REGULATORY LABELLING REQUIREMENTS AND ITS COMPARISON IN USA AND CANADA

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1 WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES Krupa et al. SJIF Impact Factor Volume 4, Issue 3, Research Article ISSN Article Received on 13 Dec 2014, REGULATORY LABELLING REQUIREMENTS AND ITS COMPARISON IN USA AND CANADA Krupa C. Thula* 1, Harita K. Odedra 2 and Dr. Dilip G. Maheshwari 3 1 Assistant Professor, Department of Quality Assurance, L. J. Institute of Pharmacy, Between Kataria Motor and Sanand-Sarkhej Circle, S. G. Highway, Ahmedabad, Gujarat , India. 2 Department of Quality Assurance, L. J. Institute of Pharmacy, Between Kataria Motor and Revised on 07 Jan 2015, Accepted on 02 Feb 2015 *Correspondence for Author Krupa C. Thula Assistant Professor, Department of Quality Sanand-Sarkhej Circle, S. G. Highway, Ahmedabad, Gujarat , India. 3 Head of Department of Quality Assurance, L. J. Institute of Pharmacy, Between Kataria Motor and Sanand-Sarkhej Circle, S. G. Highway, Ahmedabad, Gujarat , India. Assurance, L. J. Institute of Pharmacy, Between Kataria Motor and Sanand-Sarkhej Circle, S. G. Highway, Ahmedabad, Gujarat , India. ABSTRACT Labels are beneficial description of the products which is very useful for the consumers to distinguish the goods from others. Consequently, these are the unique identity of the product. Now a day, it becomes a habit of most of the population to see the product label before they go for purchase. An excellent design, description and posture also influence the buyers and consumers. This article describe about various regulatory requirements for different dosage forms with precautions in USA and Canada according to their code of regulations and comparison of labelling requirement in both countries. In the USA, The content & format requirements of labelling for human prescription drug & biological products comes under 21 CFR (d) & In the Canada, Labelling of Pharmaceutical Drugs for Human Use replaces the Health Canada guidance document labelling of Drugs for Human Use. In 1989, this guidance document came into effect, was revised in 1991, Health Canada had remove it from circulation because most of its content was deemed to be out-of-date. The inner label affixed to an immediate container of the drug. The outer label includes any label affixed to the drug packaging, including a pouch, card, accordion label, or other construct. KEYWORDS: Study, Labelling, Requirements, USA, Canada and Comparison. Vol 4, Issue 3,

2 INTRODUCTION Label 1. Labels are definite part of pharmaceutical products which manufacturers affix to their products to indicate their customers that the product meet certain standards. Labels are most probably printed papers which entitle information like weight, bar code, service time and many other things. The term labeling designates all labels and other written, printed or graphic matter upon or in package or wrapper in which it is enclosed. 2. Also label must indicate the name of manufacturer or distributer and carry an identifying lot number. Types of label [1] A variety of materials are used for labeling such as paper, fabric and foil. The choice mainly depends on the need and economics. The various types are as follows:- 1. Paper label Most labels are printed on paper, since this is the most economical and sensible method for any quantities i.e. either large or small. There is no label to the colors and techniques that can be used for paper label. 2. Foil labels It is nearly always necessary to laminate with paper so that label will work properly in the labeling machines. The foil and paper together should measure to inch for ideal results. 3. Transfer labels There are several processes for transferring inks from a pre-printed strip so that the container that is to be decorated. Out of these the electrical system is more economical but it is limited to lines and solids. Tools costs are nominal and the equipment are relatively inexpensive. The operating temperature of the die is around 350f with pressure around 100 to 200 psi, depending on the size of the label. Vol 4, Issue 3,

3 4. Sieve labels There are two types of labels Stretch band Shrink band Two-mil low density polythene films are used for stretch band labels. Heat shrinkable labels are made up of 3-mil polyvinyl chloride film. Functions of label [2] 1. Physical Protection 2. Barrier protection 3. Containment or agglomeration Information transmission 4. Marketing A. General labeling requirements according to usfda (united states food and drug administration) The content and format requirements of labelling for human prescription drug and biological products comes under 21 CFR (d) and This guidance provides recommendation on developing Highlights of prescribing Information (Highlights), procedural information and formatting of labelling. On January 24, 2006, FDA published a final rule that amended the requirements for the content and format of labelling for human prescription drug and biological products. Code of federal Regulations (d) [3] A. Prescription drug labeling described must meet the following general requirements: 1) It must contain a succinct summary of essential scientific information. 2) The labeling must be descriptive and accurate. 3) The labeling must be based whenever possible on data derived from human experience. B. Categories of prescription drugs subject to the labeling content and format requirements: 1) The hereunder categories of prescription drug products are subject to the labeling requirements: i. Prescription drug products for which a new drug application (NDA), biologics license application (BLA), or efficacy supplement was approved by the Food and Drug Administration (FDA). ii. Prescription drug products for which an NDA, BLA, or efficacy supplement is unresolved Vol 4, Issue 3,

4 on June 30, 2006; or iii. Prescription drug products for which an NDA, BLA, or efficacy supplement is given to submit anytime on or after June 30, C. Schedule for implementing the labeling content and format requirements. D. Recently approved prescription drug products. 1) Prescription drug labeling described in (d) contain the specific information in the following order: Highlights of Prescribing Information 1. Product Names, Other Required Information 2. Boxed Warning 3. Recent Major Changes 4. Contraindications 5. Indications and Usage 6. Dosage and Administration 7. Dosage Forms and Strengths 8. Warnings and Precautions 9. Drug Interactions 10. Use in Specific Populations 11. Adverse Reactions 12. Full Prescribing Information: Contents 13. Full Prescribing Information Boxed Warning 1. Warnings and Precautions 2. Indications and Usage 3. Dosage and Administration 4. ms and Strengths 5. Adverse Reactions 6. Contraindications 7. Drug Interactions 8. Use in Specific Populations a) Pregnancy b) Labor and delivery Vol 4, Issue 3,

5 c) Nursing mothers d) Pediatric use e) Geriatric use 9. Drug Abuse and Dependence a) Controlled substance b) Dependence c) Abuse 10. Over dosage 11. Clinical Pharmacology a) Mechanism of action b) Pharmacodynamics c) Pharmacokinetics 12. Nonclinical Toxicology a) Carcinogenesis, mutagenesis, impairment of fertility b) Animal toxicology 13. Description 14. Clinical Studies 15. References 16. How Supplied/Storage and Handling 17. Patient Counseling Information E. Labeling requirements for older prescription drug products. 1) Prescription drug labeling description must contain the particular information required under the following section headings and with the following order: a) Description b) Clinical Pharmacology c) Indications and Usage 2) Contraindications 3) Precautions 4) Warnings 5) Adverse Reactions Vol 4, Issue 3,

6 6) Drug Abuse and Dependence 7) Over dosage 8) Dosage and Administration 2) The labeling may contain the following section headings: a. Animal Pharmacology and/or Animal Toxicology b. Clinical Studies c. References 3) Remove clearly inapplicable sections, subsections, or specific information. 4) The labeling may contain a "Product Title" section preceding the "Description" section. Code of federal regulation [4] (a) Highlights of prescribing information The following information must appear in all prescription drug labeling (1) Highlights limitation statement. (2) Drug names (3) Initial U.S. approval. (4) Boxed warning. (5) Recent major changes. (6) Indications and usage. (7) Dosage and administration. (8) Dosage forms and strengths. (9) Contraindications. (10) Warnings and precautions. (11) Drug interactions. (12) Use in specific populations. (13) Revision date. (b) Full prescribing information contents: Contents must contain a list of heading and subheading required in the full prescribing information. Contents must also contain any additional subheading(s). Vol 4, Issue 3,

7 (b) Full prescribing information: The full prescribing information must contain the information in the order together with the headings, subheadings, and identifying numbers. Format Requirements All labelling information must be printed in accordance with the following specification: All headings and sub headings required must be highlighted by bold type that distinguishes the headings and subheadings from other labelling information. Reverse type is not permitted as a form of highlighting. 1. A horizontal line must separate the information. 2. The heading must be in the center of a horizontal line. 3. If there are multiple subheadings, each subheadings must be indicated by a bullet point. 4. The labelling information must be in bold print. 5. The letter height or type size for all labelling information, headings, and subheadings must be a minimum of 8 points. 6. The identifying numbers must be presented in bold print and must precede the heading or subheading by at least two square cm. 7. Section or sub section of labelling that are identified as containing recent major changes must be highlighted in the full prescribing information by the inclusion of a vertical line on the left edge of the new or modified text. 8. For the information each section heading must be in bold print. Each subheading within a section must be intended and not bolded. 9. The information must be limited in length to an amount that, if printed in 2 columns on a standard sized piece of typing paper (81/2 by 11 inches), single spaced, in 8 point type with 12 inch margins on all sides and between columns, would fit on one half of the page. B. Labelling requirements according to canada [5] Labelling of Pharmaceutical Drugs for Human Use has replaced the Health Canada guidance document labelling of Drugs for Human Use. This guidance document came into effect in 1989, was afterwards revised in 1991, and has since been removed from dissemination by Health Canada because much of its content was supposed to be out-of-date. The inner label is the label stick to an immediate container of the drug. The outer label includes any label affixed to the drug packaging, including a pouch, card, accordion label, or other construct. Manufacturer should note that shipping cartons must be labelled in such a manner as to Vol 4, Issue 3,

8 ensure compliance with the good manufacturing practices (GMP) requirements. Health Canada recommends that manufacturers label the shipping carton with sufficient information to enable product identification (e.g., brand name, common or proper name, strength, and manufacturer s name). General labelling requirements The main panel or principal display panel is the main product display surface visible to the user under normal or customary conditions of display or use. The main panel of an inner or outer label should carry the following information: 1. The brand name or if brand name does not exists, then the proper or common name is applied, 2. The proper or common name of the finished product is applied. 3. The standard for the drug, if any, 4. The scheduling symbol, if required; 5. The drug identification number 6. The name and address of the manufacturer, and of the distributor if the manufacturer is not Canadian; 7. The lot number; 8. The expiration date; 9. Directions for use of the drug. 10. Medicinal ingredients are also quantitatively enlisted. 11. The following information is to be disclosed on outer label of any panel: 12. The net amount of drug 13. In parenteral preparations, quantitative list of all preservatives and of all mercurial preservatives in any drug containing mercury. Label to be included 1. Brand Name 2. Common name 3. Proper name 4. Pharmaceutical Form 5. Standard of manufacture 6. Drug identification number 7. Lot number Vol 4, Issue 3,

9 8. Expiration date 9. Name and Address of Manufacturer 10. Adequate Directions for Use 11. Storage Conditions 12. Limit Dose Drug Products 13. Warnings and Precautions 14. Declaration of Medicinal Ingredient Comparison of Labelling Requirement In Usa And Canada Table 1: Comparison of labelling requirement in USA and Canada Parameter USA Canada Rule Section It mainly comes under section 21 CFR (d) & It became final rule in Mainly labelling requirements divided into 3 section: Highlights of prescribing information (highlights) A table of contents (contents) The full prescribing information (FPI) It mainly comes under guidance document labelling of pharmaceutical drugs for human use. It came into action into 1989 and amended in Previously it was amended in Mainly label is called display label or principal label & it is divided into 2 panel: Inner panel Outer panel Language English English or French Order of Label display Highlights of Prescribing Information Product names, other required information Boxed Warning Recent Major Changes Indication and Usage Dosage and Administration Dosage forms and Strengths Contraindications Warning and Precautions Adverse Reactions Drug Interactions Use in Specific Populations Full Prescribing Information contents Full Prescribing Information The brand name or if no brand name exists, then the proper name The proper or common name of the finished product The standard for the drug, if any; The notation sterile, The Drug Identification Number (DIN) The scheduling symbol, if required; The name and address of the manufacturer, and of the distributor if the manufacturer is not Canadian; The lot number The expiration date Adequate directions for use of the drug; and Medicinal ingredients are also Vol 4, Issue 3,

10 Product name and Strength Initial approval process Barcode no. Batch number & Expiration date Dosage & Administration Warning & precautions Adverse reaction Drug interaction Specific issues: Proprietary name and established name of drug is given. Statement of initial approval process should be displayed with year NDC (National drug Code) number It should be included. A summary of information with subheadings including dose range, dosage regimen, starting dose, critical differences among population subsets. A summary of the most clinically significant information is needed with any Appropriate subheadings. It should be included but not repeated if it is already in warning & precaution section. A concise summary of the information required with any appropriate subheadings. NA quantitatively enlisted. Common name assigned by manufacturer and approved by Health Canada. NA DIN (Drug identification number) The lot number may be any combination of letters, figures, or both by which a drug can be traced to the manufacturer and if applicable, to the distributor or importer. The expiration date must be on the inner and outer labels of all drug products. Examples: 2008 April 30, 08AL30, or 08AL. The pharmacological classification may substitute specific indications on the labels, in cases where indications are specified, the dosage directions applicable to each indication or a dosage range encompassing all the indications should appear where possible. Caution shown within quotation marks & should be printed exactly. If the caution or warning does not appear within quotation marks, the wording may be altered but the meaning must be retained. It should be included in all panels. NA The inner and outer labels show adequate directions for use of the drug. This is interpreted to include: Indications for use or pharmacological classification; Recommended single and daily dose; Vol 4, Issue 3,

11 Table 2: Labelling requirements for specific dosage form Dosage form USA Canada Solid oral Liquid dosage form Topical Injectable products Biological products The established name of the drug and the quantity of the active ingredient per dosage unit The expiration date The lot number The name and place of business of the manufacturer Special storage conditions. These products are non-sterile but may be monitored for changes in bio burden. If co solvents are present in dosage form then extractable information should be given. If it is sterile then microbial limit should be included. The total amount of active ingredient (medicine name) must be identified, including units (e.g., mg). The total volume of fluid contained in the syringe must be identified in milliliters (ml). The concentration (units/ml) must be identified. Labelling of product name, batch number and expiry date. The proper name of the product; The name, address, and license number of manufacturer; The lot number The expiration date; The preservative used and its concentration, The amount of product in the container The recommended storage temperature; The adjuvant, if present; Minimum potency of product The statement: Rx only for prescription biological. The brand name The proper or common name of the finished product. The standard for the drug. The scheduling symbol. The Drug Identification Number The name and address of the distributor. The lot number; The expiration date Medical ingredient Pharmaceutical forms Indication Dosage directions There should be antimicrobial preservative included. Common name Product concentration Declaration of medical ingredient A if liquid preparation SVP then it should be declared per milliliter. B. if liquid preparation LVP then it should be declared in percentage. c. Parenteral salt must be declared in mill equivalents per unit final volume. Scientific name Trade name Expiry date Serial number Route of administration Dosage recommendation for use Precautions The establishment number of the firm Vol 4, Issue 3,

12 CONCLUSION Labelling is one of the crucial documents for filling any drug product. Comparison of labelling requirements in different countries make easier for person to make & prepare simple, accurate & precise label from country requirements when they are filling their product in different countries. Labelling reduces medication error. Labelling should be readable and it should be easily accessible to the consumer. Omission and inaccuracy of drug labeling information on pharmaceutical excipients may expose susceptible individuals to adverse reactions caused by preservatives and dyes. Out-of-date or incomplete drug product labeling information may increase the risk of otherwise preventable adverse drug events. Proper label design attracts the consumers which may lead to the increase in demand of the product. Package labels are proficient to steer the product differentiation and to gain the trust and attractiveness of the consumers by product labels and can also attain communication with different consumer segment by regularly maintaining their quality. ACKNOWLEDGEMENT The authors are thankful to Dr. Pundarikakshudu, Director of L. J. Institute of Pharmacy, Ahmedabad, India for providing facilities and encouragements to carry out the research work. REFERENCES 1. Walter L. Pharmaceutical Codex: Principal and Practice of Pharmaceutics. 12 th ed., Pharmaceutical press, 1994; : Drug Labelling URL: 3. Code of federal regulation 21 Labelling Requirements for Prescription Drugs and/or Insulin 4. Code of federal regulation 21 Labelling Requirements for Prescription Drugs and/or Insulin 5. Guidance document labelling of pharmaceutical drugs for human use Vol 4, Issue 3,