Biologics ppt
- 1. REGULATORY REQUIREMENTS FOR THE PRODUCT APPROVAL OF BIOLOGICS Presented By, Tanuja yadav M.pharmacy Drug Regulatory Affairs
- 2. CONTENTS INTRODUCTION SOURCES AND TYPES OF BIOLOGICS DIFFERENCES BETWEEN BIOLOGICS AND CHEMICAL DRUGS REGULATORY AUTHORITY FOR BIOLOGICS DEVELOPMENT AND APPROVAL PROCESS BIOLOGICAL LICENSE APPLICATION (BLA) COMPARISON BETWEEN US AND EUROPIAN GUIDELINES REGARDING BIOLOGICS CONCLUSION REFERENCES A.U COLLEGE OF PHARMACEUTICAL SCIENCES 2
- 3. INTRODUCTION • WHAT ARE BIOLOGICS? Biologics are the products manufactured, extracted from or semi synthesized from a biological source which are regulated by FDA and are used to prevent cure and treat diseases and medical conditions. These are generally large, complex molecules produced through biotechnology in a living system such as a microorganism, plant cell or animal cell. These could be made of sugars, proteins, nucleic acids or complex combinations of these substances or may be living entities. These are complex mixtures that are not easily identifiable and charcterized these tend to be heat sensitive and susceptible to microbial contamination hence, it is necessary to use aspetic principles from intial manufacturing process. EXAMPLES: Botox, Herceptin, Vaccines, Enbrel A.U COLLEGE OF PHARMACEUTICAL SCIENCES 3
- 4. SOURCES AND TYPES OF BIOLOGICS SOURCES Mammalian cell culture Bacteria Insect cell culture Plant cell culture Yeast Transgenics Avian cell culture Humans TYPES Blood derivatives Vaccines Allergenic extracts Whole blood Blood components Proteins Human tissues Cellular and gene therapies Xenotransplantation products A.U COLLEGE OF PHARMACEUTICAL SCIENCES 4
- 5. DIFFERENCES BETWEEN BIOLOGICS AND CHEMICAL DRUGS A.U COLLEGE OF PHARMACEUTICAL SCIENCES 5 PROPERTIES BIOLOGICS CHEMICAL DRUGS SIZE Large Small STRUCTURE Complex Simple STABILITY Unstable Stable MODIFICATION Many options Well defined MANUFACTURING Impossible to ensure identical copy Identical copy can be made CHARCTERIZATION Impossible to charcterize Easy to charcterize
- 6. REGULATORYAUTHORITY FOR BIOLOGICS Center for biologics evalution and research (CBER) is the center within FDA that regulates biological products for human use under applicable Federal laws including the Public Health Services Act (PHS) and the Federal, Food, Drug and Cosmetics Act CBER protects and advances the public health by ensuring that biological products are safe and effective. FDA's regulatory authority for the approval of biologics resides in (PHS) Act. Biologics are subjected to regulation under Federal, Food, Drug And Cosmetics act (FD&C) Act. Some medical devices which are used to produce biologics are regulated by CBER under FD&C Act's medical device amendments of 1976. FDA also reviews new biological products and new indications and usage for already approved products on the market for the treatment of known diseases. It protects against threats of emerging infectious diseases. It provides the public with information to promote safe and appropriate use. A.U COLLEGE OF PHARMACEUTICAL SCIENCES 6
- 7. DEVELOPMENT AND APPROVAL PROCESS Advertising and Labeling Investigational New Drug Application (IND) or Device exemption process (IDE) Expanded Access Premarket Approval (PMA) Biologics License Application (BLA) New Drug Application Process (NDA) Biologics Approvals By Year A.U COLLEGE OF PHARMACEUTICAL SCIENCES 7
- 8. BIOLOGICS LICENSE APPLICATION (BLA) The Biologics License Application (BLA) is a request for permission introduce or deliver for introduction a Biologic product into the market It is mainly regulated by 21 CFR 600-800. It is submitted by any legal person or entity who engaged in manufacture or an applicant for a license who takes responsibilty for compliance with product and establishment of standards. A Biologic License application generally applies to vaccines and other Allergenic drug products and cellular and genetic therapies. Form 356h specifies the requirements for a BLA . It mainly includes the following: 1. Applicant information 2. Product / manufacturing information 3. Pre clinical studies 4. Labelling A.U COLLEGE OF PHARMACEUTICAL SCIENCES 8
- 9. BIOLOGIC LICENSE APPLICATION (BLA) A.U COLLEGE OF PHARMACEUTICAL SCIENCES Applicants must submit the form356h to the CBER and Await for the review of FDA. FDA receives the BLA and reviews it if the manufacturers produce inappropriate information then it issues a letter called Refuse To File (RTF) . If FDA approves the BLA they will issue a approval letter which authorizes the manufacturer to distribute the product. 9
- 10. A.U COLLEGE OF PHARMACEUTICAL SCIENCES 10 UNITED STATES EUROPE REGULATORY BODY Food And Administration (FDA) FDA adopted the S6 Guidance European Medicines Evaluation Agency (EMEA) CHMP has adopted ICH S6 guideline APPROVAL STANDARD Biological Lisence Application (BLA) Marketing Authorization Application (MAA) PRECLINICAL STUDIES SPECIES SELECTION IMMUNOGENICITY Chimpanzee Elicit immune response Rodent and Non Rodent species Sponser should measure ADA'S STUDY DESIGN Pharmacodynamic studies Pharmacokinetic and Pharmacodynamic studies
- 11. A.U COLLEGE OF PHARMACEUTICAL SCIENCES 11 CARCINOGENICITY REPRODUCTIVE AND DEVELOPMENTAL TOXICITY Inappropriate May or May not be recommended Inappropriate Fertility studies,Embryo -Fetal development,Pre and Postnatal development studies (PPND) CLINICAL STUDIES Involves 3 phases(Phase I,II,III) It must have IND in effect Begins only when FDA approves it Must comply with GCP as described in E6 Guideline which the CHMP has adopted PHASE I Frequently involve administration to patients rather than healthy volunteers Done for maximum tolerated dose , Product's metabolism, Pharmacology,and safety at high doses Initial Safety, and Tolerability,PK and PD activity
- 12. A.U COLLEGE OF PHARMACEUTICAL SCIENCES 12 PHASE II Evalution of Safety and Short term Adverse Events Safety and Efficacy PHASE III Begin If preliminary Evidence of effectiveness is shown during Phase II Therapautic confirmatory studies and Explore the Dose Response Relationships
- 13. Conclusion The study introduces the legal and regulatory aspects pertaining to biologics in the united states and european union. The Drug approvals in the US, Europe are the most demanding in the world . The main objective of the rules governing medicinal products in US , Europe is to safe guard the public health It is the role of regulatory authorities to ensure that pharmaceutical companies shall comply with regulations mentioned above . A.U COLLEGE OF PHARMACEUTICAL SCIENCES 13