By Anupam Chanda, Sun Pharma Laboratories Ltd, 25/05/2015 The cold - - PowerPoint PPT Presentation

By Anupam Chanda, Sun Pharma Laboratories Ltd, 25/05/2015

The cold chain refers to the temperature management of perishable/highly moisture and temperature sensitive products in

• rder to maintain quality and safety from

the point of slaughter or harvest/manufacturing location through the distribution chain to the final consumer

Different industries require their raw materials and finished goods to be transported under temperature controlled conditions. This is necessary to preserve the integrity and quality of the overall product The implementation of an effective cold chain solution minimizes loss

• f texture and flavour to produce

and delivers fresh products to the end user both in and out of season

• Increasing regulatory scrutiny. During an inspection you

need to be able to answer the usual quality-focused questions about your cold chain integrity: “How do you know? Can you prove it?” Anyone complaint with GxP who manages any link in the supply chain needs to be prepared for these questions

First

• More biopharmaceutical products coming onto the

market all the time. By some estimates, 50% of the entire drug market will be biologics by 2018. These drugs tend to be more sensitive to environmental conditions and therefore require more care as they move through the supply chain. You should be aware of this if you handle these types of products

Second

• New focus on drugs that must be kept at controlled room

temperature (CRT). This is usually defined as 20°C to 25°C with allowable excursion between 15°C and 30° as long as the mean kinetic temperature remains in the defined range. (Refer to USP 1079 for more information

• n CRT). Drugs in this category are typically less

sensitive to environmental conditions, but when storage temperatures are defined, it is reasonable to ask if they have actually been maintained properly.

Third

uploaded manually to a PC

provide a time history of the transport duration provide a temperature history of the transport duration

Temperature data loggers

These devices are usually started at the beginning of a shipment, stopped at the end

solution providers clamoring for position

“temperature management through the supply chain Offering different solutions

There are more complex data loggers that can measure temperature, humidity, shock, vibration, and other parameters. They may have GPS capability and even the possibility of real- time tracking and reporting. Some communicate via RFID to simplify the gathering of information. There are also software solutions available to capture and track all of the information from the data loggers.. There are also packaging providers with a variety of package- based temperature control solutions. Some packaging is completely passive and custom-designed for a specific

• application. There are also active containers that can heat and/or

cool the drug product as necessary. Some active containers are specifically designed to fit the mode of transport, such as airplanes.

Some global supply chain solutions. Some are smaller companies that can organize your supply chain for you, using a variety of resources as necessary and complying with all applicable regulations. There are firms that can map your transportation routes and the storage areas. vehicles that travel these routes

The EU Guide to Good Manufacturing Practice,

The Guidelines on Good Distribution Practice (GDP) of Medicinal Products CDC Guidelines for Maintaining and Managing the Vaccine Cold Chain WHO Guidelines

• n 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)

Understand your current supply chain. Map it

• ut so that you know where your facility and/or

process is in the context of a product’s entire supply chain. Consider where your supply chain is going. 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). This will require consultation with other people in your company and

• ther parties in a product’s

supply chain. 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

• f having to fix a broken system later on.

• www.pda.org

The Parenteral Drug Association

• www.gcca.org

Global Cold Chain Alliance

• www.ista.org

International Safe Transit Association International Society for Pharmaceutical Engineering - www.ispe.org

GCCA is an umbrella organization which acts as the platform for communication, networking and education for each link of the cold chain, and is comprised of members from Core Partners

Our members represent critical links in the cold chain across N. America and in 65 countries around the world. GCCA members are comprised of 345 public refrigerated warehouse (PRW) companies, 1006 facilities, 80 construction companies, 112 transportation companies and 387 suppliers to the

industry. IRTA: International Refrigerated Transportation Association IACSC: International Association for Cold Storage Construction WFLO: World Food Logistics Organization

IACSC: International Association for Cold Storage Construction

creation

implementation

adoption

Vertical Frozen Chilled QSR

• 4 to -6 oC

Pharmaceutical

• 22 oC (vaccines)

2 oC to 8 oC Meat & Poultry

• 20 oC
• --

Processed Food

• 18 oC
• Ice cream
• 25 oC
• Dairy
• 2 oC to 4 oC

Chocolates

• 16 oC to 18 oC

Retail

• 18 oC to -22 oC
• 18 oC to -22 oC

Proven track record Domain and technical expertise Trained staff Modern & young fleet of reefer vehicles Risk mitigation strategies Experienced technical team

98 115 134 175 228 298 389 497 624 100 200 300 400 500 600 700 2009 2010 2011 2012 2013 2014 2015 2016 2017 INR BILLION YEARS

storage 12% transport 88%

Cold chain segments

currently India has 6300 cold storage facilities unevenly spread across the country. With an installed capacity 30.11 million metric tonnes

1) Organized players contribute only 8 to 10 % of the cold chain industry market, 2) 36% cold storage capacily below 1000 MT 1) 65% of India’s cold chain storage capacity is contributed by the states

• f UP & West Bengal.

2) As per current capacity only less than 11% of what is produced can be stored.

Selection of right insulated packaging material Proportionate use of cooling materials inside the primary and secondary pack Perfect Packaging Design

Polyurethane, the best insulating material

Using polyurethane insulation ensures that products can be kept cooler for longer with reduced energy inputs and also that lighter and more compact packaging can be used. All these are key factors in reducing specific cool-chain costs.

• Polyurethane remains unrivaled as an

insulation medium. It combines light weight, low cost and easy fabrication with very low thermal conductivity of 0.025 W/mK.

• Polyurethane is also a flexible material,

easier to process than polystyrene. It can easily be moulded into shapes to suit specific requirements. This means that polyurethane can be used to manufacture custom-designed insulated pharma packaging solutions.

• polyurethane is also a material that is

easy to recycle, both mechanically and

• chemically. Examples of polyurethane

recycling include rebonded carpet underlay or to create polyols used in automotive components.

• Identify product
• Product stability Profile
• Transportation process flow consideration
• Bulk & Intermediate ,Finished goods, Analytical

samples Process Flow Diagram

Generate documents for component specification Develop OQ protocol Develop PQ protocol Design testing

Distribution chain training

• Implement

the process

Develop training

• Quality

system

Auditing distribution chain

• Regulatory

perspective

• Perform

monitoring

• Validation is documented

testing that consistently produces a result meeting pre-determined specifications.

Definition of validation

• Qualification is documented

testing that demonstrates with a high degree of assurance that a specific process will meet the pre-determined acceptance criteria.

Definition of qualification

Drug substance manufacture East coast US Shipment at – 80 deg.C to drug product manufacturing site EU Shipment of semi finished product at 2- 8

• deg. C to

distribution center in EU Shipment of semi finished product to packaging site in US at 2- 8

• deg. C

Distribution of final product to customer at 2- 8 deg.C

steps

Each manufacturing step at RT to capture

Total processing time at RT is covered by analytical stability data of the product

Sum of all manufacturing steps has to be within limit

Each manufacturing step has an acceptance limit

Calibration of sensors (pre/post validation) Temperature distribution (empty/loaded) Critical alarm functions tested Predefined acceptance criteria Written and preapproved protocols

External sensors calibrated to +/- 2°C

Data recording:

• Every 5 min
• Continously over 3 days
• 15 sensors distributed within

(bottom/middle/top) freezer

Acceptance criteria:

• No single value

+/- 20°C of target

• Mean of data per

h: +/- 5°C

Recalibration every year

Equilibration period 3 h

Revalidation every 2 years

1 2 3 4 5 6 7 8

• Product temperature NMT –25°C for at least 66 h
• Ambient temperature profile (+18°C to +55 °C)
• 2 x 2L of product
• Approx. 32 lbs dry ice refrigerant

Thermal qualification

• Free fall testing (ASTM D 5276)
• Vibration test (ASTM D 999)
• Random vibration test (ASTM D 4228)

Transportation qualification

• Need to include all necessary data
• Packing process

Test Worksheet

Understanding the various methods of cold chain distribution and their advantages/disadvantages

• Understanding the cold chain requirements for various

temperature sensitive healthcare products and the impact

• f temperature excursions
• Understanding the key steps required in the setting and
• rganization of an efficient cold chain distribution process
• Understanding the various costs involved in cold chain

transportation and comparing it with non-cold chain transportation

222 294 294 366 432 498 630 810 1002 690 804 936 1104 1290 1482 1704 1944 2202 500 1000 1500 2000 2500 2007 2008 2009 2010 2011 2012 2013 2014 2015 export total indian Pharma (INR Billion)

Demand from the Pharmaceutical Industries

Estimated compound annual growth (CAGR) of 13% during the period FY 2009- 2013. The Indian Pharma market is poised to grow to Rs 3300 billion by 2020 from the 2009 levels of Rs 756 billion Cold chain acts like a backbone for pharma industry.It’s a big responsibility to have a regulatory supervision and to maintain the efficacy of the drug throughout the supply chain in order to maintain quality of drugs and comply with statutory requirements.

Expectations from Government

To provide Technical and Financial support to Medium and small industries to start this business. Provide an enabling environment for the cold chain sector to gain prominence and invite the much needed private sector involvement.