MODULE 7: TARGET PRODUCT PROFILES

1 MODULE 7: TARGET PRODUCT . PROFILES . DNDi/Scholars & Gentlemen 126. 1. INTRODUCTION. TARGET PRODUCT PROFILES are key strategic The global community, including WHO, UNAIDS, documents used to communicate summary the Global Fund to Fight AIDS, Tuberculosis requirements for new products that fulfil a and Malaria (Global Fund), the United States priority need. The purpose of TARGET PRODUCT President's Emergency Plan for AIDS Relief PROFILES is to guide industry during the drug (PEPFAR) and the United Nations Children's Fund development process and serve as a planning (UNICEF), have a responsibility to define the tool that can facilitate discussions with requirements around paediatric medicines and regulatory agencies and be updated as new have clear, transparent communication to industry information becomes available. on the products that are required to meet the unique needs of children.

2 The importance of TARGET PRODUCT PROFILES resides in their role in identifying the critical attributes of Some organizations, such as WHO, UNICEF and a PRODUCT before development begins, to ensure the Drugs for Neglected Diseases initiative, have that the final PRODUCT is adapted and responds developed TARGET PRODUCT PROFILES for specific to the needs of the end-users (Fig. ). TARGET desired products such as medicines, diagnostics PRODUCT PROFILES can help address issues early in and vaccines that have served to guide industry the PRODUCT development process and prevent in their own PRODUCT development The late-stage development failures. TARGET PRODUCT profile describes how the end- user will use the PRODUCT and is based on such Fig. A TARGET PRODUCT profile as a strategic attributes as indications, targeted population, planning tool clinical efficacy, safety and tolerability, stability, route of administration, dosing frequency and cost, along with development timelines.

3 Research and Table outlines various properties of TARGET development PRODUCT PROFILES and the optimum or ideal characteristics and minimum characteristics. Key properties include the ability to use the PRODUCT across the age spectrum of children and adolescents, ease of administration, heat stability, TARGET Regulatory PRODUCT Market palatability and swallowability and acceptable advice research production costs. profile Manufacturers and suppliers 2. ; ; pdf;jsessionid=6D9A30 EDDBCC978978CF9928 FAB921AE?sequence=1. 127. Table Properties of TARGET PRODUCT PROFILES Property Optimum or ideal TARGET PRODUCT profile Minimum TARGET PRODUCT profile TARGET One dosage form for ages 0 6 years Ages 0 2, 2 6 and >6 years population >6 years: adult Safety, Excipients selected from already used excipients in the Excipients selected in tolerability new drug application or abbreviated new drug application accordance with regulatory and in accordance with the Inactive Ingredients Guide of guidelines on inactive the United States Food and Drug Administration ingredients Limited use of excipients, minimum toxicity and drug interactions Drug attributes Accommodates a wide range of doses and drug A set of 3 5 technologies that properties (such as solubility) accommodate 80% or a majority Durability high barrier to resistance of drug types and doses and fixed-dose combinations Weight based Possible to administer the same dosage form across Possible to administer the same dosing multiple weight bands dosage form across multiple 1 formulation for children age <6 years.

4 Weight bands 1 formulation for age >6 years: adult (or half a dose). Administration Easy to administer minimum manipulation by the Solid oral dosage forms considerations caregiver preferred Minimal opportunity for child to reject medication If bottle pack, then it should Easy to apply with no irritation (non-oral) have a child-resistant cap Fixed-dose combination, dispersible or small tablet size Administration PRODUCT does not need device or appropriate device Minimum instructions necessary device supplied if needed to use device if needed consideration Intuitive no use instructions necessary Taste and texture Palatable, child-friendly flavour, good mouth feel Palatable, acceptable taste and (oral dosage) mouth feel Manufacturing Accessible development and manufacturing capability in Low technology easy to low- and middle-income countries manufacture in resource-limited Robust and able to deliver medicines of adequate quality settings at an affordable price Feasibility for technology transfer Cost Acceptable cost to caregivers and funders Low-cost (total cost of goods and landed costs)

5 Options Preparation Should not require complex preparation by the end-user Easy to prepare and administer, before before administration such as with water, milk or food administration Include recommendations for extemporaneous Suitable for low-literacy settings compounding in the summary of PRODUCT characteristics Heat stable, Suitable for all climatic zones, including International Suitable for the supply chain and longer shelf life Council for Harmonisation Zone IVb (30 C and 75% end-user relative humidity) and 24 month total shelf life No special transport and See Annex 2, Stability conditions for WHO Member storage handling requirements States by region (5). or No special transport and storage handling requirements Easy to transport and store 128. Property Optimum or ideal TARGET PRODUCT profile Minimum TARGET PRODUCT profile Packaging Compact, light weight, easy to open and administer, Same inexpensive, easy and low cost to transport, sustainable packaging Disability For example, Braille labelling or talking patient information Due consideration for end-user disabilities Regulatory Clear regulatory approval pathways considered up front Regulatory pathways in end- approval both in source and end-user countries user countries considered up front Patents Full geographical access, open licences, no data exclusivity Equitable geographical access Feasible to have PRODUCT monographs in official pharmacopoeia as soon as possible to produce generics Sources.

6 Special Programme for Research and Training in Tropical Diseases (1), WHO Expert Committee on Specifications for Pharmaceutical Preparations: fifty-first report (2), TARGET PRODUCT profile paediatric HIV (3), Lopez et al. (4) and Annex 2, Stability testing of active pharmaceutical ingredients and finished pharmaceutical products (5). Additional considerations in the drug formulation Table outlines the advantages and development process include TARGET candidate disadvantages of various formulations. Oral PROFILES and critical quality attributes. These include liquid preparations and oral solid preparations various drug characteristics that impact what are the most common formulations used for type of formulations can be manufactured and antiretroviral (ARV) drugs. In general, oral solid include: solubility and permeability of the active preparations are preferred to liquids since they pharmaceutical ingredients (Biopharmaceutical require less space and are easier to procure and Classification System classification); bioavailability store.

7 Nevertheless, young children may not be + food effects of the active pharmaceutical able to swallow solid dosage forms. Depending ingredients; polymorphism; particle size; stability on the active pharmaceutical ingredients, of the active pharmaceutical ingredients; taste granules, pellets or chewable tablets may be and potential to mask taste during manufacture; difficult to taste mask, and children may refuse content of active pharmaceutical ingredients these products because of poor taste (7 13). per dosage form; dose variability versus age; Liquid formulations allow better accuracy in dose accuracy requirements; manufacturability; dosing but may be less palatable. Refrigeration good technology fit to manufacture the active may be required for some liquid formulations, pharmaceutical ingredients into a finished which will increase the difficulty of storage, pharmaceutical PRODUCT ; possibility to combine both during transport and for the end-user.

8 For several active pharmaceutical ingredients into specialized products, more expensive production fixed-dose combinations (pharmacokinetics, costs or equipment may be required. pharmacodynamics and drug drug interactions);. active pharmaceutical ingredients amenable to age-appropriate simple dosage forms; and environmental pollution with active pharmaceutical ingredients during production (6). 129. Table Advantages and disadvantages of various formulations Active pharmaceutical TARGET age Formulation Procurement ingredients Oral solution Younger age group In principle, easy to Soluble, chemically stable Difficult Oral liquid preparations (unable to swallow) manufacture Oral Younger age group Other particles can Non-soluble, chemically stable. Difficult suspension (unable to swallow) be suspended, like Better than solutions for active coated pellets pharmaceutical ingredients that do not taste good syrups Younger age group In principle, easy to Soluble, chemically stable Difficult (unable to swallow) manufacture Emulsions Younger age group In principle, easy to Non-soluble, chemically stable Difficult (unable to swallow) manufacture Effervescent All ages Difficult technology Soluble, non-chemically stable Difficult tablets available Oral powder, Better suited for Can contain beads Palatable and unpalatable active Easy Oral solid preparations granules and young age or mini-tablets pharmaceutical ingredients multiparticulate Technology readily systems available Tablets Older children (able In principle, easy to Soluble, non-chemically stable Easy to swallow)

9 Manufacture Chewable Older children Easy to manufacture. Soluble, non-chemically stable, Easy tablets Technology readily palatable active pharmaceutical available ingredients Oro- All ages In principle, easy to Soluble, non-chemically stable, Easy dispersible manufacture palatable active pharmaceutical tablets ingredients Splitting Older children (able In principle, easy to Soluble, non-chemically stable, Difficult tablets to swallow) manufacture palatable active pharmaceutical (big size). ingredients Solids for Younger age group In principle, easy to Soluble and non- soluble, non- Easy reconstitution (unable to swallow) manufacture chemically stable Oral All ages Requires specific Palatable active pharmaceutical Easy lyophilizates equipment ingredients Oral films Limitation with Limited quantity of Palatable active pharmaceutical Easy high doses ingredients ingredients Source: adapted from: Penazzato et al.

10 (14). 2015 Penazzato M et al.; licensee International AIDS Society. 130. Special Storage Palatability Acceptability Administration precautions Difficult Only for acceptable taste Volumes >5 ml Solvents Quality of water or easy-to-mask active problematic for children Measuring device Measurement pharmaceutical ingredients <5 years problems Only low doses Difficult Suspensions allow better Volumes >5 ml Clear information on taste-masking than problematic for children shaking before use solutions <5 years Measuring device Only low doses Difficult Only for acceptable taste Volumes >5 ml Problems measuring Alcohol, sugar or easy-to-mask active problematic for children Only low doses content pharmaceutical ingredients <5 years Difficult Only for acceptable taste Volumes >5 ml Clear information on or easy-to-mask active problematic for children shaking before use pharmaceutical ingredients <5 years Measuring device Only low doses Difficult Only for acceptable taste Effervescent or easy to mask active technology pharmaceutical ingredients required Easy Taste can be an issue if Can be administered Information on food.