What can be done to increase the affordability of a quality assured combi-packs? Analysis of the cost components and dynamics behind the pricing ...
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
What can be done to increase the affordability of a quality assured combi-packs? Analysis of the cost components and dynamics behind the pricing of combi-packs. 26/01/2021 1
MEDICAL ABORTION
• There are multiple challenges to be overcome in order to improve access to medical abortion (MA) –
from creating an enabling enviroment to effect legal and policy change, increasing market demand,
procurement & distribution through to regulatory barriers.
• These products need to accessible and affordable in LMIC settings.
• In addition, there are ongoing manufacturing challenges that impact the availability of combi-packs –
linked to the challenges above:
• There are multiple manufacturers of combi-packs and stand-alone mifepristone, misoprostol
products, but a limited number which are quality-assured (QA).
• The manufacturing processes are challenging.
• Registration requirements/pathway to registration modalities are complex and can be costly
• There is limited access to affordable mifepristone & misoprostol active pharmaceutical ingrediants
(API), which, for LMIC, need to be both AFFORDABLE + DOCUMENTED QUALITY ASSURED.
• Concept Foundation engaged directly with selected industry in order to understand these barriers from
a manufacturers perspective and identify possible solutions.
• The outcome was the recently published “Cost of goods sold analysis and recommendations to reduce
costs of co-packaged mifepristone–misoprostol for medical abortion “.
26/01/2021 This document contains proprietary information belonging to Concept Foundation . Unauthorized use, duplication, dissemination to third parties is strictly prohibited
2API MIFEPRISTONE MANUFACTURERS
26/01/2021 This document contains proprietary information belonging to Concept Foundation . Unauthorized use, duplication, dissemination to third parties is strictly prohibited
3QUALITY ASSURED (QA) MIFEPRISTONE MANUFACTURERS
How could we identify QA assured API manufacturers?
• Manufacturers with WHO-PQ, CEP or SRA approval
• Manufacturers included as part of the finished drug product application that are already WHO-PQ or
SRA approved.
Some examples: PCAS (France), Expansia (France), VLG CHEM (France), Crystal Pharma (Spain),
Qinhuangdao Zizhu Pharmaceutical Co Ltd (China)
• Other manufacturers of mifepristone API should provide evidence for GMP compliance and API
quality documentation as per the WHO guidelines.
26/01/2021 This document contains proprietary information belonging to Concept Foundation . Unauthorized use, duplication, dissemination to third parties is strictly prohibited
4MISOPROSTOL API MANUFACTURERS
26/01/2021 This document contains proprietary information belonging to Concept Foundation . Unauthorized use, duplication, dissemination to third parties is strictly prohibited
5QUALITY ASSURED MISOPROSTOL MANUFACTURERS
How could we identify QA assured API manufacturers?
• Manufacturers with WHO-PQ, CEP or SRA approval
• Manufacturers included as part of the finished drug product application that are already WHO-PQ or SRA
approved.
Some examples: Piramal Healthcare (UK), Chinoin Pharmaceutical and Chemical Works Private Co., Ltd
(Hungary)
• Other manufacturers of misoprostol API should provide evidence for GMP compliance and API quality
documentation as per the WHO guidelines.
26/01/2021 This document contains proprietary information belonging to Concept Foundation . Unauthorized use, duplication, dissemination to third parties is strictly prohibited
6LIMITED SOURCE OF QA MIFE/MISO API SUPPLIER
• Geographical location: suppliers are mainly located in Europe or US leading to highly costly APIs.
• Marketing strategy: QA suppliers located in other areas are mainly focused on supplying SRAs markets
VERY LIMITED NBR OF SRA/WHO PQ COMBI-PACK
26/01/2021 This document contains proprietary information belonging to Concept Foundation . Unauthorized use, duplication, dissemination to third parties is strictly prohibited
7BUILDING A COGS MODEL
The COGs report is the outcome of a collaboration between various services: Safe abortion dept., Technical dept. and
Market Access Team dept.
Defining the components of Identify the technical and
Understanding the current the COGs with data that can commercial assumptions that
Building a COGs Model
public health context be collected ACROSS should be considered
countries/manufacturers (ponderation requ.)
Collecting the data:
- Manufacturers
Providing policy Analyzing the COGs
recommendation - Suppliers
- Publicly available
documentation
Each manufacturer has its own COGs model reflecting its company’s specific costs settings
26/01/2021 This document contains proprietary information belonging to Concept Foundation . Unauthorized use, duplication, dissemination to third parties is strictly prohibited
8Cost of Goods Model sold: The COGS ≠ Final cost
The sum of the direct costs attributable to Commercial cost factors may vary
the production of the goods sold by a drastically from one manufacturer to
company. It includes the cost : another and involve different
considerations such as:
Admin cost were • manufacturer’s pricing strategy,
included to better
understand the • Cash flow and return on Investment
drug benchmark timeline,
Admin price
Material
cost • etc…
cost
Direct
Operating
Labour
Expenses
cost
26/01/2021 This document contains proprietary information belonging to Concept Foundation . Unauthorized use, duplication, dissemination to third parties is strictly prohibited
9ASSUMPTIONS BEHIND THE MODEL
TECHNICAL ASSUMPTIONS: COMMERCIAL ASSUMPTIONS:
1. Formulation. The combi-pack is the 1. Production location and structural costs.
combination of two drugs: misoprostol (4 Manufactures are located in LMICs countries
tablets) and mifepristone (1 tablet) in the with an existing pharmaceutical industry:
strength 0.2 mg and 200 mg respectively, ▪ India , Bangladesh
packaged and ideally blistered in Alu/Alu 2. Existing combi-pack manufacturer.
2. Corrections to apply formulation. Assay, manufacturers are already producing the
anhydrous basis + the manufacturer’s combi-pack with the following implications:
experience in producing the product. discount on raw material applied (15%)
3. The batch size is set at 100,000 units for 3. Material. The raw material, API are outsourced
each product; which in terms of combi- 4. Depreciation. The depreciation on equipment
pack is equivalent to: is set at 15%/year
• 100,000 units of mifepristone; 5. Optimal market situation (i.e. all manufactured
• 400,000 units of misoprostol. units are consumed)
4. Etc.. 6. etc…
26/01/2021 This document contains proprietary information belonging to Concept Foundation . Unauthorized use, duplication, dissemination to third parties is strictly prohibited
10FINDINGS
The COGS modelling exercise showed that the combi- pack direct production cost ranges from US$1.08 to US$3.05
(Total COGS), which means that with a 30% administrative fee applied to those prices, a combi-pack could be made
available at a cost of between US$1.40 and US$3.97 depending on location, type of material.
Scenario where the combi-pack is the cheapest : Bangladesh with Non QA API Scenario where the combi-pack is the most expansive: India with QA API source
source ✓ Cost of the Combi-pack $3,97
✓ Cost of Combi-pack $1.40 o $1,0477 (4xmiso)+$1,695 (mife) +$0,346 (pack.) + $0,92 (Admin
o $0,48 (4 miso) + $0,2513 (mife) + $0,346 (pack) + $0,32 (Admin 30%)
30%)
MISOPROSTOL COGS - NON QA MIFEPRISONE COGS – NON-QA API MISOPROSTOL COGS - QA API MIFEPRISTONE COGS - QA API
API (BANGLADESH) –TOTAL (BANGLADESH) – TOTAL USD (INDIA) - TOTAL $ 0,2619/UNIT (INDIA ) - TOTAL -$1,6595/UNIT
USD 0,1208/UNIT 0,2513/UNIT
$0.3000 $1.7000
$0.1400 $0.3000 $1.6500
$0.2500
COST IN USD
$1.6000
COST IN USD
$0.1200
COST IN (USD)
$0.2500 $0.2000 $1.5500
Cost in USD
$0.1000
$0.0800 $0.2000 $0.1500 $1.5000
$0.0600 $0.1500 $0.1000 $1.4500
$0.0400 $1.4000
$0.1000 $0.0500 $1.3500
$0.0200
$- $0.0500 $- $1.3000
1 $- 1 1
Operating 1 Operating Operating
$0.0882 $0.1890 $0.1890
Expenses Operating Expenses Expenses
$0.0882
Expenses labour cost $0.0060 labour cost $0.0060
labour cost $0.0033
labour cost $0.0033 Excipients $0.0138 Excipients $0.0138
Excipients $0.0138
Excipients $0.0064 QA API (Assay QA API (Assay
API (Assay $1.4508
$0.0156 API (Assay 97%) $0.0532 97%)
95%) $0.1534 95%)
26/01/2021 This document contains proprietary information belonging to Concept Foundation . Unauthorized use, duplication, dissemination to third parties is strictly prohibited
11Analysis of Misoprostol (QA): Analysis of Mifeprostone (QA):
✓ Operating expenses is the primary cost component of ✓ API is the primary cost component of mifepristone and
misoprostol. It accounts for 72% of the production cost (excl. accounts for 87% of the production cost (excl. packaging)
packaging)
MISOPROSTOL COGS - QA API MIFEPRISTONE COGS - QA API (INDIA ) - TOTAL -
(INDIA) - TOTAL $ 0,2619/UNIT $1,6595/UNIT
$0.3000 $1.7000
$1.6500
$0.2500
$1.6000
COST IN USD
$0.2000
COST IN USD
$1.5500
$0.1500 $1.5000
$1.4500
$0.1000
$1.4000
$0.0500 $1.3500
$1.3000
$- 1
1
Operating Expenses $0.1890
Operating Expenses $0.1890
labour cost $0.0060
labour cost $0.0060
Excipients $0.0138
Excipients $0.0138
QA API (Assay 97%) $1.4508
QA API (Assay 95%) $0.0532
26/01/2021 This document contains proprietary information belonging to Concept Foundation . Unauthorized use, duplication, dissemination to third parties is strictly prohibited
12COMPARAISON OF THE COGS: INDIA, BANGLADESH (QA MATERIAL VS NON QA MATERIAL) IN USD
PRODUCTION OF MISOPROSTOL/UNIT PRODUCTION OF MIFEPRISTONE
1.66
1.55
Analysis
✓ Mifepristone is the most expansive
component of the combi-pack
✓ QA material is more expansive than
non-QA. The gap in pricing is very
important for mifepristone
production.
✓ The manufacturing cost are higher in
0.36 India than in Bangladesh. However,
0.26
0.22
0.25 this is driven by the OPERATING
0.16
0.12 EXPENSES COST and not by the
labour cost.
Prod. miso in India Prod. miso in Bangladesh Prod. mife in India Prod. mife in Bangladesh
❑ Dark column. QA Material
❑ Light column. Non QA Material
26/01/2021 This document contains proprietary information belonging to Concept Foundation . Unauthorized use, duplication, dissemination to third parties is strictly prohibited
13WHY A QUALITY ASSURED API IS MORE EXPENSIVE?
• Manufacturers usually need to invest on facilities and equipment to ensure the compliance with SRAs
requirements:
• containment (environmental and workers protection) and cross contamination risks mitigation.
• Keeping a quality management system is costly.
• The product documentation (APIMF) is more detailed and complex to prepare and keep it updated.
• Any post submission variation requires regulatory screening.
• Additional controls during manufacturing and API release are needed.
• Stability data needs to be provided to support the expire date or retest date.
• Cost of production in higher in HICs.
26/01/2021 This document contains proprietary information belonging to Concept Foundation . Unauthorized use, duplication, dissemination to third parties is strictly prohibited
14WHY A QUALITY ASSURED API IS MORE EXPENSIVE?
Some examples:
• To reach lower impurities level:
• Additional purification steps are usually required – increases the cost and decreases the yield.
• Less toxic and high purity solvents are required. Recycling solvents cannot be incorporated in final
steps.
• Synthetic route evaluation to control/mitigate risks related to mutagenic substances and
nitrosamines.
• Additional costing on validation
• All manufacturing steps need to be validated (since starting material introduction).
• Analytical methods, including the ones used to test intermediates, needs to be validated
26/01/2021 This document contains proprietary information belonging to Concept Foundation . Unauthorized use, duplication, dissemination to third parties is strictly prohibited
15MIFEPRISTONE API ADDITIONAL CHALLENGES
• Mifepristone is an established active substance however not described in the US, European, or
International Pharmacopoeia.
• An in-house specification should be established according to ICH's Q6A guideline, with additional controls
on polymorphism and particle size distribution (PSD).
• Polymorphism: Mifepristone may exist in two types of polymorphic forms. The polymorphic Form I is
used by the innovator product.
• PSD: the PSD can have an effect on the in vitro and/or in vivo behaviour of the drug product and its
control is important to ensure consistency with the material in the batch used in the bioequivalence
study.
Why polymorphism is so important?
• Different polymorphic forms of the same chemical compound may possess different chemical and physical
properties, which can impact the product manufacturability and product quality and performance,
including stability, dissolution and bioavailability.
• The specification of mifepristone API should include a test and acceptance criteria for a preferred
polymorphic form to ensure polymorphic equivalence to that used in the innovator product.
26/01/2021 This document contains proprietary information belonging to Concept Foundation . Unauthorized use, duplication, dissemination to third parties is strictly prohibited
16MISOPROSTOL API ADDITIONAL CHALLENGES
• Misoprostol API is viscous oil, which must be stored below -20C. It is extremely susceptible to
degradation.
• A dispersion of misoprostol in hydroxypropyl methyl cellulose (HPMC) is more stable than the pure
misoprostol oil and is commonly used as the API for misoprostol tablets manufacturing.
• The specification of misoprostol API should be in line with a pharmacopoeial monograph (Ph.Int.,
Ph.Eur./BP or USP).
• Misoprostol dispersion (1:100 in HPMC) should be in line with a pharmacopoeial monograph (Ph.Int. or
USP).
Note: the dispersion water content control is important to avoid the Misoprostol degradation to A-type
misoprostol.
26/01/2021 This document contains proprietary information belonging to Concept Foundation . Unauthorized use, duplication, dissemination to third parties is strictly prohibited
17IS IT POSSIBLE TO SEE QA COMBI-PACK AT A MORE AFFORDABLE PRICE IN THE FUTURE?
The cost of the Combi-pack could be lowered as a result of:
Additional QA API source of mifepristone and misoprostol in order to reduce the price
Delocalisation of manufacturing site in countries where operational costs are more competitive.
Cheaper commodity doesn’t automatically mean healthier market
The production of the good must remain sustainable and thus profitable to the manufacturers, otherwise
they may leave the market.
The Covid pandemic has highlighted the danger of overreliance on a single source/geography location.
26/01/2021 This document contains proprietary information belonging to Concept Foundation . Unauthorized use, duplication, dissemination to third parties is strictly prohibited
18IMPACT ON THE COGS OF AN AFFORBALE QA API FOR MIFEPRISTONE
The modelling undertaken and shown COMBI-PACK COGS: IMPACT REDUCTION COST OF QA MIFE
$4.50
above is based upon a price of US$8,278/kg $3,97
$4.00
with a discount of 15% making the material $3.50
$3,42
$3,29
available at US$7,036/kg. If mifepristone $3.00 $2,74
$2.50
API was made available to manufacturers at
$2.00
US$5,000/kg, a price which we believe is $1.50
both feasible and viable for the producers, $1.00
$0.50
the reduction by itself, would be sufficient
$-
to reduce the cost of the combi-pack to Customer Price - India Prosp. Customer Price
QA API - India with Red. QA
Customer Price - Prosp. Customer Price
Bangladesh QA API - Bangladesh with Red.
Mife QA Mife
$3.42 in India and $2,74 in Bangladesh.
26/01/2021 This document contains proprietary information belonging to Concept Foundation . Unauthorized use, duplication, dissemination to third parties is strictly prohibited
19CONCEPT FOUNDATION - SUPPORTING SAFE MEDICAL ABORTION 2021
• Is currently supporting selected manufacturers with the objective of having one
misoprostol API and one mifepristone API prequalified by WHO.
• Is currently supporting two manufacturers towards the prequalification of their combi-
packs.
• Is supporting the government of Argentina on the introduction of MA drugs following
the recent change of law.
• Is collaborating with IPPF on the quality assessment of MA drugs in 10 markets.
• Is supporting combi- pack registration in two countries.
• Is developing a business case for manufactures to support their investments in MA
drugs.
26/01/2021 This document contains proprietary information belonging to Concept Foundation . Unauthorized use, duplication, dissemination to third parties is strictly prohibited
20THANK YOU
26/01/2021 This document contains proprietary information belonging to Concept Foundation . Unauthorized use, duplication, dissemination to third parties is strictly prohibited
21You can also read
