Evaluation of the Safety & Performance of 2 Intradermal Safety Devices

Volunteers will be asked to attend Surrey CRC for two visits with a follow up telephone call. A subset of volunteers will be aske to attend an additional visit and follow up call.

Visit 1 - Screening Visit (Day - 28 to -1) Visit 1 will take place up to 28 days prior to the injections being administered (Visit 2). At this visit consent will be taken and the following procedures performed: demography, medical history and concomitant medication, vital signs (blood pressure, heart rate, oral temperature), symptoms-directed physical examination including assessment of deltoid area, measurement of height and weight, blood sample taken for haematology and coagulation screen, completion of a medical health questionnaire. Inclusion/exclusion criteria will be assessed and volunteers that continue to be eligible will be invited back to attend Visit 2a.

Visit 2a - Injection (Day 0) At Visit 2a, continuing eligibility will be assessed and both adverse events and concomitant medication will be recorded. Vital signs will be measured and if the volunteer is still eligible then they will be randomised onto the study.

The volunteer will receive a total of 6 injections, 3 in each upper arm. In each arm there will be one Mantoux injection and 2 device injections (the same device or different). In total they will receive 2 Mantoux injections and 2 injections from each device. To maintain the blind of the study the volunteers will be asked to wear a blindfold during the injections. After each injection a number of measurements will be performed including assessing wheal size and wetness at the injection site as well as subjectively assessing pain. In addition the devices will be weighed before and after use.

Following the injections, vital signs will be recorded again and volunteers will be discharged and provided with a diary card to complete over the following 24 hours. They should record side effects and any medications taken, including over the counter medications as well as any skin reactions.

Visit 2b - Mandatory Follow Up telephone call (Day 1) The volunteer will be telephoned by a member of the study team 24 hours after the injection visit and both adverse events and concomitant medication will be recorded. Volunteers will be asked to return their diary cards to the CRC in the mail.

A subset of volunteers will be invited back to attend Visits 3a and 3b.

Visit 3a - Injection (Within days 7 to 28) At Visit 3a, continuing eligibility will be assessed and both adverse events and concomitant medication will be recorded. Vital signs will be measured and if the volunteer is still eligible then they will be randomised onto the study.

The volunteer will receive a total of 6 injections, 3 in each upper arm. In each arm there will be one Mantoux injection and 2 device injections (the same device or different). In total they will receive 2 Mantoux injections and 2 injections from each device. To maintain the blind of the study the volunteers will be asked to wear a blindfold during the injections. After each injection a number of measurements will be performed including assessing wheal size and wetness at the injection site as well as subjectively assessing pain. At this visit, ultrasound echography will be performed for each injection site. In addition the devices will be weighed before and after use.

Following the injections, vital signs will be recorded again and volunteers will be discharged and provided with a diary card to complete over the following 24 hours. They should record side effects and any medications taken, including over the counter medications as well as any skin reactions.

Visit 3b - Follow Up telephone call (24 h after Visit 3a) The volunteer will be telephoned by a member of the study team 24 hours after the injection visit and both adverse events and concomitant medication will be recorded. Volunteers will be asked to return their diary cards to the CRC in the mail.

Inclusion criteria

• Healthy male or female volunteers aged 18 to 60 years inclusive. Attempts will be made to achieve an equal gender ratio through appropriate screening procedures, but a failure to do so will not preclude analysis of the final data set.
• The volunteer is, in the opinion of the investigator, healthy on the basis of self-reported medical history, vital signs, a physical examination (including the skin overlying the deltoids of the upper arms), and the results of routine haematology and coagulation laboratory tests, with no active disease process that could interfere with the study endpoints.
• Body Mass Index ≥18.5 and <29.5.
• The volunteer is able to read and understand the Informed Consent Form (ICF), and understand study procedures.
• The volunteer has signed the ICF and is willing to comply with study procedures.
• Available for follow-up for the duration of the study.

Exclusion criteria

• 1. Clinically significant psychiatric, cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological (particularly myasthenia gravis), immunological, or haematological disease or abnormality, as determined by the study physician, which might interfere with consenting or self-recording of safety events.

• Presence of large or dark tattoos or other marking or abnormal variation in skin pigmentation in the area of the deltoids that would preclude measurement of six injection site wheals.

• Acute, self-reported needle phobia. 4. Regular use of anti-coagulant medication, non-steroidal anti-inflammatory drugs, topical or oral steroids, anti-histamines and opiates for longer than six months.

• Pregnant or lactating at any point during the study from screening to final follow up.

• Any condition that, in the investigator's opinion, compromises the volunteers' ability to meet protocol requirements or to complete the study.

• Unable to read and speak English to a fluency level adequate for the full comprehension of procedures required in participation and consent.

• Dermatological and other conditions likely to cause excessive soreness, bleeding or pain at the site of injection or subsequent scarring; these might include hyperkeratosis and bleeding disorders.

• Peripheral neuropathy, which might interfere with pain perception.