Overview of: Packaging Development

1. Original: Jan fourmAn Condensed: Fran Eckenrode Overview of: Packaging Development

2. Packaging is the technology of enclosing or protecting products for distribution, storage, sale, and use. packaging also refers to the process of design, evaluation, and production of packages. Package labeling is any written, electronic, or graphic communication on the package or on a separate but associated label. PACKAGE LABELING

3. The purpose of Packaging/Labeling Parts of the Product: • The physical product – tablet, capsule, solution, etc. • The labeling – the summary of product information that: • Enables correct use of the product • Allows patients and Healthcare Providers to consider the benefit/risk of the drug: • About risks of use • How to minimize risks • The packaging – “…preserves the stability and quality of medicinal products and protects them against all forms of spoilage and tampering “ WHO Annex 9

4. Target Product Profile (TPP) (US) • In the US, a “Target Product Profile” (TPP): • Provides a format for summarizing the drug development program, described in terms of labeling concepts • Facilitates non-binding discussions of clinical plans between sponsors and the FDA • Is typically submitted in a Briefing Document (BD) to the FDA reviewing division or to the Office of Prescription Drug Promotion (OPDP) • Can be updated and submitted as early as pre-IND, or as late as post-approval for new indications or new formulations

5. Labeling All finished drug products should be identified by labelling, as required by the national legislation, bearing at least the following: (a) the name of the drug product (b) a list of the active ingredients showing the amount of each present, and a statement of the net contents, e.g. number of dosage units, mass or volume (c) the batch number assigned by the manufacturer (d)  the expiry date in an uncoded form (e)  any special storage conditions or handling precautions that may be necessary (f)  the directions for use, and any warnings and precautions that may be necessary (g)  the name and address of the manufacturer or the company or person responsible for placing the product on the market

6. Labeling Terminology MedDRA (Medical Dictionary for Regulatory Activities) • 1990s: the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) developed MedDRA, a rich and highly specific standardised medical terminology to facilitate sharing of regulatory information internationally for medical products used by humans. • MedDRA is available to all for use in the registration, documentation and safety monitoring of medical products both before and after a product has been authorised for sale. • Products covered by the scope of MedDRA include pharmaceuticals, biologics, vaccines and drug-device combination products. • used worldwide by regulatory authorities, pharmaceutical companies, clinical research organizations and health care professionals

7. Packaging Criteria (wHO Annex 9) • Packaging must meet the following requirements: • protect against all adverse external influences that can alter the properties of the product, e.g. moisture, light, oxygen and temperature variations • protect against biological contamination; • protect against physical damage • carry the correct information and identification of the product • The packaging and the materials used must be chosen such that: • the packaging itself does not have an adverse effect on the product (e.g. through chemical reactions, leaching of packaging materials or absorption); • the product does not have an adverse effect on the packaging, changing its properties or affecting its protective function.

8. Packaging The packaging process consists of the following stages: — filling and assembling;— sterilization in the final container, if applicable; — placing labels on the container;— storage at the manufacturing and shipping sites. Packaging documentation includes aspects related to: — specifications and quality control, including batch records; — labels, inks and adhesive materials (e.g. glue);— package inserts for patients.

9. Packaging & Labeling Quality • Packaging requirements must be met throughout the whole of the intended shelf-life of the product. • Given the link between the quality of a pharmaceutical product and the quality of its packaging, pharmaceutical packaging materials and systems must be subject to the same quality assurance requirements as pharmaceutical products. • The appropriate system of quality assurance for the manufacture of pharmaceutical products should therefore follow the WHO guidelines for good manufacturing practices (GMP). • Label changes are made as Post-Approval CMC Supplements • Major potential to cause adverse effects (Prior approval supplement) • Moderate potential to cause adverse effects (Changes Being Effected ((CBE))_supplement) • Minor (minimal) potential to cause adverse effects (Annual Report)

10. adulteration • A drug is adulterated if: • it is "filthy, putrid, or decomposed" • It is "prepared, packed or held under unsanitaryconditions. . . " • if “. . .the facilities or controls used for, its manufacture, processing, packing or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice . . . as to safety. . .identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess” • “if its strength differs from, or its quality or purity falls below the standards set forth in an official compendium” • If “any substance has been (1) mixed or packed therewith so as to reduce its quality or strength or (2) substituted wholly or in part. . .” 34

11. Tamper-Evident Closures Tampering includes altering, pilfering and falsifying the pharmaceutical product. • US passed the Poison-Prevention Packaging Act in 1970 • The ISO has published an internationally agreed standard test procedure for reclosable child-resistant packaging. In Europe several norms have been introduced which complement the ISO standard. • The European Committee for Standardization (CEN) has defined a child-resistant package as one “which makes it difficult for young children to gain access to the contents, but which is not too difficult for adults to use properly in accordance with the requirement of this European standard”. References • Poison Prevention Act of 1970 Regulations in US Code of Federal Regulations Title 16 Commercial Practices. Chapter 2. Consumer Product Safety Commission • “Child resistant Packaging- requirements and Testing Procedures for Reclosable Packages.” International Standard ISO 8317. Geneva, International Organization for Standardization, 1989.

12. 1970 –US Poison Prevention Act & Environmental Protection Agency • Required child resistant packaging • Specified tamper-resistant packaging • transparent film wrapper • blister or strip packs • bubble packs • heat shrink bands or wrappers • foil or plastic pouches • container mouth inner seals • tape seals • breakable caps • sealed metal tubes • aerosol containers