ASSESSING LOCAL MANUFACTURING CAPACITY FOR CHILD SPECIFIC DOSAGE FORMULATIONS: THE CASE OF GHANA Annan, Edith 1 ; Gyansa- Lutterodt, Martha 2 ; Boateng, Kwesi Poku 3 ; Adu Asare, Brian 2 ; Koduah, Augustina 2 ; 1 World Health Organization/Ghana; 2 Ministry of Health; 3 Indepedent Consultant

2 Abstract Abstract ID: 404 Title: ASSESSING LOCAL MANUFACTURING CAPACITY FOR CHILD SPECIFIC DOSAGE FORMULATIONS: THE CASE OF GHANA Authors: Andrews-Annan E. 1,Gyansa-Lutterodt M. 2, Boateng K. P. 3 Asare A.B. 2, Koduah A. 2, 1 World Health Organization/Ghana; 2 Ministry of Health; 3 Indepedent Consultant Institution: WHO, Ministry of Health Problem Statement: Reducing child mortality are global priorities expressed in the Millennium Development Goals. Interventions to achieve these goals include the availability of essential medicines for children. In Ghana, infant and under five mortality rates are estimated at 50 and 80 respectively. Most of these deaths are caused by childhood diseases such as malaria, pneumonia, and diarrhea which could be averted by the use of safe paediatric formulations of medicines. An assessment was therefore undertaken under the Better Medicines for Children’s Project to determine the technical capacity of some local pharmaceutical manufacturers to produce a selected list of paediatric dosage formulations. Objectives: To conduct a situation analysis of the domestic production of medicines made specifically for children. Design: Descriptive cross-sectional study. Setting: The study was conducted at the national level and was based on local manufacturers’ institutions which were all privately owned. Study Population: The study identified a convenient sample of twenty two (22) out of thirty four (34) local manufacturers across the country from a database of the Pharmaceutical Manufacturers Association of Ghana. Intervention(s): Data was collected through visits to the selected pharmaceutical manufacturers for key informant interviews. A standardised questionnaire was used to collect background information on the manufacturer, manufacturing and starting materials and the potential for the manufacturer to produce additional paediatric dosage forms as per a list of target medicines to be used for children. Outcome Measure(s): A mapping of domestic manufacturers in Ghana producing a target list of twenty six (26) paediatric medicines. Results: The local manufacturer in Ghana was found to have the capacity to produce medicines containing 20 out of the 26 Active Pharmaceutical Ingredients (APIs) on the list of dosage forms targeted. It was found that only 27% of the target medicines are produced locally in the required dosage form and strength. Conclusions: Local manufacturing facilities in Ghana have the capacity to produce medicines in most of the therapeutic categories of the target paediatric medicines. If the potential to produce a majority of the target medicines locally is to be realized, then constraints with regards to equipment, regulatory and international cGMP, low investment in Research and Development, limited capacity to produce some paediatric dosage forms and procurement of raw materials from reliable sources need to be addressed. Key Words: Local Manufacture, medicines, children. Funding Source(s): Bill and Melinda Gates Foundation

3 Introduction In Ghana infant and under five mortality rates are estimated at 50 and 80 respectively per 1000 births. Most of these deaths are caused by diseases that could be prevented by access to safe essential child- specific medicines. Child-specific medicines are those manufactured to suit the age, physical condition and body weight of the child taking them. Healthcare workers and parents often use fractions of adult dosage forms or formulate their own prescriptions of medicines by crushing tablets or dissolving portions of capsules in water as alternatives to unavailable paediatric formulations. These are unsafe practices because they may alter the pharmacokinetics of most formulations and thus affect the health outcomes in medicines use. Manufacturing capacity is also a factor in the design of formulations appropriate for children

Background The Better Medicines for Children (BMC) Project funded by the Bill and Melinda Gates Foundation aims to improve access to essential medicines for children through addressing issues of availability, safety efficacy suitability and price. With support from the Bill and Melinda Gates Foundation through the World Health Organization, Ghana embraced the BMC agenda due to its relevance to the national context on access to medicines. As part of the BMC project, a situational analysis to assess the technical capacity of pharmaceutical manufacturers in Ghana to produce generic medicines in paediatric formulations of selected list of 26 paediatirc medicines for national use was undertaken. 4

5 Objectives To conduct a situation analysis of the domestic production of generic essential medicines in paediatric dosage forms. SCOPE To Assess the technical capacity of local pharmaceutical manufacturers to produce paediatric formulations of 26 selected paediatric medicines. It did not include a complete situation analysis and in- depth appraisal of the technical feasibility of such production or a market analysis of the economic viability of the production of paediatric formulations.

6 Methods 1 Local pharmaceutical manufacturers were identified from the database of the Pharmaceutical Manufacturers Association of Ghana. Twenty two (22) out of the thirty four (34) companies were selected for the study. Twelve (12) were not included in the survey for the following reasons: – Two (2) of these produce mainly large volume parenteral preparations. – Three (3) produce one or few products and had limited or no capacity to produce the targeted essential paediatric medicines. – Seven (7) were currently not in production or undergoing restructuring.

7 Methods 2 A draft data collection form was tested and finalised. Data collection occurred through visits to each of the 22 pharmaceutical manufacturers. The purpose of the study was discussed with the contact persons interviewed and they were also taken through the data collection form. Follow up visits were made to some of the companies, s and telephone calls to collect the completed forms. At the end of the data collection period, (14) completed forms had been received, one (1) manufacturer indicated that their company did not have the capacity at the time to produce paediatric dosage forms, two (2) declined to participate and the remaining even though they had indicated their preparedness to participate had not been able to complete and return the forms. The respondent rate was thus 68%.

8 Results 1 Graph of Companies Producing or Planning to Produce Products in the Target Therapeutic Categories OAD -Obstructive airway disease Fe preps – Iron preparations

9 Results 2 Companies with capacity to produce products containing Active Pharmaceutical Ingredients (API) of the 26 Target products AS+AQ – Artesunate and Amodiaquine (co-blistered ) Art +Lum – Artemether +Lumefantrine (co formulated) DHQ- Dihydroartemisinin + piperaquine (co formulated ) Cotri- cotrimoxazole

10 Results 3 Companies with capacity to produce products containing APIs of the 26 target products

Results 4 27% of the targeted child-specific essential medicines are produced locally in the required dosage form and strength. There is local capacity to produce a further 38%. There is thus the potential to produce 65% of the targeted child-specific essential medicines locally. There is however no capacity with regards to the respondents to produce the inhalers, injections and rectal solution locally. 29% of respondents did not provide any information with regards to their sources of raw materials. 50% have available Drug Master Files (DMF), 21% had made a request to their suppliers but had not yet received the DMFs. For those that provided information with regards to sourcing of raw material, about 50% of their raw materials were from brokers and not original manufacturers; the other 50% was from manufacturers. 60% of these raw materials were from India, 18% from Europe (mainly UK and Germany), 14% from China and 7% from USA. 11

12 Results 5 Requirements to Enable Production of Additional/Alternate Paediatric Dosage Forms – Facility modification and installation of Air Handling Units and dehumidifiers – Acquisition of extra equipment – Acquisition of Laboratory Equipment – Reformulation of some of the products into dispersible tablets or oral liquids and the redesigning of packaging material. – Technology transfer and Technical Assistance

Summary There is the domestic capacity to produce a high percentage of child-specific medicines. The current level of production of these medicines in the required strength and dosage forms is however relatively low; about 27%. Constraints with regards, to some facility and equipment inadequacies, regulatory and international cGMP compliance, low investment in R&D, limited capacity to produce some child friendly dosage forms and procurement of raw materials from reliable sources pose a challenge that need to be addressed to enhance domestic production of child-specific medicines. 13

14 Implications Recognition of the strategic importance of the local pharmaceutical manufacturers in helping Ghana to achieve her national healthcare agenda including access to child specific medicines. The need for a public private partnership approach in supporting local manufacturers to: – Obtain technical assistance for capacity building in the development of child-friendly formulations and dosage forms and capacity towards cGMP compliance. – Engage the necessary expertise to redesign some of their facilities for improved cGMP compliance.

15 Implications Attain compliance to international cGMP and possibly WHO prequalification for specific dosage forms for children Explore the opportunity for pooled procurement by local manufacturers in order to benefit from economies of scale and possibly enhance the capacity to source good quality raw materials (APIs) from credible suppliers Guarantee a certain level of market access to local manufacturers for a specified period on condition that there will be a reciprocal improvement in product quality, cGMP compliance and cost reduction