Harvard University Egg Supply Science Case Study

do only parts b & c.

BENG0028 Vaccine Project Management – Case Study
This case study is designed to provide an overview of the annual manufacturing
challenges associated with manufacturing influenza vaccine. The manufacturing
challenges presented in this scenario are common to all flu manufacturers and has
been developed by MedImmune A/Z.
As such, some data is anonymised, and uses arbitrary units in order not to reveal the
actual manufacturing capacity of a given facility.
The numbers in this case study are designed to be representative, but are not actual
data for cost, manufacturing, or schedule parameters
Your task is to develop a base case scenario.
1) You will be required to project the following:
a) Manufacturing Schedule (bulk drug substance and filled drug product)
i)
Number of batches / strain of drug substance
ii) Number of batches / week of drug substance
iii) Start date / end date
iv) Key dates and milestone
b) Cost of manufacture (Cost of Goods / Dose)
c) What are the key areas of risk?
[60 % of mark]
2) There is an issue at the egg supplier and they can only deliver a maximum of 3
batches / week for the month of March.
a) What is the commercial impact of this event compared to the original plan?
b) Impact on manufacturing schedule
c) Impact on Cost of Goods / Dose
d) What could you do in future to avoid this from happening?
[40 % of mark]
Definitions:
Drug substance (DS) is the pure material that stimulates any pharmacological
action. It is the most important ingredient in any drug that is available in the market.
Bulk Drug Substance means any substance that is represented for use in a drug
and that, when used in the manufacturing, processing, or packaging of a drug,
becomes an active ingredient or a finished dosage form of the drug. The term does
not include intermediates used in the synthesis of such substances.
Drug product (DP) is the finished product of any drug that is available in the market
and is ready to use (this includes its packaging).
Batch – the quantity produced at one operation.
Background Data
Early Planning
n You are currently in Winter of 2022
w Forecast demand for August 2023 = 83.4M Doses (70% accurate)
w No strain information available at present; however expected to be the
same as in Southern Hemisphere due to Southern Hemisphere
surveillance
Manufacturing Assumptions
n Bulk Drug Substance (DS) Yield (million doses per batch)
w Previous year: H1N1 – 3.8, H3N2 – 3.5, B – 2.5
w Typical (historic): H1N1 – 4.0 ± 0.3, H3N2 – 3.4 ± 0.2, B – 2.6 ± 0.2
n Stability overage requirements
§ % of DS that needs to be included in addition to the dose requirement and
Fill/Finish/Packaging (FFP) yield losses
§ Antigen has a shelf life (i.e. 12 months) with a certain potency, potency at
t=0 not the same as t=12 months
§ Stability studies of historic strains allow statistical modelling
w
w
Previous year: H1N1 – 30%, H3N2 – 30%, B – 10%
Typical (historic): H1N1 – 30±20%, H3N2 – 30±10%, B – 15±5%
n Fill/Finish/Packaging (FFP)
§ Relates to formulated product, i.e. loss due to rejects at filling line,
inefficient uptake into syringe etc.
w
w
75% Net Yield (bulk to finished product)
750,000 Units / Batch
n Cycle Times
§ Fertilised chicken eggs incubated for 10-11 days for embryo development
(primary incubation)
§ Injection of virus stock into allantoic cavity
§ Incubation for a 2-4 days,
§ eggs chilled, then de-capped, allantoid fluid is harvested, primary
recovery and purification etc.
w
w
w
w
Bulk DS = 16 Days (primary incubation to bulk drug substance)
Bulk Run Rate = 1 batch of eggs set per day
Strain Changeover (bulk) = 5 Days
Packaged DP = 5 Days (blend to packaged final product)
n Release Times
§ QC carried out on each batch, i.e. titre from eggs, antigen purity etc.
§ Antigen bulk cleared for release
§ Then formulation, bulk-filled material tested
§ Final batch released, sterility test
w
w
All QC Testing Complete (Bulk DS) = 60 Days
Final Batch Release (Packaged DP) = 14 Days
Hints:
n The loss (overage) should be taken into account when calculating the total
number of batches you need to produce a total of 83.4 M doses.
n Start with clinical batch for clinical trials (remember 3 strains need blending),
then do production batches
n Think about QC
Cost Assumptions
n Fixed Operating Costs = £100M
n Variable Costs / Batch Bulk DS
w Labour = £20,000
w Utilities = £5,000
w Eggs = £50,000
w Raw Materials = £50,000
w Testing = £20,000
n Variable Costs / FFP Batch (1,000,000 units)
w Labour = £15,000
w Utilities = £3,000
w Raw Materials = £500,000
w Testing = £10,000
n Deliveries are spread across August (15%), September (25%), October
(35%) and November (25%)
w Each day late = lost sales (i.e. product is wasted)
Planning Constraints
n Lead Times
w Raw Materials = 4 Months (expedited delivery at 2 months = 50%
premium)
w Eggs = 6 Months (no expedited delivery options)
§
§
Note that cold fertilised eggs can be stored for a few weeks, eggs
cannot be frozen
Delivery approximately once a week
n Key Dates
w WHO / CDC Strain Selection (confirmation) = 15th February 2023
w
Annual Safety Trail (clinical trial) takes 2 months to complete and
requires 1 lot of finished drug product
w
Strain Change Regulatory submission takes 2 months to approve
> Clinical trial must be complete
> All process changes must be implemented
w
First customer order = 1st August