There is a need for a fully-informed laboratory in combination device validation services. The ideal is a laboratory that understands both the pharmaceutical and medical device requirements; from extractables and leachables, through bioavailability, to dose accuracy and ease of use. A good pre-clinical partner/test facility, such as Medical Engineering Technologies Ltd. (MET, www.met.uk.com) can provide regulatory guidance and Design Validation Testing (DVT) to help assist in getting a product to the marketplace.
The process of generating performance and safety data should be planned to ensure efficient project management and to help reduce costs.
Design Validation Planning
The pre-requisites to developing a design validation programme are:
- Competitor submissions review
- Design inputs / targeted product performance
- European and/or FDA Guidance review
- Risk analysis
- ISO /EN /ASTM/ ICH/ pharmacopeia standards review
- (If this is a first foray into combination devices) A gap analysis of the Quality Managements System (QMS) and production processes and qualifications in place.
A review of existing product standards and Guidance, along with detailed risk analysis, is essential to defining test programmes. This approach ensures that all the necessary testing has been carried out, and can also reduce any unnecessary testing. Additionally, the key performance requirements must be identified in a product review; this includes design inputs and a literature review. To assist you in saving time and money, MET has developed standard study plans for a large range of devices.
These reviews and risk analyses can then be used to develop the test programme and design test protocols.
Developing a Protocol
The testing regimes in a DVT could include:
- Assessment of hazards identified in the risk analysis
- Bioavailability studies
- Biocompatibility studies
- Drug / container interaction analysis
- Extractables and leachables studies, toxicological risk analysis
- Human factors studies
- Performance and dose accuracy assessments
- Reference Listed Drug (RLD) comparison
- Standard / FDA Guidance compliance testing
Gantt charts and a more descriptive plan, provided by your partner laboratory, keep you informed. These plans can include test cost, time requirements, sample numbers, and an indication of whether a test is essential (or just helpful).
MET testing plans shown below use a transdermal patch as an example and give an idea of the types of testing, sample sizes and time requirements that would need to be considered. These tables are not comprehensive.
Transdermal biocompatibility and chemical safety:
Transdermal performance tests:
Transdermal distribution testing:
Design Validation Testing (DVT)
All planned tests will require agreed test protocols. These are developed by your test facility, with your approval.
The testing stage might be preceded by a Gauge Repeatability and Reliability (GR&R) study, to provide evidence that the test protocol is robust and that there can be confidence in the DVT results.
The use of a laboratory with ISO/IEC 17025 accreditation will ensure that there is a good, fully audited, QMS and that equipment is qualified and calibrated, whilst processes are subjected to internal audits. It is entirely possible that not all the tests will be specifically accredited. As long as these are carried out to an agreed protocol under the ISO/IEC 17025 QMS, there can be confidence in the results.
Test reports can be succinct or extensive. For regulatory submissions, a Certificate of Analysis will be too brief whilst as 100 page report will not be helpful.
The report should include at least:
- The test protocol (this can be an appendix)
- The rationale for analyses included and excluded
- Any deviations from test protocol
- Details of equipment and technicians
- Details of the product/s tested (batches, dates, description, etc…)
- Test results
When developing a combination device, a pharmaceutical company must decide whether to carry out testing in-house or externally. There is no compulsion for independent testing, as long as a company’s own laboratory is fully equipped, has all the control systems in place, and will act without bias.
The advantages of using an experienced, well informed external laboratory are:
- Clear independence
- No capital costs
- Efficiency of project management, testing and reporting
- Good advice from a knowledgeable source.
Things to look for when selecting a laboratory are:
- A good QMS and good quality control
- Informed and helpful staff
- Rapid, accurate responses to queries
- Openness of access
- A comprehensive range of services, in order to reduce multiple sourcing and adding several companies to your supplier list.
Medical Engineering Technologies (MET) has staff that have developed plans for many projects and a wide variety of devices. These have been successfully implemented within an ISO/IEC 17025 QMS, helping clients achieve a smooth entry into the market (www.met.uk.com).
At DeviceTalks Boston, Tyler Shultz will give attendees an inside look at Theranos and how he was able to sound the alarm after he realized the company was falling apart. Shultz will take attendees behind the story that everyone is talking about: the rise and fall of Elizabeth Holmes and her diagnostic company, Theranos.
Join Shultz and 1,000+ medical device professionals at the 8th annual DeviceTalks Boston.