Lab Technology

Many leading pharmaceutical companies run their ownstability storage and testing facilities in-house, andpurchase their stability suites from one of the majorequipment manufacturers. The range of equipmentrequired is wide-ranging and can potentially includecontrolled environment rooms, biological cabinets, andpharmaceutical fridges and freezers.

Healthy competition certainly makes business anongoing challenge for all companies as they strive forever-increasing quality standards, allied to overall costreduction wherever possible. We all share common issues– many of them related to finding extra resources and,when secured, using them to their fullest potential. Thisis where outsourcing can play a valuable part in acompany’s stability testing regime.

Pharmaceutical and biotechnology companies thatchoose to utilise the expertise of a contract stabilitystorage organisation for the storage of their productsstand to benefit initially from such a move as iteliminates the need for large capital outlay on stabilitychambers or rooms. A second advantage is that it reducesthe requirement for costly laboratory space, and a third isthat it eliminates the need to regularly service and

calibrate equipment, as this is all part of the stabilitystorage company’s remit.

Other factors that can often be overlooked whenconsidering outsourcing include the requirement for24/7 engineering cover and, of equal importance,disaster recovery planning in the event that a room orchamber failure cannot be rectified in the requisitetime-frame.

CHOOSING THE RIGHT PARTNER

The benefits of outsourcing are substantial, but how doyou choose the right partner? When looking to outsourcestability storage, it is important to thoroughly appraisethe company first. Factors to consider include:

� The length of time the company has beenundertaking stability storage

� The availability of a team of validation engineers

� Financial stability� Computerised monitoring systems and effective

sample tracking software� Flexibility of both the company and its staff� The capability to accept small and large studies� Sufficient equipment and back-up facilities� Comprehensive alarm systems� Service engineers on call around

the clock

Only the right partner can help a company get thebest from its stability storage function. Experiencecounts – and choosing a partner that understandsspecific market sectors will ensure a more efficient process and thus help drive the businessforward. The service provider must offer an extremelycost-effective solution for controlled environmentalstorage of materials at temperatures ranging from -197˚C to +55˚C, and humidities ranging from 10%to 95% RH.

While some companies will always prefer 100% control of their ownstorage, outsourcing stability storage requirements to an experiencedcontract organisation can bring significant cost benefits – leaving companiesto focus their internal resources on drug development and production.

42 Innovations in Pharmaceutical Technology

By Patrick Jackson atVindon Scientific Limited

Stability Storage: the Case for Outsourcing

Figure 1: Storage at -86ºC

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A CONTROLLED ENVIRONMENT

It is the norm for controlled environmentrooms to be built and validated to providethe climatic conditions specified in theICH Guidelines, simulating the conditionsfor all four climatic zones for long-term,intermediate and accelerated testing. Thecompany providing outsourced storagemust also be able to provide uniqueconditions, as there are many instanceswhere drugs and drug-related productsneed to be stressed/tested at conditionsoutside of ICH Guidelines.

Temperature and humidity control iscrucial. Humidity must be generated ‘ondemand’ by high-efficiency humidifiersfeaturing ultrasonic transducers, as changesin temperature and/or humidity can put considerablestress on storage samples, and potentially lead toinaccurate or unsuccessful results. It is therefore essentialthat the temperature and humidity within each stabilitystorage room or cabinet is monitored strictly, and that thechambers are routinely validated.

Regular validation to ensure the accurate and repeatableperformance of an environmental room or cabinet isessential. At Vindon, we use a combination of UnitedKingdom Accreditation Service (UKAS) calibrated probesand state-of-the-art data acquisition systems to ensure thatthe temperature and humidity of all our rooms aremonitored at all times. Typical systems are Eurotherm6000 series data loggers which are 21 CFR Part II-compliant; this is a requirement that no data can betampered with without leaving an audit trail.Performance-mapping tests are also undertaken annuallyfor temperature and humidity. This ensures that the roomand system are operating correctly, and that the probeshave not ‘drifted’ from their set points. All documentationis designed to show compliance with relevant guidelinesand to meet requirements.

For some pharmaceutical companies, there may beslightly different needs and special environments, andprotocols will need to be set up. Different conditions arecertainly required for some of the emerging markets inAsia and the Middle East. Even if, strategically, thepreference is to continue to run an in-house operation, itmay still be worth considering a third party for handling,for example, retained samples, secondary storage, storage of quarantine samples, freeze/thaw testing andaerosol testing.

UNIFORM CONDITIONS

It is imperative that stored samples are all exposed to thesame uniform, identical, repeatable and reproducibleconditions. All chambers must have pre-conditioned airflow circulation to ensure uniformity for all test sampleson all shelves. In addition, the stability storage chambershave to be temperature- and humidity-mapped, and theyshould operate independently with separate real-timetemperature and humidity controls as and whenapplicable. Most of the modern rooms currently availableare monitored by computer-controlled logging systems sothat alarms are recorded immediately. Should a room orcabinet alarm go off, there can be an immediate responsefrom one of the technicians available to deal with theproblem straightaway. Loss of valuable samples can delayan important project and be very costly to an organisation.

The contract storage facility should be capable ofaccommodating all ICH and non-ICH conditions, as wellas new conditions, and the contract stability storagecompany must be able to provide a range of requirementseasily and effectively, and have sufficient room in itsfacility to accept more storage space when required.

STABILITY SAMPLE TRACKING

Effective stability sample tracking is extremely important;managing thousands of stability samples for differentcompanies, all with different protocols, requires a solidstability sample tracking system to ensure that all samplesare handled correctly. When samples are outsourcedproperly, identification of each sample is essential toprevent confusion when pulling stability samples from the

43Innovations in Pharmaceutical Technology

Figure 2:Pharmaceuticals instability storage room

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chambers. Samples should be clearlylabelled – typically with quantity,storage conditions, product name,product code, lot number and dateof manufacture. Reliable stabilitysoftware can also make a significantdifference when tracking pull datesand sample locations and quantities;it is important to comply withregulations for audit trails andsecurity compliance in order to meetinspection regulations.

BULK CHEMICALS

Pharmaceutical products are manufactured using bulkpharmaceutical chemicals and, as such, manufacturersof inactive ingredients have to comply with GMPguidelines. Although the GMP regulations apply only tofinished dosage forms, the US Federal Food, Drug, andCosmetic Act requires that all drugs be manufactured,processed, packed, and held in accordance with current good manufacturing practice. No distinction ismade between bulk pharmaceutical chemicals andfinished pharmaceuticals, and the failure of either to

meet cGMP standards constitutes a failure to complywith the requirements of the Act.

During the development of a pharmaceutical productand after its manufacture, the stability of the chemicalconstituents should be analysed according to a stabilitystudy programme that will reveal any stability issues.Undetected changes in raw materials specifications, orsubtle changes in manufacturing procedures, may affectthe stability of bulk pharmaceutical chemicals. Stabilitysamples should be stored in containers that are verysimilar to the packaged finished product, as they wouldappear on the pharmacy shelf. It is also recommendedby the FDA that additional samples be stored understressful conditions (for example, elevated temperature,light, humidity or freezing) if such conditions can bereasonably anticipated. A complete range of WorldClimatic ICH conditions for the stability storage ofbulk pharmaceutical chemicals should be available tothe industry. There is also a need for completeflexibility in terms of setting up chambers to reproduceother environments to meet specific product and

client requirements.

STEM CELL STORAGE

Medical researchers believe thatstem cell therapy has the potentialto dramatically change thetreatment of human disease and anumber of adult stem cell therapiesalready exist. In the future, it isanticipated that we will be able touse technologies derived from stemcell research to treat a wide varietyof diseases, including cancer. Bystoring stem cells taken from ababy’s umbilical cord, it is nowpossible for parents to insure their child’s future health against

diseases such as cancer, diabetes, cardiovascular problemsand blood disorders.

Stem cell storage is still very much in its infancy, but there is little doubt that stem cell storage will bethe norm in years to come – not just in the privatesector but also in the public arena. Stem cells caneasily be collected from the umbilical cord of anewborn baby and then stored under cryogenicconditions (usually at minus 190ºC) in special tankscontaining liquid nitrogen. At Vindon, we arecurrently constructing a cryobank to satisfy the needsof this emerging market.

44 Innovations in Pharmaceutical Technology

Figure 3: Walk-instability storagerooms in Vindon’sStability Suite

Figure 4: Regular validation of stabilitystorage rooms and cabinets is essential

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ULTRA-LOW TEMPERATURE STORAGE

There are some well-established, finely-tuned methods ofpreserving biological materials by freezing and storingthem at ultra low or cryogenic temperatures (-86˚C). Theprovision of a secure low temperature and ultra lowtemperature storage facility for samples and laboratoryresearch materials is often required, and any such facilityshould ideally provide for a single box of samples – up tovirtually any volume – all the way through to completionof a research project.

For cryogenic storage, constant monitoring is normallyperformed with a paperless data logging system that,ideally, should also be compliant with the requirements ofthe US Code of Federal Regulations.

BACK-UP SECONDARY STORAGE

The probability of any company experiencing fire, power-cuts, flood, storm or any other potential disaster isdistinctly uncertain, but any one of these events couldsignificantly affect a company’s stability storage and testingoperations. Commercial organisations are increasinglyreviewing their approach to disaster recovery plans; theobjectives of any such plan can be summarised as follows:

� To minimise potential economic loss� To insure against the loss of products in storage� To counteract the disruption to stability

storage activities� To reduce critical loss to a company� To provide an orderly recovery of product

One potential way forward could be to maintain an in-house stability storage suite and then, in parallel to this,a set of duplicate samples could be retained by a thirdparty in a different, but secure, second geographicallocation. This approach is well worth considering in thatit virtually eliminates the risk of a disaster scenariodestroying a company’s valuable stability storage samples,and causing commercial damage to the organisation.

CONCLUSION

In recent times, there has been a trend in the industry tomove away from in-house stability storage towards the useof third parties. Clearly this will depend on companystrategy – some organisations will always prefer 100%control of their own storage. In many cases, however, itcan make sense to outsource stability storage requirementsto an experienced operator based elsewhere. This kind ofmove needs careful thought in terms of price, quality ofservice and flexibility of approach; in essence, whilestorage would take place elsewhere, actual testing wouldcontinue to be handled in-house.

In view of the current financial crisis, the option of storingmaterials under controlled ICH and non-ICH conditionsin a purpose-designed off-site stability suite can reapsignificant cost-benefits. Once the decision has been madeto outsource stability storage, pharmaceutical companiescan then focus their internal resources on their corecompetencies, and concentrate their efforts on new drug development.

46 Innovations in Pharmaceutical Technology

Patrick Jackson is Business Development Director atVindon Scientific Limited. A qualified engineer, he hasover 30 years’ experience in project management andbusiness development, with a track record of businessand client development. He has held a number ofBoard appointments, and has successfully managed anddirected 30 to 40 diverse projects each year ranging

from £250K to over £20 million; he has also has been responsible for developing systems to sustain growth for a number of companies in highly competitive markets. Email: patj@vindon.co.uk

Figure 5: Puttingpharmaceuticalson store inVindon’s StabilitySuite

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