Chlorhexidine for Umbilical Cord Care

Transcription

1 Chlorhexidine for Umbilical Cord Care Ensuring Supply of a Quality Product The Regional Dissemination Meeting Nepalgunj September 15-16, 2011

2 Outline of Presentation Selection of dosage forms Stability testing of aqueous solution and gel chlorhexidine (CHX). Selection of partners who can ensure sustainable product supply items to consider. Listing of 4% CHX on the WHO EML

3 Selecting Dosage Forms Stability testing of aqueous solution and gel CHX.

4 Composition Components 20% CHX gluconate, BP 50% benzalkonium chloride, NF Formulation 1 (aqueous solution) 7.103% (w/w) (eq. 4% CHX) Formulation 2 (aqueous solution) 7.103% (w/w) (eq. 4% CHX) 0% 0.10% 0.10% Guar gum NF 0% 0% 1% Formulation 3 (gel) 7.103% (w/w) (eq. 4% CHX) Purified water, USP q.s. to 100 gm q.s. to 100 gm q.s. to 100 gm Benzalkonium chloride (BAK) was added as a preservative. Due to the amount of BAK added in the formulation, it is considered to be non-api* in this formulation * API=active pharmaceutical ingredient

5 Major Specifications Appearance Aqueous Solution Gel clear, colorless solution ph 5.5 to 7.0 Viscosity N/A 3,000 cp to 5,000 cp CHX Potency 3.6% to 4.4% (or 90% to 110% in CHX gluconate potency assay)

6 Protocol Primary container: 4 ml high-density polyethylene bottle and polypropylene screw closure (materials commonly used for commercial CHX-based products). Testing conditions: 5 o C, 25 o C /60% RH*, and 40 o C/75% RH to establish 24-months stability. Tested at: 0, 1, 3, and 6 months. Tested for: appearance, ph, potency, and amount of p-chloroaniline present (a substance that is produced when chlorhexidine is degredated.) *RH=relative humidity

7 Results All three formulations passed the stability test. Formulations 1 and 2 did not show any difference in potency, ph and purity. The two formulations that contained BAK showed discoloration. This discoloration did not affect the potency of the formulations.

8 Results The potency of the gel formulation tended to decrease (from 95.3% to 90.0%), although it remained within the acceptable range, which indicates that there is a need for: Achieving homogeneity. A quantitative assay to evaluate the formulation for quality assurance and quality control.

9 Considerations for Selecting Partners Keep in mind: 20% chlohexidine glucoante is widely available. Twelve (12) companies are listed in US FDA Drug Master File (DMF) as of Q2/2011. And more Easy to manufacture MFs/default.htm#download

10 Considerations for Selecting Partners Whom should you talk to in order to ensure product supply? Should this be always a manufacturer?

11 Supply Chain The entire supply chain: Production Regulatory approval Marketing Distribution How integrated is it? Who controls the most elements of the supply chain?

12 Supply Chain Production Regulatory approval Marketing Distribution Model 1 Manufacturers are contracted only for production. Different companies handle marketing and distribution. Model 2 Manufacturers handle production through marketing and contract distribution to third parties. Model 3 Manufacturers control the entire supply chain.

13 Supply Chain Implications for partner selection Production Regulatory approval Marketing Distribution Focus on partnering with companies that control the majority of the critical elements of the supply chain for the product. Partnering with more than one company or contracting with other companies through major partners might be necessary for the product to effectively reach the target population.

14 Supply Chain Implications for partner selection Produce Regulatory approval Market Distribute Partner directly with manufacturers or be heavily involved in the selection of the manufacturer when technology is complex. Production process requires special equipment/skills. Raw materials/components of products are unique. Visit and discuss with potential partners face to face before making a final decision.

15 Other Factors to Consider Alliance with the project goal Business continuity Production capability and capacity Partners Distribution capability Regulatory capability Marketing capability

16 EML Status An application was submitted to WHO Model List of Essential Medicines (EML) to include 4% CHX for topical umbilical cord care in the WHO EML (2008) 20% CHX digluconate solution being listed in the WHO EML with the instruction to dilute for umbilical cord care. A letter was submitted to WHO EML to include 4% CHX gel and aqueous solution (2010). Amendment is pending until a product of the strength and formulation used in the trials will be commercially available (i.e., availability of the product on the open market).

17 Thank you. PATH Team: Patricia Coffey, PhD, MPH Abra Greene Manjari Lal, PhD Carol Markham Mutsumi Metzler, MBA Shirley Villadiego, MD, MPH