FAQ-Simbec

What are the minimum preclinical requirements to enter
Phase I?

For Single dose studies in Man:

Safety Pharmacology Screen, including general pharmacology screen (similar to Irwin Screen).  Acute toxicity in two species, usually one a non-rodent.  [If intravenous is the only route of administration in man, then only this route needs to be studied.]  Repeat dose toxicity - 14 days toxicity in two species (one non-rodent), by the intended route of administration in man. Depending on the nature of the compound, this requirement may be waived (FDA guideline) although a wide range of doses and 14 day observation period would be required for acute toxicity, so little time would be saved and it is expensive on material. Mutagenicity: a bacterial (or in-vitro mammalian cell) mutation test and an in-vitro chromosome damage test (or in vivo mouse micronucleus test) eg: AMES test and human lymphocytes (or CHO cells) in-vitro chromosome damage test, or AMES test and mouse micronucleus test.  Pharmacokinetic data: from animal studies. 

For Multiple dose studies in Man:

Repeat dose toxicity – minimum of 14 days toxicity data in two species (one non-rodent), by the intended route of administration in man, for repeated dosing up to 14 days.  For repeated dosing greater than 14 days, the minimum will be equal to the duration of proposed dosing in man.

The studies listed above are the general series of studies conducted in order to be able to enter Phase l clinical research stage.  There are exceptions that may apply under certain circumstances. For examples of these, please refer to the EMA Guidance on Exploratory IND and Microdosing.

What are your lead-in times for Phase I?

Ethics Approval: South East Wales REC (3 different panels). Each REC panel meets once a month and there is a specific submission deadline (approx. 3 weeks before the meeting).

Regulatory Approval: Application for a Clinical Trial Authorisation (CTA). Submit in parallel to REC submission. No set meeting dates (submit anytime), typically 14 Day review timeline (MHRA target an average of 14 days for healthy participant trials). Screening of participants for the study starts immediately after receipt of EC and MHRA approvals.  Usually 2 weeks is required after ethics and MHRA approvals before study dosing can commence. 

How large is your participant panel and have you any special populations?

Simbec’s participant database contains over 18,000 subjects comprising both male and female subjects in the age range 18-75 years.  We have sub-groups including post-menopausal subjects, obese, mild hypertensives, hyper-cholesterolemics and a small panel of healthy elderly. Patient groups include asthmatics, COPD, Type II diabetics, renal and hepatic impaired.

What are Simbec’s key advantages for Phase I?

Simbec has over 35 years of experience in the field, having worked with many of the world’s major Pharma and many SMEs in a wide range of therapeutic areas. Staff retention is very high, key personnel are less likely to change during the course of projects and direct access by clients to experienced/expert staff is encouraged. Phase I/IIa Unit, Bioanalytical Lab and Clinical Lab on the same site giving excellent communications. Direct links from Phase I to Phases II/III of medium size, Simbec offers high quality and cost effectiveness and every project is important to us. Established links with specialised services including Pre-clinical, Gamma Scintigraphy, Ophthalmology, Dermatology, Respiratory, Clinical Trials Supplies to GMP and Radiolabelled Synthesis.

Do you have experience in performing early Phase II studies in your clinic and, if so, in what therapeutic categories?

Simbec regularly performs early proof of concept studies in patients in the Clinical Unit at our UK headquarters. Such studies are carefully controlled, ensuring patient compliance with the study protocol; particularly useful when pharmacokinetic sampling is required.

Patients are recruited by our network of GPs and hospital departments or by direct advertising. Simbec has conducted early Phase II studies in many therapeutic areas. In recent times studies have been conducted in the following therapeutic areas: diabetes, asthma, eye disease, renal impairment and hypertension in the UK.

We know you run bioanalyses, but what is your track record of developing novel methods for measuring new compounds in biological fluids?

Since Simbec’s formation, our Bioanalytical services have developed alongside the clinical services.  This has given us a vast experience in the field, developing many novel methods for NCEs. Simbec always invests in leading edge technology, so that the majority of methods commissioned have been developed and validated by LC-MS-MS and GC-MS techniques. Many of the successful relationships we have built with Sponsors have developed from an initial Bioanalytical problem, which we have solved for the Sponsor. Often stepping in when competitors have already failed. Simbec’s Bioanalytical Unit is inspected by the MHRA GCP Inspectorate and is part of the UK GLP Compliance Programme.

Many novel methods are published in the literature.

Most Sponsors recognise the benefits of using central laboratories for multi-centre trials.  What are Simbec’s advantages?

Simbec’s Central Laboratory Service, with fully GLP and GCP compliant laboratories, is also accredited by the CPA (UK). Proven systems for collection and safe transport of specimens internationally. Project management and study support eg customised, CRF orientated reports, investigator site training in study specific procedures, co-ordination of supplies (including sample collection materials, centrifuges, freezers etc).

Customised electronic data reporting to investigators and sponsors.  Highly cost competitive service. Extensive experience of supporting clinical trials both in the UK and internationally.

What facilities do you have for handling IMP?

We have an dedicated Pharmacy on-site featuring:

• restricted access 
• controlled ambient (15-25°C), refrigerated (2-8°C) and frozen (-25 - -15°C) storage
• GCP & GMP compliant facilities
• dedicated Production Suite, featuring Grade A Isolator for Steriles and Grade C Production Room for Non-Steriles

Can you Import, Manufacture and QP Certify IMP?

We have a team of QPs with a vast amount of experience in the industry. We can import IMP from non EU/EEA countries, and we can certify IMP manufactured on site.

Can you produce double blind randomisations and codebreak envelopes?

We have a team of statisticians who, in collaboration with the pharmacy department, can produce double blind randomisation schedules. We have validated codebreak envelope production facilities on site.