FDA container closure system & drug stability saurav anand 23 iip
FDA GUIDELINES OF CONTAINER CLOSURE SYSTEM FOR PACKAGING & DRUG STABILITYSaurav Anand(+091-9974564659,89800775590)Alembic Research CenterPGDPT,IIP
FDA GUIDELINES OFCONTAINER CLOSURE SYSTEM FOR PACKAGING
CONTAINER CLOSURE SYSTEM FOR PACKAGING HUMAN DRUGS & BIOLOGICS CONTENTS: DEFINITION CGMP, CPSC AND USP REQUIREMENTS. QUALIFICATION AND QUALITY CONTROL OF PACKAGING COMPONENTS. POSTAPPROVAL PACKAGING CHANGES. TYPE III DRUG MASTER FILES. BULK CONTAINERS. REGULATORY REQUIREMENTS. COMPLIANCE POLICY GUIDES THAT CONCERN PACKAGING. EXTRACTION STUDIES DRUG STBILITY
DEFINITION MATERIALS OF CONSTRUCTION- Substances (e.g., glass, Plastic resin, metal) used to manufacture a packaging component. A PACKAGING COMPONENT- Any single part of a container closure system.(e.g., ampules, vials, bottles), container liners (e.g., tube liners), closures (e.g., screw caps, stoppers),stopper overseals, inner seals, container labels etc. A PRIMARY PACKAGING COMPONENT-Packaging component that is or may be in direct contact with the dosage form. A SECONDARY PACKAGING COMPONENT-Packaging component that is not and will not be in direct contact with the dosage form. A CONTAINER CLOSURE SYSTEM- Sum of packaging components that together contain and protect the dosage form. This includes primary packaging components and secondary packaging components, if the latter are intended to provide additional protection to the drug product. A packaging system is equivalent to a container closure system.
CGMP, CPSC and USP REQUIREMENTS Current good manufacturing practice (CGMP)CGMP– 21CFR 210 & 211. Consumer Product Safety Commission (CPSC) The United States Pharmacopeial Convention has established requirements for containers which are described in many of the drug product monographs in The United States Pharmacopeia/National Formulary (USP/NF).i) General Notices and Requirementsii) General test and assay section of the USP.
CGMP[CODE OF FEDERAL REGULATIONS (CFR)] 21 CFR 211.80 - 211.94 - Control of Components and Drug Product Containers and Closuresa) Shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug beyond the official or established requirements.b) Adequate protection against foreseeable external factors in storage and usec) sterilized and processed to remove pyrogenic properties to ensure for use also documented. 21 CFR 211.122 - 211.137 - Packaging and Labeling Control 16 CFR 1700-1702 - Special Packaging. Regulations issued under the PPPA establish performance standards and test methods that determine if a packaging system is child-resistant and adult-use-effective (16 CFR 1700.15 and 16 CFR 1700.20, respectively). The Poison Prevention Packaging Act of 1970 (PPPA). 21 CFR 174-186 - Indirect Food Additive Regulations
U.S.P./NATIONAL FORMULARYFOR PACKAGING COMPONENT General Notices - Preservation, Packaging, Storage, & Labeling. General Tests and Assays.<1> Injections<51> Antimicrobial Preservatives - Effectiveness<61> Microbial Limit Tests<71> Sterility Tests<87> Biological Reactivity Tests, in vitro<88> Biological Reactivity Tests, in vivo<161> Transfusion and Infusion Assemblies<381> Elastomeric Closures for InjectionsBiological Test ProceduresPhysicochemical Test Procedures<601> Aerosols<661> Containers<671> Containers - Permeation Multiple-Unit Containers for Capsules and TabletsSingle-Unit Containers and Unit-Dose Containers for Capsules and Tablets<691> Cotton (or the monograph for Purified Rayon USP)<771> Ophthalmic Ointments<1041> Biologics<1151> Pharmaceutical Dosage Forms
QUALIFICATION AND QUALITY CONTROL OF PACKAGING COMPONENTS CDER and CBER approve a container closure system to be used in the packaging of a human drug or biologic as part of the application (NDA, ANDA or BLA) for the drug or biologic. The type and extent of information that should be provided in an application will depend on the dosage form and the route of administration.
TYPES OF DOSAGE FORMS Inhalation Drug Products (section III.D) Drug Products for Injection and Ophthalmic Drug Products (Section III.E) Liquid-based Oral and Topical Drug Products and Topical Delivery Systems (section III.F) Solid Oral Dosage Forms and Powders for Reconstitution (section III.G) Other Dosage Forms (section III.H)
INFORMATION TO BE SUBMITTED TO FDA DESCRIPTION SUITABILITY FOR THE INTENDED USEa) Protectionb) Compatibilityc) Safetyd) Performancei) Container Closure System Functionalityii) Drug Delivery QUALITY CONTROL(section III.C.3)a) Physical Characteristicsb) Chemical Composition Associated Components (sections III.B.1 and III.B.2) Secondary Packaging Components (sections III.B.1 and III.B.2) STABILIYT
INFORMATION TO BE SUBMITTED TO FDA Inhalation Drug Products (section III.D)i) Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Drug Productsii) Nasal Spray and Inhalation Solution, Suspension, and Spray Drug Products; Chemistry, Manufacturing and Controls Documentation. Drug Products for Injection and Ophthalmic Drug Products (section III.E) Liquid-Based Oral and Topical Drug Products and Topical Delivery Systems (section III.F) Solid Oral Dosage Forms and Powders for Reconstitution (section III.G) Other Dosage Forms (section III.H)
THE FEDERAL FOOD,DRUG,& COSMETIC ACT Section 501 -A drug or device shall be deemed to be adulterated. Section 502 - A drug or device shall be deemed to be misbranded.EXTRACTION STUDIES Study of a packaging component typically involves exposing a sample of the component, often subdivided into small pieces to increase surface area, to an appropriate solvent or preferred solvent would be the drug product or placebo vehicle system at elevated temperatures, followed by chemical analysis.Purposes: To perform USP characterization tests on plastics (USP <661>) or elastomers (USP <381>) To perform USP Biological Reactivity Tests (USP <87> and <88>) on plastics or elastomers To obtain qualitative & quantitative extraction profiles of plastics or elastomers To evaluate whether the FDA indirect food additive regulations provide an adequate indicator of safety.
POSTAPPROVAL PACKAGING CHANGESThe safety or effectiveness of the product depends on the identity,strength, quality, purity, or potency of a product as they may varywhen making a change to or in the container closure system.THE CONTAINER CLOSURE SYSTEMi) Interaction between the packaging component and the dosage form.ii) Performance. 21 CFR 314.70 for an NDA or ANDA 21 CFR 601.12 for BLAPACKAGING CHANGES Major Changes (Prior Approval Supplement) Moderate Changes (Supplement - Changes Being Effected) Minor Changes (Annual Report)LABELING CHANGES Major Changes (Prior Approval Supplement) Moderate Changes (Supplement - Changes Being Effected) Minor Changes (Annual Report)
TYPE III DRUG MASTER FILES The letter of authorization(LOA) is a letter from the manufacturer(Vendor) to the applicant Descriptive Information Information About Suitability Information About Quality Control BULK CONTAINERS Containers for Bulk Drug Substances Containers for Bulk Drug Products
DRUG STABILITY Container/closure system in which Formulation is remain within its physical, chemical, microbiological therapeutic and toxicological specification. The USP definition:“extent to which a product retains within specified limits” and throughout its period of storage and use (i.e. its shelf life) the same properties and characteristics that it possessed at the time of its manufacturer’’. Assurance of drug stability come from an accumulation of valid data on the drug in its commercial package. These data involves selected parameters that taken together from the stability profile. Pharmaceutical products are expected to meet their specification for identifying purity, quality and strength throughout their defined storage period at specific storage condition.
DRUG STABILITYThere are five types of stability that must beconsider for each drug.
ROLE OF STABILITY TESTING Provides evidence on how the drug substance or product quality varies with time under environmental conditions during distribution. Helps to recommend storage conditions including establishment of shelf life, expiry date or retest period Key assurance of quality of pharmaceuticals.
INTERNATIONAL CONFERENCE ON HARMONIZATION (ICH)ICH stands for International Conference on Harmonization ofTechnical Requirements for Registration of Pharmaceuticals for Human useOBJECTIVES OF ICH: Harmonization of registration applications within the three regions of the EU, Japan and the United States. ICH is a joint initiative involving both regulators and industry as equal partners in the scientific and technical discussions of the testing procedures which are required to ensure and assess the safety, quality and efficacy of medicines. Tripartite guideline on stability testing of new drug substances and products (Q1A) in 1993, has become standard for stability evaluation in Japan, US, Europe.
TYPE, SIZE, NUMBER OF BATCHESICH/ WHO GUIDELINES: At least 3 primary batches of drug product, should be of the same formulation, packaged in same container as proposed for marketing 2 out of 3 batches should be pilot scale batches. Stability to be performed on each strength, container size.
CLIMATIC ZONES & STABILITY CONDITIONSTUDY CLIMATIC ZONE CLIMATIC ZONE I & II III & IV (US & EUROPE) (DOMESTIC &BRAZIL) TEMP & % RH COND. TEMP & % RH COND.LONG 25 + 2 C & 30 + 2 C & 60 + 5 % RH 65 + 5 % RHINTERMEDIATE 30 + 2 C & --- 65 + 5 % RHACCELERATED 40 + 2 C & 40 +2 C & 75 + 5 % RH 75 + 5 % RH
CLIMATIC ZONES/STORAGE COND. (ICH)DRUG PRODUCTS – GENERAL CASESTUDY STORAGE CONDITION MIN. TIME PERIOD COVERD BY DATA AT SUBMISSIONLONG TERM 25°C ± 2°C / 60% ± 5% r.h. or 12 months 30°C ± 2°C / 65% ± 5% r.h.INTERMEDIATE 30°C ± 2°C / 65% ± 5% r.h. 6 monthsACCELERATED 40°C ± 2°C / 75% ± 5% r.h. 6 monthsDRUG PRODUCTS–PACKAGED IN SEMI-PERMEABLE CONTAINERSSTUDY STORAGE CONDITION MIN. TIME PERIOD COVERD BY DATA AT SUBMISSIONLONG TERM 25°C ± 2°C / 40% ± 5% r.h. or 12 months 30°C ± 2°C / 35% ± 5% r.h.INTERMEDIATE 30°C ± 2°C / 65% ± 5% r.h. 6 monthsACCELERATED 30°C ± 2°C / 65% ± 5% r.h. 6 months
CLIMATIC ZONES/STORAGE CONDITIONSDRUG SUBSTANCES –INTENDED FOR STORAGE IN A REFRIGERATOR STUDY STORAGE CONDITION MIN. TIME PERIOD COVERD BY DATA AT SUBMISSIONLONG TERM 5°C ± 3°C 12 monthsACCELERATED 25°C ± 2°C / 60% ± 5% 6 months r.h.DRUG SUBSTANCES/PRODUCTS –INTENDED FOR STORAGE IN FREEZER STUDY STORAGE CONDITION MIN. TIME PERIOD COVERD BY DATA AT SUBMISSIONLONG TERM -20°C ± 5°C 12 months
SHELF LIFEMaximum and Minimum time at which potency mustbe at least 90% of label claim at the temperatureindicated in order to predict a shelf life of twoyears at Room Temperature.Temperature Maximum time for study Minimum time for study37°C 12 Months 6.4 Months45°C 8.3 Months 2.9 Months60°C 4.1 Months 3 Weeks85°C 06 Weeks 2.5 Days