consuming Development requires expertise, multiple technologies, manufacturing facilities, clinical trials, sophisticated scale up processes and analytical methods Quality assurance required to ensure reliability of the data and repeatable process for right decision making Good documentation from R&D essential to later phase of product/ process development and dossier preparation Rochapon W. 24

25 References Accelerating Vaccine Development and Manufacturing Priyabrata Pattnaik, PhD Director Worldwide Vaccine Initiative- April, 2014 Nature review: Drug Discovery QPBR WHO ICH Q 10 Rochapon W. 25