Stability in Biopharmaceutical Storage

Outsourcing stability storage is a highly efficient way to cut costs, improve services, and generate revenue by effective cost management. Switching to an outsourced stability storage facility could provide the benefit of increased customer satisfaction and improved efficiency. Outsourcing stability storage can free up aspects of a company's operations that might not be running efficiently. Finding the right outsourcing partner, however, can be quite a challenge. Consider the following before arriving at an off-site solution.

KEEPING STABILITY STORAGE IN-HOUSE IS COSTLY

By its nature, any controlled environment storage facility needs a large investment in tailor-built premises. Floor space comes at a premium and much of the equipment needed has a large footprint, because it may have to be capable of accommodating bulk products. Typically, a resource with several million cubic litres of environmentally controlled storage space and storage suites that can house thousands of cubic meters of product is required.

Patrick Jackson

Geographic location should also be considered. The location of the facility should be well away from natural disaster areas and be in a convenient location for shipping options. Proximity to major highways and airports can be a distinct advantage, particularly considering the speed at which new global markets are opening up.

Equipment investment

An average-sized storage room could cost anywhere between $63,000 to $190,000 to set up. A typical cabinet could cost upwards of $23,500. With separate rooms needed to suit different environmental conditions, costs can quickly mount up.

Walk-in stability room's cabinets and chambers should always be available, with additional chambers to be called upon for specific requirements such as retained samples, secondary storage, quarantine samples, freeze and thaw testing, and aerosol testing.

Design knowledge

Rooms and chambers need to be versatile. Through their lifetime, these rooms will serve many purposes including stability storage, commercial environmental testing, corrosion testing, UV testing, environmental stress screening, shock testing, temperature and humidity testing, and photostability.

Ambient temperature and stability storage should be available, regardless of the size of product. Designing and building controlled-environment rooms and chambers is a skill that is developed over many years. Unique airflow technology systems should be incorporated to deliver definitive environmental conditions.

REGULATORY CONTROLS

Any facility working to cGMP guidelines should incorporate chambers and rooms that are built using the most modern techniques. They must be mapped and validated for pharmaceutical stability storage and biotech storage. Outsourcing companies can tailor these temperature and humidity controlled rooms and chambers to suit individual customer requirements as well as shelf life studies, intermediate testing, and accelerated testing per International Conference on Harmonization's (ICH) Q1A (R2) guideline (1).

The assessment of drug substance stability is a vital and essential aspect of the development of pharmaceutical products. Stability testing is capable of providing information on how environmental factors such as temperature, humidity, and light affect their quality over a period of time. Data derived from a stability study enables recommended storage conditions, re-test intervals, and shelf lives to be evaluated and established.

It is the norm for controlled environment rooms to be built and validated to provide climatic conditions specified in ICH guidelines. This should include equipment to allow for simulating conditions in all four climatic zones for long-term, intermediate, and accelerated testing. An outsourcing facility should have a comprehensive range of conditions including ICH Photostability Option 1 and Option 2 studies, as well as the capacity for customization. All staff should be fully accountable and provide a service that complies with regulatory requirements.

TAILORING OF SERVICES

An independent storage facility should be able to offer unique conditions, as there are many instances where drugs and drug-related products need to be stressed and tested in situations outside ICH guidelines. Any independent storage facility should offer conditions specifically suited to a company's product. It should meet the needs of companies that require off-site stability storage, redundant stability storage, short-term growth needs, back-up storage, or long-term stability storage.

Biopharmaceuticals, for instance, are particularly sensitive to environmental factors, making strict storage conditions necessary for the maintenance of biological activity and product integrity. The choice of temperature for the storage of biological, medical, and pharmaceutical materials is dependent upon the sample to be stored. An outsourcing facility should offer the option for storing materials under controlled ICH and non-ICH conditions in a purpose-designed storage suite. This service will provide an extremely cost-effective solution for controlled-environmental storage at temperatures that should range from minus 196 ºC to plus 55 ºC and relative humidities from 15% to 90%.

Pure DNA will exist for long periods at 4 ºC in buffer solution. For long-term storage, DNA is stored at minus 40 ºC, while proteins are better stored at minus 80 ºC and stem cells are stored at minus 196 ºC. A comprehensive cryobank will provide a solution for these and almost all other storage applications.

CRYOGENICS

There is an ever-increasing need for cutting edge cryogenics in today's controlled storage world. Cryopreservation is a process where cell (biology) or whole biological tissues are preserved by cooling to low sub-zero temperature, such as (typically) 77K or minus 196 °C (the boiling point of liquid nitrogen). At these low temperatures, any biological activity, including the biochemical reactions that would lead to cell death, is effectively stopped. However, when vitrification solutions are not used, the cell (biology) being preserved is often damaged due to freezing during the approach to low temperatures or warming to room temperature. These factors are further proof that it makes economic sense for pharmaceutical and related industries to adopt an outsourcing partnership for their complex cryobiological programs.

An outsourced controlled environment storage facility needs to provide a full range of services to store and manage biological materials at any given temperature. From bar-coding frozen vials through to relocating an entire repository, the quality policy should be reinforced by a positive commitment. This starts with an assurance that samples are stored in a high security facility with convenient access.

SAFE STORAGE

The storage of cells at temperatures below minus 150 ºC is necessary to preserve materials unaltered. This is the point at which biological activity ceases. Although mechanical devices can be used to maintain temperatures below this level, they can be noisy and generate heat. They also require liquid nitrogen backup to avert disaster should the electricity supply be disrupted or the freezer fail. Liquid nitrogen is the most logical choice for storage at temperatures below minus 130 ºC. But there are risks associated with its use. To ensure there can be no cross-contamination with the stored samples, it is generally recommended that materials are stored in the vapour phase above the actual nitrogen, where temperatures are in the region of minus 150 ºC down to minus 178 ºC.

An efficient cryobank should provide a management solution for short-term, medium-term, and long-term temperature controlled storage. It should incorporate secure storage and real-time tracking of the stored samples and all safety issues should be in strict accordance with the latest regulations. It is also essential that sites have the staff and systems to offer foolproof biological storage conditions. A purpose-built state-of-the-art biorepository should accommodate biological samples, culture collections, microbial, viral seed stocks, DNA and bone marrow, as well as all-important stem cells and cord-stem tissue.

Stem-cell and cord-blood storage

Stem-cell research is a market that is in its infancy, but there is little doubt that frozen sperm, eggs, embryos, and stem cells being stored at clinics and hospitals will eventually become the norm across the world. A good storage company should already be constructing cryobanks to satisfy the needs of this emerging market. In the United Kingdom, cord blood has become the most frequent source of stem cells for transplantation in children. It is estimated that by the year 2015, there will be up to 10,000 cord- blood transplants worldwide per year, using banked cord blood. A vital aspect of this program will be to develop repositories for the storage of cells to guarantee continued successes in this exciting arena.

Long-term storage

There are some finely tuned methods of preserving biological materials by freezing and storing them at ultra-low temperatures. The provision of long-term preservation of biologics, reagents and specimens is often required, together with a secure facility for samples and laboratory research materials. Ideally this should cater for anything from a single box of samples, up to virtually any volume, for the duration of any research project and be capable of storing millions of samples, vials or tube racks.

VALIDATION

A comprehensive storage facility should have full regulatory compliance to guarantee the integrity of the samples it stores. They should have the latest equipment to ensure that the facility is technically fit for purpose, meets the highest standards of environmental control, and includes built-in redundancy and emergency backup. Every piece of equipment should also be protected by an individual preventative maintenance schedule.

Constant monitoring is normally performed with a paperless data logging system that, ideally, should also be compliant with the requirements of the US Code of Federal Regulations. An ultra-low temperature storage facility of minus 70 ºC to minus 85 ºC can be tailored to the needs of biotechnology, pharmaceutical, and agrochemicals companies, including veterinary industries and academic institutes.

Expertise in sample management underpins the secure storage of samples and should include constant monitoring of the storage conditions, the ability to track and retrieve samples to GLP standards, and full traceability in regulated environments.

Validation must be carried out regularly to ensure that an environmental room, cabinet, or cryogenic freezer is capable of accurate and repeatable performance. Temperature and humidity levels should be monitored at all times to incorporate an identifiable audit trail.

SAMPLE TRACKING

Managing hundreds of thousands of samples for different companies, with dissimilar protocols, requires an efficient sample tracking system to ensure that they are all handled properly. When samples are outsourced properly, identification of each sample is needed to prevent confusion when removing the samples from chambers. Samples should be clearly labeled, typically with quantity, storage conditions, product name, product code, lot number, and date of manufacture. Reliable software can also make a significant difference when tracking pull dates, sample locations, and quantities.

A comprehensive information management system is at the heart of all storage solutions. The inventory management solution should enable the user to record all data associated with the samples including location, temperature, and humidity, as well as recording all user-defined information. Every sample handled should ideally be given a unique barcode label and be recorded on the system. This system significantly simplifies handling, tracking, and processing. Supplementary information relating to individual samples in terms of movement within the facility, time, and duration of storage vessel openings and who accessed the vessel must also be available within the audit trail.

DISASTER RECOVERY PLAN

The outsourced storage facility should provide secure secondary storage as an essential insurance policy. A third party should retain duplicate samples in a different but secure second geographical location. This step can help to eliminate the risk of a disaster scenario destroying valuable stability storage samples and causing commercial damage.

COST CONSIDERATIONS

All this expertise can come at an affordable price, usually levied as a standard monthly or annual fee, but charges for set-up, transactions, or removing samples should not be extra. The controlled-environment facility should offer a simple cost-effective arrangement for a precise and intricately managed service.

CONCLUSIONS

Controlled-environment storage is a demanding business. It presents many challenges including high costs, management expertise, and regulatory procedures. The decision to outsource will depend on a company's current resources and future needs. Outsourcing provides qualified and knowledgeable staff that will keep abreast of topical developments, offering unique conditions with state-of-the-art facilities to match. Outsourcing is the logical choice to navigate through the maze of equipment, technologies, controls, and procedures that lay ahead.

Choose carefully, and a strategy can be developed that is not only tailored to a specific organization, creates and maintains a successful and trustworthy relationship for every program.

Patrick Jackson is business development director at Vindon Scientific Limited.

REFERENCE

1. ICH, Q1A (R2), Stability Testing of New Drug Substances and Products (Aug. 2003).