Almac
Almac

Headquarters
Craigavon, UK

Location(s)
Craigavon, UK; East Lothian, UK; Audubon, USA; Durham, USA; San Francisco, USA and Yardley, USA

Years in Drug Formulation
Over 30 Years

Spokesperson
Mr. John McQuaid, Technical Development Manager

Web site 

Areas of research
•	Small Molecule			Biological			Other

 

Drug Formulation Services Offered
•	Analytical method development		•	Bioavailability enhancement
•	Compatibility studies of active ingredients		•	Dosage form selection
•	Excipient compatibility		•	Formulation optimization
•	Formulation stress testing		•	in silico studies
•	Manufacture of clinical supplies			Novel delivery system
•	Packaging compatibility assessment		•	Particle size reduction
•	Preclinical studies		•	Solubilizing water-insoluble drugs
•	Stability studies		•	Taste masking/flavorings

 

 

 

 

 

 

 

 

 

Other Services Offered
	Disease Research		•	Target Identification
•	Lead Identification			Early Safety Tests
•	Lead Optimization			Pre-clinical Studies
	IND Submission			Clinical Trials
	NDA Submission			Post-marketing Studies

 

 

 

 

 

 

 

Types of Drugs
•	Generics		•	Prescription		•	OTC

 

Dosage Forms
•	Capsules			Implantable
	Inhalation			Injectible
•	Oral			Parenteral
•	Peptide and Protein		•	Tablets
	Topical

 

 

 

 

 

 

Company’s role in drug discovery and developmnet
Working with over 600 companies, including all the world leaders in the pharmaceutical and biotech sectors, Almac offers an extensive range of drug development services from biomarker discovery and validation; genomic services; chemical development and supply of API; pharmaceutical development, manufacture, preparation, distribution, and management of clinical supplies (including IVRS/EDC/ePRO); through to commercial manufacture and packaging of pharmaceutical product.

Company’s experience and expertise in drug formulation
Almac has over 30 years’ experience in drug formulation specializing in solid, oral dose presentations. A dedicated team of Formulation Development scientists focus on developing robust formulations for all stages of clinical development (Phase 1-4) right through to manufacture of registration batches and subsequently commercialization. Continual investment in people, facilities, and equipment enables a flexible and fast response to today’s formulation challenges. We have the expertise to develop and scale-up solid, oral dosage formulations on a single site using a wide range of blending and granulation technologies, most of which have high containment capabilities. We also have experience in developing formulation solutions for poorly soluble compounds. The formulation development group ensures a sound scientific approach for all stages of drug formulation working closely with our on-site Chemical Development and Solid State Characterization experts where appropriate. Our formulation experts also use design of experiments (DoE) software to write protocols for development and scale-up activities.

Relationship with pharma companies
Almac has highly talented, multidisciplinary teams to address the wide range of challenges encountered during the drug formulation process. Expertise can be called upon across these teams and team integration can be used as necessary. All development activities occur on a contractual (fee for service) basis – this can take the form of discreet projects, client multi-project “umbrella agreements”, or standalone FTE agreements covering multiple projects. This flexibility has worked well for Almac, demonstrated by a high level of repeat business. We encourage our clients to work as our partners with on-site client presence, as appropriate, but are equally content to assume full responsibility with periodic client updates.

Factors critical for drug formulation
Understanding the physico-chemical properties of the API to be formulated is probably the most critical factor, in particular API solubility. Almac has a dedicated solid state group which supports the generation of critical preformulation data. Almac also has capabilities of designing formulations which enhance drug solubility.

Potency and unknown toxicity – to address these challenges Almac has installed high containment solutions allowing handling of potent compounds whilst providing maximum protection for operators.

Limited availability of API – it has become necessary to provide formulations using small amounts of API. Almac provides solutions to ensure that equipment losses are minimized, to the extent of using manual operation with in-house engineered solutions to obtain the best results with minimal amounts of drug substance.

Finally, as product time to clinic/market is a critical consideration, our dedicated Project Managers facilitate team efforts to deliver product and services on time.

Scientific/business/regulatory trends impacting drug formulation
Recent trends show that an increasing number of drug candidates possess poor aqueous solubility, creating a challenge to manufacture formulations that maximize bioavailability. Also, drug companies are tending to develop more potent compounds as a more specific and targeted mechanism of action maximizes benefits and patient compliance whilst minimizing potential side-effects. Potent compounds bring their own unique formulation issues particularly in terms of increased Engineering and Health & Safety requirements. There is also evidence that big Pharma are increasing the number of biologicals in their development portfolios.

The Pharma industry has increased spending on R&D but the number of candidates reaching market has decreased. To address this trend, one major business objective is to accelerate early drug candidates into clinic by reducing time from drug synthesis to regulatory submission. This can be achieved by understanding risk and running trials with development work progressing in parallel. A “Quality by Design” approach has also impacted drug formulation as the Pharma industry attempts to enhance product and process understanding (even from as early as Phase 1) in order to deliver better and more robust products.

Success story
A powder-in-capsule formulation was manufactured which was suitable for a Phase 1 clinical trial with the poor flow properties of the drug overcome by manual capsule filling. After successful clinical results, the client requested a tablet formulation for Phase 2, which had to possess sufficient flow properties to allow automated processing. To overcome the challenge of poor flow, the on-site chemists manufactured the drug substance with four different particle size distributions and these were evaluated using a range of techniques. The drug substance with the optimum particle size distribution was chosen for further investigation. The flow properties were assessed and although significantly improved, were still short of being acceptable for automated processing. Therefore roller compaction was introduced as a further way to improve flow. Even with drug loading up to 80% w/w of the formulation, this approach led to a formulation suitable for automated processing with the tablets produced currently under Phase 2 clinical assessment.

How will roles of CROs and contract manufacturers change over the next few years?
Preclinical and clinical development outsourcing will continue to grow with clients seeking more integration of services. Those providers that can offer a joined up development continuum will benefit. This can further extend into commercialization with potential to create value integrating backwards from the retail end of the supply chain.

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Filed Under: Drug Discovery

 

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