John: +44 (0)7515 934073 Caroline: +44 (0)7929 264499 John: john@jkonsult.co.uk Caroline: caroline@jkonsult-hr.co.uk

Specialist Areas

Jkonsult services cover a number of areas with key expertise and specialist experience and prefers to work very closely with clients (and their suppliers as appropriate) as part of the team. This enables Dr John Knight to impart experience and expertise when it is needed with the goal to avert issues rather than having to resolve problems; prevention is always better than a cure.

Jkonsult projects vary from short-term issues such as urgent trouble-shooting to overcome a supply or process failure, through to regular involvement in the detailed project discussions over a period of time.

Chemical process and development of small molecules

Jkonsult offer targeted and pragmatic suggestions to either direct or help guide your team or contractor to an appropriate solution, in line with the phase of development of your product – whether in research, development or commercial manufacture.  A common theme in the approach is to ensure solutions are appropriate to the degree of urgency and phase of development of the specific target(s). 

Synthesis, development and scale-up of fine chemicals, intermediates and active pharmaceutical ingredients

Selection of cost-effective, safe and efficient routes is crucial to underpinning scalable processes. Jkonsult assists clients with devising alternative synthetic routes as well as providing a review and critique service for clients who need assistance. Having identified the preferred route, Dr John Knight can continue to work with a client (or a client’s contractor) to ensure a safe, scalable and cost-effective process is defined with due regard also for regulatory requirements.

CMC support for early stage drug development assets

With over 20 years experience in early phase drug development, from gram-scale syntheses through to validated commercial processes, Jkonsult can provide valuable inputs to your CMC package, as well as co-author the submission dossier.

A common feature of the work that Jkonsult does is to advise and guide selection of a CRO, including drafting Requests for Proposal and then reviewing and assessing CRO proposals both from a technical viewpoint as well as cost.

Once a given project has started, Jkonsult can help in the project management to secure on-time delivery of intermediates and/or product, including detailed technical interactions with the CROs involved. For this type of work Dr John Knight brings to bear his extensive experience from having worked for a CRO coupled with experience in his consultant role of being the client.

CMC support for programmes moving through clinical development, process validation and to commercialisation

Following on from the early stage development experience noted above, Jkonsult also works with clients moving programmes through from Phase I and II clinical trials an into Phase III and process validation to position the asset for commercial launch.

Salt selection, polymorphism and crystallisation

During his time at a CRO, Dr John Knight established and managed a small team devoted to salt selection and polymorph screening work. Subsequent to this, during his consultancy career, he has taught courses on solid state, including crystallisation. As a result, Jkonsult is well positioned to assist in the design and development of processes to access the desired solid state, whether for a final API or for any intermediate. Dr John Knight has also worked with patent lawyers in litigation cases, most frequently as a fact witness. A typical project would involve Jkonsult identifying an independent contract laboratory to make samples of the product under question and then to manage these activities including acquisition of the requisite analytical data. Dr John Knight reports the findings and supports the case as required through deposition or court appearance as necessary.

If you have a legal dispute and would be interested in seeking assistance, please contact Jkonsult for a completely confidential discussion.

Good manufacturing practices (GMP)

Dr John Knight has extensive experience in GMP-compliant manufacture of APIs from Phase I clinical trial material through to commercial lots. Dr John Knight has been involved in the design and construction of two cGMP-compliant small-scale plants (100L to 1600L vessels) and their subsequent staff recruitment and management. Jkonsult can assist in staff training, reviewing plans for new facilities or facility upgrades for operational compliance as well as writing and reviewing SOPs.

 

Project management, outsourcing, technology transfer and due diligence

Dr John Knight has over 20 years experience managing projects for the delivery of key starting materials, fine chemicals and APIs. During this time, Jkonsult has come across and solved many challenges and been involved in transferring technology both in and out of a number of sites/locations. Additionally, during his time in a CRO, Dr John Knight co-hosted many audits, which included quality audits as well as technical competence due diligence visits from existing or potential clients. Subsequently, in his consultancy role, Dr John Knight completed technical competency and due diligence audits, often during the selection process of a CRO for clients. Whilst not a regulatory expert, Dr John Knight can bring his cGMP experience to bear and has carried out GMP compliance visits, again often as part of the CRO selection process.

A key aspect of our work is to provide a conduit between client and CRO or CMO to ensure the deliverables are realistic and technical challenges appropriately judged to guard against misguided (over) expectations and the resultant disappointment. We work with clients world-wide, across different time-zones and cultures, with the common theme to define a realistic cost and time structure then delivery in accord with the time-lines.

Staff development and mentoring

Dr John Knight has an excellent track record in developing and mentoring staff. During the 14 years at a CRO he was responsible for establishing the process research and development group, recruiting staff for the pilot plants and ensuring staff were development both from a technical standpoint as well as more generally to ensure effective communication and excellent customer focus.

The foundation has been put to good use as a onsultant. Dr John Knight worked for several years with a rapidly growing Asian CRO to help with staff development and mentoring to enhance a sound scientific basis through guidance on communication and cultural differences. In addition, Dr John Knight has given many public training courses, internal seminars and in-house training internationally.

Jkonsult is a firm believer that staff development and mentoring is an excellent route to staff retention and overall performance improvement as well of course for succession planning and management.

Return on investment

How can you measure return on investment from engaging a consultant? A frequent question and not one that is easy to answer and this very difficulty can result in delays. In cases where a consultant is engaged to fill a specific knowledge gap or help fix a defined technical issue, then it is easier to gauge the benefit, but where a consultant is engaged to review or challenge internal opinion, it may sometimes be less clear. Below are a few selected examples where Dr John Knight has made a clear difference. Obviously the details cannot be shared for confidentiality reasons, but they do give a flavour of the benefits the right consultant can bring.

Technology transfer project

A small European company wanted to transfer their commercial manufacture to a lower cost manufacturer. Dr John Knight was closely involved in the CMO selection process and an Asian supplier was chosen based on regulatory expertise, technical competencies and facilities. During the transfer process an existing impurity (NMT 0.1%) was found in the first pilot plant trial batch at elevated level (ca 0.6%). Dr John Knight reviewed the executed batch sheets and analytical data and diagnosed a failure to adequately inert the reactors at plant scale – the elevated impurity was generated by aerobic oxidation. The rapid assessment and diagnosis of the issue enable simpleremedial measures to be established (including staff training and added instructions in the batch sheet) which enable on-time project progression to successful process validation and completion of the transfer. ROI: The correct diagnosis of the issue took about 0.5 to 1 day of consultant time. The CRO had proposed an action plan of experimental work to first try to determine the impurity structure, then back-track to its formation – this was of the order of 1-2 weeks work. The intervention by the consultant therefore saved at least 2 weeks and ensured the overall programme remained on schedule – significant project delay beyond 2 weeks could have resulted in losing the planned product slot and hence further delays.

Crystallisation failure

A virtual company was having its development candidate scaled up for the first time to make multi-kilo quantities under cGMP. The final stage was to crystallise the API prior to final purification and form control. During his first plant run the API failed to crystallise, remaining as a solution. Despite many sensible approaches by the CRO, and successes at laboratory scales, the main batch failed to crystallise. The CRO has exhausted their range of process solutions. Dr John Knight suggested a specific operational change which resulted in the API precipitating from solution, albeit not in the desired solid state. A recrystallisation of this semi-purified aterial worked and the clinical trial could be started on time.

ROI: The CRO had exhausted their potential solutions to the problem. The input form the consultant brought a new approach which ultimately proved successful and ensured on-time delivery.

CRO/Client relationship

A relatively simple example where Dr John Knight was working with a growing CRO, helping mentor and develop staff and give technical and operational guidance. The issues was that the CRO has secured a very attractive project with a multinational pharmaceutical company; this profile met precisely the business direction the CRO wished to follow and so was a crucial project for the CRO. As can often be the case with projects on aggressive timelines, there was a delay in the raw material supply to the CRO, the implication of which was about a 6 week delay in delivery. Dr John Knight urged the CRO to work with their raw material supplier and establish an alternative supply schedule. Having secured a revised supply schedule for raw material, the CRO could adjust their internal schedule and manufacture the first half of the client order in line with the existing schedule and follow with the second batch about 3-4 weeks later. A proposal was presented to the client and found to fully meet their needs – based on experience, batch sizes and the fact this was a project in clinical development, Dr John Knight speculated that the client would be running at least 2 campaigns and so would not need the full inventory on the date specified, hence the proposed delivery schedule. The CRO had a telephone meeting with the client (which Dr John Knight joined) and the revised delivery proposal was accepted. The CRO met both the initial and second batch delivery schedules and the client was very satisfied with the overall interactions. The CRO has had further business with the client.

ROI: The project was delivered to meet client requirements and the CRO secured further business on other projects. The cost of consultancy nteractions was about $3000 set against a project revenue of about $250,000 plus of course a retained and satisfied client.