Pharmaceutical Technology 1/Industrial Pharmacy 1 PDF

Pharmaceutical Technology 1 / Industrial Pharmacy 1 Lec. 7 1- 2- 1. Cost  bringing a new drug to market, is complex and controversial.  Capital costs: costs included to take into account the long time...

Pharmaceutical Technology 1 / Industrial Pharmacy 1 Lec. 7 1- 2- 1. Cost  bringing a new drug to market, is complex and controversial.  Capital costs: costs included to take into account the long time period (often at least ten years) during which the out-of-pocket costs are expended.  The costs are controversial varies from around $500 million to $2 billion 2. Success rates  attrition rate : The high failure rates associated with pharmaceutical development  to decrease attrition rate :. 1- Well-designed clinical trials 2- dose-finding studies 3- comparisons against both a placebo and a standard treatment reliable data 3. Novel  Partnering between governmental organizations and industry. initiatives to boost drug " innovative medicines initiative: is a European initiative development to improve the competitive situation of European Union in the field of pharmaceutical research. pg. 1 Pharmaceutical Technology 1 / Industrial Pharmacy 1 Lec. 7 4. What is to be 1- Drug products & biological products called " medicinal products" registered? 2- Veterinary products 3- Medicinal device 4- Cosmetics Drug product Biological product  Most commonly an organic small  The biological products are molecule that activates or inhibits medicinal products made of The function of a bio-molecule such substances extracted from or as a protein, which in turn results in Produced by living source a therapeutic benefit to the patient  they are genetically either  Used in medicine to diagnose, cure Modified living organisms or Or prevent the occurrence of Liquids and tissues extracted Diseases and disorders. From various human or animal  Classified to innovator & generic. sources.  Classified to innovator & biosimilar. Why? as the production of identical bio molecule is very complicated. A generic product Biosimilar product  Generic drugs, short: generics) is  is a biological product having a a drug product with the same similar(not same ) active active ingredient as substance, dosage form, brand/reference listed drug strength and route of product administration of a reference  has the same dosage form, biological product strength, route of administration,  Has same quality, performance comparability program that its characteristics, and intended quality, performance use characteristics is equivalent to a reference biological product when.prescribed in a claimed indication The chemical structure of a biosimilar product varies to a certain extent from the reference product. pg. 2  Pharmaceutical Technology 1 / Industrial Pharmacy 1 Lec. 7 2- ICH ICH Countries Europe, USA and Japan Non-ICH countries any country other than Europe, USA and Japan Regulators Regulatory authorities Industry Pharmaceutical companies responsible for innovative drug development or even generics production Medicinal product covers both pharmaceutical and biological medicinal drug products = drug product. Active substance Drug substance EMA European medicines agency (European union). FDA Food and drug administration (USA). MHLW Ministry of health, labor and work (Japan). The basic for approving and authorizing new medicinal products: 1. Quality 2. Safety 3. Efficacy  The ICH 1990 is unique in bringing together the regulatory authorities and pharmaceutical industry of Europe, Japan and the US to discuss scientific and technical aspects of drug registration.  ICH's mission is to : 1- achieve greater harmonization in the interpretation and application of technical guidelines and requirements for product registration 2- ↓↓reducing duplication of testing and reporting carried out during the research and development of new medicines. 3- to ensure that safe, effective, and high quality pg. 3 Pharmaceutical Technology 1 / Industrial Pharmacy 1 Lec. 7 Quality guidelines  Harmonization in quality area include pivotal milestones such as:  The conduct of stability studies  Defining relevant thresholds for impurities testing.  From Q1-Q14  Q1A------- to Q1F  Q2 without sub division  Q3A--------to Q3A Letters for sub division Safety guidelines  To cover potential risks like:  Carcinogenicity  Genotoxicity  Repro-toxicity Efficacy guidelines  Concerned with: design, conduct, safety, reporting of clinical trials. M1 :  Terminology guidelines = terminology dictionary= medical Multidisciplinary guidelines MEdDRA dictionary  Rich & highly specific to facilitate sharing of regulatory information internationally  unifying medical dictionary  Used for: registration, documentation, safety monitoring of medical products both before & after a product has been authorized for sale M4: CTD  Internationally agreed format (Common For: preparation of applications to be submitted to regulatory technical authorities in the three ICH region (Europe, USA, Japan) document) Before CTD?  Each regulatory authority required: jurisdiction- specific format  Companies had to recognize each jurisdiction format & repeat trials for each drug submission  ↑cost & waste time After CTD?  ↑ more unified approach in presenting regulatory submission for drugs & biologicals.  ↑ time-saving  ↑ resources-saving  Facilitates simultaneous submission, approval, launching of new drugs.  CTD format applicable to all types of products (new chemical entitles, radiopharmaceuticals, vaccines, herbals, etc.)  CTD is an appropriate format, but Applicants should not modify the overall organization of Their technical document as outlined in the guideline  To determine the applicability of this format for a particular type of product consult with the responsible regulatory authority pg. 4 Pharmaceutical Technology 1 / Industrial Pharmacy 1 Lec. 7 Module 1 Not a part of CTD jurisdiction-specific Modules 2 to 5 Part of CTD intended to be common across jurisdiction Module 1  Include submission documents & administrative info  Specific for each jurisdiction & cannot be harmonize not a part of CTD 2.1 CTD table of contents (Module 2-5) 2.2 Introduction 2.3 Quality overall summary 2.4 Non-clinical overview Module 2 2.5 Clinical overview 2.6 Non-clinical written and tubulated summaries 2.7 Clinical summaries numbers for sub division  in CTD format Letters for sub division in ICH guideline  These summary documents should be cross-referenced to modules 3,4 and 5 to facilitate regulatory review. Overview: short document provides a critical assesment of data The summuray: longer document focuses on data summarization & integration Module 3 Quality : identity, characterstics, manufacturing methods, control, packaging & stability of the substance & drug product. Module 4 Non-clinical study reports : reports of pharmacological & toxicological properties of the drug substance & drug product. Module 5 Clinical study reports : clinical trials reports & raw data reports where applicable to demonstrate safety & efficacy of the drug in humans. pg. 5  Pharmaceutical Technology 1 / Industrial Pharmacy 1 Lec. 7 Information relevant to the active substance master file (ASMF)  The applicant for a marketing authorization (of a CTD) may not be the manufacturer of the active substance.  The ASMF, consists of applicant's ("open") part and the active substance manufacturer's restricted ("closed") part.  it is the responsibility of the applicant for a marketing authorization for a medicinal product to ensure that the complete ASMF is supplied to the authorities.  The applicant's ("open") part is supplied by the applicant to the authorities.  The active substance manufacturer's restricted ("closed") part with original signed Letter of Access is supplied to the authorities directly by the active substance manufacturer in the CTD format in the same time as the marketing authorization application. NB: The CTD gives no information about the content of a dossier and does not indicate which studies and data are required for a successful approval. From where does the manufacturer get this information??? From ICH, CTD is just a format pg. 6 Pharmaceutical Technology 1 / Industrial Pharmacy 1 Lec. 7 i. Governmental regulatory control Central Departments of EDA 1. Central Administration of the Office of the Chairman of the Authority 2. Central Administration for Pharmaceutical Policies and Market Support 3. Central Department of Biological and Innovative Preparations and Clinical Studies 4. Central Administration of Pharmaceuticals 5. Central Administration of Medical Supplies 6. Central Administration of Pharmaceutical Care 7. Central Operations Department 8. Central Administration for Drug Control 9. Central Administration of the General Secretariat Assessment before giving registration license to ensure quality, safety & efficacy of products with affordable prices. NFSA for registration of Dietary supplement pg. 7  Pharmaceutical Technology 1 / Industrial Pharmacy 1 Lec. 7 ii. Laws Article59 OF Law127/ 1955 stipulates that:  pharmaceutical products (medicines) may not be traded in unless they are registered with the Ministry of Health.  This applies both to locally prepared and imported medicines. Ministerial Decree 174/ 1974 makes it compulsory to:  re-register products every 10 years and if the concerned party fails to submit a reregistration request, the permit is cancelled and re-manufacture or importation is no longer permitted. Ministerial decree 450/ 2023 According to which the registration procedures are followed now in Egypt. Many tracks are present: 1- Fast track submission 2- Normal track submission 3- Imported drug register easier than local 4- Drug from ref countries is easier from non ref countries Qualification of person who work in registration department must be: Accuracy and concentration iii. Who will apply for a drug registration? Factory Where manufacturing takes place Toll Pharmaceutical A company having a contract with other manufacturing sites. Manufacturer Agent or distributor This is a company which distributes products of another manufacturing company. (Importation) Scientific office Is every office carrying out advertisements for medical products. pg. 8  Pharmaceutical Technology 1 / Industrial Pharmacy 1 Lec. 7 Brief of Drug Registration procedures 1. Box inquiry (Maximum limit for the same active ingredient is 12 in the market). 2. Box of approval with in 3 working days  if ok , company need to deliver a) Naming b) Pricing c) Pharmaco-vigilance report  (RMP)= risk management plan 3. Importation approval for raw material API 4. Pilot batch manufacturing (10% of production batch) to ensure efficacy, safety, and quality not form marketing a) Assay b) Stability testing c) Bioequivalence center ( test invivo and invitro) 5. GMP file 6. Patient information leaflet pg. 9