Debashis Basu, 25th September’14, 3rd Pharma Supply Chain Forum, Mumbai

“ Holistic management of risk in temperature controlled shipments – an operations and quality partnership”

Presentation Overview

Identify and implement proper risk management to ensure both shelf life and quality of products.

Developing the right storage conditions and packaging infrastructure in your cold chain.

Validating logistics providers to confirm efficient transportation of goods.

AN OVERVIEW

Identify and implement proper risk management to ensure both shelf life and quality of products.

Defining cold chain

What are Cold Chain Medicines?

Cold chain medicines are those that require special temperature-controlled cold storage to maintain their quality and efficacy.

Two commonly recommended temperatures specified on the labels of cold chain products:

Products requiring temperatures of between 2°C and 8°C Products requiring temperatures of around (-15°C) and (-25°C)

What is Cold Chain Management?

A cold chain is an uninterrupted series of storage and distribution activities that maintains products at a required temperature range of 2°C and 8°C or between --15 -25°C as per their requirements

Why is cold chain management important ?

Cold chain products are sensitive biological substances. Become less effective or lose their potency if

i. They are frozen or stored below 2°Cii. Exposed to temperatures above 8°Ciii. Exposed to direct sunlight or fluorescent lightThe loss of potency is cumulative and

irreversible.

Products exposed to conditions outside the established temperature range

Quality may be negatively affected.

Reduces their assigned shelf life, diminishing their

effectiveness or making them ineffective.

Loss of potency

Direct impact on patients.

Cold Chain regulatory landscape

It’s complicated and there are more than 30 good distribution practice (GDP) documents from various organizations in multiple countries, and they are not all the same. Currently, an incomplete list of regulatory and guidance stakeholders includes: The EU Guide to Good Manufacturing Practice, Annex 13 The Guidelines on Good Distribution Practice (GDP) of Medicinal Products CDC Guidelines for Maintaining and Managing the Vaccine Cold Chain WHO Guidelines on the international packaging and shipping of vaccines PDA Technical Report 49 The US Code of Federal Regulations US and European Pharmacopoeia

The International Committee for Harmonization (ICH) is attempting to harmonize key documents, but this process might take some time.

Build your own cold chain

Understand your current supply chain--Map it out with other stakeholders and know where your facility and/or process is in the context of a product’s entire supply chain.

Consider the Geographic scope- If your geographic scope is currently limited and you have made your decisions accordingly, you may have to re-think everything if your geographic reach expands.

Determine whether you need simple solutions (use of discrete data loggers) or more complex solutions (GPS-enabled measurements with real time reporting 24/7).

Prepare to validate whatever it is you decide to implement . Current regulatory scrutiny expects a qualified cold chain.

Be willing to reach out to solution providers. They may have more expertise in cold chain than you and your organization. Seek guidance from the outset to save the trouble of having to fix a broken system later on.

Stakeholders in bringing the cold chain medicines from manufacturers to patients

Transporters Airports/seaports CFAs/Distributors Stockists Retailers Doctors Pharmacists Hospitals.• Products require stringent cold chain management and spreading of awareness today is the

urgent need.

Protect your perishable cargo “End to End”Excursion points

Loading at point of origin

Airport CS to aircraft

Transshipment in some hot country

Excursion after landing.

Possible Solutions

Reefer vans to connect from manufacturing/warehouse site to airport.

Goods ideally should be moved in Cool Dolly's or a white cover for loading , unloading aircraft pallets for passive solutions.

Connect tail to tail. Use cool dolly’s for loading or unloading. In case of flight delays move the

perishable cargo to airport CS. Active solutions like Envirotainers will take

care end to end .For passive sufficient Ice Jellies / Dry ice to be packed.

Send the perishable cargo immediately to airport CS.

Arrange for immediate clearance.

Avoid temperature excursions at Airports/seaports

Ensure cold storage shipments are brought on week days since customs and other statutory bodies are available/ accessible freely.

Principal Cos to ensure adequate dry ice or ice jellies are put in sufficient quantities to take care of contingencies like connectivity issues.

Cold chain shipments are to be booked by flights which normally lands during the night as possibility of an excursion is minimum.

All shipping documents like suppliers invoice, packing list, COA etc. should be available at least 72 hours in advance with CHA before arrival of the cargo .

This facilitates advance filing of bill of entry, get same assessed under RMS, clearing drug control formalities and duty payment.

All necessary Form X Licenses, no objection certificate from Drug control , New Delhi, should be with CHA to facilitate clearance procedure.

Avoid temperature excursions at Airports/seaports

Documentation should be proper as partial shipments will not facilitate same day clearance.

Obtain out of charge (OOC) from the custom duty appraiser stationed round the clock at airport cargo complex.

Connect the released shipment tail to tail with the cold chain vehicle already waiting at the airport straight to the company warehouse facility.

Eliminate the possibility of exploring the space availability at Airport CS.

Avail E- payment of duty facility from own offices for faster release of cargo and lower transaction costs.

OPPI representation to Health Secretary on creation of Pharma Zones at major seaports and airports.

Current Indian Pharma market estimated at $22 Billion .and likely to become $50 billion by 2020.

Separate dedicated Pharma Zone will assure the quality, safety and efficacy of Drugs / Pharma products meant for Import / Export as per GMP.

A separate dedicated area to accommodate the imported and exported pharmaceutical products only .

Cold rooms with different temperature to meet the specific requirements to store the pharmaceutical products, Cool Place (10 to 25 degree Celsius), Cold Place (2 to 8 degree Celsius) and having chamber for temperature -20 degree Celsius and below etc.

Proposed Zone should be temperature controlled/air conditioned including the bonded as well as the examination area for drugs.

Dedicated power backup to ensure uninterrupted power supply. The movement for loading into the vessel or after unloading from vessel to

Pharmaceutical Zone should be done in temperature controlled vans. There should a process to monitor and record the temperature at various

storage areas and made available to exporters and importers.

OPPI representation to Health Secretary on creation of Pharma Zones at major seaports and airports.

The Pharmaceutical Zone should be equipped with a laboratory for testing and analysis of the imported/exported drugs including dispensing and sterile area for withdrawing of samples.

The office of the Customs & Assistant Drug Controller (India) should also be situated inside the Pharmaceutical Zone to ensure all clearances from authorities under one roof.

Proper SOP to handle each process as per GMP norms with well trained and dedicated staffs.

Delivery of products to and from these pharmaceutical zones should be fast and ensure there is minimum temperature exposure for the products.

AN OVERVIEW

Developing the right storage conditions and packaging infrastructure in your cold chain.

Power saving Insulation (Roofing)

4mm Polynum; 24 kg/m3 ThermocolTemp difference of 7-10 deg between outside and inside

Cold room Validation

Installation qualification(IQ) to be done with empty load for 24X7 for at least 7 days with multiple probes.

Performance qualification (PQ) to be done with full load for 24X7 for at least 7 days with multiple probes.

Both hot and cold spot to be decided based on average of all probe readings.

Set point to be defined. Alarm system to be installed.

Warehouse temperature maintenance and monitoring

Temperature range for each cold room should be indicated on the equipment.

For Cold rooms, the temperature in different parts shall be mapped as per a protocol for temperature mapping of chambers once in a year.

The cold storage areas should be constantly monitored through a

continuous temperature recording mechanism / equipment, installed in the warehouse or by installing a pre-calibrated temperature gauge/probe in the cooler / freezer / ambient area.

The installation of the probes shall be based on the Temperature

mapping report i.e. the hot spot/cold spot.

Managing temperature excursions and maintaining product quality standards

• Planned Events Loading/unloading products into cold storage. Preventive maintenance (PM) of the cold storage chambers. Any other maintenance work of the cold storage chambers The temperature of the chamber is bound to deviate when the chamber is

opened. Hence, the door can be kept open for maximum time of 5 minutes. The doors can be opened again only after the temperature of chambers

return to the specified range. In case of PM or other maintenance work the warehouse team should

ensure that the products are transferred to the backup chamber before initiating the maintenance activity.

Managing temperature excursions and maintaining product quality standards

Un-Planned Events Breakdown of systems Power failure Unplanned maintenance Breakdown linked to but not limited to; Not able to maintain the temperature due to unplanned

incidents Compressor not working Fan and coil unit not working DG set not working during power outage, etc.

Managing temperature excursions and maintaining product quality standards

In-case of any unplanned breakdown the first notification is made by an alarm system.

For excursion of 30 minutes and above the alarm will get activated.

In case of alarm the warehouse in-charge /operator/supervisor and (in night security) should check which chamber has the alarm and ensure the following

Door is properly closed Dispatches is going on If power off and generator not on Any other abnormalities

Managing temperature excursions and maintaining product quality standards

Warehouse in-charge shall take appropriate action to correct the above & document the corrective action, If still the alarm continues the following steps have to be followed: Inform the service vendor and the warehouse manager immediately

by a telephonic call. Immediate action within 2 hours shall be taken to resolve the problem

for temperature imbalance by the service vendor. It should be ensured that within next 2 hours i.e. total 4 hours from

the point of excursion, the products have to be shifted to the backup location as per the contingency plan

In case if the problem is not resolved with in the 6 hours from the point of excursion then supply chain manager shall be informed by a telephonic call & email.

Contingency Plan

The contingency plan has to be activated within 4 hours from the point of excursion. Step 1: In case of break down, Shift the Material to spare cold room or backup

room. Step 2: If a backup cold room is not available then then material is packed as per

the packing specification and stored in the warehouse. Step 3: If the material is large in number or if the space for keeping material

/packing material is less than the required quantity than contact for an immediate cold van container and shift the material to it. Please ensure that the data is archived and checked immediately post completion of movement.

Receipts and storage of incoming products

• Responsibilities Warehouse in charge Ensure that incoming inspection of product is carried out. Ensure

transfer of products to appropriate location upon receipt. Raise Nonconformance if any issue related to incoming inspection.

Supply chain. The overall process responsibility is maintained by the Head of

Supply Chain. The Head of the logistics / supply chain operation is responsible for the correct understanding and implementation of the process.

Receipts and storage

For RF & FZ products, the shipper shall be opened only in ambient temperature (15°C to

25°C). If the products are stored in boxes/shippers, an outer label should clearly indicate the

Identification of the product in terms of product codes or name. No products shall be stored on the floor but shall be stored on racks at specified places. The products should be stored lot-wise, product-wise and product group–wise; each

product group should be physically segregated distinctly from each other, In case of damaged goods received with the supplies, the damaged goods should be

stored separately, segregated (Quarantine) from others.

Packaging Proper validated packaging must be used to sustain temperature in

transit during transportation.

Validation of boxes to be done with maximum and minimum payload factor.

Proper packaging SOP should be in place.

Nature of product and storage condition should be on the outer of the packaging box.

Proper training to be imparted to follow the Packaging SOP.

Packing and despatch

Procedure Keep the required box ready for packing the products as per the

order. As per the product quantity appropriate size of thermocol box has to be selected.

The packaging of RF (2°C to 8°C) and FZ (-25°C to -15°C) products

shall be done only in ambient (15°C to 25°C) temperature. Products are first wrapped in bubble cup packing sheet and packed

with the tape as shown in the below figure. The data loggers shall be placed in the bubble sheet prior to bubble cap wrapping (if required)

Wrap the products with three folds of bubble sheet and place the product with in the thermocol box.As per the product quantity appropriate size of thermocol box has to be selected.

AN OVERVIEW

Validating logistics providers to confirm efficient transportation of goods

Temperature Monitoring in Data loggers/Temp Monitors

Refrigerated vans should have re-usable data loggers to record the temperature in transit.

One data logger should be placed at the hottest point and another at the coldest point.

Temperature data loggers should be calibrated annually to ensure accurate recording.

Temperature data loggers should have sufficient battery and shelf life.

The data loggers should be replaced every three years.

Temperature Monitoring in Data loggers

Refrigeration van drivers and service operators must undergo mandatory training before they commence work.

• Loading Guidelines: The vehicle must be clean. The required temperatures and alarms must be set as per

requirements. The van should be precooled at the required temperature for

at least 1-2 hours before loading is started. The data logger should be restarted and set. Pallets must be placed on the floor of the vehicle

Temperature Monitoring in Data loggers

Unloading Guidelines:

The data loggers should be monitored to check if the required temperature was maintained during transit.

Unloading should be done through a small window to minimize temperature excursions.

Unloading should be completed within a minimum stipulated limit.

Preventive Maintenance Programme for Refrigerated Vans

Contingency Plan:

Documented procedure, with training, for drivers to deal with contingencies like refrigeration breakdown, or any other event that compromises product safety.

A list of contact numbers should be available in van so that the people concerned can be immediately contacted.

Tie-ups with regional service centers so that vans can be rushed there for repairs.

All efforts should be made to minimize temperature excursions and transfer or restore the products to the prescribed temperature storage limits.

Thank You